gebhart/patrepeval huggingface dataset:
Synthesis of -gal epitopes (Gal 1-3Gal 1-4GlcNAc-R) on human tumor cells by recombinant 1,3galactosyltransferase produced in Pichia pastoris (2001)

This study describes the processing of human tumor cells or cell membranes to express alpha-gal epitopes (Galalpha1-3Gal-beta1-4GlcNAc-R) by the use of New World monkey (marmoset) recombinant alpha1,3galactosyltransferase (ralpha1,3GT), produced in the yeast Pichia pastoris. Such tumor cells and membranes may serve, in cancer patients, as autologous tumor vaccines that are targeted in vivo to antigen-presenting cells by the anti-Gal antibody. This ralpha1,3GT lacks transmembrane and cytoplasmic domains, ensuring its solubility without detergent. It is effectively produced in P. pastoris under constitutive expression of the P(GAP) promoter and is secreted into the culture medium in a soluble, truncated form fused to a (His)(6) tag. This tag enables the simple affinity purification of ralpha1,3GT on a nickel-Sepharose column and elution with imidazole. The purified enzyme appears in SDS-PAGE as two bands with the size of 40 and 41 kDa and displays the same acceptor specificity as the mammalian native enzyme. ralpha1,3GT is very effective in synthesizing alpha-gal epitopes on membrane-bound carbohydrate chains and displays a specific activity of 1.2 nM membrane bound alpha-gal epitopes/min/mg. Incubation of very large amounts of human acute myeloid leukemia cells (1 x 10(9 )cells) with neuraminidase, ralpha1,3GT, and UDP-Gal resulted in the synthesis of approximately 6 x 10(6 )alpha-gal epitopes per cell. Effective synthesis of alpha-gal epitopes could be achieved also with as much as 2 g cell membranes prepared from the tumor of a patient with ovarian carcinoma. These data imply that ralpha1,3GT produced in P. pastoris is suitable for the synthesis of alpha-gal epitopes on bulk amounts of tumor cells or cell membranes required for the preparation of autologous tumor vaccines.
Functional Properties of a Drosophila Homolog of the E2F1 Gene (1994)

A variety of studies have now implicated the cellular transcription factor E2F as a key participant in transcription control during the cell growth cycle. Although the recent isolation of molecular clones encoding proteins that are components of the E2F activity (E2F1 and DP-1) provides an approach to defining the specific involvement of E2F in these events, definitive experiments remain difficult in the absence of appropriate genetic systems. We have now identified a Drosophila equivalent of E2F1 that we hope will allow an eventual genetic approach to the role of E2F in cellular regulatory events. A cDNA clone was isolated from a Drosophila cDNA library by using a probe containing sequence from the E2F1 DNA binding domain. The sequence of the clone, which we term drosE2F1, demonstrates considerable homology to the human E2F1 sequence, with over 65% identity in the DNA binding region and 50% identity in the region of E2F1 known to interact with the retinoblastoma gene product. A glutathione S-transferase-drosE2F1 fusion protein was capable of binding specifically to an E2F recognition site, and transfection assays demonstrated that the drosE2F1 product was capable of transcription activation, dependent on functional E2F sites as well as sequences within the C terminus of the protein. Finally, we have also identified E2F recognition sequences within the promoter of the Drosophila DNA polymerase alpha gene, and we demonstrate that the drosE2F1 product activates transcription of a test gene under the control of this promoter. We conclude that the drosE2F1 cDNA encodes an activity with extensive structural and functional similarity to the human E2F1 protein.
The creation and selection of mutations resistant to a gene drive over multiple generations in the malaria mosquito (2017)

Gene drives have enormous potential for the control of insect populations of medical and agricultural relevance. By preferentially biasing their own inheritance, gene drives can rapidly introduce genetic traits even if these confer a negative fitness effect on the population. We have recently developed gene drives based on CRISPR nuclease constructs that are designed to disrupt key genes essential for female fertility in the malaria mosquito. The construct copies itself and the associated genetic disruption from one homologous chromosome to another during gamete formation, a process called homing that ensures the majority of offspring inherit the drive. Such drives have the potential to cause long-lasting, sustainable population suppression, though they are also expected to impose a large selection pressure for resistance in the mosquito. One of these population suppression gene drives showed rapid invasion of a caged population over 4 generations, establishing proof of principle for this technology. In order to assess the potential for the emergence of resistance to the gene drive in this population we allowed it to run for 25 generations and monitored the frequency of the gene drive over time. Following the initial increase of the gene drive we observed a gradual decrease in its frequency that was accompanied by the spread of small, nuclease-induced mutations at the target gene that are resistant to further cleavage and restore its functionality. Such mutations showed rates of increase consistent with positive selection in the face of the gene drive. Our findings represent the first documented example of selection for resistance to a synthetic gene drive and lead to important design recommendations and considerations in order to mitigate for resistance in future gene drive applications.
Nordihydroguaiaretic Acid: A Review of Its Numerous and Varied Biological Activities (2004)

Nordihydroguaiaretic acid (NDGA) is a lignan found in large amounts in the ethnobotanically important plant, Larrea tridentata (Moc. & Sess.) Cov. (Zygophyllaceae). Research on this compound and its natural and synthetic derivatives has shown them to be potentially useful in the treatment of cancer, diabetes, viral and bacterial infections, and as regulators of fertility. The usefulness of these compounds is hindered by the lack of understanding of the mechanisms of action for each activity. While a great deal of observational and correlative data have been reported, there have been few comprehensive mechanistic or structure-function studies conducted on NDGA. Additionally, toxicological and pharmacokinetic data on NDGA is rather sparse and the metabolic breakdown products of this compound have not been reported. The present review is meant to summarize many of the biological activities reported for NDGA and its derivatives and to draw attention to areas which need to be further explored in the hopes of stimulating research on this potentially useful natural product.
Development of a web‐based mobile airline ticketing model with usability features (2005)

Purpose Development of mobile commerce (m‐commerce) environments that have user‐friendly features is important to accelerate the adoption of m‐commerce. The current research studies web‐based features that are crucial to the success of mobile air ticketing commerce. Design/methodology/approach There are two phases involved. In the first phase, the current research develops a web‐based mobile airline ticketing (W‐MAT) model to study usability features necessary to perform mobile air ticketing commerce. Thirty‐six features are mapped and identified based on the W‐MAT model. In the second phase, the air ticketing web sites for 27 most popular airline companies and online air travel agencies are examined to analyze their existing implementation patterns on these 36 features. The pattern analysis is based on web site features analysis and web site versatility analysis. Findings The analysis of web site features resulted in the development of an adoption feature pyramid that classified the 36 features into three categories. The analysis of web site versatility was based on multivariate cluster analysis that classified these 27 web sites into four groups. Practical implications The findings on web site features and web site versatility analyses in the current research are beneficial to future m‐commerce airline companies and air travel agencies, mobile device developers, and air ticketing m‐commerce interface designers. Originality/value The study concludes that the W‐MAT model‐based air ticketing features with usability emphasis are crucial to develop efficient mobile air ticketing web sites; and thereby, accelerating the adoption of m‐commerce for the air travel industry in the near future.
Phase I clinical study of fish oil fatty acid capsules for patients with cancer cachexia: cancer and leukemia group B study 9473. (1999)

The purpose of this study was to determine the maximum tolerated dose and dose-limiting toxicities of fish oil fatty acid capsules containing omega-3 fatty acid ethyl esters. Twenty-two patients with neoplastic disease not amenable to curative therapy who had lost 2% of body weight over a previous 1 month time period were given an escalating dose of fish oil fatty acids. The maximum tolerated dose was found to be 0.3 g/kg per day of this preparation. This means that a 70-kg patient can generally tolerate up to 21 1-g capsules/day containing 13.1 g of eicosapentaenoic acid + docosahexaenoic acid, the two major omega-3 fatty acids. Dose-limiting toxicity was gastrointestinal, mainly diarrhea, and a poorly described toxicity designated as "unable to tolerate in esophagus or stomach." A patient with chronic lymphocytic leukemia taking the fish oil provided an unusual opportunity to perform a detailed biochemical study of the effect of fish oil capsules on the lipids of malignant cells at several sequential time points in treatment. Studies of the malignant lymphocytes, serum, and whole blood of this one patient revealed an increase in eicosapentaenoic acid, the major component of the fish oil capsules, during fish oil capsule treatment. This study provides a scientific basis for the selection of omega-3 fatty acid doses for future studies in cancer. The maximum tolerated dose found is considerably higher than anticipated from published studies of many human diseases. The observation of a modification of the lipids of leukemic cells, serum, and blood in a patient with chronic leukemia provides a biochemical basis for a possible effect of fish oil supplements on cancer cachexia and tumor growth.
Factors influencing the immune response. I. Effects of the physical state of the antigen and of lymphoreticular cell proliferation on the response to intravenous injection of bovine serum albumin in rabbits. (1967)

The degree of aggregation of bovine serum albumin has been shown to influence not only the quantity of antibody produced but also the magnitude and increase of the relative binding affinity of the antibodies. Corynebacterium parvum which causes massive lymphoreticular cell proliferation initiates `non-specific' factors in the immune system enabling aggregate free bovine serum albumin, which normally induces unresponsiveness or hyporesponsiveness, to induce a hyperresponsive state in rabbits. This organism not only augments antibody production but the magnitude and evolution of the relative binding affinity of the antibodies.
Myocardial Ischemia and Increased Heart Work Modulate the Phosphorylation State of Eukaryotic Elongation Factor-2 (2003)

Protein synthesis, in particular peptide chain elongation, is an energy-consuming biosynthetic process. AMP-activated protein kinase (AMPK) is a key regulatory enzyme involved in cellular energy homeostasis. Therefore, we tested the hypothesis that, as in liver, it could mediate the inhibition of protein synthesis by oxygen deprivation in heart by modulating the phosphorylation of eukaryotic elongation factor-2 (eEF2), which becomes inactive in its phosphorylated form. In anoxic cardiomyocytes, AMPK activation was associated with an inhibition of protein synthesis and an increase in phosphorylation of eEF2. Rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), did not mimic the effect of oxygen deprivation to inhibit protein synthesis in cardiomyocytes or lead to eEF2 phosphorylation in perfused hearts, suggesting that AMPK activation did not inhibit mTOR/p70 ribosomal protein S6 kinase (p70S6K) signaling. Human recombinant eEF2 kinase (eEF2K) was phosphorylated by AMPK in a time- and AMP-dependent fashion, and phosphorylation led to eEF2K activation, similar to that observed in extracts from ischemic hearts. In contrast, increasing the workload resulted in a dephosphorylation of eEF2, which was rapamycin-insensitive, thus excluding a role for mTOR in this effect. eEF2K activity was unchanged by increasing the workload, suggesting that the decrease in eEF2 phosphorylation could result from the activation of an eEF2 phosphatase.
Molecular cloning of a gene encoding the immunogenic 21 kDa protein of Cowdria ruminantium (1994)

Major immunogenic polypeptides (21, 32, 40, 46, 58, 85 and 160 kDa) of Cowdria ruminantium were identified by immunoprecipitation and immunoblotting. A pUC13 library of C. ruminantium genomic DNA was screened with hyperimmune sheep serum to identify Escherichia coli colonies which expressed genes encoding these immunogenic proteins. A recombinant E. coli colony, F5.2, was identified containing plasmid insert DNA of 2773 bp. The cloned DNA insert contained two long open reading frames (ORFs) of 627 bp (complete) and 831 bp (incomplete), both potentially encoding proteins containing an N-terminal signal peptide. Deletion experiments suggested that the hyperimmune sheep serum recognized a protein that was encoded by the 627 bp ORF. The 627 bp ORF was amplified by polymerase chain reaction (PCR), subcloned and expressed to a high level in E. coli. A sheep antiserum made to the expressed recombinant fusion protein recognized a 21 kDa protein of all strains of C. ruminantium tested, confirming that the 627 bp ORF encodes a native 21 kDa protein in C. ruminantium. Similarly, the recombinant protein was recognized by all sera tested from heartwater-infected animals. The antigenic conservation of the 21 kDa protein and its immunogenic nature are reasons for further testing of this recombinant protein in subunit diagnostic tests.
Phase from chromatic aberrations (2010)

We show that phase objects may be computed accurately from a single color image in a brightfield microscope, with no hardware modification. Our technique uses the chromatic aberration that is inherent to every lens-based imaging system as a phase contrast mechanism. This leads to a simple and inexpensive way of achieving single-shot quantitative phase recovery by a modified Transport of Intensity Equation (TIE) solution, allowing real-time phase imaging in a traditional microscope.
Coronavirus: how a large RNA viral genome is replicated and transcribed. (1995)

Coronaviruses are important human and animal pathogens and contain an extraordinarily long (27-31 kb) RNA genome. Its RNA synthesis involves complex mechanisms of regulation, similar to those of DNA viruses. In this treatise, mouse hepatitis virus (MHV) is used as a model for the discussion of the mechanism of viral RNA synthesis. We show that MHV RNA synthesis requires interactions of multiple RNA components, which are likely mediated by protein-RNA and protein-protein, as well as RNA-RNA, interactions. This virus also provides a unique example of a discontinuous transcription mechanism, which involves a trans-acting RNA component. Finally, study of the cis-acting signals for the various steps of RNA synthesis revealed an insight into the regulation of viral RNA synthesis. This discussion suggests that the regulation of RNA synthesis in coronavirus is more complex than previously thought possible for RNA viruses. Coronavirus RNA transcription and replication may serve as a paradigm of RNA synthesis for RNA viruses in general.
Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers (2005)

Lamotrigine produces significantly fewer untoward cognitive and behavioral effects compared to topiramate (TPM) at the dosages, titrations, and timeframes employed in this study. The dosages employed may not have been equivalent in efficacy. Future studies are needed to delineate the cognitive and behavioral effects of TPM at lower dosages.
A review of models for the therapy of experimental infections. (1978)

During a National Live Stock association conference resolutions regarding federal laws concerning grazing conditions in the West have been drawn up and will be presented to a special land commission appointed by President Theodore Roosevelt. The cattlemen are confident that their resolutions will be successful.
Cloning and Expression of Human Anti-Tumor Necrosis Factor-a Monoclonal Antibodies from Epstein-Barr Virus Transformed Oligoclonal Libraries (2001)

Peripheral blood was obtained from a healthy human volunteer and transformed with Epstein-Barr virus (EBV). This produced an oligoclonal cell library in culture medium that was screened by ELISA for anti-human tumor necrosis factor-alpha (TNFalpha) activity. RNA from two positive clones was applied to RT-PCR using antibody-specific primers, and the light (kappa and lambda) and heavy chain genes (gamma and mu) were cloned into the plasmid vector pFab1-His2. The antibodies produced in Escherichia coli as Fab fragments were assayed for anti-TNFalpha activity utilizing ELISA. Two IgG1/kappa anti-TNFalpha antibodies and two IgM/kappa anti-TNFalpha antibodies were isolated. DNA sequence analysis showed that the VL and VH gene families of IgM and IgG were the same. Both the antibodies showed almost the same activity on ELISA-testing. Ten clones randomly selected from light (kappa and lambda) and heavy (gamma and mu) chain genes in the oligoclonal cell library 1D5 were sequenced, and each gene (kappa, lambda, gamma, and mu) was found to be composed of one to three different genes. These data support the conclusion that the cell clone is oligoclonal at the molecular level.
Diabetic Neuropathy (2010)

The modest correlation coefficients seen between the different testing modalities suggest that these techniques measure different neurophysiological parameters and are therefore not interchangeable. However, the data suggest that only a small number of neurophysiological tests are actually required to clinically differentiate individuals with neuropathy from those without. The natural clustering of both patients and healthy control subjects suggests that variations in the population will need to be considered in future studies of diabetic neuropathy.
Differential Activities of the Two Closely Related Withanolides, Withaferin A and Withanone: Bioinformatics and Experimental Evidences (2012)

In the present study, we have employed bioinformatics tools on four genes, i.e., mortalin, p53, p21 and Nrf2, identified by loss-of-function screenings. We examined the docking efficacy of Wi-N and Wi-A to each of the four targets and found that the two closely related phytochemicals have differential binding properties to the selected cellular targets that can potentially instigate differential molecular effects. We validated these findings by undertaking parallel experiments on specific gene responses to either Wi-N or Wi-A in human normal and cancer cells. We demonstrate that Wi-A that binds strongly to the selected targets acts as a strong cytotoxic agent both for normal and cancer cells. Wi-N, on the other hand, has a weak binding to the targets; it showed milder cytotoxicity towards cancer cells and was safe for normal cells. The present molecular docking analyses and experimental evidence revealed important insights to the use of Wi-A and Wi-N for cancer treatment and development of new anti-cancer phytochemical cocktails.
Two Monoclonal Antibodies with Defined Epitopes of P44 Major Surface Proteins NeutralizeAnaplasma phagocytophilumby Distinct Mechanisms (2006)

ABSTRACT Anaplasma phagocytophilum is an obligatory intracellular bacterium that causes human granulocytic anaplasmosis. The polymorphic 44-kDa major outer membrane proteins of A. phagocytophilum are dominant antigens recognized by patients and infected animals. However, the ability of anti-P44 antibody to neutralize the infection has been unclear due to a mixture of P44 proteins with diverse hypervariable region amino acid sequences expressed by a given bacterial population and lack of epitope-defined antibodies. Monoclonal antibodies (MAbs) 5C11 and 3E65 are directed to different domains of P44 proteins, the N-terminal conserved region and P44-18 central hypervariable region, respectively. Passive immunization with either MAb 5C11 or 3E65 partially protects mice from infection with A. phagocytophilum . In the present study, we demonstrated that the two monoclonal antibodies recognize bacterial surface-exposed epitopes of naturally folded P44 proteins and mapped these epitopes to specific peptide sequences. The two MAbs almost completely blocked the infection of the A. phagocytophilum population that predominantly expressed P44-18 in HL-60 cells by distinct mechanisms: MAb 5C11 blocked the binding, but MAb 3E65 did not block binding or internalization. Instead, MAb 3E65 inhibited internalized A. phagocytophilum to develop into microcolonies called morulae. Some plasma from experimentally infected horses and mice reacted with these two epitopes. Taken together, these data indicate the presence of at least two distinct bacterial surface-exposed neutralization epitopes in P44 proteins. The results indicate that antibodies directed to certain epitopes of P44 proteins have a critical role in inhibiting A. phagocytophilum infection of host cells.
Phase I study of CPT-11 and etoposide in patients with refractory solid tumors. (1993)

The recommended dose of CPT-11/VP-16 for this regimen with G-CSF is 60/60 mg/m2 on days 1 through 3 every 3 to 4 weeks. We suggest that the combination of topoisomerase I and II inhibitors is likely to be an effective treatment strategy. The activity of this regimen against NSCLC is particularly encouraging and should be evaluated in a phase II trial.
Performance of a step-and-scan system for DUV lithography (1997)

To meet the high productivity standards, set by current top- end stepper systems, the use of excimer laser sources and high scanning speeds are essential. This paper reports on a new Step &amp; Scan system capable of exposing 26 X 33 mm fields, using a 248 nm DUV-lens with a variable Numerical Aperture of 0.40 to 0.63. The system is equipped with an advanced AERIAL<SUP>TM</SUP> illuminator which allows the user to choose coherence and illumination modes on a job-by-job basis. The double telecentric lens is equipped with lens manipulators to allow on-site aberration control. Results are presented on dynamic image distortion, field flatness and dynamic imaging performance. Performance of the overlay accuracy and dose accuracy at high scanning speeds proves that Step &amp; Scan technology is now developed to a level suitable for use in high volume sub 0.25 micrometers manufacturing.
Improving Variational Inference with Inverse Autoregressive Flow (2016)

The framework of normalizing flows provides a general strategy for flexible variational inference of posteriors over latent variables. We propose a new type of normalizing flow, inverse autoregressive flow (IAF), that, in contrast to earlier published flows, scales well to high-dimensional latent spaces. The proposed flow consists of a chain of invertible transformations, where each transformation is based on an autoregressive neural network. In experiments, we show that IAF significantly improves upon diagonal Gaussian approximate posteriors. In addition, we demonstrate that a novel type of variational autoencoder, coupled with IAF, is competitive with neural autoregressive models in terms of attained log-likelihood on natural images, while allowing significantly faster synthesis.