gebhart/patrepeval huggingface dataset:
Eradication of Breast Cancer Xenografts by Hyperthermic Suicide Gene Therapy under the Control of the Heat Shock Protein Promoter (2000)

To investigate the usefulness of heat shock protein (HSP) promoter for breast cancer gene therapy, hyperthermia and HSV thymidine kinase (tk) suicide gene combination therapy was examined with mouse mammary cancer cell line FM3A. HSP promoter activity was markedly increased after heat shock (41-45 degrees C), with maximum activation (about 400-fold) at 3 hr. An in vitro cytotoxic assay showed that HSP-tk-transduced FM3A cells became more sensitive (more than 50,000 times) to ganciclovir (GCV) with heat shock, but untreated cells showed no increased cytotoxic sensitivity to GCV compared with control FM3A cells. In addition to promoter-oriented selective cell killing, a "chemosensitization effect" as a bystander effect was demonstrated by hyperthermia and suicide gene combination therapy, using a non-heat-inducible promoter. Immunohistochemical analysis revealed that this synergistic killing effect was dependent on apoptotic cell death with upregulation of both Fas and FasL (Fas ligand) expression. We also examined the efficacy of HSP-tk gene therapy in vivo by implanting breast cancer in subcutaneous and intraperitoneal models of BALB/c nude mice targeted by the HVJ-anionic liposome method. Significant tumor regression was observed in HSP-tk-transduced tumors followed by hyperthermia therapy, but no such inhibition was noted in either the mock vector transfection or hyperthermia group compared with control tumor-bearing mice. Our results demonstrate that this combination system is synergistically effective in mediating Fas-dependent apoptosis for a specific gene therapy targeting HSP-expressing mammary carcinomas, even in advanced and heat-resistant breast cancer.
Engineering, Characterization and in vitro Efficacy of the Major Peanut Allergens for Use in Immunotherapy (2001)

These modified allergen genes and proteins should provide a safe immunotherapeutic agent for the treatment of peanut allergy.
Understanding and constructing shared spaces with mixed-reality boundaries (1998)

We propose an approach to creating shared mixed realities based on the construction of transparent boundaries between real and virtual spaces. First, we introduce a taxonomy that classifies current approaches to shared spaces according to the three dimensions of transportation, artificiality, and spatiality. Second, we discuss our experience of staging a poetry performance simultaneously within real and virtual theaters. This demonstrates the complexities involved in establishing social interaction between real and virtual spaces and motivates the development of a systematic approach to mixing realities. Third, we introduce and demonstrate the technique of mixed-reality boundaries as a way of joining real and virtual spaces together in order to address some of these problems.
CHO cell expression, long‐term stability, and primate pharmacokinetics and brain uptake of an IgG–paroxonase‐1 fusion protein (2010)

Paraoxonase (PON)-1 is the most potent human organophosphatase known, but recombinant forms of human PON1 have been difficult to produce owing to poor secretion by host cells. In the present investigation, human PON1 is re-engineered as an IgG-PON1 fusion protein. The 355 amino acid human PON1 is fused to the carboxyl terminus of the heavy chain of a chimeric monoclonal antibody (MAb) against the human insulin receptor (HIR), and this fusion protein is designated HIRMAb-PON1. The HIRMAb part of the fusion protein enables brain penetration of the PON1, which was considered important, because organophosphate toxicity causes death via a central nervous system site of action. A high producing line of stably transfected Chinese hamster ovary (CHO) cells secreting the HIRMAb-PON1 fusion protein in the absence of serum or lipid acceptors was cloned. The bioreactor generated fusion protein was purified to homogeneity with low impurities by protein A affinity chromatography and anion exchange chromatography. The HIRMAb-PON1 fusion protein was stable as a sterile liquid formulation stored at 4°C for at least 1 year. The plasma pharmacokinetics (PK) of the HIRMAb-PON1 fusion protein was evaluated in Rhesus monkeys, which is the first PK evaluation of a recombinant PON1 protein. The fusion protein was rapidly removed from blood, primarily by the liver. The blood-brain barrier permeation of the HIRMAb-PON1 fusion protein was high and comparable to other HIRMAb fusion proteins. Re-engineering human PON1 as the HIRMAb fusion protein allows for production of a stable, field-deployable formulation of the enzyme that is brain-penetrating.
Three-dimensional modelling of an injection experiment in the anaerobic part of a landfill plume, (1998)

Analytical and numerical three-dimensional (3-D) simulations have been conducted and compared to data obtained from a large-scale (50 m), natural gradient field injection experiment. Eighteen different xenobiotic compounds (i.e. benzene, toluene, o-xylene, naphthalene, 1,1,1-TCA, PCE, and TCE) and bromide as a conservative tracer, were injected for 195 days in the anaerobic part of the leachate plume downgradient of the Grindsted Landfill, Denmark. The injection area is an unconfined sandy aquifer with heterogeneities of clay and silt layers. Simulations with homogeneous and heterogeneous hydraulic conductivity compared well to the observed breakthrough curves and snapshots of the injection plumes.
Active Site Mutations of Pseudomonas aeruginosa Exotoxin A (1995)

Pseudomonas aeruginosa exotoxin A (ETA) is a member of the family of bacterial ADP-ribosylating toxins which use NAD+ as the ADP-ribose donor. By analogy to diphtheria and pertussis toxins, the His440 residue of ETA has been proposed to be one of the critical residues within the active site of the toxin. In this study the role of the His440 residue was explored through site-directed mutagenesis which resulted in the production of ETA proteins containing Ala, Asn, and Phe substitutions at the 440 position. The His440-substituted ETA proteins were purified and analyzed. All substitutions at the 440 site displayed severely reduced ADP-ribosylation activity (> 1000-fold). However, NAD glycohydrolase activity remained intact and in the case of ETAH440N actually increased 10-fold. NAD+ binding is not affected by substitutions at the 440 site as indicated by similar Km values for the ETA variants tested. Conformational integrity of the mutant toxins appears to be largely unaffected as assessed by analysis with a conformation-sensitive monoclonal antibody as well as sensitivity to proteinase digestion. In view of the location of His440 residue within or close to the proposed NAD(+)-binding site, these results suggest that His440 may be a catalytic residue involved in the transfer of the ADP-ribose moiety to the EF-2 substrate.
Downregulation of cyclin-dependent kinase 2 activity and cyclin A promoter activity in vascular smooth muscle cells by p27(KIP1), an inhibitor of neointima formation in the rat carotid artery. (1997)

Abnormal proliferation of vascular smooth muscle cells (VSMCs) contributes to intimal hyperplasia during atherosclerosis and restenosis, but the endogenous cell cycle regulatory factors underlying VSMC growth in response to arterial injury are not well understood. In the present study, we report that downregulation of cyclin-dependent kinase 2 (cdk2) activity in serum-deprived VSMCs was associated with the formation of complexes between cdk2 and its inhibitory protein p27(KIP1) (p27). Ectopic overexpression of p27 in serum-stimulated VSMCs resulted in the inhibition of cdk2 activity and repression of cyclin A promoter activity. Collectively, these findings indicate that p27 may contribute to VSMC growth arrest in vitro. Using the rat carotid model of balloon angioplasty, a marked upregulation of p27 was observed in injured arteries. High levels of p27 expression in the media and neointima correlated with downregulation of cdk2 activity at 2 wk after angioplasty, and adenovirus-mediated overexpression of p27 in balloon-injured arteries attenuated neointimal lesion formation. Thus, the inhibition of cdk2 function and repression of cyclin A gene transcription through the induction of the endogenous p27 protein provides a mechanism for the inhibition of VSMC growth at late time points after angioplasty.
Evaluation of bovine, cold-adapted human, and wild-type human parainfluenza type 3 viruses in adult volunteers and in chimpanzees (1991)

In an attempt to evaluate the level of attenuation of live parainfluenza type 3 virus (PIV3) vaccine candidates, we compared the responses of partially immune adult volunteers inoculated intranasally with 10(6) to 10(7) 50% tissue culture infective dose (TCID50) of bovine PIV3 (n = 18) or cold-adapted (ca) PIV3 (n = 37) with those of 28 adults administered 10(6) to 10(7) TCID50 of wild-type PIV3. The candidate vaccine viruses and the wild-type virus were avirulent and poorly infectious for these adults even though all of them had a low level of nasal antibodies to PIV3. To determine whether the ca PIV3 was attenuated, we then administered 10(4) TCID50 of ca PIV3 (cold-passage 12) or wild-type PIV3 intranasally and intratracheally to two fully susceptible chimpanzees, respectively, and challenged the four primates with wild-type virus 1 month later. Compared with wild-type virus, which caused upper respiratory tract illness, the ca PIV3 was highly attenuated and manifested a 500-fold reduction in virus replication in both the upper and lower respiratory tracts of the two immunized animals. Despite restriction of virus replication, infection with ca PIV3 conferred a high level of protective immunity against challenge with wild-type virus. The ca PIV3 which had been passaged 12 times at 20 degrees C did not retain its ts phenotype. These findings indicate that ca PIV3 may be a promising vaccine candidate for human beings if a passage level can be identified that is genetically stable, satisfactorily attenuated, and immunogenic.
Quantitative analysis of two‐dimensional protein profiles of inbred lines of maize (Zea mays L.) (1991)

Two-dimensional electrophoresis and fluorography of [35S]methionine labeled maize germinated embryo proteins were performed at Cold Spring Harbor Laboratory. Fluorographs of 63 gels representing 37 inbred lines were subsequently scanned and spot-detected at Protein and DNA Imageware Systems (Huntington Station, NY). The digitized images were then matched with the aid of PDQUEST-II computer software. Over 1500 different protein spots were included in the resulting dataset. The optical density data were normalized to parts per million, then transformed to their natural logarithms. Analyses of variance were performed on each spot in order to select for further study those spots with most of their variation partitioned among inbred lines rather than within inbred lines. Using this method of spot selection, over 100 protein spots were included in the set of spots which display significant differences among inbred lines of maize.
Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update. (2010)

Epidermal growth factor receptor is a trans-membrane glycoprotein with an extracellular epidermal growth factor binding domain and an intracellular tyrosine kinase domain that regulates signaling pathways to control cellular proliferation. Epidermal growth factor receptor binding to its ligand results in autophosphorylation by intrinsic tyrosine/kinase activity, triggering several signal transduction cascades. Constitutive or sustained activation of these sequences of downstream targets is thought to yield more aggressive tumor phenotypes. Mutations in epidermal growth factor receptor have been discovered in association with some lung cancers. Lung adenocarcinomas with mutated epidermal growth factor receptor have significant responses to tyrosine kinase inhibitors, although for unselected patients it does not appear to have a survival benefit. However, in a subset of patients (non-smoking Asian women with adenocarcinoma, particularly with a bronchioloalveolar carcinoma), there appears to be a significant survival advantage. Both EGFR mutation and gene amplification status may be important in determining which tumors will respond to tyrosine kinase inhibitors.
A Study of Cobalt and Manganese Fluorides as Cathode Materials for Rechargeable Lithium Cells (2012)

This paper describes a study of the lithium/transition metal fluoride cells using nanocomposites of carbon with cobalt or manganese fluorides as cathode materials. The nanocomposite cathode materials were prepared by high energy milling of carbon and metal fluorides. It was, however, found that cobalt trifluoride reacted with carbon during the high energy milling process to form carbon fluoride. The Li/cobalt fluoride cells were, therefore, studied by using nanocomposite cathodes prepared by high energy milling of carbon, cobalt metal and lithium fluoride or cathodes prepared by mixing carbon and cobalt trifluoride without subjecting the mixture to the high energy milling process. The charge- discharge characteristics of lithium/transition metal fluoride cells were studied at 22oC and 50oC using a 1M LiPF6-sulfolane solution as the electrolyte. The cells were found to be electrochemically reversible but could not be completely charged due to simultaneous oxidation of the electrolyte at potentials above ~4.5 Volts.
Arene chromium complexes with functionalized anellated rings. Selective formation of highly substituted polycycles (2002)

Abstract Tricarbonylchromium complexes of benzocyclobutenone, benzocyclobutenedione, and 1,3-indandione are readily prepared by hydrolysis of the complexes of the corresponding acetals. Reduction of the benzocyclobutenone complex gives rise to an oxy-anion-driven ring opening to the corresponding ortho-quinodimethane intermediate, which can be trapped with dienophiles. Addition of 1-ethoxy-1-lithioethene allows a stereoselective ring expansion followed by an anionic ketol rearrangement with complete diastereoselectivity. Addition of 1-lithio-1-methoxyallene gives rise to a rare anionic 1-vinylcyclobutenol-cyclohexadienol rearrangement. Diaddition of alkenylmetal reagents at both keto groups in benzoyclobutenedione complexes causes dianionic oxy-Cope rearrangements to occur at ­78 °C, which are followed by diastereoselective intramolecular aldol additions. In some cases, a completely regioselective mono hydrolysis of di(enolates) was observed. Dianionic oxy-Cope rearrangements can also be realized with unstrained benzil derivatives giving 1,6-hexanediones and the corresponding aldol adducts. The 1,2,3-indantrione complex is obtained by oxidation of the 1,3-indandione complex with dimethyldioxirane in good yield and reacts with its central ketone group in hetero Diels­Alder cycloadditions.
A Versatile Platform to Analyze Low-Affinity and Transient Protein-Protein Interactions in Living Cells in Real Time (2014)

Protein-protein interactions (PPIs) play central roles in orchestrating biological processes. While some PPIs are stable, many important ones are transient and hard to detect with conventional approaches. We developed ReBiL, a recombinase enhanced bimolecular luciferase complementation platform, to enable detection of weak PPIs in living cells. ReBiL readily identified challenging transient interactions between an E3 ubiquitin ligase and an E2 ubiquitin-conjugating enzyme. ReBiL's ability to rapidly interrogate PPIs in diverse conditions revealed that some stapled α-helical peptides, a class of PPI antagonists, induce target-independent cytosolic leakage and cytotoxicity that is antagonized by serum. These results explain the requirement for serum-free conditions to detect stapled peptide activity, and define a required parameter to evaluate for peptide antagonist approaches. ReBiL's ability to expedite PPI analysis, assess target specificity and cell permeability, and reveal off-target effects of PPI modifiers should facilitate the development of effective, cell-permeable PPI therapeutics and the elaboration of diverse biological mechanisms.
Evaluating WordNet-based Measures of Lexical Semantic Relatedness (2006)

The quantification of lexical semantic relatedness has many applications in NLP, and many different measures have been proposed. We evaluate five of these measures, all of which use WordNet as their central resource, by comparing their performance in detecting and correcting real-word spelling errors. An information-content-based measure proposed by Jiang and Conrath is found superior to those proposed by Hirst and St-Onge, Leacock and Chodorow, Lin, and Resnik. In addition, we explain why distributional similarity is not an adequate proxy for lexical semantic relatedness.
Production of furfural and carboxylic acids from waste aqueous hemicellulose solutions from the pulp and paper and cellulosic ethanol industries (2011)

In this paper we present a new process to produce furfural and co-products of formic and acetic acids from waste aqueous hemicellulose solutions using a continuous two zone biphasic reactor. We estimate this approach uses 67% to 80% less energy than the current industrial processes to produce furfural. An economic analysis indicates that furfural can be produced with this process at 366 US$ per metric ton which is 25% of the selling price of furfural in the U.S. market today. This analysis assumes a plant capacity of 78 kiloton per year of furfural, 12 kiloton per year of formic acid and 44 kiloton per year of acetic acid (processing 160 ton per hour of hemicellulose solutions with a xylose concentration of 10.7 wt%) and is based on the data collected in this paper. Formic acid and acetic acid are probably produced from the acid hydrolysis of formylated and acetylated xylose oligomers, respectively. Furfural is produced in a two-step process consisting of the hydrolysis of xylose oligomers followed by the dehydration of xylose monomers and then extraction of the furfural into an organic solvent. Two types of hemicellulose solutions were used as the feedstock including a hot water extract and a green liquor extract derived from Northeastern hardwood trees. The hemicellulose solution contains mainly xylose oligomers as well as glucose, arabinose, lactic acid, acetic acid, formic acid, and other minor products. We found that the reaction temperature, the space velocity, the volumetric organic to aqueous phase ratio, and the acid concentration have significant effects on the furfural production. Under the optimized condition, a furfural yield of 90% can be achieved in the reactor from the hot water extract containing 10.7 wt% xylose. A conceptual design is performed for the integration of the production of furfural, formic and acetic acids, the liquid–liquid split, and subsequent three-stage distillations. We demonstrate that high purity (>99%) of furfural, formic and acetic acids can be obtained, with a final recovery of more than 97%, 56%, and 88% of the furfural, formic acid and acetic acid, respectively.
Characterization of hypoxia-inducible factor 1 and regulation of DNA binding activity by hypoxia. (1993)

Hypoxia-inducible factor 1 (HIF-1) is a DNA binding activity detected in nuclear extracts from Hep3B cells cultured in 1% O2 but not in extracts from cells cultured in 20% O2. HIF-1 binds to a sequence within the human erythropoietin gene enhancer that is required for hypoxic activation of transcription. Induction of HIF-1 is inhibited by cycloheximide, which also inhibits induction of erythropoietin RNA. We now demonstrate that induction of both HIF-1 and erythropoietin RNA is inhibited by the protein kinase inhibitor 2-aminopurine. HIF-1 binding to DNA was eliminated by phosphatase treatment of nuclear extracts. Actinomycin D also inhibited HIF-1 induction, suggesting that de novo transcription is required. The kinetics of HIF-1 induction by hypoxia paralleled the kinetics of erythropoietin gene transcriptional induction. HIF-1 DNA binding activity decayed rapidly when hypoxic cells were exposed to increased oxygen tension. In vitro, the kinetics of HIF-1 association with, and dissociation from, its binding site were extremely rapid, with a t1/2 for both processes of < 1 min. These findings are consistent with the proposed function of HIF-1 as a physiologic regulator of gene expression that responds to changes in cellular oxygen tension. Methylation interference analysis indicated that HIF-1 makes specific contacts with DNA in the major groove.
Virtual tomography: a new approach to efficient human-computer interaction for medical imaging (2003)

By utilizing virtual reality (VR) technologies the computer system virtusMED implements the concept of virtual tomography for exploring medical volumetric image data. Photographic data from a virtual patient as well as CT or MRI data from real patients are visualized within a virtual scene. The view of this scene is determined either by a conventional computer mouse, a head-mounted display or a freely movable flat panel. A virtual examination probe is used to generate oblique tomographic images which are computed from the given volume data. In addition, virtual models can be integrated into the scene such as anatomical models of bones and inner organs. virtusMED has shown to be a valuable tool to learn human anaotomy and to udnerstand the principles of medical imaging such as sonography. Furthermore its utilization to improve CT and MRI based diagnosis is very promising. Compared to VR systems of the past, the standard PC-based system virtusMED is a cost-efficient and easily maintained solution providing a highly intuitive time-saving user interface for medical imaging.
Bacillopeptidase F of Bacillus subtilis: purification of the protein and cloning of the gene (1990)

We have purified a minor extracellular serine protease from Bacillus subtilis. Characterization of this enzyme indicated that it was most likely the previously reported enzyme bacillopeptidase F. The amino-terminal sequence of the purified protein was determined, and a "guess-mer" oligonucleotide hybridization probe was constructed on the basis of that sequence. This probe was used to identify and clone the structural gene (bpr) for bacillopeptidase F. The deduced amino acid sequence for the mature protein (496 amino acids) was preceded by a putative signal sequence of 30 residues and a putative propeptide region of 164 amino acids. The bpr gene mapped near pyrD on the chromosome and was not required for growth or sporulation.