gebhart/patrepeval huggingface dataset:
Abstract B022: Functional bifurcation in T cells expressing chimeric antigen receptors (2016)

Abstract Adoptive transfer of T cells engineered to express chimeric antigen receptors (CARs) can induce durable regressions in cancer patients, particularly in the treatment of B-cell malignancies. The production and expansion of CAR-T cells relies on in vitro T-cell stimulation and more work is needed to explore the phenotypic changes that occur in this process to elucidate features that are predictive of anti-tumor functionality. Here, we present a systematic study of T cells expressing a second-generation, anti-CD19 CAR and use flow cytometry to interrogate the dynamic phenotypic and functional changes exhibited by CAR-T cells undergoing varied antigen stimulation courses. By tracking CAR–T-cell viability, proliferation, cytokine production, lytic abilities, and expression of various T-cell activation markers and inhibitory receptors across time, we find that CAR-T cells consistently bifurcate into two distinct subpopulations with dramatically different functional capacities and surface marker expression profiles. Furthermore, the proportion of CAR-T cells that demonstrate the superior functions is dependent on the particular degree of antigen stimulation and the composition of the T cell population (CD4 vs CD8, T-cell memory compartment breakdown, % transduced). Altogether, the systematic characterization methods and results reported here can guide future efforts to improve CAR–T-cell therapies. Citation Format: ZeNan L. Chang, Pamela A. Silver, Yvonne Y. Chen. Functional bifurcation in T cells expressing chimeric antigen receptors. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B022.
Homozygous deletions of the p15 (MTS2) and p16 (CDKN2/MTS1) genes in adult T-cell leukemia (1995)

Adult T-cell leukemia (ATL) is associated with prior infection with human T-cell leukemia virus type I (HTLV-I). Twenty to 40 years often elapse from viral infection to overt ATL, suggesting that other genetic events must occur to produce frank leukemia. The p15 (MTS2) and p16 (CDKN2/MTS1) genes located on chromosome 9p have been implicated as candidate tumor-suppressor genes in several types of tumors. We examined for alterations of these genes in ATL using Southern blot and polymerase chain reaction-single-strand conformation polymorphism analyses. Both p15 and p16 genes were homozygously deleted in 4 of 23 acute/lymphomatous ATL (17%). An additional 3 (13%) and 4 (17%) acute/lymphomatous samples had hemizygous deletions in at least one exon of p15 and p16, respectively. One of 14 chronic ATL samples had a homozygously deleted p16 gene and another had a hemizygous deletion of p16. Neither homozygous nor hemizygous deletions of the p15 gene were found in chronic ATL. In total, 10 of 37 (27%) ATL samples had loss of the p15 and/or p16 genes. No point mutations of the p15 and p16 genes were found. The ATL patient with a homozygously deleted p16 in the chronic phase rapidly progressed to acute ATL and died within 6 months of the initial diagnosis. One instructive patient had no detectable deletion of the p15 and p16 genes during the chronic phase of ATL but had a homozygous deletions of both genes when she progressed to acute ATL. Our results suggest an association of p15/p16 deletions with development of acute ATL.
A Conserved Virulence Plasmidic Region Contributes to the Virulence of the Multiresistant Escherichia coli Meningitis Strain S286 Belonging to Phylogenetic Group C (2013)

Recent isolation of the non-K1 Escherichia coli neonatal meningitis strain S286, belonging to phylogroup C, which is closely related to major group B1, and producing an extended-spectrum beta-lactamase, encouraged us to seek the genetic determinants responsible for its virulence. We show that S286 belongs to the sequence O type ST23O78 and harbors 4 large plasmids. The largest one, pS286colV (~120 kb), not related to resistance, contains genes characteristic of a Conserved Virulence Plasmidic (CVP) region initially identified in B2 extra-intestinal avian pathogenic E. coli (APEC) strains and in the B2 neonatal meningitis E. coli strain S88. The sequence of this CVP region has a strong homology (98%) with that of the recently sequenced plasmid pChi7122-1 of the O78 APEC strain Chi7122. A CVP plasmid-cured variant of S286 was less virulent than the wild type strain in a neonatal rat sepsis model with a significant lower level of bacteremia at 24 h (4.1 ± 1.41 versus 2.60 ± 0.16 log CFU/ml, p = 0.001) and mortality. However, the mortality in the model of adult mice was comparable between wild type and variant indicating that pS286colV is not sufficient by itself to fully explain the virulence of S286. Gene expression analysis of pS286colV in iron depleted environment was very close to that of pS88, suggesting that genes of CVP region may be expressed similarly in two very different genetic backgrounds (group C versus group B2). Screening a collection of 178 human A/B1 extraintestinal pathogenic E. coli (ExPEC) strains revealed that the CVP region is highly prevalent (23%) and MLST analysis indicated that these CVP positive strains belong to several clusters and mostly to phylogroup C. The virulence of S286 is explained in part by the presence of CVP region and this region has spread in different clusters of human A/B1 ExPEC, especially in group C.
A True Jak of All Trades (2004)

Discovered roughly 10 yr ago, Jak2 tyrosine kinase has emerged as a critical molecule in mammalian development, physiology, and disease. Here, we review the early history of Jak2 and its role in health and disease. We will also review its critical role in mediating cytokine-dependent signal transduction. Additionally, more recent work demonstrating the importance of Jak2 in G protein-coupled receptor and tyrosine kinase growth factor receptor signal transduction will be discussed. The cellular and biochemical mechanisms by which Jak2 tyrosine kinase is activated and regulated within the cell also will be reviewed. Finally, structure‐function and pharmacological-based studies that identified structural motifs and amino acids within Jak2 that are critical for its function will be examined. By reviewing the biology of Jak2 tyrosine kinase at the molecular, cellular, and physiological levels, we hope to advance the understanding of how a single gene can have such a profound impact on development, physiology, and disease. Index Entries: Jak2; tyrosine kinase; signal transduction; gene transcription; disease.
Visual web mining for website evaluation (2010)

In this paper we present an interactive system named Website Exploration Tool (WET) that aims at supporting the evaluation of websites through the exploration of web data. Our prototype offers a set of coordinated visual abstractions in the form of interactive graphs and trees to analyse data graphs within meaningful contexts such as the website structure and users' flow. Apart from classical approaches, our highly interactive system introduces a wide variety of information visualisation techniques that provide visual cues to assist in the process of digging into usage data. Among them, we present a new hierarchical approach for characterising users' flow which simplifies the intricate graphs generated by real users browsing, and a technique for extracting contextual subgraphs simplifying the task of visualising very large websites. The interface of the system has been evaluated with expert analysts that validated the usefulness of the tool for analysing a wide variety of websites.
Cooperative Disengagement of Fas and Intercellular Adhesion Molecule-1 Function in Neoplastic Cells Confers Enhanced Colonization Efficiency (2005)

Understanding the mechanisms of tumor progression is crucial toward the development of therapeutic interventions. Although the loss of sensitivity to cell death is a hallmark of neoplastic progression, it is likely one of several essential features that underlie a malignantly proficient or aggressive tumorigenic phenotype. Here, we identified intercellular adhesion molecule-1 (ICAM-1) as a molecule with expression coordinately regulated with Fas and inversely correlated with malignant phenotype between matched pairs of differentially aggressive malignant subpopulations in three mouse models. To determine whether coordinate expression of Fas and ICAM-1 regulated malignant behavior, tumor sublines were produced that expressed either lower levels of both Fas and ICAM-1, lower levels of Fas, or lower levels of ICAM-1 and then assessed for metastatic lung tumor growth. Tumor sublines rendered both Fas incompetent and ICAM-1 incompetent displayed significantly higher numbers of tumor nodules compared with tumor sublines separately expressing low levels of Fas or ICAM-1. However, all tumor sublines regardless of their Fas and ICAM-1 levels comparably infiltrated the lung, suggesting that Fas- and ICAM-1-based interactions ultimately influenced lung colonization efficiency. Overall, these data suggested that both Fas and ICAM-1 pathways cooperated to regulate tumor progression and that the coordinate down-regulation of Fas and ICAM-1 intensified malignant progression at the level of colonization. Thus, a Fas(lo)ICAM-1(lo) phenotype may be characteristic of at least certain advancing, immune-resistant neoplastic subpopulations.
SERS nanotags for folate receptor α detection at the single cell level: discrimination of overexpressing cells and potential for live cell applications (2022)

Folate receptor α (FRα) is a high affinity folate membrane receptor that is overexpressed in a wide variety of cancers. Detecting the overexpression of this receptor is important for cancer cells identification and to potentially guide the choice of treatment since several FRα-targeted drugs are currently in clinical trials. In this work, we built SERS nanotags based on core@shell Au@Ag nanoparticles labelled with resonant Raman-reporter and functionalised with a thiolated PEG linker bearing folic acid at the chain end. Using SERS mapping on single cells, we showed that the nanotags (FR-nanotags) could specifically target FRα on overexpressing HeLa cells and could measure the gradual blocking of FRα by free folic acid introduced in the media along the nanotags. With a control nanotag, we showed that the SERS response was 10-fold higher on HeLa cells when folic acid is present on the PEG linker compared to PEG chains without folic acid. Non-specific binding of the FR-nanotags was demonstrated to be low and mainly caused by the folic acid molecule at the PEG chain end. When comparing cancer cells with different expression levels of FRα, we obtained 4-fold higher SERS response on overexpressing HeLa cells compared to non-overexpressing A549 cells, allowing the discrimination of both cell lines with a high contrast. Owing to the biocompatibility of the developed nanotags, we demonstrated that measurements of FRα on live HeLa cells were also possible and gave similar results to measurements on fixed cells, indicating the versatility of the developed nanotags for detecting FRα under various experimental conditions.
Analysis of Tumor-Infiltrating Lymphocytes from Helicobacter pylori Positive and Negative Gastric Cancer Patients (2004)

s for the 19th Annual Scientific Meeting of the International Society for Biological Therapy of Cancer, San Francisco, California, November 4-7, 2004: Other
Role of 3D Volumetric and Perfusion Imaging for Detecting Early Changes in Pancreatic Adenocarcinoma (2021)

TIDC and 3D volumetric analysis can play a significant role in defining the response of the tumor to treatment and identifying early-stage aggressiveness.
Cytosolic phospholipase A2-p11 interaction controls arachidonic acid release as a function of epithelial cell confluence (2004)

Madin-Darby canine kidney type II cells were shown to release low amounts of AA (arachidonic acid) and prostaglandin E2 in response to various stimuli when analysed after cell confluence. In contrast, non-confluent Madin-Darby canine kidney type II cells released much higher amounts of AA and prostaglandin E2. In both stationary and non-confluent cells, AA was released by type IV cPLA2 (cytosolic phospholipase A2), as shown by the use of specific inhibitors and by analysis of the profile of fatty acids released. This confluence-dependent cPLA2 activation was not due to a difference in expression, or in phosphorylation of the enzyme, or in the amount of its substrate. To find out the mechanism by which cPLA2 activation may be regulated as a function of cell confluence, immunofluorescence and co-immunoprecipitation experiments were performed using cPLA2, p11, a natural inhibitor of the enzyme, and annexin II, the natural ligand of p11. These three proteins were expressed at a constant level, regardless of the cell confluence. In contrast, whereas annexin II and cPLA2 interacted at a constant rate, p11 and cPLA2 interacted more strongly in stationary cells, thus indicating that cPLA2 activation is regulated by its accessibility to p11, independent of their expression level. Our results indicate that, in epithelial cells, the cell confluence, i.e. the establishment of cell-cell contacts, rather than cell proliferation directly controls cPLA2 activation by changing the stoichiometry of p11/cPLA2 interaction.
Photonic microwave-to-digital conversion (2013)

In this tutorial, photonic microwave-to-digital conversion architectures and system design issues will be discussed taking full advantage of recent photonic, electronic and signal processing technologies.
PLC Cybersecurity Test Platform Establishment and Cyberattack Practice (2023)

Programming logic controllers (PLCs) are vital components for conveyors in production lines, and the sensors and actuators controlled underneath the PLCs represent critical points in the manufacturing process. Attacks targeting the exploitation of PLC vulnerabilities have been on the rise recently. In this study, a PLC test platform aims to analyze the vulnerabilities of a typical industrial setup and perform cyberattack exercises to review the system cybersecurity challenges. The PLC test platform is a sorting machine consisting of an automatic conveyor belt, two Mitsubishi FX5U-32M PLCs, and accessories for material sorting, and Modbus is the selected protocol for data communication. The O.S. on the attacker is Kali ver. 2022.3, runs Nmap and Metasploit to exploit the target Modbus registers. On the other hand, the target host runs the O.S., Ubuntu 22.04 in the cyberattack exercises. The selected attack method for this study is packet reply which can halt operations sending custom data packets to the PLC. In summary, this study provides a basic step-by-step offensive strategy targeting register modification, and the testbed represents a typical industrial environment and its vulnerabilities against cyberattacks with common open-source tools.
Tight Weyl-Heisenberg frames in l/sup 2/(Z) (1998)

Tight Weyl-Heisenberg frames in l/sup 2/(Z) are the tool for short-time Fourier analysis in discrete time. They are closely related to paraunitary modulated filter banks and are studied here using techniques of the filter bank theory. Good resolution of short-time Fourier analysis in the joint time-frequency plane is not attainable unless some redundancy is introduced. That is the reason for considering overcomplete Weyl-Heisenberg expansions. The main result of this correspondence is a complete parameterization of finite length tight Weyl-Heisenberg frames in l/sup 2/(Z) with arbitrary rational oversampling ratios. This parameterization follows from a factorization of polyphase matrices of paraunitary modulated filter banks, which is introduced first.
Supplementary Table S4 from Mutational Landscape and Antiproliferative Functions of ELF Transcription Factors in Human Cancer (2023)

&lt;p&gt;Genes specifically induced by ELF4(L211M) in T3M-1 Cl-10 cells&lt;/p&gt;
Single-Pulse Standoff Raman Detection of Chemicals from 120 m Distance during Daytime (2012)

The capability to analyze and detect the composition of distant samples (minerals, organics, and chemicals) in real time is of interest for various fields including detecting explosives, geological surveying, and pollution mapping. For the past 10 years, the University of Hawaii has been developing standoff Raman systems suitable for measuring Raman spectra of various chemicals in daytime or nighttime. In this article we present standoff Raman spectra of various minerals and chemicals obtained from a distance of 120 m using single laser pulse excitation during daytime. The standoff Raman system utilizes an 8-inch Meade telescope as collection optics and a frequency-doubled 532 nm Nd : YAG laser with pulse energy of 100 mJ/pulse and pulse width of 10 ns. A gated intensified charge-coupled device (ICCD) detector is used to measure time-resolved Raman spectra in daytime with detection time of 100 ns. A gate delay of 800 ns (equivalent to target placed at 120 m distance) was used to minimize interference from the atmospheric gases along the laser beam path and near-field scattering. Reproducible, good quality single-shot Raman spectra of various inorganic and organic chemicals and minerals such as ammonium nitrate, potassium perchlorate, sulfur, gypsum, calcite, benzene, nitrobenzene, etc., were obtained through sealed glass vials during daytime. The data indicate that various chemicals could easily be identified from their Raman fingerprint spectra from a far standoff distance in real time using single-shot laser excitation.
Optimization of an immunotherapeutic protocol with poly(I,C)-LC. (1985)

The development of successful immunotherapeutic protocols requires new therapeutic strategies as well as the development of clinically predictive tumor models and protocols. A bell-shaped response curve is observed with many biological response modifiers (BRMs), not only for immunomodulation, but also for therapeutic activity. Although most BRMs, including poly(I,C)-LC, are toxic at high doses, the administration of nontoxic doses by an optimal protocol and route of injection results in significant therapeutic benefit and increased immunomodulation in tumor-bearing animals compared to the administration of a maximum tolerated dose (MTD). We suggest that Phase II clinical trials using an optimal immunomodulatory protocol may result in increased therapeutic activity compared to protocols based on the MTD.
<i>In vitro</i>splicing of fibronectin pre-mRNAs (1990)

We have investigated the alternative splicing of the EIIIB exon of the rat fibronectin gene. Mini-gene constructs containing this exon and portions of adjacent introns and exons, when transfected into HeLa cells, are transcribed and spliced, but omit the EIIIB exon. In vitro, HeLa nuclear extracts similarly splice out (skip) the EIIIB exon from similarly structured transcripts. Therefore, the HeLa splicing apparatus recognizes as atypical the EIIIB exon and its flanking intron sequences, both in vivo and in vitro. We also report that alterations in the ionic conditions of the in vitro splicing reaction can promote the initiation of EIIIB exon inclusion, as reflected by the formation of intermediate and product RNAs related to the removal of the intron upstream of EIIIB. Processing of this intron correlates with the formation of complexes resembling intermediates in spliceosome assembly. The branch sites involved in this alternative processing pathway are rather distant from the EIIIB 3' splice site, and lie within a region which is well conserved in the fibronectin genes of other species. Thus, the intron upstream of EIIIB shows singular structure and behavior which probably have a bearing on the regulated alternative splicing of this exon.
90°-apart-stem RFQ structure for wide range of frequencies (2002)

At present, many different resonant RFQ structures for accelerating both light and heavy ions are successfully used. Usually they are divided into two well known groups: 4-vane and 4-rod structures, each of them having its merits and drawbacks. In this paper a new resonant structure is considered, which combines the advantages of both. It may be seen as a 4-vane structure with holes ("windows") in the vanes, or as a 4-rod one having stems located 90/spl deg/ apart from each other and from the beam direction. Thus, changing the window size, such a structure can be modified from a typical 4-rod resonator, working at 50 MHz or less, to a typical 4-vane one, working at higher frequencies (up to 500 MHz) and having a better frequency distinction between operating and unwanted dipole modes, due to the magnetic coupling between neighbouring quadrants through the holes. It also should be noted that no voltage arises on the beam axis in the gap between end plate and electrodes, provided that horizontal and vertical windows have the same longitudinal position. Computer simulations with MAFIA codes are presented and compared with cold model measurements.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Trial Implementation of the High-Impact, Low-Frequency Power Grid Event Risk Framework to Support Informed Decision-Making (2022)

In 2015, Pacific Northwest National Laboratory (PNNL) developed a multi-hazard risk-assessment framework for modeling high-impact, low-frequency (HILF) power grid events to support risk-informed decisions for power grid management and emergency planning. The identified framework elements are based on a systematic and comprehensive characterization of hazards to the level of detail required for modeling risk. In 2016, PNNL performed a trial implementation of the framework for a single hazard category and a set of key power grid asset types as a way to test the framework. A specific realization of a HILF event is referred to as an initiating event, or initiator. An initiating event is the manifestation of a hazard, and can be, for example, an earthquake of specified magnitude at a specified epicenter. Other examples of HILF events include geomagnetic disturbances and pandemics. For this test implementation, grid assets of a benchmark power system transmission network were assigned proxy geographical coordinates associated with Washington State locations; and real-world seismic hazard information was used for those locations. Based on the fragility of the grid assets to events of different severities, the set of possible failure scenarios (i.e., combinations of different asset failures) and their associated probabilities were determined, and recovery of grid assets and restoration of the network were considered. These combinations of failures and their subsequent recovery constitute a HILF event sequence that results in a given level of consequence, such as loss of power over a given geographic area for a given duration. The concurrent quantitative consideration of event probabilities and event consequences characterizes a risk model. For HILF event sequences, risk was expressed as expected unserved energy per year. This implementation demonstrates the feasibility and value of using the HILF event risk framework despite some of the identified challenges. This report discusses this trial implementation and presents risk results and insights from the implementation.
<i>Ex vivo</i> hypothermic recirculatory adenoviral gene transfer to the transplanted pig heart (2006)

This model can be applied to a large isolated heart and will greatly facilitate the investigation of gene therapy in large animal models of heart transplantation.