gebhart/patrepeval huggingface dataset:
Novel Synthetic Oleanane and Ursane Triterpenoids with Various Enone Functionalities in Ring A as Inhibitors of Nitric Oxide Production in Mouse Macrophages (2000)

We initially randomly synthesized about 60 oleanane and ursane triterpenoids as potential anti-inflammatory and cancer chemopreventive agents. Preliminary screening of these derivatives for inhibition of production of nitric oxide induced by interferon-gamma in mouse macrophages revealed that 3-oxooleana-1, 12-dien-28-oic acid (B-15) showed significant activity (IC(50) = 5.6 microM). On the basis of the structure of B-15, 19 novel olean- and urs-12-ene triterpenoids with a 1-en-3-one functionality having a substituent at C-2 in ring A have been designed and synthesized. Among them, 3-oxooleana-1,12-diene derivatives with carboxyl, methoxycarbonyl, and nitrile groups at C-2 showed higher activity than the lead compound B-15. In particular, 2-carboxy-3-oxooleana-1, 12-dien-28-oic acid (3) had the highest activity (IC(50) = 0.07 microM) in this group of triterpenoids. The potency of 3 was similar to that of hydrocortisone (IC(50) = 0.01 microM), although 3 does not act through the glucocorticoid receptor. Interesting structure-activity relationships of these novel synthetic triterpenoids are also discussed.
The Glitazone Family of Antidiabetic Agents (1996)

Abstract: In 1982, Takeda Inc. reported the discovery of ciglitazone (5-[4-(l­ methylcyclohexylmethoxy)-benzyl]thiazolidine-2,4-dione, ADD-3878), a compound which lowers blood glucose in animal models of Non Insulin Dependent Diabetes without an increase in insulin release, and which does not have an effect on the glycemia in normal animals. Since then many analogs have been produced, including troglitazone, pioglitazone, englitazone and darglitazone, and compounds where the thiazolidinedione ring has been replaced by other acidic moieties. Pharmacological studies have revealed effects on gluconeogenesis, glucose transport and glucose transporter expression, and a putative receptor in fat cells, PPARy, has been proposed. Clinical studies on troglitazone and darglitazone have shown these compounds to have glucose lowering effects, as well as effects on insulin sensitivity, lipid levels and blood pressure.
Structure of an intermolecular complex between cytosine and 5-fluorouracil (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure of an intermolecular complex between cytosine and 5-fluorouracilDonald H. Voet and Alexander RichCite this: J. Am. Chem. Soc. 1969, 91, 11, 3069–3075Publication Date (Print):May 1, 1969Publication History Published online1 May 2002Published inissue 1 May 1969https://pubs.acs.org/doi/10.1021/ja01039a041https://doi.org/10.1021/ja01039a041research-articleACS PublicationsRequest reuse permissionsArticle Views216Altmetric-Citations29LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Crystal structures that suggest late development of genetic code components for differentiating aromatic side chains (2003)

Early forms of the genetic code likely generated "statistical" proteins, with similar side chains occupying the same sequence positions at different ratios. In this scenario, groups of related side chains were treated by aminoacyl-tRNA synthetases as a single molecular species until a discrimination mechanism developed that could separate them. The aromatic amino acids tryptophan, tyrosine, and phenylalanine likely constituted one of these groups. A crystal structure of human tryptophanyl-tRNA synthetase was solved at 2.1 A with a tryptophanyl-adenylate bound at the active site. A cocrystal structure of an active fragment of human tyrosyl-tRNA synthetase with its cognate amino acid analog was also solved at 1.6 A. The two structures enabled active site identifications and provided the information for structure-based sequence alignments of approximately 45 orthologs of each enzyme. Two critical positions shared by all tyrosyl-tRNA synthetases and tryptophanyl-tRNA synthetases for amino acid discrimination were identified. The variations at these two positions and phylogenetic analyses based on the structural information suggest that, in contrast to many other amino acids, discrimination of tyrosine from tryptophan occurred late in the development of the genetic code.
Nitric Oxide and Its Gatekeeper Thrombospondin-1 in Tumor Angiogenesis (2007)

Nitric oxide (NO) plays a central role in angiogenesis as a mediator of signaling by vascular endothelial growth factor and other angiogenic factors. Low concentrations of NO produced in response to angiogenic factors stimulate angiogenesis, whereas higher concentrations typical of inflammatory responses inhibit angiogenesis. The proangiogenic activity of NO is mediated by activation of soluble guanylyl cyclase, leading to cyclic guanosine 3',5'-monophosphate accumulation and activation of its target kinases and ion channels. The four angiogenesis inhibitors currently approved for clinical use target components of the signaling cascade upstream of NO. New research has identified components downstream of NO as the primary target of the endogenous angiogenesis inhibitor thrombospondin-1 and has shown that circulating levels of thrombospondin-1 are sufficient to limit angiogenic responses by antagonizing NO signaling. This provides new insights into the significance of the widespread loss of thrombospondin-1 expression during malignant progression. Although clinical trials suggest that blocking NO signaling can inhibit tumor angiogenesis, this approach also inactivates inhibitory signaling from thrombospondin-1. We discuss the implications of the balance between these pathways for applying thrombospondin-1 mimetics and redox modifiers as cancer therapeutics.
Effect of the Polyunsaturated Fatty Acid Composition of Beef Muscle on the Profile of Aroma Volatiles (1999)

The effect of n-3 polyunsaturated fatty acids (PUFAs) in beef muscle on the composition of the aroma volatiles produced during cooking was measured. The meat was obtained from groups of steers fed different supplementary fats: (i) a palm-oil-based control; (ii) bruised whole linseed, which increased muscle levels of alpha-linolenic (C18:3 n-3) and eicosapentaenoic acid (EPA, C20:5 n-3); (iii) fish oil, which increased EPA and docosahexaenoic acid (C22:6 n-3); (iv) equal quantities of linseed and fish oil. Higher levels of lipid oxidation products were found in the aroma extracts of all of the steaks with increased PUFA content, after cooking. In particular, n-alkanals, 2-alkenals, 1-alkanols, and alkylfurans were increased up to 4-fold. Most of these compounds were derived from the autoxidation of the more abundant mono- and di-unsaturated fatty acids during cooking, and such autoxidation appeared to be promoted by increased levels of PUFAs.
Conformational transition of amyloid β-peptide (2005)

The amyloid beta-peptides (Abetas), containing 39-43 residues, are the key protein components of amyloid deposits in Alzheimer's disease. To structurally characterize the dynamic behavior of Abeta(40), 12 independent long-time molecular dynamics (MD) simulations for a total of 850 ns were performed on both the wide-type peptide and its mutant in both aqueous solution and a biomembrane environment. In aqueous solution, an alpha-helix to beta-sheet conformational transition for Abeta(40) was observed, and an entire unfolding process from helix to coil was traced by MD simulation. Structures with beta-sheet components were observed as intermediates in the unfolding pathway of Abeta(40). Four glycines (G(25), G(29), G(33), and G(37)) are important for Abeta(40) to form beta-sheet in aqueous solution; mutations of these glycines to alanines almost abolished the beta-sheet formation and increased the content of the helix component. In the dipalmitoyl phosphatidylcholine (DPPC) bilayer, the major secondary structure of Abeta(40) is a helix; however, the peptide tends to exit the membrane environment and lie down on the surface of the bilayer. The dynamic feature revealed by our MD simulations rationalized several experimental observations for Abeta(40) aggregation and amyloid fibril formation. The results of MD simulations are beneficial to understanding the mechanism of amyloid formation and designing the compounds for inhibiting the aggregation of Abeta and amyloid fibril formation.
Elastomeric Composites for Use in Well Cementing Operations (1993)

Abstract Considerable work has been conducted in the study of cement sheath stress failure. Laboratory and field tests indicate that conventional cementing compositions are susceptible to the effects of excessive casing test pressure or temperature changes experienced during production or workover operations. More specifically, those studies show that the typical range of compressive strengths used in most cementing operations, as well as the limited tensile properties afforded by pore-filling latex cements, are not adequate to prevent failure under conditions of excessive differential temperature and pressure. A crosslinked synthetic polymer containing a quick-setting cement has been developed that provides unique resilient properties better suited for those conditions where Portland cements will not suffice. These elastomeric formulations enhance tensile and shear strength, as well as increase resistance to chemicals and heat. Thus, both pipe support and sufficient ductility to complement pipe expansion are achieved with little or no permeability. These properties can be further enhanced by the addition of reinforcing agents such a silica, ground rubber, hard hydrocarbon, natural and synthetic fiber, barite, clays, carbon black and microspheres. Data from field case histories and laboratory studies are discussed. This investigation was limited to the evaluation of a synthetic rubber, styrene-butadiene. The use of the elastomeric system in other applications is also discussed.
Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation. (1994)

Eosinophil accumulation is a prominent feature of allergic inflammatory reactions, such as those occurring in the lung of the allergic asthmatic, but the endogenous chemoattractants involved have not been identified. We have investigated this in an established model of allergic inflammation, using in vivo systems both to generate and assay relevant activity. Bronchoalveolar lavage (BAL) fluid was taken from sensitized guinea pigs at intervals after aerosol challenge with ovalbumin. BAL fluid was injected intradermally in unsensitized assay guinea pigs and the accumulation of intravenously injected 111In-eosinophils was measured. Activity was detected at 30 min after allergen challenge, peaking from 3 to 6 h and declining to low levels by 24 h. 3-h BAL fluid was purified using high performance liquid chromatography techniques in conjunction with the skin assay. Microsequencing revealed a novel protein from the C-C branch of the platelet factor 4 superfamily of chemotactic cytokines. The protein, "eotaxin," exhibits homology of 53% with human MCP-1, 44% with guinea pig MCP-1, 31% with human MIP-1 alpha, and 26% with human RANTES. Laser desorption time of flight mass analysis gave four different signals (8.15, 8.38, 8.81, and 9.03 kD), probably reflecting differential O-glycosylation. Eotaxin was highly potent, inducing substantial 111In-eosinophil accumulation at a 1-2 pmol dose in the skin, but did not induce significant 111In-neutrophil accumulation. Eotaxin was a potent stimulator of both guinea pig and human eosinophils in vitro. Human recombinant RANTES, MIP-1 alpha, and MCP-1 were all inactive in inducing 111In-eosinophil accumulation in guinea pig skin; however, evidence was obtained that eotaxin shares a binding site with RANTES on guinea pig eosinophils. This is the first description of a potent eosinophil chemoattractant cytokine generated in vivo and suggests the possibility that similar molecules may be important in the human asthmatic lung.
Interferon induces a unique protein in mouse cells bearing a gene for resistance to influenza virus. (1983)

Mouse cells carrying the dominant resistance gene Mx develop a more efficient antiviral state toward influenza viruses in response to interferon than do Mx-negative cells. We have identified an Mx gene-associated product by labeling cultured peritoneal macrophages and embryonic cells with [35S]methionine in the presence or absence of interferon. The radioactive proteins from unfractionated cytoplasmic extracts were separated electrophoretically in two dimensions and were revealed by fluorography. A protein with a Mr of 72,500 and an isoelectric point of 6.3 was induced by mouse interferon type I (a mixture of alpha and beta interferons) in cells carrying the gene Mx but not in cells lacking Mx. The induction of this protein could be blocked by actinomycin D. The maximal rate of synthesis was reached in embryonic cells 4-5 hr after treatment with 10(3) reference units of interferon per ml. When the allele Mx (present in the inbred mouse strain A2G) was repeatedly backcrossed on different genetic backgrounds (BALB/c, C57BL/6, A/J), a clear correlation between the inducibility by interferon of this protein and the presence of the allele Mx was observed. The results suggest that this protein induced by the interaction of interferon with Mx plays a role in the selective antiviral state against influenza viruses that is observed in interferon-treated Mx-bearing cells.
Posttranslational N-glycosylation of the hepatitis B virus large envelope protein (2007)

These data together with previous results implicate that the N-glycosylation requirements of virion release are due to functional inhibition of cell glycoproteins engaged by HBV.
Identification of Cancer Stem Cell–Like Side Population Cells in Human Nasopharyngeal Carcinoma Cell Line (2007)

Side population (SP) cells have been isolated from several solid tumors. They lack distinct molecular markers for cancer stem cells (CSC) and increasing evidence suggests that they may play an important role in tumorigenesis and cancer therapy. However, there are no reports about the existence and function of SP cells in nasopharyngeal carcinoma (NPC) cells thus far. In this study, we scanned SP cells from five NPC cell lines and investigated stem cell characteristics, such as proliferation, self-renewal, and differentiation, using SP cells from the widely-used CNE-2 NPC cell line. We observed a strong tumorigenesis ability of SP cells following in vivo transplantation into nonobese diabetic/severe combined immunodeficient mice. Immunofluorescence revealed that cytokine 19 was highly expressed on SP cells. SP cells were found to be more resistant to chemotherapy and radiotherapy and this was related to the ATP-binding cassette half transporter member 2 of G family protein and Smoothened protein expression, respectively. Our results not only showed that SP cells in human NPC cell line CNE-2 had stem cell characteristics in vitro but also showed that they had a strong ability to form tumors in vivo. Importantly, we found the cell marker, cytokine 19, may serve as a potential molecular marker for further characterization of CSC. Taken together, our data shed light on tumorigenesis and therapeutic-resistant mechanisms, which are helpful for developing novel targets for effective clinical treatment of NPC.
Localization of gastric peroxidase and its inhibition by mercaptomethylimidazole, an inducer of gastric acid secretion (1992)

Mercaptomethylimidazole (MMI) is a potent inducer of gastric acid secretion which is associated with significant inhibition of peroxidase activity of rat gastric mucosa in vivo. A time-dependent increase in acid secretion correlates well with time-dependent decrease in the peroxidase activity. In a chamber experiment in vitro using isolated gastric mucosa, MMI stimulates acid secretion, showing an almost linear response up to 600 microM. The time-dependent increase in acid secretion is also correlated with time-dependent inhibition of the peroxidase activity. This effect is not mediated through oxidation of MMI by flavin-containing mono-oxygenase, which is absent from gastric mucosa. The peroxidase has been localized mainly in parietal cells isolated and purified from gastric mucosa by controlled digestion with collagenase followed by Percoll-density-gradient centrifugation. Peroxidase activity was further localized in the outer membrane of the purified mitochondria of the parietal cell by some membrane-impermeant reagents, indicating outward orientation of the enzyme. MMI can inhibit the peroxidase activity of both the parietal cell and its mitochondria in a concentration-dependent manner. The possible involvement of the parietal-cell peroxidase-H2O2 system in MMI-induced acid secretion may be suggested.
Bronchoprotective effects of atrial natriuretic peptide against propranolol‐induced bronchoconstriction after allergic reaction in guinea pigs (2000)

These results suggest that ANP possesses protective effects against propranolol-induced and histamine-induced bronchoconstriction, albeit by a non-specific mechanism in guinea pig in vivo.
On half-band, third-band, and Nth-band FIR filters and their design (1982)

Half-band FIR digital filters are known to be important due to their reduced computational requirements. They are especially valuable when used to decimate or interpolate by a factor of 2 [1], where their characteristics well match the filtering requirements. Computational savings can also be achieved by extending the concept of half-band filters to Nth-band filters for use in decimation or interpolation by a factor of N. In this paper, it is shown that for certain filter requirements, common to decimation and interpolation, an Nth-band filter exists with passband and stopband ripples only slightly larger than those of the optimal FIR filter. It is demonstrated that optimal half-band filters can be designed by using the computer program of McClellan, Parks, and Rabiner [2]. It is also shown that useful Nth-band filters can be designed by using this program, which is perhaps the most widely available filter design program.
Light Responsive Polymer Membranes: A Review (2012)

In recent years, stimuli responsive materials have gained significant attention in membrane separation processes due to their ability to change specific properties in response to small external stimuli, such as light, pH, temperature, ionic strength, pressure, magnetic field, antigen, chemical composition, and so on. In this review, we briefly report recent progresses in light-driven materials and membranes. Photo-switching mechanisms, valved-membrane fabrication and light-driven properties are examined. Advances and perspectives of light responsive polymer membranes in biotechnology, chemistry and biology areas are discussed.
Experimental research into the influence of ion dynamics when measuring the electron density from the Stark broadening of the H and H lines (2003)

In this work we have performed experimental research into the influence of ion dynamics on the profiles of the Hα and Hβ lines of the hydrogen Balmer series. In order to understand this influence the electron density of a microwave plasma column at atmospheric pressure is measured from the Stark broadening of both lines. However, in this case Kepple–Griem's theory is not used, as usual, but a new computational model based on the μ-ion model that includes the effect of the ion dynamics on the profiles. The results obtained show that the difference between the electron density values from both the Hα and Hβ lines is about 3%. So, it is possible to use the Hα line for the diagnosis of the electron density in those cases in which it is not possible to use the Hβ line; for example, when the Hβ line is not intense enough.
Rising pp65 antigenemia during preemptive anticytomegalovirus therapy after allogeneic hematopoietic stem cell transplantation: risk factors, correlation with DNA load, and outcomes (2001)

To determine the risk factors and outcomes associated with rising cytomegalovirus (CMV) antigenemia levels during preemptive therapy among stem cell allograft recipients, 119 patients with CMV antigenemia were studied. Patients were prospectively monitored for CMV antigenemia weekly; those with positive findings on antigenemia tests were treated with intravenous ganciclovir (5 mg/kg twice daily for 1 week, followed by 5 mg/kg per day for 5-6 d/wk). While on therapy, 47 of 119 (39%) patients demonstrated increases that were 2 or more times greater than their baseline values, whereas 33 of 119 (28%) patients demonstrated increases that were 5 or more times greater. Rising antigenemia was confirmed by polymerase chain reaction for CMV DNA. Multivariate analysis identified corticosteroids as the primary risk factor for increasing antigenemia: for increases greater than or equal to twice the baseline, 1 to 2 mg/kg steroids was associated with an odds ratio (OR) of 4.0. For increases greater than or equal to 2 mg/kg steroids, the OR was 10.1. CMV isolates obtained at the time of rising antigenemia were susceptible to ganciclovir, indicating that resistance was not a major factor. Overall, rising antigenemia levels were not correlated with CMV disease. All 4 patients in whom CMV disease developed during therapy, however, had rising antigenemia levels. Among the 47 patients with antigenemia increases greater than or equal to twice the baseline, 15 were re-induced with antivirals, whereas 32 continued to receive maintenance therapy. All 4 patients in whom CMV disease developed during therapy received maintenance therapy, and 3 died with CMV disease. Thus, host factors such as the receipt of corticosteroids explain increasing viral load during the early phase of preemptive therapy. Continued induction dosing or re-induction may protect against early breakthrough CMV disease and CMV-related death among patients with rising antigenemia on preemptive therapy. Subjects: Clinical Trials and Observations, Transplantation Topics: allogeneic hematopoietic stem cell transplant, antiviral agents, cytomegalovirus, dna, ganciclovir, polymerase chain reaction, glucocorticoids, adrenal corticosteroids, mineralocorticoids, viral load result