gebhart/patrepeval huggingface dataset:
The primary structure of carboxypeptidase S1 from Penicillium janthinellum (1993)

The complete amino acid sequence of carboxypeptidase S1 from Penicillium janthinellium has been determined by N-terminal sequencing of the reduced and vinylpyridinated protein and of peptides obtained by cleaved with cyanogen bromide, iodosobenzoic acid, hydroxylamine, endoproteinase LysC, endoproteinase AspN and Glu-specific proteinase from B. licheniformis. The enzyme consists of a single peptide chain of 433 amino acid residues and contains 9 half-cystine residues and one glycosylated asparagine residue. A comparison to other carboxypeptidases shows that the enzyme is homologous to carboxypeptidase-Y and carboxypeptidase-MIII from malt. Specificity and binding of substrates are discussed from a three-dimensional model based on the known structure of carboxypeptidase-Y from Saccharomyces cereviciae and carboxypeptidase II from wheat.
Targeted Doxorubicin-Loaded Bacterially Derived Nano-Cells for the Treatment of Neuroblastoma (2018)

Advanced stage neuroblastoma is an aggressive disease with limited treatment options for patients with drug-resistant tumors. Targeted delivery of chemotherapy for pediatric cancers offers promise to improve treatment efficacy and reduce toxicity associated with systemic chemotherapy. The EnGeneIC Dream Vector (EDV<sup>TM</sup>) is a nanocell, which can package chemotherapeutic drugs and target tumors via attachment of bispecific proteins to the surface of the nanocell. Phase I trials in adults with refractory tumors have shown an acceptable safety profile. Herein we investigated the activity of EGFR-targeted and doxorubicin-loaded EDV<sup>TM</sup> (<sup>EGFR</sup>EDV<sup>TM</sup><sub>Dox</sub>) for the treatment of neuroblastoma. Two independent neuroblastoma cell lines with variable expression of EGFR protein [SK-N-BE(2), high; SH-SY-5Y, low] were used. <sup>EGFR</sup>EDV<sup>TM</sup><sub>Dox</sub> induced apoptosis in these cells compared to control, doxorubicin, or non-doxorubicin loaded <sup>EGFR</sup>EDV<sup>TM</sup> In three-dimensional tumor spheroids, imaging and fluorescence life-time microscopy revealed that <sup>EGFR</sup>EDV<sup>TM</sup><sub>Dox</sub> had a marked enhancement of doxorubicin penetration compared to doxorubicin alone, and improved penetration compared to non-EGFR-targeted EDV<sup>TM</sup><sub>Dox</sub>, with enhanced spheroid penetration leading to increased apoptosis. In two independent orthotopic human neuroblastoma xenograft models, short-term studies (28 days) of tumor-bearing mice led to a significant decrease in tumor size in <sup>EGFR</sup>EDV<sup>TM</sup><sub>Dox</sub>-treated animals compared to control, doxorubicin, or non-EGFR EDV<sup>TM</sup><sub>Dox</sub> There was increased TUNEL staining of tumors at day 28 compared to control, doxorubicin, or non-EGFR EDV<sup>TM</sup><sub>Dox</sub> Moreover, overall survival was increased in neuroblastoma mice treated with <sup>EGFR</sup>EDV<sup>TM</sup><sub>Dox</sub> (<i>P</i> < 0007) compared to control. Drug-loaded bispecific-antibody targeted EDVs<sup>TM</sup> offer a highly promising approach for the treatment of aggressive pediatric malignancies such as neuroblastoma. <i>Mol Cancer Ther; 17(5); 1012-23. ©2018 AACR</i>.
Persistent Low Back Pain (2005)

A 49-year-old maintenance worker with a history of depression and previous reports of minor back pain is seen during four months of continuing low back pain. He has remained out of work for fear of worsening the injury. Magnetic resonance imaging two weeks after the onset of pain showed only mild degenerative changes in the lumbar region without spinal stenosis or disk collapse or extrusion. How should this patient be evaluated and treated?
Principles of Plasma Discharges and Materials Processing (2005)

1. Introduction. 2. Basic Plasma Equations and Equilibrium. 3. Atomic Collisions. 4. Plasma Dynamics. 5. Diffusion and Transport. 6. DC Sheaths. 7. Chemical Reactions and Equilibrium. 8. Molecular Collisions. 9. Chemical Kinetics and Surface Processes. 10. Particle and Energy Balance in Discharges. 11. Capacitive Discharges. 12. Inductive Discharges. 13. Wave-Heated Discharges. 14. DC Discharges. 15. Etching. 16. Deposition and Implantation. 17. Dusty Plasmas. 18. Kinetic Theory of Discharges. Appendix A: Collision Dynamics. Appendix B: The Collision Integral. Appendix C: Diffusion Solutions for Variable Mobility Model.
Finite element analysis for a wing wall of a large scale dock in construction period (2013)

The wing wall with anchor rod is widely used in the large scale dock.But there are varieties of assumptions which are introduced in the calculation of the dock structure,so that ideal answers can′t be obtained.In order to find out the characteristics of deformation and force of the wing wall,this paper focuses on the realities of the wing wall engineering in Qidong Fengshun dockyard.Finite element calculating models are set up to calculate the displacement and stress of the dock wall structure for typical working conditions respectively with the aid of the large-scale software MSC.Marc and a sufficiently large foundation is selected to reduce the impact of the foundation.Then the calculation results of the finite element method are compared with the measured data to analyze how the construction process affects the force of the wing wall.The anchor structure can enhance the stability of the system by reducing the horizontal displacement of the wing wall and effective stress of solum and concrete structure effectively.The stress that part solum was originally subjected to give by the load difference before and after the wall almost through the steel bars are transmitted to anchorage pile bear after the system had been formed.Thus the dock chamber wall and overall deformation are significantly improved.
Functional Classification, Genomic Organization, Putatively cis-Acting Regulatory Elements, and Relationship to Quantitative Trait Loci, of Sorghum Genes with Rhizome-Enriched Expression (2006)

Rhizomes are organs of fundamental importance to plant competitiveness and invasiveness. We have identified genes expressed at substantially higher levels in rhizomes than other plant parts, and explored their functional categorization, genomic organization, regulatory motifs, and association with quantitative trait loci (QTLs) conferring rhizomatousness. The finding that genes with rhizome-enriched expression are distributed across a wide range of functional categories suggests some degree of specialization of individual members of many gene families in rhizomatous plants. A disproportionate share of genes with rhizome-enriched expression was implicated in secondary and hormone metabolism, and abiotic stimuli and development. A high frequency of unknown-function genes reflects our still limited knowledge of this plant organ. A putative oligosaccharyl transferase showed the highest degree of rhizome-specific expression, with several transcriptional or regulatory protein complex factors also showing high (but lesser) degrees of specificity. Inferred by the upstream sequences of their putative rice (Oryza sativa) homologs, sorghum (Sorghum bicolor) genes that were relatively highly expressed in rhizome tip tissues were enriched for cis-element motifs, including the pyrimidine box, TATCCA box, and CAREs box, implicating the gibberellins in regulation of many rhizome-specific genes. From cDNA clones showing rhizome-enriched expression, expressed sequence tags forming 455 contigs were plotted on the rice genome and aligned to QTL likelihood intervals for ratooning and rhizomatous traits in rice and sorghum. Highly expressed rhizome genes were somewhat enriched in QTL likelihood intervals for rhizomatousness or ratooning, with specific candidates including some of the most rhizome-specific genes. Some rhizomatousness and ratooning QTLs were shown to be potentially related to one another as a result of ancient duplication, suggesting long-term functional conservation of the underlying genes. Insight into genes and pathways that influence rhizome growth set the stage for genetic and/or exogenous manipulation of rhizomatousness, and for further dissection of the molecular evolution of rhizomatousness.
Redemption of autoantibodies on anergic B cells by variable-region glycosylation and mutation away from self-reactivity (2014)

The best-understood mechanisms for achieving antibody self/non-self discrimination discard self-reactive antibodies before they can be tested for binding microbial antigens, potentially creating holes in the repertoire. Here we provide evidence for a complementary mechanism: retaining autoantibodies in the repertoire displayed as low levels of IgM and high IgD on anergic B cells, masking a varying proportion of autoantibody-binding sites with carbohydrates, and removing their self-reactivity by somatic hypermutation and selection in germinal centers (GCs). Analysis of human antibody sequences by deep sequencing of isotype-switched memory B cells or in IgG antibodies elicited against allogeneic RhD+ erythrocytes, vaccinia virus, rotavirus, or tetanus toxoid provides evidence for reactivation of anergic IgM(low) IgD+ IGHV4-34+ B cells and removal of cold agglutinin self-reactivity by hypermutation, often accompanied by mutations that inactivated an N-linked glycosylation sequon in complementarity-determining region 2 (CDR2). In a Hy10 antibody transgenic model where anergic B cells respond to a biophysically defined lysozyme epitope displayed on both foreign and self-antigens, cell transfers revealed that anergic IgM(low) IgD+ B cells form twice as many GC progeny as naïve IgM(hi) IgD+ counterparts. Their GC progeny were rapidly selected for CDR2 mutations that blocked 72% of antigen-binding sites with N-linked glycan, decreased affinity 100-fold, and then cleared the binding sites of blocking glycan. These results provide evidence for a mechanism to acquire self/non-self discrimination by somatic mutation away from self-reactivity, and reveal how varying the efficiency of N-glycosylation provides a mechanism to modulate antibody avidity.
Identification of matrix metalloproteinases 3 (stromelysin-1) and 9 (gelatinase B) in abdominal aortic aneurysm. (1994)

A prominent metalloproteinase activity with an apparent molecular mass of 80 kD and additional activities at 67 through 70, 50, and 32 kD have been observed on casein, gelatin, and elastin gel zymography in extracts from abdominal aortic aneurysms (AAAs). The forms at 80, 50, and 32 kD were isolated by affinity to recombinant tissue inhibitor of metalloproteinases, and the 80-kD and 50-kD components were shown to be derived from matrix metalloproteinase-9 (MMP-9). The relative electrophoretic mobility of these forms under reducing and nonreducing conditions corresponds to those of MMP-9 generated by MMP-3 (stromelysin-1) cleavage, and the active forms of MMP-3 at 45 and 35 kD were detected in aneurysmal extracts under reducing conditions by using specific antibody. Confirmation that the major proteolytic activity observed at 80 kD is MMP-9 was also demonstrated by immunoprecipitation of the activity with specific antibody. Comparative immunoblots of tissue extracts from 10 typical AAA patients, using specific antibody against MMP-9, revealed bands at 92, 82, 67, 51 through 53, 27, 23, and 20 kD under reducing conditions; six aortic control specimens displayed negligible immunoreactivity. This report is the first to show that known activated forms of MMP-3 and MMP-9 are present in the aneurysmal aortic wall and that they may play a role in the destruction of aortic matrix in AAA disease.
Generation of Sequence-specific, High Affinity Anti-DNA Antibodies (2001)

By taking advantage of the extreme stability of a protein-DNA complex, we have obtained two highly specific monoclonal antibodies against a predetermined palindromic DNA sequence corresponding to the binding site of the E2 transcriptional regulator of the human papillomavirus (HPV-16). The purified univalent antibody fragments bind to a double-stranded DNA oligonucleotide corresponding to the E2 binding site in solution with dissociation constants in the low and subnanomolar range. This affinity matches that of the natural DNA binding domain and is severalfold higher than the affinity of a homologous bovine E2 C-terminal domain (BPV-1) for the same DNA. These antibodies discriminate effectively among a number of double- and single-stranded synthetic DNAs with factors ranging from 125- to 20,000-fold the dissociation constant of the specific DNA sequence used in the immunogenic protein-DNA complex. Moreover, they are capable of fine specificity tuning, since they both bind less tightly to another HPV-16 E2 binding site, differing in only 1 base pair in a noncontact flexible region. Beyond the relevance of obtaining a specific anti-DNA response, these results provide a first glance at how DNA as an antigen is recognized specifically by an antibody. The accuracy of the spectroscopic method used for the binding analysis suggests that a detailed mechanistic analysis is attainable.
γ-Glutamyl hydrolase modulation and folate influence chemosensitivity of cancer cells to 5-fluorouracil and methotrexate (2013)

Modulation of GGH affects chemosensitivity of cancer cells to 5FU and MTX, and exogenous folate levels can further modify the effects.
Differential Power Analysis in the Presence of Hardware Countermeasures (2000)

The silicon industry has lately been focusing on side channel attacks, that is attacks that exploit information that leaks from the physical devices. Although different countermeasures to thwart these attacks have been proposed and implemented in general, such protections do not make attacks infeasible, but increase the attacker&amp;apos;s experimental (data acquisition) and computational (data processing) workload beyond reasonable limits. This paper examines different...
Expression and Responsiveness of P2Y2 Receptors in Human Endometrial Cancer Cell Lines (1999)

In single endometrial carcinoma HEC-1A and Ishikawa cells, ATP induced a rapid and extracellular Ca2+-independent rise in cytosolic Ca2+ concentration ([Ca2+]i) in a dose-dependent manner, with an ED50 of about 10 μm. The spike phase was followed by a sustained plateau phase that was dependent on Ca2+ influx through voltage-insensitive Ca2+ channels, whose gating was controlled by a capacitative Ca2+ entry mechanism. ADP was less potent in raising the cystolic Ca2+ concentration, and AMP and adenosine were ineffective. The order of agonist potency for this receptor was ATP = UTP > ATP-γ-S≫ADP. Several other agonists, including β,γ-methylene-ATP, 2-MeS-ATP, and BzATP were ineffective. This ligand-selective profile indicates the expression of the P2Y2R subtype in endometrial cells. Accordingly, reverse transcription-PCR using P2Y2 primers amplified the expected transcript from both cell lines. The coupling of these receptors to phospholipase C was confirmed by the ability of ATP to increase inositol 1,4,5-trisphosphate and diacylglycerol productions. These receptors are also coupled to the phospholipase D-1 pathway, leading to accumulation of phosphatidic acid. Activation of P2Y2 receptors by a slowly degradable ATP analog, ATP-γ-S, was associated with a significant suppression of cell proliferation without affecting the cellular apoptosis. These results indicate that P2Y2 receptors may participate in control of the cell cycle of endometrial carcinoma cells.
Quantification of experimental myocardial infarction using nuclear magnetic resonance imaging and paramagnetic ion contrast enhancement in excised canine hearts. (1982)

Determination of myocardial infarct size is important for clinical management of patients with ischemic heart disease and for research on limiting infarct size. Nuclear magnetic resonance (NMR) imaging permits tomographic depiction of the distribution of mobile tissue protons. NMR images have demonstrated high spatial resolution and contrast. To evaluate the potential of this technique in measuring myocardial infarct size, NMR imaging was performed in six canine hearts excised 24 hours after circumflex coronary artery ligation. Before sacrifice, the dogs received i.v. manganous chloride (0.05 mmol/kg). After NMR imaging, the heart were sectioned and the myocardial slices were stained with triphenyl tetrazolium chloride. The pathologically determined infarct size was compared with the infarct size measured by NMR imaging. The correlation was good (regression line slope 1.06; r = 0.94). We conclude that NMR imaging with paramagnetic contrast agents can be used to determine infarct size in excised hearts.
A selective small molecule agonist of the melanocortin-1 receptor inhibits lipopolysaccharide-induced cytokine accumulation and leukocyte infiltration in mice (2006)

It is well established that melanocortins are peptides that have potent anti-inflammatory activity. Recent research has focused on understanding which of the known melanocortin receptors mediates the anti-inflammatory actions of the melanocortins. The aim of this study was to assess the anti-inflammatory activity of a synthetic MC-1R agonist. BMS-470539 is a potent, selective, full agonist of human and murine MC-1R with EC(50) values in a cAMP accumulation assay of 16.8 and 11.6 nM, respectively. BMS-470539 dose-dependently inhibited TNF-alpha-induced activation of a NF-kappaB transcriptional reporter in human melanoma cells, which endogenously express MC-1R. In vivo studies with BMS-470539 demonstrated that subcutaneous administration of BMS-470539 resulted in a dose-dependent inhibition of LPS-induced TNF-alpha production in BALB/c mice. In this model, the compound had an ED(50) of approximately 10 micromol/kg and a pharmacodynamic half-life of approximately 8 h. Pharmacokinetic analysis of the compound indicated that the compound had a t(1/2) of 1.7 h. In a model of lung inflammation, administration of 15 micromol/kg BMS-470539 resulted in a 45% reduction in LPS-induced leukocyte infiltration (an infiltrate comprised primarily of neutrophils). The compound was also effective in a model of delayed-type hypersensitivity, reducing paw swelling by 59%, comparable with that seen with 5 mg/kg dexamethasone. These studies demonstrate that a selective small molecule agonist of the melanocortin-1 receptor is a potent anti-inflammatory agent in vivo and provides compelling evidence for the involvement of this receptor in the modulation of inflammation.
Id gene expression as a key mediator of tumor cell biology. (1999)

Id genes encode members of the helix-loop-helix (HLH) family of transcription factors that inhibit transcription by forming inactive heterodimers with basic HLH (bHLH) proteins. There are four members of the Id gene family recognized in mammals, and the proteins they encode share homology primarily in their HLH domain. bHLH proteins typically form heterodimers with other bHLH proteins, and their basic domain binds to a DNA sequence element, the E-box, activating transcription. Products of Id genes lack the basic DNA binding domain of the bHLH transcription factors, and when they heterodimerize with bHLH proteins, the complexes are inactive. Generally, high levels of Id mRNA are detected in proliferative undifferentiated, embryonal cells and lower levels are detected in well-differentiated, mature, adult tissues. In vitro, these genes are generally expressed at lower levels in cells after the induction of differentiation. Recently, high levels of expression of Id genes have been identified in cell lines derived from a wide variety of different tumors and in tumor tissues as well. These findings suggest that not only the inappropriate proliferation of tumors but also the anaplastic characteristics that contribute to their malignant behavior may be regulated by Id gene expression.
Investigation of enzyme activity by SERRS using poly-functionalised benzotriazole derivatives as enzyme substrates (2006)

New methods of measuring biologically relevant concentrations of enzymes are necessary to allow greater understanding of biological systems. We have previously shown that aryl azo benzotriazolyl alkyl esters can act as enzyme substrates, with the progress of the reaction being monitored using SERRS (see Nat. Biotechnol., 2004, 22, 1133, ref. ). This is a wholly novel analytical application of SERRS, and the low detection levels of the technique allow for an ultra-sensitive enzyme assay. Masked enzyme substrates are used that are invisible to SERRS until enzymatic hydrolysis. Turnover of the substrate by the enzyme leads to the release of the surface-seeking dye necessary for SERRS, and intense signals are produced. Here we report an improved synthesis of 2H-benzotriazolyl alkyl esters via nucleophilic substitution of a chloromethyl ester by benzotriazolyl azo dyes, giving up to a ten-fold increase on previously reported yields. Introduction of electron-withdrawing groups to the benzotriazole ring allows control over the SERRS properties of the compounds. This is of great significance in expanding the synthetic flexibility and subsequently the fundamental use of these compounds as ultra-sensitive and selective reporters of enzyme activity.
Activated bovine cytoplasts prepared by demecolcine-induced enucleation support development of nuclear transfer embryos in vitro (2005)

Demecolcine-induced enucleation (IE) of mouse oocytes has been shown to improve development to term of cloned mice. In this study, we characterized the kinetics and morphological progression of bovine oocytes subjected to IE, and evaluated their ability to support embryo development to the blastocyst stage after nuclear transfer (NT). In vitro matured bovine oocytes were parthenogenetically activated and subsequently exposed to demecolcine at various times post-activation. Onset and duration of demecolcine treatment significantly altered activation and IE frequencies, which varied from 7.1% to 100% and 33.3% to 91.7%, respectively, at 5 hr post-activation. A significant decrease in IE frequencies was observed at 17 hr post-activation (3.4%-46.1%), possibly due to reincorporation of chromosomes into the oocyte after incomplete second polar body (PB) extrusion. Oocytes were reconstructed by NT before (treatment 1) or after (treatment 2) activation and demecolcine treatment, and cultured in vitro. Cleavage (48.1%-54.2%) and blastocyst rates (15.7%-19%) were equivalent for the two treatments, as well as the total cell number in NT blastocysts. Furthermore, most of the blastocysts were completely diploid (treatment 2) or heteroploid but with a majority of diploid nuclei (treatment 1). Our results demonstrate that the IE method can be successfully used to produce enucleated bovine cytoplasts that are competent to support development to the blastocyst stage after NT. This technically simple approach may provide a more efficient method to enhance the success rate of NT procedures. Further studies are needed to improve the in vitro development efficiency and to expand our understanding of the mechanism(s) involved in demecolcine-induced enucleation.
Characterization of the Structural Features and Interactions of Sclerostin (2009)

The secreted glycoprotein sclerostin has recently emerged as a key negative regulator of Wnt signaling in bone and has stimulated considerable interest as a potential target for therapeutics designed to treat conditions associated with low bone mass, such as osteoporosis. We have determined the structure of sclerostin, which resulted in the identification of a previously unknown binding site for heparin, suggestive of a functional role in localizing sclerostin to the surface of target cells. We have also mapped the interaction site for an antibody that blocks the inhibition of Wnt signaling by sclerostin. This shows minimal overlap with the heparin binding site and highlights a key role for this region of sclerostin in protein interactions associated with the inhibition of Wnt signaling. The conserved N- and C-terminal arms of sclerostin were found to be unstructured, highly flexible, and unaffected by heparin binding, which suggests a role in stabilizing interactions with target proteins.