gebhart/patrepeval huggingface dataset:
Engineering the Protein N-Glycosylation Pathway in Insect Cells for Production of Biantennary, Complex N-Glycans (2002)

Insect cells, like other eucaryotic cells, modify many of their proteins by N-glycosylation. However, the endogenous insect cell N-glycan processing machinery generally does not produce complex, terminally sialylated N-glycans such as those found in mammalian systems. This difference in the N-glycan processing pathways of insect cells and higher eucaryotes imposes a significant limitation on their use as hosts for baculovirus-mediated recombinant glycoprotein production. To address this problem, we previously isolated two transgenic insect cell lines that have mammalian beta1,4-galactosyltransferase or beta1,4-galactosyltransferase and alpha2,6-sialyltransferase genes. Unlike the parental insect cell line, both transgenic cell lines expressed the mammalian glycosyltransferases and were able to produce terminally galactosylated or sialylated N-glycans. The purpose of the present study was to investigate the structures of the N-glycans produced by these transgenic insect cell lines in further detail. Direct structural analyses revealed that the most extensively processed N-glycans produced by the transgenic insect cell lines were novel, monoantennary structures with elongation of only the alpha1,3 branch. This led to the hypothesis that the transgenic insect cell lines lacked adequate endogenous N-acetylglucosaminyltransferase II activity for biantennary N-glycan production. To test this hypothesis and further extend the N-glycan processing pathway in Sf9 cells, we produced a new transgenic line designed to constitutively express a more complete array of mammalian glycosyltransferases, including N-acetylglucosaminyltransferase II. This new transgenic insect cell line, designated SfSWT-1, has higher levels of five glycosyltransferase activities than the parental cells and supports baculovirus replication at normal levels. In addition, direct structural analyses showed that SfSWT-1 cells could produce biantennary, terminally sialylated N-glycans. Thus, this study provides new insight on the glycobiology of insect cells and describes a new transgenic insect cell line that will be widely useful for the production of more authentic recombinant glycoproteins by baculovirus expression vectors.
A Meta-analysis of the Effect of Estrogen Replacement Therapy on the Risk of Breast Cancer (1991)

To quantify the effect of estrogen replacement therapy on breast cancer risk, we combined dose-response slopes of the relative risk of breast cancer against the duration of estrogen use across 16 studies. Using this summary dose-response slope, we calculated the proportional increase in risk of breast cancer for each year of estrogen use. For women who experienced any type of menopause, risk did not appear to increase until after at least 5 years of estrogen use. After 15 years of estrogen use, we found a 30% increase in the risk of breast cancer (relative risk, 1.3; 95% confidence interval [CI], 1.2 to 1.6). The increase in risk was largely due to results of studies that included premenopausal women or women using estradiol (with or without progestin), studies for which the estimated relative risk was 2.2 (CI, 1.4 to 3.4) after 15 years. Among women with a family history of breast cancer, those who had ever used estrogen replacement had a significantly higher risk (3.4; CI, 2.0 to 6.0) than those who had not (1.5; CI, 1.2 to 1.7).
Production of hybrids secreting bispecific antibodies recognising CEA and doxorubicin. (1994)

A monoclonal anti-CEA secreting hybridoma (11-285-14) was made hypoxanthine, aminopterin and thymidine (HAT) sensitive by back selecting it in increasing concentrations of 8-azaguanine. Eight 8-azaguanine resistant fusion partners were selected based on growth characteristics and continued anti-CEA production. Since doxorubicin (Dox) is a hapten, it was conjugated to the carrier proteins keyhole limpet hemocyanin (KLH) or bovine serum albumin (BSA) using 1-ethyl-3- (dimethyl-aminopropyl) carbodiimide. Dox-KLH and Dox-BSA conjugates were used to immunize mice and spleen cells from these mice were used for fusions with the HAT sensitive anti-CEA partner using standard hybridoma procedures. Enzyme linked immunosorbent assays (ELISAs) were developed to test the hybrids obtained for anti-CEA, anti-DOX, anti-BSA and bispecific monoclonal antibody (BsMab) activity. Sixteen fusions with spleen cells from DOX-KLH immunized mice yielded 621 hybrids of which 47 showed low level BsMab activity by ELISA. Eight fusions with spleen cells from DOX-BSA immunized mice yielded 297 hybrids. Fifty of these hybrids showing dual reactivity have been cloned and subcloned to yield 7 subclones with stable BsMab activity for CEA and doxorubicin.
Comparison and Classification of Controlled/Living Radical Polymerizations (2000)

Controlled/living radical polymerization employs the principle equilibration between growing free radicals and various types dormant species. There are several approaches to achieve good control over molecular weights, polydispersities and end functionalities in these systems. They can be classified depending on the mechanism and chemistry of the equilibration/exchange process, as well as on the structure of the dormant species. Some them are catalyzed and some are not, some of them exhibit persistent radical effect and some do not. Currently three methods appear to be most efficient and may lead to commercial applications: nitroxide mediated polymerization, atom transfer radical polymerization and degenerative transfer processes. Their relative advantages and limitations are compared herein.
A Gaussian Process Based Online Change Detection Algorithm for Monitoring Periodic Time Series (2011)

Online time series change detection is a critical component of many monitoring systems, such as space and air-borne remote sensing instruments, cardiac monitors, and network traffic profilers, which continuously analyze observations recorded by sensors. Data collected by such sensors typically has a periodic component. Most existing time series change detection methods are not directly applicable to handle such data, either because they are not designed to handle periodic time series or because they cannot operate in an online mode. We propose an online change detection algorithm which can handle periodic time series. The algorithm uses a Gaussian process based non-parametric time series prediction model and monitors the difference between the predictions and actual observations within a statistical control chart framework to identify changes. A key challenge in using Gaussian process in an online mode is the need to solve a large system of equations involving the associated covariance matrix which grows with every time step. The proposed algorithm exploits the special structure of the covariance matrix and can analyze a time series of length T in O(T2) time while maintaining a O(T) memory footprint, compared to O(T4) time and O(T2) memory requirement of standard matrix manipulation methods. We experimentally demonstrate the superiority of the proposed algorithm over several existing time series change detection algorithms on a set of synthetic and real time series. Finally, we illustrate the effectiveness of the proposed algorithm for identifying land use land cover changes using Normalized Difference Vegetation Index (NDVI) data collected for an agricultural region in Iowa state, USA. Our algorithm is able to detect different types of changes in a NDVI validation data set (with ≈ 80% accuracy) which occur due to crop type changes as well as natural disasters.
Facile Convergent Route to Molecular Caltrops (1999)

The convergent syntheses of molecular caltrops are described starting from tetraethyl orthosilicate and using organolithium additions and Pd/Cu-catalyzed coupling methods. The caltrop core is based on a tetrahedral silicon atom, and there are three legs each bearing sulfur-tipped feet for adhesion to metallic surfaces. The forth prong (arm) is non-sulfur-bearing for projection upward from the surface. Rigid phenyleneethynylene segments are used for the legs and arms. These organosilicon caltrops may have utility as scanning probe microscopy tips.
NEW EVIDENCE THAT NUCLEAR IMPORT OF ENDOGENOUS β‐CATENIN IS LEF‐1 DEPENDENT, WHILE LEF‐1 INDEPENDENT IMPORT OF EXOGENOUS β‐CATENIN LEADS TO NUCLEAR ABNORMALITIES (2001)

The once accepted idea that LEF-1 transports beta-catenin into nuclei has recently been challenged by experiments using exogenous beta-catenin. Here, we investigated the effects of beta-catenin and LEF-1 on nuclear import of beta-catenin using different combinations of exogenous and endogenous molecules over longer lengths of time than previously studied. Nuclear beta-catenin is not detectable in corneal fibroblasts and epithelia or NIH 3T3 and MDCK cells. In LEF-1 transfections, we show that the B-box of LEF-1 is required to move cytoplasmic endogenous beta-catenin into the nuclei of such cells, proving that LEF-1 does transport endogenous beta-catenin into nuclei. Moreover, transfection of uveal melanoma cells with B-box deficient LEF-1 inhibits nuclear import of beta-catenin by endogenous LEF-1. However, the movement of overexpressed exogenous beta-catenin into nuclei is unaffected by the presence or absence of LEF-1 and forms abnormal nuclear aggregates that are a prelude to subsequent apoptosis. We conclude that nuclear transport of exogenous beta-catenin independently of LEF-1 has questionable physiological significance.
Review: Anti–CTLA-4 Antibody Ipilimumab: Case Studies of Clinical Response and Immune-Related Adverse Events (2007)

The immune system is a powerful natural agent against cancer. Cytotoxic T lymphocyte antigen 4 (CTLA-4), a key negative regulator of T-cell responses, can restrict the antitumor immune response. Ipilimumab (MDX-010) is a fully human, monoclonal antibody that overcomes CTLA-4-mediated T-cell suppression to enhance the immune response against tumors. Preclinical and early clinical studies of patients with advanced melanoma show that ipilimumab promotes antitumor activity as monotherapy and in combination with treatments such as chemotherapy, vaccines, or cytokines. Emerging data on the kinetics of response to ipilimumab and associated adverse events are increasing our understanding about how to manage patients treated with this therapy. For example, short-term tumor progression prior to delayed regression has been observed in ipilimumab-treated patients, and objective responses may be of prolonged duration. In some patients clinical improvement manifests as stable disease, which may also extend for months or years. Immune-related adverse events (IRAEs) have been observed in patients after CTLA-4 blockade and most likely reflect the drug mechanism of action and corresponding effects on the immune system. Early clinical data suggest a correlation between IRAEs and response to ipilimumab treatment. This paper briefly reviews the results from several ongoing and completed ipilimumab clinical trials, provides a synopsis of current trials, and presents several cases that demonstrate the kinetics of antitumor responses and the relationship to IRAEs in patients receiving ipilimumab.
Electrochemistry of Conducting Polymers—Persistent Models and New Concepts (2010)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTElectrochemistry of Conducting Polymers—Persistent Models and New Concepts†Jürgen Heinze*‡§, Bernardo A. Frontana-Uribe∥#, and Sabine Ludwigs§⊥View Author Information Institute for Physical Chemistry, University of Freiburg, 79104 Freiburg, Germany, Freiburg Materials Research Center, University of Freiburg, 79104 Freiburg, Germany, Centro Conjunto de Investigación en Química Sustentable, UAEM-UNAM, 50200 Toluca, Edo. Mex., México, and Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, 79104 Freiburg, Germany* Corresponding author: Telephone: +49-761-2036202. Fax: +49-761-2036237. E-mail: [email protected]†This paper was part of the Molecular and Biomolecular Electrochemistry thematic issue (http://pubs.acs.org/toc/chreay/108/7).‡Institute for Physical Chemistry, University of Freiburg.§Freiburg Materials Research Center, University of Freiburg.∥Centro de Investigación en Química Sustentable, UAEM-UNAM.#Researcher of the Instituto de Química, UNAM.⊥Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg.Cite this: Chem. Rev. 2010, 110, 8, 4724–4771Publication Date (Web):June 17, 2010Publication History Received23 June 2009Published online17 June 2010Published inissue 11 August 2010https://pubs.acs.org/doi/10.1021/cr900226khttps://doi.org/10.1021/cr900226kreview-articleACS PublicationsCopyright © 2010 American Chemical SocietyRequest reuse permissionsArticle Views23945Altmetric-Citations1023LEARN 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 SUBJECTS:Electrodes,Electropolymerization,Plastics,Polymers,Redox reactions Get e-Alerts
Baboon anti‐idiotype antibodies mimic a carcinoembryonic antigen epitope (1990)

A baboon was immunized with NP-4, a murine monoclonal antibody (MAb) to carcinoembryonic antigen (CEA). Anti-idiotype antibodies were purified from the baboon serum by affinity chromatography on a NP-4-coupled matrix, followed by adsorption of the non-specific antibodies on an irrelevant MAb. Baboon anti-idiotype antibodies inhibited specifically the binding between NP-4 and CEA. Mice immunized with baboon anti-idiotype antibodies produced antibodies to the CEA epitope recognized by NP-4. These results indicate that baboon anti-idiotype antibodies functionally mimic a CEA epitope and that they can be suitable for idiotype therapy of human CEA-producing carcinomas.
Insights into pathophysiology and therapy from a mouse model of Dravet syndrome (2011)

Mutations in voltage-gated sodium channels are associated with epilepsy syndromes with a wide range of severity. Complete loss of function in the Na(v) 1.1 channel encoded by the SCN1A gene is associated with severe myoclonic epilepsy in infancy (SMEI), a devastating infantile-onset epilepsy with ataxia, cognitive dysfunction, and febrile and afebrile seizures resistant to current medications. Genetic mouse models of SMEI have been created that strikingly recapitulate the SMEI phenotype including age and temperature dependence of seizures and ataxia. Loss-of-function in Na(v) 1.1 channels results in severely impaired sodium current and action potential firing in hippocampal γ-aminobutyric acid (GABA)ergic interneurons without detectable changes in excitatory pyramidal neurons. The resulting imbalance between excitation and inhibition likely contributes to hyperexcitability and seizures. Reduced sodium current and action potential firing in cerebellar Purkinje neurons likely contributes to comorbid ataxia. A mechanistic understanding of hyperexcitability, seizures, and comorbidities such as ataxia has led to novel strategies for treatment.
Transient expression of phosphatidylserine at cell-cell contact areas is required for myotube formation (2001)

Cell surface exposure of phosphatidylserine (PS) is shown to be part of normal physiology of skeletal muscle development and to mediate myotube formation. A transient exposure of PS was observed on mouse embryonic myotubes at E13, at a stage of development when primary myotubes are formed. The study of this process in cell cultures of differentiating C2C12 and H9C2 myoblasts also reveals a transient expression of PS at the cell surface. This exposure of PS locates mainly at cell-cell contact areas and takes place at a stage when the structural organization of the sarcomeric protein titin is initiated, prior to actual fusion of individual myoblast into multinucleated myotubes. Myotube formation in vitro can be inhibited by the PS binding protein annexin V, in contrast to its mutant M1234, which lacks the ability to bind to PS. Although apoptotic myoblasts also expose PS, differentiating muscle cells show neither loss of mitochondrial membrane potential nor detectable levels of active caspase-3 protein. Moreover, myotube formation and exposure of PS cannot be blocked by the caspase inhibitor zVAD(OMe)-fmk. Our findings indicate that different mechanisms regulate PS exposure during apoptosis and muscle cell differentiation, and that surface exposed PS plays a crucial role in the process of myotube formation.
Theory and design of an orthotic device for full or partial gravity-balancing of a human leg during motion (2004)

Gravity balancing is often used in industrial machines to decrease the required actuator efforts during motion. In the literature, a number of methods have been proposed for gravity balancing that include counterweights, springs, and auxiliary parallelograms that determine the center of mass. However, these concepts have not yet been seriously applied to rehabilitation machines. This paper presents the underlying theory and design of an orthosis for the human leg that can fully or partially balance the human leg over the range of its motion. This design combines the use of auxiliary parallelograms to determine the center of mass along with springs to achieve a full or partial gravity balanced orthosis design. A first prototype has been constructed to demonstrate the effectiveness of the idea. Future prototypes will have parameters that will be tuned to the geometry and inertia of a human subject and be tailored to an individual's needs.
THE EFFECT OF PRICE-INSULATING POLL POLICIES ON EXCHANGE RATE ANALYSIS (1980)

A model derived to compute exchange rate effects on trade uses foreign internal demand elasticities and price transmission elasticities which account for government price-insulating policies Appreciation of the Japanese yen relative to the dollar is analyzed for impacts on Japanese imports of U S wheat, feed grains, and soybeans
Regional localization on the human X chromosome and polymorphism of the coagulation factor IX gene (hemophilia B locus). (1984)

Hemophilia B is an X-linked disease caused by a functional deficiency in coagulation factor IX. A cDNA clone corresponding to factor IX has been used to detect homologous sequences in the human genome. All DNA fragments hybridizing to the probe, under medium- or high-stringency conditions, are X-linked, and the patterns obtained suggest that a single large (greater than or equal to 20 kilobases) gene is detected. The gene has been mapped to the q26-q27 region of the long arm of the X chromosome by hybridization to DNA from a panel of human-mouse hybrid cell lines. A search for restriction fragment length polymorphisms using seven restriction enzymes has led to the detection of a Taq I polymorphism, with allelic frequencies of about 0.71 and 0.29. This genetic marker should be useful for the detection of carriers of the hemophilia B trait and for prenatal diagnosis in informative families and, more generally, for the establishment of a linkage map of the human X chromosome.
Automated replay and failure detection for web applications (2005)

User-session-based testing of web applications gathers user sessions to create and continually update test suites based on real user input in the field. To support this approach during maintenance and beta testing phases, we have built an automated framework for testing web-based software that focuses on scalability and evolving the test suite automatically as the application's operational profile changes. This paper reports on the automation of the replay and oracle components for web applications, which pose issues beyond those in the equivalent testing steps for traditional, stand-alone applications. Concurrency, nondeterminism, dependence on persistent state and previous user sessions, a complex application infrastructure, and a large number of output formats necessitate developing different replay and oracle comparator operators, which have tradeoffs in fault detection effectiveness, precision of analysis, and efficiency. We have designed, implemented, and evaluated a set of automated replay techniques and oracle comparators for user-session-based testing of web applications. This paper describes the issues, algorithms, heuristics, and an experimental case study with user sessions for two web applications. From our results, we conclude that testers performing user-session-based testing should consider their expectations for program coverage and fault detection when choosing a replay and oracle technique.
Interaction of Phytoestrogens with Estrogen Receptors .ALPHA. and .BETA.. (2001)

The human estrogen receptor (hER) exists as two subtypes, hER alpha and hER beta, that differ in the C-terminal ligand-binding domain and in the N-terminal transactivation domain. In this study, we investigated the estrogenic activities of soy isoflavones after digestion with enteric bacteria in competition binding assays with hER alpha or hER beta protein, and in a gene expression assay using a yeast system. The estrogenic activities of these isoflavones were also investigated by the growth of MCF-7 breast cancer cells. Isoflavone glycoside binds weakly to both receptors and estrogen receptor-dependent transcriptional expression is poor. The aglycones bind more strongly to hER beta than to hER alpha. The binding affinities of genistein, dihydrogenistein and equol are comparable to the binding affinity of 17 beta-estradiol. Equol induces transcription most strongly with hER alpha and hER beta. The concentration required for maximal gene expression is much higher than expected from the binding affinities of the compounds, and the maximal activity induced by these compounds is about half the activity of 17 beta-estradiol. Although genistin binds more weakly to the receptors and induces transcription less than does genistein, it stimulates the growth of MCF-7 cells more strongly than does genistein.
Early treatment of HER2-amplified brain tumors with targeted NK-92 cells and focused ultrasound improves survival (2016)

Many tumor proteins could be exploited for targeted therapy with the NK-92 cell line; combined with the mounting safety evidence for transcranial ultrasound, these results may soon be translatable to a highly targeted treatment option for patients with brain tumors.