gebhart/patrepeval huggingface dataset:
Synthesis and antiviral activity of distamycin A analogs: substitutions on the different pyrrole nitrogens and in the amidine function (1983)

Several new analogues of the antiviral antibiotic distamycin A were synthesized and assayed for their effects on influenza and herpes simplex virus. The new compounds 5b-j (R1-3 = H, CH3, and C2H5, R4,5 = H and CH3) were obtained via stepwise prepared formylated trimeric benzyl 4-aminopyrrole-2-carboxylates 3a-h, which after catalytic hydrogenolysis were coupled as N-succinimidyl esters directly with the proper beta-aminopropionamidine, unsubstituted or substituted with one or two methyl groups in the amidine function. Most of the new analogues did not exhibit significant effects on the viruses studied, but three compounds (5f-h) displayed activity on herpes virus as demonstrated in plaque formation and virus yield assays. Elevated cytotoxicity was simultaneously observed for 5g and 5h. For compound 5f, a partial separation of antiherpes activity and cytotoxicity was accomplished. The differences in antiherpes activity did not correspond to the differences in the inhibition of herpes virus DNA polymerase.
A two-dimensional microwave luneberg lens (1953)

Summary-A two-dimensional microwave model of the Luneberg lens has been designed employing the TE <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">10</inf> mode. It consists of two 36-inch diameter, almost-parallel, conducting plates with the space between plates filled with polystyrene. Its thickness varies with the normalized radius, T, to give the desired index of refraction n = <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\sqrt{2-r_2}</tex> Due to symmetrp about the center, this lens maintains constant gain and beam shape as a feed is scanned over its circumference, while the side lobe level remains at least 18 db below peak power. Experimental patterns show good agreement with computed patterns in the two principal planes.
Hepatobiliary abnormalities in patients with metastatic cancer treated with lapatinib (2009)

1043 Background: Lapatinib (LAP), a dual tyrosine kinase inhibitor (TKI), is effective in the treatment of HER-2-positive metastatic breast cancer. Liver toxicity has been reported as a side effect of several TKIs. We analyzed the liver safety of LAP using available data from 16 metastatic cancer trials. Methods: LAP (as monotherapy or in combination) was administered to 2,968 patients (pts) in metastatic cancer trials. Liver function tests were prospectively evaluated. We defined liver toxicity events as either NCI CTCAE grade (Gr) 3 or 4 alanine and aspartate aminotransaminases (ALT/AST) or meeting Hy's Law criteria (liver injury with jaundice). Results: Overall Gr 3 and 4 ALT/AST events were seen in 45/2,968 (1.5%) and 2/2,968 (0.07%) pts, respectively. Of LAP monotherapy pts, Gr 3 and 4 ALT/AST was seen in 13/1,470 (0.9%) and 1/1,470 (0.07%), respectively. Of LAP + monoclonal antibody (mAb) pts (trastuzumab or bevacizumab), Gr 3 and 4 ALT/AST was seen in 2/199 (1.0%) and 1/199 (0.5%), respectively. Ten of 645 pts (1.6%) treated with LAP + chemotherapy (capecitabine or paclitaxel) had Gr 3 ALT/AST. Twenty of 654 pts (3%) treated with LAP + letrozole had Gr 3 ALT/AST. Among 2,968 pts, Hy's law toxicity occurred in 8 (0.3%) pts: 2/1,470 (0.14%) pts treated with LAP alone, 1/199 (0.5%) pts treated with LAP + mAb, 4/645 (0.6%) pts treated with LAP + chemotherapy, and 1/654 (0.2%) pts treated with LAP + letrozole. Alternative causes of liver toxicity such as metastatic liver disease, infectious hepatitis, and heart failure will be reported at the meeting. Conclusions: Review of data from 16 clinical trials in metastatic cancer revealed low levels of liver toxicity for LAP. Oncologists should be vigilant for this rare side effect of LAP. A proposed monitoring algorithm of symptom assessment and frequency of hepatobiliary laboratory monitoring will be shown. [Table: see text]
Cyclophosphamide Induced CD11b+ Cells Can Inhibit Anti-CD40 Monoclonal Antibody (mAb) Therapy of B-Cell Lymphoma. (2004)

Abstract Immunotherapy with mAb is emerging as an important component of treatment for B-cell lymphoma. Furthermore, anti-tumor effects may be enhanced by combining mAb with a range of conventional cancer treatments and recently impressive results have been acheived with mAb in combination with chemotherapy. Here, we have assessed the efficacy of combining an agonistic anti-CD40 mAb with cyclophosphamide (CY). We have previously shown that large repeated doses of anti-CD40 mAb alone may stimulate cytotoxic T-cell lymphocyte (CTL) responses and provide robust protection in syngeneic murine tumors, such as BCL1 lymphoma. In this study we therefore used single smaller doses of the mAb that alone fail to provide long-term clearance thus allowing us to look for additive or synergistic effects of anti-CD40 and CY. Interestingly, the timing of CY relative to mAb administration appeared critical to therapeutic outcome. Cohorts given CY 7 days (d7 CY) prior to anti-CD40 show reduced survival compared to those receiving mAb alone. In contrast treatment with CY given 1 day before, or on the same day as mAb resulted in greatly increased tumor free survival. In vivo tracking experiments revealed that there is a potent CTL response that clears tumor around 5 days after anti-CD40 treatment. However, when CY was given d7 prior to anti-CD40 mAb, CTL expansion was reduced compared with other treatments, and instead resulted in increased numbers of splenic CD11b+ cells. These CD11b+ cells have an immature myeloid precursor phenotype and were able to produce nitric oxide (NO). Co-culture of CD11b+ cells with murine splenocytes resulted in greatly reduced cytotoxic CTL proliferation, but no apoptosis, which was reversed in the presence of NO inhibitors. Similarly, splenic CTL proliferation in vivo is inhibited by this increased population of CD11b+ cells. Importantly adoptive transfer of CY-induced CD11b+ into non-CY-treated mice inhibited anti-CD40 mAb tumor protection in BCL1 lymphoma. This data indicate that combining CY with immunotherapy can enhance therapeutic responses, but the timing of CY relative to immunotherapy is critical to the therapeutic outcome.
Genetic and Pharmacologic Inhibition of Complement Impairs Endothelial Cell Function and Ablates Ovarian Cancer Neovascularization (2012)

Complement activation plays a critical role in controlling inflammatory responses. To assess the role of complement during ovarian cancer progression, we crossed two strains of mice with genetic complement deficiencies with transgenic mice that develop epithelial ovarian cancer (TgMISIIR-TAg). TgMISIIR-TAg mice fully or partially deficient for complement factor 3 (C3) (Tg(+)C3(KO) and Tg(+)C3(HET), respectively) or fully deficient for complement factor C5a receptor (C5aR) (Tg(+)C5aR(KO)) develop either no ovarian tumors or tumors that were small and poorly vascularized compared to wild-type littermates (Tg(+)C3(WT), Tg(+)C5aR(WT)). The percentage of tumor infiltrating immune cells in Tg(+)C3(HET) tumors compared to Tg(+)C3(WT) controls was either similar (macrophages, B cells, myeloid-derived suppressor cells), elevated (effector T cells), or decreased (regulatory T cells). Regardless of these ratios, cytokine production by immune cells taken from Tg(+)C3(HET) tumors was reduced on stimulation compared to Tg(+)C3(WT) controls. Interestingly, CD31(+) endothelial cell (EC) function in angiogenesis was significantly impaired in both C3(KO) and C5aR(KO) mice. Further, using the C5aR antagonist PMX53, tube formation of ECs was shown to be C5a-dependent, possibly through interactions with the VEGF(165) but not VEGF(121) isoform. Finally, the mouse VEGF(164) transcript was underexpressed in C3(KO) livers compare to C3(WT) livers. Thus, we conclude that complement inhibition blocks tumor outgrowth by altering EC function and VEGF(165) expression.
Retardation of Prostate Tumor Progression in the Noble Rat by 4-Methyl-4-aza-steroidal Inhibitors of 5α-Reductase<xref ref-type="fn" rid="FN2">2</xref> (1985)

The effect of 4-methyl-4-aza-steroidal inhibitors of 5 alpha-reductase has been evaluated on tumor growth in the Noble rat model of prostatic adenocarcinoma. The growth characteristics of the tumor line 2Pr-121D(1) were consistent with heterogeneity of cell types, composed of androgen-sensitive and androgen-insensitive malignant cells. Both sodium 4-methyl-3-oxo-4-aza-5 alpha-pregnane-20 (s)-carboxylate and 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 and 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one significantly retarded tumor progression. Each agent increased tumor volume doubling time by approximately 62%. On the basis of their similarities to female rats and male castrate group, in terms of growth rate, tumor doubling time, and histologic characteristics, the treatments with the 4-methyl-4-aza-steroids appeared to produce effects common to both castration and estrogenization (chronic administration of pharmacologic doses of estrogen). The failure of 5 alpha-reductase inhibitors to be active as antiprostatic agents in vivo has hitherto detracted from their use of therapeutic agents. Present studies demonstrate that the 4-methyl-4-aza-steroidal inhibitors of 5 alpha-reductase may represent an alternative to orchiectomy and chronic estrogen therapy for the management of the hormone-dependent phase of prostate cancer.
Natural transformation of Neisseria gonorrhoeae: from DNA donation to homologous recombination (2005)

Gonococci undergo frequent and efficient natural transformation. Transformation occurs so often that the population structure is panmictic, with only one long-lived clone having been identified. This high degree of genetic exchange is likely necessary to generate antigenic diversity and allow the persistence of gonococcal infection within the human population. In addition to spreading different alleles of genes for surface markers and allowing avoidance of the immune response, transformation facilitates the spread of antibiotic resistance markers, a continuing problem for treatment of gonococcal infections. Transforming DNA is donated by neighbouring gonococci by two different mechanisms: autolysis or type IV secretion. All types of DNA are bound non-specifically to the cell surface. However, for DNA uptake, Neisseria gonorrhoeae recognizes only DNA containing a 10-base sequence (GCCGTCTGAA) present frequently in the chromosome of neisserial species. Type IV pilus components and several pilus-associated proteins are necessary for gonococcal DNA uptake. Incoming DNA is subject to restriction, making establishment of replicating plasmids difficult but not greatly affecting chromosomal transformation. Processing and integration of transforming DNA into the chromosome involves enzymes required for homologous recombination. Recent research on DNA donation mechanisms and extensive work on type IV pilus biogenesis and recombination proteins have greatly improved our understanding of natural transformation in N. gonorrhoeae. The completion of the gonococcal genome sequence has facilitated the identification of additional transformation genes and provides insight into previous investigations of gonococcal transformation. Here we review these recent developments and address the implications of natural transformation in the evolution and pathogenesis N. gonorrhoeae.
Predicting myelinated axon activation using spatial characteristics of the extracellular field (2011)

The computation time required for modeling the nonlinear response of an axon to an applied electric field is a significant limitation to optimizing a large number of neural interface design parameters through use of advanced computer algorithms. This paper introduces two methods of predicting axon activation that incorporate a threshold that includes the magnitude of the extracellular potential to achieve increased accuracy over previous computationally efficient methods. Each method uses a modified driving function that includes the second spatial difference of the applied extracellular voltage to predict the electrical excitation of a nerve. The first method uses the second spatial difference taken at a single node of Ranvier, while the second uses a weighted sum of the second spatial differences taken at all nodes of Ranvier. This study quantifies prediction accuracy for cases with single and multiple point source stimulating electrodes. While both new methods address the major criticism of linearized prediction models, the weighted sum method provides the most robust response across single and multiple point sources. These methods improve prediction of axon activation based on properties of the applied field in a computationally efficient manner.
A fast nearest-neighbor algorithm based on a principal axis search tree (2001)

A new fast nearest-neighbor algorithm is described that uses principal component analysis to build an efficient search tree. At each node in the tree, the data set is partitioned along the direction of maximum variance. The search algorithm efficiently uses a depth-first search and a new elimination criterion. The new algorithm was compared to 16 other fast nearest-neighbor algorithms on three types of common benchmark data sets including problems from time series prediction and image vector quantization. This comparative study illustrates the strengths and weaknesses of all of the leading algorithms. The new algorithm performed very well on all of the data sets and was consistently ranked among the top three algorithms.
Design of robust constrained model‐predictive controllers with volterra series (1995)

Abstract Sufficient conditions are developed in this work for robust stability and pefformance of nonlinear model‐predictive control systems that use an end‐condition and second‐order Volterra model with parametric uncertainty in the time domain. The robust stabilfly conditions involve the lengths of the prediction and control horizons, as well as the coefficients of the control move suppression terms in the on‐line objective function. These conditions may be used for both analysis and synthesis purposes. A case study of a chemical reactor is presented to elucidate these issues.
Nitrogen uptake, assimilation and remobilization in plants: challenges for sustainable and productive agriculture (2010)

This review presents the complexity of NUE and supports the idea that the integration of the numerous data coming from transcriptome studies, functional genomics, quantitative genetics, ecophysiology and soil science into explanatory models of whole-plant behaviour will be promising.
Topographic Templating of Islands and Holes in Highly Asymmetric Block Copolymer Films (2003)

Asymmetric diblock copolymers with a spherical domain structure form islands or holes on the free surface of a thin film when the initial spun-cast film thickness does not match that of an integral number of layers of spheres plus a brush. When this film is cast on a substrate topologically patterned with rectangular, flat bottomed wells as deep as a layer of spheres, the edges of these wells act as sinks for excess material. As a result, we observe the movement of material away from the raised areas (mesas) toward the adjacent wells so that if a mesa surface initially contains holes exposing the underlying layer of spheres or brush, these holes will coalesce and grow until the top layer of spheres forms a bicontinuous structure with the holes, and finally this structure will break up into discrete islands. If the islands exist on top of only a brush layer, their shrinkage is limited by the detachment kinetics of a chain from the island into the brush. If the islands are on top of another layer of spheres, the shrinkage of the islands is much faster than would be expected if it were controlled by the diffusion of chains through the underlying nanodomain structure.
Vandalio, el amador veleidoso de la poesía de Gutierre de Cetina (2004)

La idealizacion del amor no permite que el petrarquismo ni las teorias amorosas neoplatonicas renacentistas den cabida al cese del sentimiento amoroso. No obstante, Gutierre de Cetina escribio un grupo de poemas cuyo tema central, el desenamoramiento del pastor Vandalio de Dorida y su enamoramiento de Amarilida, deja subversivamente al descubierto la naturaleza mutable del amor. Partiendo de los rasgos del amador ideal, establecidos en la poesia de Francesco Petrarca, y de los tratados filograficos del siglo XVI, entre ellos el Dialogo della infinita de amore, de Tullia d'Aragona, este ensayo analiza como algunos textos de Cetina quebrantan las convenciones literarias y filosoficas de su epoca.In both Petrarchism and the Neoplatonic love theories of the Renaissance, the idealization of love does not allow for the possibility of the end of the feeling of love. Nevertheless, Gutierre de Cetina wrote a group of poems whose main topic, the shepherd Vandalio falling out of love with Dorida and in love with Ama...
Induction of Immunological Tolerance to Single‐stranded and Double‐stranded DNA (1982)

Single-stranded (ss) and double-stranded (ds) DNA were conjugated with the copolymers of d-glutamic acid and d-lysin (d-GL). Administration of ss-DNA-d-GL conjugates to C3H/H3 and NZB/W F1 mice could render the mice tolerant to both direct and indirect anti-ss-DNA antibody-forming cell responses, irrespective of their immune status. Repeated administration of ss-DNA- or ds-DNA-d-GL conjugates decreased the levels of anti-ss-DNA and anti-ds-DNA antibody titres and reduced the occurrence of ss-DNA and ds-DNA antibody-forming cells even in old female NZB/W F1 mice that had already developed an autoimmune state with lupus nephritis. The unresponsiveness was DNA-specific, and the state of tolerance was stable in vitro at the cellular level after the removal of the tolerogen. This tolerance model would be useful in analysing the regulatory mechanisms in anti-ss-DNA nd anti-ds-DNA antibody production, and application of this kind of therapy in the treatment of systemic lupus erythematosus is suggested.
Genetic deficiency in low density lipoprotein receptor-related protein confers cellular resistance to Pseudomonas exotoxin A Evidence that this protein is required for uptake and degradation of multiple ligands (1994)

The low density lipoprotein receptor-related protein (LRP) is a large multifunctional receptor implicated in the cellular uptake of functionally diverse ligands. Biochemical evidence suggests that LRP is a clearance receptor for apoE-rich remnant lipoproteins, lipoprotein lipase, alpha 2-macroglobulin/protease complexes, plasminogen activator/inhibitor complexes, the active protease tissue-type plasminogen activator and exotoxin A from Pseudomonas aeruginosa. Mice genetically deficient in LRP die early during gestation, underscoring the essential physiological role of this gene in vivo. To study the effect of LRP deficiency at the cellular level, we have used Pseudomonas exotoxin A (PEA) to select murine embryonic fibroblasts that are genetically deficient in LRP. Our results demonstrate that this single gene defect is sufficient to confer resistance to PEA on cultured cells. In addition, embryonic fibroblasts lacking LRP are unable to bind, internalize and degrade methylamine-activated alpha 2-macroglobulin and complexes of urokinase with plasminogen activator inhibitor-1. Furthermore, cellular uptake and degradation of receptor-associated protein, a 39 kDa accessory protein of LRP, is reduced by 90% in the absence of LRP. These results provide genetic evidence for the multifunctional nature of LRP and its crucial role in protease/inhibitor complex metabolism.
15-Desmethyl FK-506 and 15,31-desmethyl FK-506 from human liver microsomes: isolation, identification (by fast atom bombardment mass spectrometry and NMR), and evaluation of in vitro immunosuppressive activity (1994)

15-Desmethyl FK-506 and 15,31-desmethyl FK-506 metabolites extracted from incubated human liver microsomes were separated by normal and reversed-phase HPLC. The metabolites were identified by fast atom bombardment/mass spectrometry and nuclear magnetic resonance spectroscopy. The in vitro 50% inhibitory concentration, tested against bidirectional mixed lymphocyte reactions, was 325 mg/L for 15,31-desmethyl FK-506 and 4 mg/L for 15-desmethyl FK-506, indicating that these products of FK-506 demethylation retain in vitro immunosuppressive activity.
Anti‐amyloidogenic activity of tetracyclines: studies in vitro (2001)

Cerebral deposition of beta-amyloid is a major neuropathological feature in Alzheimer's disease. Here we show that tetracyclines, tetracycline and doxycycline, classical antibiotics, exhibit anti-amyloidogenic activity. This capacity was determined by the exposure of beta 1-42 amyloid peptide to the drugs followed by the electron microscopy examination of the amyloid fibrils spontaneously formed and quantified with thioflavine T binding assay. The drugs reduced also the resistance of beta 1-42 amyloid fibrils to trypsin digestion. Tetracyclines not only inhibited the beta-amyloid aggregates formation but also disassembled the pre-formed fibrils. The results indicate that drugs with a well-known clinical profile, including activity in the central nervous system, are potentially useful for Alzheimer's therapy.
Influenza A Viruses Expressing Intra- or Intergroup Chimeric Hemagglutinins (2016)

A panel of influenza A viruses expressing chimeric hemagglutinins (cHA) with intragroup or intergroup head/stalk combinations was generated. Viruses were characterized for growth kinetics and preservation of stalk epitopes. With a few notable exceptions, cHA viruses behaved similarly to wild-type viruses and maintained stalk epitopes, which indicated their potential as vaccine candidates to induce stalk-specific antibodies.
Free Solution Identification of Candidate Peptides from Combinatorial Libraries by Affinity Capillary Electrophoresis/Mass Spectrometry (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFree Solution Identification of Candidate Peptides from Combinatorial Libraries by Affinity Capillary Electrophoresis/Mass SpectrometryYen-Ho Chu, Daniel P. Kirby, and Barry L. KargerCite this: J. Am. Chem. Soc. 1995, 117, 19, 5419–5420Publication Date (Print):May 1, 1995Publication History Published online1 May 2002Published inissue 1 May 1995https://pubs.acs.org/doi/10.1021/ja00124a049https://doi.org/10.1021/ja00124a049research-articleACS PublicationsRequest reuse permissionsArticle Views113Altmetric-Citations58LEARN 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 (2)»Supporting Information Supporting Information Get e-Alerts