gebhart/patrepeval huggingface dataset:
Lipopolysaccharide binds to and activates A1 adenosine receptors on human pulmonary artery endothelial cells (2002)

Previously, it was reported that A(1) adenosine receptor antagonists prevent endotoxin-induced acute lung injury and pulmonary arterial endothelial cell damage. In competition radioligand binding experiments in membranes prepared from human pulmonary artery endothelial cells (PAECs), lipopolysaccharides (LPSs) of Escherichia coli, Salmonella typhimurium, Klebsiella pneumoniae, and Pseudomonas aeruginosa displaced the binding of a selective A(1) adenosine receptor antagonist [(125)I]-BWA844U (IC(50) values: 195 ng/ml, 290 ng/ml, 602 ng/ml, and 693 ng/ml, respectively) in a dose-dependent, competitive manner. There was no displacement of this radioligand by enterotoxin (< or = 10 microg/ml), diphosphoryl lipid A (< or = 10 microg/ml), and glycolipids, monosialoganglioside (< or = 1 microg/ml), lactocerebroside (< or = 100 microg/ml), or NBD galactocerebroside (< or = 100 microg/ml). Based on calculated IC(50) values, LPS (E. coli, IC(50) 111 ng/ml) displaced the selective A(1) adenosine receptor agonist, [(3)H]-2-chloro, N(6)-cyclopentyladenosine (CCPA) in human PAECs with a potency profile, CCPA > LPS > 2-phenylaminoadenosine (CV 1808), a selective A(2) adenosine receptor agonist. The potency profile for displacement of the selective A(2a) adenosine receptor agonist [(3)H]-CGS 21680 was CV 1808 > CCPA. LPS (E. coli 0.1 pg/ml-10 microg/ml) did not displace [(3)H]-CGS 21680 binding. In human PAECs, IL-6 and TXA(2) release induced by LPS (0-1 microg/ml) or CCPA (0-1 microM) at high doses was significantly reduced by the selective A(1) adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 1 microM). These data suggest that LPS binds to and activates A(1) adenosine receptors on human PAECs to induce the release of IL-6 and TXA(2). Activation of A(1) adenosine receptors on human PAECs by LPS, may contribute to the pathophysiology of acute lung injury associated with Gram-negative septicemia and endotoxemia.
Network calisthenics (2011)

Stimulation of quiescent mammalian cells with mitogens induces an abrupt increase in E2F1-3 expression just prior to the onset of DNA synthesis, followed by a rapid decline as replication ceases. This temporal adaptation in E2F facilitates a transient pattern of gene expression that reflects the ordered nature of DNA replication. The challenge to understand how E2F dynamics coordinate molecular events required for high-fidelity DNA replication has great biological implications. Indeed, precocious, prolonged, elevated or reduced accumulation of E2F can generate replication stress that culminates in either arrest or death. Accordingly, temporal characteristics of E2F are regulated by several network modules that include feedforward and autoregulatory loops. In this review, we discuss how these network modules contribute to "shaping" E2F dynamics in the context of mammalian cell cycle entry.
Overexpression of 15-Lipoxygenase in Vascular Endothelium Accelerates Early Atherosclerosis in LDL Receptor–Deficient Mice (2000)

To study the possible role of the human lipid-oxidizing enzyme 15-lipoxygenase (15-LO) in atherosclerosis, we overexpressed it specifically in the vascular wall of C57B6/SJL mice by using the murine preproendothelin-1 promoter. The mice overexpressing 15-LO were crossbred with low density lipoprotein (LDL) receptor-deficient mice to investigate atherogenesis. High levels of 15-LO were expressed in the atherosclerotic lesion in the double-transgenic mice as assessed by immunohistochemistry. The double-transgenic, 15-LO-overexpressing, LDL receptor-deficient mice (LDLR-/-/15LO) developed significantly larger atherosclerotic lesions at the aortic sinus compared with lesions in the LDL receptor-deficient (LDLR-/-) mice after 3 and 6 weeks (107,000 versus 28,000 microm(2) [P:<0.001] and 121,000 versus 87,000 microm(2) [P:<0.05], respectively) of an atherogenic diet. LDL from the LDLR-/-/15LO mice was more susceptible to oxidation than was the LDL from the control LDLR-/- mice, as shown by a shorter lag period for copper-induced conjugated diene formation. On the other hand, no differences were found in the levels of serum anti-oxidized LDL antibodies between the study groups. There were also no differences with respect to the density of macrophages and T lymphocytes infiltrating the lesions in both experimental groups. Taken together, these results support the hypothesis that 15-LO overexpression in the vessel wall is associated with enhanced atherogenesis.
New consensus research on neuropathological aspects of familial amyotrophic lateral sclerosis with superoxide dismutase 1 (SOD1) gene mutations: Inclusions containing SOD1 in neurons and astrocytes (2000)

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that primarily involves the motor neuron system. Approximately 5-10% of ALS is familial. Superoxide dismutase 1 (SOD1) gene mutations are shown to be associated with about 20% of familial ALS (FALS) patients. The neuronal Lewy-body-like hyaline inclusion (LBHI) and astrocytic hyaline inclusion (Ast-HI) are morphological hallmarks of certain SOD1-linked FALS patients with SOD1 gene mutant and transgenic mice expressing human SOD1 with G85R mutation. From the detailed immunohistochemical analyses, the essential common protein of both inclusions is SOD1. Ultrastructurally, both inclusions consist of granule-coated fibrils 15-25 nm in diameter. Based on the immuno-electron microscopical finding that these abnormal granule-coated fibrils are positive for SOD1, the formation (or aggregation) of the abnormal fibrils containing SOD1 would be essential evidence in diseases caused by various SOD1 mutations. The granule-coated fibrils are also modified by advanced glycation end products (AGEs). The AGEs themselves are insoluble molecules with direct toxic effects on cells. AGE formation of SOD1 composing the granule-coated fibrils (probable AGE-modified mutant SOD1) may amplify their aggregation and produce a more marked toxicity.
Direct Delivery of a Cytotoxic Anticancer Agent into the Metastatic Lymph Node Using Nano/Microbubbles and Ultrasound (2015)

Direct injection of an anticancer agent into a metastatic lymph node (LN) has not been used as a standard treatment because evidence concerning the efficacy of local administration of a drug into a metastatic LN has not been established. Here we show that the combination of intralymphatic drug delivery with nano/microbubbles (NMBs) and ultrasound has the potential to improve the chemotherapeutic effect. We delivered cis-diamminedichloroplatinum (II) (CDDP) into breast carcinoma cells in vitro and found that apoptotic processes were involved in the antitumor action. Next, we investigated the antitumor effect of intralymphatic chemotherapy with NMBs and ultrasound in an experimental model of LN metastasis using MXH10/Mo-lpr/lpr mice exhibiting lymphadenopathy. The combination of intralymphatic chemotherapy with NMBs and ultrasound has the potential to improve the delivery of CDDP into target LNs without damage to the surrounding normal tissues. The present study indicates that intralymphatic drug delivery with NMBs and ultrasound will potentially be of great benefit in the clinical setting.
Hepatitis B Virus (1998)

Part 1 Molecular biology of hepatitus B virus: replication of HBV, C. Seeger HBV gene expression, A. Siddiqui animal models and experimental systems for the study of hepadnaviruses, W.H. Gerlich. Part 2 Infection and chronic diseases: natural course of HBV infection, H. Blum genetic variants of HBV and their implications in disease, T. Harrison the immunology of chronic hepatitis B, B. Rehemann and F. Chisari. Part 3 Hepatocellular carcinoma: HBV DNA integrationa and insertional mutagenesis, K. Koike HBV transactivation and signal transduction, W.H. Caselmann and R. Koshy oncogenes, tumour suppressors, and co-factors in hepatocellular carcinoma, M.A. Buendia. Part 4 Rational approaches for the prevention of infection and therapy: novel vaccines, F. Schoedel cytokines and therapy, H. Thomas the development of targetable vectors for the liver and prospects for gene therapy, L. Weiss and P-H Hofschneider.
Bubble‐column and airlift photobioreactors for algal culture (2000)

Abstract Bubble columns and airlift photobioreactors can be useful for culturing phototrophic organisms requiring light as a nutrient. Light availability in bubble columns and airlift devices is influenced by aeration rate, gas holdup, and the liquid velocity (mixing and turbulence). The photosynthetically generated oxygen also needs to be removed, as excessive dissolved oxygen suppresses photosynthesis. Oxygen removal capacity is governed by the magnitude of the overall gas–liquid mass‐transfer coefficient, k L a L . This work characterizes the relevant hydrodynamic and mass‐transfer parameters in three air‐agitated reactors: bubble column, split‐cylinder airlift device and concentric draft‐tube sparged airlift vessel. The reactors are then evaluated for culture of the microalga Phaeodactylum tricornutum. All reactors were about 0.06 m 3 in working volume, and the working aspect ratio was about 10. Data were obtained in tap water for a base‐line comparison and in Mediterranean seawater, as a potential medium for algal culture. A theoretical relationship was developed and proved between k L a L and the aeration rate. In addition, a method based on mechanistic relationships was proved for predicting the liquid circulation velocity and k L a L in airlift reactors. Existing correlations applied satisfactorily to gas holdup and k L a L data obtained in the bubble column. Aqueous solution of sodium chloride (0.15 M) closely resembled seawater in terms of its hydrodynamics and oxygen transfer behavior. Under the conditions tested, all three reactors attained a biomass concentration of about 4 kg·m −3 after ∼260 h. The mean maximum specific growth rate was 0.022 h −1 in all cases at a power input of 109 W·m −3 .
Mutations of the BRAF gene in cholangiocarcinoma but not in hepatocellular carcinoma (2003)

Our data indicate that BRAF gene mutations are a relatively common event in CC but not in HCC. Disruption of the Raf/MEK/ERK (MAPK) kinase pathway, either by RAS or BRAF mutation, was detected in approximately 62% of all CC and is therefore one of the most frequent defects in cholangiocellular carcinogenesis.
Independent amplification and frequent co-amplification of three nonsyntenic regions on the long arm of chromosome 20 in human breast cancer. (1996)

DNA amplification at 20q13.2 is common in breast cancer, correlates with poor prognosis, and may reflect location of an important oncogene. Recently, other regions along 20q were also found to undergo amplification. Here, amplification levels and patterns of co-amplification were analyzed by interphase fluorescence in situ hybridization at 14 loci along 20q in 146 uncultured breast carcinomas and 14 cell lines. Three regions were independently amplified in uncultured tumors: RMC20C001 region at 20q13.2 (highly amplified in 9.6% of the cases), PTPN1 region 3 Mb proximal (6.2%), and AIB3 region at 20q11 (6.2%). Co-amplifications involving two or three of these regions were seen in 11 of the 19 highly amplified tumors. The results suggest that three distinct nonsyntenic regions along 20q may be important and that complex chromosomal rearrangements underlie their frequent co-amplification in breast cancer.
Plasminogen Is a Critical Host Pathogenicity Factor for Group A Streptococcal Infection (2004)

Group A streptococci, a common human pathogen, secrete streptokinase, which activates the host's blood clot-dissolving protein, plasminogen. Streptokinase is highly specific for human plasminogen, exhibiting little or no activity against other mammalian species, including mouse. Here, a transgene expressing human plasminogen markedly increased mortality in mice infected with streptococci, and this susceptibility was dependent on bacterial streptokinase expression. Thus, streptokinase is a key pathogenicity factor and the primary determinant of host species specificity for group A streptococcal infection. In addition, local fibrin clot formation may be implicated in host defense against microbial pathogens.
Copper, zinc superoxide dismutase catalyzes hydroxyl radical production from hydrogen peroxide. (1990)

Cu,Zn superoxide dismutase (Cu,Zn-SOD; EC 1.15.1.1) is known to be inhibited slowly by H2O2. Using EPR and the spin traps 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) and N-tert-butyl-alpha-phenylnitrone (PBN), we have shown that Cu,Zn-SOD catalyzes the formation of "free" .OH radicals from H2O2 in pH 7.6 bicarbonate buffer. Supporting evidence includes the following: (i) H2O2 and active Cu,Zn-SOD are required to yield significant signals from spin-trap-OH adducts. (ii) With O2-., Cu,Zn-SOD causes the appearance of intense resonance signals due to DMPO-OH adducts. These signals were inhibited strongly by catalase. (iii) With H2O2, Cu,Zn-SOD, and DMPO, radical scavengers formate and azide, but not ethanol, decrease DMPO-OH signals while causing new intense signals due to their corresponding DMPO-radical adducts. Failure of ethanol to quench DMPO-OH signals is discussed in light of the positively charged active channel of the enzyme. (iv) With PBN as a spin trap, ethanol quenches .OH radical signals and yields PBN-trapped hydroxyethyl radical signals. (v) Mn-SOD does not catalyze "free" .OH radical formation and it also exerts no effect on the signals of DMPO-OH adducts when added together with the Cu,Zn-SOD. The capacity of Cu,Zn-SOD to generate "free" .OH radicals from H2O2 may in part explain the biological damage associated with elevated intracellular SOD activity.
Nanoparticle building blocks (2001)

Monolayer-protected clusters (MPCs) and mixed monolayer-protected clusters (MMPCs)2 provide crucial tools for bridging the gap between ‘bottomup’ synthetic methods and ‘top-down’ fabrication. MPCs are core-shell type systems that feature a metallic or semiconductor core functionalized with a self-assembled monolayer (SAM). This monolayer provides two key functions. Firstly preventing core-core contact that would lead to agglomeration and secondly providing a structured environment for the attachment of functional molecular entities, including devices and sensors. MMPCs feature multiple functionality on the shell monolayer, greatly extending the versatility of these core-shell systems.
Benchmarking flexible adaptive time-frequency transforms for underdetermined audio source separation (2009)

We have implemented several fast and flexible adaptive lapped orthogonal transform (LOT) schemes for underdetermined audio source separation. This is generally addressed by time-frequency masking, requiring the sources to be disjoint in the time-frequency domain. We have already shown that disjointness can be increased via adaptive dyadic LOTs. By taking inspiration from the windowing schemes used in many audio coding frameworks, we improve on earlier results in two ways. Firstly, we consider non-dyadic LOTs which match the time-varying signal structures better. Secondly, we allow for a greater range of overlapping window profiles to decrease window boundary artifacts. This new scheme is benchmarked through oracle evaluations, and is shown to decrease computation time by over an order of magnitude compared to using very general schemes, whilst maintaining high separation performance and flexible signal adaptivity. As the results demonstrate, this work may find practical applications in high fidelity audio source separation.
Nonsymmetric P2/P2‘ Cyclic Urea HIV Protease Inhibitors. Structure−Activity Relationship, Bioavailability, and Resistance Profile of Monoindazole-Substituted P2 Analogues (1998)

Using the structural information gathered from the X-ray structures of various cyclic urea/HIVPR complexes, we designed and synthesized many nonsymmetrical P2/P2'-substituted cyclic urea analogues. Our efforts concentrated on using an indazole as one of the P2 substituents since this group imparted enzyme (Ki) potency as well as translation into excellent antiviral (IC90) potency. The second P2 substituent was used to adjust the physical and chemical properties in order to maximize oral bioavailability. Using this approach several very potent (IC90 11 nM) and orally bioavailable (F% 93-100%) compounds were discovered (21, 22). However, the resistance profiles of these compounds were inadequate, especially against the double (I84V/V82F) and ritonavir-selected mutant viruses. Further modification of the second P2 substituent in order to increase H-bonding interactions with the backbone atoms of residues Asp 29, Asp 30, and Gly 48 led to analogues with much better resistance profiles. However, these larger analogues were incompatible with the apparent molecular weight requirements for good oral bioavailability of the cyclic urea class of HIVPR inhibitors (MW < 610).
Developmental Regulation of Antisense-Mediated Gene Silencing in Dictyostelium (1994)

In Dictyostelium, the expression of antisense transcripts has been successfully used to reduce or eliminate gene expression. In most cases this occurs on the level of RNA stability resulting in a loss of both sense and antisense transcript accumulation. We here show that the antisense effect is regulated during the developmental cycle, i.e., in certain developmental stages and under certain developmental conditions, complementary RNAs appear not to interact with each other, resulting in a failure to abolish expression of the gene of interest. We find that this is not only the case with artificially introduced antisense constructs but also with the endogenous, antisense-regulated PSV-A gene. Our data demonstrate that antisense-mediated gene silencing is conferred by a biochemical machinery that is subject to regulation in vivo. The results provide a basis to better understand this machinery and to dissect the components. They may also explain the failure of some antisense experiments in Dictyostelium and possibly in other organisms.
Accumulation of membrane glycoproteins in lysosomes requires a tyrosine residue at a particular position in the cytoplasmic tail. (1990)

Human lysosome membrane glycoprotein h-lamp-1 is a highly N-glycosylated protein found predominantly in lysosomes, with low levels present at the cell surface. The signal required for delivery of h-lamp-1 to lysosomes was investigated by analyzing the intracellular distribution of h-lamp-1 with altered amino acid sequences expressed from mutated cDNA clones. A cytoplasmic tail tyrosine residue found conserved in chicken, rodent, and human deduced amino acid sequences was discovered to be necessary for efficient lysosomal transport of h-lamp-1 in COS-1 cells. In addition, the position of the tyrosine residue relative to the membrane and carboxyl terminus also determined lysosomal expression. Supplanting the wild-type h-lamp-1 cytoplasmic tail onto a cell surface reporter glycoprotein was sufficient to cause redistribution of the chimera to lysosomes. A similar chimeric protein replacing the cytoplasmic tyrosine residue with an alanine was not expressed in lysosomes. Altered proteins that were not transported to lysosomes were found to accumulate at the cell surface, and unlike wild-type lysosomal membrane glycoproteins, were unable to undergo endocytosis. These data indicate that lysosomal membrane glycoproteins are sorted to lysosomes by a cytoplasmic signal containing tyrosine in a specific position, and the sorting signal may be recognized both in the trans-Golgi network and at the cell surface.
6 inch High efficiency back contact crystalline Si solar cell applying heterojunction and thinfilm technology (2016)

We have developed a 6 inch heterojunction interdigitated back contact (HJBC) solar crystalline Si cell by applying our heterojunction technology and thinfilm technology. To form rear junction and front side passivation, we applied our heterojunction technology that allows efficiency of 24.5% with top/rear contact heterojunction solar cell. To secure this high quality passivation during the HJBC solar cell fabrication process, we have developed deposition technology of insulator layer originally used in thinfilm silicon solar cells. Furthermore, new structure has been designed to drastically suppress the rear electrode resistance. By adapting all these technologies, our HJBC solar cell has reached conversion efficiency of 24.91% independently confirmed at AIST (V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">OC</sub> =737 mV, I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SC</sub> =10.07 A, FF=80.2 %, P <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">MAX</sub> =5.95 W) under 1 sun illumination by total area measurement (239.0 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ).
Near-infrared optical-resolution photoacoustic microscopy (2014)

Compared with visible light (380-700 nm), near-infrared light (700-1400 nm) undergoes weaker optical attenuation in biological tissue; thus, it can penetrate deeper. Herein, we demonstrate near-infrared optical-resolution photoacoustic microscopy (NIR-OR-PAM) with 1046 nm illumination. A penetration depth of 3.2 mm was achieved in chicken breast tissue ex vivo using optical fluence within the American National Standards Institute (ANSI) limit (100 mJ/cm2). Beyond ∼0.6 mm deep in chicken breast tissue, NIR-OR-PAM has shown finer resolution than the visible counterpart with 570 nm illumination. The deep imaging capability of NIR-OR-PAM was validated in both a mouse ear and a mouse brain. NIR-OR-PAM of possible lipid contrast was explored as well.