gebhart/patrepeval huggingface dataset:
Endothelin-B Receptor Blockade Inhibits Molecular Effectors of Melanoma Cell Progression (2004)

Expression of endothelin-B receptor gradually increases as melanocytic lesions progress to melanoma, suggesting that endothelin-B receptor and its ligands, endothelin-1 and endothelin- 3, play a role in the melanoma progression. The selective blockade of endothelin-B receptor results in inhibition of focal adhesion kinase and mitogen-activated protein kinase phosphorylation and cell proliferation induced by endothelins in human melanoma cell lines. In these cells, endothelins induce downregulation of E-cadherin expression and concomitant upregulation of transcriptional factor Snail. Activation of the endothelin-B receptor pathway by endothelins also upregulates N-cadherin, phosphorylates the gap junctional protein connexin 43, increases alphavbeta3 and alpha2beta1 integrin expression and tumor proteolytic activity, thus enhancing endothelin-B receptor-mediated cell adhesion, migration and invasiveness. In this study we demonstrated that activation of the endothelin-B receptor pathway by endothelin-1 and endothelin-3 contributes to disruption of normal host-tumor interactions by downregulating, at mRNA and protein levels, the expression of E-cadherin and associated alpha-catenin and beta-catenin adhesion proteins, which are critical for E-cadherin function. A-192621, an orally active non-peptide endothelin-B receptor antagonist, significantly inhibited melanoma growth in nude mice, suggesting that the pharmacological interruption of endothelin-B receptor signaling by endothelin-B receptor antagonist may represent a new therapeutic approach in the treatment of cutaneous melanoma.
S46 Peptidases are the First Exopeptidases to be Members of Clan PA (2014)

The dipeptidyl aminopeptidase BII (DAP BII) belongs to a serine peptidase family, S46. The amino acid sequence of the catalytic unit of DAP BII exhibits significant similarity to those of clan PA endopeptidases, such as chymotrypsin. However, the molecular mechanism of the exopeptidase activity of family S46 peptidase is unknown. Here, we report crystal structures of DAP BII. DAP BII contains a peptidase domain including a typical double β-barrel fold and previously unreported α-helical domain. The structures of peptide complexes revealed that the α-helical domain covers the active-site cleft and the side chain of Asn330 in the domain forms hydrogen bonds with the N-terminus of the bound peptide. These observations indicate that the α-helical domain regulates the exopeptidase activity of DAP BII. Because S46 peptidases are not found in mammals, we expect that our study will be useful for the design of specific inhibitors of S46 peptidases from pathogens.
In vivo handling of soluble complement fixing Ab/dsDNA immune complexes in chimpanzees. (1989)

We used soluble, C-fixing antibody/dsDNA IC to investigate immune complex (IC) handling and erythrocyte (E)-to-phagocyte transfer in chimpanzees. IC bound efficiently to chimpanzee E in vitro and showed minimal release with further in vitro incubation in the presence of serum in EDTA (less than or equal to 15% within 1 h). These IC also bound rapidly to E in vivo (70-80% binding within 1 min) and did not show detectable release from E in the peripheral circulation after infusion in vivo (less than or equal to 2% within 1 h). Despite such slow C-mediated release of IC from E, IC were rapidly stripped from E by the mononuclear phagocyte system (T50 for E-IC1500 = 5 min) without sequestration of E. Treatment of the chimpanzees with the anti-Fc gamma RIII MAb 3G8 impaired the clearance of infused IC. This effect was most evident on the fraction of IC500 which did not bind to E and which presumably had captured less C3b (pre-MAb 3G8 T50: 45 min vs. post-MAb 3G8 T50: 180 min). With IC bound in vitro to E before infusion, anti-Fc gamma RIII MAb treatment led to significant amounts of non-E bound IC detectable in the circulation. Thus, the anti-Fc gamma RIII MAb appeared to interfere with the ability of fixed tissue mononuclear phagocytes to take up/or retain IC after their release from E. Both rapid stripping of IC from E, despite slow complement-mediated release of IC from E in the peripheral circulation, and blockade of IC clearance with anti-Fc gamma RIII MAb indicate that the interaction of IC with the fixed tissue phagocyte involves qualitatively different mechanisms than the interaction of IC with E. Fc gamma receptors appear to play an important role in the transfer and retention of IC by the phagocyte.
A Longitudinal Study on Vocabulary Development Variables According to Expressive Vocabulary Progress in Children from Multicultural Families (2014)

The purpose of the present study was to investigate the important variables of expressive vocabulary development in children from multicultural families. Methods: The participants of the study were 14 children from multicultural families aged between 5 and 9 years. Based on the reassessment result, the groups were divided into two: one group caught up with their normal peers while the other group continued to show signs of expressive vocabulary delay. The receptive and expressive vocabulary test scores, including nouns and verbs, and a questionnaire regarding the child's living environment were analyzed. Results: The results were as follows: with regard to receptive vocabulary ability, significant differences were observed between the initial assessment and reassessment in each group. However, there were no significant differences between-groups in receptive vocabulary ability. For expressive noun accuracy, significant differences were observed between the groups in the reassessment; the catch-up group showed higher parent's level of education and income level than the non-catch-up group; there were also significant correlations between the groups in income level, and that between parent's level of education. Conclusion: The results suggest that children showed limited use of expressive vocabulary even with their good skills in receptive vocabulary. Overall the children with delayed expressive vocabulary development are likely to have trouble using expressive nouns. Even with a similar home background (multicultural families), socioeconomic status is still an important variable in vocabulary development. Additionally, language support appears to reflect the parent's income level and their level of education.
EEG-Based Emotion Recognition in Music Listening (2010)

Ongoing brain activity can be recorded as electroencephalograph (EEG) to discover the links between emotional states and brain activity. This study applied machine-learning algorithms to categorize EEG dynamics according to subject self-reported emotional states during music listening. A framework was proposed to optimize EEG-based emotion recognition by systematically 1) seeking emotion-specific EEG features and 2) exploring the efficacy of the classifiers. Support vector machine was employed to classify four emotional states (joy, anger, sadness, and pleasure) and obtained an averaged classification accuracy of 82.29% +/- 3.06% across 26 subjects. Further, this study identified 30 subject-independent features that were most relevant to emotional processing across subjects and explored the feasibility of using fewer electrodes to characterize the EEG dynamics during music listening. The identified features were primarily derived from electrodes placed near the frontal and the parietal lobes, consistent with many of the findings in the literature. This study might lead to a practical system for noninvasive assessment of the emotional states in practical or clinical applications.
Poly(ethylene glycol) Hydrogel Microstructures Encapsulating Living Cells (2002)

We present an easy and effective method for the encapsulation of cells inside PEG-based hydrogel microstructures fabricated using photolithography. High-density arrays of three-dimensional microstructures were created on substrates using this method. Mammalian cells were encapsulated in cylindrical hydrogel microstructures of 600 and 50 micrometers in diameter or in cubic hydrogel structures in microfluidic channels. Reducing lateral dimension of the individual hydrogel microstructure to 50 micrometers allowed us to isolate 1-3 cells per microstructure. Viability assays demonstrated that cells remained viable inside these hydrogels after encapsulation for up to 7 days.
Neonatal plasminogen displays altered cell surface binding and activation kinetics. Correlation with increased glycosylation of the protein. (1990)

Plasminogen isolated from 60 full-term newborns differs from adult plasminogen in carbohydrate composition, kinetic activation constants, and cell binding. Amino acid composition and amino-terminal sequence analysis data indicate that the plasminogens of neonates and adults have the same amino acid sequence. Like the adult, the neonate has two glycoforms, but both have significantly more mannose and sialic acid than the adult forms. The difference in the neonatal glycosylation is probably responsible for the altered migration observed by isoelectric focusing. Moreover, the difference in carbohydrate composition appears to be the basis of the decreased functional activity of the neonatal plasminogen. The kcat/Km ratios indicate that the overall activation rates of the two neonatal plasminogen glycoforms are lower compared with the adult glycoforms. In addition, neonatal plasminogen does not bind as well to cellular receptors compared with adult plasminogen. These studies suggest a basis for the decreased fibrinolytic activity observed in neonates.
The role of CTCF in regulating nuclear organization (2008)

The spatial organization of the genome is thought to play an important part in the coordination of gene regulation. New techniques have been used to identify specific long-range interactions between distal DNA sequences, revealing an ever-increasing complexity to nuclear organization. CCCTC-binding factor (CTCF) is a versatile zinc finger protein with diverse regulatory functions. New data now help define how CTCF mediates both long-range intrachromosomal and interchromosomal interactions, and highlight CTCF as an important factor in determining the three-dimensional structure of the genome.
Adenine nucleotide synthesis in exercising and endurance-trained skeletal muscle (1991)

Strenuous exercise leads to increased efflux of purine nucleoside and base that should necessitate recovery of adenine nucleotides by either the de novo synthesis or salvage pathway. De novo synthesis of adenine nucleotide was measured in quiescent and contracting muscle of sedentary and exercise-trained rats using an isolated perfused hindquarter preparation. Synthesis rates were assessed by measuring the incorporation of [1-14C]glycine into adenine nucleotide in muscles of both resting and stimulated hindlimbs after 1 h of either low- or high-energy demand isometric contractions. In nonstimulated sedentary and trained muscles, rates of de novo synthesis were similar. The effect of muscle contractions on de novo synthesis varied among muscle fiber types. Contracting, nonfatigued fast-twitch muscle sections showed significant declines in de novo synthesis in both sedentary and trained groups. Rates in slow-twitch red fibers and fatigued fast-twitch white fiber sections were not different from rest. Supplementing the perfusate with 5 mM ribose caused de novo synthesis to rise three- to fourfold in each of the fiber sections. However, the response in synthesis rates due to exercise was similar with or without ribose supplementation. De novo synthesis does not increase during exercise but exhibits an unchanged or reduced rate depending on the expected energy balance within the cell. This would occur if the energy state of muscle exerts significant control over de novo synthesis of adenine nucleotide.
Stem Cell Transplantation (2009)

Hematopoietic cell transplantation (HCT) is associated with profound compromises in host defenses. The patterns of immune compromise change over time. Infections are an important cause of serious morbidity and pose substantial threats to life. Thus, the challenges of infection facing the transplant clinician are both myriad and dynamic. Early after transplant, neutropenic infections are most important. Later herpesvirus and invasive fungal infections predominate. Even late after transplant, patients with chronic graft versus host disease remain susceptible to encapsulated bacterial, varicella zoster virus, and invasive fungal infections. Over time, with robust engraftment and control of GVHD, the risk of serious infections recedes with immune reconstitution.
Recombinant Vesicular Stomatitis Virus Vaccine Vectors Expressing Filovirus Glycoproteins Lack Neurovirulence in Nonhuman Primates (2012)

The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses an individual filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). The main concern with all replication-competent vaccines, including the rVSV filovirus GP vectors, is their safety. To address this concern, we performed a neurovirulence study using 21 cynomolgus macaques where the vaccines were administered intrathalamically. Seven animals received a rVSV vector expressing the Zaire ebolavirus (ZEBOV) GP; seven animals received a rVSV vector expressing the Lake Victoria marburgvirus (MARV) GP; three animals received rVSV-wild type (wt) vector, and four animals received vehicle control. Two of three animals given rVSV-wt showed severe neurological symptoms whereas animals receiving vehicle control, rVSV-ZEBOV-GP, or rVSV-MARV-GP did not develop these symptoms. Histological analysis revealed major lesions in neural tissues of all three rVSV-wt animals; however, no significant lesions were observed in any animals from the filovirus vaccine or vehicle control groups. These data strongly suggest that rVSV filovirus GP vaccine vectors lack the neurovirulence properties associated with the rVSV-wt parent vector and support their further development as a vaccine platform for human use.
Conformational Substates in Proteins (1988)

Many bacterial clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated (Cas) systems employ the dual RNA–guided DNA endonuclease Cas9 to defend against invading phages and conjugative plasmids by introducing site-specific ...Read More
C4.5: Programs for Machine Learning (1992)

Classifier systems play a major role in machine learning and knowledge-based systems, and Ross Quinlan's work on ID3 and C4.5 is widely acknowledged to have made some of the most significant contributions to their development. This book is a complete guide to the C4.5 system as implemented in C for the UNIX environment. It contains a comprehensive guide to the system's use , the source code (about 8,800 lines), and implementation notes. The source code and sample datasets are also available for download (see below). C4.5 starts with large sets of cases belonging to known classes. The cases,
T cell cross-reactivity between coxsackievirus and glutamate decarboxylase is associated with a murine diabetes susceptibility allele. (1994)

Limited regions of amino acid sequence similarity frequently occur between microbial antigens and host proteins. It has been widely anticipated that during infection such sequence similarities could induce cross-reactive T cell responses, thereby initiating T cell-mediated autoimmune disease. However, the nature of major histocompatibility complex (MHC)-restricted antigen presentation confers a number of constraints that should make this type of T cell cross-reactivity a rare, MHC allele-dependent event. We tested this prediction using two insulin-dependent diabetes mellitus (IDDM)-associated antigens, coxsackievirus P2-C (Cox P2-C) protein and glutamate decarboxylase (GAD65), which share a prototypic sequence similarity of six consecutive amino acids within otherwise unrelated proteins. We surveyed a panel of 10 murine MHC class II alleles that encompass the spectrum of standard alleles for the ability to cross-reactively present Cox P2-C and GAD65. Out of the 10 restriction elements tested, the sequence similarity regions were both dominant determinants and were cross-reactively displayed after the natural processing of whole antigens, only in the context of I-Anod. These data show that cross-reactive T cell recognition of sequence similarity regions in unrelated proteins is confined to certain MHC alleles, which may explain MHC association with autoimmune disease. It is striking that these two diabetes-associated antigens were cross-reactively recognized only in the context of a diabetes susceptibility allele. Since the human and the murine class II alleles associated with IDDM share conserved features, cross-reactive T cell recognition of GAD65 and Cox P2-C may contribute to the pathogenesis of human IDDM and account for the epidemiological association of coxsackievirus with IDDM.
Effect of tranexamic acid (AMCA) in menorrhagia with intrauterine contraceptive devices. (1970)

The effect of tranexamic acid on the increase in menstrual blood loss after the insertion of an IUD was studied in 65 women in a double blind study. 253 cycles 65 prior to IUD insertion 97 with tranexamic acid treatment and 91 with placebo treatment were studied. In the placebo group menstrual blood loss increased 82.7% over the mean control menstruation. In the tranexamic acid cycles menstrual blood loss increased 11.5%. There was no difference in duration of bleeding between the groups.
Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine. (2001)

Immunization to multiple defined tumor antigens for specific immune therapy of human cancer has thus far proven difficult. Eighteen HLA A*0201(+) patients with metastatic melanoma received injections s.c. of CD34(+)progenitor-derived autologous dendritic cells (DCs), which included Langerhans cells. DCs were pulsed with peptides derived from four melanoma antigens [(MelAgs) MelanA/MART-1, tyrosinase, MAGE-3, and gp100], as well as influenza matrix peptide (Flu-MP) and keyhole limpet hemocyanin (KLH) as control antigens. Overall immunological effects were assessed by comparing response profiles using marginal likelihood scores. DC injections were well tolerated except for progressive vitiligo in two patients. DCs induced an immune response to control antigens (KLH, Flu-MP) in 16 of 18 patients. An enhanced immune response to one or more MelAgs was seen in these same 16 patients, including 10 patients who responded to >2 MelAgs. The two patients failing to respond to both control and tumor antigens experienced rapid tumor progression. Of 17 patients with evaluable disease, 6 of 7 patients with immunity to two or less MelAgs had progressive disease 10 weeks after study entry, in contrast to tumor progression in only 1 of 10 patients with immunity to >2 MelAgs. Regression of >1 tumor metastases were observed in seven of these patients. The overall immunity to MelAgs after DC vaccination is associated with clinical outcome (P = 0.015).
Antibodies to domains II and III of the IL-1 receptor accessory protein inhibit IL-1 beta activity but not binding: regulation of IL-1 responses is via type I receptor, not the accessory protein. (1998)

The IL-1R accessory protein (IL-1RAcP) plays a role in IL-1R signaling by forming a complex with IL-1RI bound to the IL-1 ligand. We identified four hydrophilic peptide regions of the extracellular IL-1RAcP that may be available for complex formation (peptide 1, 71-83 domain I; peptide 2, 204-211 domain II; peptide 3, 282-292 domain III; and peptide 4, 304-314 domain III). These peptides were synthesized, coupled to keyhole limpet hemocyanin, and used to produce rabbit antisera. Each affinity-purified antiserum showed specificity for the respective peptide without cross-reactivity. Anti-peptide 2, 3, and 4 recognized surface expression of IL-1RAcP on the Th2 D10S cells by FACS and inhibited IL-1-driven proliferation. Anti-peptide 4 recognized intact IL-1RAcP and soluble IL-1RAcP. Anti-IL-1RAcP-peptide 4, which targets the terminal segment of domain III, inhibited 80% of IL-1 beta-driven proliferation of D10S cells. However, these IL-1RAcP Abs had no effect on the activity of human or mouse IL-1 alpha. Whereas IL-1 beta down-regulated IL-1RI surface expression (p < 0.05), there was no change in the surface expression of IL-1RAcP. Moreover, murine IL-10 increased surface expression of IL-1RI, but did not affect expression of IL-1RAcP or the proliferation of D10S cells. Steady state levels of mRNA for IL-1RAcP and IL-1RI in D10S cells showed a similar pattern to that of surface expression of the respective receptors. We conclude that 1) blocking IL-1RAcP inhibits IL-1 signaling in D10S cells, 2) domains-II and III may be involved in complex formation with IL-1RI, 3) IL-1RAcP is not regulated as is IL-1RI in the same cells, and 4) IL-1 responsiveness is dependent on the expression of IL-1RI, not IL-1RAcP.
Highly Multiplexed Subcellular RNA Sequencing in Situ (2014)

Understanding the spatial organization of gene expression with single-nucleotide resolution requires localizing the sequences of expressed RNA transcripts within a cell in situ. Here, we describe fluorescent in situ RNA sequencing (FISSEQ), in which stably cross-linked complementary DNA (cDNA) amplicons are sequenced within a biological sample. Using 30-base reads from 8102 genes in situ, we examined RNA expression and localization in human primary fibroblasts with a simulated wound-healing assay. FISSEQ is compatible with tissue sections and whole-mount embryos and reduces the limitations of optical resolution and noisy signals on single-molecule detection. Our platform enables massively parallel detection of genetic elements, including gene transcripts and molecular barcodes, and can be used to investigate cellular phenotype, gene regulation, and environment in situ.
Immunological memory to hyperphosphorylated tau in asymptomatic individuals (2017)

Several reports have described the presence of antibodies against Alzheimer's disease-associated hyperphosphorylated forms of tau in serum of healthy individuals. To characterize the specificities that can be found, we interrogated peripheral IgG<sup>+</sup> memory B cells from asymptomatic blood donors for reactivity to a panel of phosphorylated tau peptides using a single-cell screening assay. Antibody sequences were recovered, cloned, and expressed as full-length IgGs. In total, 52 somatically mutated tau-binding antibodies were identified, corresponding to 35 unique clonal families. Forty-one of these antibodies recognize epitopes in the proline-rich and C-terminal domains, and binding of 26 of these antibodies is strictly phosphorylation dependent. Thirteen antibodies showed inhibitory activity in a P301S lysate seeded in vitro tau aggregation assay. Two such antibodies, CBTAU-7.1 and CBTAU-22.1, which bind to the proline-rich and C-terminal regions of tau, respectively, were characterized in more detail. CBTAU-7.1 recognizes an epitope that is similar to that of murine anti-PHF antibody AT8, but has different phospho requirements. Both CBTAU-7.1 and CBTAU-22.1 detect pathological tau deposits in post-mortem brain tissue. CBTAU-7.1 reveals a similar IHC distribution pattern as AT8, immunostaining (pre)tangles, threads, and neuritic plaques. CBTAU-22.1 shows selective detection of neurofibrillary changes by IHC. Taken together, these results suggest the presence of an ongoing antigen-driven immune response against tau in healthy individuals. The wide range of specificities to tau suggests that the human immune repertoire may contain antibodies that can serve as biomarkers or be exploited for therapy.