gebhart/patrepeval huggingface dataset:
The gene for the human immune interferon receptor is located on chromosome 6. (1986)

When 32P-labeled human recombinant immune interferon gamma (Hu-[32P]IFN-gamma) is crosslinked to human cells with disuccinimidyl suberate, a complex with a molecular size of approximately equal to 117,000 Da was identified by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The formation of this complex is inhibited when the binding is performed in the presence of excess unlabeled Hu-IFN-gamma. The specific formation of the 117,000-Da complex is not observed in mouse L cells or Chinese hamster ovary cells. This complex shows all of the criteria that identify it as the Hu-IFN-gamma receptor or its binding subunit. The same complex can be formed following binding and covalent crosslinking of Hu-[32P]IFN-gamma to some hamster-human or mouse-human somatic cell hybrids. The presence of human chromosome 6 in the hybrids is necessary and sufficient for the formation of this complex. More specifically, the long arm of chromosome 6 seems sufficient. Therefore, we have localized the gene for the Hu-IFN-gamma receptor (or its binding subunit) to the long arm of human chromosome 6. The presence of this chromosome in the somatic cell hybrids is not adequate, however, to confer antiviral resistance to the hybrids in the presence of Hu-IFN-gamma.
Microglia and macrophages are increased in response to ischemia-induced retinopathy in the mouse retina. (2006)

Our results suggest that resident retinal microglia proliferation occurs at a low frequency in response to injury in this model. The substantial increase in total F4/80+ cells in hyperoxia-exposed retinas in conjunction with the upregulation of CCL2 is consistent with recruitment of hematogenous macrophages into the retina. The temporal and spatial localization of MG/MAC adjacent to neovascular tufts suggests these cells are modulating the retinal response to ischemia-induced retinopathy.
The variation of residual impurities in ZnSe crystals used in light-emitting diode fabrications (1982)

Recent reports in the literature suggest that residual impurities, probably interstitial lithium, are responsible for the strong compensation of p-type conductivity in ZnSe. Data presented here support these findings. ZnSe boules that had high Li content, as determined from the pair band of the emission spectra, produced poor light-emitting diodes (LED’s). At the same time LED’s were consistently good when boules that contained less residual Li were used. Ion microprobe measurements showed that one of the processes that takes place during LED fabrication is the reduction of the residual Li content. These two findings together show that low Li content is a prerequisite for good LED formation.
In Vivo Demonstration in Humans That Large Postprandial Triglyceride-Rich Lipoproteins Activate Coagulation Factor VII Through the Intrinsic Coagulation Pathway (1996)

In vitro studies in purified plasma systems have suggested that triglyceride-rich lipoproteins such as chylomicrons, very low density lipoproteins, and their remnants promote activation of factor VII through activated factor XII (XIIa) and the intrinsic coagulation pathway. We specifically examined the roles of factors XII, XI, and IX in activation of factor VII during alimentary lipemia in vivo in humans and addressed the issue of whether generation of activated factor VII (VIIa) is accompanied by increased thrombin production. For this purpose XIIa, factor IX activation peptide (IXP), VIIa, prothrombin fragment 1 + 2 (F1 + 2), and thrombin-antithrombin complex (TAT) were determined in plasma samples taken before and 3, 6, and 9 hours after intake of a mixed meal type of oral fat load in 24 healthy men The VIIa response to fat intake was also determined in 7 patients with single coagulation-factor deficiency, of whom 2 were deficient in factor XII, 2 in factor XI, and 3 in factor IX. Postprandial activation of factors IX and VII occurred in the healthy individuals, whereas the plasma levels of XIIa did not change in response to the test meal. Of note, plasma concentrations of F1 + 2 were unaltered during alimentary lipemia, and TAT levels showed a small decrease (P < .05) in the 3-hour sample compared with the fasting level, indicating that thrombin generation is not stimulated in the postprandial state, despite the generation of activated factor IX (IXa) and VIIa. Factor VIIa increased in the postprandial period in the 2 factor XII-deficient patients who underwent the oral fat tolerance test but appeared to remain unchanged in the factor XI- and factor IX-deficient patients. Therefore, the current concept that activation of factor XII plays a pivotal role in initiating the sequence of events linking postprandial lipemia to activation of factor VII is contradicted by the present study. Whether activation of factor XI by triglyceride rich lipoproteins initiates these reactions needs to be demonstrated in future studies.
Prodrugs of HIV Protease Inhibitors (2003)

Despite the efficiency of the present polytherapies against AIDS, HIV replication continues indicating difficulties in drug adherence, drug-drug interactions, resistance issues, and the existence of reservoirs or sanctuaries for the virus. Moreover, most of the current FDA-approved HIV protease inhibitors (PIs) display disadvantageous physicochemical and pharmacological properties such as low water solubility, low oral bioavailability and/or low level of penetration into the HIV sanctuaries resulting from their in vivo binding to the plasma proteins and to the Multi-Drug-Resistant P-glycoprotein, their rapid metabolization and inactivation by the liver cytochrome P450 enzymes. To overcome these suboptimal pharmacokinetics, high daily doses must be ingested, which complicate patient adherence to the prescribed regimen and contribute to the appearance of serious long-term metabolic complications and to the decrease of the viral treatment outcome. Another attractive alternative aimed at improving the safety, pharmacokinetics, and therapeutic potency of the current PIs is to modify these PIs into pharmacologically inactive prodrugs which are converted in vivo into their parent active drug. The present review is dedicated to the different prodrug approaches, including the "lipophilic", "hydrophilic", "active transport" and "double-drug" prodrug strategies, which have been applied more particularly to the current HIV PIs used in clinic. Among the strategies explored up to now, the most successful one was the "hydrophilic" prodrug approach which has led to the discovery of fosamprenavir, a phosphate ester prodrug of amprenavir, which has reached phase III clinical trials. This success gives strong support for the search of PI prodrugs as a therapeutic alternative in addition to the development of new and well-tolerated PIs.
Biological activity of synthetic heptaacyl lipid A representing a component of Salmonella minnesota R595 lipid A (1986)

A synthetic lipid A (preparation 516), containing seven acyl groups and representing one component of natural free lipid A of Salmonella minnesota R595, has been investigated for biological activity in a number of endotoxin test systems. It was found that the synthetic preparation was, in typical in vivo endotoxin tests (lethality, pyrogenicity, Shwartzman reactivity) as well as in its antigenicity and macrophage activation capacity, significantly less active than natural Salmonella lipid A. However, in other in vitro assay systems (B-cell mitogenicity, complement activation, Limulus amoebocyte lysate gelation) it expressed similar activity as Salmonella lipid A.
Critical Role of STAT3 in IL-6–Mediated Drug Resistance in Human Neuroblastoma (2013)

Drug resistance is a major cause of treatment failure in cancer. Here, we have evaluated the role of STAT3 in environment-mediated drug resistance (EMDR) in human neuroblastoma. We determined that STAT3 was not constitutively active in most neuroblastoma cell lines but was rapidly activated upon treatment with interleukin (IL)-6 alone and in combination with the soluble IL-6 receptor (sIL-6R). Treatment of neuroblastoma cells with IL-6 protected them from drug-induced apoptosis in a STAT3-dependent manner because the protective effect of IL-6 was abrogated in the presence of a STAT3 inhibitor and upon STAT3 knockdown. STAT3 was necessary for the upregulation of several survival factors such as survivin (BIRC5) and Bcl-xL (BCL2L1) when cells were exposed to IL-6. Importantly, IL-6-mediated STAT3 activation was enhanced by sIL-6R produced by human monocytes, pointing to an important function of monocytes in promoting IL-6-mediated EMDR. Our data also point to the presence of reciprocal activation of STAT3 between tumor cells and bone marrow stromal cells including not only monocytes but also regulatory T cells (Treg) and nonmyeloid stromal cells. Thus, the data identify an IL-6/sIL-6R/STAT3 interactive pathway between neuroblastoma cells and their microenvironment that contributes to drug resistance.
In Vitro Degradation and Release Characteristics of Biodegradable Implants Containing Trypsin Inhibitor (1995)

The use of a biodegradable implant system that provides a steady, controlled release of drugs or bioactive factors can be an attractive delivery vehicle of substances that can enhance repair processes in the musculoskeletal system. The present in vitro study examined the degradative characteristics and release kinetics of a 50 to 50 polylactic acid/polyglycolic acid implant, used as a carrier of trypsin inhibitor, during a 10-week period. Morphological and scanning electron microscopic examinations demonstrated that the implant degraded in a gradual, extended fashion such that by 10 weeks the implant was completely dissolved. It also was shown that the protein was released from the implant in a sigmoidal fashion with increased release between 3 and 7 weeks. More than 95% of the trypsin inhibitor originally incorporated in the implants was released during the 10-week test period. To describe further the degradation process of the implant, temporal changes in its molecular weight and surface axial strain were determined also. It was shown that in the initial 4 weeks, there was a marked decrease in molecular weight of the implants. Axial strain decreased and then increased over time, suggesting an initial period of stiffening followed by a period of degradative softening.
Real-time image mosaicing for medical applications. (2007)

In this paper we describe the development of a robotically-assisted image mosaicing system for medical applications. The processing occurs in real-time due to a fast initial image alignment provided by robotic position sensing. Near-field imaging, defined by relatively large camera motion, requires translations as well as pan and tilt orientations to be measured. To capture these measurements we use 5-d.o.f. sensing along with a hand-eye calibration to account for sensor offset. This sensor-based approach speeds up the mosaicing, eliminates cumulative errors, and readily handles arbitrary camera motions. Our results have produced visually satisfactory mosaics on a dental model but can be extended to other medical images.
Therapeutic Antibodies against Intracellular Tumor Antigens (2017)

Monoclonal antibodies are among the most clinically effective drugs used to treat cancer. However, their target repertoire is limited as there are relatively few tumor-specific or tumor-associated cell surface or soluble antigens. Intracellular molecules represent nearly half of the human proteome and provide an untapped reservoir of potential therapeutic targets. Antibodies have been developed to target externalized antigens, have also been engineered to enter into cells or may be expressed intracellularly with the aim of binding intracellular antigens. Furthermore, intracellular proteins can be degraded by the proteasome into short, commonly 8-10 amino acid long, peptides that are presented on the cell surface in the context of major histocompatibility complex class I (MHC-I) molecules. These tumor-associated peptide-MHC-I complexes can then be targeted by antibodies known as T-cell receptor mimic (TCRm) or T-cell receptor (TCR)-like antibodies, which recognize epitopes comprising both the peptide and the MHC-I molecule, similar to the recognition of such complexes by the TCR on T cells. Advances in the production of TCRm antibodies have enabled the generation of multiple TCRm antibodies, which have been tested <i>in vitro</i> and <i>in vivo</i>, expanding our understanding of their mechanisms of action and the importance of target epitope selection and expression. This review will summarize multiple approaches to targeting intracellular antigens with therapeutic antibodies, in particular describing the production and characterization of TCRm antibodies, the factors influencing their target identification, their advantages and disadvantages in the context of TCR therapies, and the potential to advance TCRm-based therapies into the clinic.
Variable Region Domain Exchange Influences the Functional Properties of IgG (1998)

In the present study we have characterized a family of anti-dansyl Abs with the variable region of the heavy chain on human Ckappa and the variable region of the light chain on different human gamma constant regions (creating inside-out molecules). Although fully assembled molecules were secreted, this variable region exchange slowed the kinetics of Ab assembly. Although the variable region exchange does not lead to a detectable change in the microenvironment of the combining site, it did alter the kinetic parameters of binding to immobilized Ag, slowing both the on and off rates. When effector functions were evaluated, inside-out IgG1 and IgG3 were more effective in complement-mediated cytolysis than their wild-type counterparts. Variable region domain exchange may be one approach to obtaining Abs of identical specificity with altered binding characteristics.
Oral phenylalanine loading in dopa‐responsive dystonia (1997)

To determine if there is abnormal phenylalanine and biopterin metabolism in patients with dopa-responsive dystonia (DRD), we measured plasma levels of phenylalanine, tyrosine, biopterin, and neopterin at baseline, and 1, 2, 4, and 6 hours after an oral phenylalanine load (100 mg/kg). Seven adults with DRD, two severely affected children with DRD, and nine adult controls were studied. All patients had phenylalanine and tyrosine concentrations within the normal range at baseline. In the adult patients, phenylalanine levels were higher than in controls at 2, 4, and 6 hours post-load (p < 0.0005); tyrosine concentrations were lower than control levels at 1, 2, and 4 hours post-load (p < 0.05). Phenylalanine to tyrosine ratios were elevated in patients at all times post-load (p < 0.0005). Biopterin levels in the patients were decreased at baseline and 1, 2, and 4 hours post-load (p < 0.005). Pretreatment with tetrahydrobiopterin (7.5 mg/kg) normalized phenylalanine and tyrosine profiles in two adult patients. In the children with DRD, phenylalanine to tyrosine ratios were slightly elevated at baseline. Following phenylalanine loading, the phenylalanine profiles were similar to those seen in the adult patients but there was no elevation in plasma tyrosine. Baseline biopterin levels were lower in the children with DRD than in the adult patients or the controls and there was no increase in biopterin post-load. In both the children and adults with DRD, neopterin concentrations did not differ from control values at baseline or after phenylalanine load. The results are consistent with decreased liver phenylalanine hydroxylase activity due to defective synthesis of tetrahydrobiopterin in patients with DRD. The findings show that a phenylalanine load may be useful in the diagnosis of this disorder.
Streptozocin- and Alloxan-Induced H2O2 Generation and DNA Fragmentation in Pancreatic Islets: H2O2 as Mediator for DNA Fragmentation (1991)

Streptozocin (STZ) and alloxan (ALX) exhibit the most potent diabetogenicity and are used for induction of experimental diabetes mellitus. An understanding of the mechanisms of action of the typical diabetogenic agents is important for elucidating the causes of diabetes. Okamoto proposed a model in which DNA fragmentation plays an important role in the development of diabetes. DNA fragmentation supposedly results from the accumulation of superoxide or hydroxyl radicals. However, direct evidence for this accumulation is lacking. With isolated rat pancreatic islets in vitro, we demonstrated that STZ and ALX stimulated H2O2 generation and caused DNA fragmentation. Addition of STZ or ALX resulted in an increase in H2O2 generation. On DNA analysis, when incubated without STZ or ALX, DNA sedimented as a single peak; when incubated with STZ or ALX, DNA sedimented slower as a broad peak and was fragmented. Graded doses of STZ and ALX stimulated H2O2 generation and induced DNA fragmentation; their effects on H2O2 generation and DNA fragmentation were evident at a concentration of 0.1 mM and were maximal at 1 mM. Administration of STX or ALX to rats in vivo stimulated H2O2 generation and caused DNA fragmentation in pancreatic islets. H2O2 itself also induced DNA fragmentation. These findings may support Okamoto's proposal that STZ and ALX induce diabetes through the following biochemical events: STZ and ALX----H2O2 generation----DNA fragmentation----beta-cell destruction. This study may constitute the first demonstration of STZ- and ALX-stimulated H2O2 generation, which probably acts as a mediator of STZ- and ALX-induced DNA fragmentation.
From the bench to the bedside: ways to improve rituximab efficacy (2004)

Rituximab (MabThera, Rituxan) is a chimeric IgG1 monoclonal antibody that specifically targets the CD20 surface antigen expressed on normal and neoplastic B-lymphoid cells. Rituximab is currently used in the treatment of both follicular and aggressive B-cell non-Hodgkin lymphomas. Despite its demonstrated clinical effectiveness, its in vivo mechanisms of action remain unknown and could differ by subtype of lymphoma. Rituximab has been shown to induce apoptosis, complement-mediated lysis, and antibody-dependent cellular cytotoxicity in vitro, and some evidence points toward an involvement of these mechanisms in vivo. Rituximab also has a delayed therapeutic effect as well as a potential "vaccinal" effect. Here, we review the current understanding of the mechanism of action of rituximab and discuss approaches that could increase its clinical activity. A better understanding of how rituximab acts in vivo should make it possible to develop new and more effective therapeutic strategies.
Image quality with non-standard nuclides in PET. (2008)

Non-standard positron emission tomography (PET) nuclides bring with them the prospect of new chemistry leading the way to novel approaches for targeted imaging and therapy. In particular, the kinetic energy of the positron of some of these nuclides is high (as much as 4 MeV) and, thus, a highly specific PET probe can be very lethal to cancerous cells. However, the high positron energy will degrade the spatial resolution, and this degradation will be more important in high-resolution, small animal PET imaging, where most of the novel tracers are developed. This paper discusses the image quality in small animal PET imaging obtained with such nuclides. The nuclides of (60)Cu, (61)Cu and (64)Cu, (76)Br, (94)mTc, and (89)Zr will be particularly analyzed. The spatial resolution will be seen to degrade with nuclides with higher positron end-point energy, going from 1.7 mm for (18)F to 2.2 mm for (76)Br, for example. Many of these novel PET nuclides decay by the emission of cascades gamma rays that are detected in coincidence with the positron annihilation photons which create additional noise on the images. However, the use of an image reconstruction algorithm, which includes a model of the statistical nature of nuclear decay and the modeling of the tomograph response, contributes to both improve the spatial resolution and at the same time reduce the image noise.
Anatomy-based joint models for virtual human skeletons (2002)

This paper describes a new joint model for articulated human skeletons. The model is based in human anatomy and was conceived for use in medical applications. In this model, we try to overcome some limitations of other models used in computer graphics. For validation, we compared a knee modeled by our approach with a simulator, a plastic model of a knee, and images taken during a video-arthroscopy.
Molecular and applied aspects (2009)

Preface Contributors Introduction Section 1: Bacteriophage Genomics 1. Preparation of Bacteriophage Lysates and Pure DNA Derek John Juan Pickard 2. Approaches to the Compositional Analysis of DNA Richard A. Manderville and Andrew M. Kropinski 3. Determination of Bacteriophage Genome Size by Pulsed-Field Gel Electrophoresis Erika Lingohr, Shelley Frost, and Roger P. Johnson 4. Preparation of a Phage DNA Fragment Library for Whole Genome Shotgun Sequencing Elizabeth J. Summer 5. PCR and Partial Sequencing of Bacteriophage Genomes Martha R. J. Clokie 6. In Silico Identification of Genes in Bacteriophage DNA Andrew M. Kropinski, Mark Borodovsky, Tim J. Carver, Ana M. Cerdeno-Tarraga, Aaron Darling, Alexandre Lomsadze, Padmanabhan Mahadevan, Paul Stothard, Donald Seto, Gary Van Domselaar, and David S. Wishart 7. Determining DNA Packaging Strategy by Analysis of the Termini of the Chromosomes in Tailed-Bacteriophage Virions Sherwood R. Casjens and Eddie B. Gilcrease 8. In silico Characterization of DNA Motifs with Particular Reference to Promoters and Terminators Rob Lavigne, Andre Villegas, and Andrew M. Kropinksi 9. Molecular Phylogenetics: Testing Evolutionary Hypotheses David A. Walsh and Adrian K. Sharma Section 2: Bacteriophage Transcriptomics and Proteomics 10. Preparation of RNA from Bacteria Infected with Bacteriophages: A Case Study from the Marine Unicellular Synechococcus sp. WH7803 Infected by Phage S-PM2 Jinyu Shan and Martha R. J. Clokie 11. Quantification of Host and Phage mRNA Expression during Infection Using Real-Time PCR Martha R. J. Clokie 12. Oligonucleotide Microarrays for Bacteriophage Expression Studies Andrew D.Millard and Bella Tiwari 13. Purification of Bacteriophages and SDS-PAGE Analysis of Phage Structural Proteins from Ghost Particles Pascale Boulanger 14. Phage Proteomics: Applications of Mass Spectrometry Rob Lavigne, Pieter-Jan Ceyssens, and J. Robben Section 3: Community Bacteriophage Approaches 15. Isolation Independent Methods of Characterizing Phage Communities 1: Strain Typing Using Fingerprinting Methods Clemens Pausz, Jessica L. Clasen, and Curtis A. Suttle 16. Isolation Independent Methods of Characterizing Phage Communities 2: Characterizing a Metagenome K. Eric Wommack, Shellie R. Bench, Jaysheel Bhavsar, David Mead, and Tom Hanson Section 4: Applied Aspects of Bacteriophage Biology 17. Phage Typing Irina Chirakadze, Ann Perets, and Rafiq Ahmed 18. A Genetic Screen to Identify Bacteriophage Lysins Raymond Schuch, Vincent A. Fischetti, and Daniel Nelson 19. General M13 Phage Display: M13 Phage Display in Identification and Characterization of Protein-Protein Interactions Kirsten Hertveldt, Tim Belien, and Guido Volckaert 20. Isolation of Monoclonal Antibody Fragments from Phage Display Libraries Mehdi Arbabi-Ghahroudi, Jamshid Tanha, and Roger MacKenzie 21. Internet Resources of Interest to Bacteriophage Workers Andrew M. Kropinski