gebhart/patrepeval huggingface dataset:
THE GLN1 LOCUS OF SACCHAROMYCES CEREVISIAE ENCODES GLUTAMINE SYNTHETASE (1985)

Among 41 yeast glutamine auxotrophs, complementation analysis defined a single gene, GLN1, on chromosome 16 between MAK3 and MAK6. Half of the alleles fell into two intragenic complementation classes. No clustering of complementing alleles was found in a fine structure map. Altered glutamine synthetase subunits, including nonsense fragments and charge variants, were identified in several of the mutants, indicating that GLN1 is the structural gene for this enzyme. Negative complementation was observed for almost every allele associated with a protein product and all gln1/+ heterozygotes displayed reduced susceptibility to ammonia repression of the remaining glutamine synthetase activity. This latter observation is explained by the hypothesis that ammonia represses the enzyme only through its metabolism to glutamine. A basis for the two gln1 complementation classes is proposed.
Dynamic Routing Between Capsules (2017)

A capsule is a group of neurons whose activity vector represents the instantiation parameters of a specific type of entity such as an object or an object part. We use the length of the activity vector to represent the probability that the entity exists and its orientation to represent the instantiation parameters. Active capsules at one level make predictions, via transformation matrices, for the instantiation parameters of higher-level capsules. When multiple predictions agree, a higher level capsule becomes active. We show that a discrimininatively trained, multi-layer capsule system achieves state-of-the-art performance on MNIST and is considerably better than a convolutional net at recognizing highly overlapping digits. To achieve these results we use an iterative routing-by-agreement mechanism: A lower-level capsule prefers to send its output to higher level capsules whose activity vectors have a big scalar product with the prediction coming from the lower-level capsule.
A single-base-pair deletion in the beta-glucuronidase gene accounts for the phenotype of murine mucopolysaccharidosis type VII. (1993)

Murine mucopolysaccharidosis type VII is a heritable disease caused by a spontaneous mutation, gus(mps), closely linked to the beta-glucuronidase structural gene on chromosome 5. Mice homozygous for the mutation have a > 200-fold decrease in beta-glucuronidase mRNA levels and virtually no enzyme activity detectable by a sensitive fluorometric assay. Approximately 20 kb of genomic DNA containing the beta-glucuronidase gene Gus and > 2 kb of 5' and 3' flanking sequences were cloned from both a gus(mps)/gus(mps) mouse and a +/+ mouse of the progenitor strain. Restriction enzyme digests containing DNA fragments 20-400 bp in length were generated from each of the two Gus alleles and then compared by using nondenaturing polyacrylamide DNA-sequencing gels. This method rapidly identified a large number of restriction sites and was sensitive enough to detect a restriction fragment length variation resulting from a 1-bp deletion in the gus(mps) allele. DNA-sequence analysis of the mutant genomic fragment showed that the 1-bp deletion created a frameshift mutation within exon 10. Insertion of the deleted nucleotide by oligonucleotide site-directed mutagenesis restored function to the corrected mutant gene when transfected into gus(mps)/gus(mps) fibroblasts. We concluded that the frameshift mutation, which introduces a premature stop codon at codon 497 in exon 10, accounts for the molecular, biochemical, and pathological abnormalities associated with the gus(mps) phenotype.
Amyloid endostatin induces endothelial cell detachment by stimulation of the plasminogen activation system. (2003)

Endostatin is a fragment of collagen XVIII that acts as an inhibitor of tumor angiogenesis and tumor growth. Anti-tumor effects have been described using both soluble and insoluble recombinant endostatin. However, differences in endostatin structure are likely to cause differences in bioactivity. In the present study, we have investigated the cellular effects of insoluble endostatin. We previously found that insoluble endostatin shows all the hallmarks of amyloid aggregates and potently stimulates tissue plasminogen activator-mediated formation of the serine protease plasmin. We here show that amyloid endostatin induces plasminogen activation by endothelial cells, resulting in vitronectin degradation and plasmin-dependent endothelial cell detachment. Endostatin-mediated stimulation of plasminogen activation, vitronectin degradation, and endothelial cell detachment is inhibited by carboxypeptidase B, indicating an essential role for carboxyl-terminal lysines. Our results suggest that amyloid endostatin may inhibit angiogenesis and tumor growth by stimulating the fibrinolytic system.
Factors involved in specific transcription in mammalian RNA polymerase II. Functional analysis of initiation factors IIA and IID and identification of a new factor operating at sequences downstream of the initiation site. (1987)

Transcription from the major late promoter of adenovirus type 2 DNA (including DNA sequences from 56 nucleotides upstream to 33 nucleotides downstream of the CAP site) was reconstituted with transcription factors purified from HeLa cells. Five components, transcription factors (TF) IIA, -B, -E, -D and RNA polymerase II, were required for accurate initiation of transcription. Kinetic analyses combined with order of addition experiments suggested that TFIIA acted first during the initiation reaction and that this interaction was followed by the action of TFIID. In agreement with these conclusions, both TFIIA and TFIID were required to render a transcription reaction partially resistant to concentrations of Sarkosyl previously shown to inhibit an early step in the formation of a preinitiation complex. Related Sarkosyl studies indicated that the inferred complex was subsequently recognized by RNA polymerase II, which resulted in an increased level of Sarkosyl-resistant transcription (in the presence of TFIIA and TFIID), and that this interaction occurred independently of TFIIB and TFIIE. However, TFIIB and TFIIE were implicated, along with the other factors and RNA polymerase II, in the subsequent formation of a highly stable preinitiation complex, which was inferred from its ability to initiate (with added nucleotides) in the presence of heparin concentrations which blocked unbound factors. The identification of a new transcription factor, which was required only when viral sequences 3' to the major late promoter were part of the transcription unit, is also reported.
A Novel Engineered Anti-CD20 Tracer Enables Early Time PET Imaging in a Humanized Transgenic Mouse Model of B-cell Non-Hodgkins Lymphoma (2013)

The (64)Cu-Do-FN3(CD20) radiotracer represents a novel small, high-affinity binder for imaging human CD20, which may be well suited for B-cell non-Hodgkin's lymphoma imaging in patients at early time points.
Pharmacological characterisation of the highly NaV1.7 selective spider venom peptide Pn3a (2017)

Human genetic studies have implicated the voltage-gated sodium channel Na<sub>V</sub>1.7 as a therapeutic target for the treatment of pain. A novel peptide, μ-theraphotoxin-Pn3a, isolated from venom of the tarantula Pamphobeteus nigricolor, potently inhibits Na<sub>V</sub>1.7 (IC<sub>50</sub> 0.9 nM) with at least 40-1000-fold selectivity over all other Na<sub>V</sub> subtypes. Despite on-target activity in small-diameter dorsal root ganglia, spinal slices, and in a mouse model of pain induced by Na<sub>V</sub>1.7 activation, Pn3a alone displayed no analgesic activity in formalin-, carrageenan- or FCA-induced pain in rodents when administered systemically. A broad lack of analgesic activity was also found for the selective Na<sub>V</sub>1.7 inhibitors PF-04856264 and phlotoxin 1. However, when administered with subtherapeutic doses of opioids or the enkephalinase inhibitor thiorphan, these subtype-selective Na<sub>V</sub>1.7 inhibitors produced profound analgesia. Our results suggest that in these inflammatory models, acute administration of peripherally restricted Na<sub>V</sub>1.7 inhibitors can only produce analgesia when administered in combination with an opioid.
Autoantibody to the alternative pathway C3/C5 convertase and its anti-idiotypic response. A study in affinity (1992)

In an effort to understand the development and control of autoantibody production, we studied the affinity of autoantibody to the alternative pathway C3/C5 convertase (C3 nephritic factor (C3NeF)) and its autoanti-idiotypic antibodies, Ab2 alpha and Ab2 beta. These were isolated and purified from newborns, normal adults, and patients with membranoproliferative glomerulonephritis. In all cases, both IgG and IgM C3NeF were available for study. The affinity of IgG and IgM C3NeF for their natural Ag (10(8) liters/mol) as well as for the internal image of that Ag displayed on Ab2 beta was high (10(10) liters/mol). Furthermore, the affinity of IgG C3NeF was nearly 100-fold higher in patients than in newborns, whereas there were no significant changes with IgM C3NeF. By contrast, there were not differences in the affinity of IgG Ab2 alpha (which does not display any likeness to the native Ag) from normal adults and patients to any C3NeF isolate. There was, however, a progressive increase in affinity between both Ab2 alpha preparations and IgG C3NeF from newborns, adult normal subjects, and patients, implying an alteration in C3NeF to account for the changes in affinity. These data suggest that Ag-driven affinity maturation occurs with autoantibody but may not occur within the idiotypic network. These data also indicate that as autoantibody affinity matures, it appears to modify its idiotype, perhaps in an effort towards autoregulation.
Inflammatory cytokines within the central nervous system: sources, function, and mechanism of action (1992)

In recent years, there has been increasing evidence that soluble mediators such as cytokines from activated T lymphocytes and macrophages are able to modulate the growth and function of cells found within the central nervous system (CNS), specifically macroglia and microglia cells. Furthermore, glial cells, upon activation, can secrete immunoregulatory factors that influence lymphoid/mononuclear cells as well as the glial cells themselves. Thus the potential exists for bidirectional communication between lymphoid cells and glial cells within the CNS, which in part is mediated via cytokines. This review describes various neurological disease states in which both immune and glial cells may contribute to inflammation and immunologic events occurring in the CNS. The mechanisms by which glial cells both respond to and synthesize a variety of cytokines within the CNS and the capacity of glial cells to acquire major histocompatibility complex antigens and function as antigen-presenting cells within the CNS are described in detail. The implications of these functions, cytokine secretion and antigen presentation, by glial cells are discussed with respect to neurological diseases associated with autoimmunity and/or inflammation.
Aptamer Applications for Targeted Cancer Therapy (2010)

Aptamers are single-stranded DNA or RNA oligonucleotides that assume specific 3D structures and bind to target molecules with high affinity. The unique specificity of aptamers has made them attractive agents for targeted cancer therapy. Aptamers have been developed against a variety of cancer targets, including extracellular ligands and cell surface proteins. In addition, aptamers have been incorporated into novel constructs involving siRNAs, chemotherapeutic agents, cell toxins and nanoparticles, in which they function as delivery agents for therapeutic cargo. In this article, we review recent developments in the use of aptamers for targeted cancer therapy, particularly focusing on novel applications of aptamers targeting the cell surface.
Nucleolar organizer regions as a prognostic indicator for stage I non-small cell lung cancer. (1991)

When the number of silver-stained nucleolar organizer regions (Ag-NORs) was counted in 274 patients with non-small cell lung cancer, the mean number per nucleus in patients overall was 5.07 +/- 1.92 (SD). With the use of the tumor (T)-nodes (N)-metastasis (M) classification, the mean Ag-NOR count for patients with T1 and T2 disease was statistically lower than that for those with T3 and T4 disease (P less than 0.01). The mean Ag-NOR counts were lower in patients with N0 disease than in those with N1 and N2 disease (P less than 0.01); lower in patients with stage I disease than in those with stage II, IIIA, IIIB, or IV disease (P less than 0.01); and lower in patients with adenocarcinoma than in those with squamous cell carcinoma (P less than 0.01) or large-cell carcinoma (P less than 0.05). In 131 patients with stage I disease, the mean Ag-NOR count was 3.80 +/- 1.32, and the 5-year survival rates of patients with Ag-NOR counts of less than 3.80 and greater than or equal to 3.80 were 78 and 44%, respectively, including 78% and 25% for adenocarcinoma, respectively (P less than 0.01). However, there was no statistically significant difference for those in stage II, IIIA, IIIB, or IV, and in stage I (without an adenocarcinoma). Because patients with stage I non-small cell lung cancer and a high number of Ag-NORs had a poor prognosis, Ag-NORs can serve as a pertinent marker of an early recurrence.
Scaling and root-planing treatment with adjunctive subgingival minocycline. A clinical pilot study over six months, of sites adjacent to and remote from the antibiotic application. (2002)

No apparent clinical spillover effect of minocycline was demonstrated over the six months of the study. There was a trend for greater improvement in all clinical parameters at the MPTS sites compared with the Adjacent and Remote sites except for plaque scores. This trend needs to be examined in a study with a sufficient number of subjects to allow statistical significance.
An Optimized Algorithm for Association Rule Mining Using FP Tree (2015)

Data mining is used to deal with the huge size of the data stored in the database to extract the desired information and knowledge. It has various techniques for the extraction of data; association rule mining is the most effective data mining technique among them. It discovers hidden or desired pattern from large amount of data. Among the existing techniques the frequent pattern growth (FP growth) algorithm is the most efficient algorithm in finding out the desired association rules. It scans the database only twice for the processing. The issue with the FP growth algorithm is that it generates a huge number of conditional FP trees. In the proposed work, we have designed a new technique which mines out all the frequent item sets without the generation of the conditional FP trees. Unlike FP tree it scans the database only once which reduces the time efficiency of the algorithm. It also finds out the frequency of the frequent item sets to find out the desired association rules.
Polarized Type 1 Cytokine Profile in Bronchoalveolar Lavage T Cells of Patients with Hypersensitivity Pneumonitis (1999)

Hypersensitivity pneumonitis (HP) is characterized by an inflammatory lymphocytic alveolitis comprised of both CD8+ and CD4+ T cells. Animal models suggest that HP is facilitated by overproduction of IFN-gamma, and that IL-10 ameliorates severity of the disease, indicating a Th1-type response. To determine whether a Th1 phenotype in HP also exists clinically, bronchoalveolar lavage (BAL) and peripheral blood (PB) T cells were obtained from HP individuals and analyzed for Th1 vs Th2 cytokine profiles. It was determined that soluble OKT3-stimulated BAL T cells cocultured with alveolar macrophages produced more IFN-gamma and less IL-10 than PB T cells cocultured with monocytes, but no difference was observed in IL-4 production. The monocytic cells did not account for this difference, as CD80 and CD86 expressions were similar, and coculturing PB T cells with alveolar macrophages resulted in no difference in IFN-gamma production. Similarly, there was no difference in IL-12 production between stimulated BAL or PB T cells; however, addition of rIL-12 significantly increased production of IFN-gamma by BAL T cells, but not by PB T cells. This effect was due to a difference in IL-12R expression. High affinity IL-12R were only present in association with BAL T cells. These studies indicate that clinical HP is characterized by a predominance of IFN-gamma-producing T cells, perhaps resulting from a reduction in IL-10 production and an increase in high affinity IL-12R compared with blood T cells.
Comparative study of peak power tracking techniques for solar storage system (2002)

As the power supplied by solar arrays depends upon the insolation, temperature and array voltage, it is necessary to control the operating points to draw the maximum power of the solar array. The object of this paper is to investigate the maximum power tracking algorithms which were often used to compare the tracking efficiencies for the system operating under different controls. A simple method which combines a discrete time control and a PI compensator is used to track the maximum power points (MPPs) of the solar array. The implementation of the proposed converter system was based on a digital signal processor (DSP). The experimental tests were carried out, the tracking efficiencies are confirmed by simulations and experimental results.
Coincident diabetes mellitus modulates Th1‐, Th2‐, and Th17‐cell responses in latent tuberculosis in an IL‐10‐ and TGF‐β‐dependent manner (2015)

Type 2 diabetes mellitus (DM) is a risk factor for the development of active tuberculosis (TB), although its role in the TB-induced responses in latent TB (LTB) is not well understood. Since Th1, Th2, and Th17 responses are important in immunity to LTB, we postulated that coincident DM could alter the function of these CD4(+) T-cell subsets. To this end, we examined mycobacteria-induced immune responses in the whole blood of individuals with LTB-DM and compared them with responses of individuals without DM (LTB-NDM). T-cell responses from LTB-DM are characterized by diminished frequencies of mono- and dual-functional CD4(+) Th1, Th2, and Th17 cells at baseline and following stimulation with mycobacterial antigens-purified protein derivative, early secreted antigen-6, and culture filtrate protein-10. This modulation was at least partially dependent on IL-10 and TGF-β, since neutralization of either cytokine resulted in significantly increased frequencies of Th1 and Th2 cells but not Th17 cells in LTB-DM but not LTB individuals. LTB-DM is therefore characterized by diminished frequencies of Th1, Th2, and Th17 cells, indicating that DM alters the immune response in latent TB leading to a suboptimal induction of protective CD4(+) T-cell responses, thereby providing a potential mechanism for increased susceptibility to active disease.
Clinical Study of Blow Out Fracture (2011)

Orbital blowout fracture causes include violence, sports, traffic accidents, and falls, with an object striking the eyeball with some force. Subjects numbered 30 studied clinically from 1986 to 2005. The prevalent symptom was double vision requiring surgical repair in 21 subjects. Recovery was related to surgical timings, underscoring the importance of early diagnosis and intervention.
Frameshift peptide-derived T-cell epitopes: A source of novel tumor-specific antigens (2001)

Microsatellite instability (MSI) caused by defective DNA mismatch repair (MMR) is a hallmark of hereditary nonpolyposis colorectal cancers (HNPCC) but also occurs in about 15% of sporadic tumors. If instability affects microsatellites in coding regions, translational frameshifts lead to truncated proteins often marked by unique frameshift peptide sequences at their C-terminus. Since MSI tumors show enhanced lymphocytic infiltration and our previous analysis identified numerous coding mono- and dinucleotide repeat-bearing candidate genes as targets of genetic instability, we examined the role of frameshift peptides in triggering cellular immune responses. Using peptide pulsed autologous CD40-activated B cells, we have generated cytotoxic T lymphocytes (CTL) that specifically recognize HLA-A2.1-restricted peptides derived from frameshift sequences. Among 16 frameshift peptides predicted from mutations in 8 different genes, 3 peptides conferred specific lysis of target cells exogenously loaded with cognate peptide. One peptide derived from a (-1) frameshift mutation in the TGFbetaIIR gene gave rise to a CTL bulk culture capable of lysing the MSI colorectal cancer cell line HCT116 carrying this frameshift mutation. Given the huge number of human coding microsatellites and assuming only a fraction being mutated and encoding immunologically relevant peptides in MSI tumors, frameshift protein sequences represent a novel subclass of tumor-specific antigens. It is tempting to speculate that a frameshift peptide-directed vaccination approach not only could offer new treatment modalities for existing MSI tumors but also might benefit asymptomatic at-risk individuals in HNPCC families by a prophylactic vaccination strategy.
Nano-Flares:  Probes for Transfection and mRNA Detection in Living Cells (2007)

We demonstrate that novel oligonucleotide-modified gold nanoparticle probes hybridized to fluorophore-labeled complements can be used as both transfection agents and cellular “nano-flares” for detecting mRNA in living cells. Nano-flares take advantage of the highly efficient fluorescence quenching properties of gold, cellular uptake of oligonucleotide nanoparticle conjugates without the use of transfection agents, and the enzymatic stability of such conjugates, thus overcoming many of the challenges to creating sensitive and effective intracellular probes. Nano-flares exhibit high signaling, have low background fluorescence, and are sensitive to changes in the number of RNA transcripts present in cells.
Cooperation of β-galactosidase and β-N-acetylhexosaminidase from bifidobacteria in assimilation of human milk oligosaccharides with type 2 structure (2010)

Bifidobacteria are predominant in the intestines of breast-fed infants and offer health benefits to the host. Human milk oligosaccharides (HMOs) are considered to be one of the most important growth factors for intestinal bifidobacteria. HMOs contain two major structures of core tetrasaccharide: lacto-N-tetraose (Galβ1-3GlcNAcβ1-3Galβ1-4Glc; type 1 chain) and lacto-N-neotetraose (Galβ1-4GlcNAcβ1-3Galβ1-4Glc; type 2 chain). We previously identified the unique metabolic pathway for lacto-N-tetraose in Bifidobacterium bifidum. Here, we clarified the degradation pathway for lacto-N-neotetraose in the same bifidobacteria. We cloned one β-galactosidase (BbgIII) and two β-N-acetylhexosaminidases (BbhI and BbhII), all of which are extracellular membrane-bound enzymes. The recombinant BbgIII hydrolyzed lacto-N-neotetraose into Gal and lacto-N-triose II, and furthermore the recombinant BbhI, but not BbhII, catalyzed the hydrolysis of lacto-N-triose II to GlcNAc and lactose. Since BbgIII and BbhI were highly specific for lacto-N-neotetraose and lacto-N-triose II, respectively, they may play essential roles in degrading the type 2 oligosaccharides in HMOs.