gebhart/patrepeval huggingface dataset:
Approach to the use of benzylpenicillin acylase for configurational correlations of amino compounds. 2. Hydrolysis of N-(p-aminophenylacetyl) derivatives of some chiral primary amines (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTApproach to the use of benzylpenicillin acylase for configurational correlations of amino compounds. 2. Hydrolysis of N-(p-aminophenylacetyl) derivatives of some chiral primary aminesDomenico Rossi, Anna Calcagni, and Aurelio RomeoCite this: J. Org. Chem. 1979, 44, 13, 2222–2225Publication Date (Print):June 1, 1979Publication History Published online1 May 2002Published inissue 1 June 1979https://pubs.acs.org/doi/10.1021/jo01327a040https://doi.org/10.1021/jo01327a040research-articleACS PublicationsRequest reuse permissionsArticle Views109Altmetric-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
Tau Protein Mutations Confirmed as Neuron Killers (1998)

Long a suspect in the neuronal wreckage of Alzheimer's disease, the protein called tau looked like it was going to get off scot-free. Circumstantial evidence linking tau to the disease is plentiful. It is the major component of “tangles”—abnormal twists of proteins found in the dead brain cells of Alzheimer's sufferers—and the number of tangles seems to correlate with the severity of dementia. But no one could ever nail tau's guilt once and for all. Now, however, fresh revelations have reignited the case against tau.
Mechanism of Increased Mortality Risk with Erythropoietin Treatment to Higher Hemoglobin Targets (2007)

Recent randomized, controlled trials indicate that there is a strong trend for increased risk for death or adverse composite outcomes with erythropoiesis-stimulating agent treatment in kidney disease to hemoglobin targets higher than those currently recommended. The failure of these trials to find a benefit of higher hemoglobin is in stark contrast to findings from large, observational, population-based studies that continue to demonstrate the association of low hemoglobin with adverse outcomes. The mechanisms for the adverse effect of higher hemoglobin targets that are seen in the randomized, controlled trials are poorly understood. This review explores hypotheses involving (1) the effect of achieved hemoglobin itself, (2) the role of erythropoiesis-stimulating agent treatment, (3) the use of iron supplementation, (4) increased blood pressure, and (5) erythropoiesis-stimulating agent hyporesponsiveness. Because the causal pathway has yet to be determined, further research is strongly encouraged. Clinical practice, however, should avoid erythropoiesis-stimulating agent treatment to higher hemoglobin targets, particularly in those with significant cardiovascular morbidity and those who require disproportionately high dosages of erythropoietin-stimulating agents to achieve recommended hemoglobin levels.
Generation of NY-ESO-1-specific CD4+ and CD8+ T cells by a single peptide with dual MHC class I and class II specificities: a new strategy for vaccine design. (2002)

The existence of overlapping CD8+ and CD4+ T-cell epitopes within certain tumor antigens provides an opportunity to test the hypothesis that relatively short peptides could be used to generate both CD8+ and CD4+ T cells against tumor. In this report, T-cell responses to a fragment of the tumor antigen NY-ESO-1 that contained an HLA-DP4-restricted helper T cell epitope as well as an HLA-A2-restricted cytotoxic T cell epitope were analyzed. One peptide, ESO:157-170 (SLLMWITQCFLPVF) was recognized by both NY-ESO-1-reactive CD8+ and CD4+ T-cell clones. Both CD4+ and CD8+ T cells were efficiently generated from the peripheral blood of multiple melanoma patients after in vitro stimulations using ESO:157-170. Dual-specific peptides containing both cytotoxic T-cell and helper T-cell epitopes may represent an attractive strategy of vaccine design aimed at generating tumor-reactive CD4+ and CD8+ T cells.
Techniques of the Contemporary Composer (1998)

Introduction. 1. Basics. 2. The Tonal Legacy. 3. New Roles of Melody. 4. Harmony, Counterpoint, and Hierarchy. 5. Interval Exploration. 6. Serialism. 7. Pitch-Class Sets. 8. Rhythm and Meter. 9. Texture and Modulations. 10. Microtones. 11. Percussion and the Prepared Piano. 12. New Techniques and Instruments. 13. New Notations. 14. Indeterminacy. 15. Musique Concrete. 16. Electronic Music. 17. Algorithmic Composition. 18. Media Forms. 19. Minimalism. 20. Experimental Music. 21. Decategorization. Bibliography. Index.
Proenzyme to urokinase‐type plasminogen activator in the mouse in vivo (1985)

We have investigated whether urokinase-type plasminogen activator (u-PA) is present in the mouse in vivo as the proenzyme or as the active enzyme. u-PA in extracts of various murine tissues was of a one-polypeptide chain form with an electrophoretic mobility indistinguishable from purified proenzyme (pro-u-PA), as demonstrated by SDS-polyacrylamide gel electrophoresis under reducing conditions followed by immunoblotting. No 2-chain u-PA was detected in any of the extracts (detection limit 10% of that of one-chain u-PA). In bladder urine more than half of the u-PA was of the one-chain form. Together with previous immunocytochemical studies of the normal murine tissues and studies of the Lewis lung carcinoma, the present results indicate that in these tissues the one-chain proenzyme is the predominant form of u-PA in intracellular stores and for the first time demonstrates that at least in some cases the one-chain form constitutes a sizeable fraction of the u-AP in extracellular fluids in the intact organism.
Phosphorothioated Primers Lead to Loop-Mediated Isothermal Amplification at Low Temperatures (2018)

Loop-mediated isothermal amplification (LAMP) is an extremely powerful tool for the detection of nucleic acids with high sensitivity and specificity. However, LAMP shows optimal performance at around 65 °C, which limits applications in point-of-care-testing (POCT). Here, we have developed a version of LAMP that uses phosphorothioated primers (PS-LAMP) to enable more efficient hairpin formation and extension at the termini of growing concatamers, and that therefore works at much lower temperatures. By including additional factors such as chaotropes (urea) and single-stranded DNA binding protein (SSB), the sensitivities and selectivities for amplicon detection with PS-LAMP at 40 °C were comparable with a regular LAMP reaction at 65 °C.
Avoiding Tolerance Against Prostatic Antigens With Subdominant Peptide Epitopes (2001)

A potential novel therapy for prostate cancer is the induction of immune responses to normal prostate-associated antigens (PAA). One approach is to use synthetic peptides from PAA to educate T cells as a means of developing a defined and specific immunotherapy for prostate cancer. A likely major hurdle when using normal PAA for this type of therapy is the tolerance that the immune system may already have for PAA. To evaluate mechanisms for overcoming tolerance, the authors assessed the level of tolerance to SV40T antigen in a transgenic mouse. The SV40T antigen is selectively expressed in the prostates of mice from the transgenic adenocarcinoma mouse prostate (TRAMP) model. The authors have shown that TRAMP mice are tolerant to a dominant cytotoxic T-lymphocyte (CTL) epitope from the SV40T antigen compared with nontransgenic littermates. The tolerance was exhibited as early as 4 weeks and as late as 24 weeks. The use of multiple injections of an oligonucleotide that contains an unmethylated CpG induced high levels of hematopoiesis but did not overcome the tolerance. Injection of an antibody to activate CD40 increased the CTL response in normal mice but also did not overcome tolerance. However, tolerance in the TRAMP mice was avoided when an epitope that had previously been characterized as a subdominant epitope was administered. The authors are investigating the potential of subdominant epitopes to induce prostatitis and antitumor responses. The results of this work should facilitate the development of immune-based therapies for prostate cancer.
La coordinación de los museos en línea (1999)

L'isolationnisme dont font preuve de nombreux musees, s'agissant de leur site Web, est en totale contradiction avec les possibilites qu'offre le World Wide Web de connecter les musees entre eux et avec leurs utilisateurs finaux, fournissant ainsi une infinie richesse d'informations et de connaissances. Les musees d'art ont ete les chefs de file du developpement de la cooperation interinstitutions au service des professionnels comme du grand public, et Maxwell L. Anderson a ete l'une des grandes figures de ce mouvement. Directeur du Whitney Museum of American Art depuis septembre 1998, apres avoir ete directeur de l'Art Gallery of Ontario, a Toronto (1995-1998), et du Michael C. Carlos Museum d'Atlanta (1987-1995) et parmi les premiers a appliquer les nouvelles technologies aux musees, il a consacre de nombreuses conferences et publications a des sujets allant du droit international en matiere d'art a l'architecture des musees, et il a enseigne a l'Universite de Princeton et a l'Universite de Rome.
Abstract 3271: A systemically administered, conditionally active TLR8 agonist for the treatment of HER2-expressing tumors (2019)

Abstract Clinical development of systemically administered myeloid cell agonists has been hindered by acute toxicities due to peripheral activation of the targeted cell types. Intratumoral administration, the route of delivery typically used for innate immune/myeloid cell agonists, is limited by tumor accessibility and a dependence on abscopal responses. Here, we describe an example of a new composition class, termed ImmunoTAC, that allows for systemic delivery of an immune modulator with activity localized to tumor sites and secondary lymphoid structures. Agonism of TLR8 in human myeloid cells drives anti-tumor immunity by inducing direct macrophage killing of tumor cells, repolarizing suppressive myeloid cell populations to a pro-immunogenic phenotype, and inducing dendritic cells to drive tumor-specific CTL responses. SBT6050 is an ImmunoTAC comprised of a novel, potent TLR8 agonist conjugated to a HER2-directed monoclonal antibody. SBT6050 is designed to activate human monocytes and macrophages only in the presence of HER2pos tumor cells with moderate (2+ by IHC) or high (3+ by IHC) expression levels. This activity is dependent upon the ability of the Fc domain of the antibody to engage Fcγ receptors on the surface of the myeloid cells. Additionally, SBT6050 potently activates conventional dendritic cells that, in turn, drive a Th1/CTL program in T cells. Systemic delivery of a SBT6050 surrogate in mice shows robust single agent efficacy in tumor models intrinsically resistant to checkpoint blockade, such as the previously characterized HER2+ CT26 syngeneic model. The intratumoral immune response is characterized by robust activation of tumor-associated myeloid cells, infiltration of neutrophils, persistent increases in local cytokine and chemokine production, decreases in Treg infiltrate, and the generation of a potent, neo-Ag specific anti-tumor CTL response. Mice cured with single-agent treatment are resistant to tumor rechallenge, demonstrating induction of long-lived immunological memory. In contrast to observations with small molecule TLR8 agonists, ImmunoTAC does not induce peripheral cytokine production or associated CRS-like toxicity in mice, consistent with the localized activity of the molecule. Silverback’s lead candidate, SBT6050, is currently in preclinical development for patients with moderate or high HER2-expressing tumors. More broadly, the data presented here describe a novel therapeutic modality that allows for systemic administration of immune modulators with tissue-localized activity. Citation Format: Kara Moyes, Ty Brender, Sean W. Smith, Hengyu Xu, Ben Setter, Li-Qun Fan, Rebecca Brunette, Justin Killebrew, Phil Tan, Craig Coburn, Peter Baum, Valerie Odegard. A systemically administered, conditionally active TLR8 agonist for the treatment of HER2-expressing tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3271.
Defining response of ovarian carcinoma to initial chemotherapy according to serum CA 125. (1996)

Definitions based on a 50% or 75% decrease of CA 125 levels have been shown reliably to define partial response of ovarian cancer in patients receiving first-line chemotherapy. These definitions should be used in addition to or instead of standard response criteria.
CHRONIC EFFECTS OF MECHANICAL FORCE ON AIRWAYS (2005)

Airways are embedded in the mechanically dynamic environment of the lung. In utero, this mechanical environment is defined largely by fluid secretion into the developing airway lumen. Clinical, whole lung, and cellular studies demonstrate pivotal roles for mechanical distention in airway morphogenesis and cellular behavior during lung development. In the adult lung, the mechanical environment is defined by a dynamic balance of surface, tissue, and muscle forces. Diseases of the airways modulate both the mechanical stresses to which the airways are exposed as well as the structure and mechanical behavior of the airways. For instance, in asthma, activation of airway smooth muscle abruptly changes the airway size and stress state within the airway wall; asthma also results in profound remodeling of the airway wall. Data now demonstrate that airway epithelial cells, smooth muscle cells, and fibroblasts respond to their mechanical environment. A prominent role has been identified for the epithelium in transducing mechanical stresses, and in both the fetal and mature airways, epithelial cells interact with mesenchymal cells to coordinate remodeling of tissue architecture in response to the mechanical environment.
Decrease in ventricular stroke volume at apnea termination is independent of oxygen desaturation (1994)

Patients with obstructive sleep apnea experience nocturnal hemodynamic oscillations in association with repetitive respiratory events. Apnea termination (recovery) is accompanied by the nadir of arterial O2 saturation (SaO2), changes in intrathoracic pressure, and arousal from sleep. To investigate separately the contributions of hypoxemia and of arousal from sleep to changes in cardiac function, we continuously measured left ventricular stroke volume (LVSV) and mean arterial pressure (MAP) in eight subjects with severe obstructive sleep apnea (apnea-hypopnea index > 30 events/h associated with SaO2 < or = 82%) during two experimental conditions: 1) subjects slept without intervention for 1-2 h and then supplemental O2 was administered to maintain SaO2 > or = 90% (mean SaO2 nadir 92.7%) throughout the apnea-recovery cycle and 2) upper airway obstructions were abolished using nasal continuous positive airway pressure and subjects were aroused from sleep by an auditory signal. Recovery was associated with an increase in MAP and a decrease in LVSV both with and without supplemental O2. Arousal from sleep on nasal continuous positive airway pressure reproduced the postapneic elevation of MAP but not a decrease in cardiac function of the magnitude that occurred at apnea termination. We conclude that elevation of blood pressure and reduction of LVSV that occurred at apnea termination may be due to different physiological mechanisms.
Psycho-acoustics and speech perception (1997)

Computational models of speech pattern processing might be able to benefit a lot from sound and speech perception by humans. Psycho-acoustics has given us insight into the limits and the capabilities of peripheral hearing for, mainly, simple stationary sounds. Threshold phenomena and temporal and spectral resolution for such stimuli are a first indication of how the front end of a recognizer should be modeled, and what level of precision is required in rule synthesis. Much less is known about the ear's sensitivity to dynamic events with complex signals, such as formant-like transitions. Once the signal becomes a syllable or a meaningful word or sentence, our ear's behavior and our brain's interpretations become even more complex. A good example of that is our perception of stressed and unstressed syllables, including schwas. I will claim that vowel reduction manifests itself as contextual assimilation, rather than as a form of centralization, which again has implications for our phone and word models in ASR and for our coarticulation rules in a synthesizer.
Modulation of FcR function by complement: subcomponent C1q enhances the phagocytosis of IgG-opsonized targets by human monocytes and culture-derived macrophages. (1987)

We have investigated the interaction of C1q, a subunit of the first component of complement, with human monocytes and culture-derived macrophages. Adherence of these mononuclear phagocytes to surfaces coated with C1q induced a marked enhancement of the phagocytosis of sheep erythrocytes opsonized with IgG anti-Forssman antibody (EA-IgG). This C1q-mediated enhancement of phagocytosis was dose dependent, and was specifically blocked by pretreatment of the C1q-coated surfaces with F(ab')2 anti-C1q. The augmentation of FcR-mediated phagocytosis by C1q was determined to be a result of the interaction between the C1q and the phagocytic effector cell, and was not due to interaction between the surface-bound C1q and the EA-IgG. Neither resting nor N-formyl-methionyl-leucyl-phenylalanine-stimulated polymorphonuclear leukocytes were induced by C1q to increase FcR-mediated phagocytosis. Experiments conducted with purified fragments of C1q suggest that the C1q phagocytosis enhancement signal resides in the collagen-like tail domain of the molecule. This region is the same portion of the molecule previously shown to interact with the cell surface C1q receptor. Native type I collagen was unable to enhance FcR-mediated phagocytosis by mononuclear phagocytes. It has been demonstrated that C1q can be localized to areas of inflammation, and additionally C1q can be secreted by macrophages in culture. In view of these findings and the results of our present study, we hypothesize that C1q could provide local, direct, and non-opsonic enhancement of phagocytosis by mononuclear phagocytes in areas of infection and inflammation.
Prolonged pulmonary vasodilator action of inhaled nitric oxide by Zaprinast in awake lambs (1995)

Inhaled nitric oxide (NO) has been shown to selectively dilate the pulmonary vasculature. Zaprinast, an inhibitor of guanosine 3',5'-cyclic monophosphate-specific phosphodiesterase, augments smooth muscle relaxation induced by endothelium-dependent vasodilators. The present study was designed to determine whether intravenous administration of Zaprinast potentiates the vasodilating effects or prolongs the duration of action of intermittent NO inhalation. Eight awake lambs with U-46619-induced pulmonary hypertension breathed three concentrations of NO (5, 10, and 20 ppm) in a random order before and during an intravenous Zaprinast infusion (0.1 mg.kg-1.min-1). Inhaled NO decreased pulmonary arterial pressure (PAP) in a dose-dependent fashion, with mean PAP reduction at 5, 10, and 20 ppm NO inhalation of 6 +/- 1, 7 +/- 1, and 9 +/- 1 (SE) mmHg, respectively. Although the Zaprinast infusion did not change the magnitude of mean PAP reduction, it caused a statistically significant reduction of pulmonary vascular resistance and prolonged the duration of action of inhaled NO (half-times of vasodilator response to 5, 10, and 20 ppm NO inhalation: 1.9 +/- 0.1, 2.1 +/- 0.2, and 2.1 +/- 0.2 min, respectively; half-times of NO inhalation with Zaprinast: 9.7 +/- 1.7, 11.5 +/- 2.2, and 12.3 +/- 2.0, respectively). Plasma concentrations as well as the transpulmonary differences of guanosine 3',5'-cyclic monophosphate were increased by the Zaprinast infusion during NO inhalation. A stable level of pulmonary vasodilation was demonstrated in four additional lambs by combining intermittent NO breathing with an intravenous infusion of Zaprinast.
The "Wake-Sleep" Algorithm for Unsupervised Neural Networks (1995)

An unsupervised learning algorithm for a multilayer network of stochastic neurons is described. Bottom-up "recognition" connections convert the input into representations in successive hidden layers, and top-down "generative" connections reconstruct the representation in one layer from the representation in the layer above. In the "wake" phase, neurons are driven by recognition connections, and generative connections are adapted to increase the probability that they would reconstruct the correct activity vector in the layer below. In the "sleep" phase, neurons are driven by generative connections, and recognition connections are adapted to increase the probability that they would produce the correct activity vector in the layer above.
Effect of Soybean Sterols in the Diet on Plasma and Liver Cholesterol in Chicks (1951)

SummaryEvidence is presented that the addition to the chicks'diet of mixed soybean sterols and of purified sitosterols in the presence of cottonseed oil and cholesterol causes markedly lower plasma and liver levels of cholesterol than the addition to the diet of a mixture of cholesterol and cottonseed oil alone. The possibility is discussed that one or more of the constituents of the mixed soybean sterols interferes with the absorption of cholesterol.
Impact of individual intravenous iron preparations on the differentiation of monocytes towards macrophages and dendritic cells (2016)

This study demonstrates that less stable i.v. iron preparations specifically affect monocyte differentiation towards macrophages and mDCs.