gebhart/patrepeval huggingface dataset:
Releasing the Brake on the Immune System: Ipilimumab in Melanoma and Other Tumors (2010)

Advanced melanoma has proven difficult to treat for many years, and no previous agent has shown improved survival in a phase 3 trial. The deepening understanding of tumor immunobiology and the complexity of the interactions between host T cells and cancer have led to novel treatment approaches. Among these, ipilimumab is a first-in-class T-cell potentiator that works by blocking cytotoxic T-lymphocyte antigen-4, a critical negative regulator of the antitumor T-cell response. From phase 1 studies, ipilimumab has shown encouraging activity in melanoma and other cancers, with unusual response patterns and mechanism-related, predictable toxicities that are medically manageable and mostly reversible but can sometimes be life threatening unless recognized and treated early. Early indications of a survival benefit in phase 2 studies have been confirmed recently in the first randomized phase 3 trial; the primary endpoint of the trial, overall survival (OS), was met with ipilimumab significantly prolonging median OS both as a single agent (10.1 months; p = 0.003) and combined with gp100 vaccine (10.0 months; p < 0.001) compared with vaccine control (6.4 months). Even more noteworthy was the improvement in long-term survival at 24 months from 13.7% (gp100 alone) to 21.6% and 23.5% for the combination and single ipilimumab, respectively. The addition of gp100 vaccine did not appear to impact OS since data for ipilimumab alone were similar to those for the combination with vaccine. Re-induction with ipilimumab in selected patients who progressed gave further clinical benefits. Ipilimumab has also shown promising activity in melanoma patients with brain metastases, and patients with non-small cell lung cancer, renal cell cancer, and castrate-resistant prostate cancer. Ipilimumab not only has a novel mechanism of action but demonstrates unique immune-related toxicities that require particular care in their recognition and treatment.
Whole abdominal radiotherapy in ovarian cancer (2010)

Whole abdominal radiotherapy after surgery and platinum-based chemotherapy achieves high locoregional disease control with an acceptable risk of acute toxicity.
Peptide Nanotubes and Beyond (1998)

Self-assembling peptide nanotubes (such as the cyclic peptide for which the calculated crystal structure is shown on the right) display a wide range of structural and functional capabilities that have enabled their application in biological as well as materials science. Recent advances in the field and future directions are discussed.
A switched parametric and transform audio coder (1999)

In this paper, we present a system of sines+transients+noise modeling techniques that dynamically switches between parametric representations and transform coding based representations. The sines and noise are represented by parametric models using multiresolution sinusoidal modeling and Bark-band noise modeling, respectively. The transients are modeled by short regions of transform coding. In addition, new methods are presented for selection and quantization of sinusoidal trajectories based on trajectory length and signal-to-masking thresholds. This system is useful for both low bitrate audio coding (20-40 kbps) and compressed-domain processing, such as time-scale modification.
Ultrasensitive time-resolved immunofluorometric assay of prostate-specific antigen in serum and preliminary clinical studies (1993)

We developed an ultrasensitive method for measuring prostate-specific antigen (PSA) in serum. The assay includes a capture monoclonal anti-PSA antibody coated to microtiter wells, a biotinylated rabbit polyclonal detection antibody, and alkaline phosphatase (ALP)-labeled streptavidin. The activity of ALP is measured with the substrate diflunisal phosphate; the released diflunisal forms highly fluorescent complexes with Tb(3+)-EDTA that are quantified with microsecond time-resolved fluorometry. The assay is precise and accurate and correlates well with the established Hybritech Tandem-PSA kit. Its distinguishing feature is extreme sensitivity (lowest limit of detection is 0.002 micrograms/L or 2 x 10(6) PSA molecules per assay). This is the most sensitive PSA assay reported thus far; we used it to quantify PSA in patients who had undergone radical prostatectomy. Many patients had < 0.01 micrograms/L PSA in their serum. This method could have important clinical applications in postsurgical early detection of relapse or residual prostate cancer, as recently suggested in the literature (Clin Chem 1992;38:1930-2).
Subtractive screening reveals up-regulation of NADPH oxidase expression in Crohn's disease intestinal macrophages (2001)

Macrophages play a central role during the pathogenesis of inflammation. In normal intestinal mucosa surface expression of typical macrophage markers such as CD14, CD16, CD11b or T-cell co-stimulatory molecules such as CD80 or CD86 is low indicating anergy and low pro-inflammatory activity of these cells. During inflammatory bowel disease (IBD) the mucosa is invaded by a population of macrophages displaying these markers, secreting higher cytokine levels and representing an activated cell population. CD33(+) cells (macrophages) were isolated from normal and Crohn's disease mucosa and mRNA was isolated by polyT magnetic beads. A subtractive screening was performed subtracting mRNA from normal macrophages from those of Crohn's disease macrophages. Oxidative burst activity was determined by flow cytometry. Seventy clones were obtained by the subtractive mRNA screening. Sequencing showed > 99% homology to mRNA of monocyte chemoattractant protein-1 (MCP-1) for three clones. Five clones obtained by subtraction revealed > 99% homology to mRNA of cytochrome b (subunit gp91). Differential expression of the cytochrome b subunit gp91 and the cytosolic NADPH oxidase subunit p67 was confirmed by RT-PCR and 'virtual' Northern blots. The fluorescence ratio of stimulated versus unstimulated cells was 0.9 +/- 0.16 in control macrophages indicating a lack of oxidative burst activity. In Crohn's disease this ratio was significantly increased to 1.80 +/- 0.8 (P = 0.004) confirming the molecular data. In conclusion NADPH oxidase mRNA is down-regulated or absent in macrophages from normal mucosa correlating with a lack of oxidative burst activity. In IBD macrophage-oxidative burst activity is increased and NADPH oxidase mRNA induced. Inhibition of NADPH oxidase could be a new therapeutical target in IBD and reduce mucosal tissue damage in active IBD.
High-Resolution Magnetic Resonance Imaging of Disparities in the Transcapillary Transfer Rates in Orthotopically Inoculated Invasive Breast Tumors (2004)

In vivo mapping of the transcapillary fluxes in tumors can help predict the efficacy of delivery of blood-borne anticancer drugs. These fluxes are primarily affected by the vascular permeability and the pressure gradients across the blood vessels' walls. We describe herein high-resolution dynamic contrast-enhanced magnetic resonance imaging of the influx and outflux transcapillary transfer rates in vivo in invasive MDA-MB-231 tumors orthotopically inoculated in severe combined immunodeficient mice. The tumors were noted for rapid growth, impaired drainage of fluid, and subsequent formation of cysts. Consequently, the time evolution of the contrast enhancement, induced by i.v. injection of Gadolinium diethylene-triamine-penta-acetate, exhibited two distinct patterns: transcapillary transfer in the cellular regions and simple diffusion in the cyst fluid. Both processes were analyzed at pixel resolution applying to each a physiological model and a corresponding algorithm. In the cellular region, the influx and outflux transcapillary transfer rates decreased during tumor growth; however, an increased disparity between the transfer constants was observed, with the outflux rate exceeding the influx rate. This quantitative spatial and temporal mapping of this disparity can provide a means to assess the physiological barriers to tracer delivery. It is hypothesized that both the increased disparity in transcapillary transfer rates and impaired fluid drainage in these tumors could arise from the development of interstitial hypertension.
Lack of Mutations inEGFRin Gastroenteropancreatic Neuroendocrine Tumors (2005)

To the Editor: Lynch et al.1 and Paez et al.2 correlated the presence of somatic mutations in the tyrosine kinase domain of the gene that encodes the epidermal growth factor receptor (EGFR) with responsiveness to gefitinib in non–small-cell lung carcinoma. Neuroendocrine differentiation is present in a substantial number of gastroenteropancreatic neuroendocrine tumors,3 and EGFR expression occurs in such tumors.4 We sought EGFR-activating mutations in a series of rare gastroenteropancreatic neuroendocrine cancers. DNA was isolated from flash-frozen specimens of carcinoid and pancreatic endocrine tumors; EGFR exons 18, 19, and 21 were amplified by the polymerase chain reaction with primers . . .
Enantioselective Total Synthesis of .beta.-Elemene and Fuscol Based on Enantiocontrolled Ireland-Claisen Rearrangement (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnantioselective Total Synthesis of .beta.-Elemene and Fuscol Based on Enantiocontrolled Ireland-Claisen RearrangementE. J. Corey, Bryan E. Roberts, and Brian R. DixonCite this: J. Am. Chem. Soc. 1995, 117, 1, 193–196Publication Date (Print):January 1, 1995Publication History Published online1 May 2002Published inissue 1 January 1995https://pubs.acs.org/doi/10.1021/ja00106a023https://doi.org/10.1021/ja00106a023research-articleACS PublicationsRequest reuse permissionsArticle Views1815Altmetric-Citations67LEARN 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
Bulk GaN Ion Cleaving (2010)

Bulk or freestanding GaN is a key material in various devices other than the blue laser diodes. However, the high cost of bulk GaN wafers severely limits the large scale exploitation of these potential technologies. In this paper, we discuss some engineering issues involved in the application of the ion-cut process to split a thin layer from 2-inch freestanding GaN. This process combines the implantation of light ions and wafer bonding and can possibly be used to reduce the cost of the fabrication of GaN-based devices by allowing the transfer of several bulk quality thin layers from the same donor wafer. To achieve this multi-layer transfer several conditions must be fulfilled. Here issues related to bulk GaN surface irregularities and wafer bowing are discussed. We also describe a method to circumvent most of these problems and achieve high quality bonding.
Optomechanics (2009)

Coherent optical systems combined with micromechanical devices may enable development of ultrasensitive force sensors and quantum information processing technology, as well as permit observation of quantum behavior in large-scale structures.
A Ribozyme Exclusively Aminoacylates the 3‘-Hydroxyl Group of the tRNA Terminal Adenosine (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTA Ribozyme Exclusively Aminoacylates the 3'-Hydroxyl Group of the tRNA Terminal AdenosineHirohide Saito and Hiroaki SugaView Author Information Department of Chemistry, University at Buffalo State University of New York Buffalo, New York, 14260-3000 Department of Chemistry and Biotechnology Graduate School of Engineering, University of Tokyo 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan Cite this: J. Am. Chem. Soc. 2001, 123, 29, 7178–7179Publication Date (Web):June 29, 2001Publication History Received5 March 2001Revised1 June 2001Published online29 June 2001Published inissue 1 July 2001https://pubs.acs.org/doi/10.1021/ja015756shttps://doi.org/10.1021/ja015756srapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views838Altmetric-Citations40LEARN 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 (1)»Supporting Information Supporting Information SUBJECTS:Assays,Genetics,Monomers,Nucleic acids,Peptides and proteins Get e-Alerts
A novel human Fab antibody for Trop2 inhibits breast cancer growth in vitro and in vivo (2013)

Human trophoblastic cell surface antigen 2 (Trop2) has been suggested as an oncogene, which is associated with the different types of tumors. In this study, a human Fab antibody against Trop2 extracellular domain was isolated from phage library by phage display technology, and characterized by ELISA, FACS, fluorescence staining and Western blotting analysis. MTT, apoptosis assay and wound healing assay were employed to evaluate the inhibitory effects of Trop2 Fab on breast cancer cell growth in vitro, while tumor-xenograft model was employed to evaluate the inhibitory effects on breast cancer growth in vivo. The results showed that Trop2 Fab inhibited the proliferation, induced the apoptosis and suspended the migration of MDA-MB-231 cells in a dose dependent manner. The expression caspase-3 was activated, and the expression of Bcl-2 was reduced while that of Bax was elevated in MDA-MB-231 cells by treating with Trop2 Fab. In addition, Trop2 Fab inhibited the growth of breast cancer xenografts and the expression of Bcl-2 was reduced while that of Bax was elevated in xenografts. Trop2 Fab, which was isolated successfully in this research, is a promising therapeutic agent for the treatment of Trop2 expressing breast cancer.
Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, Fourth Edition. Carl A. Burtis, Edward R. Ashwood, and David E. Bruns, editors. St. Louis, MO: Elsevier Saunders, 2006, 2448 pp., $229.00, hardcover. ISBN 0-7216-0189-8. (2006)

In most clinical laboratories, the Tietz Textbook is an obligatory reference book, kept in a central place, always available to everyone—laboratory scientists, trainees, and students alike. This edition is a welcome, carefully prepared update that appears some 6 years after the previous edition, and it considers all of the recent striking developments in clinical chemistry as a leading discipline of laboratory medicine. Although the basic principles and the general outline of the book have been maintained, there are numerous changes from the previous edition, as reflected by the new title, which now includes the wording “Molecular Diagnostics”.

The size of the book has increased by ∼500 pages, increasing from 1917 to 2448 pages. There are 102 contributors (76 from the United States), with 73 new authors and a new editor, Dr. Bruns, who joins in forming a renowned triumvirate of editors. The book comprises 56 chapters with more than 10 500 references in total. Because the …
Combinations of tetrahydrouridine and cytosine arabinoside in mouse tumors. (1977)

Thirteen experimental mouse neoplasms were tested by cytidine (CR)-deaminase and deoxycytidine (dCR)-kinase levels. Four neoplasms, Sarcoma T241, Adenocarcinoma E0771, Lewis lung carcinoma (LL), and Sarcoma 180 Japan (S180J), considered to have high deaminase and sufficient dCR-kinase activities, were tested in vivo for combination chemotherapy with cytosine arabinoside (ara-C) and the CR-deaminase inhibitor, tetrahydrouridine (THU). THU did not significantly improve the growth inhibition of ara-C in a wide range of combinations in T241, E0771, LL, and the solid form of S180J, but more than doubled the survival time of the S180J ascites-bearing animals. Toxicity in the form of weight loss and toxic deaths was observed in some but not all groups, especially at high dosages of ara-C and THU. Tissue distribution of [3H]-ara-C and [14C]-THU in T241-bearing mice revealed an accelerated clearance of ara-C-derived radioactivity under the influence of THU in the tumor and five host tissues, but not in the small intestines. With the exception of the small intestines, clearance of THU-derived radioactivity was faster in all tissues studied compared to the clearance of [3H]-ara-C-derived radioactivity. Intracellular CR-deaminase levels were inhibited significantly, ie, dose dependent, in tumor and host kidney after a single ip injection of THU to E0771--bearing mice. In the solid S180J, with or without simultaneous ip administration of THU, [3H]-ara-C was not converted to 5'-di- and tri-phosphates at all. In mice bearing the ascites form of S180J, [3H]-ara-C was extensively converted to ara-C 5'-di- and tri-phosphates. THU increased both overall ara-C-derived radioactivity and the relative amounts of ara-C 5'-di- and tri-phosphates.
Assessment of the aggregation state of integral membrane proteins in reconstituted phospholipid vesicles using small angle neutron scattering (1997)

The assessment of the physical size of integral membrane protein complexes has generally been limited to samples solubilized in non-ionic detergent, a process which may introduce artifacts of unknown scope and severity. A system has been developed that allows observation of the small angle scattering profile of an integral membrane protein while incorporated in small unilamellar phospholipid vesicles. Contrast matching of isotopically substituted phospholipid eliminates the contribution of the bilayer to the observed scattering, resulting in a profile dependent only on the structure of the individual membrane protein complexes and their spatial arrangement in the vesicle. After appropriate compensation for their spatial arrangement, information about the molecular mass and radius of gyration of the individual complexes can be obtained. The validity of the approach has been established using monomeric bacteriorhodopsin as a model system.
UniFrac: an effective distance metric for microbial community comparison (2010)

UniFrac is a β-diversity measure that uses phylogenetic information to compare environmental samples. UniFrac, coupled with standard multivariate statistical techniques including principal coordinates analysis (PCoA), identifies factors explaining differences among microbial communities. A recent simulation study concluded that UniFrac is unsuitable as a distance metric and should not be used for multivariate analysis (Schloss, 2008). We counter this argument by reassessing the data that led to this conclusion and by providing a mathematical proof showing that UniFrac is a distance metric. However, we confirm with actual sequence data that UniFrac values can be influenced by the number of sequences/sample, and recommend sequence jackknifing (that is, determining how often the cluster results are recovered using random subsets of the data) to avoid this issue.
Antibodies to watch in 2010 (2010)

Monoclonal antibodies (mAbs) are a burgeoning class of therapeutics, with more than 25 approved in countries worldwide. Novel molecules are entering clinical study at a rate of nearly 40 per year, and the commercial pipeline includes approximately 240 mAb therapeutics in clinical studies that have not yet progressed to regulatory approval or been approved. Of particular interest are the 26 mAbs that are currently at Phase 3, when safety and efficacy data critical to approval is established. Phase 3 study lengths are typically two to four years, so results for some studies might be announced in 2010, but data from others might not be presented until 2014. This overview of the 26 candidates provides a brief description of the background and the on-going Phase 3 studies of each mAb. Additional mAbs that have progressed to regulatory review or been approved may also be in Phase 3 studies, but these, as well as Fc fusion proteins, have been excluded. Due to the large body of primary literature about the 26 candidates, only selected references are given, with a focus on recent publications and articles that were relevant to Phase 3 studies. Current as of October 2009, the results presented here will serve as a baseline against which future progress can be measured.
Retro and retroenantio analogs of cecropin-melittin hybrids. (1995)

Hybrid analogs of cecropin A (CA) and melittin (M), which are potent antibacterial peptides, have been synthesized. To understand the structural requirements for this antibacterial activity, we have also synthesized the enantio, retro, and retroenantio isomers of two of the hybrids and their N-terminally acetylated derivatives. All analogs of CA(1-13)M(1-13)-NH2 were as active as the parent peptide against five test bacterial strains, but one bacterial strain was resistant to the retro and retroenantio derivatives. Similarly, all analogs of CA(1-7)M(2-9)-NH2 were active against four strains, while two strains were resistant to the retro and retroenantio analogs containing free NH3+ end groups, but acetylation restored activity against one of them. From these data it was concluded that chirality of the peptide was not a critical feature, and full activity could be achieved with peptides containing either all L- or all D-amino acids in their respective right-handed or left-handed helical conformations. For most of the bacterial strains, the sequence of these peptides or the direction of the peptide bonds could be critical but not both at the same time. For some strains, both needed to be conserved.
Rapid isolation of metaphase chromosomes containing high molecular weight DNA. (1979)

Metaphase chromosomes with high molecular weight DNA were isolated from Chinese hamster ovary (CHO) cells in a neutral buffer containing polyamines and chelators. The individual, unfixed chromosomes retained their centromeric and secondary constrictions, distinct sister chromatids, and complex banding patterns. The DNA from these chromosomes was 100-fold larger (2 x 10(8) daltons) than DNA from chromosomes isolated by other procedures. These characteristics indicate preservation during isolation of considerable native structure. In contrast to chromosomes produced by other methods, these chromosomes were stable in storage and did not aggregate, thus providing useful material for studies of the structure and biochemistry of individual chromosomes.