gebhart/patrepeval huggingface dataset:
AGEN1181, a clinical stage Fc-engineered anti-CTLA-4 antibody with improved therapeutic potential for the treatment of patients with advanced malignancies. (2020)

TPS3157 Background: AGEN1181 is a novel Fc-optimized anti-CTLA4 antibody, currently being evaluated in an ongoing multi-center, open-label, phase 1 study in all advanced solid tumors as mono-therapy and combination with anti-PD-1 antibody, AGEN2034 (NCT03860272). AGEN1181 is Fc-engineered to harness a novel mechanism for enhanced FcγR-dependent functionality relative to first-generation CTLA-4 antibodies. In pre-clinical models, AGEN1181 enhances T cell priming, depletion of intratumoral regulatory T cells (Treg) and improved memory formation compared to first-generation anti-CTLA-4 antibodies. Most notably, AGEN1181 demonstrates improved binding to FcyRIIIA and superior T cell responsiveness in populations that only express the low affinity FcγRIIIA receptor relative to first-generation IgG1 CTLA-4 antibodies. The combination of AGEN1181 and AGEN2034 further enhances T cell activation and effector function. Methods: This phase 1 study is an open-label, multi-center dose-escalation designed to evaluate the safety, tolerability, dose limiting toxicity (DLT) PK, and pharmacodynamic profiles of patients with refractory advanced solid tumors who did not receive an anti-CTLA4 previously. The study is being conducted in 3 arms; with patients assigned using a standard 3+3 dose escalation design in the mono-therapy arms with AGEN1181 and an accelerated design in the combination with AGEN2034 arm. AGEN1181 is administered as IV infusion as mono-therapy on Day 1 of every 3 weeks (0.1,0.3,1,2,4 mg/kg), every 6-weeks (1,2,4 mg/kg) in parallel cohorts and every 6-weeks (0.1,0.3,1,2,4 mg/kg) in combination with AGEN2034 (3mg/kg Q2Weeks) until disease progression or unacceptable toxicity (maximum 2 years). All 3 Arms are open and enrolling patients. The study is expected to enroll approximately 80 evaluable patients with solid tumors. Dose reductions are not allowed in the event of AGEN1181-related toxicities. Currently 3 cohorts have been completed, first cohort in the combination arm and the fourth cohort in the monotherapy arm are enrolling. Preclinical and clinical assessment of AGEN1181 supports continued development as a potential therapy for refractory or relapsed advanced solid tumors. Clinical trial information: NCT03860272 .
A programmatic introduction to Neo4j (2012)

In this workshop we provide a hands-on introduction to the popular open source graph database Neo4j [1] through fixing a series of increasingly sophisticated, but broken, test cases each of which highlights an important graph modeling or API affordance.
ChemInform Abstract: Synthesis of 3‐Hydroxy‐2‐methylene Carbonyl Compounds. Effects of Catalyst and Substrate on Reaction Rate. (1989)

Abstract The aldehydes (I) are coupled with methyl vinyl ketones or methyl acrylate (II) in the presence of 3‐hydroxyquinuclidine, yielding the 3‐hydroxy‐2‐methylene ketones (IIIa) ‐ (IIIc) or the related carboxylate (IIId).
Quantifying Surface Deformation With the Edge of Light-Enhanced Visual Inspection (2008)

Edge of light (EOL) is a rapid enhanced visual inspection technique developed by the Institute for Aerospace Research, National Research Council Canada. One application of interest is the inspection of aircraft lap joints for pillowing deformation caused by hidden corrosion. The EOL technique provides an intuitive result, which is a representation of surface topography. However, a quantitative interpretation of the inspection results is still a challenge. In this paper, the quantification of surface deformation is investigated by using a laser-displacement sensor as a calibration tool. A procedure that implements the reconstruction of the deformed surface from EOL scanning is proposed. Experimental results obtained from a pillowing simulator and a service-retired aircraft lap joint are presented in this paper to demonstrate the effectiveness of the proposed approach.
Fast Earth Mover's Distance Computation for Catadioptric Image Sequences (2016)

International audience
A Stochastic Model for the HIV/AIDS Dynamic Evolution (2007)

This paper analyses the HIV/AIDS dynamic evolution as defined by CD4 levels, from a macroscopic point of view, by means of homogeneous semi-Markov stochastic processes. A large number of results have been obtained including the following conditional probabilities: an infected patient will be in state<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>j</mml:mi></mml:math>after a time<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>t</mml:mi></mml:math>given that she/he entered at time 0 (starting time) in state<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>i</mml:mi></mml:math>; that she/he will survive up to a time<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>t</mml:mi></mml:math>, given the starting state; that she/he will continue to remain in the starting state up to time<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>t</mml:mi></mml:math>; that she/he reach stage<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>j</mml:mi></mml:math>of the disease in the next transition, if the previous state was<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>i</mml:mi></mml:math>and no state change occurred up to time<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>t</mml:mi></mml:math>. The immunological states considered are based on CD4 counts and our data refer to patients selected from a series of 766 HIV-positive intravenous drug users.
A 63-year-old female patient with fever, myalgias and interstitial lung disease (2020)

Background!#!We sought to determine structure and changes in organisation and bed capacities of certified German chest pain units (CPU) in response to the emergency plan set-up as a response to the SARS-CoV-2 pandemic.!##!Methods and results!#!The study was conducted in the form of a standardised telephone interview survey in certified German CPUs. Analyses comprised the overall setting of the CPU, bed capacities, possibilities for ventilation, possible changes in organisation and resources, chest pain patient admittance, overall availability of CPUs and bail-out strategies. The response rate was 91%. Nationwide, CPU bed capacities decreased by 3% in the early phase of COVID-19 pandemic response, exhibiting differences within and between the federal states. Pre-pandemic and pandemic bed capacities stayed below 1 CPU bed per 50,000 inhabitants. 97% of CPUs were affected by internal reorganisation pandemic plans at variable extent. While we observed a decrease of CPU beds within an emergency room (ER) set-up and on intermediate care units (ICU), beds in units being separated from ER and ICU were even increased in numbers.!##!Conclusions!#!Certified German CPUs are able to maintain adequate coverage for chest pain patients in COVID-19 pandemic despite structural changes. However, at this time, it appears important to add operating procedures during pandemic outbreaks to the certification criteria of forthcoming guidelines either at the individual CPU level or more centrally steered by the German Cardiac Society or the European Society of Cardiology.
Tracking Chemical Changes in a Live Cell: Biomedical Applications of SR‐FTIR Spectromicroscopy (2003)

Synchrotron radiation‐based Fourier transform infrared (SR‐FTIR) spectromicroscopy is a newly emerging bioanalytical and imaging tool. This unique technique provides mid‒infrared (IR) spectra, hence chemical information, with high signal‐to‐noise at spatial resolutions as fine as 3 to 10 microns. Thus it enables researchers to locate, identify, and track specific chemical events within an individual living mammalian cell. Mid‐IR photons are too low in energy (0.05−0.5 eV) to either break bonds or to cause ionization. In this review, we show that the synchrotron IR beam has no detectable effects on the short‐ and long‐term viability, reproductive integrity, cell‐cycle progression, and mitochondrial metabolism in living human cells, and produces only minimal sample heating (&lt;0.5°C). We will then present several examples demonstrating the application potentials of SR‐FTIR spectromicroscopy in biomedical research. These will include monitoring living cells progressing through the cell cycle, including death, and cells reacting to dilute concentrations of toxins.
Liability in software engineering (2010)

LISE is a multidisciplinary project involving lawyers and computer scientists with the aim to put forward a set of methods and tools to (1) define software liability in a precise and unambiguous way and (2) establish such liability in case of incident. This paper provides an overview of the overall approach taken in the project based on a case study. The case study illustrates a situation where, in order to reduce legal uncertainties, the parties to a contract wish to include in the agreement specific clauses to define as precisely as possible the share of liabilities between them for the main types of failures of the system.
The proportion of cores with high‐grade prostatic intraepithelial neoplasia on extended‐pattern needle biopsy is significantly associated with prostate cancer on site‐directed repeat biopsy (2007)

Isolated HGPIN on extended biopsy conferred a 31% risk of unsampled prostate cancer. The proportion of cores with HGPIN on initial biopsy was significantly associated with the risk of cancer. The same was not true for age, race, prostate-specific antigen level, or the findings on digital rectal examination. The significant association between the proportion of cores with HGPIN and the risk of cancer suggests that patients with unifocal HGPIN on extended biopsy be managed expectantly, whereas those with multifocal HGPIN be re-biopsied.
Figure S3 from <i>RASA1</i> and <i>NF1</i> are Preferentially Co-Mutated and Define A Distinct Genetic Subset of Smoking-Associated Non–Small Cell Lung Carcinomas Sensitive to MEK Inhibition (2023)

&lt;p&gt;Survival analysis in lung cancer patients with RASA1 or NF1 mutation or both.&lt;/p&gt;
HIERARCHICAL DISCRETIZED PURSUIT (1991)

In this paper we present a new absorbing multiaction learning automaton which we prove to be epsilon-optimal. The proposed automaton (named HDPNRI) is a hierarchical discretized nonlinear one which utilizes a new pursuit learning algorithm. The HDPNRI automaton has the best performance (speed of convergence, CPU time and accuracy) among all the absorbing learning automata reported in the literature. Extensive simulation results indicate the superiority of HDPNRI's performance.
Polymorphic Variation in Susceptibility and Metabolism of Triclosan-Resistant Mutants of Escherichia coli and Klebsiella pneumoniae Clinical Strains Obtained after Exposure to Biocides and Antibiotics (2015)

Exposure to biocides may result in cross-resistance to other antimicrobials. Changes in biocide and antibiotic susceptibilities, metabolism, and fitness costs were studied here in biocide-selected Escherichia coli and Klebsiella pneumoniae mutants. E. coli and K. pneumoniae mutants with various degrees of triclosan susceptibility were obtained after exposure to triclosan (TRI), benzalkonium chloride (BKC), chlorhexidine (CHX) or sodium hypochlorite (SHC), and ampicillin or ciprofloxacin. Alterations in antimicrobial susceptibility and metabolism in mutants were tested using Phenotype MicroArrays. The expression of AcrAB pump and global regulators (SoxR, MarA, and RamA) was measured by quantitative reverse transcription-PCR (qRT-PCR), and the central part of the fabI gene was sequenced. The fitness costs of resistance were assessed by a comparison of relative growth rates. Triclosan-resistant (TRI(r)) and triclosan-hypersusceptible (TRI(hs)) mutants of E. coli and K. pneumoniae were obtained after selection with biocides and/or antibiotics. E. coli TRI(r) mutants, including those with mutations in the fabI gene or in the expression of acrB, acrF, and marA, exhibited changes in susceptibility to TRI, CHX, and antibiotics. TRI(r) mutants for which the TRI MIC was high presented improved metabolism of carboxylic acids, amino acids, and carbohydrates. In TRI(r) mutants, resistance to one antimicrobial provoked hypersusceptibility to another one(s). TRI(r) mutants had fitness costs, particularly marA-overexpressing (E. coli) or ramA-overexpressing (K. pneumoniae) mutants. TRI, BKC, and CIP exposure frequently yielded TRI(r) mutants exhibiting alterations in AraC-like global regulators (MarA, SoxR, and RamA), AcrAB-TolC, and/or FabI, and influencing antimicrobial susceptibility, fitness, and metabolism. These various phenotypes suggest a trade-off of different selective processes shaping the evolution toward antibiotic/biocide resistance and influencing other adaptive traits.
Bovine Colostrum Derived Antibodies Against SARS-CoV-2 Show Great Potential to Serve as a Prophylactic Agent (2021)

Abstract Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) until now imposes a serious burden to health systems globally. Despite worldwide vaccination, social distancing and wearing masks, the spread of the virus is still ongoing. One of the mechanisms how neutralizing antibodies (NAbs) block virus entry into cells encompasses interaction inhibition between the cell surface receptor angiotensin-converting enzyme 2 (ACE2) and the spike (S) protein of SARS-CoV-2. SARS-CoV-2 specific NAb development can be induced in the blood of cattle. Pregnant cows produce NAbs upon immunization, and antibodies move into the colostrum just before calving. Here we immunized cows with SARS-CoV-2 S1 receptor binding domain (RBD) protein in proper adjuvant solutions, followed by one boost with SARS-CoV-2 trimeric S protein, and purified immunoglobulins from colostrum. We demonstrate that this preparation indeed blocks interaction between the trimeric S protein and ACE2 in different in vitro assays. Moreover, we describe the formulation of purified immunoglobulin preparation into a nasal spray. When administered to human subjects, the formulation persists on the nasal mucosa for at least 4 hours as determined by a clinical study. Therefore, we are presenting a solution that shows great potential to serve as a prophylactic agent against SARS-CoV-2 infection as an additional measure to vaccination and wearing masks. Moreover, our technology allows for a rapid and versatile adaption for preparing prophylactic treatments against other diseases by using the defined characteristics of antibody movement into the colostrum. Significance SARS-CoV-2 infections continue to be a high-risk factor for mankind. Antibodies with the potential to neutralize the virus and thus its entry into the host cell have been shown to impose a potent measure against the infection. Human derived neutralizing antibodies are therapeutics and thus fall under the legislation of drugs. However, an alternative could be the purification of efficient neutralizing antibodies from other species. Here, we present immunization of pregnant cows with spike protein of SARS-CoV-2 which results in high quantities of colostrum immunoglobulins that can be easily harvested and safely purified within a remarkably short time. The colostrum immunoglobulin preparation has a great potential to serve in formulations that can be used as prophylactic agent against SARS-CoV-2 infection.
Effect of reticuloendothelial system stimulation on resistance to rous sarcoma virus infection in chicks (1968)

Abstract By using a non‐toxic reticuloendothelial system stimulant, lipid‐Restim, derived from shark livers, we were able to demonstrate the following effects on growing Rous sarcoma tumors in young chicks. Prechallenge Restim treatment: Significant reduction of the percentage of chicks with tumors and prolongation of the latent period resulted from combined administration of Restim and specific antiserum . Postchallenge Restim treatment: The mortality data indicated that there was a significant increase in survival time and survival rate. Complete regressions The term “regression” is used in this paper to mean complete macroscopical disappearance of the primary tumor at the site of inoculation of the virus. occurred in a significant number of the Restim‐treated chicks compared to the controls. Possible explanations of these findings are discussed.
Some Items of Interest to Process R&D Chemists and Engineers (2022)

ADVERTISEMENT RETURN TO ISSUEHighlights from the ...Highlights from the LiteratureNEXTSome Items of Interest to Process R&D Chemists and EngineersSylvain GuizzettiSylvain GuizzettiNovAlix, Building A: Chemistry, Bioparc, Bld. Sébastien Brant BP 30170, F-67405 Illkirch Cedex, FranceMore by Sylvain Guizzettihttps://orcid.org/0000-0003-4656-2431, James A. SchwindemanJames A. SchwindemanK D Pharma Group, Miami Site, 14193 SW 119th Avenue, Miami, Florida 33186, United StatesMore by James A. Schwindeman, David S. B. DanielsDavid S. B. DanielsPfizer Chemical Research & Development, Discovery Park House, IPC 533, Sandwich, Kent CT13 9NJ, U.K.More by David S. B. Danielshttps://orcid.org/0000-0002-9092-1377, James J. DouglasJames J. DouglasEarly Chemical Development, Pharmaceutical Sciences, R&D, AstraZeneca, Macclesfield SK10 2NA, U.K.More by James J. Douglashttps://orcid.org/0000-0002-9681-0459, Alex KosanovichAlex KosanovichDow, Texas Operations, 230 Abner Jackson Parkway, ECB/4B137, Lake Jackson, Texas 77566, United StatesMore by Alex Kosanovich, Wenyi ZhaoWenyi ZhaoJacobus Pharmaceutical Co. Inc., Princeton, New Jersey 08540, United StatesMore by Wenyi Zhao, Christopher B. KellyChristopher B. KellyJanssen Research & Development, 1400 McKean Road, Spring House, Pennsylvania 19477, United StatesMore by Christopher B. Kellyhttps://orcid.org/0000-0002-5530-8606, and John Knight*John KnightJKonsult Ltd, Meadow View, Cross Keys, Hereford HR1 3NT, U.K.*Email: [email protected]More by John KnightCite this: Org. Process Res. Dev. 2022, 26, 4, 1019–1028Publication Date (Web):April 5, 2022Publication History Published online5 April 2022Published inissue 15 April 2022https://pubs.acs.org/doi/10.1021/acs.oprd.2c00085https://doi.org/10.1021/acs.oprd.2c00085editorialACS PublicationsCopyright © Published 2022 by American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views4743Altmetric-Citations-LEARN 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 PDF (3 MB) Get e-AlertscloseSUBJECTS:Amides,Aromatic compounds,Catalysts,Chemical reactions,Hydrocarbons Get e-Alerts
Immunological Analysis of Nodavirus Capsid Displaying the Domain III of Japanese Encephalitis Virus Envelope Protein (2021)

Japanese encephalitis virus (JEV) is the pathogen that causes Japanese encephalitis (JE) in humans and horses. Lethality of the virus was reported to be between 20–30%, of which, 30–50% of the JE survivors develop neurological and psychiatric sequelae. Attributed to the low effectiveness of current therapeutic approaches against JEV, vaccination remains the only effective approach to prevent the viral infection. Currently, live-attenuated and chimeric-live vaccines are widely used worldwide but these vaccines pose a risk of virulence restoration. Therefore, continuing development of JE vaccines with higher safety profiles and better protective efficacies is urgently needed. In this study, the Macrobrachium rosenbergii nodavirus (MrNV) capsid protein (CP) fused with the domain III of JEV envelope protein (JEV-DIII) was produced in Escherichia coli. The fusion protein (MrNV-CPJEV-DIII) assembled into virus-like particles (VLPs) with a diameter of approximately 18 nm. The BALB/c mice injected with the VLPs alone or in the presence of alum successfully elicited the production of anti-JEV-DIII antibody, with titers significantly higher than that in mice immunized with IMOJEV, a commercially available vaccine. Immunophenotyping showed that the MrNV-CPJEV-DIII supplemented with alum triggered proliferation of cytotoxic T-lymphocytes, macrophages, and natural killer (NK) cells. Additionally, cytokine profiles of the immunized mice revealed activities of cytotoxic T-lymphocytes, macrophages, and NK cells, indicating the activation of adaptive cellular and innate immune responses mediated by MrNV-CPJEV-DIII VLPs. Induction of innate, humoral, and cellular immune responses by the MrNV-CPJEV-DIII VLPs suggest that the chimeric protein is a promising JEV vaccine candidate.
Magnetic resonance angiography for the primary diagnosis of pulmonary embolism: A review from the international workshop for pulmonary functional imaging (2018)

Pulmonary contrast enhanced magnetic resonance angiography (CE-MRA) is useful for the primary diagnosis of pulmonary embolism (PE). Many sites have chosen not to use CE-MRA as a first line of diagnostic tool for PE because of the speed and higher efficacy of computerized tomographic angiography (CTA). In this review, we discuss the strengths and weaknesses of CE-MRA and the appropriate imaging scenarios for the primary diagnosis of PE derived from our unique multi-institutional experience in this area. The optimal patient for this test has a low to intermediate suspicion for PE based on clinical decision rules. Patients in extremis are not candidates for this test. Younger women (< 35 years of age) and patients with iodinated contrast allergies are best served by using this modality We discuss the history of the use of this test, recent technical innovations, artifacts, direct and indirect findings for PE, ancillary findings, and the effectiveness (patient outcomes) of CE-MRA for the exclusion of PE. Current outcomes data shows that CE-MRA and NM V/Q scans are effective alternative tests to CTA for the primary diagnosis of PE.