gebhart/patrepeval huggingface dataset:
Liver-Specific Transcriptional Modules Identified by Genome-Wide In Silico Analysis Enable Efficient Gene Therapy in Mice and Non-Human Primates (2014)

The robustness and safety of liver-directed gene therapy can be substantially improved by enhancing expression of the therapeutic transgene in the liver. To achieve this, we developed a new approach of rational in silico vector design. This approach relies on a genome-wide bio-informatics strategy to identify cis-acting regulatory modules (CRMs) containing evolutionary conserved clusters of transcription factor binding site motifs that determine high tissue-specific gene expression. Incorporation of these CRMs into adeno-associated viral (AAV) and non-viral vectors enhanced gene expression in mice liver 10 to 100-fold, depending on the promoter used. Furthermore, these CRMs resulted in robust and sustained liver-specific expression of coagulation factor IX (FIX), validating their immediate therapeutic and translational relevance. Subsequent translational studies indicated that therapeutic FIX expression levels could be attained reaching 20-35% of normal levels after AAV-based liver-directed gene therapy in cynomolgus macaques. This study underscores the potential of rational vector design using computational approaches to improve their robustness and therefore allows for the use of lower and thus safer vector doses for gene therapy, while maximizing therapeutic efficacy.
Evidence for functionally active protease-activated receptor-3 (PAR-3) in human vascular smooth muscle cells (2003)

The present study investigates whether vascular smooth muscle cells of the human saphenous vein (SMC) express a functionally active protease-activated receptor-3 (PAR-3). PAR-3 mRNA was detected by RT-PCR. In the presence of thrombin, a rapid and transient increase in PAR-3 mRNA was observed. Stimulation of SMC with thrombin or the synthetic PAR-3-activating peptide, TFRGAP, resulted in transient mobilization of intracellular calcium. After a preceding challenge with thrombin, the calcium signal to TFRGAP was abolished, suggesting cleavage and subsequent desensitization of PAR-3 by thrombin. Activation of PAR-3 by TFRGAP elicited a time-dependent activation of the extracellular-signal-regulated kinase (ERK)-1/2 with a maximum response 10-20 min after stimulation. At 200 microM, TFRGAP increased [3H]-thymidine incorporation into cellular DNA about two-fold. These data indicate that PAR-3 is expressed in human SMC and triggers intracellular signaling. Thus, in the SMC PAR-3 might contribute to thrombin-induced responses.
Erythropoietin (1991)

THE red-cell mass is continuously adjusted to the optimal size for its function as an oxygen carrier by messages transmitted to the bone marrow from an oxygen sensor in the kidney. These messages are mediated by the hormone erythropoietin, are modulated by cardiovascular and renal factors, and form a key link in the feedback loop that controls the production of red cells (Fig. 1).1Erythropoietin is a glycoprotein growth factor synthesized by cells adjacent to the proximal renal tubules in response to signals from a renal oxygen-sensing device, probably a heme protein.2 In the bone marrow, erythropoietin binds to and . . .
Depleted Uranium and Human Health (2005)

Persistent public anxiety about the use of depleted uranium munitions since the early 1990s has been underpinned by claims of serious health consequences for both veterans and exposed civilians, alike. Whatever grounds there may have seemed to be in the aftermath of the Gulf War have been thoroughly discredited by a series of reports from various independent and expert organisations, such as the World Health Organisation and the British Royal Society.
Effect of Methyl Groups onto Imidazolium Cation Ring on Liquid Crystallinity and Ionic Conductivity of Amphiphilic Ionic Liquids (2004)

Abstract Phase transition behavior of imidazolium dodecylsulfonate was considerably affected by the introduction of methyl groups onto the imidazolium cation ring. Methyl group on the 2-position eliminated the liquid crystallinity. That on the 4-position was effective to suppress the crystallization.
Antibody response in Lewis rats injected with myelin oligodendrocyte glycoprotein derived peptides (1996)

Previous studies from our laboratory have demonstrated a predominant response to myelin oligodendrocyte glycoprotein (MOG) in patients with multiple sclerosis (MS) and showed that this molecule is able to induce in Lewis rats a chronic relapsing MS-like disease with extensive demyelination. To further study the possibility that MOG is a primary target antigen in MS, we have begun to investigate the encephalitogenicity and antibody response of different sequences of the extracellular domains of MOG in Lewis rats. We report that none of the synthetic peptides encompassing the MOG amino acid sequences 1-21, 67-87, 104-117 and 202-218 were encephalitogenic. In contrast, a single injection of MOG35-55 was able to induce severe neurological signs associated with inflammation and demyelination. All rats injected with MOG peptides 1-21, 35-55, 67-87 and 202-218 developed a high level of antibodies to their respective immunizing peptides as detected by ELISA and immunoblotting. Although all MOG peptide antisera reacted with immunoblots of native MOG separated under reducing conditions, only anti-MOG35-55 and anti-MOG202-218 antibodies reacted to native MOG, when tested under nonreducing conditions. These results indicate that the MOG35-55 peptide, which is found in the extracellular Ig V-like domain of MOG, is not only an encephalitogenic epitope but could also be an important determinant for initiating antibody-mediated demyelination. As indicated by the absence of reactivity to the other MOG peptides tested, as well as other central nervous system myelin proteins including myelin basic protein and proteolipid protein, the antibody response produced by MOG peptides is highly restricted.
Synthesis of imidazo[4,5-e]-as-triazine (6-azapurine) derivatives. (1978)

6-Benzylidenehydrazino-3-methyluracils were treated with sodium nitrite in acetic acid to give the corresponding 5-nitrosouracils. Dehydrative cyclization of the 5-nitrosouracils with acetic anhydride afforded 6-substituted 3-methyl-7-azalumazines, ethylation of which gave 6-substituted 1-ethyl-3-methyl-7-azalumazines. Treatment of these 7-azalumazines thus obtained and 6-substituted 1, 3-dimethyl-7-azalumazines with alcoholic sodium hydroxide caused a benzilic acid type rearrangement followed by decarboxylation and oxidation by air to give the respective 5H-imidazo [4, 5-e]-as-triazine-6 (7H)-ones (6-azapurines). Prolonged hydrolysis of 3-substituted 7-ethyl-5-methyl-5H-imidazo [4, 5-e]-as-triazine-6 (7H)-ones with alcoholic sodium hydroxide caused the ring cleavage to give 3-substituted 6-ethylamino-5-methylamino-as-triazines, which were fused with benzamidine hydrochloride to give rise to 3-substituted 7-ethyl-6-phenylimidazo [4, 5-e]-as-triazines.
Electrochemical Stability of Li6.5La3Zr1.5M0.5O12 (M = Nb or Ta) against Metallic Lithium (2016)

The electrochemical stability of Li6.5La3Zr1.5Nb0.5O12 (LLZNO) and Li6.5La3Zr1.5Ta0.5O12 (LLZTO) against metallic Li was studied using direct current (DC) and electrochemical impedance spectroscopy (EIS). Dense polycrystalline LLZNO (ρ=97 %) and LLZTO (ρ=92 %) were made using sol-gel synthesis and rapid induction hot-pressing at 1100 °C and 15.8 MPa. During DC cycling tests at room temperature (±0.01 mA/cm2 for 36 cycles), LLZNO exhibited an increase in Li-LLZNO interface resistance and eventually short-circuiting while the LLZTO was stable. After DC cycling, LLZNO appeared severely discolored while the LLZTO did not change in appearance. We believe the increase in Li-LLZNO interfacial resistance and discoloration are due to reduction of Nb5+ to Nb4+. The negligible change in interfacial resistance and no color change in LLZTO suggest that Ta5+ may be more stable against reduction than Nb5+ in cubic garnet versus Li during cycling.
A New Abietane and Two Dimeric Abietane Diterpenes from the Black Heartwood of <i>Cryptomeria japonica</i> (2004)

Three new diterpenes, sugikurojins A-C (1-3) were isolated from the black heartwood of Cryptomeria japonica. The structure of sugikurojin A was deduced to be 19-hydroxy-6,7-dehydroferruginol on the basis of extensive NMR experiments. Sugikurojin B was a dimer of 6,7-dihydroxyferruginol and 6,7-dehydroferruginol with a 6-O-11' linkage. Sugikurojin C was a dimeric ferruginol with 6-O-7' and 7-O-6' linkages. Also obtained in this investigation were the known compounds formosaninol (4), 15 sesquiterpenes (5-19), 16 diterpenes (20-35), three phenylpropanoids (36-38), and a phenolic compound (39).
Activated T Lymphocytes Regulate Hyaluronan Binding to Monocyte CD44 Via Production of IL-2 and IFN-γ (2001)

Interactions of the cell surface proteoglycan CD44 with the extracellular matrix glycosaminoglycan hyaluronan (HA) are important during inflammatory immune responses. Our previous studies indicated that monocyte HA binding could be induced by TNF-alpha. Moreover, monocyte HA binding could be markedly up-regulated by culturing PBMC with anti-CD3 (TCR complex) mAbs. The present study was undertaken to identify soluble factors and/or cell surface molecules of activated T lymphocytes that might regulate HA binding to monocytes. Abs to IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-10, IL-15, GM-CSF, IFN-gamma, and TNF-alpha were tested for their effects on anti-CD3 mAb-, Con A-, and PMA/ionomycin-mediated monocyte HA binding in PBMC cultures. Anti-TNF-alpha, anti-IL-2, and anti-IFN-gamma Abs, when added together to PBMC cultures, completely blocked Con A- and partially blocked anti-CD3- and PMA/ionomycin-induced monocyte HA binding. Furthermore, when added together to PBMC cultures, IL-2 and TNF-alpha induced high levels of monocyte HA binding. Likewise, IFN-gamma augmented TNF-alpha-induced monocyte HA binding. To investigate the role of T cell-monocyte direct contact in induction of monocyte HA binding, we studied PMA/ionomycin-activated, paraformaldehyde-fixed CD4(+) T cells in these assays. Fixed, PMA/ionomycin-activated CD4(+) T lymphocytes induced monocyte HA binding, but direct T cell-monocyte contact was not required. Moreover, anti-IFN-gamma and anti-TNF-alpha Abs blocked fixed PMA/ionomycin-activated CD4(+) T cell-induced monocyte HA binding. Taken together, these studies indicate roles for soluble T lymphocyte-derived factor(s), such as IL-2 and IFN-gamma, and a role for monocyte-derived TNF-alpha in Con A-, TCR complex-, and PMA/ionomycin-induced HA binding to monocyte CD44.
Neutrophil Extracellular Traps Directly Induce Epithelial and Endothelial Cell Death: A Predominant Role of Histones (2012)

Neutrophils play an important role in innate immunity by defending the host organism against invading microorganisms. Antimicrobial activity of neutrophils is mediated by release of antimicrobial peptides, phagocytosis as well as formation of neutrophil extracellular traps (NET). These structures are composed of DNA, histones and granular proteins such as neutrophil elastase and myeloperoxidase. This study focused on the influence of NET on the host cell functions, particularly on human alveolar epithelial cells as the major cells responsible for gas exchange in the lung. Upon direct interaction with epithelial and endothelial cells, NET induced cytotoxic effects in a dose-dependent manner, and digestion of DNA in NET did not change NET-mediated cytotoxicity. Pre-incubation of NET with antibodies against histones, with polysialic acid or with myeloperoxidase inhibitor but not with elastase inhibitor reduced NET-mediated cytotoxicity, suggesting that histones and myeloperoxidase are responsible for NET-mediated cytotoxicity. Although activated protein C (APC) did decrease the histone-induced cytotoxicity in a purified system, it did not change NET-induced cytotoxicity, indicating that histone-dependent cytotoxicity of NET is protected against APC degradation. Moreover, in LPS-induced acute lung injury mouse model, NET formation was documented in the lung tissue as well as in the bronchoalveolar lavage fluid. These data reveal the important role of protein components in NET, particularly histones, which may lead to host cell cytotoxicity and may be involved in lung tissue destruction.
Communication simulations for power system applications (2013)

New smart grid technologies and concepts, such as dynamic pricing, demand response, dynamic state estimation, and wide area monitoring, protection, and control, are expected to require considerable communication resources. As the cost of retrofit can be high, future power grids will require the integration of high-speed, secure connections with legacy communication systems, while still providing adequate system control and security. The co-simulation of communication and power systems will become more important as the two systems become more interrelated. This paper will discuss ongoing work at Pacific Northwest National Laboratory to create a flexible, high-speed power and communication system co-simulator for smart grid applications. The framework for the software will be described, including architecture considerations for modular, high performance computing and large-scale scalability (serialization, load balancing, partitioning, cross-platform support, etc.). The current simulator supports the ns-3 (telecommunications) and GridLAB-D (distribution systems) simulators. A test case using the co-simulator, utilizing a transactive demand response system created for the Olympic Peninsula and AEP gridSMART demonstrations, requiring two-way communication between distributed and centralized market devices, will be used to demonstrate the value and intended purpose of the co-simulation environment.
Distribution system power flow analysis-a rigid approach (1991)

This approach is oriented toward applications in three phase distribution system operational analysis rather than planning analysis. The solution method is the optimally ordered triangular factorization Y/sub BUS/ method (implicit Z/sub BUS/ Gauss method) which not only takes advantage of the sparsity of system equations but also has very good convergence characteristics on distribution problems. Detailed component models are needed for all system components in the simulation. Utilizing the phase frame representation for all network elements, a program called Generalized Distribution Analysis Systems, with a number of features and capabilities not found in existing packages, has been developed for large-scale distribution system simulations. The system being analyzed can be balanced or unbalanced and can be a radial, network, or mixed-type distribution system. Furthermore, because the individual phase representation is employed for both system and component models, the system can comprise single, double, and three-phase systems simultaneously.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Structure-function analysis of the C-terminal segment of human interleukin-6. (1993)

It has been hypothesized that interleukin-6 (IL-6) and granulocyte-colony-stimulating factor (G-CSF) may fold as four-alpha-helix bundle proteins. To probe the functional role of the putative fourth helical segment of IL-6 (D-helix), a chimeric IL-6/G-CSF analog containing the predicted D-helix of G-CSF as well as a panel of IL-6 D-helix point mutants were analyzed for their respective secondary structure, antigenicity, and receptor binding and biological activities. The putative D-helix of IL-6 could not be replaced by its G-CSF counterpart in spite of their high degree of similarity and thus is indispensable for the antigenic and functional integrity of the IL-6 receptor binding site. Conversely, the grafting of the G-CSF D-helix did not confer any G-CSF activity to IL-6. A synthetic helical peptide containing the IL-6 D-helix was inactive, even when mixed with or linked to a peptide from the A-helix known to be involved in the active site. However, the conserved residues F173, R179, and R182 found in the D-helices of both IL-6 and G-CSF critically contribute to the architecture of the IL-6 active site. Indeed, mutation of F173 or R179 markedly affected IL-6 receptor binding and biological activities, but not the conformation of a major neutralization epitope. Furthermore, substitution of R182 resulted in a significant unfolding of the D-helix accompanied by a drastic loss in IL-6 antigenicity and functional activities. Nevertheless, residues other than F173, R179, and R182 also contribute to IL-6 specificity.
Ultra-Wideband Compressed Sensing: Channel Estimation (2007)

In this paper, ultra-wideband (UWB) channel estimation based on the theory of compressive sensing (CS) is developed. The proposed approach relies on the fact that transmitting an ultra-short pulse through a multipath UWB channel leads to a received UWB signal that can be approximated by a linear combination of a few atoms from a pre-defined dictionary, yielding thus a sparse representation of the received UWB signal. The key in the proposed approach is in the design of a dictionary of parameterized waveforms (atoms) that closely matches the information-carrying pulseshape leading thus to higher energy compaction and sparse representation, and, therefore higher probability for CS reconstruction. Two approaches for UWB channel estimation are developed under a data-aided framework. In the first approach, the CS reconstruction capabilities are exploited to recover the composite pulse-multipath channel from a reduced set of random projections. This reconstructed signal is subsequently used as a referent template in a correlator-based detector. In the second approach, from a set of random projections of the received pilot signal, the Matching Pursuit algorithm is used to identify the strongest atoms in the projected signal that, in turn, are related to the strongest propagation paths that composite the multipath UWB channel. A Rake like receiver uses those atoms as templates for the bank of correlators in the detection stage. The bit error rate performances of the proposed approaches are analyzed and compared to that of traditional correlator-based detector. Extensive simulations show that for different propagation scenarios and UWB communication channels, detectors based on CS channel estimation outperform traditional correlator using just 1/3 of the sampling rate leading thus to a reduced use of analog-to-digital resources in the channel estimation stage.
MFMox ferroelectric memory transistor (2005)

Ferroelectric memory transistor is known for poor charge retention time. An alternative device structure has been developed to solve the retention problem of ferroelectric memory transistors. The gate structure of the new ferroelectric memory transistor is metal on ferroelectric thin film on bottom electrode on n-type semiconductive metal oxide on p-type silicon. The bottom electrode is in direct contact to the semiconductive metal oxide. Therefore, there is no floating gate in this device. The threshold voltage memory window of an experimental device extrapolation from 4 days of measured data to 10 years is about 1V.
Design and Construction of “Synthetic Species” (2012)

Synthetic biology is an area of biological research that combines science and engineering. Here, I merge the principles of synthetic biology and regulatory evolution to create a new species with a minimal set of known elements. Using preexisting transgenes and recessive mutations of Drosophila melanogaster, a transgenic population arises with small eyes and a different venation pattern that fulfils the criteria of a new species according to Mayr's Biological Species Concept. The population described here is the first transgenic organism that cannot hybridize with the original wild type population but remains fertile when crossed with other identical transgenic animals. I therefore propose the term "synthetic species" to distinguish it from "natural species", not only because it has been created by genetic manipulation, but also because it may never be able to survive outside the laboratory environment. The use of genetic engineering to design artificial species barriers could help us understand natural speciation and may have practical applications. For instance, the transition from transgenic organisms towards synthetic species could constitute a safety mechanism to avoid the hybridization of genetically modified animals with wild type populations, preserving biodiversity.
Benign Focal Epileptiform Discharges in Children After Severe Head Trauma: Prognostic Value and Clinical Course (1997)

Benign focal epileptiform discharges in posttraumatic EEGs have the same favorable prognosis as in benign focal epilepsy and should be handled as recommended for classic benign focal epilepsy.
Supramolecular Block Copolymers with Cucurbit[8]uril in Water (2008)

Be my guest! A supramolecular amphiphilic diblock copolymer was prepared with a cucurbit[8]uril molecular “handcuff” (see picture). It subsequently undergoes a hierarchical self-assembly process, resulting in the formation of a tertiary, compartmentalized nanostructure. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z705591_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Studies on the aminoxyalanine methyl ester and its α-N-acetyl derivative (1970)

The ability of the aminoxyalanine methyl ester and its α-N-acetyl derivative to promote the hydrolysis of cinnamoylimidazole was found to increase with time. The time-dependent increase in the activity could not be explained on the basis of the hydrolysis of the functional groups or the cyclization to yield the parent isoxazolidone ring. The formation of an active derivative in the solutions of these compounds is suggested.
Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005) (2005)

Guidelines and Expert Consensus Documents aim to present all the relevant evidence on a particular issue in order to help physicians to weigh the benefits and risks of a particular diagnostic or therapeutic procedure. They should be helpful in everyday clinical decision-making.
Dynamic Changes in Cervical Glycosaminoglycan Composition during Normal Pregnancy and Preterm Birth (2012)

Glycosaminoglycans (GAG) have diverse functions that regulate macromolecular assembly in the extracellular matrix. During pregnancy, the rigid cervix transforms to a pliable structure to allow birth. Quantitative assessment of cervical GAG is a prerequisite to identify GAG functions in term and preterm birth. In the current study, total GAG levels increased at term, yet the abundance, chain length, and sulfation levels of sulfated GAG remained constant. The increase in total GAG resulted exclusively from an increase in hyaluronan (HA). HA can form large structures that promote increased viscosity, hydration, and matrix disorganization as well as small structures that have roles in inflammation. HA levels increased from 19% of total GAG in early pregnancy to 71% at term. Activity of the HA-metabolizing enzyme, hyaluronidase, increased in labor, resulting in metabolism of large to small HA. Similar to mice, HA transitions from high to low molecular weight in term human cervix. Mouse preterm models were also characterized by an increase in HA resulting from differential expression of the HA synthase (Has) genes, with increased Has1 in preterm in contrast to Has2 induction at term. The Has2 gene but not Has1 is regulated in part by estrogen. These studies identify a shift in sulfated GAG dominance in the early pregnant cervix to HA dominance in term and preterm ripening. Increased HA synthesis along with hyaluronidase-induced changes in HA size in mice and women suggest diverse contributions of HA to macromolecular changes in the extracellular matrix, resulting in loss of tensile strength during parturition.