gebhart/patrepeval huggingface dataset:
Abstract 5543: Combining antibody-targeted radiation (radioimmunotherapy) and antibody-SN-38 conjugates (ADC) improves pancreatic cancer therapy (2010)

Abstract We previously reported effective anti-tumor activity in nude mice bearing human pancreatic tumors with 90Y-humanized PAM4 IgG (hPAM4; 90Y-clivatuzumab tetrexetan) that was enhanced when combined with gemcitabine (GEM). These studies led to clinical testing of fractionated 90Y-hPAM4 IgG combined with GEM that is showing encouraging objective responses. While GEM is known for its radiosensitizing ability, alone it is not a very effective therapeutic agent for pancreatic cancer and its dose is limited by hematologic toxicity, which is also limiting for 90Y-hPAM4 IgG. We recently reported promising anti-tumor activity with an ADC composed of hRS7 IgG (humanized anti-epithelial glycoprotein-1; EGP-1) and SN-38, the active component of irinotecan. This ADC is very well tolerated in mice (eg, ≥ 60 mg), yet just 4.0 mg (0.5 mg, twice-weekly x 4) is significantly therapeutic. Since EGP-1 is also expressed in most pancreatic cancers, we have examined combinations of 90Y-hPAM4 IgG with RS7-SN-38 in nude mice bearing 0.35 cm3 subcutaneous xenografts of the human pancreatic cancer cell line, Capan-1. Mice (n=10) were treated with a single dose of 90Y-hPAM4 IgG alone (130 µCi, ie, the maximum tolerated dose or 75 µCi), with RS7-SN-38 alone (as above), or combinations of the 2 agents at the two 90Y-hPAM4 dose levels, with the first ADC injection given the same day as the 90Y-hPAM4. All treatments were tolerated, with ≤ 15% loss in body weight. Objective responses occurred in most animals, but they were more robust in both of the combination groups as compared to each agent given alone. All animals in the 0.13 mCi 90Y-hPAM4 IgG + hRS7-SN-38 achieved a tumor-free state within 4 weeks, while other animals continued to have evidence of persistent disease. These studies provide the first evidence that combined radioimmunotherapy and ADC can enhance efficacy at safe doses. (Supported in part by SBIR grant 2R44CA1148 from the NCI.) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5543.
Caspase-, cathepsin-, and PERK-dependent regulation of MDA-7/IL-24-induced cell killing in primary human glioma cells (2008)

Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) is a novel cytokine displaying selective apoptosis-inducing activity in transformed cells without harming normal cells. The present studies focused on defining the mechanism(s) by which a GST-MDA-7 fusion protein inhibits cell survival of primary human glioma cells in vitro. GST-MDA-7 killed glioma cells with diverse genetic characteristics that correlated with inactivation of ERK1/2 and activation of JNK1-3. Activation of JNK1-3 was dependent on protein kinase R-like endoplasmic reticulum kinase (PERK), and GST-MDA-7 lethality was suppressed in PERK-/- cells. JNK1-3 signaling activated BAX, whereas inhibition of JNK1-3, deletion of BAX, or expression of dominant-negative caspase-9 suppressed lethality. GST-MDA-7 also promoted a PERK-, JNK-, and cathepsin B-dependent cleavage of BID; loss of BID function promoted survival. GST-MDA-7 suppressed BAD and BIM phosphorylation and heat shock protein 70 (HSP70) expression. GST-MDA-7 caused PERK-dependent vacuolization of LC3-expressing endosomes whose formation was suppressed by incubation with 3-methyladenine, expression of HSP70 or BiP/GRP78, or knockdown of ATG5 or Beclin-1 expression but not by inhibition of the JNK1-3 pathway. Knockdown of ATG5 or Beclin-1 expression or overexpression of HSP70 reduced GST-MDA-7 lethality. Our data show that GST-MDA-7 induces an endoplasmic reticulum stress response that is causal in the activation of multiple proapoptotic pathways, which converge on the mitochondrion and highlight the complexity of signaling pathways altered by mda-7/IL-24 in glioma cells that ultimately culminate in decreased tumor cell survival.
Abstract LB-266: Generation of antagonistic anti-TIM-3 and anti-LAG-3 monoclonal antibodies for potential novel immunotherapy combinations (2014)

Abstract Among the most promising approaches in the treatment of cancer is the activation of antitumor immunity by blockade of immune checkpoints. These inhibitory immune checkpoints are crucial for maintaining self-tolerance in the normal immune system but can be co-opted in cancer to allow tumor escape from immune surveillance. Therapeutic validation has been provided using antibodies that inhibit the CTLA-4 and PD-1 signaling pathways, which have shown significant clinical activity. Interestingly, blockade of other T-cell inhibitory signaling molecules TIM-3 and LAG-3 has also been shown to be effective in mouse models of cancer. Potential therapeutic molecules that inhibit the negative signaling of TIM-3 or LAG-3 were identified by screening the AnaptysBio Evolvable Library (ABEL) of fully human germline antibodies. The initial ABEL screens used the soluble extra cellular domains (ECD) of either TIM-3 or LAG-3, followed by screening on cell-surface expressed antigens. The resulting panels of human antibodies were matured to high affinity and potency using SHM-XEL™ which uses mammalian cell display of human IgG followed by in vitro somatic hypermutation (SHM). We have explored the activity of these antibodies both as single agents as well as simultaneous blockade of multiple pathways in in vitro cell-based assays. Inhibition of each pathway in isolation demonstrated immune stimulatory activity as evidenced by increased secretion of IL-2 in a mixed lymphocyte reaction or an activated T-cell assay. Combination of an anti LAG-3 or an anti TIM-3 antibody with an anti-PD-1 inhibitory antibody could increase IL-2 secretion over that seen with blockade of a single checkpoint alone. The magnitude of this effect was donor cell dependent. These data are suggestive that combination immunotherapy towards these targets is worthy of clinical evaluation and may lead to increased efficacy. Citation Format: H. Toni Jun, Patricia A. McNeeley, Andrew Lassen, Brandon Hynes, Larry Altobell, Mark Chhoa, Jesus Olvera, Josh MacLaren, Minjee Do, Michael Brown, Jean da Silva Correia, David King. Generation of antagonistic anti-TIM-3 and anti-LAG-3 monoclonal antibodies for potential novel immunotherapy combinations. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-266. doi:10.1158/1538-7445.AM2014-LB-266
The combined effects of antibacterial peptide cecropin A and anti-cancer agents on leukemia cells. (2003)

Anti-microbial cecropins are humoral immune peptides originally found in insects. They possess a particular function of membrane permeabilization on both gram-positive and gram-negative bacteria. Yet, they are not capable of lysing eucaryotic cells. In this experiment, we confirmed that cecropin A (CA) is a special agent able to lyse leukemia cells while exerting little toxic effect on normal lymphocytes, based on the IC50 measurements. The therapeutic index of CA ranged from 6 to 17. In contrast, chemical anti-cancer agents (ACAs) are non-specific drugs capable of damaging both cancer and normal cells. Due to the functional differences between CA and ACAs, the experiments on the combined effects of CA and ACAs were conducted in vitro. Under certain conditions, synergistic effects were found with CA/S-FU and CA/Ara-C combinations. The results suggest the need for further study into the possible application of combining anti-cancer agents with antibacterial peptides for cancer treatment.
Tumor-associated Antigen Arrays for the Serological Diagnosis of Cancer (2006)

The recognition that human tumors stimulate the production of autoantibodies against autologous cellular proteins called tumor-associated antigens (TAAs) has opened the door to the possibility that autoantibodies could be exploited as serological tools for the early diagnosis and management of cancer. Cancer-associated autoantibodies are often driven by intracellular proteins that are mutated, modified, or aberrantly expressed in tumor cells and hence are regarded as immunological reporters that could help uncover molecular events underlying tumorigenesis. Emerging evidence suggests that each type of cancer might trigger unique autoantibody signatures that reflect the nature of the malignant process in the affected organ. The advent of novel genomic, proteomic, and high throughput approaches has accelerated interest in the serum autoantibody repertoire in human cancers for the discovery of candidate TAAs. The use of individual anti-TAA autoantibodies as diagnostic or prognostic tools has been tempered by their low frequency and heterogeneity in most human cancers. However, TAA arrays comprising several antigens significantly increase this frequency and hold great promise for the early detection of cancer, monitoring cancer progression, guiding individualized therapeutic interventions, and identification of novel therapeutic targets. Our recent studies suggest that the implementation of TAA arrays in screening programs for the diagnosis of prostate cancer and other cancers should be preceded by the optimization of their sensitivity and specificity through the careful selection of the most favorable combinations of TAAs.
Optical probing of neuronal circuits with calcium indicators (2000)

An experimental difficulty in unraveling circuits in the mammalian nervous system is the identification of postsynaptic targets of a given neuron. Besides ultrastructural reconstructions, simultaneous recordings from pairs of cells in brain slices have been used to identify connected neurons. We describe in this paper a technique using calcium imaging that allows rapid identification of potential postsynaptic targets. This method consists of stimulating one neuron ("trigger") while imaging a population of cells to detect which other neurons ("followers") are activated by the trigger. By using bulk-loading of calcium indicators in slices of mouse visual cortex, we demonstrate that neurons that display somatic calcium transients time-locked to the spikes of a trigger neuron can be monosynaptically connected to it. This technique could be applied to reconstruct and assay circuits in the central nervous system.
LEW88516 and SNC meteorites (1993)

We report on the isotopic composition of Pb and the concentration of Pb, U, and Th in a sample of LEW88516 (LEW). LEW was a 13-g stone recovered from Antarctica and was classified as a new member of the Shergottite group. This work was undertaken with the hope that LEW might yield new information to elucidate further the origin and evolution of Shergottites and other SNC meteorites. We have previously studied U-Th-Pb in other Shergottites, namely Shergotty, Zagami, EETA79001, and ALHA77005, as well as Nakhla. The results indicate that the initial leads of these Shergottites were well defined, were distinct from each other, and have high Pb-204/Pb-206 (from 0.0652 to 0.0739). These leads evolved in different reservoirs over most of solar system history in a low U-238/Pb-204(micro) is approximately equal to 5 environment. The U-Th-Pb isotopic systems are quite regular, which unambiguously indicates an event of U-Th-Pb fractionation at approximately 200 m.y. The details of the data arrays are complex. The young age is in general agreement with some of the ages obtained by other methods, but precise concordance between the different methods is not established. The new results on LEW are remarkably similar to those of ALHA77005 and support the other observations based on the mineralogy, petrology, and bulk composition. The clear distinction between the Shergottites and Nakhla is confirmed. We consider that the Shergottites and possibly all the SNC's were derived from an impact on the regolith of a differentiated terrestrial type planetary body (Mars?) with a high content of volatiles as compared to the earth.
VistaMail: an integrated multimedia mailing system (1998)

VistaMail, a fully integrated multimedia mailing system, lets users easily create, send, and view audio and video components. The system treats these components as part of a single unified message rather than as additions to the text portion. This article discusses the design of the multimedia mail system and some of the issues involved in implementing it.
Endogenous loading of HLA-A2 molecules with an analog of the influenza virus matrix protein-derived peptide and its inhibition by an exogenous peptide antagonist (1992)

Episomal plasmids (p8901) with minigenes coding for the influenza virus matrix peptide amino acids 57-68 (KGILGFVFTLTV; referred to as M57-68) or coding for a modified peptide were introduced into HLA-A2-positive target cells. The association of these peptides, synthesized in the cytoplasm, with HLA-A2 and the expression of this complex at the cell surface was evaluated with HLA-A2-restricted CTL specific for the influenza virus matrix peptide M57-68. Cells expressing M57-68 were lysed effectively, as were cells expressing a peptide that retained residues 60-64 with seven flanking alanine residues (AAALGFVFAAAA). An exogenously added synthetic analog of peptide M57-68 that inhibited sensitization of targets with synthetic peptide M57-68 also inhibited lysis of cells expressing the minigene coding for the peptide with seven alanine substitutions. These results demonstrate the utility of minigene DNA constructs in creating experimental systems to develop agents to diminish the severity of CTL-mediated tissue damage in autoimmune diseases and graft rejection.
Moutiers (Ille-et-Vilaine). Bourg. Ancienne école publique (1991)

Meuret Jean-Claude. Moutiers (Ille-et-Vilaine). Bourg. Ancienne école publique. In: Archéologie médiévale, tome 21, 1991. p. 389.
In-stent restenosis. (2001)

The decrease in restenosis rates compared with conventional angioplasty, stable angiographic results with a subsequent decreased need for urgent or emergency coronary bypass graft surgery, and reliable treatment of acute or threatened closure resulting from conventional angioplasty have all made stents the treatment of choice for many patients undergoing percutaneous intervention. In-stent restenosis (ISR), however, has become a significant problem. Neointimal hyperplasia with vascular smooth muscle cells is even more exaggerated with stent placement than with conventional angioplasty. In addition, failure to deploy the stent optimally at the time of the initial placement may result in increased restenosis. Symptoms of ISR typically occur within 6 to 9 months following intervention, and range from asymptomatic angiographic narrowing, or even occlusion, to recurrent angina/ischemia or myocardial infarction. Evaluation is by repeat angiography. Treatment with balloon angioplasty is effective for focal in-stent restenotic lesions; for other lesions excimer laser, rotational atherectomy, and directional coronary atherectomy are associated with excellent initial outcome, but long-term outcome of these procedures is unclear. Brachytherapy with both gamma and beta sources has been found to result in improved outcome with less angiographic restenosis and decreased target vessel revascularization. Late thrombosis has been documented in up to 10% of patients treated with vascular gamma brachytherapy, and increased stenosis at the edges of the treated segment is also seen. Prolonged dual antiplatelet therapy and avoidance of a new stent has been shown to reduce late thrombosis in patients treated with vascular brachytherapy.
Optimised proton implantation step for vertical-cavity surface-emitting lasers (1993)

The influence of proton implantation in the distributed Bragg reflectors of vertical-cavity surface-emitting laser structures has been studied via measurement of the photoluminescence for different implantation and annealing conditions. It is shown that by optimal annealing the isolating layer can be positioned close to the active region with no detectable deterioration of photoluminescence.
La Guma, Alex (2016)

Abstract Born in Cape Town, Alex la Guma (1925–85) directed his fiction, journalism, politics, and art toward South Africa's liberation. A socialist who supported the nationalism of the African National Congress, he espoused the socialist realism canon. In practice, his journalism and radio plays are examples of satire, while his novella A Walk in the Night and the novels that followed display a range of intriguing, contradictory influences that include Jack London, Charles Dickens, the orientalism of Walter Scott, and John Steinbeck. His last three works, which include travel writing, display a tension between realism and modernism in both narrative and characterization. This is particularly evident in A Soviet Journey and Time of the Butcherbird , in which Hemingway's fiction is both vital and a source of irony. La Guma died in Cuba.
Self-Assembly of 2,8,14,20-Tetraisobutyl-5,11,17,23-tetrahydroxyresorc[4]arene (1999)

We report herein the observation of a hexameric structure of a hydroxyresorc[4]arene in the solid state, enclosing a large interior space. This artificial molecular container is stabilized only by hydrogen bonds. The tendency to form aggregates in solution is demonstrated mainly by means of ESI-MS methods.
Pot Experiments on the Chemical Treatment of Soils Infected with the Potato and Oat Strains of Heterodera schachtii (1938)

It was observed in laboratory experiments that the lethal action of dilute solutions of calcium cyanamide on the larvae of Heterodera schachtii was more rapid when these solutions were rendered slightly acid. This might be due to the rate of decomposition of calcium cyanamide in aqueous solutions of varying þH. The changes which cyanamide undergoes in acid and alkaline media have been described by Crowther &amp; Richardson (1932). Solutions of commercial calcium cyanamide are moderately alkaline because of their lime content, and in this alkalinity any free cyanamide which is formed tends to polymerise to dicyanodiamide. Experiments with solutions of dicyanodiamide showed that this substance has very little toxic action on H. schachtii larvae. In acid solution, on the other hand, cyanamide is hydrolysed to urea. This substance becomes toxic when it decomposes to ammonia, but in the slightly acid solutions used the change would be a slow process. It is probable, therefore, that the degree of toxicity of calcium cyanamide solutions would be greatest where the cyanamide radicle could be retained unchanged for the longest period.
Kinetics and mechanisms of reduction of metmyoglobins. Importance of the geometry change at the heme iron site upon reduction (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTKinetics and mechanisms of reduction of metmyoglobins. Importance of the geometry change at the heme iron site upon reductionKeiichi TsukaharaCite this: J. Am. Chem. Soc. 1989, 111, 6, 2040–2044Publication Date (Print):March 1, 1989Publication History Published online1 May 2002Published inissue 1 March 1989https://pubs.acs.org/doi/10.1021/ja00188a014https://doi.org/10.1021/ja00188a014research-articleACS PublicationsRequest reuse permissionsArticle Views105Altmetric-Citations13LEARN 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 (1)»Supporting Information Supporting Information Get e-Alerts
Expansion of the enzymatic repertoire of the CAZy database to integrate auxiliary redox enzymes (2013)

The new class introduced in the CAZy database extends the traditional CAZy families, and provides a better coverage of the full extent of the lignocellulose breakdown machinery.
Spectrum of Pulmonary Toxicity Associated with the Use of Interferon Therapy for Hepatitis C: Case Report and Review of the Literature (2004)

Hepatitis C is one of the leading causes of liver disease in the United States, and current recommendations for its treatment include the use of interferon (IFN). Pulmonary side effects, although uncommon, have been reported in association with the use of IFN. We report a case of interstitial granulomatous pneumonitis that occurred after therapy with IFN and ribavirin, and we review the literature concerning this entity and other forms of IFN-associated pulmonary toxicity in patients with hepatitis C. The purpose of the present study is to increase awareness of the unusually wide spectrum of pulmonary toxicities associated with the use of IFN and ribavirin, with the anticipation that IFN will be used more frequently in the future for the treatment of hepatitis C.
Palladium-Catalyzed C−N(sp2) Bond Formation:  N-Arylation of Aromatic and Unsaturated Nitrogen and the Reductive Elimination Chemistry of Palladium Azolyl and Methyleneamido Complexes (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTPalladium-Catalyzed C−N(sp2) Bond Formation: N-Arylation of Aromatic and Unsaturated Nitrogen and the Reductive Elimination Chemistry of Palladium Azolyl and Methyleneamido ComplexesGrace Mann, John F. Hartwig, Michael S. Driver, and Carolina Fernández-RivasView Author Information Department of Chemistry, Yale University P.O. Box 208107, New Haven, Connecticut 06520-8107 Cite this: J. Am. Chem. Soc. 1998, 120, 4, 827–828Publication Date (Web):February 4, 1998Publication History Received8 October 1997Published online4 February 1998Published inissue 1 February 1998https://pubs.acs.org/doi/10.1021/ja973524ghttps://doi.org/10.1021/ja973524grapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views8696Altmetric-Citations308LEARN 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:Aromatic compounds,Arylation,Nitrogen,Palladium,Reductive elimination Get e-Alerts