gebhart/patrepeval huggingface dataset:
Inhibition of endothelial cell activation by adenovirus-mediated expression of I kappa B alpha, an inhibitor of the transcription factor NF-kappa B. (1996)

During the inflammatory response, endothelial cells (EC) transiently upregulate a set of genes encoding, among others, cell adhesion molecules and chemotactic cytokines that together mediate the interaction of the endothelium with cells of the immune system. Gene upregulation is mediated predominantly at the transcriptional level and in many cases involves the transcription factor nuclear factor (NF) kappa B. We have tested the concept of inhibiting the inflammatory response by overexpression of a specific inhibitor of NF-kappaB, I kappa B alpha. A recombinant adenovirus expressing I kappa B alpha was constructed (rAd.I kappa B alpha) and used to infect EC of human and porcine origin. Ectopic expression of IkappaBalpha resulted in marked, and in some cases complete, reduction of the expression of several markers of EC activation, including vascular cell adhesion molecule 1, interleukins 1, 6, 8, and tissue factor. Overexpressed I kappa B alpha inhibited NF-kappa B specifically since (a) in electrophoretic mobility shift assay, NF-kappa B but not AP-1 binding activity was inhibited, and (b) von Willebrand factor and prostacyclin secretion that occur independently of NF-kappa B, remained unaffected. Functional studies of leukocyte adhesion demonstrated strong inhibition of HL-60 adhesion to I kappa B alpha-expressing EC. These findings suggest that NF-kappa B could be an attractive target for therapeutic intervention in a variety of inflammatory diseases, including xenograft rejection.
Discharge Coefficient of the Bar Screen (2000)

Applicability of the conventional discharge equation for estimating water abstraction by a torrent intake of bar screen type is experimentally investigated. The experiments carried out under a variety of hydraulic and bar screen conditions indicate that depending on length, slope and clearance of the bar, the discharge coefficient defined may take uneven values that are outside of its normal design range of 0.50 to 0.55. This implies that the conventional discharge equation is less versatile in designing a torrent intake. An alternative discharge equation is thus proposed which is expressed in terms of diameter, clearance and modified length of the bar, and its applicability is also experimentally tested. The results show that though use of the equation is limited to the intake with a bar sloping of less than 50°, it gives an appropriately even value of the discharge coefficient, i. e., 0.62, for different configurations of the bar. Experiments also show that in case that a deflector or an upright stoplog are installed in a water cushion to enhance the water abstraction form the intake, value of the coefficient should be taken as 0.68.
Pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) kinase/MAPK cascade interact synergistically with UCN-01 to induce mitochondrial dysfunction and apoptosis in human leukemia cells. (2001)

Interactions between the checkpoint abrogator UCN-01 and several pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) kinase (MEK)/MAPK pathway have been examined in a variety of human leukemia cell lines. Exposure of U937 monocytic leukemia cells to a marginally toxic concentration of UCN-01 (e.g., 150 nM) for 18 h resulted in phosphorylation/activation of p42/44 MAPK. Coadministration of the MEK inhibitor PD184352 (10 microM) blocked UCN-01-induced MAPK activation and was accompanied by marked mitochondrial damage (e.g., cytochrome c release and loss of DeltaPsi(m)), caspase activation, DNA fragmentation, and apoptosis. Similar interactions were noted in the case of other MEK inhibitors (e.g., PD98059; U0126) as well as in multiple other leukemia cell types (e.g., HL-60, Jurkat, CCRF-CEM, and Raji). Coadministration of PD184352 and UCN-01 resulted in reduced binding of the cdc25C phosphatase to 14-3-3 proteins, enhanced dephosphorylation/activation of p34(cdc2), and diminished phosphorylation of cyclic AMP-responsive element binding protein. The ability of UCN-01, when combined with PD184352, to antagonize cdc25C/14-3-3 protein binding, promote dephosphorylation of p34(cdc2), and potentiate apoptosis was mimicked by the ataxia telangectasia mutation inhibitor caffeine. In contrast, cotreatment of cells with UCN-01 and PD184352 did not substantially increase c-Jun-NH(2)-terminal kinase activation nor did it alter expression of Bcl-2, Bcl-x(L), Bax, or X-inhibitor of apoptosis. However, coexposure of U937 cells to UCN-01 and PD184352 induced a marked increase in p38 MAPK activation. Moreover, SB203580, which inhibits multiple kinases including p38 MAPK, partially antagonized cell death. Lastly, although UCN-01 +/- PD184352 did not induce p21(CIP1), stable expression of a p21(CIP1) antisense construct significantly increased susceptibility to this drug combination. Together, these findings indicate that exposure of leukemic cells to UCN-01 leads to activation of the MAPK cascade and that interruption of this process by MEK inhibition triggers perturbations in several signaling and cell cycle regulatory pathways that culminate in mitochondrial injury, caspase activation, and apoptosis. They also raise the possibility that disrupting multiple signaling pathways, e.g., by combining UCN-01 with MEK inhibitors, may represent a novel antileukemic strategy.
Bats of Skydusky Hollow, Bland County, Virginia (2005)

During the period 22 November 1999 – 11 October 2001, winter hibernacula surveys, spring staging/autumn swarming surveys, and summer surveys for bats were completed in caves of Skydusky Hollow, Bland County, Virginia. During winter, 12 caves were entered and 16,185 bats counted: 235 Myotis sodalis (Indiana bat), 14,475 Myotis lucifugus (little brown myotis), 12 Myotis septentrionalis (northern myotis), 7 Myotis leibii (eastern small-footed myotis), 1,441 Pipistrellus subflavus (eastern pipistrelle), and 15 Eptesicus fuscus (big brown bat). Myotis sodalis hibernated in thermally stable areas of 7 -9 ̊C. The largest concentration of M. lucifugus (n = 4,280) hibernated in an area that was cooler (6.5 ̊C) than areas used by M. sodalis. The remaining 6,300 M. lucifugus hibernated at temperatures similar to, or slightly cooler than, temperatures used by M. sodalis. Intra-cave (and possibly inter-cave) movements of M. lucifugus and M. sodalis during the season of hibernation concentrated bats in cooler areas of the caves. An unusually large concentration of P. subflavus (n = 920) hibernated in Coon Cave in a warm (8.6 – 9.7 ̊C, stable environment. Proportions of species of bats captured during spring staging and autumn swarming varied from proportions found during winter hibernation. Mating and perhaps other social functions affect patterns of autumn use. No concentration of bats used the caves during summer.
Biochemical quality of the pharmaceutically licensed plasma OctaplasLG® after implementation of a novel prion protein (PrPSc) removal technology and reduction of the solvent/detergent (S/D) process time (2009)

The studies confirmed that the affinity ligand chromatography under the developed conditions can be introduced into the Octaplas manufacturing process, as a mean to reduce potentially present PrP(Sc), without hampering the proven quality of this product.
Modified Phase-Shifted PWM Control for Flying Capacitor Multilevel Converters (2007)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> The issue of voltage imbalance remains a challenge for the flying capacitor multilevel converter. The phase-shifted pulsewidth modulation (PS–PWM) method has a certain degree of self-balancing properties. However, the method alone is not sufficient to maintain balanced capacitor voltages in practical applications. The paper proposes a closed-loop modified PS–PWM control method by incorporating a novel balancing algorithm. The algorithm takes advantage of switching redundancies to adjust the switching times of selected switching states and thus maintaining the capacitor voltages balanced without adversely affecting the system's performance. Key techniques of the proposed control method, including selection of switching states, calculation of adjusting times for the selected states, and determination of new switching instants of the modified PS–PWM are described and analyzed. Simulation and experimental results are presented to confirm the feasibility of the proposed method. </para>
Chemical Penetration Enhancers for Transdermal Drug Delivery Systems (2009)

Skin as an important site of drug application for both local and systemic effects. However in skin, the stratum corneum is the main barrier for drug penetration. Penetration enhancement technology is a challenging development that would increase the number of drugs availablefor transdermal administration. The permeation of drug through skin can be enhanced by both chemical penetration enhancement and physical methods. In this review, we have discussed the chemical penetration enhancement technology for transdermal drug delivery as well as the probable mechanisms of action.
Gold nanoparticles: a new X-ray contrast agent (2006)

There have been few fundamental improvements in clinical X-ray contrast agents in more than 25 years, and the chemical platform of tri-iodobenzene has not changed. Current agents impose serious limitations on medical imaging: short imaging times, the need for catheterization in many cases, occasional renal toxicity, and poor contrast in large patients. This report is the first demonstration that gold nanoparticles may overcome these limitations. Gold has higher absorption than iodine with less bone and tissue interference achieving better contrast with lower X-ray dose. Nanoparticles clear the blood more slowly than iodine agents, permitting longer imaging times. Gold nanoparticles, 1.9 nm in diameter, were injected intravenously into mice and images recorded over time with a standard mammography unit. Gold biodistribution was measured by atomic absorption. Retention in liver and spleen was low with elimination by the kidneys. Organs such as kidneys and tumours were seen with unusual clarity and high spatial resolution. Blood vessels less than 100 microm in diameter were delineated, thus enabling in vivo vascular casting. Regions of increased vascularization and angiogenesis could be distinguished. With 10 mg Au ml(-1) initially in the blood, mouse behaviour was unremarkable and neither blood plasma analytes nor organ histology revealed any evidence of toxicity 11 days and 30 days after injection. Gold nanoparticles can be used as X-ray contrast agents with properties that overcome some significant limitations of iodine-based agents.
Food and farming: the big question marks. (1990)

Food production 1985-86 is up 15% over 1979-81 and average daily calorie intake is up to 2420 in 1983-85 over 1960 in 1961-63. However these trends are on the verge of ending because of environmental pressures. The number of malnourished is growing from 460 million in 1969-71 to 512 million in 1983-85 and a projected 628 million by 2000. Africas food growth has fallen behind its population growth with 2% vs. 2.8% respectively for 1961-85. Per capita food production has been declining in 51 out of 94 African countries 9 out of 28 Asian countries 17 out of 23 Latin American and Caribbean countries. The amount of food per capita is also declining but can be compensated for by increases in yield and increases in harvested area. Although the reality of suitable land loss means that if no action is taken we will lose 544 million hectares which is a 29% reduction in total food supply. The greenhouse effects and reduction in the filtering properties of the ozone layer will lead to further reductions in total food supply.
Further studies of fluoride ion entrapment in octasilsesquioxane cages; X-ray crystal structure studies and factors that affect their formation (2011)

A range of fluoride-encapsulated octasilsesquioxane cage compounds have been prepared using the TBAF route. Our studies suggest that whilst it is relatively straightforward to prepare fluoride-encapsulated octasilsesquioxane cage compounds with adjacent sp(2) carbons, leading to a range of aryl and vinyl substituted compounds, the corresponding sp(3) carbon derivatives are more capricious, requiring an electron withdrawing group that can stabilize the cage whilst not acting as a leaving group. Analysis by X-ray crystallography and solution (19)F/(29)Si NMR spectroscopy of R(8)T(8)@F(-) reveal very similar environments for the encapsulated fluoride octasilsesquioxane cages. Migration of a fluoride ion from inside the cage to outside the cage without breaking the T(8) framework and the possibility of encapsulating other anions within silsesquioxane cages have been also investigated.
Suppression of B-RafV600E melanoma cell survival by targeting mitochondria using triphenyl-phosphonium-conjugated nitroxide or ubiquinone (2016)

Most BRAF-mutated melanomas initially responsive to the FDA-approved inhibitors preferentially targeting B-Raf mutated in Val600 residue eventually relapse, requiring additional therapeutic modalities. Recent studies report the significance of metabolic reprograming in mitochondria for maintenance of BRAF-mutated melanomas and for development of their drug resistance to B-Raf inhibitors, providing a rationale for targeting mitochondria as a potential therapeutic strategy for melanoma. We therefore determined whether mitochondria-targeted metabolism-interfering agents can effectively suppress human B-Raf<sup>V600E</sup> melanoma cell lines and their dabrafenib/PLX4032-resistant progenies using mitochondria-targeted carboxy-proxyl (Mito-CP) and ubiquinone (Mito-Q). These agents exhibited comparable efficacy to PLX4032 in suppressing SK-MEL28, A375, and RPMI-7951 cells in vitro. As determined in SK-MEL28 and A375 cells, Mito-CP induced apoptotic cell death mediated by mitochondrial membrane depolarization and subsequent oxidative stress, which PLX4032 could not induce. Of note, Mito-CP also effectively suppressed PLX4032-resistant progenies of SK-MEL28 and A375. Moreover, when orally administered, Mito-CP suppressed SK-MEL28 xenografts in mice as effectively as PLX4032 without serious adverse effects. These data demonstrate that mitochondria-targeted agents have therapeutic potential to effectively suppress BRAF-mutated melanomas via an effect(s) distinct from those of B-Raf inhibitors.
Inflammatory mediators and acute phase proteins in patients with Crohn's disease and ulcerative colitis. (1997)

Measurements of circulating IL-6 and SAA proved most useful for clinical monitoring of the activity of Crohn's disease and ulcerative colitis and thus have advantages over conventional markers such as CRP, sedimentation rate and platelet count. IL-6 is probably the main cytokine factor responsible for hepatic induction of acute phase proteins in Crohn's disease. Measurements of circulating levels of all the inflammatory mediators studied are not useful at all for differentiation between Crohn's disease and ulcerative colitis.
A Modified Serum Neutralization Test for the Detection of Antibody to Porcine Reproductive and Respiratory Syndrome Virus in Swine Sera (1994)

Various conditions were evaluated and modified to improve the sensitivity of the serum neutralization (SN) test for detecting antibody in pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV). Higher SN titers were consistently obtained by the addition of 20% fresh swine serum to the virus diluent and by the use of a permissive cell clone (MARC-145) derived from the MA-104 cell line. Test sera used to assess the SN test were obtained from 2 groups of 3-week-old pigs infected intranasally with PRRSV (MN-1b). Using the modified method, SN antibody was first detected 9-11 days postinoculation (PI), with a peak evident at 11-21 days PI. The antibody subsequently declined, and a second peak was observed between 41 and 45 days PI. The first antibody peak was not observed and the SN antibody was only detectable between 32 and 41 days PI when the test was done with 20% heated swine serum or without supplemental swine serum. The SN antibody during 2-3 weeks PI was found to be sensitive to 2-mercaptoethanol or anti-swine IgM treatment. The SN antibody titers were high when homologous PRRSV isolate was used in the test but were markedly low for heterologous PRRSV isolates. No difference in antibody titers was observed when homologous and heterologous PRRSV isolates were tested by indirect fluorescent antibody assay. These results indicate that the modified SN method is useful in detecting earlier and higher PRRSV antibody and that it can differentiate among PRRSV isolates.
Highly Enantioselective and Regioselective Biocatalytic Azidolysis of Aromatic Epoxides (2000)

[figure: see text] The halohydrin dehalogenase from Agrobacterium radiobacter AD1 catalyzed the highly enantioselective and beta-regioselective azidolysis of (substituted) styrene oxides. By means of kinetic resolutions the remaining epoxide and the formed azido alcohol could be obtained in very high ee. In a large scale conversion, the decrease in yield and selectivity due to the uncatalyzed chemical side reaction could be overcome by slow addition of azide.
Erlotinib-Mediated Inhibition of EGFR Signaling Induces Metabolic Oxidative Stress through NOX4 (2011)

Redox regulation of epidermal growth factor receptor (EGFR) signaling helps protect cells against oxidative stress. In this study, we investigated whether the cytotoxicity of an EGFR tyrosine kinase inhibitor, erlotinib (ERL), was mediated by induction of oxidative stress in human head and neck cancer (HNSCC) cells. ERL elicited cytotoxicity in vitro and in vivo while increasing a panel of oxidative stress parameters which were all reversible by the antioxidant N-acetyl cysteine. Knockdown of EGFR by using siRNA similarly increased these oxidative stress parameters. Overexpression of mitochondrial targeted catalase but not superoxide dismutase reversed ERL-induced cytotoxicity. Consistent with a general role for NADPH oxidase (NOX) enzymes in ERL-induced oxidative stress, ERL-induced cytotoxicity was reversed by diphenylene iodonium, a NOX complex inhibitor. ERL reduced the expression of NOX1, NOX2, and NOX5 but induced the expression of NOX4. Knockdown of NOX4 by using siRNA protected HNSCC cells from ERL-induced cytotoxicity and oxidative stress. Our findings support the concept that ERL-induced cytotoxicity is based on a specific mechanism of oxidative stress mediated by hydrogen peroxide production through NOX4 signaling.
Purification of a novel pancreatic secretory factor (PSF) and a novel peptide with VIP‐ and secretin‐like properties (helodermin) from Gila monster venom (1984)

A combination of three HPLC procedures applied to the venom of Gila monster (Heloderma suspectum) has led to the purification to homogeneity of two bioactive components: (i) a 17.5 kDa protein, isolated on the basis of its potent secretory effect on dispersed rat pancreatic acini, was accordingly designated PSF (pancreatic secretory factor); (ii) a 5.9-kDa peptide, designated helodermin, was purified on the basis of its ability to stimulate adenylate cyclase in rat pancreatic membranes. PSF was unable to activate adenylate cyclase and, conversely, helodermin was devoid of secretory action.
Enhancers (2012)

Transcription of eukaryotic genes is an exceedingly sophisticated and complicated process, orchestrated by layers of control mechanisms involving a myriad of transcription factors and DNA control sequences, with both groups subject to multiple modifications. The availability of various recent genomic approaches has provided previously unforeseen opportunities to examine the cis-regulatory landscape of the entire genome, resulting in the identification of a potentially overwhelming number of enhancers and novel enhancer functions. In this review, we focus on the activities of enhancers in metazoans and discuss how they serve to regulate gene expression during early development.
Cytochrome P-450-mediated O-demethylation: a route in the metabolic activation of etoposide (VP-16-213). (1987)

The antitumor agent VP-16-213 is oxidatively O-demethylated by rat liver microsomes and purified rat liver microsomal cytochrome P-450. 3-Methylcholanthrene can quantitatively induce O-demethylation of VP-16-213. The Km and Vmax values for O-demethylation by noninduced, phenobarbital-, and 3-methylcholanthrene-induced rat liver microsomes were found to be 130, 600, and 160 microM and 8.5, 11.8, and 15.6 nmol H2CO/min X mg protein, respectively. Mass spectrometric comparison of the product of O-demethylation of VP-16-213 with the synthetic metabolite resulted in identification of the orthodihydroxy derivative. In studies on the biological activity of the orthodihydroxy derivative, it was found to inactivate single- and double-stranded phiX174 DNA, to bind to calf thymus DNA and to be highly toxic against chinese hamster ovary cells.
Evaluating the Specificity of Antisense Oligonucleotide Conjugates: A DNA ARRAY ANALYSIS (2021)

Antisense oligonucleotides are potentially powerful tools for selective control of cellular and viral gene expression. Crucial to successful application of this approach is the specificity of the oligonucleotide for the chosen RNA target. Here we apply DNA array technology to examine the specificity of antisense oligonucleotide treatments. The molecules used in these studies consisted of phosphorothioate oligomers linked to the Antennapedia (Ant) delivery peptide. The antisense oligonucleotide component was complementary to a site flanking the AUG of the MDR1 message, which codes for P-glycoprotein, a membrane ATPase associated with multidrug resistance in tumor cells. Using a DNA array of 2059 genes, we analyzed cellular responses to molecules comprised of Ant peptide-oligonucleotide conjugates, as well as to the Ant peptide alone. Besides the expected reduction in MDR1 message level, 37 other genes (approximately 2% of those tested) showed changes of comparable magnitude. The validity of the array results was confirmed for selected genes using Northern blots to assess messenger RNA levels. These results suggest that studies using antisense oligonucleotide technology to modulate gene expression need to be interpreted with caution.
Deep Inductive Network Representation Learning (2018)

This paper presents a general inductive graph representation learning framework called DeepGL for learning deep node and edge features that generalize across-networks. In particular, DeepGL begins by deriving a set of base features from the graph (e.g., graphlet features) and automatically learns a multi-layered hierarchical graph representation where each successive layer leverages the output from the previous layer to learn features of a higher-order. Contrary to previous work, DeepGL learns relational functions (each representing a feature) that naturally generalize across-networks and are therefore useful for graph-based transfer learning tasks. Moreover, DeepGL naturally supports attributed graphs, learns interpretable inductive graph representations, and is space-efficient (by learning sparse feature vectors). In addition, DeepGL is expressive, flexible with many interchangeable components, efficient with a time complexity of O(|E|), and scalable for large networks via an efficient parallel implementation. Compared with recent methods, DeepGL is (1) effective for across-network transfer learning tasks and large (attributed) graphs, (2) space-efficient requiring up to 6x less memory, (3) fast with up to 182x speedup in runtime performance, and (4) accurate with an average improvement in AUC of 20% or more on many learning tasks and across a wide variety of networks.