gebhart/patrepeval huggingface dataset:
Improving T Cell Therapy for Cancer (2006)

Adoptive transfer of antigen-specific T lymphocytes is a powerful therapy for the treatment of opportunistic disease and some virus-associated malignancies such as Epstein-Barr virus-positive post-transplant lymphoproliferative disease. However, this strategy has been less successful in patients with nonviral cancers owing to their many and varied immune evasion mechanisms. These mechanisms include downregulation of target antigens and antigen-presenting machinery, secretion of inhibitory cytokines, and recruitment of regulatory immune cells to the tumor site. With increased understanding of the tumor microenvironment and the behavior and persistence of ex vivo-manipulated, adoptively transferred T cells, two novel approaches for increasing the efficacy of T cell therapy have been proposed. The first involves genetic modification of tumor-specific T cells to improve their biological function, for example by augmenting their ability to recognize tumor cells or their resistance to tumor-mediated immunosuppression. The second requires modifications to the host environment to improve the homeostatic expansion of infused T cells or to eliminate inhibitory T cell subsets. In this review, we discuss current, promising strategies to improve adoptive T cell therapy for the treatment of cancer.
Generation of Regionally Specified Neural Progenitors and Functional Neurons from Human Embryonic Stem Cells under Defined Conditions (2012)

To model human neural-cell-fate specification and to provide cells for regenerative therapies, we have developed a method to generate human neural progenitors and neurons from human embryonic stem cells, which recapitulates human fetal brain development. Through the addition of a small molecule that activates canonical WNT signaling, we induced rapid and efficient dose-dependent specification of regionally defined neural progenitors ranging from telencephalic forebrain to posterior hindbrain fates. Ten days after initiation of differentiation, the progenitors could be transplanted to the adult rat striatum, where they formed neuron-rich and tumor-free grafts with maintained regional specification. Cells patterned toward a ventral midbrain (VM) identity generated a high proportion of authentic dopaminergic neurons after transplantation. The dopamine neurons showed morphology, projection pattern, and protein expression identical to that of human fetal VM cells grafted in parallel. VM-patterned but not forebrain-patterned neurons released dopamine and reversed motor deficits in an animal model of Parkinson's disease.
Identification of 14-3-3𝛉 as an Antigen that Induces a Humoral Response in Lung Cancer (2007)

We have implemented a strategy to identify tumor antigens that induce a humoral immune response in lung cancer based on the analysis of tumor cell proteins. Chromatographically fractionated protein extracts from three lung cancer cell lines were subjected to Western blotting and hybridization with individual sera to determine serum antibody binding. Two sets of sera were initially investigated. One set consisted of sera from 19 newly diagnosed subjects with lung adenocarcinoma and 19 matched controls. A second independent set consisted of sera from 26 newly diagnosed subjects with lung adenocarcinoma and 24 controls matched for age, gender, and smoking history. One protein that exhibited significant reactivity with both sets of cancer sera (P = 0.0008) was confidently identified by mass spectrometry as 14-3-3 theta. Remarkably, significant autoantibody reactivity against 14-3-3 theta was also observed in an analysis of a third set consisting of 18 prediagnostic lung cancer sera collected as part of the Beta-Carotene and Retinol Efficacy Trial cohort study, relative to 19 matched controls (P = 0.0042). A receiver operating characteristic curve constructed with a panel of three proteins consisting of 14-3-3 theta identified in this study, plus annexin 1 and protein gene product 9.5 proteins previously identified as associated with autoantibodies in lung cancer, gave a sensitivity of 55% at 95% specificity (area under the curve, 0.838) in discriminating lung cancer at the preclinical stage from matched controls.
One Hundred Years of Quantum Physics (2000)

This year marks the 100th anniversary of Max Planck's creation of the quantum concept, an idea so revolutionary that it took nearly 30 years for scientists to develop it into the theory that has transformed the way scientists view reality. In this month's essay, Daniel Kleppner and Roman Jackiw recount how quantum theory, which they rate as "the most precisely tested and most successful theory in the history of science," came to be, how it changed the world, and how it might continue to evolve to make the dream of ultimate understanding of the universe come true.
Secular Trends in the Epidemiology of Nosocomial Fungal Infections in the United States, 1980-1990 (1993)

To identify pathogens causing nosocomial fungal infections and the secular trend in their incidence in US hospitals, data from the National Nosocomial Infections Surveillance System, 1980-1990, were analyzed. During that period, 30,477 fungal infections were reported. The rate rose from 2.0 to 3.8 infections/1000 discharges. The highest number of nosocomial fungal infections/1000 discharges was reported from the burn/trauma service (16.1). Candida albicans was the most frequently isolated fungal pathogen (59.7%), followed by other Candida species (18.6%). The rate increased at all four major anatomic sites of infection. Patients with bloodstream infections who had a central intravascular catheter were more likely to have a fungal pathogen isolated than were other patients with bloodstream infection (relative risk = 3.2; P < .001): 29% of fungemia patients and 17% of patients with bloodstream infection due to other pathogens died during hospitalization (P < .001). Fungi are emerging as important nosocomial pathogens and control efforts should target fungal infections, especially fungemia.
Squeeze me, hold me, tilt me! An exploration of manipulative user interfaces (1998)

Article Squeeze me, hold me, tilt me! An exploration of manipulative user interfaces Share on Authors: Beverly L. Harrison Xerox Palo Alto Research Center, 3333 Coyote Hill Road, Palo Alto, California Xerox Palo Alto Research Center, 3333 Coyote Hill Road, Palo Alto, CaliforniaView Profile , Kenneth P. Fishkin Xerox Palo Alto Research Center, 3333 Coyote Hill Road, Palo Alto, California Xerox Palo Alto Research Center, 3333 Coyote Hill Road, Palo Alto, CaliforniaView Profile , Anuj Gujar Xerox Palo Alto Research Center, 3333 Coyote Hill Road, Palo Alto, California Xerox Palo Alto Research Center, 3333 Coyote Hill Road, Palo Alto, CaliforniaView Profile , Carlos Mochon Intern at Xerox PARC from the MIT Department of Physics Intern at Xerox PARC from the MIT Department of PhysicsView Profile , Roy Want Xerox Palo Alto Research Center, 3333 Coyote Hill Road, Palo Alto, California Xerox Palo Alto Research Center, 3333 Coyote Hill Road, Palo Alto, CaliforniaView Profile Authors Info & Claims CHI '98: Proceedings of the SIGCHI Conference on Human Factors in Computing SystemsJanuary 1998 Pages 17–24https://doi.org/10.1145/274644.274647Online:01 January 1998Publication History 208citation4,396DownloadsMetricsTotal Citations208Total Downloads4,396Last 12 Months90Last 6 weeks14 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Monoclonal Antiphosphatidylserine Antibody Inhibits Intercellular Fusion of the Choriocarcinoma Line, JAR1 (1995)

Naturally occurring antiphospholipid antibodies are strongly associated with placental dysfunction and severe obstetrical complications. We have produced three monoclonal antiphospholipid antibodies that differentiate between phosphatidylserine (PS)- and cardiolipin (CL)-dependent antigens, 3SB9b (CL-/PS+), BA3B5C4 (CL+/PS+), and D11A4 (CL+/PS-). We tested these monoclonal antiphospholipid antibodies in an assay for intertrophoblastic fusion. A JAR choriocarcinoma cell line was induced to undergo intercellular fusion by forskolin in the presence or absence of monoclonal antiphospholipid antibodies. The amount of syncytium formation was quantified by using fluorescein isothiocyanate (FITC)-conjugated anti-desmosome antibody to visualize intercellular membranes and propidium iodide to stain nuclei and by counting those cells with multiple nuclei. Without the presence of antiphospholipid antibodies, and in cultures containing BA3B5C4 (CL+/PS+) or D11A4 (CL+/PS-), approximately 70% of JAR formed syncytial cells after 24 h of forskolin treatment. Less than 13% of the cells formed synctia in 2-day cultures that were not exposed to forskolin or that contained forskolin in the presence of 3SB9b (CL-/PS+). These data suggest that phosphatidylserine is externalized during intertrophoblastic fusion and that antiphospholipid antibody with reactivity against PS, but not CL, can affect placental development by interfering with the normal formation of syncytiotrophoblast.
Cytoplasmic transfer in oocytes: biochemical aspects (2004)

Cytoplasmic control of preimplantation development is not a 'new' concept; the first cytoplasmic transfer experiment was performed in the mouse during the early 1980s, as a means of overcoming cleavage arrest at the 2-cell stage, the '2-cell block'. Since the first human pregnancy following the transfer of cytoplasm from donor oocytes into the oocytes of a patient with a history of poor embryo development and recurrent implantation failure in 1997, >30 children have been born after direct injection of ooplasm from fresh, mature or immature, or cryopreserved-thawed donor oocytes into recipient oocytes via a modified ICSI technique. Transfer of ooplasm was thus applied with astonishing speed in humans, in the absence of extensive research to evaluate the efficacy and the possible risks of the method. This review focuses on biochemical mechanisms by which transfer of ooplasm might confer a benefit: by correcting a putative imbalance between anti- and pro-apoptotic factors and/or correction of defective mitochondrial membrane potential. We also emphasize the 'empirical' state of this technique, and the related risks.
Microglial Activation Resulting from CD40-CD40L Interaction After β-Amyloid Stimulation (1999)

Alzheimer's disease (AD) has a substantial inflammatory component, and activated microglia may play a central role in neuronal degeneration. CD40 expression was increased on cultured microglia treated with freshly solublized amyloid-beta (Abeta, 500 nanomolar) and on microglia from a transgenic murine model of AD (Tg APPsw). Increased tumor necrosis factor alpha production and induction of neuronal injury occurred when Abeta-stimulated microglia were treated with CD40 ligand (CD40L). Microglia from Tg APPsw mice deficient for CD40L demonstrated reduction in activation, suggesting that the CD40-CD40L interaction is necessary for Abeta-induced microglial activation. Finally, abnormal tau phosphorylation was reduced in Tg APPsw animals deficient for CD40L, suggesting that the CD40-CD40L interaction is an early event in AD pathogenesis.
Preliminary results of argon and carbon dioxide laser treatment of keloid scars (1984)

Argon and CO2 lasers have been used to treat 13 patients with well-established keloid scars of the trunk or earlobe. Multiple-bore-hole argon technique and total excision with the CO2 laser were attempted. One patient with an earlobe keloid responded to treatment, all other patients had no improvement.
Principles of Risk Minimization for Learning Theory (1991)

Learning is posed as a problem of function estimation, for which two principles of solution are considered: empirical risk minimization and structural risk minimization. These two principles are applied to two different statements of the function estimation problem: global and local. Systematic improvements in prediction power are illustrated in application to zip-code recognition.
Low Level Sequence Variant Analysis of Recombinant Proteins: An Optimized Approach (2012)

Sequence variants in recombinant biopharmaceuticals may have a relevant and unpredictable impact on clinical safety and efficacy. Hence, their sensitive analysis is important throughout bioprocess development. The two stage analytical approach presented here provides a quick multi clone comparison of candidate production cell lines as a first stage, followed by an in-depth analysis including identification and quantitation of aberrant sequence variants of selected clones as a second stage. We show that the differential analysis is a suitable tool for sensitive and fast batch to batch comparison of recombinant proteins. The optimized approach allows for detection of not only single amino acid substitutions in unmodified peptides, but also substitutions in posttranslational modified peptides such as glycopeptides, for detection of truncated or elongated sequence variants as well as double amino acid substitutions or substitution with amino acid structural isomers within one peptide. In two case studies we were able to detect sequence variants of different origin down to a sub percentage level. One of the sequence variants (Thr → Asn) could be correlated to a cytosine to adenine substitution at DNA (desoxyribonucleic acid) level. In the second case we were able to correlate the sub percentage substitution (Phe → Tyr) to amino acid limitation in the chemically defined fermentation medium.
Opioid Agonists Have Different Efficacy Profiles for G Protein Activation, Rapid Desensitization, and Endocytosis of Mu-opioid Receptors (2003)

The differential ability of various mu-opioid receptor (MOP) agonists to induce rapid receptor desensitization and endocytosis of MOP could arise simply from differences in their efficacy to activate G proteins or, alternatively, be due to differential capacity for activation of other signaling processes. We used AtT20 cells stably expressing a low density of FLAG-tagged MOP to compare the efficacies of a range of agonists to 1) activate G proteins using inhibition of calcium channel currents (ICa) as a reporter before and after inactivation of a fraction of receptors by beta-chlornaltrexamine, 2) produce rapid, homologous desensitization of ICa inhibition, and 3) internalize receptors. Relative efficacies determined for G protein coupling were [Tyr-D-Ala-Gly-MePhe-Glyol]enkephalin (DAMGO) (1) > or = methadone (0.98) > morphine (0.58) > pentazocine (0.15). The same rank order of efficacies for rapid desensitization of MOP was observed, but greater concentrations of agonist were required than for G protein activation. By contrast, relative efficacies for promoting endocytosis of MOP were DAMGO (1) > methadone (0.59) >> morphine (0.07) > or = pentazocine (0.03). These results indicate that the efficacy of opioids to produce activation of G proteins and rapid desensitization is distinct from their capacity to internalize mu-opioid receptors but that, contrary to some previous reports, morphine can produce rapid, homologous desensitization of MOP.
A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo (2016)

B-cell maturation antigen (BCMA) is a highly plasma cell-selective protein that is expressed on malignant plasma cells of multiple myeloma (MM) patients and therefore is an ideal target for T-cell redirecting therapies. We developed a bispecific T-cell engager (BiTE) targeting BCMA and CD3ɛ (BI 836909) and studied its therapeutic impacts on MM. BI 836909 induced selective lysis of BCMA-positive MM cells, activation of T cells, release of cytokines and T-cell proliferation; whereas BCMA-negative cells were not affected. Activity of BI 836909 was not influenced by the presence of bone marrow stromal cells, soluble BCMA or a proliferation-inducing ligand (APRIL). In ex vivo assays, BI 836909 induced potent autologous MM cell lysis in both, newly diagnosed and relapsed/refractory patient samples. In mouse xenograft studies, BI 836909 induced tumor cell depletion in a subcutaneous NCI-H929 xenograft model and prolonged survival in an orthotopic L-363 xenograft model. In a cynomolgus monkey study, administration of BI 836909 led to depletion of BCMA-positive plasma cells in the bone marrow. Taken together, these results show that BI 836909 is a highly potent and efficacious approach to selectively deplete BCMA-positive MM cells and represents a novel immunotherapeutic for the treatment of MM.
Phospholipase Dα3 Is Involved in the Hyperosmotic Response in Arabidopsis (2008)

Rapid activation of phospholipase D (PLD), which hydrolyzes membrane lipids to generate phosphatidic acid (PA), occurs under various hyperosmotic conditions, including salinity and water deficiency. The Arabidopsis thaliana PLD family has 12 members, and the function of PLD activation in hyperosmotic stress responses has remained elusive. Here, we show that knockout (KO) and overexpression (OE) of previously uncharacterized PLDalpha3 alter plant response to salinity and water deficit. PLDalpha3 uses multiple phospholipids as substrates with distinguishable preferences, and alterations of PLDalpha3 result in changes in PA level and membrane lipid composition. PLDalpha3-KO plants display increased sensitivities to salinity and water deficiency and also tend to induce abscisic acid-responsive genes more readily than wild-type plants, whereas PLDalpha3-OE plants have decreased sensitivities. In addition, PLDalpha3-KO plants flower later than wild-type plants in slightly dry conditions, whereas PLDalpha3-OE plants flower earlier. These data suggest that PLDalpha3 positively mediates plant responses to hyperosmotic stresses and that increased PLDalpha3 expression and associated lipid changes promote root growth, flowering, and stress avoidance.
Experimental allergic encephalomyelitis: activation of suppressor T lymphocytes by a modified sequence of the T effector determinant. (1981)

Deletion of certain amino acid residues from the amino acid sequence of the encephalitogenic determinant for guinea pigs, H-Phe-Ser-Trp-Gly-Ala-Glu-Gly-Gln-Lys-OH, destroyed its ability to induce experimental allergic encephalomyelitis (EAE), a cell-mediated autoimmune disease of myelin. The administration of the modified determinant in the form of 4 repeating pentameric sequences, H-(Phe-Ser-Trp-Gln-Lys)4-Gly-OH, activated an antigen-specific T suppressor lymphocyte subset that rendered both presensitized donors and recipients of donor T lymphocytes unresponsive to an encephalitogenic challenge. Treatment of donors or recipients with cyclophosphamide before or after lymphocyte transfer, respectively, obliterated the ability of peptide S42-sensitized T lymphocytes to induce a state of unresponsiveness to an EAE-challenge. The results establish the existence of antigenic determinants for both immunoinduction and immunoregulation of EAE. The immunoregulatory determinant that activates antigen-specific and cyclophosphamide-sensitive suppressor T lymphocyte subset is sequestered within the disease-inducing or T effector determinant.
Supporting worker independence in collaboration transparency (1998)

Conventional collaboration-transparency systems are inefficient in their use of network resources and lack support for key groupware principles: concurrent work, relaxed WYSIWIS, and group awareness. We present an alternative implementation approach to collaboration transparency that provides many features previously seen only in collaboration-aware applications. Our approach is based on an object-oriented replicated architecture where selected single-user interface objects are dynamically replaced by multi-user extensions. The replacement is transparent to the single-user application and its developer. As an instance of this approach, we describe its incorporation into a new Java-based collaboration-transparency system, called Flexible JAMM. We conducted an empirical study to evaluate the effectiveness of Flexible JAMM versus a representative conventional collaboration-transparency system, NetMeeting. Completion times were significantly faster in a loosely-coupled task using Flexible JAMM, and were not adversely affected in a tightly-coupled task. Accuracy was unaffected by the system used. Participants greatly preferred Flexible JAMM. The evaluation validates our aim of supporting multiple styles of collaboration.
The surrounding sensor approach - application to sleep apnea syndrome diagnosis based on image processing (2003)

This paper describes a new approach to understanding human physiological status through unrestrainedly monitoring his/her body movement. The sensors used for monitoring the human subject are not attached to the body but embedded into the surroundings. This paper clarifies the advantages of the surrounding sensors from the view point of system construction, monitoring of human body movement, and understanding of physiological status. This paper also reports a system based on this approach and proposes a new method of non-invasive and unrestrained diagnosis for sleep apnea syndrome (SAS) using the system. The effectiveness of the proposed method is proved by applying the experimental system to three SAS patients with the help of doctors and nurses at a hospital.
Enzymatic Degradation of GlycosaminogIycans (1995)

Glycosarninoglycans (GAGs) play an intricate role in the extracellular matrix (ECM), not only as soluble components and polyelectrolytes, but also by specific interactions with growth factors and other transient components of the ECM. Modifications of GAG chains, such as isomerization, sulfation, and acetylation, generate the chemical specificity of GAGs. GAGS can be depolymerized enzymatically either by eliminative cleavage with lyases (EC 4.2.2.-) or by hydrolytic cleavage with hydrolases (EC 3.2.1.-). Often, these enzymes are specific for residues in the polysaccharide chain with certain modifications. As such, the enzymes can serve as tools for studying the physiological effect of residue modifications and as models at the molecular level of protein-GAG recognition. This review examines the structure of the substrates, the properties of enzymatic degradation, and the enzyme substrate-interactions at a molecular level. The primary structure of several GAGS is organized macro-scopicallyby segregation into alternating blocks of specific sulfation patterns and microscopicallyby formation of oligosaccharide sequences with specific binding functions. Among GAGs, considerable dermatan sulfate, heparin and heparan sulfate show conformational flexibility in solution. They elicit sequence-specific interactions with enzymes that degrade them, as well as with other proteins, however, the effect of conformational flexibility on protein-GAG interactions is not clear. Recent findings have established empirical rules of substrate specificity and elucidated molecular mechanisms of enzyme-substrate interactions for enzymes that degrade GAGs. Here we propose that local formation of polysaccharide secondary structure is determined by the immediate sequence environment within the GAG polymer, and that this secondary structure, in turn, governs the binding and catalytic interactions between proteins and GAGs.