gebhart/patrepeval huggingface dataset:
IL‐6 and NF‐IL6 in Acute‐Phase Response and Viral Infection (1992)

NF-IL6 was originally identified as a DNA-binding protein responsible for IL-1-stimulated IL-6 induction. Direct cloning of NF-IL6 revealed its homology with C/EBP. C/EBP is expressed in liver and adipose tissues and is supposed to regulate several hepatocyte- and adipocyte-specific genes. In contrast, NF-IL6 is suppressed in normal tissues, but is rapidly and drastically induced by LPS or inflammatory cytokines such as IL-1, TNF, and IL-6. NF-IL6 can also bind to the regulatory region of various genes including IL-8, G-CSF, IL-1 and immunoglobulin genes. Furthermore, NF-IL6 is shown to be identical to IL-6DBP, a DNA-binding protein responsible for IL-6-mediated induction in acute-phase proteins, demonstrating that NF-IL6 is responsible for the genes regulated by IL-6. These results indicate that NF-IL6 may be a pleiotropic mediator of many inducible genes involved in acute, immune, and inflammatory responses, like NFkB. In this regard, it is noteworthy that both an NF-IL6 binding site and an NFkB binding site are present in the inducible genes such as IL-6, IL-8, and several acute-phase genes. On the other hand, accumulating evidence has revealed that overproduction of IL-6 may be responsible for the pathogenesis and/or several symptoms of a variety of diseases, including autoimmune diseases, malignancies, and viral diseases. At present, the molecular mechanisms of abnormal expression of the IL-6 gene are not known. Recently it has become evident that interplays between viral proteins and cellular proteins play an important role in viral oncogenesis and infection. The fact that NF-IL6 binds to the enhancer core sequences of various viruses strongly suggests a possible relationship of virus infection and IL-6 expression. In fact some evidence (Mahe et al. 1991, Spergel et al. 1992) indicates that NF-IL6 may interact with viral gene enhancers or viral products, although there are no definite data about the involvement of NF-IL6 in viral pathogenesis. Future studies will be required to clarify whether or not the interplay between NF-IL6 and viral infection is responsible for deregulation of the IL-6 gene.
Reproducing the dopamine pathophysiology of schizophrenia and approaches to ameliorate it: a translational imaging study with ketamine (2020)

Patients with schizophrenia show increased striatal dopamine synthesis capacity in imaging studies. The mechanism underlying this is unclear but may be due to N-methyl-D-aspartate receptor (NMDAR) hypofunction and parvalbumin (PV) neuronal dysfunction leading to disinhibition of mesostriatal dopamine neurons. Here, we develop a translational mouse model of the dopamine pathophysiology seen in schizophrenia and test approaches to reverse the dopamine changes. Mice were treated with sub-chronic ketamine (30 mg/kg) or saline and then received in vivo positron emission tomography of striatal dopamine synthesis capacity, analogous to measures used in patients. Locomotor activity was measured using the open-field test. In vivo cell-type-specific chemogenetic approaches and pharmacological interventions were used to manipulate neuronal excitability. Immunohistochemistry and RNA sequencing were used to investigate molecular mechanisms. Sub-chronic ketamine increased striatal dopamine synthesis capacity (Cohen's d = 2.5) and locomotor activity. These effects were countered by inhibition of midbrain dopamine neurons, and by activation of PV interneurons in pre-limbic cortex and ventral subiculum of the hippocampus. Sub-chronic ketamine reduced PV expression in these cortical and hippocampal regions. Pharmacological intervention with SEP-363856, a novel psychotropic agent with agonism at trace amine receptor 1 (TAAR1) and 5-HT<sub>1A</sub> receptors but no appreciable action at dopamine D<sub>2</sub> receptors, significantly reduced the ketamine-induced increase in dopamine synthesis capacity. These results show that sub-chronic ketamine treatment in mice mimics the dopaminergic alterations in patients with psychosis, that this requires activation of midbrain dopamine neurons, and can be ameliorated by activating PV interneurons and by a TAAR1/5-HT<sub>1A</sub> agonist. This identifies novel therapeutic approaches for targeting presynaptic dopamine dysfunction in patients with schizophrenia and effects of ketamine relevant to its therapeutic use for treating major depression.
Structural Determination of a Cyclic Metabolite of NAD+ with Intracellular Ca2+-mobilizing Activity (1989)

Incubation of NAD+ with extracts from sea urchin eggs resulted in production of a metabolite which could mobilize intracellular Ca2+ stores of the eggs. In this study we present structural evidence indicating that the metabolite is a cyclized ADP-ribose having an N-glycosyl linkage between the anomeric carbon of the terminal ribose unit and the N6-amino group of the adenine moiety. In view of this structure we propose cyclic ADP-ribose as the common name for the metabolite. The purification procedure for the metabolite consisted of deproteinizing the incubated egg extracts and sequentially chromatographing the extracts through three different high pressure liquid chromatography (HPLC) columns. The homogeneity of the purified metabolite was further verified by HPLC on a Partisil 5 SAX column. Using radioactive precursor NAD+ with label at various positions it was demonstrated that the metabolite was indeed derived from NAD+ and that the adenine ring as well as the adenylate alpha-phosphate were retained in the metabolite whereas the nicotinamide group was removed. This was confirmed by 1H NMR and two-dimensional COSY experiments, which also allowed the identification of all 12 protons on the two ribosyl units as well as the two protons on the adenine ring. From the chemical shifts of the two anomeric protons it was concluded that the C-1 carbons of both ribosyl units were still bonded to nitrogen. The positive and negative ion fast atom bombardment mass spectra showed (M + Na)+, (M - H + 2Na)+, (M - H)-, and (M - 2H + Na)- peaks at m/z 564, 586, 540, and 562, respectively. Exact mass measurements indicated a molecular weight of 540.0526 for (M - H)-. This together with the constraints imposed by the results from NMR, radioactive labeling, and total phosphate determination uniquely specified a molecular composition of C15H21N5O13P2. Analysis by 1H NMR and mass spectroscopy of the only major breakdown product of the metabolite after prolonged incubation at room temperature established that it was ADP-ribose, thus providing strong support for the cyclic structure.
In vitro testing of drug absorption for drug 'developability' assessment: forming an interface between in vitro preclinical data and clinical outcome. (2004)

Drug 'developability' assessment has become an increasingly important addition to traditional drug efficacy and toxicity evaluations, as pharmaceutical scientists strive to accelerate drug discovery and development processes in a time- and cost-effective manner. The fraction of drug absorbed and the maximum absorbable dose (MAD) can be estimated from in vivo clinical pharmacokinetics, mass balance studies or in vivo drug permeability in humans by different calculation methods. Unfortunately, in vivo data are usually unavailable at the early stages of drug discovery and development, and in vitro screening for the permeability, solubility, activity and toxicity of a drug has become a routine measurement in drug discovery and development. These in vitro data could be used to predict drug 'developability' with different calculation methods before selecting candidates for clinical evaluation. The fraction of drug absorbed in human could be predicted by in vivo human permeability or in vitro Caco2 permeability. For example, if drug permeability in Caco2 cells reaches 13.3 to 18.1 x 10(-6) cm/s, its predicted in vivo permeability in humans would reach 2 x 10(-4) cm/s, and its predicted fraction of drug absorbed would be > 90%, which is defined as highly permeable. The MAD could also be predicted with in vitro permeability, or calculated absorption rate constant. In addition, in vitro solubility and permeability data can also be used for the biopharmaceutics classification system (BCS) and, subsequently, to direct formulation optimization strategies. If drug 'developability' becomes an obstacle for drug delivery based on these in vitro data and predictions at the early stages of drug discovery and development, options such as prodrug approaches could be explored to enhance drug 'developability', in addition to different formulation methods. Therefore, in vitro absorption testing is a highly valuable tool in the decision-making process to select candidates for in vivo clinical studies at early-stage drug discovery and development.
An overview of data warehousing and OLAP technology (1997)

Data warehousing and on-line analytical processing (OLAP) are essential elements of decision support, which has increasingly become a focus of the database industry. Many commercial products and services are now available, and all of the principal database management system vendors now have offerings in these areas. Decision support places some rather different requirements on database technology compared to traditional on-line transaction processing applications. This paper provides an overview of data warehousing and OLAP technologies, with an emphasis on their new requirements. We describe back end tools for extracting, cleaning and loading data into a data warehouse; multidimensional data models typical of OLAP; front end client tools for querying and data analysis; server extensions for efficient query processing; and tools for metadata management and for managing the warehouse. In addition to surveying the state of the art, this paper also identifies some promising research issues, some of which are related to problems that the database research community has worked on for years, but others are only just beginning to be addressed. This overview is based on a tutorial that the authors presented at the VLDB Conference, 1996.
Distributed joint source-channel coding of video using raptor codes (2007)

Extending recent works on distributed source coding, this paper considers distributed source-channel coding and targets at the important application of scalable video transmission over wireless networks. The idea is to use a single channel code for both video compression (via Slepian-Wolf coding) and packet loss protection. First, we provide a theoretical code design framework for distributed joint source-channel coding over erasure channels and then apply it to the targeted video application. The resulting video coder is based on a cross-layer design where video compression and protection are performed jointly. We choose Raptor codes - the best approximation to a digital fountain - and address in detail both encoder and decoder designs. Using the received packets together with a correlated video available at the decoder as side information, we devise a new iterative soft-decision decoder for joint Raptor decoding. Simulation results show that, compared to one separate design using Slepian-Wolf compression plus erasure protection and another based on FGS coding plus erasure protection, the proposed joint design provides better video quality at the same number of transmitted packets. Our work represents the first in capitalizing the latest in distributed source coding and near-capacity channel coding for robust video transmission over erasure channels.
In search of general mechanisms for long-lasting plasticity:Aplysiaand the hippocampus (2003)

Long-term synaptic plasticity is thought to underlie many forms of long-lasting memory. Long-lasting plasticity has been most extensively studied in the marine snail Aplysia and in the mammalian hippocampus, where Bliss and Lømo first described long-term potentiation 30 years ago. The molecular mechanisms of plasticity in these two systems have proven to have many similarities. Here, we briefly describe some of these areas of overlap. We then summarize recent advances in our understanding of the mechanisms of long-lasting synaptic facilitation in Aplysia and suggest that these may prove fruitful areas for future investigation in the mammalian hippocampus and at other synapses in the mammalian brain.
CCR5-Mediated Human Immunodeficiency Virus Entry Depends on an Amino-Terminal gp120-Binding Site and on the Conformational Integrity of All Four Extracellular Domains (1999)

The human immunodeficiency virus type 1 coreceptor activity of CCR5 depends on certain polar and charged residues in its amino-terminal domain. Since studies of chimeric receptors have indicated that the extracellular loops of CCR5 are also involved in viral fusion and entry, we have explored the role of bulky, polar and nonpolar residues in these regions. Selected amino acids in the three extracellular loops were individually changed to alanines, and the coreceptor activities of the mutant CCR5 proteins were tested in a luciferase reporter virus-based entry assay. We found that the cysteines in the extracellular loops of CCR5 are essential for coreceptor activity. However, only minor (two- to threefold) effects on coreceptor function were noted for all of the other alanine substitutions. We also demonstrated that when the first 19 residues of the amino-terminal region were separated from the rest of CCR5, by insertion of glycine/serine spacers between proline 19 and cysteine 20, coreceptor function decreased. Together with our previous studies, these data indicate that both an amino-terminal gp120-binding site and extracellular domain geometry play a role in viral entry.
Second surface (2012)

An environment for creative collaboration is significant for enhancing human communication and expressive activities, and many researchers have explored different collaborative spatial interaction technologies. However, most of these systems require special equipment and cannot adapt to everyday environment. We introduce Second Surface, a novel multi-user Augmented reality system that fosters a real-time interaction for user-generated contents on top of the physical environment. This interaction takes place in the physical surroundings of everyday objects such as trees or houses. Our system allows users to place three dimensional drawings, texts, and photos relative to such objects and share this expression with any other person who uses the same software at the same spot. Second Surface explores a vision that integrates collaborative virtual spaces into the physical space. Our system can provide an alternate reality that generates a playful and natural interaction in an everyday setup.
In Vitro Antiallergic Activity of Flavonoids in Histamine Release Assay Using Rat Basophilic Leukemia (RBL-2H3) Cells (1994)

We used an established cell line, rat basophilic leukemia cells (RBL-2H3) to screen 40 flavonoids for inhibitory activity on antigen-induced histamine release from immunogloblin E (IgE)-sensitized RBL-2H3 cells. To exclude non-specific inhibition, the cytotoxicity to RBL-2H3 cells was simultaneously determined. Flavonoid aglycones showed a stronger activity for histamine release-inhibition and cytotoxicity than glycosides, and both activities were almost in parallel. Baicalein showed histamine release-inhibitory activity with the IC50 of 1.07×10-5 M in this bioassay system. However, it showed a potent cytotoxicity (IC50 9.62×10-6M). On the other hand, scutellarein (4′-hydroxybaicalein) showed a potent histamine release-inhibitory activity (IC50 3.15×10-6M) and low cytotoxicity (IC50 6.11×10-6M). We found that scutellarein has a potent histamine release-inhibitory y activity and low cytotoxicity.
Characterization of a dam Mutant of Serratia marcescens and Nucleotide Sequence of the dam Region (1999)

The DNA of Serratia marcescens has N6-adenine methylation in GATC sequences. Among 2-aminopurine-sensitive mutants isolated from S. marcescens Sr41, one was identified which lacked GATC methylation. The mutant showed up to 30-fold increased spontaneous mutability and enhanced mutability after treatment with 2-aminopurine, ethyl methanesulfonate, or UV light. The gene (dam) coding for the adenine methyltransferase (Dam enzyme) of S. marcescens was identified on a gene bank plasmid which alleviated the 2-aminopurine sensitivity and the higher mutability of a dam-13::Tn9 mutant of Escherichia coli. Nucleotide sequencing revealed that the deduced amino acid sequence of Dam (270 amino acids; molecular mass, 31.3 kDa) has 72% identity to the Dam enzyme of E. coli. The dam gene is located between flanking genes which are similar to those found to the sides of the E. coli dam gene. The results of complementation studies indicated that like Dam of E. coli and unlike Dam of Vibrio cholerae, the Dam enzyme of S. marcescens plays an important role in mutation avoidance by allowing the mismatch repair enzymes to discriminate between the parental and newly synthesized strands during correction of replication errors.
Expression and regulation of pyruvate dehydrogenase kinase isoforms in the developing rat heart and in adulthood: role of thyroid hormone status and lipid supply (2000)

Activation of the pyruvate dehydrogenase (PDH) complex (PDHC) promotes glucose disposal, whereas inactivation conserves glucose. The PDH kinases (PDHKs) regulate glucose oxidation through inhibitory phosphorylation of PDHC. The adult rat heart contains three PDHK isoforms PDHK1, PDHK2 and PDHK4. Using Western-blot analysis, with specific antibodies raised against individual recombinant PDHK1, PDHK2 and PDHK4, the present study investigated PDHK isoform expression in the developing rat heart and adulthood. We identified clear differences in the patterns of protein expression of each of these PDHK isoforms during the first 3 weeks of post-natal development, with most marked up-regulation of isoforms PDHK1 and PDHK4. Distinctions between the three cardiac PDHK isoforms were also demonstrated with respect to post-neonatal maturational up-regulation; with greatest up-regulation of PDHK1 and least up-regulation of PDHK4 from the post-neonatal period until maturity. The study also examined the role of thyroid hormone status and lipid supply on PDHK isoform expression. We observed marked selective increases in the amount of PDHK4 protein present relative to total cardiac protein in both hyperthyroidism and high-fat feeding. Overall, our data identify PDHK isoform PDHK1 as being of more potential regulatory importance for glucose oxidation in the adult compared with the neonatal heart, and cardiac PDHK4 as a PDHK isoform whose expression is specifically responsive to changes in lipid supply, suggesting that its up-regulation during early post-natal life may be the perinatal switch to use fatty acids as the energy source. We also identify regulation of pyruvate sensitivity of cardiac PDHK as a physiological variable, a change in which requires factors in addition to a change in lipid supply.
Cetirizine and hydrocortisone differentially regulate ICAM‐1 expression and chemokine release in cultured human keratinocytes (1998)

The results indicate that cetirizine has the capacity to block the IFNgamma-induced activation of keratinocytes, and thus can exert important regulatory effects on TH1 cell-mediated immune responses in the skin. The high doses required for evidencing these activities suggest the potential benefits of a topical use of cetirizine.
Glycation and Post-translational Processing of Human Interferon-γ Expressed in Escherichia coli (2003)

Until recently, nonenzymatic glycosylation (glycation) was thought to affect the proteins of long living eukaryotes only. However, in a recent study (Mironova, R., Niwa, T., Hayashi, H., Dimitrova, R., and Ivanov, I. (2001) Mol. Microbiol. 39, 1061-1068), we have shown that glycation takes place in Escherichia coli as well. In the present study, we demonstrate that the post-translational processing (proteolysis and covalent dimerization) observed with cysteineless recombinant human interferon-gamma (rhIFN-gamma) is tightly associated with its in vivo glycation. Our results show that, at the time of isolation, rhIFN-gamma contained early (but not advanced) glycation products. Using reverse phase high performance liquid chromatography in conjunction with fluorescence measurements, enzyme-linked immunosorbent assay, and mass spectrometry, we found that advanced glycation end products arose in rhIFN-gamma during storage. The latter were identified mainly in the Arg/Lys-rich C terminus of the protein, which was also the main target of proteolysis. Mass spectral analysis and N-terminal sequencing revealed four major (Arg140/Arg141, Phe137/Arg138, Met135/Leu136, and Lys131/Arg132) and two minor (Lys109/Ala110 and Arg90/Asp91) cleavage sites in this region. Tryptic peptide mapping indicated that the covalent dimers of rhIFN-gamma originating during storage were formed mainly by lateral cross-linking of the monomer subunits. Antiviral assay showed that proteolysis lowered the antiviral activity of rhIFN-gamma, whereas covalent dimerization completely abolished it.
Hydrolysate from Eggshell Membrane Ameliorates Intestinal Inflammation in Mice (2014)

Inflammatory bowel diseases (IBD) comprises of ulcerative colitis (UC) and Cohn's disease (CD) as two main idiopathic pathologies resulting in immunologically mediated chronic inflammatory conditions. Several bioactive peptides and hydro lysates from natural sources have now been tested in animal models of human diseases for potential anti-inflammatory effects. Eggshell membrane (ESM) is a well-known natural bioactive material. In this study, we aim to study the anti-inflammatory activity of ESM hydro lysate (AL-PS) in vitro and in vivo. In vitro, AL-PS was shown to inhibit pro-inflammatory cytokine IL-8 secretion. In vivo treatment with AL-PS was shown to reduce dextran sodium sulphate (DSS)-induced weight loss, clinical signs of colitis and secretion of interleukin (IL)-6 (p < 0.05). In addition, treatment with AL-PS also attenuated the severity of intestinal inflammation via down-regulation of IL-10 an anti-inflammatory cytokine. This validates potential benefits of AL-PS as a novel preventative target molecule for treatment of IBD.
Thermal Characteristics of Microscale Fractal-Like Branching Channels (2004)

Heat transfer through a fractal-like branching flow network is investigated using a three-dimensional computational fluid dynamics approach. Results are used for the purpose of assessing the validity of, and providing insight for improving, assumptions imposed in a previously developed one-dimensional model for predicting wall temperature distributions through fractal-like flow networks. As currently modeled, the one-dimensional code fairly well predicts the general wall temperature trend simulated by the three-dimensional model; hence, demonstrating its suitability as a tool for design of fractal-like flow networks. Due to the asymmetry in the branching flow network, wall temperature distributions for the proposed branching flow network are found to vary with flow path and between the various walls forming the channel network. Three-dimensional temperature distributions along the various walls in the branching channel network are compared to those along a straight channel. Surface temperature distributions on a heat sink with a branching flow network and a heat sink with a series of straight, parallel channels are also analyzed and compared. For the same observed maximum surface temperature on these two heat sinks, a lower temperature variation is noted for the fractal-like heat sink.
B7-H4 expression is correlated with tumor progression and clinical outcome in urothelial cell carcinoma. (2014)

The findings from this study indicate that B7-H4 has the potential to be an independent prognostic indicator for UCC.
ChemInform Abstract: Novel Heterocyclic Systems. Part 32. Convenient Synthesis of 4‐Aminopyridine‐3‐thiol and Several Thiazolo(5,4‐c)pyridines via Direct Lithiation. (1988)

Abstract 4‐(Pivaloylamino)pyridine (I) is lithiated and then treated with tetraisopropylthiuram disulfide (II) to form the dithiocarbamate (III).