gebhart/patrepeval huggingface dataset:
Paclitaxel by 1-hour infusion: an active drug in metastatic non-small-cell lung cancer. (1995)

Paclitaxel administered by 1-hour infusion is an active and well-tolerated new agent in the treatment of metastatic non-small-cell lung cancer. These results suggest that a paclitaxel dose of 200 mg/m2 is more effective than 135 mg/m2 and can produce responses in patients previously treated with cisplatin-based regimens. Incorporation into combination regimens is indicated.
Photoinitiators for free-radical-initiated photoimaging systems (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhotoinitiators for free-radical-initiated photoimaging systemsBruce M. Monroe and Gregory C. WeedCite this: Chem. Rev. 1993, 93, 1, 435–448Publication Date (Print):January 1, 1993Publication History Published online1 May 2002Published inissue 1 January 1993https://doi.org/10.1021/cr00017a019RIGHTS & PERMISSIONSArticle Views2925Altmetric-Citations219LEARN 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 (2 MB) Get e-Alertsclose Get e-Alerts
A Low Cost and Inner-round Pipelined Design of ECB-AES-256 Crypto Engine for Solid State Disk (2010)

Solid-State Disks (SSD) are widely used in government and security departments owing to its faster speed of data access, more durability, more shock and drop, no noise, lower power consumption, lighter weight compared with Magnetic disk. As a result, the demand of security for storing data has been generated. The Advanced Encryption Standard (AES) is today's key data encryption standard for protecting data, but the implementation of high-speed AES encryption engine needs to consume a large number of hardware resources. This paper presents a low-cost and inner-round pipelined ECB-256-AES encryption engine. Through sharing the resources between the AES encryption module and the AES decryption module and using the look-up table for the SubBytes and InvSubBytes operations, the logic resources have been largely reduced; by using loop rolling and inner-round pipelined techniques, a high throughput of encryption and decryption operations is achieved. A 1.986Gbits/s throughput and 232.748MHz clock frequency are achieved using 614 slices of the Xilinx xc6slx45-3fgg484. The simulation results show that the AES crypto design is able to meet the read and write speed of SATA 1.0 interface.
Constitutional Delay of Growth and Puberty: Do They Really Reach Their Target Height? (1991)

We compared the final adult height (FH) of patients with classic constitutional delay of growth and puberty with their target height (TH) and with the height prediction by the Bayley-Pinneau method (BP). 20 patients and their parents were included in our study: 6 females (mean age 19.1 years) and 14 males (mean age 20.6 years). No significant difference could be detected between TH, FH and BP prognosis. This is in contrast to recent studies using height data partly obtained by self-estimation. We measured our patients and their parents ourselves and were accurately able to calculate their genetically determined TH. This proceeding could explain our results. Our study shows that adolescents with true constitutional delay do not need treatment and that height prediction seems to be accurate.
Targeting the active β-catenin pathway to treat cancer cells (2006)

The adenomatous polyposis coli or beta-catenin genes are frequently mutated in colorectal cancer cells, resulting in oncogenic activation of beta-catenin signaling. We tried to establish in vitro and in vivo models for selectively killing human cancer cells with an activated beta-catenin/T-cell factor (Tcf) pathway. We used a recombinant adenovirus that carries a lethal gene [p53-up-regulated modulator of apoptosis (PUMA)] under the control of a beta-catenin/Tcf-responsive promoter (AdTOP-PUMA) to selectively target human colorectal cancer cells (SW480, HCT116, DLD-1, and LS174T), hepatocellular carcinoma (HepG2), and gastric cancer cells (AGS) in which the beta-catenin/Tcf pathway is activated, and compared its efficiency in killing cancer cells in which this pathway is inactive or only weakly active. AdFOP-PUMA, carrying a mutant Tcf-binding site, was used as control virus. The combined effect of AdTOP-PUMA with several chemotherapeutic agents (5-florouracil, doxorubicin, and paclitaxel) was also evaluated. The effect of AdTOP-PUMA on colorectal cancer cells was also examined in nude mice: SW480 cells were infected with the AdTOP-PUMA and AdFOP-PUMA, and then inoculated s.c. into nude mice. The TOP-PUMA adenovirus inhibited cell growth in a dose-dependent fashion, depending on the signaling activity of beta-catenin. The growth of cells displaying high levels of active beta-catenin/Tcf signaling was inhibited after infection with AdTOP-PUMA, whereas that of cells with low levels of beta-catenin signaling was not. Growth inhibition was associated with induction of apoptosis. Chemotherapy synergistically enhanced the effect of AdTOP-PUMA. A combination of the adenovirus system with standard therapy may improve the efficacy and reduce the toxicity of therapy in humans.
Light‐microscopic immunocytochemical localization of tyrosine hydroxylase in prenatal rat brain. II. Late ontogeny (1981)

The immunocytochemical localization of tyrosine hydroxylase is examined at embryonic (E) days 18 and 21 in rat brain in order to determine changes in the distribution and cytology of neurons showing immunoreactivity for the enzyme during late prenatal development. As compared with earlier stages of development, the distribution and morphology of the tyrosine hydroxylase-containing neurons at E18 and E21 more closely resemble catecholaminergic neurons in the adult brain. The changes occurring from the early to the late prenatal stages of development appear to be the result of an increase in number of cells and continued aggregation and migration of the labeled neurons. The major differences in the distribution of labeled perikarya between E18 and E21 are in the olfactory bulb and cerebral cortex. In the olfactory bulb, tyrosine hydroxylase-containing neurons are not detected until E21. In contrast in the cerebral cortex, a few neurons are transiently labeled for the enzyme at E18, but are not detected at E21 and have not been reported in the adult brain. The most striking change in the tyrosine-hydroxylase labeled structures in the late prenatal period is the increase in detectable immunoreactivity in bundles of axons and in terminal aborizations. The orderly appearance of tyrosine hydroxylase-labeled axons in the neostriatum and cortex are discussed in relation to the formation of these two contrasting regions innervated by catecholaminergic neurons.
Biology of factor IX (1993)

Within the past 20 years or so, factor IX has been at the centre of particularly intensive studies of its physiology, pathology and biochemistry as well as its molecular genetics and biology. With the complete nucleotide sequence of its human gene determined in 1985 and the molecular defects of over 600 abnormal human factor IX genes analysed to date, factor IX is among the few mammalian proteins which have been exhaustively studied in almost every aspect. The enormous amount of information we now have on this medium-sized plasma protein sheds light on how a gene and its protein evolve, how the protein carries out a highly regulated, specific and pivotal role in the delicately balanced blood coagulation reaction, and the correlation between clinical presentations and its highly diverse molecular mechanism of defects. This wealth of knowledge makes factor IX an excellent model for deeper study, such as truly quantitative analysis of its structure-function relationship andin vivofunction and regulation. It will also provide a sound foundation which may lead to improved treatment of haemophilia B and perhaps to its cure. This paper attempts to review the recent progress in research on factor IX.
Flt-1 but not KDR/Flk-1 tyrosine kinase is a receptor for placenta growth factor, which is related to vascular endothelial growth factor. (1996)

Placenta Growth Factor (PIGF) is a new member of vascular endothelial growth factor (VEGF) family. Although VEGF binds Flt family Flt-1 and KDR/Flk-1 tyrosine kinases at high affinity for signal transduction, biological activities and the receptors of PIGF have not been extensively studied. Reverse transcription-PCR showed that PIGF-2, a subtype of PIGF-1 that bears a basic amino acid-rich domain, is more abundant than PIGF-1 and thus is the major subtype in human placenta. Using antibodies specific to PIGF-1 or -2 as markers, we obtained large amounts of PIGFs in the baculovirus expression system. PIGF-2 had growth-stimulatory activity on human umbilical vein endothelial cells and vascular permeability activity in the Miles assay at levels about 10-fold lower than those of VEGF. All PIGF-1 activities were lower than those of PIGF-2. Both PIGFs competed for the binding of 125I-labeled VEGF to Flt-1 receptor but not to KDR/Flk-1 expressed on NIH3T3 cells. Furthermore, 125I-labeled PIGF bound to Flt-1 at high affinity but not to KDR/Flk-1. Supporting the notion that PIGF can use only Flt-1 as a receptor, PIGF activated Flt-1 to autophosphorylate, whereas PIGF could not generate signals from KDR/Flk-1. These results indicate that Flt-1, but not KDR/Flk-1, is a receptor for PIGF, suggesting that the weak biological activities of PIGF are due to its use of only part of the available VEGF signaling. These mild characteristics of PIGF may be important for the appropriate development and maintenance of normal placental tissue.
Approach for targeting Ras with small molecules that activate SOS-mediated nucleotide exchange (2014)

Aberrant activation of the small GTPase Ras by oncogenic mutation or constitutively active upstream receptor tyrosine kinases results in the deregulation of cellular signals governing growth and survival in ∼30% of all human cancers. However, the discovery of potent inhibitors of Ras has been difficult to achieve. Here, we report the identification of small molecules that bind to a unique pocket on the Ras:Son of Sevenless (SOS):Ras complex, increase the rate of SOS-catalyzed nucleotide exchange in vitro, and modulate Ras signaling pathways in cells. X-ray crystallography of Ras:SOS:Ras in complex with these molecules reveals that the compounds bind in a hydrophobic pocket in the CDC25 domain of SOS adjacent to the Switch II region of Ras. The structure-activity relationships exhibited by these compounds can be rationalized on the basis of multiple X-ray cocrystal structures. Mutational analyses confirmed the functional relevance of this binding site and showed it to be essential for compound activity. These molecules increase Ras-GTP levels and disrupt MAPK and PI3K signaling in cells at low micromolar concentrations. These small molecules represent tools to study the acute activation of Ras and highlight a pocket on SOS that may be exploited to modulate Ras signaling.
Nereistoxin and Cartap Neurotoxicity Attributable to Direct Block of the Insect Nicotinic Receptor/Channel (2003)

Nereistoxin (NTX) (4-dimethylamino-1,2-dithiolane) is the naturally occurring prototype for cartap [the bis(thiocarbamate) derivative of the NTX dithiol], which is generally regarded as a proinsecticide reverting to NTX. The aim of this study is to define the target site(s) for dithiolanes and dithiol esters. The affinity of [(3)H]NTX was not suitable for binding assays with honeybee (Apis mellifera) head membranes. However, NTX and cartap are equally potent, direct-acting, and competitive displacers of [(3)H]thienylcyclohexylpiperidine binding at the noncompetitive blocker (NCB) site of the Apis nicotinic acetylcholine receptor (nAChR)/channel. NTX also binds at the Apis [(3)H]imidacloprid agonist site, but cartap does not. As candidate metabolic pathways, sequential N-desmethylation and S-oxidation of NTX progressively reduce its potency at the NCB site and toxicity to houseflies. A P450 inhibitor reduces the toxicity of NTX and enhances it with cartap. Surprisingly, cartap is not just a pro-NTX but instead directly induces inhibitory neurotoxicity by blocking the nAChR/channel, whereas NTX may have dual NCB and agonist targets.
Syringolin Reprograms Wheat to Undergo Hypersensitive Cell Death in a Compatible Interaction with Powdery Mildew (2001)

We had previously isolated and characterized syringolin A, one of the molecular determinants secreted by Pseudomonas syringae pv syringae that is perceived by nonhost plant species such as rice. Here, we show that syringolin A is recognized by wheat and that it induces the accumulation of gene transcripts and increases protection against powdery mildew when applied before inoculation. Moreover, syringolin A essentially eradicates powdery mildew from infected wheat if applied after inoculation. This curative effect is accompanied by the induction of cell death and the reactivation of pathogenesis-related genes whose transcript levels initially accumulate after powdery mildew inoculation but then decline during the later course of infection. Because syringolin A has no fungicidal activity against a variety of fungi and its action on wheat cannot be mimicked by the fungicide cyprodinil, syringolin A is hypothesized to counteract the suppression of host defense reactions imposed by the pathogen on the colonized cells.
Costimulatory Molecules as Adjuvants for Immunotherapy (2006)

Tumor-associated antigens (TAAs) are by definition either weakly immunogenic or functionally nonimmunogenic. Therefore, efforts have concentrated on the development of vaccine strategies in which the presentation of TAAs to the immune system results in far greater activation of T cells than that occurring naturally in the host. Several strategies are being explored in our laboratory and others to enhance the immunogenicity of TAAs. These are: (a) placing the gene coding for the tumor antigen, as a transgene, into poxvirus vectors. (b) The use of diversified prime and boost vaccine strategies employing two different types of poxvirus vectors. (c) The use of T-cell costimulation; accomplished by placing transgenes for different T-cell costimulation molecules into viral vectors along with the transgenes for the TAA. (d) Altering the amino acid sequence of the TAA to enhance the host immune response. (e) The use of cytokines, and in particular GM-CSF, as a biologic adjuvant. This review will focus on the current state of the use of costimulatory molecules as adjuvants for immunotherapy, and in particular, as immunomodulators for cancer vaccines.
Efficient generation of a reshaped human mAb specific for the α toxin of Clostridium perfringens (1994)

We have used the technique of antibody reshaping to produce a humanized antibody specific for the alpha toxin of Clostridium perfringens. The starting antibody was from a mouse hybridoma from which variable (V) region nucleotide sequences were determined. The complementarity-determining regions (CDRs) from these V regions were then inserted into human heavy and light chain V region genes with human constant region gene fragments subsequently added. The insertion of CDRs alone into human frameworks did not produce a functional reshaped antibody and modifications to the V region framework were required. With minor framework modifications, the affinity of the original murine mAb was restored and even exceeded. Where affinity was increased, an altered binding profile to overlapping peptides was observed. Computer modelling of the reshaped heavy chain V regions suggested that amino acids adjacent to CDRs can either contribute to, or distort, CDR loop conformation and must be adjusted to achieve high binding affinity.
Oligonucleotide and Polymer Functionalized Nanoparticles for Amplification-Free Detection of DNA (2012)

Sensitive and quantitative nucleic acid testing from complex biological samples is now an important component of clinical diagnostics. Whereas nucleic acid amplification represents the gold standard, its utility in resource-limited and point-of-care settings can be problematic due to assay interferants, assay time, engineering constraints, and costs associated with both wetware and hardware. In contrast, amplification-free nucleic acid testing can circumvent these limitations by enabling direct target hybridization within complex sample matrices. In this work, we grew random copolymer brushes from the surface of silica-coated magnetic nanoparticles using azide-modified and hydroxyl oligo ethylene glycol methacrylate (OEGMA) monomers. The azide-functionalized polymer brush was first conjugated, via copper-catalyzed azide/alkyne cycloaddition (CuAAC), with herpes simplex virus (HSV)-specific oligonucleotides and then with alkyne-substituted polyethylene glycol to eliminate all residual azide groups. Our methodology enabled control over brush thickness and probe density and enabled multiple consecutive coupling reactions on the particle grafted brush. Brush- and probe-modified particles were then combined in a 20 min hybridization with fluorescent polystyrene nanoparticles modified with HSV-specific reporter probes. Following magnetic capture and washing, the particles were analyzed with an aggregate fluorescence measurement, which yielded a limit of detection of 6 pM in buffer and 60 pM in 50% fetal bovine serum. Adoption of brush- and probe-modified particles into a particle counting assay will result in the development of diagnostic assays with significant improvements in sensitivity.
DIABETES MELLITUS AND AGING: DIMINISHED PLATING EFFICIENCY OF CULTURED HUMAN FIBROBLASTS (1969)

This work concerns the effect of age and the diabetic gene(s) on the growth capacity of skin fibroblasts in culture. Cells from normal subjects and the progeny of conjugal diabetics have similar lifespans after multiple passages in mass culture. The combined lifespans in vitro are inversely proportional to the age of the donor. When individual cells are plated, more of those from normal subjects are able to form colonies. The difference in plating efficiency is apparent when first tested after 20 generations of growth, persists at 30 and 40 generations, but disappears after 50 generations. This cell culture system should be useful in studying the inheritance of the diabetic gene(s), the pathogenesis of the diabetic state, and the relationship between aging and diabetes, both of which decrease plating efficiency.
Bioactivity of Autologous Irradiated Renal Cell Carcinoma Vaccines Generated by Ex Vivo Granulocyte-Macrophage Colony-Stimulating Factor Gene Transfer (1998)

No AccessJournal of UrologyUrological Survey: Abstracts: Renal Tumors, Retroperitoneum, Ureter, and Urinary Diversion and Reconstruction1 Feb 1998Bioactivity of Autologous Irradiated Renal Cell Carcinoma Vaccines Generated by Ex Vivo Granulocyte-Macrophage Colony-Stimulating Factor Gene Transfer J.W. Simons, E.M. Jaffee, C.E. Weber, H.J. Levitsky, W.G. Nelson, M.A. Carducci, A.J. Lazenby, L.K. Cohen, C.C. Finn, S.M. Clift, K.M. Hauda, L.A. Beck, K.M. Leiferman, A.H. Owens, S. Piantadosi, G. Dranoff, R.C. Mulligan, D.M. Pardoll, and F.F. Marshall J.W. SimonsJ.W. Simons , E.M. JaffeeE.M. Jaffee , C.E. WeberC.E. Weber , H.J. LevitskyH.J. Levitsky , W.G. NelsonW.G. Nelson , M.A. CarducciM.A. Carducci , A.J. LazenbyA.J. Lazenby , L.K. CohenL.K. Cohen , C.C. FinnC.C. Finn , S.M. CliftS.M. Clift , K.M. HaudaK.M. Hauda , L.A. BeckL.A. Beck , K.M. LeifermanK.M. Leiferman , A.H. OwensA.H. Owens , S. PiantadosiS. Piantadosi , G. DranoffG. Dranoff , R.C. MulliganR.C. Mulligan , D.M. PardollD.M. Pardoll , and F.F. MarshallF.F. Marshall View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)63906-5AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Bioactivity of Autologous Irradiated Renal Cell Carcinoma Vaccines Generated by Ex Vivo Granulocyte-Macrophage Colony-Stimulating Factor Gene Transfer." The Journal of Urology, 159(2S), pp. 617–618 Oncology Center, Department of Urology, Johns Hopkins University School of Medicine, James Buchanan Brady Urological Institute, Baltimore, Maryland, University of Alabama at Birmingham, Birmingham, Alabama, Mayo Clinic, Rochester, Minnesota, Howard Hughes Medical Institute, Children's Hospital of Boston, Harvard University School of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts, and Somatix Therapy Corporation, Alameda, California.© 1998 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 159Issue 2SFebruary 1998Page: 617-618 Advertisement Copyright & Permissions© 1998 by American Urological Association, Inc.MetricsAuthor Information J.W. Simons More articles by this author E.M. Jaffee More articles by this author C.E. Weber More articles by this author H.J. Levitsky More articles by this author W.G. Nelson More articles by this author M.A. Carducci More articles by this author A.J. Lazenby More articles by this author L.K. Cohen More articles by this author C.C. Finn More articles by this author S.M. Clift More articles by this author K.M. Hauda More articles by this author L.A. Beck More articles by this author K.M. Leiferman More articles by this author A.H. Owens More articles by this author S. Piantadosi More articles by this author G. Dranoff More articles by this author R.C. Mulligan More articles by this author D.M. Pardoll More articles by this author F.F. Marshall More articles by this author Expand All Advertisement PDF downloadLoading ...
Effect of uracil on metabolism of 5-fluorouracil in vitro. (1979)

The effect of uracil on the metabolism of 5-fluorouracil (5-FU) in vitro was studied. 5-FU was mainly phosphorylated in intact Yoshida sarcoma cells, whereas it was mainly degraded in liver slices. Uracil inhibited degradation of 5-FU much more than its phosphorylation; incubation of 2,500 microM of uracil with 2.5 microM of 5-FU (molar ratio, 1,000:1) inhibited the degradation of 5-FU by 70%, but did not affect its phosphorylation. With homogenates of Yoshida sarcoma or liver uracil inhibited degradation of 5-FU greatly, phosphorylation of 5-FU by alpha-D-ribose 1-phosphate (RiblP) and ATP to some extent, and phosphorylation by 5-phospho-alpha-D-ribosyl diphosphate (PPRibP) very little. The activities of the enzymes involved in the metabolism of 5-FU in various tissues were also determined. Degradation of 5-FU was much faster in liver than in other tissues and was very slow in tumor tissue. Phosphorylation of 5-FU with RiblP and ATP was rapid in Yoshida sarcoma and bone marrow. Phosphoribosyltransferase activity was high in Yoshida sarcoma and thymus, but low in bone marrow.