gebhart/patrepeval huggingface dataset:
Human Embryonic Stem Cell Lines Derived from Discarded Embryos (2003)

Human pluripotent embryonic stem (ES) cells have important potential in regenerative medicine and as models for human preimplantation development; however, debate continues over whether embryos should be destroyed to produce human ES cells. We have derived four ES cell lines on mouse embryonic fibroblast cells in medium supplemented with basic fibroblast growth factor, human recombinant leukemia inhibitory factor, and fetal bovine serum. The source of these cell lines was poor-quality embryos that in the course of routine clinical practice would have been discarded. After continuous proliferation in vitro for more than 12 months, these ES cell lines maintained their developmental potential to form trophoblast and somatic cells, including cardiac muscle and neuronal tissue.
245. AAV2/8-Mediated Efficacy and Immune Tolerance in a Pompe Disease Mouse Model (2005)

Pompe disease is an inherited metabolic disorder caused by a deficiency of the lysosomal enzyme acid -glucosidase (GAA). The disease is characterized by accumulation of glycogen in various tissues, including the central and peripheral nervous systems, but the pathology most dramatically affects skeletal and cardiac muscles. Severely affected patients present within the first year of life with hypotonia and cardiomyopathy, resulting in death from cardiopulmonary failure. To assess the utility of gene therapy for Pompe disease, we generated recombinant AAV8-based serotype vectors encoding for GAA under the transcriptional control of a liver-restricted promoter (DC190). Systemic administration of 5X1011 drp of AAV8/DC190-GAA into Pompe mice generated high levels (25-30 g/ml) of GAA in the serum that persisted for 6 months post-administration. GAA activity was also detected in several muscle groups isolated from the AAV8-treated mice, indicating that GAA was efficiently taken up into these tissues from circulation. Glycogen storage was completely corrected in the heart and diaphragm and reduced by 50% in the skeletal muscles as early as 4 weeks post-treatment. All tissues were completely cleared of glycogen storage by 10 weeks, and remained at baseline at the 6-month time point. Histomorphometric analysis of PAS-stained tissues confirmed that glycogen deposits were effectively cleared from the affected tissues. Histopathology observed in the dorsal root ganglia of Pompe mice was also normalized suggesting that treatment may impact the peripheral nerve disease. Consistent with previous studies using the DC190 promoter, no antibodies to the human GAA were detected in the sera of AAV8/DC190-GAA-treated mice. Furthermore, no antibodies were generated following two subsequent challenges with recombinant GAA emulsified in Complete Freund's adjuvant, suggesting the AAV8/DC190-GAA-treated mice were immune tolerized. Immune responses were also assessed at the cellular level by assaying lymphocyte proliferation and IFN secretion using cells harvested from the spleens of the treated mice. Cells from the AAV8/DC190-GAA-treated mice showed an attenuated response to antigenic stimulation compared to controls. These data support the continued evaluation of AAV8-mediated gene therapy as an approach to treat the systemic manifestations of Pompe disease.
Tyrosine Phosphorylation and p72syk Activation by an Anti-Glycoprotein Ib Monoclonal Antibody (1997)

NNKY5-5, an IgG monoclonal antibody directed against the von Willebrand factor-binding domain of glycoprotein (GP) Ibα, induced weak but irreversible aggregation (or association) of platelets in citrate-anticoagulated platelet-rich plasma. This phenomenon was defined as small aggregate formation (SAF ). Platelets in hirudin-anticoagulated plasma or washed platelets showed little response to NNKY5-5 alone, but the antibody potentiated aggregation induced by low concentrations of adenosine diphosphate or platelet-activating factor. NNKY5-5 did not induce granule release or intracellular Ca2+ mobilization. However, NNKY5-5 caused tyrosine phosphorylation of a 64-kD protein and activation of a tyrosine kinase, p72syk. An anti-FcγII receptor antibody had no effect on SAF, suggesting that NNKY5-5 activated platelets by interacting with glycoprotein Ib. Fab′ fragments of NNKY5-5 did not induce SAF, but potentiated aggregation induced by other agonists. The Fab′ fragment of NNKY5-5 induced the activation of p72syk, suggesting that such activation was independent of the FcγII receptor. Cross-linking of the receptor-bound Fab′ fragment of NNKY5-5 with a secondary antibody induced SAF. GRGDS peptide, chelation of extracellular Ca2+, and an anti-GPIIb/IIIa antibody inhibited NNKY5-5-induced SAF, but had no effect on 64-kD protein tyrosine phosphorylation or p72syk activations. Various inhibitors, including aspirin and protein kinase C, had no effect on SAF, protein tyrosine phosphorylation, or p72syk activation. In contrast, tyrphostin 47, a potent tyrosine kinase inhibitor, inhibited NNKY5-5–induced SAF as well as tyrosine phosphorylation and p72syk activation. Our findings suggest that binding of NNKY5-5 to GPIb potentiates platelet aggregation by facilitating the interaction between fibrinogen and GPIIb/IIIa through a mechanism associated with p72syk activation and tyrosine phosphorylation of a 64-kD protein.
Deregulation of EIF4E: a novel mechanism for autism (2009)

These observations implicate EIF4E, and more specifically control of EIF4E activity, directly in autism. The findings raise the exciting possibility that pharmacological manipulation of EIF4E may provide therapeutic benefit for those with autism caused by disturbance of the converging pathways controlling EIF4E activity.
Loss of unstably amplified dihydrofolate reductase genes from mouse cells is greatly accelerated by hydroxyurea. (1983)

Previous work has shown that mammalian cells that carry unstably amplified genes for dihydrofolate reductase (DHFR) gradually lose the amplified DHFR genes when grown in the absence of the DHFR inhibitor methotrexate (MTX). Unstably amplified genes occur on small acentric chromosomes called double minutes (DMs) or even smaller chromatin fragments, in contrast to stably amplified genes, which reside in centromere-containing chromosomes. We have found that the rate of loss of the unstably amplified DHFR genes can be greatly oncreased by growing the cells in the presence of a nonlethal concentration of hydroxyurea. For example, in one MTX-resistant subline studied, approximately equal to 90% of the original DHFR gene dosage is lost in 25-30 cell doublings in the absence of MTX. The same degree of loss is achieved, however, in less than 4 doublings if cells are grown in the presence of 50 microM hydroxyurea. This new effect of hydroxyurea does not appear to be due to changes in plating efficiency or selective cytotoxicity. In particular, no increase in cell death occurs at 50 microM hydroxyurea, and cells continue to multiply, albeit 1/2 to 2/3 as fast as in the absence of hydroxyurea. The ability to selectively accelerate the loss of amplified genes from mammalian cells as shown in the present work may have important implications both for the problem of drug resistance in cancer chemotherapy and for curing mammalian cells of extrachromosomally maintained DNA genomes of pathogenic viruses.
Data Warehouse: From Architecture to Implementation (1996)

From the Publisher:
Data warehousing is one of the hottest topics in the computing industry today. For business executives, it promises significant competitive advantage for their companies, while information systems managers see it as the way to overcome the traditional roadblocks to providing business information for managers and other end users. With the publication of this book comes the most comprehensive, practical guide to designing, building, and implementing a data warehouse on the market today. Barry Devlin - one of the world's leading experts on data warehousing - is also one of the first practitioners in this area. In this book, he distills the insights and experiences gained over 10 years of designing and building data warehouses. Included are an explanation of the optimal three-tiered architecture for the data warehouse, with a clear division between data and information; full description of the functions needed to implement such an architecture, including reconciling existing, diverse data and deriving consistent, valuable business information; a detailed methodology for building a data warehouse in a way that provides business value and strategic infrastructure at each stage; a high-level approach to justifying the effort involved; and a view of the organizational aspects of building and maintaining a warehouse. This book will be the key reference for any team undertaking the construction of a data warehouse. It is aimed primarily at the IS managers, architects, and designers involved in this process, as well as the end users having a key role in the evolving implementation of the data warehouse.
Diagnostic molecular microbiology : principles and applications (1993)

Principles of Diagnostic Molecular Microbiology Applications of Diagnostic Molecular Microbiology Section 1: Bacterial Pathogens Secton 2: Viral Pathogens Section 3: Fungal Pathogens Section 4: Parasitic Pathogens Section 5: Novel Organisms Section 6: Antimicrobial Resistance Loci Section 7: Molecular Typing Methods Section 8: Methods
Development of an enzymatic reaction device using magnetic bead-cluster handling (2006)

We previously proposed a magnetic bead-cluster handling device for Micro-total analysis systems (Micro-TAS) and investigated its operation principle.The device does not need mechanical fluidic devices, such as pumps and valves, for handling solutions.We further developed the biochemical reaction unit chip, which is a key component in Micro-TAS, by applying a bead-cluster handling mechanism.We were able to do the enzymatic reaction by using hydrolysis between alkaline phosphatase and p-nitrophenyl phosphate.We also confirmed that the obtained calibration curves were linear during the enzymatic reaction.We had 70% reaction efficiency on the reaction chip by performing a comparative experiment.From these results, we concluded that our developed reaction chip is applicable to enzymatic immuno-assay systems.
Self‐Assembly of Organocatalysts: Fine‐Tuning Organocatalytic Reactions (2006)

A cat. with two tales: Hydrogen-bonding interactions between achiral pyridinone additives and unselective chiral proline-derived organocatalysts (see picture) result in highly effective catalysts for the Michael addition of nitroalkenes to ketones. In the absence of an additive the reaction is unselective and the product is obtained in about 15 % ee, while the same product is obtained with up to 94 % ee in the presence of an additive. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z602912_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
ENDOR Spectroscopy — A Promising Technique for Investigating the Structure of Organic Radicals (1984)

Abstract The name “ENDOR” has been known since biblical times and denotes a small town close to the Sea of Galilee (ca. 1000 B.C., 1 Sam. 28 : 7 ff). The acronym “ENDOR” ( E lectron N uclear DO uble R esonance) characterizes the extension of electron spin resonance to electron‐nuclear double resonance spectroscopy, a method that has opened up new dimensions for the investigation of complicated paramagnetic molecules. Only ENDOR spectoscopy, which has achieved technical perfection in the last decade, overcomes the resolution limitations of EPR spectroscopy, thus allowing interesting applications in the field of biochemistry. ENDOR investigations of the primary process of photosynthesis, of the mode of action of derivatives of vitamin E and K, and of the mechanism of the enzymatic catalysis of flavoenzymes in biological redox‐chains have opened up new vistas. ENDOR and its extension to the triple resonance experiment TRIPLE offer, for example, the potential for a precise determination of hyperfine coupling constants, including their signs, which are frequently especially interesting. In addition to protons, a multiple of magnetic nuclei can be studied by ENDOR, such as e.g. 2 H, 13 C, and 14 N. The ENDOR techniques is not restricted to monoradicals, but can also be applied to polyradicals in spin states of higher multiplicities (triplet, quartet, or quintet state). The experimental data accessible from ENDOR yield information about spin and charge density distributions, and about the geometrics of radicals and their internal dynamics; they also provide an excellent test for the accuracy of quantum mechanical calculations.
Bebida à base de extrato hidrossolúvel de arroz e soja (1997)

Com o objetivo de formular uma bebida de boa qualidade protéica e tendo boas características sensoriais, o arroz e a soja foram misturados nas proporções de 90:10; 80:20; 70:30; 60:40 e 50:50%, respectivamente, para o preparo de um extrato, no qual foi acrescentado o ácido cítrico (0,5%) e submetido à fervura por 15 min. Depois disso, foi adicionado açúcar (15%), obtendo-se, no final, uma bebida formulada. Através das análises químicas, foi verificado que houve um aumento no percentual protéico, de 0,77 a 1,40%, proporcional ao aumento de soja. Entretanto nas bebidas formuladas, contendo respectivamente, 20; 30 e 40% de soja, foram observados os melhores perfis de aminoácidos essenciais, sendo aquela com 30% considerada a superior. Já com 50% de soja nas bebidas formuladas, os aminoácidos sulfurados tendem a se tornar deficientes. Resultados da avaliação sensorial indicam que as bebidas formuladas, respectivamente, com 10; 20; 30 e 40% de soja, foram as de melhores aparência, sabor e corpo, sendo as de 20 e 30% de soja as mais preferidas pela equipe massal de provadores não treinados.
Use of Antipsychotics for the Treatment of Behavioral Symptoms of Dementia (2016)

Antipsychotic medications are widely used in the management of behavioral and psychological symptoms of dementia. While nonpharmacological interventions should be the first-line treatment for behavioral symptoms of dementia, these are often unfeasible and/or ineffective. Conventional and atypical antipsychotic agents appear to have modest to moderate clinical efficacy in the treatment of these symptoms, though it is unclear which individual agents are most effective. No conclusive evidence exists that any available alternative medications are safer and more effective than antipsychotics. A number of studies have shown an increased risk of mortality associated with antipsychotics in patients with behavioral symptoms of dementia, though the observed risk increase may be partially confounded by illness severity and/or preexisting health determinants. The mechanisms of increased mortality risk are not fully established, but are likely to involve cardiovascular events. It is probable, though not certain, that conventional antipsychotics are associated with a greater number of poor outcomes than atypical antipsychotics. In certain patients with refractory behavioral symptoms, antipsychotics are a viable treatment option. Key considerations for antipsychotic prescribing for this population are published in regulatory guidelines, and include minimization of dosage and duration of treatment, continuous reevaluation of symptoms, and involvement of caregivers.
RS-1 enhances CRISPR/Cas9- and TALEN-mediated knock-in efficiency (2016)

Zinc-finger nuclease, transcription activator-like effector nuclease and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) are becoming major tools for genome editing. Importantly, knock-in in several non-rodent species has been finally achieved thanks to these customizable nucleases; yet the rates remain to be further improved. We hypothesize that inhibiting non-homologous end joining (NHEJ) or enhancing homology-directed repair (HDR) will improve the nuclease-mediated knock-in efficiency. Here we show that the in vitro application of an HDR enhancer, RS-1, increases the knock-in efficiency by two- to five-fold at different loci, whereas NHEJ inhibitor SCR7 has minimal effects. We then apply RS-1 for animal production and have achieved multifold improvement on the knock-in rates as well. Our work presents tools to nuclease-mediated knock-in animal production, and sheds light on improving gene-targeting efficiencies on pluripotent stem cells.
Ultrafast Synthesis of Ultrahigh Molar Mass Polymers by Metal-Catalyzed Living Radical Polymerization of Acrylates, Methacrylates, and Vinyl Chloride Mediated by SET at 25 °C (2006)

Conventional metal-catalyzed organic radical reactions and living radical polymerizations (LRP) performed in nonpolar solvents, including atom-transfer radical polymerization (ATRP), proceed by an inner-sphere electron-transfer mechanism. One catalytic system frequently used in these polymerizations is based on Cu(I)X species and N-containing ligands. Here, it is reported that polar solvents such as H(2)O, alcohols, dipolar aprotic solvents, ethylene and propylene carbonate, and ionic liquids instantaneously disproportionate Cu(I)X into Cu(0) and Cu(II)X(2) species in the presence of a diversity of N-containing ligands. This disproportionation facilitates an ultrafast LRP in which the free radicals are generated by the nascent and extremely reactive Cu(0) atomic species, while their deactivation is mediated by the nascent Cu(II)X(2) species. Both steps proceed by a low activation energy outer-sphere single-electron-transfer (SET) mechanism. The resulting SET-LRP process is activated by a catalytic amount of the electron-donor Cu(0), Cu(2)Se, Cu(2)Te, Cu(2)S, or Cu(2)O species, not by Cu(I)X. This process provides, at room temperature and below, an ultrafast synthesis of ultrahigh molecular weight polymers from functional monomers containing electron-withdrawing groups such as acrylates, methacrylates, and vinyl chloride, initiated with alkyl halides, sulfonyl halides, and N-halides.
Cellular tropism of the human retrovirus HTLV-III/LAV. I. Role of T cell activation and expression of the T4 antigen. (1985)

In cultures of normal human lymphocytes infected with the human retrovirus HTLV-III/LAV, detectable cytoplasmic virus appears and then disappears in a proportion (1 to 10%) of cells, followed by release of virus detected by particulate reverse transcriptase activity, virus antigen assay, and infectivity titer. Virus infection is associated with loss of detectable T4 antigen on infected cells and, ultimately, complete loss of T4+ cells from the culture. Residual non-T4+ cells are not susceptible to a second infection with HTLV-III/LAV, and in cultures of separated cell populations, substantial virus replication occurred in T4+ T cells and minimally, if at all, in non-T4+ cells. We could not detect a disproportionate loss of cell surface phenotype (other than T4) in comparison of infected and noninfected cultures of lymphocytes or purified T4+ T cells when these cultures were monitored with a panel of monoclonal antibodies that detect the major mononuclear cell types (alpha-T11, alpha-T3, alpha-Mo2, alpha-B1), functional T cell subsets (alpha-T8, alpha-Leu-8, alpha-T17), or activated/proliferating cells (alpha-T10, alpha-Ia, alpha-T9, alpha-4F2, alpha-Tac). HTLV-III/LAV replication was quantitatively greatest in lymphocytes stimulated with phytohemagglutinin (PHA) and cultured in the presence of interleukin 2 (IL 2). Once activated by PHA, virus production in nondividing (irradiated) cells was similar to that in nonirradiated cells, but was substantially reduced if radiation was performed before PHA stimulation. Omission of PHA, IL 2, or both resulted in progressively lower amounts of virus replication. However, virus replication was detected and T4+ T cell depletion occurred in all cultures, regardless of medium supplement or radiation. T4+ T cells absorb infectious virus, and the binding of HTLV-III/LAV to the surface of T4+ T cells, but not to non-T4+ cells, was directly demonstrated. Binding is equivalent in activated and nonactivated cells and at 4 degrees and 37 degrees C. Reciprocal inhibition of binding was observed with alpha-T4a monoclonal antibody and virus. Exposure of cells to alpha-T4a before and during HTLV-III/LAV inoculation inhibited subsequent virus replication. We conclude that T4+ T cells are the major target for HTLV-III/LAV replication, that this tropism is related to expression of the T4 antigen that serves as a binding site for virus, that infection is inexorable in T4+ T cells regardless of subset or activation state, and that the activation/proliferative state of the cells is not a necessary determinant of infectivity, but rather, determines the amount of replication that will ensue.
Enzyme immunoassay for detection of pneumococcal antigen in cerebrospinal fluid (1984)

A solid-phase immunoassay utilizing horse antiserum against the C polysaccharide of Streptococcus pneumoniae and biotinylated rabbit antibodies to type-specific pneumococcal polysaccharides was developed to detect pneumococcal antigens in human body fluids and in broth cultures. Pneumococcal antigen could be detected in broth cultures of serotypes of S. pneumoniae containing as little as 10(2) to 10(3) organisms per ml. The assay system detected pneumococcal antigen in all 25 cerebrospinal fluid specimens obtained from patients with documented pneumococcal meningitis. There were no positive reactions noted in specimens from patients infected with Neisseria meningitidis group A or from patients without evidence of bacterial infection. The solid-phase enzyme immunoassay utilizing these reagents is a sensitive and specific assay for the immunodetection of a wide range of pneumococcal antigens.