gebhart/patrepeval huggingface dataset:
Melanoma‐associated antigen p97 continues to be expressed after prolonged exposure of cells to specific antibody (1983)

p97, a 97,000 molecular weight cell surface glycoprotein associated with human melanoma, has attracted attention as a possible target for tumor therapy. Melanoma cells were grown overnight in the presence of IgG2a or IgG1 monoclonal antibodies specific for p97, and then exposed to complement and also tested for binding of monoclonal antibodies specific for other epitopes of p97. The results indicated that melanoma cells continued to express p97 after prolonged exposure to specific antibody, a prerequisite for many therapeutic applications.
In situ Stimulation of CD40 and Toll-like Receptor 3 Transforms Ovarian Cancer–Infiltrating Dendritic Cells from Immunosuppressive to Immunostimulatory Cells (2009)

Boosting therapeutically relevant immunity against lethal epithelial tumors may require targeting tumor-induced immunosuppression on an individualized basis. Here, we show that, in the ovarian carcinoma microenvironment, CD11c(+)MHC-II(+) dendritic cells spontaneously engulf tumor materials but, rather than enhancing antitumor immunity, suppress T-cell function. In situ costimulation of CD40 and Toll-like receptor (TLR) 3 on tumor-infiltrating dendritic cells decreased their L-arginase activity, enhanced their production of type I IFN and interleukin-12 (p70), augmented their capacity to process antigens, and up-regulated costimulatory molecules in vivo in mice and in vitro in human dissociated tumors. Synergistic CD40/TLR activation also induced the migration of activated dendritic cells to lymphatic locations and promoted their capacity to present antigens. Correspondingly, without exogenous antigen, combined CD40/TLR agonists boosted measurable T-cell-mediated antitumor immunity and induced the rejection of otherwise lethal i.p. ovarian carcinomas. Our results highlight the potential of transforming tumor-infiltrating dendritic cells (the most abundant leukocyte subset in the solid ovarian carcinoma microenvironment) from an immunosuppressive to an immunostimulatory cell type. Combined administration of synergistic CD40 and TLR3 agonists could enhance their individual therapeutic effects against ovarian and other lethal epithelial cancers.
Memory Efficient Folding Algorithms for Circular RNA Secondary Structures. (2005)

Abstract. A small class of RNA molecules, in particular the tiny genomes of viroids, are circular. Yet most structure prediction algorithms handle only linear RNAs. The most straightforward approach is to compute circular structures from “internal ” and “external ” substructures separated by a base pair. This is incompatible, however, with the memory-saving approach of the Vienna RNA Package which builds a linear RNA structure from shorter (internal) structures only. Here we describe how circular secondary structures can be obtained without additional memory requirements as a kind of “post-processing ” of the linear structures.
Pharmacokinetic (PK)/pharmacodynamic (PD) results from a phase Ib study of pegylated hyaluronidase PH20 (PEGPH20) in combination with gemcitabine (Gem) in patients with pancreatic cancer. (2013)

e15005 Background: Enzymatic degradation of hyaluronan (HA) is a novel strategy to target the desmoplastic stroma of pancreatic cancer. PEGPH20, a pegylated form of recombinant human hyaluronidase PH20, is an investigational drug in clinical trials. Preclinical studies demonstrate that sustained HA removal by PEGPH20 inhibits tumor growth and enhances chemotherapeutic activity in HA-rich xenografts and genetically engineered mouse tumor models. Ph1 PEGPH20 monotherapy studies show increased tumor perfusion by DCE-MRI, metabolic partial responses by FDG-PET, and stromal remodeling in tumor biopsies from selected advanced cancer patients (pts). Methods: This was a dose-escalation study to find the recommended Ph2 dose of PEGPH20 in combination with Gem in pts with Stage IV previously untreated pancreatic cancer. Pts received Gem at 1000 mg/m 2 IV qwk for Wks 1-7 plus PEGPH20 at 1, 1.6, or 3 μg/kg IV twice a week for Wks 1-4 and qwk for Wks 5-7. Wk 8 was a rest week. Thereafter, PEGPH20 + Gem were given qwk for 3 wks in 4-wk cycles. Serial plasma samples were collected and hyaluronidase activity measured by an ultrasensitive assay to assess PEGPH20 exposure. Plasma HA catabolites were measured by quantitative HPLC to assess PD. Results: 28 pts were enrolled. Plasma PEGPH20 concentrations were proportional to dose, and kinetics were well-characterized by a 2-compartment PK model. Estimates for clearance (0.5-2 mL/hr/kg) were consistent with long t 1/2 (1-2 days) previously seen with single-dose PEGPH20 monotherapy. Wks 1 and 4 PK profiles were similar, suggesting no changes to PEGPH20 clearance mechanisms after multiple doses or effects of Gem on PEGPH20 exposure. Most pretreatment plasma HA levels were &lt;1 μg/mL and increased in a time- and dose-dependent manner after dosing. Circulating HA concentration was &gt;500 µg/mL in several pts given 3 μg/kg PEGPH20. Conclusions: PEGPH20 plasma levels can be predicted using a linear PK model and circulating HA catabolites can be used as a quantitative measure of PEGPH20 PD. Results are consistent with the mechanism of action of hyaluronidase and support further study of PEGPH20 with anticancer agents. Clinical trial information: NCT01453153.
Identification and engineering of human variable regions that allow expression of stable single-chain T cell receptors (2010)

Single-chain antibody fragments (scFv), consisting of two linked variable regions (V(H) and V(L)), are a versatile format for engineering and as potential antigen-specific therapeutics. Although the analogous format for T cell receptors (TCRs), consisting of two linked V regions (Vα and Vβ; referred to here as scTv), could provide similar opportunities, all wild-type scTv proteins examined to date are unstable. This obstacle has prevented scTv fragments from being widely used for engineering or therapeutics. To further explore whether some stable human scTv fragments could be expressed, we used a yeast system in which display of properly folded domains correlates with ability to express the folded scTv in soluble form. We discovered that, unexpectedly, scTv fragments that contained the human Vα2 region (IMGT: TRAV12 family) were displayed and properly associated with different Vβ regions. Furthermore, a single polymorphic residue (Ser(α49)) in the framework region conferred additional thermal stability. These stabilized Vα2-containing scTv fragments could be expressed at high levels in Escherichia coli, and used to stain target cells that expressed the specific pep-HLA-A2 complexes. Thus, the scTv fragments can serve as a platform for engineering TCRs with diverse specificities, and possibly for therapeutic or diagnostic applications.
Factors influencing the stabilities of nematic liquid crystals (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFactors influencing the stabilities of nematic liquid crystalsMichael J. S. Dewar and Robert M. RiddleCite this: J. Am. Chem. Soc. 1975, 97, 23, 6658–6662Publication Date (Print):November 1, 1975Publication History Published online1 May 2002Published inissue 1 November 1975https://pubs.acs.org/doi/10.1021/ja00856a010https://doi.org/10.1021/ja00856a010research-articleACS PublicationsRequest reuse permissionsArticle Views249Altmetric-Citations95LEARN 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
A Structure-Based Library Approach to Kinase Inhibitors (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTA Structure-Based Library Approach to Kinase InhibitorsThea C. Norman, Nathanael S. Gray, John T. Koh, and Peter G. SchultzView Author Information Howard Hughes Medical Institute Department of Chemistry University of California Berkeley, California 94720 Cite this: J. Am. Chem. Soc. 1996, 118, 31, 7430–7431Publication Date (Web):August 7, 1996Publication History Received6 May 1996Published online7 August 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/ja9614934https://doi.org/10.1021/ja9614934rapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views825Altmetric-Citations114LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Amines,Aromatic compounds,Organic compounds,Peptides and proteins,Reaction products Get e-Alerts
Comparison of healing in forelimb and hindlimb surgically induced core lesions of the equine superficial digital flexor tendon (2014)

Our results indicate that fore- and hindlimb SDFT surgically induced lesions exhibit significant differences in several important parameters of tendon healing 24 weeks post-surgery. These differences create significant challenges in using all four limbs and accurately interpreting the results that one might generate. Therefore these findings do not support the use of four-limb models for study of tendon injury until the reasons for these differences are much better understood.
Bead-shift isolation of protein-DNA complexes on a 5S RNA gene (1994)

Specific protein-DNA complexes formed on a Xenopus 5S RNA gene were isolated and characterized using a novel technique. A DNA template reversibly immobilized on paramagnetic beads was used to capture, affinity purify, and concentrate protein--DNA complexes formed in a whole cell extract. The complexes were then released from the beads in a soluble and transcriptionally active form via restriction enzyme digestion of the DNA. A band-shift gel was used to separate and obtain the DNase I footprints of five individual complexes. Three of the complexes resulted from the independent binding of two proteins, TFIIIA and an unidentified protein binding to a large region just downstream of the 3' end of the gene. Two more slowly migrating complexes contained an additional large central protected region covering most of the gene. The most slowly migrating complex displayed protein interactions over the 5' flanking sequences. The formation of two of these complexes was shown to be dependent on TFIIIC activity. The correlation between transcriptional activity and the formation of these complexes suggests that the observed protein--DNA interactions are important for transcription of 5S RNA genes.
Endosomal Translocation of Vertebrate DNA Activates Dendritic Cells via TLR9-Dependent and -Independent Pathways (2005)

TLRs discriminate foreign from self via their specificity for pathogen-derived invariant ligands, an example being TLR9 recognizing bacterial unmethylated CpG motifs. In this study we report that endosomal translocation of CpG DNA via the natural endocytotic pathway is inefficient and highly saturable, whereas endosomal translocation of DNA complexed to the cationic lipid N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate (DOTAP) is not. Interestingly, DOTAP-mediated enhanced endosomal translocation of otherwise nonstimulatory vertebrate DNA or of certain noncanonical CpG motifs triggers robust dendritic cell activation in terms of both up-regulation of CD40/CD69 and cytokine production, such as type I IFN and IL-6. We report that the stimulatory activity of phosphorothioated noncanonical CpG oligodeoxynucleotides is TLR9 dependent, whereas phosphodiester DNA, such as vertebrate DNA, in addition trigger TLR9-independent pathways. We propose that the inefficiency of the natural route for DNA internalization hinders low affinity TLR9 ligands in endosomes to reach threshold concentrations required for TLR9 activation. Endosomal compartmentalization of TLR9 may thus reflect an evolutionary strategy to avoid TLR9 activation by self-DNA.
Quartz Capsule Pressure Transducer for the Automotive Industry (1981)

&lt;div class="htmlview paragraph"&gt;This paper describes a low-cost, high-performance manifold absolute pressure sensor for the automotive industry. The sensor uses a pressure-dependent sealed capacitor element constructed from fused quartz plates, and circuit detection schemes to produce the voltage signal output. Temperature effects due to the thermal elastic and linear expansion coefficients of the quartz capsule are also discussed, as are electronic compensation methods to minimize these effects in the output.&lt;/div&gt;
IncA/C Plasmid-Mediated Florfenicol Resistance in the Catfish Pathogen Edwardsiella ictaluri (2008)

Florfenicol (FFC) has recently been approved by the Food and Drug Administration for the treatment of several bacterial diseases of cultured fish species in the United States, including enteric septicemia of catfish (ESC) caused by Edwardsiella ictaluri. The FFC-resistant E. ictaluri strain (M07-1) described herein was isolated from a moribund catfish obtained from the Thad Cochran National Warmwater Aquaculture Research Center (Stoneville, MS) in May of 2007 and was confirmed to be E. ictaluri by 16S rRNA gene sequencing (6). Fish showing signs of ESC were examined for FFC-resistant E. ictaluri because losses due to ESC persisted in this population despite FFC treatment. To characterize the resistance properties of this strain, conjugative transfer experiments were performed as described previously (14) using FFC (30 μg/ml) for selection. The antimicrobial susceptibilities of M07-1, the corresponding FFC-resistant transconjugant, and the isogenic parent strain (Table ​(Table1)1) were quantified using standard microdilution assays (3, 4, 11), demonstrating that the resistance phenotype observed in strain M07-1 was self-transmissible, conferring resistance to FFC, chloramphenicol, tetracycline, streptomycin, ampicillin, amoxicillin-clavulanic acid, ceftiofur, and cefoxitin, as well as decreased susceptibility to trimethoprim-sulfamethoxazole and ceftriaxone. Resistance transfer correlated to a 150-kb plasmid (referred to hereinafter as pM07-1), suggesting the presence of a multidrug resistance plasmid in this isolate (data not shown). PCR analysis (15) followed by sequencing confirmed that E. ictaluri M07-1 and its multidrug-resistant (MDR) transconjugant harbored the floR gene.
An in-vitro model of colonisation resistance to Clostridium difficile infection (1986)

To investigate the importance of the normal gut flora in preventing the establishment of Clostridium difficile in vivo we have developed an in-vitro test system based on growth in faecal emulsions. Growth of C. difficile and cytotoxin production are inhibited in faecal emulsions from healthy adults, but not in sterilised emulsions; the importance of viable bacteria in the inhibitory system is evident. Generally, faecal emulsions derived from infants, children and geriatric patients were less inhibitory than those from healthy adults. Those from bottle-fed infants were significantly less inhibitory than those from breast-fed infants. Decreased levels of cytotoxin in the latter group were attributed to the acidic pH of the stools. With the different patient groups studied, faecal samples not inhibitory to C. difficile in vitro were obtained from 21% of patients with antibiotic-associated diarrhoea, 33% of those taking antibiotics but who did not have diarrhoea, 18.7% of those with diarrhoea unassociated with antibiotics, and 79% of those with C. difficile-mediated diarrhoea. In some cases inhibition was due to low faecal pH, as in some infants, and in others to other filterable substances. The degree of inhibition could not be linked to specific volatile fatty acids or enzymes.
Post-Translational Proteolysis in Polypeptide Hormone Biosynthesis (1982)

Macrophage polarization refers to how macrophages have been activated at a given point in space and time. Polarization is not fixed, as macrophages are sufficiently plastic to integrate multiple signals, such as those from microbes, damaged tissues, and ...Read More
Enzymatic hydrolysis of agar: purification and characterization of β-neoagarotetraose hydrolase from Pseudomonas atlantica (1977)

Agarose is degraded by a beta-agarase from Pseudomonas atlantica to neoagarooligosaccharides of degree of polymerization (DP), 4, 6, 8, and 10. A beta-neoagarotetraose hydrolase cleaves the central beta-linkage in neoagarotetraose and the beta-linkage near the nonreducing end in neoagarohexaose and -octaose to yield neoagarobiose. The beta-neoagarotetraose hydrolase was localized on or outside the cytoplasmic membrane, in the cell wall region. The enzyme was activated by NaCl, KCl, CaCl2, MnCl2, and MgSO4, has a Km of 3.4 X 10(-3) M for neoagarotetraose, was free from beta-agarase and alpha-neoagarobiose hydrolase activity, and showed no transglycosidic activity.
Dehydration Rate after Solid Matrix Priming Alters Seed Performance of Shrunken-2 Corn (1994)

In a test to overcome poor seed germination and seedling vigor of sweet corn ( Zea mays L.) seeds carrying the shrunken-2 (sh2) mutant endosperm, primed seeds of two sh2 sweet corn cultivars—Crisp N'Sweet 711 (CNS-711) and How Sweet It Is (HSII)—were redried at 15, 20, 30, or 40C and 25% relative humidity after solid matrix priming (SMP). The dehydration rate was significantly lower in `CNS-711' than `HSII' at all temperatures. In both cultivars, the drying temperature after SMP was critical for seed performance. Primed seeds with a higher dehydration rate (dried at 30 or 40C) had better seed vigor, greater field emergence and seedling vigor, lower leachate conductivity and imbibition rate, and a higher respiration rate and glutamic acid decarboxylase activity than primed seeds redried at the lower temperatures or control seeds. Increased incidence of pathogen growth was observed on seeds dried at 15 and 20C relative to those dried at 30 or 40C, probably as a consequence of greater leakage from the seeds at a lower redrying temperatures. Lack of tolerance to dehydration at 15 and 20C was another factor adversely affecting the seeds redried at low temperature. A more rapid dehydration rate at a higher temperature after priming sh2 sweet corn improved many of the physiological characteristics used to measure seed quality and the subsequent emergence and vigor of the seedlings under field conditions.
The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication (2017)

Zika virus (ZIKV) is a member of the Flaviviridae family, along with other agents of clinical significance such as dengue (DENV) and hepatitis C (HCV) viruses. Since ZIKV causes neurological disorders during fetal development and in adulthood, antiviral drugs are necessary. Sofosbuvir is clinically approved for use against HCV and targets the protein that is most conserved among the members of the Flaviviridae family, the viral RNA polymerase. Indeed, we found that sofosbuvir inhibits ZIKV RNA polymerase, targeting conserved amino acid residues. Sofosbuvir inhibited ZIKV replication in different cellular systems, such as hepatoma (Huh-7) cells, neuroblastoma (SH-Sy5y) cells, neural stem cells (NSC) and brain organoids. In addition to the direct inhibition of the viral RNA polymerase, we observed that sofosbuvir also induced an increase in A-to-G mutations in the viral genome. Together, our data highlight a potential secondary use of sofosbuvir, an anti-HCV drug, against ZIKV.
Combination of Docetaxel and Recombinant Vaccine Enhances T-Cell Responses and Antitumor Activity: Effects of Docetaxel on Immune Enhancement (2008)

These findings suggest potential clinical benefit for the combined use of docetaxel and recombinant cancer vaccines.
Four-Parameter Model of the Sigmoidal Relationship between Parathyroid Hormone Release and Extracellular Calcium Concentration in Normal and Abnormal Parathyroid Tissue* (1983)

We employed a computer program to curve-fit data relating PTH release in vitro to the extracellular calcium concentration in parathyroid cells prepared from normal bovine and human as well as pathological human parathyroid tissue. In bovine cells and 82% of human cell preparations in which PTH release was more than 50% suppressible by high calcium concentrations, the data were successfully fitted to symmetrical sigmoidal curves. Such curves were defined by four parameters [A = maximum PTH release, B = slope of the curve at the setpoint, C = set-point (calcium concentration causing half-maximal inhibition of secretion), and D = minimum PTH release]. There was excellent agreement between the predicted values for these parameters and those we have obtained previously using visual fits. We also generated theoretical curves with the program to assess the possible contribution of changes in parameters A through D to hypersecretion of PTH in hyperparathyroidism. These analyses suggested that changes in maximal PTH secretion, slope of the curve, set-point, and maximal suppressibility of PTH release all might contribute to hormonal hypersecretion. On a quantitative basis, however, changes in the set-point produced the largest alteration in secretory rate for a given change in the value of a parameter. These results provide a mathematical model for the relationship between PTH release and the extracellular calcium concentration. Moreover, they provide a means of analyzing theoretically the contribution of various qualitative changes in this relationship to states of hypo- and hypersecretion of PTH.
Integration Process and Reliability for SrBi₂ Ta₂O 9 -based Ferroelectric Memories (2001)

Highly reliable packaged 64kbit fe- rroelectric memories with 0.8 µm CMOS ensuring ten-year retention and imprint at 125 o C have been successfully developed. These superior reliabilities have resulted from steady integration schemes free from the degradation, due to layer stress and attacks of process impurities. The resent results of research and development for ferroelectric memories at Hynix Semiconductor Inc. are summarized in this invited paper.
CADHERINS: A MOLECULAR FAMILY IMPORTANT IN SELECTIVE CELL-CELL ADHESION (1990)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More