gebhart/patrepeval huggingface dataset:
Radioimmunotherapy of human B-cell lymphoma with 90Y-conjugated antiidiotype monoclonal antibody. (1990)

We report the first case of 90Y-conjugated monoclonal antibody (MoAb) administration for human radioimmunotherapy. Ten mCi 90Y-labeled antiidiotype (anti-Id) MoAb were administered to a patient with B-cell lymphoma whose tumor successfully imaged with 111In-labeled anti-Id MoAb. No significant toxicities were observed. More than 2 g of unlabeled anti-Id MoAb were administered while clearing the circulating IgM idiotype prior to administration of the 90Y-MoAb. Transient partial regression of disease was observed. Serial fine needle aspirations of a malignant lymph node documented in vivo anti-Id penetration into a site that did not image by radioimmunoscintigraphy. The radiosensitivity of B-cell lymphoma, the tumor specificity of anti-Id, the antitumor activity of anti-Id alone, and the safe administration of 10 mCi 90Y-labeled anti-Id MoAb in this report suggest further investigation of this radioimmunoconjugate for therapy of B-cell lymphoma is warranted.
The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring (2016)

Viral infection during pregnancy has been correlated with increased frequency of autism spectrum disorder (ASD) in offspring. This observation has been modeled in rodents subjected to maternal immune activation (MIA). The immune cell populations critical in the MIA model have not been identified. Using both genetic mutants and blocking antibodies in mice, we show that retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt)-dependent effector T lymphocytes [for example, T helper 17 (TH17) cells] and the effector cytokine interleukin-17a (IL-17a) are required in mothers for MIA-induced behavioral abnormalities in offspring. We find that MIA induces an abnormal cortical phenotype, which is also dependent on maternal IL-17a, in the fetal brain. Our data suggest that therapeutic targeting of TH17 cells in susceptible pregnant mothers may reduce the likelihood of bearing children with inflammation-induced ASD-like phenotypes.
Copper(II)-Catalyzed Sequential C,N-Difunctionalization of 1,4-Naphthoquinone for the Synthesis of Benzo[f]indole-4,9-diones under Base-Free Condition (2013)

An efficient synthesis of benzo[f]indole-4,9-diones has been achieved by copper(II)-catalyzed naphthoquinone sequential C,N-difunctionalization reactions with β-enaminones. New C-C and C-N bonds are easily formed in the reaction course. Copper(II) salt plays a dual role as Lewis acid and oxidative catalyst, and O2 acts as the terminal oxidant. The advantage of this reaction is the high atom economy with broad substrate scope and excellent yields. The reaction can be scaled up to using at least grams of substrates.
Isolation and characterization of a cDNA clone encoding rat 5-lipoxygenase. (1988)

A full-length cDNA clone encoding 5-lipoxygenase, a key enzyme in the formation of leukotrienes, was isolated from a rat basophilic leukemia cell lambda gt11 cDNA library. The 2.5-kilobase (kb) cDNA insert, whose identity was confirmed by hybrid-select translation and DNA sequence analysis, has a 2.0-kb open reading frame encoding a protein of Mr approximately 77,600 and includes 60 base pairs of 5'-untranslated region and 0.4 kb of 3'-untranslated region to the polyadenylation signal. The deduced amino acid sequence shows significant homology with published sequences for the rabbit reticulocyte lipoxygenase and soybean lipoxygenase-1; it also contains sequences similar to a consensus sequence found in several calcium-dependent membrane-binding proteins. The cDNA recognizes a 2.6-kb mRNA species which is detected in all tissues but is particularly abundant in RNA from lung.
RNA–Magnesium–Protein Interactions in Large Ribosomal Subunit (2012)

Some of the magnesium ions in the ribosome are coordinated by multiple rRNA phosphate groups. These magnesium ions link distal sequences of rRNA, primarily by incorporating phosphate groups into the first coordination shell. Less frequently, magnesium interacts with ribosomal proteins. Ribosomal protein L2 appears to be unique by forming specific magnesium-mediated interactions with rRNA. Using optimized models derived from X-ray structures, we subjected rRNA/magnesium/water/rProtein L2 assemblies to quantum mechanical analysis using the density functional theory and natural energy decomposition analysis. The combined results provide estimates of energies of formation of these assemblies, and allow us to decompose the energies of interaction. The results indicated that RNA immobilizes magnesium by multidentate chelation with phosphate, and that the magnesium ions in turn localize and polarize water molecules, increasing energies and specificities of interaction of these water molecules with L2 protein. Thus, magnesium plays subtle, yet important, roles in ribosomal assembly beyond neutralization of electrostatic repulsion and direct coordination of RNA functional groups.
Site‐directed mutagenesis of ricin A‐chain and implications for the mechanism of action (1991)

Ricin A-chain is an N-glycosidase that attacks ribosomal RNA at a highly conserved adenine residue. The enzyme is representative of a large family of medically significant proteins used in the design of anticancer agents and in the treatment of HIV infection. The x-ray structure has been used as a guide to create several active site mutations by directed mutagenesis of the cloned gene. Glu177 is a key catalytic residue, and conversion to Gln reduces activity 180-fold. Asn209 is shown to participate in substrate binding by kinetic analysis. Conversion to Ser increases Km sixfold but has no effect on kcat. Conversion of Tyr80 and Tyr123 to Phe decreases activity by 15- and 7-fold respectively. A mechanism of action is proposed that involves binding of the substrate adenine in a syn configuration that resembles the transition state; the putative oxycarbonium ion is probably stabilized by interaction with Glu177.
On the semantics of complex events in active database management systems (1999)

Active database management systems have been developed for applications needing an automatic reaction in response to certain events. Events can be simple in nature or complex. Complex events rely on simpler ones and are usually specified with the help of operators of an event algebra. There are quite a few papers dealing with extensions of existing event algebras. However, a systematic and comprehensive analysis of the semantics of complex events is still lacking. As a consequence most proposals suffer from different kinds of peculiarities. Independent aspects are not treated independently, leading to shady mixtures of aspects in operators. Moreover, aspects are not always treated uniformly. Operators may have other semantics than expected. The paper addresses these problems by an extensive and in-depth analysis of the foundations of complex events. As a result of this analysis, a (formal) meta-model for event algebras is introduced that subdivides the semantics of complex events into elementary, independent dimensions. Each of these dimensions are discussed in detail. The resulting language specification fulfils the criteria for a good language design (like orthogonality, symmetry, homogeneity, lean set of language constructs) to a large extent.
Acylation, methylation, and carboxyalkylation of olefins by Group VIII metal derivatives (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAcylation, methylation, and carboxyalkylation of olefins by Group VIII metal derivativesRichard F. HeckCite this: J. Am. Chem. Soc. 1968, 90, 20, 5518–5526Publication Date (Print):September 1, 1968Publication History Published online1 May 2002Published inissue 1 September 1968https://pubs.acs.org/doi/10.1021/ja01022a034https://doi.org/10.1021/ja01022a034research-articleACS PublicationsRequest reuse permissionsArticle Views7533Altmetric-Citations683LEARN 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
Toward Chemical Ribonucleases. 2. Synthesis and Characterization of Nucleoside-Bipyridine Conjugates. Hydrolytic Cleavage of RNA by Their Copper(II) Complexes (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTToward Chemical Ribonucleases. 2. Synthesis and Characterization of Nucleoside-Bipyridine Conjugates. Hydrolytic Cleavage of RNA by Their Copper(II) ComplexesAmil Modak, Janice Gard, Michael Merriman, Kimberly Winkeler, James Bashkin, and Michael SternCite this: J. Am. Chem. Soc. 1991, 113, 1, 283–291Publication Date (Print):January 1, 1991Publication History Published online1 May 2002Published inissue 1 January 1991https://doi.org/10.1021/ja00001a041RIGHTS & PERMISSIONSArticle Views419Altmetric-Citations79LEARN 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 InReddit PDF (1 MB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
A new adaptive law for robust adaptation without persistent excitation (1987)

A new adaptive law motivated by the work of loannou and Kokotovic (1983) is proposed for the robust adaptive control of plants with unknown parameters. In this adaptive law the output error plays a dual role in the adjustment of the control parameter vector. The advantages of using the adaptive law over others proposed in the literature are discussed. In the ideal case the adaptive system has bounded solutions; in addition, the origin of the error equations is exponentially stable when the reference input is persistently exciting and has a sufficiently large amplitude. The adaptive system is also shown to be robust under bounded external disturbances. Finally, it is shown that, by suitably modifying the adaptive law, the overall system can be made robust in the presence of a class of unmodeled dynamics of the plant. Simulation results are presented throughout the paper to complement the theoretical developments.
The Effect of Batch Normalization on Deep Convolutional Neural Networks (2016)

Batch normalization is a recently popularized method for accelerating the training of deep feed-forward neural networks. Apart from speed improvements, the technique reportedly enables the use of higher learning rates, less careful parameter initialization, and saturating nonlinearities. The authors note that the precise effect of batch normalization on neural networks remains an area of further study, especially regarding their gradient propagation. Our work compares the convergence behavior of batch normalized networks with ones that lack such normalization. We train both a small multi-layer perceptron and a deep convolutional neural network on four popular image datasets. By systematically altering critical hyperparameters, we isolate the effects of batch normalization both in general and with respect to these hyperparameters. Our experiments show that batch normalization indeed has positive effects on many aspects of neural networks but we cannot confirm significant convergence speed improvements, especially when wall time is taken into account. Overall, batch normalized models achieve higher validation and test accuracies on all datasets, which we attribute to its regularizing effect and more stable gradient propagation. Due to these results, the use of batch normalization is generally advised since it prevents model divergence and may increase convergence speeds through higher learning rates. Regardless of these properties, we still recommend the use of variance-preserving weight initialization, as well as rectifiers over saturating nonlinearities.
Red Blood Cell Enzyme Disorders: An Overview (2008)

CME Educational Objectives 1. Review the metabolic pathways critical to maintaining red cell membrane integrity. 2. Summarize a classification scheme for red cell enzyme disorders and remark on a strategy for their diagnostic workup. 3. Discuss the most commonly encountered red cell enzyme disorders in the pediatric population.
An Autonomous Reading Machine (1968)

Abstract—An unconventional approach to character recognition is developed. The resulting system is based solely on the statistical properties of the language, therefore it can read printed text with no previous training or a priori information about the structure of the characters. The known letter-pair frequencies of the language are used to identify the printed symbols in the following manner.
Synthesis and Structure−Activity Relationship Effects on the Tumor Avidity of Radioiodinated Phospholipid Ether Analogues (2006)

Radioiodinated phospholipid ether analogues have shown a remarkable ability to selectively accumulate in a variety of human and animal tumors in xenograft and spontaneous tumor rodent models. It is believed that this tumor avidity arises as a consequence of metabolic differences between tumor and corresponding normal tissues. The results of this study indicate that one factor in the tumor retention of these compounds in tumors is the length of the alkyl chain that determines their hydrophobic properties. Decreasing the chain length from C12 to C7 resulted in little or no tumor accumulation and rapid clearance of the compound in tumor-bearing rats within 24 h of administration. Increasing the chain length had the opposite effect, with the C15 and C18 analogues displaying delayed plasma clearance and enhanced tumor uptake and retention in tumor-bearing rats. Tumor uptake displayed by propanediol analogues NM-412 and NM-413 was accompanied by high levels of liver and abdominal radioactivity 24 h postinjection to tumor-bearing rats. Addition of a 2-O-methyl moiety to the propanediol backbone also retarded tumor uptake significantly. A direct comparison between NM-404 and its predecessor, NM-324, in human PC-3 tumor bearing immune-compromised mice revealed a dramatic enhancement in both tumor uptake and total body elimination of NM-404 relative to NM-324. On the basis of imaging and tissue distribution studies in several rodent tumor models, the C18 analogue, NM-404, was chosen for follow-up evaluation in human lung cancer patients. Preliminary results have been extremely promising in that selective uptake and retention of the agent in tumors is accompanied by rapid clearance of background radioactivity from normal tissues, especially those in the abdomen. These results strongly suggest that extension of the human trials to include other cancers is warranted, especially when NM-404 is radiolabeled with iodine-124, a new commercially available positron-emitting isotope. The relatively long physical half-life of 4 days afforded by this isotope appears well-suited to the pharmacodynamic profile of NM-404.
Recognition of human melanoma cells by HLA-A2.1-restricted cytotoxic T lymphocytes is mediated by at least six shared peptide epitopes (1993)

HLA-A2.1-associated peptides were extracted from human melanoma cell lines and used to study epitopes for melanoma-specific HLA-A2.1-restricted CTL. CTL were generated from tumor-involved nodes by in vitro stimulation, initially with autologous melanoma cells and subsequently with allogeneic A2.1+ melanoma cells. These CTL lysed autologous melanoma plus four allogeneic HLA-A2.1+ melanomas, including an HLA-A2.1-transfected melanoma. K562, HLA-A2- melanomas and HLA-A2+ nonmelanomas were not lysed. HLA-A2.1 molecules were purified from human melanoma cell lines by immunoaffinity column chromatography of detergent-solubilized cell pellets. Peptides bound to the MHC molecules were acid eluted and fractionated by reversed phase HPLC. Individual fractions were assessed for their ability to reconstitute melanoma-specific epitopes by addition to the HLA-A2.1+ Ag-processing mutant, 721.174XCEM.T2 (T2). Five peaks of reconstitution were observed. Second dimension HPLC separations of reconstituting fractions revealed evidence for two distinct reconstituting peptides within one of these peaks. Based on these data, a minimum of six distinct peptides associated with HLA-A2.1 and recognized by melanoma-specific CTL are present on these different melanoma lines. These data document the presence of multiple peptide-defined CTL epitopes that are shared by at least three unrelated human melanoma cell lines.
Specifications for the Network Voice Protocol (NVP) (1977)

Abstract : The Network Voice Protocol (NVP) described in this report was developed by the Network Secure Communications group at ISI at the host-to-host protocol level, since the 'regular' host-to-host protocol was found unsuitable for real-time network voice communication. The report describes in detail the control and data components of the protocol. Appendix 1 defines associated tables, and Appendix 2 presents some implementation recommendations.
Molecular Analyses of the Arabidopsis TUBBY-Like Protein Gene Family (2004)

In mammals, TUBBY-like proteins play an important role in maintenance and function of neuronal cells during postdifferentiation and development. We have identified a TUBBY-like protein gene family with 11 members in Arabidopsis, named AtTLP1-11. Although seven of the AtTLP genes are located on chromosome I, no local tandem repeats or gene clusters are identified. Except for AtTLP4, reverse transcription-PCR analysis indicates that all these genes are expressed in various organs in 6-week-old Arabidopsis. AtTLP1, 2, 3, 6, 7, 9, 10, and 11 are expressed ubiquitously in all the organs tested, but the expression of AtTLP5 and 8 shows dramatic organ specificity. These 11 family members share 30% to 80% amino acid similarities across their conserved C-terminal tubby domains. Unlike the highly diverse N-terminal region of animal TUBBY-like proteins, all AtTLP members except AtTLP8 contain a conserved F-box domain (51-57 residues). The interaction between AtTLP9 and ASK1 (Arabidopsis Skp1-like 1) is confirmed via yeast (Saccharomyces cerevisiae) two-hybrid assays. Abscisic acid (ABA)-insensitive phenotypes are observed for two independent AtTLP9 mutant lines, whereas transgenic plants overexpressing AtTLP9 are hypersensitive to ABA. These results suggest that AtTLP9 may participate in the ABA signaling pathway.
Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images (2018)

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumor-infiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment.
3-(Alkylamino)-4H-pyrido[4,3-e]1,2,4-thiadiazine 1,1-dioxides as powerful inhibitors of insulin release from rat pancreatic B-cells: a new class of potassium channel openers? (1993)

peer reviewed
Human mononuclear phagocytes express adenosine A1 receptors. A novel mechanism for differential regulation of Fc gamma receptor function. (1993)

Using monoclonal anti-adenosine A1 receptor antibodies that bind the A1 receptor ligand binding site, we demonstrate that A1 receptors are expressed on cultured monocytes and rheumatoid synovial fluid mononuclear phagocytes. This finding is associated with the acquisition of reactivity with selective adenosine A1 receptor agonists and is temporally coordinated with the induction of adenosine A2 receptors on cultured monocytes. In a rapid, concentration-dependent fashion, these two distinct adenosine receptors modulate Fc gamma receptor-mediated phagocytosis, a response critical to the pathogenesis of immune complex diseases. Occupancy of A1 receptors by N6-cyclopentyladenosine (an A1-specific adenosine analogue) or mAb AA1 (an anti-A1 mAb) results in a potent stimulation that is blocked by adenosine receptor antagonists. This A1 receptor-induced enhancement of Fc gamma receptor-mediated phagocytosis is a consequence of preferential augmentation of Fc gamma RI function, suggesting distinct mechanisms for receptor-effector coupling of Fc gamma receptor families. In contrast, ligation of A2 receptors by A2-specific agonists decreases Fc gamma receptor-mediated phagocytosis in cultured monocytes. The opposing effects of adenosine A1 and A2 receptors allow for a concentration-dependent feed-back loop that responds more rapidly than effects elicited by other endogenous modulators. Low concentrations of adenosine are proinflammatory providing enhanced Fc gamma receptor function via A1 receptors, whereas higher concentrations that can occur with tissue damage are anti-inflammatory providing inhibition via A2 receptors. This rapid and potent modulation of Fc gamma receptor-mediated function suggests that adenosine is an important local regulator of the inflammatory response.
GAD65: a prospective vaccine for treating Type 1 diabetes? (2017)

In spite of modern techniques, the burden for patients with type 1 diabetes (T1D) will not disappear and T1D remains a life-threatening disease causing severe complications and increased mortality. We have to learn how to preserve residual insulin secretion or even increase beta cell regeneration. This would give a milder disease, simpler treatment and perhaps even cure. Thus, there are good reasons to try therapies that may preserve beta cell function. Areas covered: In this review the author reviews the literature and registered ongoing trials using GAD-alum put in relation to the high number of published different immune interventions. Expert opinion: GAD-alum treatment is safe, tolerable and easy for the patients and healthcare. It seems probable that treatment with GAD65-alum 20 µg sc can preserve residual beta cell function in T1D, but efficacy needs to be improved. This may be achieved by the use of combination therapies and new approaches for administration.