gebhart/patrepeval huggingface dataset:
Free radical production and DNA cleavage by copper chelating peptide-anthraquinones. (1990)

Two pseudopeptides incorporating a peptide metal-chelating moiety (Gly-His-Lys) and a polyhydroxy anthraquinone ring related to the nuclei of anti-tumor drugs such as mitoxantrone and ametantrone, have been synthesized. The goal was to conjugate the redox effects of a quinone ring with the iron-chelating properties of the peptide in order to generate free radical species capable of damaging DNA. Indeed quinone-containing drugs undergo, in vivo, one-electron reduction to the corresponding semiquinone radicals which, in the presence of molecular oxygen, produce a superoxide anion radical, hydrogen peroxide and ultimately, in the presence of metal, hydroxyl radical (Fenton reaction). Hydroxyl radicals (OH.) are short-lived and extremely reactive with their bioenvironment. The interaction of both drugs with DNA has been studied by fluorescence quenching and DNA melting experiments. Spectroscopic and e.s.r. studies demonstrated that several types of Cu-complex are formed depending on the copper-drug ratio. The production of free radicals, as evidenced by spin-trapping, is optimum with a Cu/drug ratio of 0.1; in this case the metal ion is chelated by the peptide moiety. This latter complex is able to induce DNA breakage at a high level. Thus, it appears that the proposed concept works but that care must be taken in the choice of the relative concentration of copper.
Synthesis of dithienothiophenes (1971)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of dithienothiophenesFeike De Jong and Matthijs J. JanssenCite this: J. Org. Chem. 1971, 36, 14, 1998–2000Publication Date (Print):July 1, 1971Publication History Published online1 May 2002Published inissue 1 July 1971https://pubs.acs.org/doi/10.1021/jo00813a032https://doi.org/10.1021/jo00813a032research-articleACS PublicationsRequest reuse permissionsArticle Views445Altmetric-Citations120LEARN 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
The challenge of utilising new technology in design education (2000)

This paper examines some of the many problems and issues associated with integrating new\nand developing technologies in the design of products. As technology in general races ahead\nchallenges arise for both commercial designers and educators on how best to keep track and\nutilise the advances. The challenge is particularly acute within tertiary education where the\nintroduction of new cutting edge technology is often encouraged. Although this is generally\nachieved through the feedback of research activity, integrating new concepts at an appropriate\nlevel is a major task. Of particular concern is how focussed areas of applied technology can\nbe made part of the multidisciplinary scope of design education.\nThis paper provides examples of the successful interaction of research and education within a\nUK higher education institution. It highlights that, through selective tuition of research topics\nand appropriate technical support, innovative design solutions can result. In addition, it shows\nthat by introducing leading edge and, in some cases, underdeveloped technology, specific key\nskills of independent learning, communication and research methods can be encouraged.\nFurthermore, the paper examines both the successes and failures of the process and provides\nconclusions relating to curriculum development, effective learning, and assessment.
Expanded polyglutamine peptides alone are intrinsically cytotoxic and cause neurodegeneration in Drosophila (2000)

Several dominant, late-onset neurodegenerative diseases (e.g. Huntington's disease) are caused by expansion of polyglutamine (polyQ) repeats within specific proteins. The diverse, yet overlapping, pathology of these diseases could be due to novel deleterious functions unique to each protein or to a common pathophysiology mediated by the long polyQ chains themselves. By engineering Drosophila to express different polyQ peptides, we find that expanded polyQ chains alone are intrinsically cytotoxic and cause neuronal degeneration and early adult death. We further find that this intrinsic toxicity is dependent on cell type and polyQ length and that the inclusion of other amino acids modifies and reduces toxicity. This is the first in vivo evidence that polyQs, when removed from their disease gene context, cause neurotoxicity. These studies provide a basis for understanding the diverse clinical presentations in terms of the intrinsic cytotoxic effect of polyQ peptides being modulated by protein context. Parallel experiments in which cytotoxic polyQ expansions were engineered into Dishevelled, a Drosophila protein containing a naturally occurring polyQ tract, strongly suggest that the effect of a toxic polyQ peptide can be neutralized by protein context. This animal model provides a simple and effective means of screening for therapeutics that relieves the polyQ-induced lethality, independent of any particular disease gene. By quantifying the degree of lethality in several transgenic lines, we have identified a number of genetically modified strains that are suitable for eventual testing of compounds or genes that ameliorate the pathology of polyQ peptides.
Cancer statistics, 2014 (2014)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data were collected by the National Center for Health Statistics. A total of 1,665,540 new cancer cases and 585,720 cancer deaths are projected to occur in the United States in 2014. During the most recent 5 years for which there are data (2006-2010), delay-adjusted cancer incidence rates declined slightly in men (by 0.6% per year) and were stable in women, while cancer death rates decreased by 1.8% per year in men and by 1.4% per year in women. The combined cancer death rate (deaths per 100,000 population) has been continuously declining for 2 decades, from a peak of 215.1 in 1991 to 171.8 in 2010. This 20% decline translates to the avoidance of approximately 1,340,400 cancer deaths (952,700 among men and 387,700 among women) during this time period. The magnitude of the decline in cancer death rates from 1991 to 2010 varies substantially by age, race, and sex, ranging from no decline among white women aged 80 years and older to a 55% decline among black men aged 40 years to 49 years. Notably, black men experienced the largest drop within every 10-year age group. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population.
Activation of the coagulation mechanism on tumor necrosis factor-stimulated cultured endothelial cells and their extracellular matrix. The role of flow and factor IX/IXa (1991)

Infusion of tumor necrosis factor (TNF) into tumor-bearing mice led to intravascular clot formation with fibrin deposition in microvessels in the tumor bed in close association with the vessel wall, which could be prevented by active site-blocked factor IXa (IXai). This observation prompted us to examine the role of the intrinsic system in activation of the coagulation mechanism on TNF-stimulated human endothelial cell monolayers and endothelial-derived matrix during exposure to purified coagulation factors or flowing blood. Treatment of endothelial cells in intact monolayers with TNF induced expression of the procoagulant cofactor tissue factor (TF) in a dose-dependent manner, and after removal of the cells, TF was present in the matrix. TNF-treated endothelial cell monolayers exposed to blood anticoagulated with low molecular weight heparin induced activation of coagulation. Addition of IXai blocked the procoagulant response on TNF-treated endothelial cells, and consistent with this, the presence of factor IX/VIIIa enhanced endothelial TF/factor VII(a) factor X activation over a wide range of cytokine concentrations (0-600 pM). When TF-dependent factor X activation on endothelial cells was compared with preparations of subendothelium, the extracellular matrix was 10-20 times more effective. IXai blocked TF/factor VII(a) mediated activated coagulation on matrix, but only at lower concentration of TNF (less than 50 pM). Similarly, enhancement of factor Xa formation on matrix by factors IX/VIIIa was most evident at lower TNF concentrations. When anticoagulated whole blood flowing with a shear of 300 s-1 was exposed to matrices from TNF-treated endothelial cells, but not matrices from control cells, fibrinopeptide A (FPA) generation, fibrin deposition, and platelet aggregate formation were observed. FPA generation could be prevented by a blocking antibody to TF and by active site-blocked factor Xa (Xai) over a wide range of TNF concentrations (0-600 pM), whereas IXai only blocked FPA generation at lower TNF concentrations (less than 50 pM). Activation of coagulation on matrix from TNF-stimulated endothelial cells was dependent on the presence of platelets, indicating the important role of platelets in propagating the reactions leading to fibrin formation. These observations demonstrate the potential of cytokine-stimulated endothelium and their matrix to activate coagulation and suggest the importance of the intrinsic system in factor Xa formation on cellular surfaces.
Synthesis and antiviral activity of 9-alkoxypurines. 1. 9-(3-Hydroxypropoxy)- and 9-[3-hydroxy-2-(hydroxymethyl)propoxy]purines (1990)

Reaction of hydroxyl-protected derivatives of hydroxyalkoxyamines (3a,b,c) with either 4,6-dichloro-2,5-diformamidopyrimidine (5) or 4,6-dichloro-5-formamidopyrimidine (31) and subsequent cyclization of the resultant 6-(alkoxyamino)pyrimidines (6, 17, 32, 35) by heating with diethoxymethyl acetate afforded 9-alkoxy-6-chloropurines (7, 18, 33, 36), which were converted subsequently to 9-(3-hydroxypropoxy)- and 9-[3-hydroxy-2-(hydroxymethyl)propoxy] derivatives of guanine, 2-amino-6-chloropurine, 2-amino-6-alkoxypurines, 2-aminopurine, 2,6-diaminopurine, adenine, hypoxanthine, and 6-methoxypurine (8, 12, 13, 19-21, 23-26, 34, 37-39). Carboxylic acid esters (9-11, 14-16, 27-29) and a cyclic phosphate derivative (22) of the 9-(hydroxyalkoxy)guanines (8, 21) and 2-amino-9-(hydroxyalkoxy)purines (13, 26) were also prepared. The guanine derivatives (8, 21) showed potent and selective activity against herpes simplex virus types 1 and 2 and varicella zoster virus in cell cultures and 8 is more active than acyclovir. Although without significant antiviral activity in cell cultures, the 2-aminopurines (13, 14-16, 26-29) and 2-amino-6-alkoxypurines (12, 23-25) are well absorbed after oral administration to mice and are converted efficiently to the antiviral guanine derivatives (8, 21) in vivo.
Ligation with T4 RNA ligase of an oligodeoxyribonucleotide to covalently-linked cross-sectional base-pair analogues of short, normal, and long dimensions (1991)

Compounds that are covalent analogues of nucleic acid base pairs of normal, long, and short C1' to C1' dimensions [B. Devadas and N.J. Leonard (1990) J. Am. Chem. Soc., 112, 3125-3135.] have been added to the oligodeoxyribonucleotide d(A)6 with bacteriophage T4 RNA ligase as a prelude to placing them at defined loci within nucleic acid duplexes. Analogue cross sections that represent a normal Watson-Crick base pair as well as a pyrimidine-pyrimidine and a purine-purine apposition were ligated in modest yields (approximately 20%) to the oligonucleotide. Ligation conditions were optimized for each analogue, and the cross section was joined to only a single oligonucleotide in each case. The structures of the ligated products were proved by HPLC, enzymatic degradation, and spectroscopic analyses.
Transpupillary diode laser retinopexy in dogs: ophthalmoscopic, fluorescein angiographic and histopathologic study (2003)

The diode laser effectively produces lesions suitable for retinopexy in both the nontapetal, pigmented fundus and the tapetal fundus, although variably so in the latter region. Initial laser settings of 100-150 mW/200 mS for the pigmented fundus, and 150 mW/200-300 mS for the peripheral tapetal fundus are recommended, and the clinician should gradually increase time interval settings to achieve a grayish-white lesion in the nontapetum, and a bronze to slightly black lesion in the tapetal fundus. If possible, retinopexy should be applied to the peripheral tapetal area or tapetal/nontapetal junction.
Pedestal antiresonant reflecting waveguides for robust coupling to microsphere resonators and for microphotonic circuits (2000)

Strip-line pedestal antiresonant reflecting waveguides are high-confinement, silica integrated optical waveguides in which the optical modes are completely isolated from the substrate by thin high-index layers. These waveguides are particularly well suited for whispering-gallery mode excitation in high-Q microspheres. They can also be used in microphotonic circuits, such as for microring resonators. The theory and design of these structures are highlighted. Experiments that show high coupling efficiency to microspheres are also demonstrated.
Kisspeptin/GPR54 system as potential target for endocrine disruption of reproductive development and function (2009)

Kisspeptins, the products of Kiss1 gene acting via G protein-coupled receptor 54 (also termed Kiss1R), have recently emerged as essential gatekeepers of puberty onset and fertility. Compelling evidence has now documented that expression and function of hypothalamic Kiss1 system is sensitive not only to the activational effects but also to the organizing actions of sex steroids during critical stages of development. Thus, studies in rodents have demonstrated that early exposures to androgens and oestrogens are crucial for proper sexual differentiation of the patterns of Kiss1 mRNA expression, whereas the actions of oestrogen along puberty are essential for the rise of hypothalamic kisspeptins during this period. This physiological substrate provides the basis for potential endocrine disruption of reproductive maturation and function by xeno-steroids acting on the kisspeptin system. Indeed, inappropriate exposures to synthetic oestrogenic compounds during early critical periods in rodents persistently decreased hypothalamic Kiss1 mRNA levels and kisspeptin fibre density in discrete hypothalamic nuclei, along with altered gonadotropin secretion and/or gonadotropin-releasing hormone neuronal activation. The functional relevance of this phenomenon is stressed by the fact that exogenous kisspeptin was able to rescue defective gonadotropin secretion in oestrogenized animals. Furthermore, early exposures to the environmentally-relevant oestrogen, bisphenol-A, altered the hypothalamic expression of Kiss1/kisspeptin in rats and mice. Likewise, maternal exposure to a complex cocktail of endocrine disruptors has been recently shown to disturb foetal hypothalamic Kiss1 mRNA expression in sheep. As a whole, these data document the sensitivity of Kiss1 system to changes in sex steroid milieu during critical periods of sexual maturation, and strongly suggest that alterations of endogenous kisspeptin tone induced by inappropriate (early) exposures to environmental compounds with sex steroid activity might be mechanistically relevant for disruption of puberty onset and gonadotropin secretion later in life. The potential interaction of xeno-hormones with other environmental modulators (e.g., nutritional state) of the Kiss1 system warrants further investigation.
Transcutaneous vaccination via laser microporation (2012)

Driven by constantly increasing knowledge about skin immunology, vaccine delivery via the cutaneous route has recently gained renewed interest. Considering its richness in immunocompetent cells, targeting antigens to the skin is considered to be more effective than intramuscular or subcutaneous injections. However, circumvention of the superficial layer of the skin, the stratum corneum, represents the major challenge for cutaneous immunization. An optimal delivery method has to be effective and reliable, but also highly adaptable to specific demands, should avoid the use of hypodermic needles and the requirement of specially trained healthcare workers. The P.L.E.A.S.E. (Precise Laser Epidermal System) device employed in this study for creation of aqueous micropores in the skin fulfills these prerequisites by combining the precision of its laser scanning technology with the flexibility to vary the number, density and the depth of the micropores in a user-friendly manner. We investigated the potential of transcutaneous immunization via laser-generated micropores for induction of specific immune responses and compared the outcomes to conventional subcutaneous injection. By targeting different layers of the skin we were able to bias polarization of T cells, which could be modulated by addition of adjuvants. The P.L.E.A.S.E. device represents a highly effective and versatile platform for transcutaneous vaccination.
Correlation between Oxytocin Receptor Concentration and Responsiveness to Oxytocin in Pregnant Rat Myometrium: Effects of Ovarian Steroids* (1983)

Marked changes in the uterine binding of oxytocin (OT) occur in rats at the time of parturition or after treatment of ovariectomized rats with estrogen or progesterone. To ascertain that these binding sites represent the biological receptors for OT, we measured the uterine response to OT in various groups of rats in which specific OT binding was also determined. Intact pregnant rats and rats ovariectomized on day 20 of gestation and treated thereafter with oil, estradiol benzoate (5 micrograms/24 h), progesterone (5 mg/24 h), or estradiol and progesterone together had indwelling balloons inserted on day 20 for the recording of uterine response to either iv bolus injections or iv infusions of OT. The uterus was removed 24-48 h after balloon insertion, and OT binding to the particulate fraction as well as nuclear estrogen and cytosolic estrogen receptor concentrations were determined. An inverse correlation (r2 = 0.758) was found between the concentration of OT-binding sites and the threshold dose of OT, and a linear correlation was found between the concentration of binding sites and the uterine activity induced by OT infusion (r2 = 0.852). We conclude, therefore, that the high affinity (Kd, 1-2 nM) binding sites for OT represent the physiological receptors. The concentration of these sites increased progressively during estrogen treatment. Progesterone completely inhibited this estrogen-induced rise. After ovariectomy, there was a modest, but significant, increase in OT receptor concentration which also was prevented by progesterone. The increase in OT receptor concentration was correlated with the estrogen receptor concentration in intact pregnant and estrogen-treated ovariectomized animals, but not in the other groups of animals. The apparent affinity of the receptors for OT was not significantly affected by hormone treatment. We conclude that the concentration of receptors is a major factor controlling the uterine responsiveness to OT, and that the receptor concentrations are regulated by ovarian hormones in a manner related to estrogen receptor activation. In addition, estrogen appeared to enhance the coupling of OT receptor occupancy to the tissue response to OT.
Gold Nanoparticles in Organic Capsules: A Supramolecular Assembly of Gold Nanoparticles and Cucurbituril (2007)

Gold nanoparticles (<or=1 nm) have been encapsulated inside cucurbit[7]uril (CB[7]) by vapor deposition or chemical reduction in aqueous solutions. CB[7] has unique host properties compared with CB[5] and CB[6]. The particle size distribution obtained with CB[5] and CB[6] is similar to that obtained in the absence of CBs and the particles obtained are much too large to be incorporated inside the organic capsules. When gold nanoparticles are prepared inside CB[7] the resulting supramolecular assembly has shape-selective properties for gold interactions with amines, cyanide, and quaternary ammonium ions. Thus, CB[7] has the potential to be used in applications such as selective adsorption, sensing, and catalysis.
Performance comparison of dynamic policies for remote caching (1993)

Abstract In a distributed system, data servers (file systems and databases) can easily become bottlenecks. We propose an approach to offloading data access requests from overloaded data servers to nodes that are Idle or less busy. This approach is referred to as remote caching , and the idle or less busy nodes are called mutual servers as they help out the busy server nodes on data accesses. In addition to server and client local caches, frequently accessed data are cached in the main memory of mutual servers, thus improving the data access time in the system. We evaluate several data propagation strategics among data servers and mutual servers. These include policies in which senders are active/passive and receivers are active/passive in initiating data propagation. For example, an active sender takes the initiative to offload data onto a passive receiver. Simulation results show that the active‐sender/passive‐receiver policy is the method of choice In most cases. Active‐Sender policies are best able to exploit the main memory of other Idle nodes in the expected normal condition where some nodes are overloaded and others are less loaded. AH active policies perform far better than the policy without remote caching even in the degenerated case where each node is equally loaded.
Separation And Dereverberation Performance Of Frequency Domain Blind Source Separation (2001)

In this paper, we investigate the separation and dereverberation performance of frequency domain Blind Source Separation (BSS) based on Independent Component Analysis (ICA) by measuring impulse responses of a system. Since ICA is a statistical method, i.e., it only attempts to make outputs independent, it is not easy to predict what is going on in a BSS system physically. We therefore investigate the detailed components in the processed signals of a whole BSS system from a physical and acoustical viewpoint. In particular, we focus on the direct sound and reverberation in the target and jammer signals. As a result, we reveal that the direct sound of a jammer can be removed and the reverberation of the jammer can be reduced to some degree by BSS, while the reverberation of the target cannot be reduced. Moreover, we show that a long frame length causes pre-echo noise, and this damages the quality of the separated signal.