gebhart/patrepeval huggingface dataset:
DNA duplexes covalently labeled at two sites: synthesis and characterization by steady-state and time-resolved optical spectroscopies (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDNA duplexes covalently labeled at two sites: synthesis and characterization by steady-state and time-resolved optical spectroscopiesJoshua Telser, Kenneth A. Cruickshank, Larry E. Morrison, Thomas L. Netzel, and Chi Kin ChanCite this: J. Am. Chem. Soc. 1989, 111, 18, 7226–7232Publication Date (Print):August 1, 1989Publication History Published online1 May 2002Published inissue 1 August 1989https://pubs.acs.org/doi/10.1021/ja00200a050https://doi.org/10.1021/ja00200a050research-articleACS PublicationsRequest reuse permissionsArticle Views306Altmetric-Citations63LEARN 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
Cestode vaccines. (1991)

Studies over the past 20 years have clearly shown the potential for developing vaccines against larval cestode infections of man and animals. The important larval cestode infections of man (Echinococcus granulosus--hydatidosis: Taenia solium--cysticercosis) involve domesticated animals as intermediate hosts in their natural life-cycles. These animals develop strong immunity against reinfection, and immunity can be artificially induced by vaccination with oncosphere antigens. A major stumbling block in developing commercial vaccines against cestodes has been the difficulty in obtaining adequate supplies of these antigens. Recent studies with Taenia ovis, a larval cestode causing cysticercosis in sheep, have demonstrated the feasibility of developing commercial vaccines against cestodes using recombinant DNA technology. A cDNA library prepared using mRNA obtained from T. ovis oncospheres was used to isolate a clone which expressed T. ovis polypeptide antigen 45W as a fusion protein with Schistosoma japonicum glutathione S-transferase (GST-45W). GST-45W gave up to 94% protection against challenge infection when used to vaccinate sheep with saponin as adjuvant. The vaccine antigen was shown by SDS PAGE to be unstable, a major disadvantage in subsequent attempts to obtain high yields of antigen for commercial production. The fusion protein has now been stabilized by reducing the size of GST-45W cDNA through deleting 19 carboxyl terminal hydropathic acids, and the resultant fusion protein GST-45W (B/X) was highly host-protective. Another experiment showed that the 45W T. ovis polypeptide cleaved enzymatically from GST-45W was still host-protective, suggesting that GST had no influence on the immunogenicity of GST-45W fusion protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical and differential utility of VEGF inhibitors in wet age-related macular degeneration: focus on aflibercept (2012)

Age-related macular degeneration (AMD) has become a major public health problem and a leading cause of blindness in industrialized nations. AMD results from the ageing eye's inability to metabolize and dispose completely of photoreceptor outer segments and other waste products. As a result, lipids, particularly apolipoproteins, accumulate within Bruch's membrane, leading to chronic ischemia and inflammation. The subsequent upregulation of inflammatory cytokines and growth factors, including vascular endothelial growth factor (VEGF), induces the growth of neovascular membranes from the choriocapillaris into the subretinal or subretinal pigment epithelium spaces. To counter this, intravitreally administered drugs (pegaptanib, bevacizumab, ranibizumab) that specifically target VEGF have become the standard treatment for exudative AMD. Aflibercept, a recently approved fusion protein, binds to all isoforms of both VEGF-A and placental growth factor with high affinity. Phase III trials showed that monthly or every other month injections of aflibercept prevent vision loss (fewer than 15 letters) in 95% of patients. Additionally, aflibercept injections every 4 or 8 weeks produce average vision gains of 6.9 letters to 10.9 letters, comparable with those achieved with monthly ranibizumab. After one year of regularly administered aflibercept injections, patients required an average of only 4.2 injections during the second year. Aflibercept promises to decrease the injection frequency required for many patients and appears to serve as an effective "salvage" therapy for patients who respond poorly to other anti-VEGF drugs.
The effect of interferon-alpha A on two cases of Japanese encephalitis in Thailand. (1985)

Two Japanese encephalitis cases with serious comatous symptoms were treated with the Human Recombinant Interferon-alpha A. The clinical responses to IFN were found to be satisfactory. The first case showed improvement on the 5th day of IFN treatment and the general condition slowly improved. The second case recovered from the comatous stage on the 6th day of IFN, followed by quick improvement of general symptoms in the 2nd week and complete recovery without any mental sequelae. Leukopenia and neutropenia occurred during the first week of administration of IFN, but were only temporary. Slight elevation of SGOT and SGPT was observed in the first case. No other side effects including general toxicity, neurotoxicity or allergy, or any abnormal hematological and blood chemistry changes were observed in these 2 cases. Two other JE cases (the 3rd and 4th consecutive JE cases) were not treated with IFN, but received the usual regimens of symptomatic and supportive drugs. Both patients died on the 7th-9th day of illness. This study suggests that the Human Recombinant Leukocyte A Interferon possibly is an effective and promising agent in the treatment of Japanese encephalitis in Thailand. More studies to treat JE cases with this IFN are being performed in order to assess the efficacy, tolerance and safety of rIFN-alpha A on Japanese encephalitis in Thailand.
Signal, noise power spectrum, and detective quantum efficiency of indirect-detection flat-panel imagers for diagnostic radiology (1998)

The performance of an indirect-detection, active matrix flat-panel imager (FPI) at diagnostic energies is reported in terms of measured and theoretical signal size, noise power spectrum (NPS), and detective quantum efficiency (DQE). Based upon a 1536 x 1920 pixel, 127 microns pitch array of a-Si:H thin-film transistors and photodiodes, the FPI was developed as a prototype for examination of the potential of flat-panel technology in diagnostic x-ray imaging. The signal size per unit exposure (x-ray sensitivity) was measured for the FPI incorporating five commercially available Gd2O2S:Tb converting screens at energies 70-120 kVp. One-dimensional and two-dimensional NPS and DQE were measured for the FPI incorporating three such converters and as a function of the incident exposure. The measurements support the hypothesis that FPIs have significant potential for application in diagnostic radiology. A cascaded systems model that has shown good agreement with measured individual pixel signal and noise properties is employed to describe the performance of various FPI designs and configurations under a variety of diagnostic imaging conditions. Theoretical x-ray sensitivity, NPS, and DQE are compared to empirical results, and good agreement is observed in each case. The model is used to describe the potential performance of FPIs incorporating a recently developed, enhanced array that is commercially available and has been proposed for testing and application in diagnostic radiography and fluoroscopy. Under conditions corresponding to chest radiography, the analysis suggests that such systems can potentially meet or even exceed the DQE performance of existing technology, such as screen-film and storage phosphor systems; however, under conditions corresponding to general fluoroscopy, the typical exposure per frame is such that the DQE is limited by the total system gain and additive electronic noise. The cascaded systems analysis provides a valuable means of identifying the limiting stages of the imaging system, a tool for system optimization, and a guide for developing strategies of FPI design for various imaging applications.
Stress Injuries to Bone in College Athletes (2003)

The grading system used at this institution is a standardized tool that can be used to predict time to return to sport. A standardized rehabilitation protocol allowed for an appropriate plan to return the athletes to pain-free competition.
Meizothrombin formation during factor Xa-catalyzed prothrombin activation. Formation in a purified system and in plasma. (1991)

Meizothrombin and thrombin formation were quantitated during factor Xa-catalyzed activation of human prothrombin in reaction systems containing purified proteins and in plasma. In the purified system considerable amounts of meizothrombin accumulated when prothrombin was activated by factor Xa (with or without accessory components) under initial steady state conditions. The ratio of the rates of meizothrombin and thrombin formation was not influenced by variation of the pH, temperature, or ionic strength of the reaction medium. When 2 microM prothrombin was activated by the complete prothrombinase complex (factor Xa, factor Va, Ca2+, and phospholipid) 80-90% of the initially formed reaction product was meizothrombin. Lowering the prothrombin concentration from 2 to 0.03 microM caused a gradual decrease in the ratio of meizothrombin/thrombin formation from 5 to 0.6. When the phosphatidylserine content of the phospholipid vesicles was varied between 20 and 1 mol % and prothrombin activation was analyzed at 2 microM prothrombin the relative amount of meizothrombin formed decreased from 85 to 55%. With platelets, cephalin, or thromboplastin as procoagulant lipid, thrombin was the major reaction product and only 30-40% of the activation product was meizothrombin. We also analyzed complete time courses of prothrombin activation both with purified proteins and in plasma. In reaction systems with purified proteins substantial amounts of meizothrombin accumulated under a wide variety of experimental conditions. However, little or no meizothrombin was detected in plasma in which coagulation was initiated via the extrinsic pathway with thromboplastin or via the intrinsic pathway with kaolin plus phospholipid (cephalin, platelets, or phosphatidylserine-containing vesicles). Thus, thrombin was the only active prothrombin activation product that accumulated during ex vivo coagulation experiments in plasma.
Selection of sequences recognized by a DNA binding protein using a preparative Southwestern blot (1991)

We have tested the feasibility of using a preparative scale Southwestern blot to select DNA sequences specifically recognized by a DNA binding protein. We constructed a library of random 15-mer oligonucleotides and screened it using a preparative Southwestern blot with the transcriptional repressor, PRDI-BF1. Several sequences specifically recognized by PRDI-BF1 were isolated. All of these sequences are similar to PRDI, a regulatory element previously demonstrated to bind PRDI-BF1.
Packet Loss Recovery for Streaming Video (2002)

While there is an increasing demand for streaming video applications on the Internet, various network characteristics make the deployment of these applications more challenging than traditional TCP-based applications like email and the Web. Packet loss can be detrimental to compressed video with interdependent frames because errors potentially propagate across many frames. While latency requirements do not permit retransmission of all lost data, we leverage the characteristics of MPEG-4 to selectively retransmit only the most important data in the bitstream. When latency constraints do not permit retransmission, we propose a mechanism for recovering this data using postprocessing techniques at the receiver. We quantify the effects of packet loss on the quality of MPEG-4 video, develop an analytical model to explain these effects, present a system to adaptively deliver MPEG-4 video in the face of packet loss and variable Internet conditions, and evaluate the effectiveness of the system under various network conditions.
Synthesis and Biological Evaluation of Novel Analogues of the Pan Class I Phosphatidylinositol 3-Kinase (PI3K) Inhibitor 2-(Difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474) (2011)

A structure-activity relationship (SAR) study of the pan class I PI 3-kinase inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474) identified substitution at the 4 and 6 positions of the benzimidazole ring as having significant effects on the potency of substituted derivatives. The 6-amino-4-methoxy analogue displayed a greater than 1000-fold potency enhancement over the corresponding 6-aza-4-methoxy analogue against all three class Ia PI 3-kinase enzymes (p110α, p110β, and p110δ) and also displayed significant potency against two mutant forms of the p110α isoform (H1047R and E545K). This compound was also evaluated in vivo against a U87MG human glioblastoma tumor xenograft model in Rag1(-/-) mice, and at a dose of 50 mg/kg given by ip injection at a qd × 10 dosing schedule it dramatically reduced cancer growth by 81% compared to untreated controls.
Learning Graph Representations with Embedding Propagation (2017)

We propose Embedding Propagation (EP), an unsupervised learning framework for graph-structured data. EP learns vector representations of graphs by passing two types of messages between neighboring nodes. Forward messages consist of label representations such as representations of words and other attributes associated with the nodes. Backward messages consist of gradients that result from aggregating the label representations and applying a reconstruction loss. Node representations are finally computed from the representation of their labels. With significantly fewer parameters and hyperparameters an instance of EP is competitive with and often outperforms state of the art unsupervised and semi-supervised learning methods on a range of benchmark data sets.
Review article: drug interactions with agents used to treat acid‐related diseases (1999)

Patients with acid-related diseases often need to take multiple medications. Treatment of Helicobacter pylori infection often includes either a histamine type 2 (H2)-receptor antagonist or a proton pump (H+,K(+)-ATPase) inhibitor (proton pump inhibitor), administered in conjunction with one or more antimicrobials. Also, treatment for acid-related diseases often requires extended therapy during which many concomitant medications may be administered for concurrent disease states. Polypharmacy may be the result, particularly in elderly patients, who are at increased risk for both acid-related and many other diseases. Thus, it is important to understand the potential for clinically significant drug-drug interactions in this setting. H2-receptor antagonists and proton pump inhibitors can influence the pharmacokinetic profiles of other commonly administered medications by elevating intragastric pH, which can alter drug absorption, and by interacting with the cytochrome P (CYP) 450 enzyme system, which can affect drug metabolism and clearance. Such interactions are particularly important when they affect the pharmacokinetics of drugs with narrow therapeutic ranges (e.g. warfarin, digoxin). In these cases, drug-drug interactions can result in significant toxicity and even death. There are marked differences among H2-receptor antagonists and proton pump inhibitors in their potential for such interactions. The oldest drugs in each class, cimetidine and omeprazole, respectively, have the greatest potential to alter CYP activity and change the pharmacokinetics of other drugs. The most recently developed H2-receptor antagonist, famotidine, and the newer proton pump inhibitors, rabeprazole and pantoprazole, are much less likely to induce or inhibit CYP and thereby change the metabolism of other medications. These differences are important when choosing medications for the safe treatment of patients with acid-related diseases.
Distributed multimedia database: a design and application study (2000)

In this paper, we present the concept, design, and applications of a distributed multimedia database. A standard three-tier client-server architecture is proposed, including (i) database server (ii) middleware and underlying network infrastructure, and (iii) client module. We provide our evaluation of the latest technique developments related to different parts of the configuration, and discuss various options for distributed computing in a heterogeneous environment. We also present a case study/application of concept and configuration discussed in the paper, and review our implementation of an object-relational multimedia database using Informix Universal Server (IUS), CORBA/Java, and a client interface developed by our team.
Induction of Oxidative Stress Response by the Mycotoxin Patulin in Mammalian Cells (2006)

Patulin (PAT), a mycotoxin mainly produced by Penicillium and Aspergillus, is found in various foods and feeds. In the present study, its effects on oxidative stress in various mammalian cell lines were investigated. When cell-permeating fluorescent dyes were used as indicators of the generation of reactive oxygen species (ROS), we found that PAT treatment directly increased intracellular oxidative stress in human embryonic kidney (HEK293) and human promyelocytic leukemia (HL-60) cells. Lipid peroxidation levels were also significantly increased in HL-60 cells and mouse kidney homogenates treated with PAT. Suppression of CuZn-superoxide dismutase (SOD) expression in mammalian cells by small interfering RNA resulted in an increase in PAT-mediated membrane damage, while overexpression of human CuZn-SOD or catalase led to a reduction in damage, indicating the involvement of ROS in PAT toxicity. Pretreatment of HEK293 cells with Tiron, a free radical scavenger, reduced the phosphorylation levels of extracellular signal-regulated kinase (ERK) 1/2 elicited by PAT. The ERK1/2 signaling pathway inhibitor, U0126, also significantly decreased the levels of ROS associated with PAT treatment. These findings indicate that PAT treatment results in the ROS production in mammalian cells, and ROS partially contributes to PAT-induced cytotoxicity. Activation of ERK1/2 signaling pathway is correlated with PAT-mediated ROS.
Lipidic nanoparticle CPT-11 in a bioluminescent orthotopic pancreas cancer model (2007)

5648 Efforts to treat pancreas cancer have been hampered by a lack of effective therapeutic options as well as predictive preclinical models. We hypothesized that nanoparticle agents encapsulating potent cytotoxic compounds may be useful against pancreatic cancer; and that antibody-targeted versions directed against EGFR may further increase efficacy against EGFR-overexpressing pancreatic cancers. We applied a liposome-based drug loading and stabilization technique to generate nanoliposomal CPT-11, a novel lipidic nanoparticle agent containing the prodrug CPT-11 (irinotecan) that has entered clinical trials. In addition, Fab9 fragments of C225 were conjugated to nanoliposomal CPT-11 to generate EGFR-targeted immunoliposomal CPT-11. Another objective of this study was to develop a bioluminescent-based orthotopic xenograft model of pancreas cancer with EGFR-overexpression to test this therapeutic approach. COLO357, a human pancreatic cell line, was passaged multiple times in vivo to generate the sub-line L3.6pl. This cell line was subsequently modified by lentiviral transduction to generate a firefly luciferase-expressing cell line, L3.6pl-T. L3.6pl-T cells were injected, during surgery, directly into the pancreas of a nude mouse to generate a tumor xenograft. Following ip administration of luciferin, animals were immediately imaged using a Xenogen IVIS 100 bioluminescent imager, and subsequently imaged at weekly intervals. Tumor burden was quantified by measuring luminescence. The signal was quantified by defining regions of interest (ROIs) and measuring photons/sec/str. Agents evaluated in this model included EGFR-targeted immunoliposomal CPT-11, nanoliposomal CPT-11, free drug or vehicle control. All treatments were administered i.v. by tail vein beginning at 7 days post- tumor implantation and continued weekly for a total of three treatments. Both nanoliposomal CPT-11 and immunoliposomal CPT-11 showed potent antitumor activity, including durable tumor regressions, and were markedly superior to the equivalent dose of free drug. While both nanoparticle constructs were highly potent, the immunoliposome agent appeared to provide more prolonged duration of responses than the non-targeted version. Systemic toxicity was not observed with any treatment. We conclude that nanoparticle-mediated delivery of CPT-11 via nanoliposomal CPT-11 or anti-EGFR immunoliposomal CPT-11 greatly enhances antitumor efficacy in the orthotopic COLO357 pancreatic xenograft model. This therapeutic approach offers potential advantages for pancreatic cancer treatment, and this type of model system may be useful in preclinical evaluation.
Radiosensitization by the poly(ADP-ribose) polymerase inhibitor 4-amino-1,8-naphthalimide is specific of the S phase of the cell cycle and involves arrest of DNA synthesis (2006)

Radiosensitization caused by the poly(ADP-ribose) polymerase (PARP) inhibitor 4-amino-1,8-naphthalimide (ANI) was investigated in 10 asynchronously growing rodent (V79, CHO-Xrs6, CHO-K1, PARP-1+/+ 3T3, and PARP-1-/- 3T3) or human (HeLa, MRC5VI, IMR90, M059J, and M059K) cell lines, either repair proficient or defective in DNA-PK (CHO-Xrs6 and M059J) or PARP-1 (PARP-1-/- 3T3). Pulse exposure to ANI (1-hour contact) potentiated radiation response in rodent cells except in PARP-1(-/-) 3T3 fibroblasts. In contrast, ANI did not significantly enhance radiation susceptibility in asynchronously dividing human cells; yet, single-strand break rejoining was lengthened by ca. 7-fold in all but mouse PARP-1-/- 3T3s. Circumstantial evidence suggested that radiosensitization by ANI occurs in rapidly dividing cells only. Experiments using synchronized HeLa cells consistently showed that ANI-induced radiosensitization is specific of the S phase of the cell cycle and involves stalled replication forks. Under these conditions, prolonged contact with ANI ended in the formation of de novo DNA double-strand breaks hours after irradiation, evoking collision with uncontrolled replication forks of DNA lesions whose repair was impaired by inhibition of the PARP catalytic activity. The data suggest that increased response to radiotherapy by PARP inhibitors may be achieved only in rapidly growing tumors with a high S-phase content.
Induction of Autoimmune Diabetes by Oral Administration of Autoantigen (1996)

An antigen administered orally can induce immunological tolerance to a subsequent challenge with the same antigen. Evidence has been provided for the efficacy of this approach in the treatment of human autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. However, oral administration of autoantigen in mice was found to induce a cytotoxic T lymphocyte response that could lead to the onset of autoimmune diabetes. Thus, feeding autoantigen can cause autoimmunity, which suggests that caution should be used when applying this approach to the treatment of human autoimmune diseases.