gebhart/patrepeval huggingface dataset:
Experimental Autoimmune Encephalomyelitis Induced with a Combination of Myelin Basic Protein and Myelin Oligodendrocyte Glycoprotein Is Ameliorated by Administration of a Single Myelin Basic Protein Peptide (1998)

Multiple sclerosis is an autoimmune disease of the central nervous system in which T cell reactivity to several myelin proteins, including myelin basic protein (MBP), proteolipid protein, and myelin oligodendrocyte glycoprotein (MOG), has been implicated in the perpetuation of the disease state. Experimental autoimmune encephalomyelitis (EAE) is used commonly as a model in which potential therapies for multiple sclerosis are evaluated. The ability of T cell epitope-containing peptides to down-regulate the disease course is well documented for both MBP- and proteolipid protein-induced EAE, and recently has been shown for MOG-induced EAE. In this study, we describe a novel EAE model, in which development of severe disease symptoms in (PL/J x SJL)F1 mice is dependent on reactivity to two different immunizing Ags, MBP and MOG. The disease is often fatal, with a relapsing/progressive course in survivors, and is more severe than would be predicted by immunization with either Ag alone. The MOG plus MBP disease can be treated postinduction with a combination of the MOG 41-60 peptide (identified as the major therapeutic MOG epitope for this strain) and the MBP Ac1-11[4Y] peptide. A significant treatment effect can also be obtained by administration of the MBP peptide alone, but this effect is strictly dose dependent. This MBP peptide does not treat the disease induced only with MOG. These results suggest that peptide immunotherapy can provide an effective means of mitigating disease in this model, even when the treatment is targeted to only one component epitope or one component protein Ag of a diverse autoimmune response.
Probabilistic data association methods for tracking complex visual objects (2001)

We describe a framework that explicitly reasons about data association to improve tracking performance in many difficult visual environments. A hierarchy of tracking strategies results from ascribing ambiguous or missing data to: 1) noise-like visual occurrences, 2) persistent, known scene elements (i.e., other tracked objects), or 3) persistent, unknown scene elements. First, we introduce a randomized tracking algorithm adapted from an existing probabilistic data association filter (PDAF) that is resistant to clutter and follows agile motion. The algorithm is applied to three different tracking modalities-homogeneous regions, textured regions, and snakes-and extensibly defined for straightforward inclusion of other methods. Second, we add the capacity to track multiple objects by adapting to vision a joint PDAF which oversees correspondence choices between same-modality trackers and image features. We then derive a related technique that allows mixed tracker modalities and handles object overlaps robustly. Finally, we represent complex objects as conjunctions of cues that are diverse both geometrically (e.g., parts) and qualitatively (e.g., attributes). Rigid and hinge constraints between part trackers and multiple descriptive attributes for individual parts render the whole object more distinctive, reducing susceptibility to mistracking. Results are given for diverse objects such as people, microscopic cells, and chess pieces.
The Catalytic Nanodiode: Detecting Continous Electron Flow at Oxide–Metal Interfaces Generated by a Gas‐Phase Exothermic Reaction (2006)

Continuous flow of ballistic charge carriers is generated by an exothermic chemical reaction and detected using the catalytic metal-semiconductor Schottky diode. We obtained a hot electron current for several hours using two types of catalytic nanodiodes, Pt/TiO2 or Pt/GaN, during carbon monoxide oxidation at pressures of 100 Torr of O2 and 40 Torr of CO at 413-573 K. This result reveals that the chemical energy of an exothermic catalytic reaction is directly converted into hot electrons flux in the catalytic nanodiode. By heating the nanodiodes in He, we could measure the thermoelectric current which is in the opposite direction to the flow of the hot electron current. The chemicurrent is well correlated with the turnover rate of CO oxidation, which is separately measured with gas chromatography. The influence of the flow of hot charge carriers on the chemistry at the oxide-metal interface, and the turnover rate in the chemical reaction are discussed.
Antibodies Against Infliximab Are Associated with De Novo Development of Antibodies to Adalimumab and Therapeutic Failure in Infliximab-to-Adalimumab Switchers with IBD (2014)

Switchers with anti-IFX Abs are prone to develop de novo anti-ADL Abs, which may result in therapeutic failure. Assessment of ADL immunogenicity in anti-IFX Ab-positive switchers is required to ensure optimal interventions at inadequate treatment responses and to avoid inappropriate ADL intensification regimens.
Ultramicroelectrodes: Design, Fabrication, and Characterization (2002)

Ultramicroelectrodes (UMEs) have led to unprecedented advances in electrochemical studies since their introduction to electroanalytical chemistry about twenty five years ago. During this time, several UME geometries have been reported of which disk, ring, ring-disk, hemispherical, spherical, and etched (finite cone) UMEs are the most commonly used. In this review, the design and fabrication procedures for each are described. Issues related to UME electrode surface treatment and characterization are also addressed.
Tumor-induced angiogenesis studied in confrontation cultures of multicellular tumor spheroids and embryoid bodies grown from pluripotent embryonic stem cells (2001)

Tumor vascularization is the rate-limiting step for the progression of cancer. Differential steps of tumor-induced angiogenesis were studied by a novel in vitro confrontation culture of avascular multicellular prostate tumor spheroids and embryoid bodies grown from pluripotent embryonic stem (ES) cells. Vascularization in embryoid bodies started on day 5 of cell culture and was paralleled by down-regulation of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and vascular endothelial growth factor (VEGF). In parallel, a dissipation of gradients in the pericellular oxygen pressure was observed as measured by O(2)-sensitive microelectrodes. After 24--48 h of confrontation culture, cells positive for platelet endothelial cell adhesion molecule (PECAM-1) became visible in the contact region between the embryoid body and the tumor spheroid and sprouted within the confrontation cultures during subsequent days. Tumor-induced angiogenesis resulted in growth stimulation of tumor spheroids, disappearance of central necrosis and a reduction of the pericellular oxygen pressure. Furthermore, tumor vascularization resulted in elevated levels of HIF-1 alpha, VEGF, heat shock protein 27 (HSP27), and P-glycoprotein. Tumor-induced angiogenesis may augment the oxygen consumption in tumors resulting in an increased expression of hypoxia-related, proangiogenic genes as well as of HSP27 and P-glycoprotein, which are involved in a multidrug resistance phenotype.
Transforming function of the HOX11/TCL3 homeobox gene. (1997)

The HOX11/TCL3 homeobox gene was identified at the breakpoint region in pediatric T-cell acute lymphoblastic leukemia harboring 10q24 chromosomal translocations. We previously reported that primary murine bone marrow cells transduced ex vivo with a recombinant HOX11-containing retrovirus, MSCV-HOX11, gave rise to cell lines at high frequency having characteristics of early myeloid cells. Cell lines were also established from the bone marrow and spleen of transplant recipients sacrificed 5 months after engraftment with MSCV-HOX11-transduced bone marrow cells. These latter lines, which exhibited a more differentiated myelomonocytic phenotype, harbored proviruses encoding a smaller HOX11 protein. None of the mice that received HOX11-expressing bone marrow cells or myeloid cell lines developed leukemia during 6-month observation periods. Here, we report that two bone marrow transplant recipients eventually developed T-cell acute lymphoblastic leukemia-like malignancies at 7 and 12 months posttransplant, indicating that progression to a fully malignant state required additional mutations. One tumor synthesized full-length HOX11 whereas the other expressed the smaller version of the protein. The smaller HOX11 protein suffered a carboxyl-terminal truncation. We subsequently constructed MSCV-based retroviral vectors expressing deleted forms of HOX11 and identified an amino-terminal region that was dispensible for generation of myeloid cell lines having a similar phenotype as those induced by full-length HOX11. We thus conclude that regions near the amino and carboxyl termini of HOX11 are not essential for transforming function, nor do they appear to determine the lineage or stage of differentiation of the target cell for transformation.
Logical routing specification in office information systems (1984)

A message management system is an office information system for managing structured messages, integrating the facilities of computer-based message systems and database management systems, and adding to them the capability of "intelligent" handling of messages. This allows the office information system to support messages that can use information about themselves (such as structure and content) or about the system to effect their own processing. Logical routing of messages in an office information system is a function that can benefit from such intelligent processing.
Effect of Electrolyte Composition on Lithium Dendrite Growth (2008)

Lithium deposition is observed in situ using a microfluidic test cell. The microfluidic device rapidly sets up a steady concentration gradient and minimizes ohmic potential loss, minimizes electrolyte usage, and shows good repeatability. Dendrite growth is observed at different current densities for electrolytes containing lithium hexafluorophosphate or lithium bis(trifluoromethane sulfonyl) imide (LiTFSI) in mixtures of propylene carbonate (PC) and dimethyl carbonate. Dendrites are formed at shorter times in electrolytes containing LiTFSI and high amounts of PC. The time to first observed dendrites increases linearly (for all electrolyte compositions) with a resistance given by the Tafel slope of the lithium reduction polarization curve.
Postbinding events mediated by human immunodeficiency virus type 1 are sensitive to modifications in the D4-transmembrane linker region of CD4 (1996)

Evidence from both structural and functional studies of the CD4 molecule suggests that several domains, including the transmembrane (TM) domain and the adjoining extracellular region (D4-TM linker), contribute to the post-gp12O-binding events leading to human immunodeficiency virus-mediated membrane fusion. To investigate such a role in syncytium formation and cell-free infectivity, we generated several deletion and substitution mutations in the TM and D4-TM linker regions of the CD4 molecule. We found that while the TM domain of CD4 was dispensable for cell-cell and virus-cell interactions, modifications in the D4-TM linker led to perturbations in both processes. Deletion of the five amino acid residues linking D4 to the TM domain resulted in a delayed and reduced capacity to form syncytia, whereas replacement of the residues with the heterologous sequence from the CD8 molecule restored the kinetic profile to wild-type CD4 levels. On the other hand, both mutants of the CD4 D4-TM linker demonstrated delayed cell-free human immunodeficiency virus type 1 infectivity profiles. The defective fusion capacity may be linked to structural perturbations identified with anti-CD4 monoclonal antibodies in the D1-D2 interface and D3 domain of the deletion mutant yet absent in D1 and D4. While all cells were found to bind comparable levels of gp120, both D4-TM linker mutants appeared to induce a decrease in the V3 loop exposure of bound gp120. This underexposure may explain the delays in cell-free infectivities observed for both of these mutants. Together, these findings confirm a role for regions of the CD4 molecule located outside D1 in post-gp120-binding events and suggest that the D4-TM interface contributes to the conformational changes that direct the fusion process.
Discovery of RG7112: A Small-Molecule MDM2 Inhibitor in Clinical Development (2013)

The p53 tumor suppressor is a potent transcription factor that plays a key role in the regulation of cellular responses to stress. It is controlled by its negative regulator MDM2, which binds directly to p53 and inhibits its transcriptional activity. MDM2 also targets p53 for degradation by the proteasome. Many tumors produce high levels of MDM2, thereby impairing p53 function. Restoration of p53 activity by inhibiting the p53-MDM2 interaction may represent a novel approach to cancer treatment. RG7112 (2g) is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2. In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts.
SYSTEMATIC THERAPEUTIC EXERCISES IN THE MANAGEMENT OF THE PARALYSES IN HEMIPLEGIA (1918)

Dogs that had received by vein the minimum uni¬ formly lethal doses of mercuric chlorid died in spite of intravenous injections of sodium acetate-sodium phosphite solutions, even when the latter were given immediately after the poison had been given, and when the weights of sodium phosphite were from twenty to thirty-five times as great as the weights of the mercuric chlorid administered.The sodium phos¬ phite-sodium acetate therapy has proved of no value in counteracting or preventing the deleterious effects of intravenously administered mercuric chlorid.Dogs and rabbits that had received by vein the minimum uniformly lethal dose of mercuric chlorid died in spite of the use of the best known forms of alimentary medication.CONCLUSIONS
Current Progress of Genetically Engineered Pig Models for Biomedical Research (2014)

The first transgenic pigs were generated for agricultural purposes about three decades ago. Since then, the micromanipulation techniques of pig oocytes and embryos expanded from pronuclear injection of foreign DNA to somatic cell nuclear transfer, intracytoplasmic sperm injection-mediated gene transfer, lentiviral transduction, and cytoplasmic injection. Mechanistically, the passive transgenesis approach based on random integration of foreign DNA was developed to active genetic engineering techniques based on the transient activity of ectopic enzymes, such as transposases, recombinases, and programmable nucleases. Whole-genome sequencing and annotation of advanced genome maps of the pig complemented these developments. The full implementation of these tools promises to immensely increase the efficiency and, in parallel, to reduce the costs for the generation of genetically engineered pigs. Today, the major application of genetically engineered pigs is found in the field of biomedical disease modeling. It is anticipated that genetically engineered pigs will increasingly be used in biomedical research, since this model shows several similarities to humans with regard to physiology, metabolism, genome organization, pathology, and aging.
Mobilization of Genomic Islands of Staphylococcus aureus by Temperate Bacteriophage (2016)

The virulence of Staphylococcus aureus, in both human and animal hosts, is largely influenced by the acquisition of mobile genetic elements (MGEs). Most S. aureus strains carry a variety of MGEs, including three genomic islands (νSaα, νSaβ, νSaγ) that are diverse in virulence gene content but conserved within strain lineages. Although the mobilization of pathogenicity islands, phages and plasmids has been well studied, the mobilization of genomic islands is poorly understood. We previously demonstrated the mobilization of νSaβ by the adjacent temperate bacteriophage ϕSaBov from strain RF122. In this study, we demonstrate that ϕSaBov mediates the mobilization of νSaα and νSaγ, which are located remotely from ϕSaBov, mostly to recipient strains belonging to ST151. Phage DNA sequence analysis revealed that chromosomal DNA excision events from RF122 were highly specific to MGEs, suggesting sequence-specific DNA excision and packaging events rather than generalized transduction by a temperate phage. Disruption of the int gene in ϕSaBov did not affect phage DNA excision, packaging, and integration events. However, disruption of the terL gene completely abolished phage DNA packing events, suggesting that the primary function of temperate phage in the transfer of genomic islands is to allow for phage DNA packaging by TerL and that transducing phage particles are the actual vehicle for transfer. These results extend our understanding of the important role of bacteriophage in the horizontal transfer and evolution of genomic islands in S. aureus.
Human immunoglobulin transgenes undergo rearrangement, somatic mutation and class switching in mice that lack endogenous IgM (1994)

We have generated transgenic mice that contain human-sequence Ig miniloci and, because they are also homozygous for a targeted disruption of their endogenous heavy chain genes, must rely on the transgene sequences for B cell receptor expression. Although the human transgenes contain only a fraction of the intact human heavy chain locus, these defined sequences are able to at least partially restore the humoral immune system in the mouse. B cells expressing human heavy chains develop in the bone marrow, populate peripheral lymphoid tissue and respond specifically to antigen. Furthermore, the heavy chain transgenes contain both human mu and gamma 1 coding exons as well as the respective mu and gamma 1 switch regions. The sequences included within the transgene are sufficient to direct class switch recombination. Transgene sequences are also sufficient to direct somatic mutation of the class-switched heavy chain genes. These observations define the upper limit of the cis-acting sequences necessary to direct heavy chain class switching and somatic mutation.
New molecular forms of human liver alcohol dehydrogenase: isolation and characterization of ADHIndianapolis. (1980)

The biochemical determinants of alcoholism and genetic correlates for the variability in man's response to alcohol have remained obscure until recently. The identification of genetically determined isoenzymes of alcohol dehydrogenase with different catalytic properties may bear importantly upon this problem. New molecular forms of human liver alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) have recently been identified in 16% of the liver specimens from an urban population from Indianapolis, Indiana [Bosron, W. F., Li, T.-K. & Vallee, B. L. (1979) Biochem. Biophys. Res. Commun. 91, 1549-1555]. The distinguishing features of these specimens were (i) they showed activity optima for ethanol oxidation at both pH 7.0 and 10.0 and (ii) they formed electrophoretic bands cathodic to the beta beta isoenzyme. From such livers, three new ADH forms have now been isolated, one of which has a single pH optimum at 7.0 and two of which have dual optima at pH 7.0 and 10.0. These new forms were designated ADHIndianapolis forms 1,2, and 3, respectively. They can be differentiated from previously described ADH isoenzymes, including the so-called "atypical" isoenzyme, by their electrophoretic mobility, pH optima, and Km for ethanol (approximately 60 mM at pH 7.5). Based upon the electrophoretic pattern of livers containing ADHIndianapolis and the mobility of the three isolated molecular forms, ADHIndianapolis may be the result of polymorphism at the ADH2 gene locus, which codes for the beta subunit.
Interferon Lambda: Modulating Immunity in Infectious Diseases (2017)

Interferon lambdas (IFN-λs; IFNL1-4) modulate immunity in the context of infections and autoimmune diseases, through a network of induced genes. IFN-λs act by binding to the heterodimeric IFN-λ receptor (IFNLR), activating a STAT phosphorylation-dependent signaling cascade. Thereby hundreds of IFN-stimulated genes are induced, which modulate various immune functions <i>via</i> complex forward and feedback loops. When compared to the well-characterized IFN-α signaling cascade, three important differences have been discovered. First, the IFNLR is not ubiquitously expressed: in particular, immune cells show significant variation in the expression levels of and susceptibilities to IFN-λs. Second, the binding affinities of individual IFN-λs to the IFNLR varies greatly and are generally lower compared to the binding affinities of IFN-α to its receptor. Finally, genetic variation in the form of a series of single-nucleotide polymorphisms (SNPs) linked to genes involved in the IFN-λ signaling cascade has been described and associated with the clinical course and treatment outcomes of hepatitis B and C virus infection. The clinical impact of IFN-λ signaling and the SNP variations may, however, reach far beyond viral hepatitis. Recent publications show important roles for IFN-λs in a broad range of viral infections such as human T-cell leukemia type-1 virus, rotaviruses, and influenza virus. IFN-λ also potentially modulates the course of bacterial colonization and infections as shown for <i>Staphylococcus aureus</i> and <i>Mycobacterium tuberculosis</i>. Although the immunological processes involved in controlling viral and bacterial infections are distinct, IFN-λs may interfere at various levels: as an innate immune cytokine with direct antiviral effects; or as a modulator of IFN-α-induced signaling <i>via</i> the suppressor of cytokine signaling 1 and the ubiquitin-specific peptidase 18 inhibitory feedback loops. In addition, the modulation of adaptive immune functions <i>via</i> macrophage and dendritic cell polarization, and subsequent priming, activation, and proliferation of pathogen-specific T- and B-cells may also be important elements associated with infectious disease outcomes. This review summarizes the emerging details of the IFN-λ immunobiology in the context of the host immune response and viral and bacterial infections.
Brain-specific src oncogene mRNA mapped in rat brain by in situ hybridization. (1988)

Brain src protooncogene is expressed in two forms, one identical to message in other tissues, and one containing an 18-nucleotide insert specific to brain. We have mapped mRNA for the two forms of src in rat brain with selective antisense oligonucleotide probes to the brain (src+) and peripheral (src-) forms. Fetal rat src mRNA levels were much higher in the central nervous system than any peripheral organ. In adult brain, src+ mRNA level was highest in the internal granular layer of the olfactory bulb, pyramidal cells of the hippocampus, granule cells of the dentate gyrus, and cerebellar granule cells. src+ and src- levels were similar in hindbrain, but src+ levels were higher than those of src- in forebrain. These distributions suggest that src+ may play roles in a number of neural processes, possibly including neuronal plasticity.