gebhart/patrepeval huggingface dataset:
Kinetics of entry and distribution of 5-fluorouracil in cerebrospinal fluid and brain following intravenous injection in a primate. (1973)

Summary The distribution of systemically or locally administered 5-fluorouracil-2-14C (5-FU) in brain and cerebrospinal fluid (CSF) of the monkey (Macaca mulatta) has been investigated. Following controlled i.v. injection, there was rapid penetration of the 5-FU into brain and CSF, concomitant with a rapid loss of 5-FU from the systemic plasma compartment. CSF repeatedly sampled from various sites (lumbar, cisternal, intraventricular, and cortical surface) displayed characteristic and different kinetic profiles (drug concentrations versus time) following initial i.v. injection of 5-FU. Despite the fact that 91% of the injected dose of 5-FU was cleared from the vascular compartment within 5 min after the start of the i.v. injection (5 ml at 1.086 ml/min) and 98% of the injected dose was cleared by 1 hr, approximately 0.126% of the total administered dose represented the average integrated content of the drug in the entire CSF compartment over the experimental hr. Similarly, the average integrated content of the drug in the brain over the experimental hr represented 0.172% of the total administered dose of 5-FU, as determined by sampling cerebral and cerebellar cortex, subcortical cerebral and cerebellar white matter, striatum, pons, and medulla oblongata. Labeled 5-FU gained access to the CSF from the plasma by simple diffusion. The average integrated concentration of 5-FU in CSF over the experimental hr was increased by 48% when the rate of i.v. injection was increased fourfold. As demonstrated by bilateral perfusion over the exposed cerebral cortex or by bilateral ventriculocisternal perfusion, 5-FU in the CSF was an adequate source for delivery of the drug to contiguous brain tissue. Studies of the regional brain contents of 5-FU following combined i.v. and ventriculocisternal administration of the drug are presented, together with investigations of the physicochemical and metabolic characteristics of the drug. Our studies provide in the primate a model for the determination of the kinetics of distribution of antineoplastic agents in brain and CSF following i.v. administration or following perfusion into the CSF pathway.
Systematic humanization of yeast genes reveals conserved functions and genetic modularity (2015)

To determine whether genes retain ancestral functions over a billion years of evolution and to identify principles of deep evolutionary divergence, we replaced 414 essential yeast genes with their human orthologs, assaying for complementation of lethal growth defects upon loss of the yeast genes. Nearly half (47%) of the yeast genes could be successfully humanized. Sequence similarity and expression only partly predicted replaceability. Instead, replaceability depended strongly on gene modules: Genes in the same process tended to be similarly replaceable (e.g., sterol biosynthesis) or not (e.g., DNA replication initiation). Simulations confirmed that selection for specific function can maintain replaceability despite extensive sequence divergence. Critical ancestral functions of many essential genes are thus retained in a pathway-specific manner, resilient to drift in sequences, splicing, and protein interfaces.
Inhibitory effects of fumagillin and its analogue TNP-470 on the function, morphology and angiogenesis of an oestrogen-induced prolactinoma in Fischer 344 rats (1996)

The process of angiogenesis occurs in many physiological states, but it is also essential for the growth of solid tumours and metastasis formation. An abnormal arterial vascularization has been shown in prolactin-secreting pituitary adenomas induced by prolonged treatment with oestrogens in Fischer 344 (F344) rats. It is thought that anti-angiogenic agents might be useful in therapy for these tumours. Fumagillin and its analogue TNP-470 are known to inhibit endothelial cell proliferation selectively, but their effect on lactotroph cell secretory function and prolactinoma formation has not yet been described. The aim of the present study was to examine the effects of fumagillin and TNP-470 on prolactin secretion, and morphological and vascular changes within the anterior pituitary in long-term oestrogen-treated male F344 rats in vivo and in vitro. As expected, 7 weeks after s.c. implantation of Silastic tubes containing 10 mg diethyl-stilboestrol (DES), a very high rise in serum prolactin levels was found. Both angiogenesis inhibitors injected s.c. at doses of 10 mg/kg body weight for 24 days attenuated the stimulatory effect of DES on prolactin production and release. They also diminished prolactin cell density and inhibited cell proliferation expressed as the number of anterior pituitary cells labelled with bromodeoxyuridine (BrdU), but the effect of TNP-470 was minor compared with fumagillin. Both angioinhibitors suppressed neo-vascularization within the anterior pituitary with similar potency but, on the other hand, they did not affect DES-induced increases in prolactin secretion from cultured rat pituitary cells and cell proliferation in vitro. In conclusion, our results provide strong evidence for the anti-tumour and anti-prolactin activity of angiogenesis inhibitors in the experimentally oestrogen-induced pituitary adenoma; this might be mediated indirectly through the inhibition of angiogenesis.
Simultaneous correlation of cytokine production with Treg and Th17 cell proliferation (138.21) (2010)

Abstract Functionally-polarized CD4+ T cell subsets have been identified based on their distinctive patterns of cytokine secretion, transcription factor expression and function. As a signature cytokine, Th17 express high levels of interleukin 17A (IL-17) whereas Treg are characterized by the expression of the Foxp3 transcription factor. In the mouse system TGFb is required for the production of IL-17A, although additional cytokines are produced including Th1 (IL-2, IFNg) and Th2 (IL-4, IL-10 ) cytokines. The goal of the experiment was to evaluate the correlation of cell cycle (VFSE), cytokine production via both CBA and intracellular staining, Foxp3 expression (Treg), and cytokine-induced phosphorylation events. Multiple fixation and permeabilization conditions were used to allow resolution of intracellular cytokines, Foxp3, and phospho-proteins. FoxP3+ CD4 T cells were present at initiation of culture and were shown to divide by appearing on subsequent VFSE peaks. IL-17A began to appear after day 2 and was restricted to newer generations of cells, unlike FoxP3 which was expressed at time 0 and restricted to the older generations. Further analysis showed the IL-17A population coexpressed IL-2 at day 2, but the populations diverged upon maturation, becoming mutually exclusive by day 4. Analysis of Stat5 phosphorylation revealed heterogeneous responses to secreted cytokines, with newer generations of cells showing the most robust phosphorylation responses.
Monocyte suppressor factor is plasminogen activator inhibitor inhibition of membrane bound but not soluble IL-1. (1989)

Human monocytes cultured in monolayer for 6 days were found to secrete a factor that suppressed the T cell proliferative response to soluble Ag and to alloantigens. The elaboration of this monocyte suppressor factor (MSF) was not inhibited by indomethacin. It has an apparent Mr of 50 to 60 kDa. It does not inhibit soluble IL-1 in the murine thymocyte costimulator assay but does inhibit the activity of membrane bound IL-1, which we observed to be almost exclusively IL-1 alpha. MSF contains elevated amounts of plasminogen activator inhibitor (PAI) when measured either as bioactivity or in an ELISA. Its immunosuppressive properties are inhibited by anti-PAI antibody. Furthermore, the eluate but not the effluent of an anti-PAI immunoabsorbent column contains all of the immunosuppressive activity. Based on these data we suggest that MSF is, in fact, PAI and postulate that the mechanism of action is inhibition of the plasmin cascade, thereby preventing the release of membrane bound IL-1. This suggests that monocytes possess an autoregulatory circuit that may have implications for the kinetics of the inflammatory response.
Trisubstituted Imidazoles with a Rigidized Hinge Binding Motif Act As Single Digit nM Inhibitors of Clinically Relevant EGFR L858R/T790M and L858R/T790M/C797S Mutants: An Example of Target Hopping (2017)

The high genomic instability of non-small cell lung cancer tumors leads to the rapid development of resistance against promising EGFR tyrosine kinase inhibitors (TKIs). A recently detected triple mutation compromises the activity of the gold standard third-generation EGFR inhibitors. We have prepared a set of trisubstituted imidazoles with a rigidized 7-azaindole hinge binding motif as a new structural class of EGFR inhibitors by a target hopping approach from p38α MAPK inhibitor templates. On the basis of an iterative approach of docking, compound preparation, biological testing, and SAR interpretation, robust and flexible synthetic routes were established. As a result, we report two reversible inhibitors 11d and 11e of the clinically challenging triple mutant L858R/T790M/C797S with IC<sub>50</sub> values in the low nanomolar range. Furthermore, we developed a kinome selective irreversible inhibitor 45a with an IC<sub>50</sub> value of 1 nM against the EGFR L858R/T790M double mutant. Target binding kinetics and metabolic stability data are included. These potent mutant EGFR inhibitors may serve as a basis for the development of structurally novel EGFR probes, tools, or candidates.
The Production of Uranium by the Reduction of UF4 by Mg (1945)

Abstract : Due to difficulties encountered in the production of calcium metal in adequate quantity and of adequate purity at low cost, it became desirable to replace calcium by a cheaper metal in the production of uranium. Because of the heats of formation of its compounds, its relative stability in air, and its cheapness in high purities, magnesium was the best suited metal for the purpose. Since the heat of reaction of the reduction of UF4 by Mg was not sufficient to melt the products, it was necessary to add heat to the system. This was done in experimental studies both by preheating the reactants before reaction was initiated and by the use of a simultaneous auxiliary reaction producing more heat than the primary reaction. For the latter purpose the reductions of KClO3, K2S2O8 and of other salts by Mg were suitable reactions. The use of 'boosters' or auxiliary oxidants involved extra work and materials, thus increasing costs and offering additional opportunity for contamination, hence the preheating of the reactants was adopted for large scale production.
Synthesis and characterization of hydroxy‐bisphosphonate micrometer‐sized particles by dispersion polymerization of a new styrylbisphosphonate monomer (2013)

Abstract Bisphosphonates (BPs) are nonhydrolyzable pyrophosphate (P‐O‐P) analogs possessing two phosphonate groups linked to a single carbon (P‐C‐P). The hydroxy‐bisphosphonates (hydroxyBPs) are obtained when the hydroxy group is also linked to this bridging carbon. Their ability to form bidentate or tridentate chelates with calcium ions results in a high affinity to hydroxyapatite (HAP) in dentin, enamel and bones. In this study, we designed and prepared crosslinked poly(styrylbisphosphonate) (PStBP) micrometer‐sized particles by dispersion polymerization of the styrylbisphosphonate (StBP) and ethylene glycol dimethacrylate (EDMA) monomers. The new StBP monomer was synthesized in an efficient one‐pot synthesis using tris(trimethylsilyl)phosphite as the phosphorus source followed by methanolysis. The StBP monomer was successfully isolated and characterized as tri‐sodium salt. Polymerization of the StBP monomer was carried out in two steps: in situ conversion of the tri‐sodium StBP monomer back to its acid form, followed by radical dispersion polymerization in the presence of the crosslinker EDMA monomer. The resulting crosslinked PStBP micrometer‐sized particles retained the unique high affinity of the hydroxy‐bisphosphonate side groups to calcium ions and exhibited good adhesive properties to HAP. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013
Variant of<i>TYR</i>and Autoimmunity Susceptibility Loci in Generalized Vitiligo (2010)

We observed associations between generalized vitiligo and markers implicating multiple genes, some associated with other autoimmune diseases and one (TYR) that may mediate target-cell specificity and indicate a mutually exclusive relationship between susceptibility to vitiligo and susceptibility to melanoma.
Instance-based Anomaly Method for Android Malware Detection (2013)

The usage of mobile phones has increased in our lives because they offer nearly the same functionality as a personal computer. Besides, the number of applications available for Android-based mobile devices has increased. Android application distribution is based on a centralized market where the developers can upload and sell their applications. However, as it happens with any popular service, it is prone to misuse and, in particular, malware writers can use this market to upload their malicious creations. In this paper, we propose a new method that, based upon several features that are extracted from the AndroidManifest file of the legitimate applications, builds an anomaly detection system able to detect malware.
Improvement of the Heat Balance in Combined Blowing Process of the LD Converter (1985)

Tests of post combustion of CO gas in 15 t pilot converter and 160 t and 250 t commercial combined blowing converter were carried out for aiming to improve heat balance.And also coal injection test through top lance with post combustion system was carried out in 15 t pilot converter with bottom gas stirring.Following results were obtained.(1) The optimum amount of oxygen for post combustion was about 20% of total oxygen rate, and the jet angle of 3035° was desirable for obtaining the good condition of post combustion.(2) The heat transfer efficiency of post combustion to metal bath was 70 to 100%.Accordingly around 10% increase of scrap ratio was obtained.(3) In the case of blasting of pulverized coal on metal surface, the heat transfer was nearly equal to the theoretical value and the scrap ratio increased in proportion to the amount of coal added.
Generalized Algorithms for Distribution Feeder Deployment and Sectionalizing (1980)

Increasing effort is being focused on automated remote control of distribution feeder deployment and sectionalizing to improve service restoration time to unfaulted feeder sections and for transferring load between feeders. Digital processor algorithms which determine fault location and generate switching instructions automatically based on tree searching techniques utilizing switch tables that can be readily defined by an operator are described. Simulation results for fault location, fault isolation, and service restoration, including balancing between feeders using an illustrative simplified feeder configuration are shown.
Myc confers androgen-independent prostate cancer cell growth (2003)

Prostate cancer is one of the most diagnosed and mortal cancers in western countries. A major clinical problem is the development of androgen-independent prostate cancer (AIPC) during antihormonal treatment. The molecular mechanisms underlying the change from androgen dependence to independence of these tumors are poorly understood and represent a challenge to develop new therapies. Based on genetic data showing amplification of the c-myc gene in AIPC, we studied the ability of c-myc to confer AIPC cell growth. Human androgen-dependent prostate cancer cells overexpressing c-myc grew independently of androgens and presented tumorigenic properties in androgen-depleted conditions. Analysis of signalling pathways by pharmacological inhibitors of the androgen receptor (AR) or by RNA interference directed against AR or c-myc showed that c-myc acted downstream of AR through multiple growth effectors. Thus c-myc is required for androgen-dependent growth and following ectopic expression can induce androgen-independent growth. Moreover, RNA interference directed against c-myc showed that growth of human AIPC cells, AR-positive or -negative, required c-myc expression. Furthermore, we showed that c-myc-overexpressing cells retain a functional p53 pathway and thus respond to etoposide.
Interworking between the Session Initiation Protocol (SIP) and the Extensible Messaging and Presence Protocol (XMPP): Groupchat (2015)

This document defines a bidirectional protocol mapping for the exchange of instant messages in the context of a multi-party chat session among users of the Session Initiation Protocol (SIP) and users of the Extensible Messaging and Presence Protocol (XMPP). Specifically, this document defines a mapping between the SIP-based Message Session Relay Protocol (MSRP) and the XMPP Multi-User Chat (MUC) extension.
Growth and ellipsometric characterizations of highly (111)-oriented Bi2Ti2O7 films on platinized silicon by metal organic decomposition method (2008)

Optical properties and electronic structure of Bi2Ti2O7 (BTO) films on platinized silicon substrates have been investigated using near-infrared-ultraviolet spectroscopic ellipsometry. The optical dispersion in the photon energy range of 0.73–5.8eV has been extracted by fitting the experimental data with a four-phase layered model. The Tauc–Lorentz dispersion function has been fundamentally applied and describes the optical response of the BTO films well. The refractive index in the transparent region can be reasonably fitted by a single oscillator function and the maximum electronic transition occurs near 4.2eV for the BTO material. The long wavelength refractive index n(0) can be estimated to about 1.7 at zero point. The fundamental band gap energy was determined to be about 3.2eV, which was supported by different theoretical evaluation methods. The present results can be important for future applications of BTO-based electro-optics and optoelectronic devices.
Acute surface‐induced thrombosis in the canine <i>ex vivo</i> model: Importance of protein composition of the initial monolayer and platelet activation (1986)

The initial events occurring at the blood-polymer interface were examined using a canine ex vivo arteriovenous shunt model. Thrombogenic (fibrinogen) and nonthrombogenic (albumin) proteins were preadsorbed on poly(vinyl chloride), polyethylene, and silicone rubber shunt surfaces, and the blood responses were analyzed using the platelet deposition profile as an indicator of surface thrombogenicity. The distributions of preadsorbed protein molecules on the various polymer surfaces were studied using an immunogold bead (colloidal gold particles coated with antibodies) staining technique and shown to be homogeneous. A sequential protein adsorption technique was developed to probe the nature of competitive protein adsorption and to observe the effect of surface protein concentration on thrombogenicity. The thrombogenicity of a surface was determined by the composition of the initial protein layer rather than the total concentration of protein on the polymer surfaces. The composition of this layer determines the extent of platelet activation and the adhesive strength between platelets and the polymer surface.
Web analytics and the art of data summarization (2011)

Web Analytics has become a critical component of many business decisions. With an ever growing number of transactions happening through web interfaces, the ability to understand and introspect web site activity is critical. In this paper, we describe the importance and intricacies of summarization for analytics and report generation on web log data. We specifically elaborate on how summarization is exposed in Splunk and discuss analytics search design trade-offs.
A Novel Timing Synchronization Method for OFDM Systems (2010)

In this letter, a novel timing offset estimation method is presented for orthogonal frequency division multiplexing (OFDM) systems. The proposed method is developed on the basis of the cyclic structure of OFDM symbol and uses a new noise subspace based metric to estimate the timing offset. Simulation results show that the proposed method has a significantly higher probability of correct estimation of the timing offset than the other methods in multipath channels.
Fibrinogen heterogeneity: inherited and noninherited (2005)

In this review the authors discuss the noninherited and inherited variations of fibrinogen and the clinical implications (e.g. when determining the risk of cardiovascular disease).
Tight junctions contain oligomeric protein assembly critical for maintaining blood–brain barrier integrity <i>in vivo</i> (2007)

Tight junctions (TJs) are major components of the blood-brain barrier (BBB) that physically obstruct the interendothelial space and restrict paracellular diffusion of blood-borne substances from the peripheral circulation to the CNS. TJs are dynamic structures whose intricate arrangement of oligomeric transmembrane and accessory proteins rapidly alters in response to external stressors to produce changes in BBB permeability. In this study, we investigate the constitutive trafficking of the TJ transmembrane proteins occludin and claudin-5 that are essential for forming the TJ seal between microvascular endothelial cells that inhibits paracellular diffusion. Using a novel, detergent-free OptiPrep density-gradient method to fractionate rat cerebral microvessels, we identify a plasma membrane lipid raft domain that contains oligomeric occludin and claudin-5. Our data suggest that oligomerization of occludin involves disulfide bond formation within transmembrane regions, and that assembly of the TJ oligomeric protein complex is facilitated by an oligomeric caveolin scaffold. This is the first time that distribution of oligomeric TJ transmembrane proteins within plasma membrane lipid rafts at the BBB has been examined in vivo. The findings reported in this study are critical to understand the mechanism of assembly of the TJ multiprotein complex that is essential for maintaining BBB integrity.
Seismic moment and long-period radiation of underground nuclear explosions (1973)

abstract The moment function of an explosion is introduced, using the equivalence of an explosive point source and three mutually perpendicular linear dipoles. The seismic moment of an explosion is the final value, for large times, of the moment function. Its relation to source parameters is similar to that of the moment of an earthquake: M1 = (λ + 2μ)S1D1 (λ, μ = Lamé's parameters, S1 = surface area of a sphere surrounding the explosion in the elastic zone, D1 = static radial displacement on this sphere). From strain observations of other authors (Romig et al., 1969; Smith et al., 1969), the moment of the underground nuclear explosion BENHAM is estimated to be about 1024 dyne cm. This moment value supports the assumption that the source-time function for the long-period radiation from large nuclear explosions (periods greater than about 10 sec) is essentially a step-function. On the other hand, a quantitative estimate of the long-period P-wave spectrum of the explosions JORUM, HANDLEY and MILROW and a comparison with observed spectra of Molnar (1971) for JORUM and HANDLEY and Wyss et al. (1971) for MILROW support the assumption of an impulsive source-time function. This discrepancy, which is typical of current opinions among seismologists, is not resolved. It is concluded that an explosive point source is possibly not a sufficient model for the long-time radiation and the static displacement field of a nuclear underground explosion whose elastic radius is about equal to its depth and which is detonated in a prestressed medium.
Triatomine bugs (Triatominae) (2008)

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