gebhart/patrepeval huggingface dataset:
790 DSP502 — A novel approach for targeting TIGIT and PD1 pathways for cancer immunotherapy (2021)

<h3>Background</h3> TIGIT, an inhibitory immune checkpoint, is a target of interest for immuno-oncology combination therapies. TIGIT is part of a complex molecular network containing four receptors (DNAM1, TIGIT, PVRIG and CD96) and two ligands (PVR and PVRL2). Here we describe Dual Signaling Protein 502 (DSP502), a novel, multi-functional IgG1-Fc-fusion protein targeting this molecular pathway in a unique way. DSP502, comprising the extracellular domains of TIGIT and PD1, is designed to simultaneously bind its two respective ligands, PVR and PD-L1, overexpressed on cancer and myeloid cells in the tumor microenvironment. DSP502 binds PVR preventing inhibitory signaling through TIGIT and CD96 and promoting DNAM1 costimulatory signaling on activated T- and NK-cells. DSP5029s PD1 arm binds PD-L1 to unleash effector T-cells through checkpoint inhibition. In parallel, DSP5029s IgG1-Fc delivers an immune-activating signal via Fc receptors. The net effect is enhanced anti-tumor immunity (figure 1). <h3>Methods</h3> DSP502 heterodimer was successfully produced in a mammalian expression system. DSP502 was evaluated for binding to its cognate ligands on cells and in ELISA-based assays, with and without competing antibodies. NK and PBMC killing activity were evaluated against human K562 CML cells overexpressing PVR. Simultaneous binding of DSP502 to fluorescently-labeled tumor and NK-cells was evaluated by FACS. In vivo activity of DSP502 was evaluated in a humanized NSG A549 NSCLC xenograft mouse model. <h3>Results</h3> Both DSP502 arms were shown to bind their cognate ligands in ELISA and on cell surface. DSP502 binding was dependent on the presence of both ligands on cells and was abolished by competing antibodies to the respective targets, demonstrating binding specificity and the 9AND-gate9 phenomenon. Overexpression of PVR reduced the sensitivity of K562 cells to NK-cell mediated killing, while DSP502 treatment restored it as measured by target cell killing and granzyme-B secretion. Increased, dose-dependent, complexation of NK- and tumor cells was observed following DSP502 treatment and was abolished by both PVR and FcR antibodies. Treatment with DSP502 markedly inhibited tumor growth of A549-NSCLC xenograft in a humanized NSG mouse model, with all mice being tumor-free at the end of the experiment, compared to control PBMC-injected mice. <h3>Conclusions</h3> Here we report the design and function of a novel immunotherapeutic fusion protein, DSP502, that offers multiple functionalities that can coordinately and synergistically drive anti-tumor immunity. Beyond targeting PVR and PDL1, DSP502 has the potential to additionally impact the TIGIT pathway through its effects on CD96 and DNAM1. DSP502 is currently in IND-enabling studies and CMC development. <h3>Ethics Approval</h3> The study was conducted at the Authority of Biological and Preclinical Models, the Hebrew University of Jerusalem, Ein Kerem, Sharet Specific Pathogen-Free (SPF) Unit under the Hebrew university ethic committee board approval (number MD-19-15815-5).
The Nerve Growth Factor 35 Years Later (1987)

Embryogenesis is in some way a model system. It has always been distinguished by the exactitude even punctitio, of its anatomical descriptions. An experiment by one of the great masters of embryology could be made the text of a discourse on scientific method. But something is wrong, or has been wrong. There is no theory of development in the sense in which Mendelism is a theory that accounts for the results of breeding experiments. There has therefore been little sense of progression or timeliness about embryological research. Of many papers delivered at embryological meetings, however good they may be in themselves . . . one too often feels that they might have been delivered five years beforehand without making anyone much the wiser, or deferred for five years without making anyone conscious of a great (1). This feeling of frustration so incisively conveyed by these considerations by P. Medawar, pervaded, in the forties, the field of experimental embryology which had been enthusiastically acclaimed in the mid-thirties, when the upper lip of the amphibian blastopore brought this area of research to the forefront of the biological stage. The side branch of experimental neuroembryology, which had stemmed out from the common tree and was entirely devoted to the study of the tropic interrelations between neuronal cell populations and between these and the innervated organs and tissues, was then in its initial vigorous growth phase. It in turn suffered from a sharp decrease in the enthusiasm that had inflamed the pioneers in this field, ever since R. G. Harrison delivered his celebrated lecture on this topic at the Royal Society in London in 1935 (2). Although the alternate wax and cycles are the rule rather than the exception in all fields of human endeavor, in that of biological sciences the wane is all too often indicative of a justified loss of faith in the rational and methodical approach that had at first raised so much hope. A brief account of the state-of-the-art of experimental neuroembryology in the
Structural basis for the binding of high affinity phosphopeptides to Stat3 (2007)

Signal transducer and activator of transcription 3 (Stat3) is constitutively active in a number of cancers where it participates in aberrant transcription of prosurvival, cell cycling, and angiogenesis genes. Since Stat3 initiates its signaling activity through binding of its SH2 domain to phosphotyrosine residues on cell surface receptors, inhibitors targeting this region of the protein are potential chemotherapeutic agents. To date, no NMR or X-ray crystallographic structures of high-affinity phosphopeptides complexed with the Stat3 SH2 domain are available to aid in the development of peptidomimetic antagonists. Examination of the crystal structures of several STAT proteins and the complex of Stat1 with Ac-pTyr-Asp-Lys-Pro-His-NH(2) led to a hypothesis that the specificity determinant for Stat3, glutamine at position pY+3 in pTyr-Xxx-Xxx-Gln sequences, resides in a unique pocket on the protein surface at the juncture of the third strand of the central beta-sheet and a unique, STAT specific alpha-helix. Docking of Ac-pTyr-Leu-Pro-Gln-NHBn to the SH2 domain of Stat3 using molecular modeling showed that the Gln binds tightly in this pocket and participates in a network of hydrogen bonds. Novel interactions between the peptide main chain and the protein were also discovered. Phosphopeptide structure-affinity studies using unnatural amino acids and glutamine derivatives provide evidence for the peptide-protein interactions revealed by the model and lend support to the binding hypothesis.
A broadband, high-resolution spatial heterodyne spectrometer (2009)

Design and performance parameters of a broadband, high-resolution spatial heterodyne spectrometer (SHS) with a transmitting beamsplitter are described. This Mark 1 SHS achieves more than a factor of five in continuous wavenumber coverage with a resolving power in hundreds of thousands. Progress toward an all reflection, broadband, high-resolution Mark 2 SHS is reported.
High-Temperature Luminescence Quenching of Colloidal Quantum Dots (2012)

Thermal quenching of quantum dot (QD) luminescence is important for application in luminescent devices. Systematic studies of the quenching behavior above 300 K are, however, lacking. Here, high-temperature (300-500 K) luminescence studies are reported for highly efficient CdSe core-shell quantum dots (QDs), aimed at obtaining insight into temperature quenching of QD emission. Through thermal cycling (yoyo) experiments for QDs in polymer matrices, reversible and irreversible luminescence quenching processes can be distinguished. For a variety of core-shell systems, reversible quenching is observed in a similar temperature range, between 100 and 180 °C. The irreversible quenching behavior varies between different systems. Mechanisms for thermal quenching are discussed.
Blood pressure estimation in the human fetal descending aorta (2008)

This study demonstrates the feasibility of estimating arterial blood pressure in the human fetus. The method described is of potential use in assessing fetal blood pressure non-invasively, particularly for studying relative changes with time.
The many faces of Mac‐1 in autoimmune disease (2015)

Mac-1 (CD11b/CD18) is a β2 integrin classically regarded as a pro-inflammatory molecule because of its ability to promote phagocyte cytotoxic functions and enhance the function of several effector molecules such as FcγR, uPAR, and CD14. Nevertheless, recent reports have revealed that Mac-1 also plays significant immunoregulatory roles, and genetic variants in ITGAM, the gene that encodes CD11b, confer risk for the autoimmune disease systemic lupus erythematosus (SLE). This has renewed interest in the physiological roles of this integrin and raised new questions on how its seemingly opposing biological functions may be regulated. Here, we provide an overview of the CD18 integrins and how their activation may be regulated as this may shed light on how the opposing roles of Mac-1 may be elicited. We then discuss studies that exemplify Mac-1's pro-inflammatory versus regulatory roles particularly in the context of IgG immune complex-mediated inflammation. This includes a detailed examination of molecular mechanisms that could explain the risk-conferring effect of rs1143679, a single nucleotide non-synonymous Mac-1 polymorphism associated with SLE.
Synthesis and evaluation of diaryl oxalate esters for low-intensity chemiluminescent illumination (1984)

Various diaryl oxalate esters have been prepared from oxalyl chloride and substituted salicylates. A number of intermediates and byproducts were obtained from chlorinations of salicyclic acid and their mechanistic significance has been discussed. The chemiluminescent emission from the oxalates in the presence of hydrogen peroxide has been examined in the search for low-intensity illumination of at least 10 h duration. Bis(2-alkoxycarbonyl-4,6-dinitrophenyl) oxalates were too unstable while the chemiluminescence of the bis(6-alkoxycarbonyl-2,4,5-trichloropheny) oxalates could not be adjusted suitably. Some bis(6-alkoxycarbonyl-2,4-dichlorophenyl) oxalates were prepared and, by treatment with various combinations of potassium salicylate and oxalic acid, satisfactory low-intensity light emission could be achieved.
The System Iron—Oxygen. II. Equilibrium and Thermodynamics of Liquid Oxide and Other Phases (1946)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe System Iron—Oxygen. II. Equilibrium and Thermodynamics of Liquid Oxide and Other PhasesL. S. Darken and R. W. GurryCite this: J. Am. Chem. Soc. 1946, 68, 5, 798–816Publication Date (Print):May 1, 1946Publication History Published online1 May 2002Published inissue 1 May 1946https://pubs.acs.org/doi/10.1021/ja01209a030https://doi.org/10.1021/ja01209a030research-articleACS PublicationsRequest reuse permissionsArticle Views2799Altmetric-Citations643LEARN 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
Immunohistochemical analysis as a means to predict responsiveness to rituximab treatment (2007)

These data provide novel insights into the mechanisms of CD20-mediated B cell depletion in the lymphoid and solid tissues of RA patients and suggest a pivotal role for ACPA IgM-producing plasmablasts in RA.
Increased Collagen Deposition and Diastolic Dysfunction but Preserved Myocardial Hypertrophy After Pressure Overload in Mice Lacking PKCε (2005)

Overexpression and activation of protein kinase C-epsilon (PKCepsilon) results in myocardial hypertrophy. However, these observations do not establish that PKCepsilon is required for the development of myocardial hypertrophy. Thus, we subjected PKCepsilon-knockout (KO) mice to a hypertrophic stimulus by transverse aortic constriction (TAC). KO mice show normal cardiac morphology and function. TAC caused similar cardiac hypertrophy in KO and wild-type (WT) mice. However, KO mice developed more interstitial fibrosis and showed enhanced expression of collagen Ialpha1 and collagen III after TAC associated with diastolic dysfunction, as assessed by tissue Doppler echocardiography (Ea/Aa after TAC: WT 2.1+/-0.3 versus KO 1.0+/-0.2; P<0.05). To explore underlying mechanisms, we analyzed the left ventricular (LV) expression pattern of additional PKC isoforms (ie, PKCalpha, PKCbeta, and PKCdelta). After TAC, expression and activation of PKCdelta protein was increased in KO LVs. Moreover, KO LVs displayed enhanced activation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), whereas p42/p44-MAPK activation was attenuated. Under stretch, cultured KO fibroblasts showed a 2-fold increased collagen Ialpha1 (col Ialpha1) expression, which was prevented by PKCdelta inhibitor rottlerin or by p38 MAPK inhibitor SB 203580. In conclusion, PKCepsilon is not required for the development of a pressure overload-induced myocardial hypertrophy. Lack of PKCepsilon results in upregulation of PKCdelta and promotes activation of p38 MAPK and JNK, which appears to compensate for cardiac hypertrophy, but in turn, is associated with increased collagen deposition and impaired diastolic function.
Interferometric Vibration Analysis by Wavefront Reconstruction (1965)

A study of the Leith–Upatnieks hologram for the time average of the coherent wavefronts scattered from a vibrating object is reported. The image reconstructed by the hologram is found to contain a system of interference fringes which map contours of constant vibration amplitude, thus providing a method of analysis of the vibration of objects with arbitrary surfaces. Experimental results are presented and interpreted for a simple periodic vibration; statistical motion of objects is discussed.
Implications of the Charge Regulation Model for the Interaction of Hydrophilic Surfaces in Water (2001)

Both attraction and repulsion can be found when hydrophilic surfaces in aqueous solutions are only a few nanometers apart. These forces determine to a large extent the interaction of such diverse systems as large molecules, lipid bilayers, and clay platelets. When attraction changes into repulsion below a certain separation, a potential minimum is observed. There is no good explanation for the potential minimum and the repulsion. They are not predicted by the DLVO theory and have therefore been ascribed to a range of phenomena. Here, an existing modification of the DLVO theory by incorporating regulation of the surface charge is used to quantitatively describe published experiments on the repulsion between oxidic surfaces. The agreement suggests that charge regulation is the cause of the minimum and the repulsion. The implications of the potential minimum are discussed.
Chromenes, chromanones, and chromones (1977)

Chromenes, Chromanones, and Chromones-Introduction (G. P. Ellis). 2H - and 4H -1-Benzopyrans (E. E. Schweizer and Deborah Meeder-Nycz). 3- and 4- Chromanols (I. M. Lockhart). 3-Chromanones (I. M. Lockhart). 4-Chromanones (I. M. Lockhart). 2,4-Chromandiones and 2,3,4-Chromantriones (I. M. Lockhart). Naturally Occurring Chromones (G. P. Ellis). Analytical Aspects of Chromones (G. P. Ellis). General Methods of Preparing Chromones (G. P. Ellis). Chromone and Its Benzo Derivatives (G. P. Ellis). Alkylchromones (G. P. Ellis). Hydroxychromones (G. P. Ellis). Alkoxychromones (G. P. Ellis). Halochromones (G. P. Ellis). Nitrochromones (G. P. Ellis). Aminochromones (G. P. Ellis). Ketonic Chromones (G. P. Ellis). Chromone Carbonitriles and Tetrazole Derivates (G. P. Ellis). Chromone Carboxaldehydes (G. P. Ellis). Chromone Carboxylic Acids and Their Derivatives (G. P. Ellis). Bischromones and Bichromones (G. P. Ellis).
Human fibroblasts express functional IL-2 receptors formed by the IL-2R α- and β-chain subunits: association of IL-2 binding with secretion of the monocyte chemoattractant protein-1 (1996)

Expression of IL-2R was examined on human fibroblasts isolated from different tissues. By specific binding assay it is shown that [125I]IL-2 bound to subconfluent adult bone marrow and embryonic skin and lung fibroblasts. The presence of binding sites for IL-2 was also confirmed by immunofluorescence and flow cytometry analysis using mAbs specific for the p55 IL-2R alpha (anti-CD25), p75 IL-2R beta, and p64 IL-2R gamma subunits. Fibroblasts also constitutively transcribed the genes coding for IL-2R alpha and IL-2R beta and accumulated their respective mRNAs but failed to exhibit the IL-2R gamma-chain on the mRNA and protein level. Although addition of IL-2 to fibroblast cultures did not significantly alter growth kinetics of these cells, the IL-2R complex displayed by fibroblasts appeared to be functional in that addition of IL-2 to these cells led to enhanced expression of the JE gene coding for the monocyte chemoattractant protein-1 (MCP-1). Enhancement of fibroblast MCP-1/JE gene expression by IL-2 appeared to result from delayed MCP-1/JE mRNA decay rather than as a consequence of an acceleration of the MCP-1/JE gene transcription rate. IL-2 had, however, no effect on the expression of other cytokine genes including IL-1, IL-5, IL-6, IL-7, IL-8, IL-9, granulocyte-macrophage-CSF, macrophage-CSF or TNF. These observations suggest that the range of cellular targets of IL-2 is broader than originally appreciated. IL-2 may thus serve to integrate fibroblasts and monocytes into a coordinated response of the connective tissue initiated by T lymphocytes.
Polysaccharides in fungi. XIV. Anti-inflammatory effect of the polysaccharides from the fruit bodies of several fungi. (1983)

Anti-inflammatory assays on the carrageenin-induced edema and scald-induced hyperalgesia in the hindpaw of rats were studied on polysaccharides obtained from the fruit bodies of various fungi (polysaccharide AC, BC: Tremella fuciformis;MEA, MHA, MCW-A, MCW-N: Auricularia auricula-judae; T-2-HN: Dictophora indusiata;G-A: Ganoderma japonicum). The purified polysaccharides MHA, MCW-A, G-A and T-2-HN exhibited a significant inhibitory effect on carrageenin edema. Among these polysaccharides, T-2-HN (partially O-acetylated alpha-D-mannan) also showed the marked inhibitory effect on scald hyperalgesia. We have found that T-2-HN has more potent anti-inflammatory activity than phenylbutazone in the above two inflammatory models. Since the purified polysaccharide is free from protein and lipid, it is clear that anti-inflammatory effect arises from the polysaccharide itself. The polysaccharides (T-2-HN, locust bean gun, xanthan gum) had little effect on the metabolism of arachidonic acid in canine platelets. The mechanism of the anti-inflammatory activity of the polysaccharide remains obscure.
A Dynamic Zoom ADC With 109-dB DR for Audio Applications (2017)

This paper presents the first dynamic zoom ADC. Intended for audio applications, it achieves 109-dB DR, 106-dB signal-to-noise ratio, and 103-dB SNDR in a 20-kHz bandwidth, while dissipating only 1.12 mW. This translates into the state-of-the-art energy efficiency as expressed by a Schreier FoM of 181.5 dB. It also achieves the state-of-the-art area efficiency, occupying only 0.16 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> in the 0.16-μm CMOS. These advances are enabled by the use of concurrent fine and coarse conversions, dynamic error-correction techniques, and a dynamically biased inverter-based operational transconductance amplifier.
A review of color vision in white-tailed deer (2003)

A better understanding of the color vision abilities of white-tailed deer (Odocoileus virginianus) helps to determine how these animals interpret their environment. We review and summarize the literature related to the color vision abilities of white-tailed deer. Physiological measurements using advanced techniques such as molecular genetics, electroretinography, and electron microscopy have demonstrated conclusively that whitetailed deer possess the anatomical requisites for color vision. Operant conditioning techniques employed in pen studies using trained cervids confirm that deer see color. The eyes of white-tailed deer are characterized by 3 classes of photopigments: a short-wavelengthsensitive cone mechanism, a middle-wavelength-sensitive cone mechanism, and a short wavelength- sensitive rod pigment. The number and distribution of rod, and cones in the retina, augmented by adaptations of the eye, give white-tailed deer high visual sensitivity and visual acuity in light and darkness. During the day deer discriminate colors in the range blue to yellow-green and can also distinguish longer (orange and red) wavelengths. At night deer see color in the blue to blue-green range, although the moderately wide spectral sensitivity of rods permits some discrimination of longer wavelengths. Rods serve a discriminatory role in color vision, especially at low to moderate illumination levels. Benefits of color vision to deer include the ability to discriminate between plant species and parts and enhanced predator-detection capabilities. This information can be used to define methods of resolving deer-human conflicts and provide insight to deer researchers, photographers, and hunters on how to he more inconspicuous to their subject.
Studies on the thermal generation and reactivity of a class of (.sigma.,.pi.)-1,4-biradicals (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStudies on the thermal generation and reactivity of a class of (.sigma.,.pi.)-1,4-biradicalsAndrew G. Myers, Peter S. Dragovich, and Elaine Y. KuoCite this: J. Am. Chem. Soc. 1992, 114, 24, 9369–9386Publication Date (Print):November 1, 1992Publication History Published online1 May 2002Published inissue 1 November 1992https://pubs.acs.org/doi/10.1021/ja00050a017https://doi.org/10.1021/ja00050a017research-articleACS PublicationsRequest reuse permissionsArticle Views1297Altmetric-Citations179LEARN 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