gebhart/patrepeval huggingface dataset:
Nipah Virus: Vaccination and Passive Protection Studies in a Hamster Model (2003)

Nipah virus, a member of the paramyxovirus family, was first isolated and identified in 1999 when the virus crossed the species barrier from fruit bats to pigs and then infected humans, inducing an encephalitis with up to 40% mortality. At present there is no prophylaxis for Nipah virus. We investigated the possibility of vaccination and passive transfer of antibodies as interventions against this disease. We show that both of the Nipah virus glycoproteins (G and F) when expressed as vaccinia virus recombinants induced an immune response in hamsters which protected against a lethal challenge by Nipah virus. Similarly, passive transfer of antibody induced by either of the glycoproteins protected the animals. In both the active and passive immunization studies, however, the challenge virus was capable of hyperimmunizing the vaccinated animals, suggesting that although the virus replicates under these conditions, the immune system can eventually control the infection.
Hypusine formation in protein by a two-step process in cell lysates. (1987)

The putative protein synthesis initiation factor eukaryotic initiation factor 4D (eIF-4D) is post-translationally modified by the polyamine spermidine, forming the rare amino acid hypusine from a lysine residue. The hypusine precursor, deoxyhypusine, was formed in crude cell lysates at pH 9.5 and converted to hypusine at pH 7.1. The modification occurred in eIF-4D, since the isoelectric points and molecular weights of the proteins modified in intact cells and lysates were indistinguishable. Only lysates from cells treated with alpha-difluoromethylornithine, to deplete endogenous polyamine pools, supported the formation of deoxyhypusine, suggesting that unmodified eIF-4D accumulated in spermidine deficient cells. Guazatine, an inhibitor of enzymes which form delta 1-pyrroline from spermidine, blocked deoxyhypusine formation in lysates by nearly 70% at 100 microM and completely at 1 mM. Other mammalian amine oxidase inhibitors had little or no effect on this reaction. Thus, deoxyhypusine formation in eIF-4D is catalyzed by a guazatine-sensitive enzyme with a basic pH optimum.
Induction of RNA-binding proteins in mammalian cellsby DNA-damaging agents. (1994)

A technique to detect RNA-binding proteins (RBP) involving hybridization of RNA probe to proteins transferred to a membrane was used to study RBP in different mammalian cells and in cells after genotoxic stress. With this approach, up to 13 proteins of different sizes were detected in crude nuclear extracts by using a viral RNA probe consisting of the trans-activation-responsive (TAR) element of human immunodeficiency virus type 1 (HIV-1). The TAR RNA probe contains a stem-loop structure found in nascent HIV-1 transcripts. A G+C-rich probe with similar structure also bound to many of these RBP. Only a 102-kDa protein strongly bound to other RNA probes lacking this structure, while a probe with an A+U-rich stem-loop structure fail to bind most RBP, thus indicating a RNA secondary structure preference. The expression of these RBP varied substantially in nine different human and hamster cell lines, with no detectable RBP in two human myeloid lines. Evidence for induction of these RBP was found in six of seven lines after treatment with DNA-damaging agents; UV radiation was the most effective agent. In Chinese hamster ovary cells, which showed the strongest response, all five RBP present in untreated cells rapidly increased in activity after UV irradiation, and eight additional RBP were detected. The induction of these RBP by DNA-damaging agents indicates one or more possible roles for these proteins in the cellular response to genotoxic stress and in viral activation after such stress.
Galaxy: a comprehensive approach for supporting accessible, reproducible, and transparent computational research in the life sciences (2010)

Increased reliance on computational approaches in the life sciences has revealed grave concerns about how accessible and reproducible computation-reliant results truly are. Galaxy http://usegalaxy.org, an open web-based platform for genomic research, addresses these problems. Galaxy automatically tracks and manages data provenance and provides support for capturing the context and intent of computational methods. Galaxy Pages are interactive, web-based documents that provide users with a medium to communicate a complete computational analysis.
Enzyme-Responsive Liposomes for the Delivery of Anticancer Drugs (2017)

Liposomes are nanocarriers that deliver the payloads at the target site, leading to therapeutic drug concentrations at the diseased site and reduced toxic effects in healthy tissues. Several approaches have been used to enhance the ability of the nanocarrier to target the specific tissues, including ligand-targeted liposomes and stimuli-responsive liposomes. Ligand-targeted liposomes exhibit higher uptake by the target tissue due to the targeting ligand attached to the surface, while the stimuli-responsive liposomes do not release their cargo unless they expose to an endogenous or exogenous stimulant at the target site. In this review, we mainly focus on the liposomes that are responsive to pathologically increased levels of enzymes at the target site. Enzyme-responsive liposomes release their cargo upon contact with the enzyme through several destabilization mechanisms: (1) structural perturbation in the lipid bilayer, (2) removal of a shielding polymer from the surface and increased cellular uptake, (3) cleavage of a lipopeptide or lipopolymer incorporated in the bilayer, and (4) activation of a prodrug in the liposomes.
Role of YKL-40 in the Angiogenesis, Radioresistance, and Progression of Glioblastoma (2011)

Glioblastoma is one of the most fatal cancers, characterized by a strong vascularized phenotype. YKL-40, a secreted glycoprotein, is overexpressed in patients with glioblastomas and has potential as a novel tumor biomarker. The molecular mechanisms of YKL-40 in glioblastoma development, however, are poorly understood. Here, we aimed to elucidate the role YKL-40 plays in the regulation of VEGF expression, tumor angiogenesis, and radioresistance. YKL-40 up-regulated VEGF expression in glioblastoma cell line U87, and both YKL-40 and VEGF synergistically promote endothelial cell angiogenesis. Interestingly, long term inhibition of VEGF up-regulated YKL-40. YKL-40 induced coordination of membrane receptor syndecan-1 and integrin αvβ5, and triggered a signaling cascade through FAK(397) to ERK-1 and ERK-2, leading to elevated VEGF and enhanced angiogenesis. In addition, γ-irradiation of U87 cells increased YKL-40 expression that protects cell death through AKT activation and also enhances endothelial cell angiogenesis. Blockade of YKL-40 activity or expression decreased tumor growth, angiogenesis, and metastasis in xenografted animals. Immunohistochemical analysis of human glioblastomas revealed a correlation between YKL-40, VEGF, and patient survival. These findings have shed light on the mechanisms by which YKL-40 promotes tumor angiogenesis and malignancy, and thus provide a therapeutic target for tumor treatment.
Banco do Brasil Principal agente financeiro do governo (2004)

A missao institucional do Ministerio da Agricultura, Pecuaria e Abastecimento (Mapa) e estimular o aumento da producao agropecuaria e o desenvolvimento do agronegocio, com o
objetivo de atender ao consumo interno e formar excedentes para exportacao.
Differentiation or immune destruction: two pathways for therapy of squamous cell carcinomas with antibodies to the epidermal growth factor receptor. (1994)

We have carried out an immunohistochemical investigation of xenografts of epidermal growth factor receptor (EGFR)-overexpressing tumors that have been induced to regress by treatment with rat monoclonal antibodies (mAbs) to the human EGFR [ICR16 (IgG2a), ICR62 (IgG2b), and ICR64 (IgG1)]. When mice bearing xenografts of the HN5 squamous cell carcinoma were treated for 5 days with mAb ICR62 or ICR16, the antibodies were found to be localized uniformly on the tumor cell membranes. However, the foci of tumor cells that remained following treatment with ICR62 were smaller than with ICR16 and the former showed a more pronounced host mononuclear cell infiltrate. Examination of the few tumors that had not regressed completely and were still present as static nodules 77 days following the final treatment with anti-EGFR mAbs revealed significant levels of therapeutic mAb in the nonviable areas of the tumors. The microscopic areas of apparently viable tumor cells that did not stain when only secondary antibody was used stained positive when the sections were treated first with an anti-EGFR antibody. This suggests that loss of the target antigen was not a significant factor and that these residual cells might be eradicated by further treatment with mAb. Furthermore, the finding of keratinized areas in the tumors undergoing regression suggested that the carcinoma cells had undergone terminal differentiation following exposure to antibody. This possibility was supported by the finding that treatment of HN5 cells in vitro with mAbs ICR16, ICR62, or ICR64 resulted in the accumulation of cells in the G0-G1 phases of the cell cycle and expression of the terminal differentiation markers involucrin and cytokeratin 10. We found no evidence of apoptosis in such cells. We conclude that antibodies which block the binding of EGF and transforming growth factor alpha to the EGFR can inhibit the growth of EGFR-overexpressing tumors by directing terminal differentiation and that a further therapeutic benefit may be obtained via immunological mechanisms with rat IgG2b mAbs such as ICR62.
Evolutionary drivers of thermoadaptation in enzyme catalysis (2016)

With early life likely to have existed in a hot environment, enzymes had to cope with an inherent drop in catalytic speed caused by lowered temperature. Here we characterize the molecular mechanisms underlying thermoadaptation of enzyme catalysis in adenylate kinase using ancestral sequence reconstruction spanning 3 billion years of evolution. We show that evolution solved the enzyme's key kinetic obstacle-how to maintain catalytic speed on a cooler Earth-by exploiting transition-state heat capacity. Tracing the evolution of enzyme activity and stability from the hot-start toward modern hyperthermophilic, mesophilic, and psychrophilic organisms illustrates active pressure versus passive drift in evolution on a molecular level, refutes the debated activity/stability trade-off, and suggests that the catalytic speed of adenylate kinase is an evolutionary driver for organismal fitness.
Determined to Succeed : Researching Student Stories of Resilience (2013)

To respond to an identified gap in the literature, a qualitative research project was developed to explore if students had stories around continuing to study despite having experienced significant challenges and to locate what supported these students to avoid ‘dropping out’. Meaning attribution was also explored, along with seeing if students had advice for others. This article reports on the project, the relevant literature, research methodology and findings. The results confirmed that students who experience significant challenges do have stories to tell, and that they are keen to give advice for the benefit of others. Thematic analysis of the research data showed that the two main factors of ‘determination’ and ‘support’ were important to students’ continuation in courses, and that student services play a vital role in this. The data also showed that ‘determination’ was the preferred student language for attributing meaning to what they had done, and the clinical application of this is discussed. A major research outcome was the publication of the book - ‘Determined to Succeed’ in print and on-line formats (see www.acu.edu.au\determinedtosucceed). Converting the ‘Determined to Succeed’ book to an e-book positioned the student stories in the public domain, increasing access to the resource and contributing to student retention, all of which makes a valuable contribution to the tertiary education sector.
Elimination of a major inhibitor epitope in factor VIII. (1994)

The A2 and C2 domains of human blood coagulation factor VIII (fVIII) contain the epitopes targeted by most inhibitory allo- and autoantibodies. Human inhibitors usually display limited or no reaction with porcine fVIII. We constructed an active, recombinant hybrid human/porcine fVIII molecule by replacing the putative human fVIII A2 domain epitope with the homologous porcine sequence. The hybrid retained full activity in the presence of antibodies with specificity restricted to the human A2 epitope. In contrast, the hybrid was neutralized by an anti-C2 antibody. These findings provide a basis for fine epitope mapping and for therapy of the inhibitor patient.
Enforced CD19 Expression Leads to Growth Inhibition and Reduced Tumorigenicity (1999)

In multiple myeloma (MM), the cell surface protein, CD19, is specifically lost while it continues to be expressed on normal plasma cells. To examine the biological significance of loss of CD19 in human myeloma, we have generated CD19 transfectants of a tumorigenic human myeloma cell line (KMS-5). The CD19 transfectants showed slower growth rate in vitro than that of control transfectants. They also showed a lower capability for colony formation as evaluated by anchorage-independent growth in soft agar assay. The CD19 transfectants also had reduced tumorigenicity in vivo when subcutaneously implanted into severe combined immunodeficiency (SCID)-human interleukin-6 (hIL-6) transgenic mice. The growth-inhibitory effect was CD19-specific and probably due to CD19 signaling because this effect was not observed in cells transfected with a truncated form of CD19 that lacks the cytoplasmic signaling domain. The in vitro growth-inhibitory effect was confirmed in a nontumorigenic human myeloma cell line (U-266). However, introduction of the CD19 gene into a human erythroleukemia cell line (K-562) also induced growth inhibition, suggesting that this effect is CD19-specific, but not restricted to myeloma cells. These data suggest that the specific and generalized loss of CD19 in human myeloma cells could be an important factor contributing to the proliferation of the malignant plasma cell clones in this disease.
Efficient register allocation via coloring using clique separators (1994)

Although graph coloring is widely recognized as an effective technique for register allocation, memory demands can become quite high for large interference graphs that are needed in coloring. In this paper we present an algorithm that uses the notion of clique separators to improve the space overhead of coloring. The algorithm, based on a result by R. Tarjan regarding the colorability of graphs, partitions program code into code segments using clique separators. The interference graphs for the code partitions are constructed one at a time and colored independently. The colorings for the partitions are combined to obtain a register allocation for the entire program. This approach can be used to perform register allocation in a space-efficient manner. For straight-line code (e.g., local register allocation), an optimal allocation can be obtained from optimal allocations for individual code partitions. Experimental results are presented demonstrating memory demand reductions for interference graphs when allocating registers using clique separators.
An Overview of Adjuvant Use (2003)

Adjuvants have been used to augment the immune response to antigens for more than 70 years. Ramon first demonstrated that it was possible to increase levels of diphtheria or tetanus antitoxin by the addition of bread crumbs, agar, tapioca, starch oil, lecithin, or saponin to the vaccines (1). In this chapter, an overview is provided of modern vaccine adjuvants as background for more detailed discussions of promising adjuvants in chapters to follow. After a more general discussion of adjuvants including their definition, mechanisms of action, safety, ideal characteristics, impediments to development, and preclinical and clinical regulatory issues, examples will be provided of experimental vaccine adjuvants that have entered clinical trial to enhance a variety of licensed and experimental vaccines in humans. For additional expositions on this complex subject and for a historical perspective, the reader is referred to recent textbooks on vaccine adjuvants (2–4) and a selection of useful review articles published over the past 18 years (5,10).
Crystal structure of a pH-regulated luciferase catalyzing the bioluminescent oxidation of an open tetrapyrrole (2005)

The luciferase of Lingulodinium polyedrum, a marine bioluminescent dinoflagellate, consists of three similar but not identical domains in a single polypeptide. Each encodes an active luciferase that catalyzes the oxidation of a chlorophyll-derived open tetrapyrrole (dinoflagellate luciferin) to produce blue light. These domains share no sequence similarity with any other in the GenBank database and no structural or motif similarity with any other luciferase. We report here the 1.8-A crystal structure of the third domain, D3, at pH 8, and a mechanism for its activity regulation by pH. D3 consists of two major structural elements: a beta-barrel pocket putatively for substrate binding and catalysis and a regulatory three-helix bundle. N-terminal histidine residues previously shown to regulate activity by pH are at the interface of the helices in the bundle. Molecular dynamics calculations indicate that, in response to changes in pH, these histidines could trigger a large molecular motion of the bundle, thereby exposing the active site to the substrate.
Quantification of effectiveness of bilateral and unilateral neuromodulation in the rat bladder rhythmic contraction model (2013)

Using the bladder rhythmic contraction model, bilateral stimulation was more effective than unilateral stimulation of the SN. Clinical testing should be conducted to further compare efficacies of unilateral and bilateral stimulation. Bilateral stimulation may allow the use of lower stimulation intensities to achieve higher efficacy for neurostimulation therapies on urinary tract control.
Resolution Below the Least Significant Bit in Digital Systems with Dither (1984)

Effet de l'addition au singla audio d'un signal «dither» pour ameliorer les effets des pas de quantification du convertisseur AN. Etude des erreurs de quantification
THE EQUIVALENCE BETWEEN g-STABILITY AND R~n-STABILITY (1993)

In this paper,the equivalence between the space C_g and space R~n is studied.The resultsshow that C_g has a good property in this respect.As an application,the existence,uniquenceand stability,of the periodic solution of Volterra integro-differential equations are dealtwith,and new and interesting results are obtained.
Influenza A virus infection engenders a poor antibody response against the ectodomain of matrix protein 2 (2006)

The results provide convincing evidence that M2e-specific Ab-mediated protection is currently lacking or suboptimal in humans.
Plasmids in Lactobacillus (1997)

This review describes Lactobacillus plasmids on distribution, structure, function, vector construction, vector stability, application, and prospective. About 38% of species of the genus Lactobacillus were found to contain plasmids with different sizes (from 1.2 to 150 kb) and varied numbers (1 or more). Some Lactobacillus plasmids with small sizes were highly similar to those of single strand plasmids from other Gram-positive bacteria. The extensive sequence homologies of plus origins, replication initiation proteins, minus origins, cointegration sites, and the presence of single strand intermediates supported the fact that these small Lactobacillus plasmids replicate with a rolling-circle replication mechanism. Some Lactobacillus plasmid replicons were of broad host range that could function in other Gram-positive bacteria, and even in Escherichia coli, while replicons of other Gram-positive bacteria also function in Lactobacillus. Although most Lactobacillus plasmids are cryptic, some plasmid-encoded functions have been discovered and applied to vector construction and Lactobacillus identification, detection, and modification.
Two separate and distinct syntheses of stereospecifically deuteriated samples of (2S)-proline (2006)

Two distinct syntheses of samples of the amino acid L-proline which are stereospecifically deuteriated on the beta-carbon atom are reported. In the first of these, the labelled diazoketones 6, prepared by a chemico-enzymatic synthesis, have been photolysed in alkaline conditions to give the corresponding labelled methyl pyroglutamates 10 via hydrolysis and intramolecular trapping of the resultant ketene intermediates 9. These were then converted into (2S,3S)-[3-(2)H1]- and (2S,3R)-[2,3-(2)H2]-proline, 1a and 1b respectively. The second synthesis provides (2S)-[3,3-(2)H2]-, (2S,3S)- and (2S,3R)-[3-(2)H1]-proline, 1d, 1a and 1c respectively, and has as its key step the highly stereoselective hydrolysis of the silylenol ethers 14 and 14a respectively in which deuteriation or protonation occurs from the re-face of the enol ether.
Critical evaluation of search algorithms for automated molecular docking and database screening (1997)

The DOCK program explores possible orientations of a molecule within a macromolecular active site by superimposing atoms onto precomputed site points. Here we compare a number of different search methods, including an exhaustive matching algorithm based on a single docking graph. We evaluate the performance of each method by screening a small database of molecules to a variety of macromolecular targets. By varying the amount of sampling, we can monitor the time convergence of scores and rankings. We not only show that the site point–directed search is tenfold faster than a random search, but that the single graph matching algorithm boosts the speed of database screening up to 60-fold. The new algorithm, in fact, outperforms the bipartite graph matching algorithm currently used in DOCK. The results indicate that a critical issue for rapid database screening is the extent to which a search method biases run time toward the highest-ranking molecules. The single docking graph matching algorithm will be incorporated into DOCK version 4.0. © 1997 John Wiley & Sons, Inc. J Comput Chem 18: 1175–1189
Enhancement of cytolytic T lymphocyte precursor frequency in melanoma patients following immunization with the MAGE-1 peptide loaded antigen presenting cell-based vaccine. (1996)

Identification of human melanoma-associated peptide antigens for CTLs has opened unprecedented opportunities for active specific immunotherapy for melanoma with synthetic peptide. We have shown that immunization with a MAGE-1 gene encoded nonapeptide (EADPT-GHSY)-pulsed autologous antigen presenting cell-based vaccine induces autologous melanoma-reactive and peptide-specific CTL response, in situ, at the vaccination site and at distant tumor deposits in patients who are HLA-A1+ and whose melanoma cells express the MAGE-1 mRNA. Here, we show that such immunization is also capable of increasing the frequency of autologous melanoma-reactive CTL precursors in the circulation. We further show that in vitro stimulation of the postimmunization peripheral blood lymphocytes with the MAGE-1 nonapeptide-loaded antigen presenting cell and interleukin-2 leads to significant expansion of peptide-specific and autologous melanoma-reactive CTL response.
Complexity in Treatment of Syntactic Deficits (2007)

Using complex language material as a starting point for treatment of sentence structural deficits in aphasia results in cascading generalization to simpler, linguistically related material and expands spontaneous language production in many language-disordered adults with aphasia. Clinicians are, therefore, urged to adopt this approach in clinical practice, even though it is counterintuitive and departs significantly from conventional treatment methods.