gebhart/patrepeval huggingface dataset:
Pharmacological Studies with 5-Fluorocytosine (1972)

A cylinder plate bioassay for 5-fluorocytosine (5-FC) is described which permits determination of 5-FC concentrations in biological fluids in the presence of amphotericin B. Using this assay, we determined serum concentrations in 12 patients after a single dose of drug and in 8 patients receiving daily 5-FC at 6-hr intervals (4 to 120 days). Drug was detectable in serum as early as 0.5 hr and concentrations were measurable as long as 24 hr after a dose, regardless of renal function. Peak concentrations occurred 6 hr after the initial drug dose, but were seen between 1 and 2 hr after a dose in all patients receiving a minimum of 4 days of therapy. Mild to moderate renal impairment produced marked increases in peak 5-FC concentrations in the serum of a group of eight patients on three different dosage schedules. Five patients were studied before and after amphotericin B-induced renal insufficiency. Peak concentrations increased from 14 to 142% concomitant with the change in renal function. Parallel studies in rabbits confirmed the results in our patients. 5-FC half-life in the serum of 10 rabbits increased from 3.35 +/- 0.27 to 24.63 +/- 0.70 hr after experimentally induced acute renal failure. Concentrations of 5-FC in the cerebrospinal fluid of five patients ranged from 17 to 62 mug/ml and were 74.4 +/- 5.6% of simultaneously determined serum concentrations. The effect of renal function on 5-FC concentrations in cerebrospinal fluid was similar to that seen with serum.
Polymerization of styrene with nickel complex/methylaluminoxane catalytic systems (1998)

Polymerization of styrene using catalytic systems based on nickel derivatives and methylaluminoxane (MAO) was studied. Among tested catalysts, nickel bis(acetylacetonate) and nickel dichloride show the maximum activity. Bis(phosphine)nickel dichlorides exhibit lower activity, depending on the nature of the phosphine ligand. Polymer yields decrease by lowering the catalyst concentration, by increasing the reaction temperature, or by carrying out the polymerization in a polar donor solvent. Weight average molecular weight of most of the prepared polystyrenes ranges from 9000 to 25,000, with polydispersity indexes of 1.6–3.8. However, polystyrene prepared in dioxane solvent exhibits a small fraction of very high molecular weight (about 140,000). From NMR analysis, the products seem generally to be constituted of two polymers with different steric microstructure: atactic polystyrene and partially isotactic polystyrene (ca. 75–85% meso diads). Catalytic site specificity is correlated with the type of nickel ligand, while the effect of reaction temperature is less defined. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 2119–2126, 1998
Signal transduction pathways via guanylin and uroguanylin in stomach and intestine (1997)

Guanylin and uroguanylin are peptides that activate receptor guanylate cyclases (GCs) and elicit increased intestinal secretion. Bacteria that cause traveler's diarrhea produce heat-stable toxins (STs) that mimic this action. Investigation of the distribution and identity of receptor GCs in the gastrointestinal tract of rats revealed that receptors were localized to epithelial cells in stomach and intestine. Clusters of cells in gastric mucosa and enterocytes lining the intestine exhibited specific binding of 125I-labeled ST. Ligated loops of stomach and intestine treated with intraluminal ST had significant increases in guanosine 3',5'-cyclic monophosphate (cGMP), with duodenum exhibiting the greatest response. Expression of guanylate cyclase C (GCC) mRNA and a truncated, GCC-like mRNA was found in both stomach and intestine. Both mRNAs were isolated as cDNAs encoding the GC catalytic domain. The 0.9-kilobase (kb) cDNA is 99.8% identical to GCC, whereas the truncated, 0.75-kb GCC-like cDNA has a 159-nucleotide deletion and is 96.6% identical to GCC at the protein level. Uroguanylin and guanylin mRNAs were detected in stomach and intestine. Uroguanylin mRNA was most abundant in small intestine, whereas guanylin mRNA was highest in large intestine. Thus the stomach and intestine are targets for regulation of transport by guanylin and uroguanylin via cGMP.
Identification of Protein-Protein Interaction Inhibitors Targeting Vaccinia Virus Processivity Factor for Development of Antiviral Agents (2011)

Poxvirus uracil DNA glycosylase D4 in association with A20 and the catalytic subunit of DNA polymerase forms the processive polymerase complex. The binding of D4 and A20 is essential for processive polymerase activity. Using an AlphaScreen assay, we identified compounds that inhibit protein-protein interactions between D4 and A20. Effective interaction inhibitors exhibited both antiviral activity and binding to D4. These results suggest that novel antiviral agents that target the protein-protein interactions between D4 and A20 can be developed for the treatment of infections with poxviruses, including smallpox.
Investigating ultrasonic positioning on mobile phones (2010)

In this paper we evaluate the innate ability of mobile phone speakers to produce ultrasound and the possible uses of this ability for accurate indoor positioning. The frequencies in question are a range between 20 and 22 KHz, which is high enough to be inaudible but low enough to be generated by standard sound hardware. A range of tones is generated at different volume settings on several popular modern mobile phones with the aim of finding points of failure. Our results indicate that it is possible to generate the given range of frequencies without significant distortions, provided the signal volume is not excessively high. This is preceded by the discussion of why such ability on off-the-shelf mobile devices is important for Location Based Services (LBS) applications research. Specifically, this ability could be used for indoor sound trilateration positioning. Such an approach is uniquely characterized by the high accuracy inherent to sound trilateration, with little computational burden on the mobile device, and no specialized hardware or audible noise. Combined with a fast internet connection and other sensors present in modern smartphones, such as accelerometers and magnetometers, our approach confirms mobile phones as a suitable platform for indoor LBS applications.
Origin of surface and metal-induced interface states in InP (1984)

Surface states on $p$- and $n$-type InP UHV-cleaved (110) surfaces and chemically etched (100) surfaces have been determined with the use of surface photovoltage spectroscopy (SPS). No intrinsic surface states are found on cleaved or ion-bombarded surfaces. The origin of extrinsic surface states is attributed to compositional and stoichiometric variations identified by Auger-electron spectroscopy (AES). Chemical treatment, metal deposition, oxidation, and ${\mathrm{Ar}}^{+}$ bombardment of these surfaces produce a host of changes in the interface-state distribution within the InP band gap. Comparison of AES and SPS data from the various interfaces leads to explanation of the origin of the observed states and of their roles in determining interface electronic properties such as Fermi-energy-pinning positions.
Neuronal loss in the hippocampus in Huntington's disease: a comparison with HIV infection. (1993)

The hippocampus is usually affected in primary dementias and the pathological changes may be severe. Knowledge of hippocampal pathology in HIV infection and Huntington's disease (HD), however, is extremely limited. A stereological technique (the optical "disector") has been used to assess neuronal populations in four areas of the hippocampus in 11 patients with HIV infection and in nine patients with HD. The HIV patients died without opportunistic infections or neoplasms affecting the brain; they had HIV encephalitis or minimal changes. The HD cases were all clinically diagnosed, had a positive family history and showed the characteristic lesions in the caudate nucleus. The neuronal counts were compared with those in nine controls. In the granule cell layer of the dentate, CA3 and CA4, there was no significant difference in the neuronal numerical density between the three groups. A striking difference between the HIV and HD groups was seen in the CA1 region. The neuronal numerical density in the CA1 area was significantly lower in the HD patients than in either the HIV patients or the controls (mean (SD) 37.5 (5.0); 70.1 (13.4); 57.9 (15.4) x 10(3) per mm3, p < 0.001 (Students' t test)). This difference represents a neuronal loss of 35%. In all four hippocampal areas the neuronal density was higher in the HIV group than in the controls but the differences were not significant and can be explained by the higher average age of the control group. These findings contribute to the understanding of the mechanism of dementia in both AIDS and in Huntington's disease.
Blind detection of interfering cell data channel power level in 3GPP LTE/LTE-Advanced downlink (2016)

Nowadays wireless cellular networks can be seen as ubiquitous systems used by a majority of the world's population and their usage continues to grow in the future. Continuously higher data rates and shorter latencies are required due to the introduction of new mobile devices and services. In addition, mobile networks are more and more used as a primary connectivity solution in several places. Thus, new technologies are required to improve the capacity and latency of mobile networks. Long Term Evolution (LTE) and LTE-Advanced are technologies standardized by Third Generation Partnership Project (3GPP) with the potential to fulfill these requirements for future mobile networks.&#13;\n&#13;\nLTE/LTE-Advanced cellular networks are usually interference limited, because neighbouring cells use the same frequency band for data transmission. Because of this, several users may experience high interference levels and thus cannot achieve high data rates without proper counteractions. Consequently, advanced techniques to control, suppress or cancel the interference are of interest to be studied for LTE and LTE-Advanced by 3GPP.&#13;\n&#13;\nNetwork Assisted Interference Cancellation and Suppression (NAICS) techniques are currently been studied by 3GPP. One of the recent studies on NAICS is so called blind detection of interfering cell parameters in a user equipment for advanced non-linear receivers. Such receivers have the capability to suppress or cancel interference significantly but they require the knowledge of specific parameters of the interfering cell to perform efficiently. These parameters have to be either signaled by the network or blindly detected from the received signal in user equipment.&#13;\n&#13;\nThe topic of this thesis is to study the feasibility of blind detection of interfering cell's data channel power level, which is crucial knowledge to non-linear receivers. The study is performed at radio link level by using numerical simulations, in which the transmitter and receiver processing are modeled in detail. In addition, also the effects caused by the radio channel to the transmitted signals are modeled. &#13;\n&#13;\nThe performance of one non-linear receiver, namely Symbol Level Interference Cancellation (SLIC) receiver, with blind detection is compared to the performance of SLIC receiver which has the knowledge of all required parameters. While Linear Minimum Mean Squared Error - Interference Rejection Combiner (LMMSE-IRC) receiver operates as the baseline. From the simulation results it can be seen that the blind detector performs well. Consequently this blind detector can be one noteworthy option to avoid signaling of interfering cell's data channel power level.
Free radical chemistry. Part 3. Substituent effects in additions of ethers to fluorinated alkenes (1985)

Systematic studies on free-radical additions of acyclic ethers to hexafluoropropene reveal the influence of steric effects on the competitive formation of mono-, di-, and tri-adducts. It is concluded that ‘capto-dative’ effects are not dominant in systems containing polyfluoroalkyl groups. Remarkably efficient free-radical additions of trialkyl borates, to fluorinated alkenes occur, but in a series X-OMe (X = MeCO, HCO, MeOCO etc.) reactivity is reduced by electron withdrawal.
Involvement of Aldose Reductase in Vascular Smooth Muscle Cell Growth and Lesion Formation After Arterial Injury (2000)

Abnormal proliferation of vascular smooth muscle cells (VSMCs) is an important feature of atherosclerosis, restenosis, and hypertension. Although multiple mediators of VSMC growth have been identified, few effective pharmacological tools have been developed to limit such growth. Recent evidence indicating an important role for oxidative stress in cell growth led us to investigate the potential role of aldose reductase (AR) in the proliferation of VSMCs. Because AR catalyzes the reduction of mitogenic aldehydes derived from lipid peroxidation, we hypothesized that it might be a potential regulator of redox changes that accompany VSMC growth. Herein we report several lines of evidence suggesting that AR facilitates/mediates VSMC growth. Stimulation of human aortic SMCs in culture with mitogenic concentrations of serum, thrombin, basic fibroblast growth factor, and the lipid peroxidation product 4-hydroxy-trans-2-nonenal (HNE) led to a 2- to 4-fold increase in the steady-state levels of AR mRNA, a 4- to 7-fold increase in AR protein, and a 2- to 3-fold increase in its catalytic activity. Inhibition of the enzyme by sorbinil or tolrestat diminished mitogen-induced DNA synthesis and cell proliferation. In parallel experiments, the extent of reduction of the glutathione conjugate of HNE to glutathionyl-1,4-dihydroxynonene in HNE-exposed VSMCs was decreased by serum starvation or sorbinil. Immunohistochemical staining of cross sections from balloon-injured rat carotid arteries showed increased expression of AR protein associated with the neointima. The media of injured or uninjured arteries demonstrated no significant staining. Compared with untreated animals, rats fed sorbinil (40 mg. kg(-1). d(-1)) displayed a 51% and a 58% reduction in the ratio of neointima to the media at 10 and 21 days, respectively, after balloon injury. Taken together, these findings suggest that AR is upregulated during growth and that this upregulation facilitates growth by enhancing the metabolism of secondary products of reactive oxygen species.
Protected .beta.- and .gamma.-aspartic and -glutamic acid fluorides (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProtected .beta.- and .gamma.-aspartic and -glutamic acid fluoridesLouis A. Carpino and El Sayed M. E. MansourCite this: J. Org. Chem. 1992, 57, 23, 6371–6373Publication Date (Print):November 1, 1992Publication History Published online1 May 2002Published inissue 1 November 1992https://pubs.acs.org/doi/10.1021/jo00049a065https://doi.org/10.1021/jo00049a065research-articleACS PublicationsRequest reuse permissionsArticle Views457Altmetric-Citations17LEARN 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
Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function (2006)

Phosphodiesterase-5 (PDE5) inhibitors (sildenafil, tadalafil, and vardenafil) are agents currently in clinical use for nonmalignant conditions. We report the use of PDE5 inhibitors as modulators of the antitumor immune response. In several mouse tumor models, PDE5 inhibition reverses tumor-induced immunosuppressive mechanisms and enables a measurable antitumor immune response to be generated that substantially delays tumor progression. In particular, sildenafil, down-regulates arginase 1 and nitric oxide synthase-2 expression, thereby reducing the suppressive machinery of CD11b+/Gr-1+ myeloid-derived suppressor cells (MDSCs) recruited by growing tumors. By removing these tumor escape mechanisms, sildenafil enhances intratumoral T cell infiltration and activation, reduces tumor outgrowth, and improves the antitumor efficacy of adoptive T cell therapy. Sildenafil also restores in vitro T cell proliferation of peripheral blood mononuclear cells from multiple myeloma and head and neck cancer patients. In light of the recent data that enzymes mediating MDSC-dependent immunosuppression in mice are active also in humans, these findings demonstrate a potentially novel use of PDE5 inhibitors as adjuncts to tumor-specific immune therapy.
Enzyme-Catalyzed Regioselective Hydrolysis of Aspartate Diesters (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnzyme-Catalyzed Regioselective Hydrolysis of Aspartate DiestersKarin A. Stein and Peter L. ToogoodCite this: J. Org. Chem. 1995, 60, 24, 8110–8112Publication Date (Print):December 1, 1995Publication History Published online1 May 2002Published inissue 1 December 1995https://pubs.acs.org/doi/10.1021/jo00129a066https://doi.org/10.1021/jo00129a066research-articleACS PublicationsRequest reuse permissionsArticle Views1053Altmetric-Citations16LEARN 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
Identification of an Interleukin-15α Receptor-binding Site on Human Interleukin-15 (2004)

To identify the epitopes in human interleukin-15 (IL-15) that are responsible for binding to the interleukin-15 receptor alpha chain, antibody and receptor mapping by peptide scanning and site-directed mutagenesis was used. By using peptide scanning, we identified four regions in IL-15. The first region ((85)CKECEELEEKN(95)) is located in the C-D loop and is recognized by a set of non-inhibitory antibodies. The second region ((102)SFVHIVQMFIN(112)) is located in helix D and is recognized by two antibodies that are inhibitory of IL-15 bio-activity but not of IL-15 binding to IL-15Ralpha. The two remaining regions react with a recombinant soluble form of the IL-15Ralpha; the first ((44)LLELQVISL(52), peptide 1) corresponds to a sequence located in the B-helix and the second ((64)ENLII(68), peptide 2) to a sequence located in helix C. The latter is also contained in the epitope recognized by an antibody (monoclonal antibody B-E29) that prevents IL-15 binding to IL-15Ralpha. By site-directed mutagenesis, we confirmed that residues present in peptide 1 (Leu-45, Glu-46, Val-49, Ser-51, and Leu-52) and peptide 2 (Leu-66 and Ile-67) are involved in the binding of IL-15 to IL-15Ralpha. Furthermore, the results presented indicate that residues in the second peptide (Glu-64, Asn-65, and Ile-68) participate in IL-2Rbeta recruitment. This finding could have implications for the dynamics of receptor assembly. These results also indicate that the modes of interaction of IL-15 and IL-2 with their respective alpha chains are not completely analogous. Finally, some of the IL-15 mutants generated in this study displayed agonist or antagonist properties and may be useful as therapeutic agents.
Simpler Network Configuration with State-Based Network Policies (2013)

Operators make hundreds of changes to a network’s router and switch configurations every day—a painstaking, errorprone process. If the network configuration could instead encode different forwarding behavior for different network states a priori, a network controller could automatically alter forwarding behavior when conditions change. To enable this capability, we introduce state-based network policies, which describe how a network’s forwarding behavior should change in response to arbitrary network events. A state-based network policy comprises many tasks, each of which encodes the forwarding behavior for a single network management operation (e.g., intrusion detection) or part of the network (e.g., a sub-organization), and how that behavior should change when network conditions change. Composing these policies produces a networkwide control program that adapts to different operating conditions. We implement state-based network policies in a system called PyResonance and demonstrate with real-world examples and use cases that PyResonance is expressive enough to specify a wide range of network policies and simple enough for many operators to use. Our evaluation based on event traces from the Georgia Tech campus network shows that PyResonance can achieve good performance in operational settings. 1
Epigenetic Events of Disease Progression in Head and Neck Squamous Cell Carcinoma (2006)

Gene silencing through promoter hypermethylation was observed in 5 of 6 cell lines and contributed to primary and progressive events in HNSCC. In addition to genetic alterations of gains and losses, epigenetic events appear to further undermine a destabilized genomic repertoire in HNSCC.
Inhibition of the visual cycle by A2E through direct interaction with RPE65 and implications in Stargardt disease (2010)

Stargardt disease (STGD) is the major form of inherited juvenile macular degeneration. Pyridinium bis-retinoid A2E is a major component of lipofuscin which accumulates in retinal pigment epithelium (RPE) cells in STGD and contributes to the disease pathogenesis. However, the precise role of A2E in vision loss is unclear. Here we report that A2E efficiently inhibits RPE65 isomerohydrolase, a key enzyme in the visual cycle. Subretinal injection of A2E significantly inhibited retinoid isomerohydrolase activity in mice. Likewise, A2E also inhibited isomerohydrolase activity in cells coexpressing RPE65, lecithin retinol acyltransferase (LRAT), and cellular retinaldehyde-binding protein. In vitro isomerohydrolase activity assays confirmed that A2E inhibited enzymatic activity of recombinant RPE65 in a concentration-dependent manner, but did not inhibit LRAT activity. The inhibition type for isomerohydrolase was found to be reversible and competitive with K(i) = 13.6 μM. To determine the direct interaction of A2E with RPE65 protein, fluorescence binding assays were performed. As shown by fluorimetric titration, binding of purified RPE65 with A2E enhanced the bis-retinoid fluorescence. Consistently, the fluorescence of RPE65 decreased upon incubation with A2E. Both of these experiments suggest a direct, specific binding of A2E to RPE65. The binding constant for A2E and purified RPE65 was calculated to be 250 nM. These results demonstrate that A2E inhibits the regeneration of 11-cis retinal, the chromophore of visual pigments, which represents a unique mechanism by which A2E may impair vision in STGD.