gebhart/patrepeval huggingface dataset:
Cancer Neoantigens and Applications for Immunotherapy (2015)

Recent advances in immune checkpoint blockade therapy have revolutionized the treatment of cancer. Tumor-specific antigens that are generated by somatic mutation, neoantigens, can influence patient response to immunotherapy and contribute to tumor shrinkage. Recent evidence demonstrating the success of checkpoint blockade immunotherapy in boosting T-cell reactivity against patient-specific neoantigens constitutes a strong rationale for the development of personalized vaccines against these nonself peptides. With the decreasing cost of next-generation sequencing, peptide manufacturing, and improvement of in silico prediction of peptide immunogenicity, it is increasingly important to evaluate the potential use of neoantigens in both diagnosis and treatment. Specifically, these neoantigens could be useful both as predictors of immune checkpoint blockade therapy response and/or incorporated in therapeutic vaccination strategies.
XLVI.—The velocity of oxidation of paraffin wax. Parts I—IV (1924)

F. Francis, W. F. Millard, C. H. Rutt, C. M. Watkins, R. W. Wallington and C. P. Garner, J. Chem. Soc., Trans., 1924, 125, 381 DOI: 10.1039/CT9242500381
Reduced-complexity Viterbi detector architectures for partial response signalling (2002)

The objective of this paper is to provide a general framework for optimizing the design of Viterbi detectors to achieve substantial reductions in hardware complexity as well as power consumption. Specific application of the framework to partial response systems is discussed. It is shown that the complexity of the add-compare-select unit for an N-state Viterbi detector is approximately N adders. Compared to conventional architectures, this represents a 50% savings for partial response signals of interest in magnetic storage.
Bioactive bromopyrrole metabolites from the Caribbean sponge Agelas conifera (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBioactive bromopyrrole metabolites from the Caribbean sponge Agelas coniferaPaul A. Keifer, Robert E. Schwartz, Moustapha E. S. Koker, Robert G. Hughes Jr., Dan Rittschof, and Kenneth L. RinehartCite this: J. Org. Chem. 1991, 56, 9, 2965–2975Publication Date (Print):April 1, 1991Publication History Published online1 May 2002Published inissue 1 April 1991https://pubs.acs.org/doi/10.1021/jo00009a008https://doi.org/10.1021/jo00009a008research-articleACS PublicationsRequest reuse permissionsArticle Views849Altmetric-Citations148LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Theoretical Performance of Intraocular Lenses Correcting Both Spherical and Chromatic Aberration (2011)

This is the first study that evaluates IOLs correcting both LSA and LCA in the presence of corneal higher order aberrations. Intraocular lenses that correct both LSA and LCA improve simulated retinal image quality over spherical IOLs and IOLs that correct LSA alone, without sacrificing depth of field or tolerance to decentration. Correction of LCA in combination with LSA shows the potential to improve visual performance.
CGRP-RCP, a Novel Protein Required for Signal Transduction at Calcitonin Gene-related Peptide and Adrenomedullin Receptors (2000)

It is becoming clear that receptors that initiate signal transduction by interacting with G-proteins do not function as monomers, but often require accessory proteins for function. Some of these accessory proteins are chaperones, required for correct transport of the receptor to the cell surface, but the function of many accessory proteins remains unknown. We determined the role of an accessory protein for the receptor for calcitonin gene-related peptide (CGRP), a potent vasodilator neuropeptide. We have previously shown that this accessory protein, the CGRP-receptor component protein (RCP), is expressed in CGRP responsive tissues and that RCP protein expression correlates with the biological efficacy of CGRP in vivo. However, the function of RCP has remained elusive. In this study stable cell lines were made that express antisense RCP RNA, and CGRP- and adrenomedullin-mediated signal transduction were greatly reduced. However, the loss of RCP did not effect CGRP binding or receptor density, indicating that RCP did not behave as a chaperone but was instead coupling the CGRP receptor to downstream effectors. A candidate CGRP receptor named calcitonin receptor-like receptor (CRLR) has been identified, and in this study RCP co-immunoprecipitated with CRLR indicating that these two proteins interact directly. Since CGRP and adrenomedullin can both signal through CRLR, which has been previously shown to require a chaperone protein for function, we now propose that a functional CGRP or adrenomedullin receptor consists of at least three proteins: the receptor (CRLR), the chaperone protein (RAMP), and RCP that couples the receptor to the cellular signal transduction pathway.
Src and the control of cell division (1996)

The finely tuned mechanisms that control cell cycle progression go awry in cancer, pointing to proto-oncogene products as important players in cell-cycle regulation. One such proto-oncoprotein, c-Src, has previously been directly implicated, based on its requirement for growth factor-stimulated DNA synthesis. Roche et al. have now shown that c-Src or its close relatives are also required for cell division to occur. The demonstration of essential functions for the Src family at multiple points in the cell cycle raises important questions about the normal and transforming activities of these and other proto-oncoproteins.
The UL16‐binding proteins, a novel family of MHC class I‐related ligands for NKG2D, activate natural killer cell functions (2001)

The UL16-binding proteins (ULBPs) are a novel family of MHC class I-related molecules (MICs) that were identified based on their ability to bind to the human cytomegalovirus (HCMV) glycoprotein UL16. UL16 also binds to a member of another family of MHC class I-like molecules, MICB. The ULBPs and MICs are ligands for NKG2D/DAP10, an activating receptor expressed by natural killer (NK) cells and other immune effector cells, and this interaction can be blocked by UL16. Engagement of NKG2D/DAP10 by ULBPs or MICs expressed on a target cell can overcome an inhibitory signal generated by NK-cell recognition of MHC class I molecules and trigger NK cytotoxicity. ULBPs elicit their effects on NK cells by activating the janus kinase 2, signal transducer and activator of transcription 5, extracellular-signal-regulated kinase mitogen-activated protein kinase and Akt/protein kinase B signal transduction pathways. Although ULBPs alone activate multiple signaling pathways and induce modest cytokine production, ULBPs synergize strongly with interleukin-12 for production of interferon-gamma by NK cells. This finding is consistent with reports in T cells that NKG2D/DAP10 can act as a co-stimulatory receptor in a similar manner as CD28. The possible roles of ULBPs in mediating immune responses to viruses and tumors and the potential mechanisms by which UL16 may allow HCMV to evade immune detection are areas of active investigation.
Plasma and Rectal Adenosine in Inflammatory Bowel Disease: Effect of Methotrexate (1999)

In animal models, the antiinflammatory mechanism of action of methotrexate has been attributed to elevation of the extracellular concentration of the endogenous autocoid, adenosine. Our goal was to determine if methotrexate elevates adenosine concentrations in plasma and at the site of disease in patients with inflammatory bowel disease. In 10 patients with Crohn's disease or ulcerative colitis, rectal adenosine and plasma adenosine concentrations were measured before and immediately after a subcutaneous injection of methotrexate, 15 or 25 mg. The mean predose rectal adenosine concentration of 2.4 mumol/l was not significantly different from the postdose concentration of 2.1 mumol/l, p = 0.17, (paired two-tailed t test). Rectal adenosine concentration tended to correlate with rectal endoscopic disease activity, r = 0.59, p = 0.067 (Spearman rank order correlation). After methotrexate injection, neither the mean daily plasma adenosine concentration, nor the plasma adenosine at any individual time point, were significantly different from preinjection values. In patients with inflammatory bowel disease, an injection of methotrexate in the clinically effective dose range does not raise rectal or plasma adenosine concentrations. A role for adenosine as the mediator of the antiinflammatory action of methotrexate is not supported.
Monodisperse nanoparticles of poly(ethylene glycol) macromers and N‐isopropyl acrylamide for biomedical applications (2002)

Abstract Poly(ethylene glycol)‐based nanoparticles have received significant attention in the field of biomedicine. When they are copolymerized with pH‐ or temperature‐sensitive comonomers, their small size allows them to respond very quickly to changes in the environment, including changes in the pH, ionic strength, and temperature. In addition, the high surface‐to‐volume ratio makes them highly functionalized. In this work, nanoparticles composed of temperature‐sensitive poly( N ‐isopropylacrylamide), poly(ethylene glycol) 400 dimethacrylate, and poly(ethylene glycol) 1000 methacrylate were prepared by a thermally initiated, free‐radical dispersion polymerization method. The temperature‐responsive behavior of the hydrogel nanoparticles was characterized by the study of their particle size with photon correlation spectroscopy. The size of the nanoparticles varied from 200 to 1100 nm and was a strong function of the temperature of the system, from 5 to 40°C. The thermal, structural, and morphological characteristics were also investigated. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1678–1684, 2003
Tear film osmolality determination: An evaluation of potential errors in measurement (1986)

The technique of tear film osmolality determination using a nanoliter freezing point depression type osmometer was studied to determine what factors affect the accuracy of the technique. Reflex tearing during microcapillary sampling of the tears caused a 5% decrease in tear film osmolality. Evaporation effects of sampling, retrieval and osmolality determination of samples resulted in an increase of 0.2% for one microliter volumes and 1.2% and 1.3% for 0.50 and 0.25 microliter volumes of samples, respectively. Evaporation of the sample during storage between layers of immersion oil resulted in increasing osmolalities of 0.5, 0.2 and 0.2%/day for sample volumes of 0.25, 0.50 and 1.0 microliter respectively over 14 days. Samples (1.0 microliter) stored at 4 degrees C showed an increase in osmolality of 1.25 mos/kg/day. These results suggest that reflex tearing is one major source of variation in tear film osmolality determinations and that avoidance of reflex tearing is critical to the accuracy of the technique.
Optimizing pH Response of Affinity between Protein G and IgG Fc (2009)

Protein-protein interaction in response to environmental conditions enables sophisticated biological and biotechnological processes. Aiming toward the rational design of a pH-sensitive protein-protein interaction, we engineered pH-sensitive mutants of streptococcal protein G B1, a binder to the IgG constant region. We systematically introduced histidine residues into the binding interface to cause electrostatic repulsion on the basis of a rigid body model. Exquisite pH sensitivity of this interaction was confirmed by surface plasmon resonance and affinity chromatography employing a clinically used human IgG. The pH-sensitive mechanism of the interaction was analyzed and evaluated from kinetic, thermodynamic, and structural viewpoints. Histidine-mediated electrostatic repulsion resulted in significant loss of exothermic heat of the binding that decreased the affinity only at acidic conditions, thereby improving the pH sensitivity. The reduced binding energy was partly recovered by "enthalpy-entropy compensation." Crystal structures of the designed mutants confirmed the validity of the rigid body model on which the effective electrostatic repulsion was based. Moreover, our data suggested that the entropy gain involved exclusion of water molecules solvated in a space formed by the introduced histidine and adjacent tryptophan residue. Our findings concerning the mechanism of histidine-introduced interactions will provide a guideline for the rational design of pH-sensitive protein-protein recognition.
Nanobodies as Tools for In Vivo Imaging of Specific Immune Cell Types (2010)

The observed in vivo biodistribution of the Nanobodies reflects the main in vivo locations of the cells recognized by the Nanobodies and is determined by the antigen-binding loops of the Nanobodies. Thus, Nanobodies represent elegant targeting probes for imaging the in vivo biodistribution of specific immune cell types.
Thematic review series: Patient-Oriented Research. What we have learned about VLDL and LDL metabolism from human kinetics studies (2006)

Lipoprotein metabolism is the result of a complex network of many individual components. Abnormal lipoprotein concentrations can result from changes in the production, conversion, or catabolism of lipoprotein particles. Studies in hypolipoproteinemia and hyperlipoproteinemia have elucidated the processes that control VLDL secretion as well as VLDL and LDL catabolism. Here, we review the current knowledge regarding apolipoprotein B (apoB) metabolism, focusing on selected clinically relevant conditions. In hypobetalipoproteinemia attributable to truncations in apoB, the rate of secretion is closely linked to the length of apoB. On the other hand, in patients with the metabolic syndrome, it appears that substrate, in the form of free fatty acids, coupled to the state of insulin resistance can induce hypersecretion of VLDL-apoB. Studies in patients with familial hypercholesterolemia, familial defective apoB, and mutant forms of proprotein convertase subtilisin/kexin type 9 show that mutations in the LDL receptor, the ligand for the receptor, or an intracellular chaperone for the receptor are the most important determinants in regulating LDL catabolism. This review also demonstrates the variance of results within similar, or even the same, phenotypic conditions. This underscores the sensitivity of metabolic studies to methodological aspects and thus the importance of the inclusion of adequate controls in studies.
Amphipathic α-Helix Bundle Organization of Lipid-Free Chicken Apolipoprotein A-I (1999)

Apolipoprotein A-I (apoA-I), the major protein component of plasma high-density lipoprotein (HDL), exists in alternate lipid-free and lipid-bound states. Among various species, chicken apoA-I possesses unique structural properties: it is a monomer in the lipid-free state and it is virtually the sole protein component of HDL. Near-UV circular dichroism (CD) spectroscopic studies provide evidence that chicken apoA-I undergoes a major conformational change upon binding to lipid, while far-UV CD data indicate its overall alpha-helix content is maintained during this transition. The fluorescence emission wavelength maximum (excitation 295 nm) of the tryptophans in apoA-I (W74 and W107) displayed a marked blue shift in both the lipid-free (331 nm) and HDL-bound (329 nm) states, compared to free tryptophan in solution. The effect of aqueous quenchers on tryptophan fluorescence was determined in lipid-free, dimyristoylphosphatidylcholine (DMPC)- and HDL-bound states. The most effective quencher in the lipid-free and HDL-bound states was acrylamide, giving rise to Ksv values of 1.6 +/- 0.1 and 1.2 +/- 0.1 M-1, respectively. Together, these data suggest that a hydrophobic environment around the two tryptophan residues (W74 and W107) is maintained in alternate conformations of the protein. To further probe the molecular organization of lipid-free apoA-I, its effect on the fluorescence properties of 8-anilino-1-naphthalenesulfonic acid (ANS) was determined. Human and chicken apoA-I induced a similar increase in ANS fluorescence quantum yield, in keeping with the hypothesis that these proteins adopt a similar global fold in the absence of lipid. When considered with near- and far-UV CD experiments, the data support a model in which lipid-free chicken apoA-I is organized as an amphipathic alpha-helix bundle. In other studies, lipid-soluble quenchers, 5-, 7-, 10-, and 12-DOXYL stearic acid (DSA), were employed to investigate the depth of penetration of apoA-I into the surface monolayer of spherical HDL particles. 5-DSA was the most effective quencher, suggesting that apoA-I tryptophan residues localize near the surface monolayer, providing a structural rationale for the reversibility of apoA-I-lipoprotein particle interactions.
Risk factors for clinically diagnosed Alzheimer's disease (1986)

We conducted a case-control study of 116 patients with the clinical diagnosis of Alzheimer's disease (AD) in seven Italian centers. One hundred sixteen hospital controls and 97 population controls were matched by age, sex, and region of residence to the cases. A structured questionnaire was administered to the next-of-kin of cases and controls by trained interviewers to identify possible risk factors. Genetic, viral, toxic, immunologic, medical, surgical, and personality factors were investigated. Dementia among first- or second-degree relatives and advanced age of the mother at subject's birth (age over 40) were associated with AD. Head trauma was more frequent in cases than in either hospital or population controls, but the differences were not significant. Our data did not confirm the previously reported association with antecedent thyroid disease or family history of Down's syndrome.
The novel bispecific diabody αCD40/αCD28 strengthens leukaemic dendritic cell‐induced T‐cell reactivity (2008)

Dendritic cell (DC)-based immunotherapy faces new challenges because the efficacy of DC vaccines in clinical trials has been inconsistent. Strategies to improve immune responses induced by DC are currently being explored. We have recently shown the feasibility of generating fully functional DC from acute myeloid leukaemic (AML) blasts, but with varying expression levels of the important costimulatory molecule CD86. To overcome this variability, we developed a novel bispecific diabody that simultaneously and agonistically targeted CD40 on AML-DC and CD28 on naïve T cells. Beside optimization of CD28-mediated signalling, the resulting cellular cross-linking was also hypothesized to increase the strength and duration of T cell/AML-DC interactions, thus increasing T-cell responsiveness to AML antigens. The alphaCD40/alphaCD28-bispecific diabody was found to bind to its target antigens and provoked increased T-cell-DC cluster formation. The alphaCD40/alphaCD28 diabody is capable of increasing T-cell proliferation induced by AML-DC as well as the induction of DC maturation. Importantly, priming efficacy of tumour-specific cytotoxic T cells can also be improved by cross-linking AML-DC and T cells with the alphaCD40/alphaCD28 diabody. We propose that the alphaCD40/alphaCD28-bispecific diabody can serve as a potent therapeutic tool to effectively augment anti-tumour T-cell responses elicited by AML-DC.
Real-time rendering systems in 2010 (2005)

We present a case for future real-time rendering systems that support non-physically-correct global illumination techniques by using ray tracing visibility algorithms, by integrating scene management with rendering, and by executing on general-purpose single-chip parallel hardware (CMP's). We explain why this system design is desireable and why it is feasible. We also discuss some of the research questions that must be addressed before such a system can become practical.
Illusion of Causality in Visualized Data (2019)

Students who eat breakfast more frequently tend to have a higher grade point average. From this data, many people might confidently state that a before-school breakfast program would lead to higher grades. This is a reasoning error, because correlation does not necessarily indicate causation -- X and Y can be correlated without one directly causing the other. While this error is pervasive, its prevalence might be amplified or mitigated by the way that the data is presented to a viewer. Across three crowdsourced experiments, we examined whether how simple data relations are presented would mitigate this reasoning error. The first experiment tested examples similar to the breakfast-GPA relation, varying in the plausibility of the causal link. We asked participants to rate their level of agreement that the relation was correlated, which they rated appropriately as high. However, participants also expressed high agreement with a causal interpretation of the data. Levels of support for the causal interpretation were not equally strong across visualization types: causality ratings were highest for text descriptions and bar graphs, but weaker for scatter plots. But is this effect driven by bar graphs aggregating data into two groups or by the visual encoding type? We isolated data aggregation versus visual encoding type and examined their individual effect on perceived causality. Overall, different visualization designs afford different cognitive reasoning affordances across the same data. High levels of data aggregation by graphs tend to be associated with higher perceived causality in data. Participants perceived line and dot visual encodings as more causal than bar encodings. Our results demonstrate how some visualization designs trigger stronger causal links while choosing others can help mitigate unwarranted perceptions of causality.
Space Alignment for Cognitive Transmission in MIMO Uplink Channels (2010)

This paper investigates a new transmission technique for cognitive access in multiple-input multiple-output (MIMO) uplink channels with waterfilling power allocation- (WPA-) based primary transmission. The proposed technique allows a cognitive node to access the common destination simultaneously with the primary node, without affecting the MIMO primary performance. By using an appropriate precoding design, the cognitive node aligns its transmitted signal to the unused primary eigenmodes and ensures an orthogonality between the primary and the cognitive links. In order to overcome the limitation of the conventional WPA at high signal-to-noise ratios, a modified WPA enables the primary node to release some eigenmodes in order to provide a positive cognitive rate for all the cases.