gebhart/patrepeval huggingface dataset:
Abstract 3281: GEN1042 (DuoBody-CD40x4-1BB)®in combination with PD-1 blockade reverses T-cell exhaustion in vitro (2023)

Abstract GEN1042 (DuoBody®-CD40x4-1BB) is an investigational, novel, agonistic, bispecific antibody that combines targeting and conditional activation of CD40 and 4-1BB on immune cells for priming and (re-) activation of tumor-specific immune responses. We previously showed that GEN1042 induces conditional CD40 and 4-1BB agonist activity, leading to dendritic-cell maturation and enhanced T-cell activation and effector functions in vitro. However, dysfunction of exhausted T cells in the solid tumor microenvironment may represent a potential resistance mechanism to checkpoint inhibitors/agonists. Here we utilized a multi-omics approach to evaluate whether GEN1042 could reverse T-cell exhaustion in vitro. Publicly available single cell RNA sequencing datasets were harmonized across multiple solid-tumor indications (including treatment-naïve and anti-PD-1 and/or anti-CTLA-4 pretreated samples) and analyzed for expression of CD40, 4-1BB and PD-1 on various immune-cell subsets based on their transcriptomic signatures to characterize target prevalence. In vitro mixed lymphocyte reaction (MLR) functional assays were performed where unstimulated healthy donor CD3+ T cells or CD3+ T cells exhausted by repeated stimulation with anti-CD3/CD28 beads were co-cultured with allogeneic lipopolysaccharide (LPS)-matured dendritic cells. Cultures were analyzed for cytokine secretion and expression of cell surface proteins. In the unstimulated T cell/mDC MLR assay, concurrent treatment with GEN1042 and PD-1 blockade potentiated IFNγ, TNFα and IL-2 production compared with either compound alone. In the T-cell exhaustion MLR assay, T cells showed increased expression of inhibitory receptors (e.g., TIM-3, LAG-3) and exhibited hyporesponsiveness for both proliferation and cytokine secretion upon restimulation with anti-CD3/CD28 beads. Here, the combined functional effect of GEN1042 plus PD-1 blockade further potentiated IFNγ secretion compared to single agent activity and induced IL-2 at similar levels to that observed for GEN1042 alone. These data suggest that, in addition to enhancing T-cell effector functions during T cell priming, GEN1042 can amplify the magnitude of the immune response in combination with PD-1 blockade by re-establishing the functional activity of dysfunctional T cells. GEN1042 is currently being evaluated in patients with advanced solid tumors in a phase 1/2 clinical trial (NCT04083599). Citation Format: Vanessa M. Spires, Gregg Masters, Christina Yu, Matt Hancock, Monique N. Luijten, Alexander Muik, Kristina Nuermberger, Friederike Gieseke, Tahamtan Ahmadi, Özlem Türeci, Maria Jure-Kunkel, Ugur Sahin, Mark Fereshteh, Homer C. Adams, Jordan M. Blum. GEN1042 (DuoBody-CD40x4-1BB)®in combination with PD-1 blockade reverses T-cell exhaustion in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3281.
Glow Discharge Ionization (2016)

This document contains recommendations for terminology in mass spectrometry. Development of standard terms dates back to 1974 when the IUPAC Commission on Analytical Nomenclature issued recommendations on mass spectrometry terms and definitions. In 1978, the IUPAC Commission on Molecular Structure and Spectroscopy updated and extended the recommendations and made further recommendations regarding symbols, acronyms, and abbreviations. The IUPAC Physical Chemistry Division Commission on Molecular Structure and Spectroscopy’s Subcommittee on Mass Spectroscopy revised the recommended terms in 1991 and appended terms relating to vacuum technology. Some additional terms related to tandem mass spectrometry were added in 1993 and accelerator mass spectrometry in 1994. Owing to the rapid expansion of the field in the intervening years, particularly in mass spectrometry of biomolecules, a further revision of the recommendations has become necessary. This document contains a comprehensive revision of mass spectrometry terminology that represents the current consensus of the mass spectrometry community.
Interband transitions in photonic crystals (1999)

We present a formalism to describe transitions between photon modes in a photonic crystal with a temporally and spatially varying dielectric constant, in analogy to optical transitions between electronic states in metals and semiconductors. Resonant transitions between different photonic bands are discussed, and predictions of the theory are compared to electromagnetic simulations. We contrast the cases of electronic and photonic transitions, and explore how the photonic band structure allows opportunities for phase matching and stationary-wave generation in nonlinear optical frequency-conversion processes.
Immune response to human papillomavirus 16 L1E7 chimeric virus-like particles: Induction of cytotoxic T cells and specific tumor protection (1999)

Expression of human papillomavirus type 16 (HPV 16) fusion proteins LI deltaCE7(1-55) and LI deltaCE7(1-60) (carboxy-terminal deletion of LI replaced by 55 or 60 amino-terminal amino acids of E7) leads to formation of chimeric papillomavirus-like particles (CVLPs). After "infection" of cells by CVLPs, the chimeric proteins can be detected in the cytosol and the endoplasmic reticulum (ER), suggesting that they are intracellularly processed via the MHC class I pathway and, therefore, able to activate cytotoxic T lymphocytes (CTLs). To investigate the cytotoxic immune response against HPV 16 LI deltaCE7(1-60) and LI deltaCE7(1-55) CVLPs, we immunized C57Bl/6 mice with various CVLP doses without adjuvant. Two weeks after immunization, spleen cells were prepared and stimulated in vitro using HPV 16 E7-expressing transfectants of the tumor cell line RMA. In 51Cr-release cytotoxicity assays, spleen cells of mice vaccinated with LI deltaCE7(1-60) CVLPs specifically lysed the RMA-E7 transfectants as well as RMA cells loaded with the peptide E7(49-57), which represents an H2-Db-restricted CTL epitope. This demonstrates that CVLPs induce an E7-specific CTL response in mice in the absence of an adjuvant. Furthermore, immunization with CVLPs prevented outgrowth of E7-expressing tumor cells even if inoculation of cells was performed 2 weeks before vaccination. We conclude from our data that CVLPs show promise for therapy of HPV-associated lesions.
Effects of Poly(acrylic acid) on Rheological and Dispersion Properties of Aqueous TiO2Suspensions (2007)

The poly(acrylic acid) was used as dispersant to prepare aqueous TiO2/poly(acrylic acid) suspensions. The poly(acrylic acid) was adsorbed on the surface of the TiO2 particles. The zeta potential of the TiO2 particles in TiO2/poly(acrylic acid) suspensions was higher than that of the TiO2 particles in TiO2 suspensions, and the zeta potential of the TiO2 particles increased with increasing poly(acrylic acid) content. At the same shear rate, the viscosity of TiO2/poly(acrylic acid) suspensions was lower than that of TiO2 suspensions, and the liquidity was improved. The dispersion of TiO2 particles in TiO2/poly(acrylic acid) suspensions was improved compared with that of TiO2 particles in TiO2 suspensions.
The Role of inclusion size in toughening of epoxy resins by spherical micelles Part B Polymer physics (2009)

We report our finding of an optimal length scale for toughening of epoxies using spherical micelles formed by block copolymers. The amphiphilic diblock copolymer poly(hexylene oxide)-poly(ethylene oxide) (PHO-PEO) with 30 wt % PEO self-assembled to form spherical micelles in a bisphenol A epoxy resin with a phenol novolac hardener. We systematically increased the size of the spherical micelles from 20-30 nm to 0.5-10 μm by swelling their PHO core using PHO homopolymer. Although all the blends were tougher than the unmodified epoxy, the largest enhancement of fracture resistance was measured in blends containing 0.1-1 μm spherical inclusions. This enhanced toughness was correlated with plastic deformation by shear banding in tensile test and greater roughness of the fracture surface. Smaller micelles neither induced plastic deformation nor contributed to surface roughness significantly whereas larger micelles acted as local defects resulting in early failure. These findings provide a framework in assessing the toughening effects of blended block copolymers on epoxy resins.
Human Embryonic Stem Cells Prevent T-Cell Activation by Suppressing Dendritic Cells Function via TGF-Beta Signaling Pathway (2014)

Human embryonic stem cells (hESCs) represent a potential source of transplantable cells for regenerative medicine, but development of teratoma even in syngenic recipients represents a critical obstacle to safe stem cell-based therapies. We hypothesized that hESCs escape the immune surveillance by regulating the environmental immune system. Using cocultures of hESCs with allogenic peripheral blood mononuclear cells, we demonstrated that hESCs prevent proliferation and activation of human CD4+ T lymphocytes, an effect dependent upon monocytes. Altered expression of key signaling molecules responsible for the crosstalk of monocytes with T cells was detected in the presence of hESCs. Analyzing the mechanism of action, we demonstrated that hESCs were able to downregulate intracellular glutathione levels in both monocytes and CD4+ cells by suppressing glutamate cysteine ligase expression and to alter MHCII and CD80 expression in monocytes. These effects were achieved at least partially via TGF-beta signaling, and both monocyte phenotype and GCLC expression were affected by Caspase-3 proteolytic activity. Altogether, our results demonstrate a novel immune-suppressive mechanism used by hESCs.
Hypothalamic melanin concentrating hormone neurons communicate the nutrient value of sugar (2013)

Sugars that contain glucose, such as sucrose, are generally preferred to artificial sweeteners owing to their post-ingestive rewarding effect, which elevates striatal dopamine (DA) release. While the post-ingestive rewarding effect, which artificial sweeteners do not have, signals the nutrient value of sugar and influences food preference, the neural circuitry that mediates the rewarding effect of glucose is unknown. In this study, we show that optogenetic activation of melanin-concentrating hormone (MCH) neurons during intake of the artificial sweetener sucralose increases striatal dopamine levels and inverts the normal preference for sucrose vs sucralose. Conversely, animals with ablation of MCH neurons no longer prefer sucrose to sucralose and show reduced striatal DA release upon sucrose ingestion. We further show that MCH neurons project to reward areas and are required for the post-ingestive rewarding effect of sucrose in sweet-blind Trpm5(-/-) mice. These studies identify an essential component of the neural pathways linking nutrient sensing and food reward. DOI: http://dx.doi.org/10.7554/eLife.01462.001.
Extrinsic time-dependent dielectric breakdown of low-k organosilicate thin films from vacuum-ultraviolet irradiation (2017)

In this work, the effect of vacuum ultraviolet (VUV) photon irradiation on the time-dependent dielectric breakdown (TDDB) of low-k organosilicate thin films was investigated, with particular emphasis on extrinsic TDDB (includes Cu migration effects). State-of-the-art low-k a-SiOC:H thin films were utilized because of their relevance as both an interlayer dielectric and as a candidate Cu capping-layer material. Synchrotron radiation was used to mimic VUV photon irradiation from processing plasmas without the presence of charged particles. TDDB characteristic lifetimes of the low-k a-SiOC:H dielectrics, before and after VUV photon exposure, were measured based on a Ti/a-SiOC:H/Cu metal-insulator-metal structure. The deterioration of extrinsic TDDB was observed in the film after exposure to VUV photons with 9 eV energy. The most notable degradation of the dielectric characteristic lifetime was found when the Cu electrode was used as an anode in the sample after 9.0 eV VUV photon exposure (photon fluence is 4.0 × 1015 photons/cm2). This is believed to be related to the Cu+ ions created by a VUV photon-assisted reaction. In the presence of an electric field, these Cu ions drift into the low-k dielectric and deteriorate TDDB performance.
Image edges from area morphology (2002)

This paper introduces an edge detection process based on area morphology. Area open-close and area close-open operators are used to generate scaled image representations for feature extraction. The edges are defined by the boundaries of the scaled objects in the area-filtered images. From the area open-close and close-open operators, thin closed contours suitable for image segmentation are produced. The edge maps allow exact specification of the minimum area for the extracted regions and are Euclidean invariant and causal through scale space. Results are given that demonstrate the effectiveness of the area operator-based edge detection. In contrast to traditional edge detectors, edge detection via area morphology provides well-localized boundaries and does not require thresholding.
Hemolytic‐Uremic Syndrome Following Urinary Tract Infection with EnterohemorrhagicEscherichia coli: Case Report and Review (1998)

A 6-week-old child with acute urinary tract infection caused by Shiga toxin-producing Escherichia coli (STEC) O5:H-developed hemolytic-uremic syndrome (HUS). Molecular and phenotypic analysis of the urinary isolate indicated that it lacked uropathic properties and that it was probably of intestinal origin. Nevertheless, the patient did not experience a diarrheal prodrome, nor was STEC or Shiga toxin detected in his feces at any time. Examination of the patient's serum pointed to recent infection with E. coli O5, with no evidence of exposure to E. coli O157, O111, or O26. A review of 13 previously reported cases of HUS associated with acute urinary tract infection indicated that this was the first case of nondiarrheal HUS in which infection with the most common STEC serogroups was specifically excluded. This case illustrates the need to investigate patients with nondiarrheal HUS for infection with STEC.
An Engineered Aryl Azide Ligase for Site‐Specific Mapping of Protein–Protein Interactions through Photo‐Cross‐Linking (2008)

Markiert und verknüpft: Die Bindungsstelle für kleine Moleküle in der Lipoyl-Protein-Ligase von Escherichia coli wurde so verändert, dass sie eine fluorierte Arylazidsonde statt Liponsäure akzeptiert. Mit dieser Mutante lassen sich LAP-Fusionsproteine hochspezifisch markieren. In Zelllysaten wurde das FK506-Bindeprotein markiert und die rapamycinabhängige Photovernetzung mit seinem Wechselwirkungspartner bewiesen.
Leptin deficiency enhances sensitivity to endotoxin-induced lethality (1999)

Leptin is induced by lipopolysaccharide (LPS) and cytokines. We investigated the role of leptin in LPS-induced toxicity using leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice. Sensitivity to LPS-induced mortality is significantly greater in ob/ob mice compared with their own lean littermates but not in db/db mice. LPS reduced serum glucose in both ob/ob and db/db mice but induced corticosterone only in db/db mice. Despite the very high basal levels of serum leptin in db/db mice, a twofold increase in serum leptin levels was observed after LPS in both db/db mice and their lean littermates. No differences were detected in LPS-induced serum levels of interleukin (IL)-1beta, tumor necrosis factor, macrophage inflammatory protein-1alpha, and interferon-gamma in ob/ob mice compared with their own littermates. In contrast, a blunted induction of IL-10 and IL-1 receptor antagonist (IL-1Ra) was observed in ob/ob mice compared with their littermates. In vitro, leptin induced IL-1Ra production and upregulated the IL-1Ra induction by LPS in macrophages. Moreover, treatment with leptin reversed the increased sensitivity to LPS-induced lethality found in ob/ob mice. These results suggest that leptin participates in the host response to inflammation by modulating the host immune and cytokine responses after LPS.
Optoelectronic high-speed HDMI cable with compact optical sub-assembly and 4×3.4 Gbit/s plastic optical fibre link (2012)

Presented is a composite optoelectronic high-speed high-definition multimedia interface (HDMI) cable with the application of an optical link running on four thin GI 50/125 µm plastic optical fibres to serve upcoming demand in consumer electronics. The thin fibres enable a compact optical sub-assembly that in return fits inside the cable connector. The main advantages of this technology are pointed out and the packaging of the composite HDMI connectors outlined. Cable performance and in particular the waveform diagrams as well as bit error ratio results at 3.4 Gbit/s that enable full HD video transmission over 10 m are included.
Abstract A175: Memory T-cells targeting unique and shared oncogenic mutations detected in peripheral blood of epithelial cancer patients (2019)

Abstract T-cells targeting shared oncogenic mutations can induce durable tumor regression in epithelial cancer patients. These T-cells can be detected in tumor-infiltrating lymphocytes, but whether such cells can be detected in the peripheral blood of patients with common metastatic epithelial cancer is unknown. Using a highly sensitive in vitro stimulation and enrichment of peripheral memory T-cells from six metastatic cancer patients, we identified and isolated memory T-cells targeting the mutated KRASG12D and KRASG12V variants, in three patients. In an additional two metastatic colon cancer patients, we detected CD8+ neoantigen-specific cells targeting the unique mutated SMAD5 and MUC4 proteins. Therefore, memory T-cells targeting KRAS and neoantigens can be detected in the peripheral blood of epithelial cancer patients and can potentially be used for the development of effective personalized T-cell-based cancer immunotherapy across multiple patients. Citation Format: Gal Cafri, Rami Yossef, Anna Pasetto, Drew Deniger, Jared J. Gartner, Todd Prickett, Paul F. Robbins, Steven A. Rosenberg. Memory T-cells targeting unique and shared oncogenic mutations detected in peripheral blood of epithelial cancer patients [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A175.
Effect of treatment with 17 alpha-alkylated androgens on C4 conversion products in hereditary angioedema studied by crossed immunoelectrophoresis. (1982)

During agarose electrophoresis C4 in the normal human serum is converted into cleavage products of Beta 1 and Beta 2 mobility. By contrast in the serum of untreated patients with hereditary angiodema C4 gives only one Beta 2 peak on crossed immunoelectrophoresis. The normal C4 electrophoretic pattern is restored in serum of patients treated with stanazolol but not with danazol despite the same C1-esterase inhibitor (C1 INH) activities and C4 serum concentration. We suggest that stanazolol besides having specific effect on C1 INH activity can interfere with other protease inhibitors affecting C1 activation.
Total synthesis of (.+-.)-4'-demethyl-4-epipodophyllotoxin by insertion-cyclization (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal synthesis of (.+-.)-4'-demethyl-4-epipodophyllotoxin by insertion-cyclizationAndrew S. Kende, Margaret Logan King, and Dennis P. CurranCite this: J. Org. Chem. 1981, 46, 13, 2826–2828Publication Date (Print):June 1, 1981Publication History Published online1 May 2002Published inissue 1 June 1981https://pubs.acs.org/doi/10.1021/jo00326a056https://doi.org/10.1021/jo00326a056research-articleACS PublicationsRequest reuse permissionsArticle Views617Altmetric-Citations33LEARN 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
Spatio-temporal Facial Features for HRI Scenarios (2011)

Human faces are mostly seen in actions conveying various information in our daily life communication. On the other hand, human brains are capable of extracting this essential information in a very short interval of time resulting in a better interaction with others. For example, in interactive scenarios where human beings are assisted by intelligent systems or robots, it is quite useful to extract sufficient information about the interacting person. In this paper we study biometric and soft-biometric traits of the humans by using their face information using a single feature set which is representative of person's identity, gender and facial behavior. This problem is addressed using spatio-temporal multifeatures (STMF) extracted from image sequences using a 3D face model. Further, this feature set provides robustness against varying head poses and facial expressions. Experiments have been performed on laboratory captured images and three benchmark databases under varying poses and facial expressions. The results have been discussed comparatively with different approaches.
A Gold Standard Methodology for Evaluating Accuracy in Data-To-Text Systems (2020)

Most Natural Language Generation systems need to produce accurate texts. We propose a methodology for high-quality human evaluation of the accuracy of generated texts, which is intended to serve as a gold-standard for accuracy evaluations of data-to-text systems. We use our methodology to evaluate the accuracy of computer generated basketball summaries. We then show how our gold standard evaluation can be used to validate automated metrics
Construction of a novel phagemid to produce custom DNA origami scaffolds (2018)

Abstract DNA origami, a method for constructing nanoscale objects, relies on a long single strand of DNA to act as the “scaffold” to template assembly of numerous short DNA oligonucleotide “staples”. The ability to generate custom scaffold sequences can greatly benefit DNA origami design processes. Custom scaffold sequences can provide better control of the overall size of the final object and better control of low-level structural details, such as locations of specific base pairs within an object. Filamentous bacteriophages and related phagemids can work well as sources of custom scaffold DNA. However, scaffolds derived from phages require inclusion of multi-kilobase DNA sequences in order to grow in host bacteria, and thus cannot be altered or removed. These fixed-sequence regions constrain the design possibilities of DNA origami. Here we report the construction of a novel phagemid, pScaf, to produce scaffolds that have a custom sequence with a much smaller fixed region of only 381 bases. We used pScaf to generate new scaffolds ranging in size from 1,512 to 10,080 bases and demonstrated their use in various DNA origami shapes and assemblies. We anticipate our pScaf phagemid will enhance development of the DNA origami method and its future applications.