gebhart/patrepeval huggingface dataset:
Alternatives to Packed‐Bed Chromatography for Antibody Extraction and Purification (2008)

This chapter contains sections titled: Introduction Increasing the Selectivity of Harvest Procedures: Flocculation of Particulate and Nonparticulate Impurities Solutions for Antibody Extraction, Concentration, and Purification Nonchromatographic Solutions for Antibody Purification and Formulation Membrane Adsorbers Conclusions Acknowledgments References
Synthesis and Some Properties of Modified Oligonucleotides. II. Oligonucleotides Containing 2′-Deoxy-2′-fluoro-β-D-arabinofuranosyl Pyrimidine Nucleosides (1993)

Abstract In order to find the effects of unnatural nucleosides on the stability of duplex, several oligonucleotides containing 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-uracil(FAU),-cytosine (FAC) and -thymine (FMAU) were synthesized by two alternative approaches: phosphoramidite method on an ABI 392 synthesizer and H-phosphonate procedure on our GeneSyn I universal module synthesizer. It was shown from the melting profiles that the presence of FMAU has a large stabilizing effect on the duplex. Replacement of thymidine with FAU, or deoxycytidine with FAC resulted in the formation of less stable duplexes. Temperature-dependent CD spectroscopy demonstrated that the structures of the fluorine containing oligomers are very similar to those of unmodified oligomers.
p53 mutations in colorectal cancer. (1990)

Immunohistological staining of primary colorectal carcinomas with antibodies specific to p53 demonstrated gross overexpression of the protein in approximately 50% of the malignant tumors examined. Benign adenomas were all negative for p53 overexpression. To determine the molecular basis for this overexpression we examined p53 protein expression in 10 colorectal cancer cell lines. Six of the cell lines expressed high levels of p53 in ELISA, cell-staining, and immunoprecipitation studies. Direct sequencing and chemical-mismatch-cleavage analysis of p53 cDNA by using the polymerase chain reaction in these cell lines showed that all cell lines that expressed high levels of p53 were synthesizing mRNAs that encoded mutant p53 proteins. In two of those four cell lines where p53 expression was lower, point mutations were still detected. Thus, we conclude that overexpression of p53 is synonymous with mutation, but some mutations would not be detected by a simple immunohistochemical analysis. Mutation of the p53 gene is one of the commonest genetic changes in the development of human colorectal cancer.
PUTTING THE NANO FINGER ON ATOMS (1996)

RETURN TO ISSUEPREVNewsNEXTPUTTING THE NANO FINGER ON ATOMSAdvances in scanning probe microscopy are giving scientists new ways to create and manipulate nanoscale structuresRON DAGANIView Author Information C&EN WashingtonCite this: Chem. Eng. News 1996, 74, 49, 20–23Publication Date (Print):December 2, 1996Publication History Published online12 November 2010Published inissue 2 December 1996https://pubs.acs.org/doi/10.1021/cen-v074n049.p020https://doi.org/10.1021/cen-v074n049.p020newsACS PublicationsCopyright © 1996 American Chemical SocietyArticle Views9Altmetric-Citations5LEARN 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 options SUBJECTS:Probes Get e-Alerts
Large Photoresponsivity in High‐Mobility Single‐Crystal Organic Field‐Effect Phototransistors (2005)

Photons control number of mobile charge carriers: Organic field-effect transistors based on dithiophene-tetrathiafulvalene (DT-TTF) and dibenzo-tetrathiafulvalene (DB-TTF) show enhanced conductivity under illumination (see figure). A very high ratio of photocurrent to dark current of the order of ≈104 was observed for DT-TTF due to the photogeneration of mobile charge carriers (holes). These materials have the potential to be employed as light sensors or optoelectronic memory devices.
A stochastic reconfigurable architecture for fault-tolerant computation with sequential logic (2012)

Computation performed on stochastic bit streams is less efficient than that based on a binary radix because of its long latency. However, for certain complex arithmetic operations, computation on stochastic bit streams can consume less energy and tolerate more soft errors. In addition, the latency issue could be solved by using a faster clock frequency or in combination with a parallel processing approach. To take advantage of this computing technique, previous work proposed a combinational logic-based reconfigurable architecture to perform complex arithmetic operations on stochastic streams of bits. In this paper, we enhance and extend this reconfigurable architecture using sequential logic. Compared to the previous approach, the proposed reconfigurable architecture takes less hardware area and consumes less energy, while achieving the same performance in terms of processing time and fault-tolerance.
Altered Subcellular Distribution of c-Abl in Alzheimer's Disease (2009)

c-Abl is a non-receptor tyrosine kinase that participates in multiple signaling pathways linking the cell surface, cytoskeleton, and the nucleus. Recent in vitro studies have also linked c-Abl to amyloid-beta-induced toxicity and tau phosphorylation. To further characterize a potential role of c-Abl in Alzheimer's disease (AD), we examined the expression and distribution of total and phosphorylated forms of c-Abl in the hippocampus of AD and control subjects. Laser scanning confocal microscopy was used to examine the colocalization of c-Abl with AD pathology. Our results demonstrate alterations in the presence and distribution of c-Abl and phosphorylated isoforms of c-Abl within the hippocampus during AD. Total unphosphorylated c-Abl was highest in non-demented control hippocampus. Activated isoforms of c-Abl were most abundant in AD hippocampus and co-localized with AD pathology, including granulovacuolar degeneration bodies, c-Abl interacts with phosphorylated tau in AD brain and may contribute to the formation of tau pathology. These studies demonstrate altered activation and distribution of c-Abl during AD, suggesting a role for c-Abl in Abeta signal transduction and generation of tau pathology in AD.
How to Compile A Quantum Bayesian Net (1998)

We show how to express the information contained in a Quantum Bayesian (QB) net as a product of unitary matrices. If each of these unitary matrices is expressed as a sequence of elementary operations (operations such as controlled-nots and qubit rotations), then the result is a sequence of operations that can be used to run a quantum computer. QB nets have been run entirely on a classical computer, but one expects them to run faster on a quantum computer.
Molecular Cloning and Characterization of a Novel UDP-GlcNAc:GalNAc-peptide β1,3-N-Acetylglucosaminyltransferase (β3Gn-T6), an Enzyme Synthesizing the Core 3 Structure of O-Glycans (2002)

The core 3 structure of the O-glycan, GlcNAcbeta1-3GalNAcalpha1-serine/threonine, an important precursor in the biosynthesis of mucin-type glycoproteins, is synthesized by UDP-N-acetylglucosamine:GalNAc-peptide beta1,3-N- acetylglucosaminyltransferase (beta3Gn-T; core 3 synthase). The core 3 structure is restricted in its occurrence to mucins from specific tissues such as the stomach, small intestine, and colon. A partial sequence encoding a novel member of the human beta3Gn-T family was found in one of the data bases. We cloned a complementary DNA of this gene and named it beta3Gn-T6. The putative amino acid sequence of beta3Gn-T6 retains the beta3Gn-T motifs and is predicted to comprise a typical type II membrane protein. The soluble form of beta3Gn-T6 expressed in insect cells showed beta3Gn-T activity toward GalNAcalpha-p-nitrophenyl and GalNAcalpha1-serine/threonine. The beta1,3-linkage between GlcNAc and GalNAc of the enzyme reaction product was confirmed by high performance liquid chromatography and NMR analyses. beta3Gn-T6 effectively transferred a GlcNAc to the GalNAc residue on MUC1 mucin, resulting in the synthesis of a core 3 structure. Real time PCR analysis revealed that the beta3Gn-T6 transcript was restricted in its distribution, mainly to the stomach, colon, and small intestine. We concluded that beta3Gn-T6 is the most logical candidate for the core 3 synthase, which plays an important role in the synthesis of mucin-type O-glycans in digestive organs.
Non-cross-linking gold nanoparticle aggregation as a detection method for single-base substitutions (2005)

Aggregation of DNA-modified gold nanoparticles in a non-cross-linking configuration has extraordinary selectivity against terminal mismatch of the surface-bound duplex. In this paper, we demonstrate the utility of this selectivity for detection of single-base substitutions. The samples were prepared through standard protocols: DNA extraction, PCR amplification and single-base primer extension. Oligonucleotide-modified nanoparticles correctly responded to the unpurified products from the primer extension: aggregation for the full match and dispersion for all the mismatches. Applicability of this method to genomic DNA was tested with five human tumor cell lines, and verified by conventional technologies: mass spectrometry and direct sequencing. Unlike the existing methods for single-base substitution analysis, this method does not need specialized equipments, and opens up a new possibility of point-of-care diagnosis for single-nucleotide polymorphisms.
Protective Efficacy of Neutralizing Monoclonal Antibodies in a Nonhuman Primate Model of Ebola Hemorrhagic Fever (2012)

Ebola virus (EBOV) is the causative agent of severe hemorrhagic fever in primates, with human case fatality rates up to 90%. Today, there is neither a licensed vaccine nor a treatment available for Ebola hemorrhagic fever (EHF). Single monoclonal antibodies (MAbs) specific for Zaire ebolavirus (ZEBOV) have been successfully used in passive immunization experiments in rodent models, but have failed to protect nonhuman primates from lethal disease. In this study, we used two clones of human-mouse chimeric MAbs (ch133 and ch226) with strong neutralizing activity against ZEBOV and evaluated their protective potential in a rhesus macaque model of EHF. Reduced viral loads and partial protection were observed in animals given MAbs ch133 and ch226 combined intravenously at 24 hours before and 24 and 72 hours after challenge. MAbs circulated in the blood of a surviving animal until virus-induced IgG responses were detected. In contrast, serum MAb concentrations decreased to undetectable levels at terminal stages of disease in animals that succumbed to infection, indicating substantial consumption of these antibodies due to virus replication. Accordingly, the rapid decrease of serum MAbs was clearly associated with increased viremia in non-survivors. Our results indicate that EBOV neutralizing antibodies, particularly in combination with other therapeutic strategies, might be beneficial in reducing viral loads and prolonging disease progression during EHF.
Multiplex Genome Engineering Using CRISPR/Cas Systems (2013)

Functional elucidation of causal genetic variants and elements requires precise genome editing technologies. The type II prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)/Cas adaptive immune system has been shown to facilitate RNA-guided site-specific DNA cleavage. We engineered two different type II CRISPR/Cas systems and demonstrate that Cas9 nucleases can be directed by short RNAs to induce precise cleavage at endogenous genomic loci in human and mouse cells. Cas9 can also be converted into a nicking enzyme to facilitate homology-directed repair with minimal mutagenic activity. Lastly, multiple guide sequences can be encoded into a single CRISPR array to enable simultaneous editing of several sites within the mammalian genome, demonstrating easy programmability and wide applicability of the RNA-guided nuclease technology.
Rapid assessment of ligand actions with nicotinic acetylcholine receptors using calcium dynamics and FLIPR (1998)

Due to the complex mechanism of cation transport by neuronal nicotinic acetylcholine receptors (nAChR), potential ligands of these receptors must be characterized with respect to functional activity and corresponding subtype selectivity. Conventional radioactive binding assays have been established in high throughput screening (HTS) formats for rapid assessment of ligand subtype selectivity; however, the current radiometric methods of functionally profiling these ligands are not suitable for HTS formats. In this article, a high throughput, cell-based assay is described which exploits the Ca2+ transport activity of nAChRs as a method of functional assessment. By coupling the use of Fluo-3, a Ca2+-chelating fluorescent dye, with a fluorescence imaging plate reader (FLIPR), the movement of Ca2+ by nAChRs can be observed. Fluorescence changes can be measured simultaneously over an entire 96-well plate, allowing six to eight concentrations of six ligands to be examined in duplicate on each plate within minutes. In the data presented, 36 nAChR ligands were functionally profiled in IMR-32 cells, a model of ganglionic nAChR subtypes. The calculated potency values (pEC50 values) from this fluorescence assay compare well with those determined by 86Rb+-efflux and demonstrate a correlation coefficient of 0.91 between the two methods. Thus, the functional profile of novel nAChR ligands can rapidly be assessed by monitoring the flux of calcium upon activation of these ligand gated ion channels (LGICs). Moreover, this HTS assay can be easily adapted for any cell line expressing receptors involved directly or indirectly with the influx of calcium into the cytosol, including similar LGICs and G-protein coupled receptors. Drug Dev. Res. 44:14–20, 1998. © 1998 Wiley-Liss, Inc.
The Crystal Structure of Shikimate Dehydrogenase (AroE) Reveals a Unique NADPH Binding Mode (2003)

Shikimate dehydrogenase catalyzes the NADPH-dependent reversible reduction of 3-dehydroshikimate to shikimate. We report the first X-ray structure of shikimate dehydrogenase from Haemophilus influenzae to 2.4-A resolution and its complex with NADPH to 1.95-A resolution. The molecule contains two domains, a catalytic domain with a novel open twisted alpha/beta motif and an NADPH binding domain with a typical Rossmann fold. The enzyme contains a unique glycine-rich P-loop with a conserved sequence motif, GAGGXX, that results in NADPH adopting a nonstandard binding mode with the nicotinamide and ribose moieties disordered in the binary complex. A deep pocket with a narrow entrance between the two domains, containing strictly conserved residues primarily contributed by the catalytic domain, is identified as a potential 3-dehydroshikimate binding pocket. The flexibility of the nicotinamide mononucleotide portion of NADPH may be necessary for the substrate 3-dehydroshikimate to enter the pocket and for the release of the product shikimate.
Chemical Triggering : Reactions of Potential Utility in Industrial Processes (1987)

Chemical reactions which can, on demand, be switched on and off are valuable for industrial applications. In order to make the best use ofthese reactions, it is essential to have them readily available for a research chemist. The chemical literature, in general, has not yet identified or grouped such reactions. However, their existence is relatively abundant. This book is meant as a survey ofthose reactions which have potential utility in industrially useful processes. These reactions are grouped under the title ofchemical release reactions which can be triggered by heat, light, electric current, etc., to release a specific compound from, or change in the physical or chemical properties of, a unimolecular reactant. The book is divided into chapters covering ways to trigger the release of certain chemicals. Each chapter is further divided into sections, each beginning with a brief introduction ofanalogies ofthe discussed reactions and of how they were used in reported industrial processes. This survey is not meant to be absolute or exhaustive but rather to be directive, to be as complete as possible, and to provide food for further thought.
Chemotherapy for advanced adrenal cancer: improvement from a molecular approach? (2011)

Advanced adrenal carcinoma remains a significant therapeutic challenge, with conventional approaches to systemic therapy having failed to achieve sustained objective remissions or major survival benefit in most instances. Several systemic therapies, including mitotane, suramin and gossypol, as well as cytotoxic agents, such as cisplatin and etoposide, have produced responses of ≈15-30%, with median survival figures of ≈6-15 months, depending on case selection bias, with only <10% 5-year survival rates. Recent preclinical and pathological studies have indicated a range of potential targets for drugs, including WNT/beta-catenin, epidermal growth factor receptor, RAF and k-RAS; similar applications in melanoma and renal carcinoma have achieved significant gains, and these targets are worthy of further, structured investigation. Advanced adrenal carcinoma constitutes an orphan disease, with a high mortality rate, and merits investment in clinical trials.
Synthesis of Glycosides of Glucuronic, Galacturonic and Mannuronic Acids: An Overview (2011)

Uronic acids are carbohydrates present in relevant biologically active compounds. Most of the latter are glycosides or oligosaccharides linked by their anomeric carbon, so their synthesis requires glycoside-bond formation. The activation of this anomeric center remains difficult due to the presence of the electron-withdrawing C-5 carboxylic group. Herein we present an overview of glucuronidation, mannuronidation and galacturonidation reactions, including syntheses of prodrugs, oligosaccharides and stereochemical aspects.
Isolation and characterization of an inhibitory human monoclonal antibody specific to the urokinase-type plasminogen activator, uPA (2010)

The serine protease urokinase (uPA, urokinase-type plasminogen activator) is over-expressed in certain tumors and is considered to be the strongest single indicator of poor prognosis in patients with metastatic breast cancer. In this article, we describe the isolation and affinity maturation of a fully human recombinant antibody (termed DS2), specific to the human uPA and capable of inhibiting its enzymatic activity with an IC(50) value in the low nanomolar range. The novel antibody cross-reacts with murine uPA. It was expressed both as scFv fragment and in IgG format, allowing a systematic comparative immunofluorescence (IF) analysis of the uPA expression patterns in a large panel of human und murine tumors and of normal human tissues. Although uPA was strongly expressed in virtually all tumor specimens tested, it exhibited only a weak expression in certain normal tissues (mainly in the colon, lung, spleen and bone marrow). IgG(DS2) was not able to inhibit cancer growth in immunocompromised mice bearing subcutaneous human MDA-MB-231 or DoHH-2 tumors. However, an ex vivo IF analysis confirmed the ability of the DS2 antibody to preferentially localize at the tumor site compared with normal organs. Collectively, these data suggest that uPA blocking antibodies may not be indicated for cancer growth inhibition strategies, but may serve as valuable tools for the implementation of pharmacodelivery strategies against a variety of different tumors.
c-Jun NH2-terminal Kinase Regulation of the Apoptotic Response of Small Cell Lung Cancer Cells to Ultraviolet Radiation (1997)

Exposure of cultured small cell lung cancer (SCLC) cells to UV radiation induces apoptosis. We observed that the UV sensitivity of a panel of SCLC lines and the activation of c-Jun NH2-terminal kinases (JNKs) by UV in the individual SCLC lines, assessed by binding and phosphorylation of glutathione S-transferase (GST)-c-Jun fusion proteins, ranged widely. In fact, increased JNK activity in this assay was closely correlated with decreased sensitivity to apoptosis following UV irradiation. Increased JNK activity was also detected in anti-JNK1 immune complexes collected from UV-irradiated SCLC cells, although the level of activity was similar among the various SCLC lines and correlated poorly with UV sensitivity. Immunoblot analysis of JNK polypeptides that bound to GST-c-Jun revealed at least two JNK polypeptides, one of which appeared only in extracts from UV-irradiated SCLC. To test the role of JNKs in UV-induced apoptosis, nonphosphorylatable mutants of JNK1 or JNK2 in which the phosphorylation site Thr-Pro-Tyr is changed to Ala-Pro-Phe (JNK-APF) and are predicted to behave as competitive inhibitors were stably expressed in SCLC. Expression of JNK1-APF or JNK2-APF significantly reduced UV-stimulated JNK activity. However, JNK1-APF markedly increased the resistance of the cells to UV-induced apoptosis, while JNK2-APF did not influence SCLC sensitivity to UV. The findings suggest that UV-stimulated JNK1 activation promotes UV-induced SCLC apoptosis, while a JNK isoform that is variably activated among the SCLC lines may signal a UV-protective response. We hypothesize that integration of distinct JNK activities dictates the relative responsiveness of SCLC to UV and ionizing radiation.
Oxygen Independent DNA Interstrand Cross-Link Formation by a Nucleotide Radical (2005)

A 5-(2'-Deoxyuridinyl)methyl radical (1) was independently generated from three photochemical precursors and is the first example of a DNA radical that forms interstrand cross-links. Oxygen labeling experiments support generation of 1 by all precursors. Interstrand cross-links are produced upon irradiation of DNA containing any of the precursors. Cross-linking occurs via reaction with the opposing 2'-deoxyadenosine and is independent of O(2). The independence of cross-link formation on O(2) is explained by kinetic analysis, which shows that the radical reacts reversibly with O(2). Examination of the effects of glutathione on cross-link formation under anaerobic conditions suggests that adoption of the syn-conformation by 1 is the rate-limiting step in the process. Interstrand cross-link formation is reversible in the presence of a good nucleophile. The stability of the interstrand cross-link suggests that the isolated molecule is a rearrangement product of that formed in solution. The rearrangement is a consequence of the isolation procedure but also occurs slowly in solution. Oxygen independent cross-link formation may be useful for the purposeful damage of DNA in hypoxic tumor cells, where O(2) is deficient.