gebhart/patrepeval huggingface dataset:
Simian virus 40 (SV40) large T antigen-dependent amplification of an Epstein-Barr virus-SV40 hybrid shuttle vector integrated into the human HeLa cell genome (1992)

We analysed the DNA rearrangements that occurred during the integration and amplification of an Epstein-Barr virus (EBV)-simian virus 40 (SV40) hybrid shuttle vector in human cells. The human HeLa cell line was episomally transformed with the EBV-SV40 p205-GTI plasmid. After a 2 month culture in a selective medium, a HeLa cell-derived population (H-G1 cells) was obtained in which the p205-GTI vector was integrated as a single intact copy deleted in the EBV latent origin of replication (OriP). Sequencing data showed that the endpoints of the plasmid sequences, at the plasmid-cell DNA junctions, are located within the two essential elements of EBV OriP, which may form several secondary structures. This result suggests that a specific DNA sequence (OriP) or palindromic structures could play a role in this integration process. This represents the first fully characterized site of integration of an EBV vector in human cells. The transient expression of the SV40 large T antigen in H-G1 cells leads to the appearance of episomal molecules with an extremely heterogeneous size pattern. Individual analysis of these episomes after rescue in bacteria indicated that they retained sequences of both the p205-GTI plasmid and cellular DNA. Comparison of the structure of these circular DNAs with those of the integrated p205-GTI copy indicated that large T antigen expression in human cells leads to the amplification of the integrated shuttle vector according to the 'onion skin' model developed for transformed rodent cells. Indeed, amplified sequences were colinear with the integrated p205-GTI copy and its surrounding cellular sequences, distributed almost equally around the SV40 replication origin, and circularized by illegitimate recombination which did not involve specific nucleotide sequences. This system is of interest in that it enables easy recovery of individual recombined molecules in host bacteria. Each isolated clone contains a unique recombination junction which is easily and rapidly characterized and sequenced.
Molecular Epidemiology of Norovirus Infections in Stockholm, Sweden, during the Years 2000 to 2003: Association of the GGIIb Genetic Cluster with Infection in Children (2005)

The incidence of norovirus-associated gastroenteritis and the molecular epidemiology of norovirus strains were studied during three seasons (2000-2001, 2001-2002, and 2002-2003) among patients of all ages, mainly from the Stockholm region in Sweden. A total of 3,252 fecal samples were analyzed by reverse transcription-PCR. The incidences of norovirus infection among adults were 23, 26, and 30% during the three seasons studied and 18, 11, and 15% among children 0 to 15 years of age. During the first season, all norovirus strains detected by PCR were typed either by reverse line blot hybridization or nucleotide sequence analysis. During the two successive seasons, a total of 60 norovirus-positive strains from the beginning, peak, and end of the seasons were selected for nucleotide sequence analysis. We identified two dominant norovirus variants over the seasons: a new norovirus variant, recently described as the GGIIb genetic cluster, dominated among children during the first season, and during the following two seasons, a GGII-4 variant dominated. Our data suggest that norovirus infections are common, not only among adults, but also among children, and that some strains may predominantly affect children.
Homeostasis and regeneration of the hematopoietic stem cell pool are altered in SHIP-deficient mice (2003)

SH2-containing inositol 5-phosphatase (SHIP) is an important negative regulator of cytokine and immune receptor signaling. SHIP-deficient mice have a number of hematopoietic perturbations, including enhanced cytokine responsiveness. Because cytokines play an important role in the maintenance/expansion of the primitive hematopoietic cell pool, we investigated the possibility that SHIP also regulates the properties of cells in these compartments. Primitive hematopoietic cells were evaluated in SHIP-deficient mice and wild-type littermate controls using the colony-forming unit-spleen (CFU-S) and competitive repopulating unit (CRU) assays for multipotent progenitors and long-term lympho-myeloid repopulating cells, respectively. Absence of SHIP was found to affect homeostasis of CFU-S and CRU compartments. Numbers of primitive cells were increased in extramedullary sites such as the spleen of SHIP-deficient mice, although total body numbers were not significantly changed. In vivo cell cycle status of the CRU compartment was further evaluated using 5-fluorouracil (5-FU). SHIP-deficient CRUs were more sensitive to 5-FU killing, indicating a higher proliferative cell fraction. More strikingly, SHIP was found to regulate the ability of primitive cells to regenerate in vivo, as CRU recovery was approximately 30-fold lower in mice that received transplants of SHIP-deficient cells compared with controls. These results support a major role for SHIP in modulating pathways important in homeostasis and regeneration of hematopoietic stem cells, and emphasize the importance of negative cytokine regulation at the earliest stages of hematopoiesis.
The effect of conjugated linoleic acid on fat to lean repartitioning and feed conversion in pigs (1997)

The repartioning effect of CLA was evaluated using 108 pigs (54 gilts and 54 barrows) fed from 61.5 to 106 kg liveweight. Pigs were fed a cereal-based basal diet containing either 2% CLA or 2% sunflower oil (a rich source of α-linoleic acid). Irrespective of gender, pigs fed CLA tended to have reduced feed intakes (−5.2%, P = 0.07), improved feed conversion efficiences (−5.9%, P = 0.06) and similar rates of gain relative to sunflower oil fed pigs. In addition, pigs fed CLA deposited less subcutaneous fat (−6.8%, P = 0.01) and gained more lean (+2.3%, P = 0.03) than pigs fed sunflower oil. These data suggest CLA can be used as a repartioning agent in pigs and that further research to optimize the repartitioning effect is warranted. Key words: Pig, pork, swine, conjugated linoleic acid, CLA, repartioning
A sodium carbonate-bicarbonate buffer for alkaline phosphatases (1945)

Research Article| January 01 1945 A sodium carbonate-bicarbonate buffer for alkaline phosphatases G. E. Delory; G. E. Delory 1Royal Infirmary, Preston Search for other works by this author on: This Site PubMed Google Scholar E. J. King E. J. King 2British Postgraduate Medical School, London Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1945) 39 (3): 245. https://doi.org/10.1042/bj0390245 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation G. E. Delory, E. J. King; A sodium carbonate-bicarbonate buffer for alkaline phosphatases. Biochem J 1 January 1945; 39 (3): 245. doi: https://doi.org/10.1042/bj0390245 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1945 CAMBRIDGE UNIVERSITY PRESS, ENGLAND1945 Article PDF first page preview Close Modal You do not currently have access to this content.
p53 gene mutations are associated with decreased sensitivity of human lymphoma cells to DNA damaging agents. (1994)

The present study assessed the role of the p53 tumor suppressor gene in cell cycle arrest and apoptosis following treatment of Burkitt's lymphoma and lymphoblastoid cell lines with gamma-rays, etoposide, nitrogen mustard, and cisplatin. Cell cycle arrest was measured by flow cytometry; p53 and p21Waf1/Cip1 protein levels were measured by Western blotting; cell survival was measured in 72-96-h growth inhibition assays and by trypan blue staining, and apoptotic DNA fragmentation was assessed by either agarose gel electrophoresis or a modified filter elution method. We found that gamma-rays and etoposide induced a strong G1 arrest in the wild-type p53 lines while nitrogen mustard and cisplatin induced relatively little G1 arrest. All agents failed to induce G1 arrest in cells containing mutant p53 genes. The degree of G1 arrest observed with these agents correlated with the rate of p53 and p21Waf1/Cip1 protein accumulation: gamma-rays and etoposide induced rapid accumulation of both p53 and p21Waf1/Cip1; nitrogen mustard and cisplatin induced slow accumulation of p53 and no major accumulation of the p21Waf1/Cip1 protein. Despite differences in G1 arrest and kinetics of p53 or p21Waf1/Cip1 protein accumulation, all agents tended to decrease survival to a greater extent in the wild-type p53 lines compared to the mutant p53 lines. Cell death in the wild-type p53 lines was associated with intracellular DNA degradation into oligonucleosomal sized DNA fragments, indicative of apoptosis. We also observed an inverse sensitivity relationship between nitrogen mustard/cisplatin and etoposide in the mutant p53 lines and this was found to correlate with topoisomerase II mRNA levels in the cells. Our results suggest that p53 gene status is an important determinant of both radio- and chemosensitivity in lymphoid cell lines and that p53 mutations are often associated with decreased sensitivity to DNA damaging agents.
Purification, Potency, and Efficacy of the Botulinum Neurotoxin Type A Binding Domain fromPichia pastorisas a Recombinant Vaccine Candidate (1998)

Recombinant botulinum neurotoxin serotype A binding domain [BoNT/A(Hc)], expressed in Pichia pastoris, was developed as a vaccine candidate for preventing botulinum neurotoxin type A (BoNT/A) intoxication. After fermentation and cell disruption, BoNT/A(Hc) was purified by using a three-step chromatographic process consisting of expanded-bed chromatography, Mono S cation-exchange chromatography, and hydrophobic interaction chromatography. Two pools of immunogenic product were separated on the Mono S column and processed individually. Both products were more than 95% pure and indistinguishable by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blot analysis, and enzyme-linked immunosorbent assay (ELISA). Each protein was assayed for potency in mice at immunogen doses ranging from 2.4 ng to 10 microg, followed by challenge with 1,000 mouse intraperitoneal 50% lethal doses (i.p. LD50) of BoNT/A. The calculated 50% effective dose for both peaks was approximately 0.1 microg/mouse. Peak 1 was evaluated further in a mouse efficacy assay. Mice were injected either once, twice, or three times at five different doses and subsequently challenged with 100,000 mouse i.p. LD50 of BoNT/A. In general, multiple injections protected better than one, with complete or nearly complete protection realized at doses of >/=0.5 microg/mouse. Serum neutralization and ELISA titers were also determined. Tellingly, 82 of 83 mice with antibody titers of >/=1, 600, as measured by ELISA, survived, but only 6 of 42 mice with titers of </=100 survived. This work shows that the purified BoNT/A(Hc) produced was a highly effective immunogen, able to protect against a high challenge dose of neurotoxin.
A phase I clinical, plasma, and cellular pharmacology study of gemcitabine. (1991)

A novel deoxycytidine analog, gemcitabine (2',2'-difluorodeoxycytidine [dFdC]), has been studied in a phase I clinical and pharmacology trial. Doses ranging from 10 to 1,000 mg/m2 were administered over 30 minutes weekly times 3 weeks every 4 weeks. The maximum-tolerated dose (MTD) was 790 mg/m2. The dose-limiting toxicity was myelosuppression, with thrombocytopenia and anemia quantitatively more important than granulocytopenia. Nonhematologic toxicity was minimal. Two responses in patients with adenocarcinomas of the colon and lung were documented. The maximum dFdC plasma concentration, reached after 15 minutes of infusion, was proportional to the total dose administered. Elimination, due mainly to deamination, was rapid (terminal half-life [t1/2], 8.0 minutes) and dose independent. The deamination product 2',2'-difluorodeoxyuridine (dFdU) was eliminated with biphasic kinetics characterized by a long terminal phase (t1/2, 14 hours); it was the sole metabolite detected in urine. The concentration of dFdC 5'-triphosphate in circulating mononuclear cells increased in proportion to the dFdC dose at infusions between 35 and 250 mg/m2. No further increment in dFdC 5'-triphosphate (dFdCTP) was observed at higher doses, which resulted in plasma dFdC concentrations greater than 20 mumol/L (350 to 1,000 mg/m2), suggesting saturation of dFdC 5'-phosphate accumulation. The recommended dose for phase II clinical trials in solid tumors is 790 mg/m2/wk.
Cytochemical Methods for the Detection of Apoptosis (1999)

Detection of apoptotic cell death in cells and tissues has become of paramount importance in many fields of modern biology, including studies of embryonic development, degenerative disease, and cancer biology. In addition to methods that employ biochemical analysis of large populations of cells, cytochemical methods have recently been extensively used both in individual cells and in tissues. Most of these methods exploit properties of dying cells that are more or less specific for the apoptotic process. However, considerable confusion exists over the interpretation of some of these methods and their usefulness in all settings. This review attempts to summarize the more recent advances in cytochemical detection of apoptosis and emphasizes some of the pitfalls that confuse the interpretation of results of these methods.
Determining association constants from titration experiments in supramolecular chemistry (2010)

The most common approach for quantifying interactions in supramolecular chemistry is a titration of the guest to solution of the host, noting the changes in some physical property through NMR, UV-Vis, fluorescence or other techniques. Despite the apparent simplicity of this approach, there are several issues that need to be carefully addressed to ensure that the final results are reliable. This includes the use of non-linear rather than linear regression methods, careful choice of stoichiometric binding model, the choice of method (e.g., NMR vs. UV-Vis) and concentration of host, the application of advanced data analysis methods such as global analysis and finally the estimation of uncertainties and confidence intervals for the results obtained. This tutorial review will give a systematic overview of all these issues-highlighting some of the key messages herein with simulated data analysis examples.
Polyriboadenylic and polydeoxyriboadenylic acids. Optical rotatory studies of pH-dependent conformations and their relative stability (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPolyriboadenylic and polydeoxyriboadenylic acids. Optical rotatory studies of pH-dependent conformations and their relative stabilityAlice J. Adler, Lawrence Grossman, and Gerald D. FasmanCite this: Biochemistry 1969, 8, 9, 3846–3859Publication Date (Print):September 1, 1969Publication History Published online1 May 2002Published inissue 1 September 1969https://pubs.acs.org/doi/10.1021/bi00837a051https://doi.org/10.1021/bi00837a051research-articleACS PublicationsRequest reuse permissionsArticle Views136Altmetric-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
Deterministic entanglement of ions in thermal states of motion (2009)

We give a detailed description of the implementation of a Molmer-Sorensen gate entangling two Ca+ ions using a bichromatic laser beam near-resonant with a quadrupole transition. By amplitude pulse shaping and compensation of AC-Stark shifts we achieve a fast gate operation without compromising the error rate. Subjecting different input states to concatenations of up to 21 individual gate operations reveals Bell state fidelities above 0.80. In principle, the entangling gate does not require ground state cooling of the ions as long as the Lamb-Dicke criterion is fulfilled. We present the first experimental evidence for this claim and create Bell states with a fidelity of 0.974(1) for ions in a thermal state of motion with a mean phonon number of <n>=20(2) in the mode coupling to the ions' internal states.
Conditional Gene Expression in Human Intracranial Xenograft Tumors (2001)

In an initial effort to determine the effect of expressing potentially therapeutic gene products on the growth properties of glioma tumor xenografts, we describe the development of cell lines that can conditionally express beta-galactosidase (beta-gal). To achieve this, we generated stable cell lines that express the modified tetracycline repressor molecule (rtTA) and the beta-gal gene under control of tetracycline-responsive cis-elements. The resulting cell lines express functional beta-gal following treatment with the tetracycline analog doxycyclin (Dox). These cells were then used to form intracranial tumors after injection into the brain using an implantable guide-screw system. The xenografts were found to express beta-gal when the animals were fed drinking water containing Dox. From these studies, we conclude that the expression of a target gene in a human xenograft growing in the brain of a living mouse can be conditionally regulated.
A Potent HER3 Monoclonal Antibody That Blocks Both Ligand-Dependent and -Independent Activities: Differential Impacts of PTEN Status on Tumor Response (2016)

HER3/ERBB3 is a kinase-deficient member of the EGFR family receptor tyrosine kinases (RTK) that is broadly expressed and activated in human cancers. HER3 is a compelling cancer target due to its important role in activation of the oncogenic PI3K/AKT pathway. It has also been demonstrated to confer tumor resistance to a variety of cancer therapies, especially targeted drugs against EGFR and HER2. HER3 can be activated by its ligand (heregulin/HRG), which induces HER3 heterodimerization with EGFR, HER2, or other RTKs. Alternatively, HER3 can be activated in a ligand-independent manner through heterodimerization with HER2 in HER2-amplified cells. We developed a fully human mAb against HER3 (KTN3379) that efficiently suppressed HER3 activity in both ligand-dependent and independent settings. Correspondingly, KTN3379 inhibited tumor growth in divergent tumor models driven by either ligand-dependent or independent mechanisms in vitro and in vivo Most intriguingly, while investigating the mechanistic underpinnings of tumor response to KTN3379, we discovered an interesting dichotomy in that PTEN loss, a frequently occurring oncogenic lesion in a broad range of cancer types, substantially blunted the tumor response in HER2-amplified cancer, but not in the ligand-driven cancer. To our knowledge, this represents the first study ascertaining the impact of PTEN loss on the antitumor efficacy of a HER3 mAb. KTN3379 is currently undergoing a phase Ib clinical trial in patients with advanced solid tumors. Our current study may help us optimize patient selection schemes for KTN3379 to maximize its clinical benefits. Mol Cancer Ther; 15(4); 689-701. ©2016 AACR.
Saccharomyces cerevisiae Hsp104 protein. Purification and characterization of ATP-induced structural changes. (1994)

Heat-shock proteins (hsps) function in a variety of ways to help cells and organisms cope with environmental changes. One class of hsps, the Hsp100 proteins, is especially important for tolerance to a variety of extremely stressful conditions (e.g. high temperatures or high concentrations of ethanol). To begin to characterize the mechanism of action of Hsp100 proteins, we have initiated an in vitro analysis of the Saccharomyces cerevisiae Hsp104 protein. Here, we report the purification and initial structural characterization of the wild-type protein and three variants carrying mutations in the two ATP-binding site consensus elements. As demonstrated by both gel filtration chromatography and by cross-linking studies with glutaraldehyde, Hsp104 forms a homohexameric particle. By electron microscopy, these particles are ring-shaped and reminiscent of proteins in the Hsp60 and TF55/TCP families. In contrast to these other proteins, Hsp104 forms single rings, each containing only six subunits. More strikingly, the assembly and maintenance of Hsp104 particles are dependent upon the presence of adenine nucleotides. Oligomerization appears to primarily depend upon the second of the two ATP-binding sites in the protein.
High-resolution genetic mapping of allelic variants associated with cell wall chemistry in Populus (2015)

This study illustrates the utility of complementary QTL and association mapping as tools for gene discovery with no a priori candidate gene selection. This proof of concept in a perennial organism opens up opportunities for discovery of novel genetic determinants of economically important but complex traits in plants.
Issues and strategies for the physical design of system-on-a-chip ASICs (2002)

The density and performance of advanced silicon technologies have made system-on-a-chip ASICs possible. SoCs bring together a diverse set of functions and technology features on a single die of enormous complexity. The physical design of these complex ASICs requires a rich set of functional elements that integrate efficiently with a set of design flows and tools productive enough to meet product requirements successfully, without consuming more time or design resources than a simpler design. The architecture described, including functional libraries and physical design conventions, enables the creation of multiple SoC ASIC designs from a common infrastructure that addresses silicon integration, electrical robustness, and packaging challenges. An implementation strategy follows from this design infrastructure that includes hierarchical design concepts, placement, routing, and verification processes.
Midkine, a heparin-binding cytokine with multiple roles in development, repair and diseases (2010)

Midkine is a heparin-binding cytokine or a growth factor with a molecular weight of 13 kDa. Midkine binds to oversulfated structures in heparan sulfate and chondroitin sulfate. The midkine receptor is a molecular complex containing proteoglycans. Midkine promotes migration, survival and other activities of target cells. Midkine has about 50% sequence identity with pleiotrophin. Mice deficient in both factors exhibit severe abnormalities including female infertility. In adults, midkine is expressed in damaged tissues and involved in the reparative process. It is also involved in inflammatory reactions by promoting the migration of leukocytes, induction of chemokines and suppression of regulatory T cells. Midkine is expressed in a variety of malignant tumors and promotes their growth and invasion. Midkine appears to be helpful for the treatment of injuries in the heart, brain, spinal cord and retina. Midkine inhibitors are expected to be effective in the treatment of malignancies, rheumatoid arthritis, multiple sclerosis, renal diseases, restenosis, hypertension and adhesion after surgery.