gebhart/patrepeval huggingface dataset:
Extremely potent triterpenoid inducers of the phase 2 response: Correlations of protection against oxidant and inflammatory stress (2005)

A series of synthetic triterpenoid (TP) analogues of oleanolic acid are powerful inhibitors of cellular inflammatory processes such as the induction by IFN-gamma of inducible nitric oxide synthase (iNOS) and of cyclooxygenase 2 in mouse macrophages. Here, we show that these analogues are also extremely potent inducers of the phase 2 response [e.g., elevation of NAD(P)H-quinone oxidoreductase and heme oxygenase 1], which is a major protector of cells against oxidative and electrophile stress. Moreover, like previously identified phase 2 inducers, the TP analogues use the antioxidant response element-Nrf2-Keap1 signaling pathway. Thus, induction of the phase 2 response and suppression of the iNOS induction was abrogated in nrf2(-/-) and keap1(-/-) mouse embryonic fibroblasts. The high potency of TP analogues in inducing the phase 2 response and blocking inflammation depends on the presence of activated Michael reaction (enone) functions at critical positions in rings A and C. The most potent TP doubles NAD(P)H-quinone oxidoreductase in murine hepatoma cells at 0.28 nM and has an IC(50) for suppression of iNOS induction in primary mouse macrophages of 0.0035 nM. The direct interaction of this TP with thiol groups of the Keap1 sensor for inducers is demonstrated spectroscopically. The antiinflammatory and phase 2 inducer potencies of 18 TP are closely linearly correlated (r(2) = 0.91) over 6 orders of magnitude of concentration. Thus, in addition to blocking inflammation and promoting differentiation, these TP exhibit another very important protective property: the induction of the phase 2 response.
Gene Action in Wheat Cultivars for Durable, High-Temperature, Adult-Plant Resistance and Interaction with Race-Specific, Seedling Resistance toPuccinia striiformis (1995)

Stephens and Druchamp wheat (Triricum aestivum) cultivars have both durable, high-temperature, adult-plant (HTAP) resistance and race-specific, seedling resistance to stripe rust caused by Puccinia striiformis. Gene action for the HTAP resistance was studied in parental and F 1 , F 2 , and backcross populations from reciprocal crosses among Stephens, Druchamp, Paha (a cultivar with race-specific resistance), and Michigan Amber (a susceptible cultivar) using stripe rust intensity data from the field transformed to area under the disease progress curve (AUDPC). Based on a joint scaling test, the additive component for HTAP resistance was significant for both Stephens and Druchamp. When HTAP resistance was effective and seedling resistance was ineffective in the same parent, the dominant component and the additive-additive, additive-dominant, and dominant-dominant epistatic interactions contributed significantly to HTAP resistance in Druchamp but not in Stephens. When HTAP resistance and seedling resistance were effective in the same parent, the dominant component and additive-additive and dominant-dominant epistatic interactions were significant in both Stephens and Druchamp and the additive-dominant epistatic interaction was significant in Stephens but not in Druchamp. When HTAP resistance was effective in one parent and seedling resistance was effective in the other parent, the dominant component and the additive-additive and dominant-dominant epistatic interactions were significant in the Druchamp crosses but not in the Stephens crosses. When HTAP resistance was effective in both parents, the additive and dominant components were detected at the Mount Vernon, WA, site but not the Pullman, WA, site. A constant cytoplasmic effect and a cytoplasm-dominance interaction were significant in reciprocal crosses of Stephens with Paha inoculated with race CDL-29; HTAP resistance was greater when Stephens was the female parent. A cytoplasmadditive gene interaction was significant in the reciprocal crosses of Druchamp with Paha tested with race CDL-25. Based on the gene action of HTAP resistance and its interactions with seedling resistance, it should be possible to exploit both HTAP and seedling resistances in breeding programs and in crosses; Stephens and Druchamp should be used as female parents to obtain the highest HTAP resistance
Increased liver uptake of liposomes and improved targeting efficacy by labeling with asialofetuin in rodents (1998)

To improve liposome-directed therapy of liver disease and gene delivery, it would be beneficial to selectively target hepatocytes. For this purpose, conventional liposomes (CL) were labeled with asialofetuin (AF), an asialoglycoprotein. The biodistribution of AF-labeled liposomes (AF-L) in mice and their incorporation into rat hepatocytes, and their potential use in acute liver injury, were investigated. AF-L displayed a quicker plasma clearance than CL, and 25.4%, 2.7%, and 1.2% of the injected dose remained in the plasma versus 47.0%, 26.1%, and 9.5% of CL, respectively at 2, 4, and 20 hours after the injection. Total liver uptake of AF-L (73%+/-3.9%) was markedly higher (P < .005) than CL (16.5%+/-1.8%) 4 hours after the injection. Liposomal radioactivity (cpm/mg) was greatly enhanced in the liver (11-fold) during the first 4 hours after the administration of 14C-AF-L, and was much higher than in 14C-CL-injected mice (1.5-fold). In vitro incubation of isolated rat hepatocytes with 14C-AF-L or intravenous injection of 14C-AF-L in rats resulted in higher hepatocyte-bound radioactivity compared with 14C-CL (P < .01-.005). AF-L-associated 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) fluorescent signals were not only located in Kupffer cells, but also in hepatocytes, in which bile canaliculus networks were imaged. Intravenous administration of vitamin E (VE)-associated CL (VE-CL, 1 mg/mouse) significantly lowered alanine transaminase (ALT) levels in CCl4-treated mice (196+/-79 vs. 2,107+/-235 U/mL; P < .01). The ALT level in CCl4 + VE-AF-L group was decreased to 38+/-16 units/mL, which was significantly lower than the CC14 + VE-CL group (P < .05). In conclusion, labeling liposomes with AF led to a shortened liposome plasma half-life and greatly enhanced uptake of AF-L liposome by the liver. The enhanced uptake resulted from an increased incorporation of hepatocytes with AF-L liposomes. VE-associated AF liposomes further improved the protective effect of VE liposomes on CC14-induced acute liver injury in mice. Preferential hepatocyte incorporation of AF-L liposomes suggests a useful hepatocyte-targeting approach for drug delivery and gene transfection.
Effect of Various Antiplatelet Agents on Acute Arterial Thrombosis in the Rat (1993)

Electrical stimulation of the rat carotid artery causes a deep medial injury and the formation of a platelet-rich thrombus. Occlusive thrombosis at sites of vessel wall injury was significantly reduced after the oral administration of clopidogrel, a potent analogue of ticlopidine, which showed dose-dependent inhibition of the thrombus formation (ED50 = 1.0 +/- 0.2 mg/kg, p.o.). Accumulation of thrombotic material was also considerably reduced after the i.v. administration of SR 27417, a highly potent and selective platelet activating factor receptor antagonist (ED50 = 10 micrograms/kg, i.v.), nafagrel, a thromboxane A2 synthetase inhibitor (ED50 = 1.3 mg/kg, i.v.) and hirudin (ED50 = 140 micrograms/kg, i.v.). A high dose (20 mg/kg, i.v.) of the anti-adhesive tetrapeptide Arg-Gly-Asp-Ser (RGDS) showed only a slight effect on thrombus formation whereas aspirin was ineffective. These results confirm that ADP and thromboxane A2 play key roles in the initiation and progression of arterial thrombus formation and suggest that platelet activating factor may also modulate thrombosis in this experimental model.
Ex vivo gene therapy using intravitreal injection of GDNF-secreting mouse embryonic stem cells in a rat model of retinal degeneration. (2009)

ES cells engineered to secrete GDNF exerted a neuroprotective effect for at least three months on retinal structure in the TgN S334ter rat model of retinal degeneration. Immunosuppression was not required for this. Several adverse effects were identified which require further investigation to make cell-based delivery of neuroprotection a viable clinical strategy.
A novel low‐friction surface for biomedical applications: Modification of poly(dimethylsiloxane) (PDMS) with polyethylene glycol(PEG)‐DOPA‐lysine (2008)

Aqueous biocompatible tribosystems are desirable for a variety of tissue-contacting medical devices. L-3,4-dihydroxyphenylalanine (DOPA) and lysine (K) peptide mimics of mussel adhesive proteins strongly interact with surfaces and may be useful for surface attachment of lubricating polymers in tribosystems. Here, we describe a significant improvement in lubrication properties of poly (dimethylsiloxane) (PDMS) surfaces when modified with PEG-DOPA-K. Surfaces were characterized by optical and atomic force microscopy, contact angle, PM-IRRAS, and X-ray photoelectron spectroscopy. Such surfaces, tested over the course of 200 rotations ( approximately 8 m in length), maintained an extremely low friction coefficient (mu) (0.03 +/- 0.00) compared to bare PDMS (0.98 +/- 0.02). These results indicate the potential applications of PEG-DOPA-K for the modification of device surfaces. Extremely low mu values were maintained over relatively long length scales and a range of sliding speeds without the need for substrate pre-activation and in the absence of excess polymer in aqueous solution. These results were only obtained when DOPA was bound to lysine (modification with PEG-DOPA did not have an effect on mu) suggesting the critical role of lysine in obtaining a lowered friction coefficient.
RGD-independent Binding of Integrin α9β1 to the ADAM-12 and -15 Disintegrin Domains Mediates Cell-Cell Interaction (2000)

ADAMs (a disintegrin and metalloproteases) mediate several important processes (e.g. tumor necrosis factor-alpha release, fertilization, and myoblast fusion). The ADAM disintegrin domains generally lack RGD motifs, and their receptors are virtually unknown. Here we show that integrin alpha(9)beta(1) specifically interacts with the recombinant ADAMs-12 and -15 disintegrin domains in an RGD-independent manner. We also show that interaction between ADAM-12 or -15 and alpha(9)beta(1) supports cell-cell interaction. Interestingly, the cation requirement and integrin activation status required for alpha(9)beta(1)/ADAM-mediated cell adhesion and cell-cell interaction is similar to those required for known integrin-extracellular matrix interaction. These results are quite different from recent reports that ADAM-2/alpha(6)beta(1) interaction during sperm/egg fusion requires an integrin activation status distinct from that for extracellular matrix interaction. These results suggest that alpha(9)beta(1) may be a major receptor for ADAMs that lack RGD motifs, and that, considering a wide distribution of ADAMs and alpha(9)beta(1), this interaction may be of potential biological and pathological significance.
Adenine specific DNA chemical sequencing reaction (1987)

Reaction of DNA with K2PdCl4 at pH 2.0 followed by a piperidine workup produces specific cleavage at adenine (A) residues. Product analysis revealed the K2PdCl4 reaction involves selective depurination at adenine, affording an excision reaction analogous to the other chemical DNA sequencing reactions. Adenine residues methylated at the exocyclic amine (N6) react with lower efficiency than unmethylated adenine in an identical sequence. This simple protocol specific for A may be a useful addition to current chemical sequencing reactions.
Cellular and Molecular Mechanisms of Dendrite Growth (2000)

Proper growth and branching of dendrites are crucial for nervous system function; patterns of dendritic arborization determine the nature and amount of innervation that a neuron receives and specific dendritic membrane properties define its computational capabilities. Until recently, there was relatively little known about the cellular and molecular mechanisms of dendritic growth, perhaps because dendrites were historically considered to be intrinsically determined, passive elements in the formation of connections in the nervous system. In the last few years, however, overwhelming evidence has accumulated indicating that dendritic growth is remarkably dynamic and responsive to environmental signals, including guidance molecules and levels and patterns of activity. This manuscript reviews our current understanding of the cellular and molecular mechanisms of dendritic growth, the influence of activity in sculpting specific patterns of dendritic arbors, and a potential integral role for dendrites in activity-dependent development of circuits in the nervous system.
Polymorphisms in the prostate cancer susceptibility gene HPC2/ELAC2 in multiplex families and healthy controls. (2001)

Two polymorphisms in the newly cloned prostate cancer susceptibility gene, HPC2/ELAC2, are suspected to be associated with an increased risk of developing the disease. These missense variants result in a serine (S) to leucine (L) substitution at amino acid residue 217 and an alanine (A) to threonine (T) substitution at residue 541. We genotyped these polymorphisms in 257 multiplex prostate cancer sibships and in 355 race-matched healthy unrelated controls. A significant increase in the frequency of the T allele is seen in the prostate cancer subjects compared with controls. There is, however, little evidence for excess clustering of the T allele within the multiplex families known to be segregating this allele, and there is no evidence for linkage of prostate cancer to the HPC2/ELAC2 region of chromosome 17p11.2 in these families. The T allele shows no association with either Gleason score or age-of-onset in segregating families.
Horizontal Well Completion Recommendations Through Optimized Formation Evaluation (1991)

Abstract Use of horizontal well completion to enhance hydrocarbon recovery has increased considerably in the past several years. Projections for future horizontal wells hold considerable promise as long as well productivity enhancement outweighs the incremental cost. The success of horizontal wells to date appears to be related to the development and application of specific technology. Optimized completion techniques are on top of the list of such required technology. Recent publications clearly demonstrate that without proper formation evaluation, adequate completion is typically unachievable and often results in premature well abandonment. This paper targets the three most common horizontal well formations subject to completion: naturally fractured, matrix permeability dominated systems and formations bounded by a gas cap or an aquifer or both. The formation parameters that best define matrix permeability dominated systems are quite different than those associated with naturally fractured formations. The paper first identifies the parameters that best define individual formations. Possible completion options for these formations are then discussed. Optimized completion recommendations are presented for each of the formations through use of case studies. Recommended completion procedures for naturally fractured formations require use of external casing packers and alternating perforated or slotted and blank pipes. Zonal isolation is of prime importance in matrix permeability dominated systems, especially when the pay interval is bounded by a gas cap or an aquifer or both. The recommended completion procedure for these types of formations uses cemented casing and selective perforating.
Cloning and expression of the 1.3S biotin-containing subunit of transcarboxylase. (1985)

We have cloned the gene coding for the 1.3S biotin-containing subunit of transcarboxylase (EC 2.1.3.1) from Propionibacterium shermanii. Transcarboxylase is a well-characterized enzyme composed of 30 polypeptides of three different types: twelve 1.3S biotinyl subunits, six 5S dimeric outer subunits, and one 12S hexameric central subunit. In propionic acid fermentation, the enzyme catalyzes the transfer of a carboxyl group from methylmalonyl-CoA to pyruvate in two partial reactions. The 1.3S subunit binds the outer and central subunits of the enzyme together, and its biotin serves as carboxyl carrier between subsites on the central and outer subunits where each partial reaction occurs. The cloned gene has been expressed in Escherichia coli, and the 1.3S subunit accumulates to 7% of total cellular protein. The foreign protein is recognized and biotinated by biotin holoenzyme synthetase of E. coli. The identifications of the gene and its product were confirmed by four independent approaches: DNA sequence analysis, immunoprecipitation, incorporation of labeled biotin, and measurement of enzymatic activity in the first partial reaction.
Post-synthetically Ligated Ribozymes:  An Alternative Approach to Iterative Solid-Phase Synthesis (1997)

To improve the overall yield of ribozyme synthesis, a convergent approach, based on the post-synthetic formation of an amino linker between two half-ribozymes was investigated. Borane.pyridine-mediated reductive amination of 3'-phosphoglycaldehyde-5'-half-ribozymes with 5'-aminohexyl-3'-half-ribozymes generated the corresponding amino-linked ribozymes in yields > 77% on different scales. The investigation of a variety of reducing agents is discussed together with a kinetic analysis of the selected coupling reaction. These post-synthetically ligated ribozymes exhibited slightly reduced in vitro catalytic activity and cell efficacy.
Immobilization of DNA on an Aluminum(III) Alkanebisphosphonate Thin Film with Electrogenerated Chemiluminescent Detection (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTImmobilization of DNA on an Aluminum(III) Alkanebisphosphonate Thin Film with Electrogenerated Chemiluminescent DetectionXiao-Hong Xu, Huey C. Yang, Thomas E. Mallouk, and Allen J. BardCite this: J. Am. Chem. Soc. 1994, 116, 18, 8386–8387Publication Date (Print):September 1, 1994Publication History Published online1 May 2002Published inissue 1 September 1994https://doi.org/10.1021/ja00097a064RIGHTS & PERMISSIONSArticle Views525Altmetric-Citations122LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (261 KB) Get e-Alertsclose Get e-Alerts
Free radical damage to protein and DNA: Mechanisms involved and relevant observations on brain undergoing oxidative stress (1992)

Iron mediates damage to proteins and DNA. The mechanisms of damage not only involve iron but also oxygen free radical intermediates. Oxidative damage to DNA causes not only strand breaks, but also formation of specific base adducts, such as 8-hydroxy-2'-deoxyguanosine. Oxidative damage also inactivates certain enzymes such as glutamine synthetase. Novel methods of assessing oxidative damage to tissue, including quantitation of salicylate hydroxylation as an index of hydroxyl free radical flux as well as specific lesions to proteins and DNA, have yielded results that clearly show that ischemia/reperfusion injury to mongolian gerbil brain involves oxidatively damaging events. Aging in gerbil as well as human brain is also associated with increased oxidative damage. Recent novel observations have shown that the spin-trapping agent phenyl alpha-tert-butylnitrone (PBN) offers protection in gerbil brain during ischemia/reperfusion injury. We also show that oxidative damage to brain during aging is decreased by chronic administration of PBN. The mechanism of action of PBN may be related to its trapping of specific free radicals, which triggers a cascade of oxidative events that eventually lead to tissue injury.
Simultaneous measurement of two DC magnetic field components by a single magnetoresistor (1995)

The method relies on a special excitation mode which causes uniform rotation of magnetization in the plane of a barber-pole magnetoresistive sensor. It is interesting that the uniform rotation of the magnetization is attained when the excitation field is not uniformly rotating. The rotation of this field should rather be elliptically polarized. The two orthogonal components of an external in-plane measured dc field disturb the uniform rotation of the magnetization in different instances of time. This behavior of the magnetization enables simultaneous but still separate measurements of both external field components by detection of the time shifts between the corresponding zero-crossing points of the sensor ac output and the zero-crossing points of the corresponding orthogonal components of the excitation field. The experimental results confirm the applicability of the method. Possible applications are reviewed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Epigenetics and immunotherapy: The current state of play (2017)

Cancer cells employ a number of mechanisms to escape immunosurveillance and facilitate tumour progression. The recent explosion of interest in immunotherapy, especially immune checkpoint blockade, is a result of discoveries about the fundamental ligand-receptor interactions that occur between immune and cancer cells within the tumour microenvironment. Distinct ligands expressed by cancer cells engage with cell surface receptors on immune cells, triggering inhibitory pathways (such as PD-1/PD-L1) that render immune cells immunologically tolerant. Importantly, recent studies on the role of epigenetics in immune evasion have exposed a key role for epigenetic modulators in augmenting the tumour microenvironment and restoring immune recognition and immunogenicity. Epigenetic drugs such as DNA methyltransferase and histone deacetylase inhibitors can reverse immune suppression via several mechanisms such as enhancing expression of tumour-associated antigens, components of the antigen processing and presenting machinery pathways, immune checkpoint inhibitors, chemokines, and other immune-related genes. These discoveries have established a highly promising basis for studies using combined epigenetic and immunotherapeutic agents as anti-cancer therapies. In this review, we discuss the exciting role of epigenetic immunomodulation in tumour immune escape, emphasising its significance in priming and sensitising the host immune system to immunotherapies through mechanisms such as the activation of the viral defence pathway. With this background in mind, we highlight the promise of combined epigenetic therapy and immunotherapy, focusing on immune checkpoint blockade, to improve outcomes for patients with many different cancer types.
Mechanisms of tissue destruction and cellular activation in rheumatoid arthritis (1992)

Rheumatoid arthritis is a chronic inflammatory disease of unknown etiology that is marked by synovial inflammation and destruction of articular extracellular matrix. Several studies of the pathogenesis of tissue destruction have focused on the production of metalloproteinases and their inhibitors in synovium as determinants of joint preservation. Also, the role of cytokines in the perpetuation of synovitis and of superantigens in synovial T-cell activation have led to novel hypotheses that attempt to explain abnormalities of synovial structure and function in rheumatoid arthritis. Recent studies that dealt with these topics are briefly reviewed in the context of current paradigms of inflammatory synovitis.