gebhart/patrepeval huggingface dataset:
Myocardial extracellular matrix remodeling in transgenic mice overexpressing tumor necrosis factor α can be modulated by anti-tumor necrosis factor α therapy (2000)

Myocardial fibrosis caused by maladaptive extracellular matrix (ECM) remodeling is implicated in the dysfunction of the failing heart. Matrix metalloproteinases (MMPs) regulate ECM remodeling, and are regulated by cytokines. Transgenic mice with cardiac-specific overexpression of tumor necrosis factor alpha (TNF-alpha) (TNF1.6) develop heart failure. We hypothesized that modulation of TNF-alpha and/or MMP activity might alter the myocardial ECM remodeling process and the development of heart failure. To test this hypothesis, we took advantage of the TNF1.6 mice and studied soluble and total collagens and collagen type profiling by using hydroxyproline quantification, Sircol collagen assay, Northern blot analysis, and immunohistochemistry and studied myocardial function by using echocardiography. Progressive ventricular hypertrophy and dilation in the TNF1.6 mice were accompanied by a significant increase in MMP-2 and MMP-9 activity, an increase in collagen synthesis, deposition, and denaturation, and a decrease in undenatured collagens. In young TNF1.6 mice, these changes in the ECM were associated with marked diastolic dysfunction as demonstrated by significantly reduced transmitral Doppler echocardiographic E/A wave ratio. Anti-TNF-alpha treatment with adenoviral vector expressing soluble TNF-alpha receptor type I attenuated both MMP-2 and MMP-9 activity, prevented further collagen synthesis, deposition and denaturation, and preserved myocardial diastolic function in young, but not old, TNF1.6 mice. The results suggest a critical role of TNF-alpha and MMPs in myocardial matrix remodeling and functional regulation and support the hypothesis that both TNF-alpha and MMPs may serve as potential therapeutic targets in the treatment of heart failure.
The detergent Triton X‐100 induces a death pattern in human carcinoma cell lines that resembles cytotoxic lymphocyte‐induced apoptosis (1994)

The detergent Triton X-100 (TX100) was used with the intention to establish a model for necrotic cell death. However, TX100 was found to induce apoptotic and necrotic death in prostate and colon cancer cell lines. Apoptosis was characterized by the typical morphological features and internucleosomal DNA fragmentation. The rapid onset within 60 min and the lack of inhibition by cycloheximide indicated that apoptosis induced by TX100 was not dependent on protein synthesis. Removal of extracellular calcium blocked internucleosomal DNA fragmentation. This pattern of cell death shows a striking similarity to the effect of cytotoxic lymphocytes on their target cells.
Measuring bandwidth (1999)

Accurate network bandwidth measurement is important to a variety of network applications. Unfortunately, accurate bandwidth measurement is difficult. We describe some current bandwidth measurement techniques: using throughput, and packet pair. We explain some of the problems with these techniques, including poor accuracy, poor scalability, lack of statistical robustness, poor agility in adapting to bandwidth changes, lack of flexibility in deployment, and inaccuracy when used on a variety of traffic types. The authors solutions to these problems include the use of a packet window to adapt quickly to bandwidth changes, receiver only packet pair to combine accuracy and ease of deployment, and potential bandwidth filtering to increase the accuracy. These techniques are at least as accurate as previously used filtering algorithms, and in some situations, they are more than 37% more accurate.
Interleukin-1 beta suppresses apoptosis in rat ovarian follicles by increasing nitric oxide production. (1995)

A growing body of evidence suggests that intraovarian interleukin-1 beta (IL-1 beta) may play an intermediary role in the ovulatory process. Furthermore, induction of nitric oxide (NO) by IL-1 beta has been reported in a wide variety of tissues. As the majority of ovarian follicles undergo an atretic degeneration process involving apoptotic cell death, we set out to determine whether IL-1 beta rescues follicles from apoptosis and the possible involvement of NO. Preovulatory follicles obtained from PMSG-primed rats were cultured for 24 h in serum-free medium with or without hormone treatments. After culture, follicular apoptotic DNA fragmentation was analyzed by autoradiography of size-fractionated DNA labeled at 3'-ends with [32P]dideoxy-ATP. Follicular NO production was also determined by a colorimetric method. Treatment with IL-1 beta dose-dependently suppressed the spontaneous onset of apoptosis in cultured follicles, but stimulated NO production. In contrast, the addition of IL-1 receptor antagonist eliminated both effects of IL-1 beta, confirming receptor mediation. Follicles treated with sodium nitroprusside, a NO generator or an analog of cGMP, the second messenger for NO, also showed decreased follicle apoptosis. Moreover, the addition of NG-monomethyl-L-arginine, a NO synthase inhibitor, reversed both IL-1 beta stimulation of NO production and suppression of apoptosis, suggesting a mediatory role of NO in these IL-1 beta effects. Gonadotropins also prevent follicle apoptosis. Of interest, treatment with hCG stimulated NO production, and the hCG suppression of follicle apoptosis and stimulation of NO production were partially blocked by cotreatment with IL-1 receptor antagonist, indicating the mediation of endogenous IL-1 beta. Treatment with IL-1 beta also stimulated a small increase in the production of cAMP, estrogen, and progesterone. Taken together, these findings suggest that IL-1 beta is a survival factor for ovarian follicles, and its action is partially mediated via NO and cGMP generation. Moreover, part of the suppressive action of gonadotropins on follicle apoptosis is mediated by endogenously produced IL-1 beta.
Synthesis and Evaluation of Novologues as C-Terminal Hsp90 Inhibitors with Cytoprotective Activity against Sensory Neuron Glucotoxicity (2012)

Compound 2 (KU-32) is a first-generation novologue (a novobiocin-based, C-terminal, heat shock protein 90 (Hsp90) inhibitor) that decreases glucose-induced death of primary sensory neurons and reverses numerous clinical indices of diabetic peripheral neuropathy in mice. The current study sought to exploit the C-terminal binding site of Hsp90 to determine whether the optimization of hydrogen bonding and hydrophobic interactions of second-generation novologues could enhance neuroprotective activity. Using a series of substituted phenylboronic acids to replace the coumarin lactone of 2, we identified that electronegative atoms placed at the meta-position of the B-ring exhibit improved cytoprotective activity, which is believed to result from favorable interactions with Lys539 in the Hsp90 C-terminal binding pocket. Consistent with these results, a meta-3-fluorophenyl substituted novologue (13b) exhibited a 14-fold lower ED(50) for protection against glucose-induced toxicity of primary sensory neurons compared to 2.
Critical Role of Integrin α5β1 in Urokinase (uPA)/Urokinase Receptor (uPAR, CD87) Signaling (2003)

Urokinase-type plasminogen activator (uPA) induces cell adhesion and chemotactic movement. uPA signaling requires its binding to uPA receptor (uPAR/CD87), but how glycosylphosphatidylinositol-anchored uPAR mediates signaling is unclear. uPAR is a ligand for several integrins (e.g. alpha 5 beta 1) and supports cell-cell interaction by binding to integrins on apposing cells (in trans). We studied whether binding of uPAR to alpha 5 beta 1 in cis is involved in adhesion and migration of Chinese hamster ovary cells in response to immobilized uPA. This process was temperature-sensitive and required mitogen-activated protein kinase activation. Anti-uPAR antibody or depletion of uPAR blocked, whereas overexpression of uPAR enhanced, cell adhesion to uPA. Adhesion to uPA was also blocked by deletion of the growth factor domain (GFD) of uPA and by anti-GFD antibody, whereas neither the isolated uPA kringle nor serine protease domain supported adhesion directly. Interestingly, anti-alpha 5 antibody, RGD peptide, and function-blocking mutations in alpha 5 beta 1 blocked adhesion to uPA. uPA-induced cell migration also required GFD, uPAR, and alpha 5 beta 1, but alpha 5 beta 1 alone did not support uPA-induced adhesion and migration. Thus, binding of uPA causes uPAR to act as a ligand for alpha 5 beta 1 to induce cell adhesion, intracellular signaling, and cell migration. We demonstrated that uPA induced RGD-dependent binding of uPAR to alpha 5 beta 1 in solution. These results suggest that uPA-induced adhesion and migration of Chinese hamster ovary cells occurs as a consequence of (a) uPA binding to uPAR through GFD, (b) the subsequent binding of a uPA.uPAR complex to alpha 5 beta 1 via uPAR, and (c) signal transduction through alpha 5 beta 1.
Optically Stimulated Luminescence Response of Al2O3 to Beta Radiation (1999)

High sensitivity dosemeters based on Al2O3:C have been prepared and tested for use as beta dosemeters using optically stimulated luminescence (OSL). Two types of sample were prepared and tested, namely unpolished thick, single crystal chips and thin powder layers on aluminium substrates. The samples were used in two OSL readout modes: (a) cw-OSL using a tungsten lamp, and (b) pulsed-OSL using a Nd:YAG laser. Comparisons were made with TL properties, where possible. The samples were irradiated using a variety of sources, including 147Pm, 204Tl, 90Sr-90Y and 60Co, and under a variety of cover thicknesses. The response per unit Hp(0.07), normalised to 60Co, is compared for each dosemeter type and discussed within the framework of DOELAP and EU recommended limits.
Reintroduction of a normal retinoblastoma gene into retinoblastoma and osteosarcoma cells inhibits the replication associated function of SV40 large T antigen. (1991)

The product of the retinoblastoma (Rb) gene can form complexes with the transforming proteins of small DNA tumor viruses, including SV40 large T antigen (Tag), adenovirus E1A, and the human papilloma virus E7. The strong correlation between their ability to transform and their ability to bind Rb protein suggests that these oncoproteins exert their effect through blocking the Rb function. SV40 Tag causes oncogenic cell transformation of rodent cells, and it is also required for viral DNA replication. In this paper, we investigated the effect of the Rb protein on the SV40 replication associated function of Tag. We present evidence suggesting that the complex formation between Rb and Tag interferes with the viral DNA replication. In Y79 retinoblastoma and Saos-2 osteosarcoma cells, which lack functional Rb protein, a SV40 based plasmid vector, pSVEpR4, replicates well. In the same cells reconstituted for Rb expression with an intact Rb gene introduced by retroviral mediated gene transfer, pSVEpR4 replicates to a considerably lower level. The inhibitory effect of Rb protein was surmounted by increasing the intracellular level of Tag. Increasing amounts of Tag in wild-type Rb negative Y79 cells had virtually no effect on SV40 replication. Furthermore, the overexpression of Tag in Rb reconstituted Y79 cells did not alter the growth rate of the cells. These data suggest that Rb protein interacts with Tag and modulates its ability to promote SV40 DNA replication.
Structure and Topology of the Influenza Virus Fusion Peptide in Lipid Bilayers (1995)

The secondary structure of a 20-amino acid length synthetic peptide corresponding to the N terminus of the second subunit of hemagglutinin (HA2) of influenza virus A/PR8/34 and its interaction with phospholipid bilayers are investigated using ESR, Fourier transform infrared (FTIR), and CD spectroscopy. N-terminal spin labeling of the peptide did not affect the secondary structure of the peptide either in solution or when bound to liposomes as revealed by FTIR and CD spectroscopy. ESR spectra show that the mobility of the labeled peptide is dramatically restricted in the presence of phosphatidylcholine liposomes, suggesting a strong binding to the lipid membranes. The N terminus of the peptide penetrates into the membrane and is located within the hydrophobic core. We find an oblique insertion of the peptide into the lipid bilayer with an angle of about 45 degrees between helix axis and membrane plane using FTIR spectroscopy. No gross changes of the peptide's orientation, motion, and secondary structure were observed between pH 7.4 and pH 5.0. A model of the insertion of the fusion sequence of HA2 into a lipid bilayer is presented taking into account recent investigations on the low pH conformation of HA2 (Bullough, P. A., Hughson, F. M., Skehel, J. J., and Wiley, D. C. (1994) Nature 371, 37-43).
Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study (2000)

In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia. Any reduction in HbA(1c) is likely to reduce the risk of complications, with the lowest risk being in those with HbA(1c) values in the normal range (<6.0%).
Minimum-Time Maneuvers of Thrust-Vectored Aircraft (1998)

The new aircraft technology of thrust vectoring (TV) enables the execution of new types of poststall maneuvers. Aircraft agility and e ight safety are greatly enhanced. The objective and main contribution of the present work are the suboptimal solution of minimum-time pitch-reversal (there and back ) and yaw-reversal standard agility comparison maneuvers (SACOM). It is demonstrated that, due to asymmetric and coupling moments at high ® and high ¯, pure pitch and yaw maneuvers are impossible; a full six-degree-of-freedom model must be employed. A novel parametric two-stage suboptimization algorithm was developed to copewith the complexity ofthe optimal control problem. All four aerodynamic and three TV controls are simultaneously active in the execution of a low g load, nearly pure 80-deg pitch-reversal and a 30-deg yaw-reversal SACOM of an F-15B aircraft.
<title>Two-color two-photon excitation of fluorescence</title> (1997)

We observed fluorescence emission from p-terphenyl, 2,5- diphenyl-1,3,4-oxadiazole (PPD) and indole resulting from two-photon excitation with two different wavelengths near 380 and 760 nm. For two-color two-photon (2C2P) excitation the emission spectra and intensity decays were the same as observed with single photon excitation with an equivalent energy near 250 nm. The two-color two-photon induced emission was observed when the samples were illuminated with both wavelengths, but only when the ps laser pulses were spatially and temporally overlapped. The signals were typically 50-fold to 1000-fold less for illumination at 380 or 760 nm alone. When illuminated with both wavelengths, and when both beams were simultaneously attenuated to the same extent, the emission intensity depended quadratically on the total illumination power, indicating two-photon excitation. When the illumination intensity at one wavelength was attenuated, the signal depended linearly on the power at each wavelength, indicating the participation of one-photon at each wavelength to the excitation process. For 2C2P excitation with both beams vertically polarized the time- zero anisotropies were larger than possible for single photon excitation. For PPD and p-terphenyl with intensity depended on the polarization of each beam in a manner consistent with co-linear transitions, but more complex behavior was found for indole. These results demonstrate that two-color two-photon excitation can be readily observed with modern ps laser sources. This phenomenon can have numerous applications in the chemical and biomedical sciences, as a method for spatial localization of the measured volume.
Microengineering design and manufacture using the LIGA process (1994)

The need for design rules, new processes and methodologies for both the visualisation and analysis of microcomponents is outlined. Conventional planar microengineering has successfully resulted in producing transducer systems employing cantilevers and diaphragms. Artefacts possessing greater structural heights cannot be produced using this technology. The LIGA process, using X-ray radiation, is capable of producing microstructures in materials such as ceramics, polymers and electrodeposited metals having structural heights of up to 1000 μm and height-to-width aspect ratios of 100:1 to 1000:1. Where less stringent accuracy is required, visible radiation, such as UV and laser, may be used to form the structures. Optical LIGA has been used to produce fluidic valves, microwave couplers, microlens arrays and micro-optic devices. The basic steps in the design, processing and manufacture of LIGA components is described. Attention is drawn to the need to adapt existing finite element software in order to deal with components having small physical dimensions. LIGA microengineered components are handled on a laboratory scale using micromanipulators. A critical factor affecting the adoption of complex microengineered systems is the need for bulk handling and mass assembly techniques to be developed.
Natural Systems for Waste Management and Treatment (1994)

Biologically-based systems for handling waste are gathering international attention as a more reliable, less costly alternative to energy intensive mechanical systems, and are being used by increasing numbers of communities and municipalities. The natural process of waste treatment deals with processing waste and wastewater naturally in streams and the soil. The process in wastewater treatment plants is virtually the same process used in treating the material with bacteria only at a more rapid rate. This results in higher energy consumption and more accumulated sludge than the natural process. This edition features recent advances in the use of wetlands and aquatic systems, the treatment of sludges, and other areas in the field of waste management. It also includes current EPA regulations and coverage of small-scale on-site systems.
Constrained parametric min-cuts for automatic object segmentation (2010)

We present a novel framework for generating and ranking plausible objects hypotheses in an image using bottom-up processes and mid-level cues. The object hypotheses are represented as figure-ground segmentations, and are extracted automatically, without prior knowledge about properties of individual object classes, by solving a sequence of constrained parametric min-cut problems (CPMC) on a regular image grid. We then learn to rank the object hypotheses by training a continuous model to predict how plausible the segments are, given their mid-level region properties. We show that this algorithm significantly outperforms the state of the art for low-level segmentation in the VOC09 segmentation dataset. It achieves the same average best segmentation covering as the best performing technique to date, 0.61 when using just the top 7 ranked segments, instead of the full hierarchy in. Our method achieves 0.78 average best covering using 154 segments. In a companion paper, we also show that the algorithm achieves state-of-the art results when used in a segmentation-based recognition pipeline.
Composition of rubber particles of Hevea brasiliensis, Parthenium argentatum, Ficus elastica, and Euphorbia lactiflua indicates unconventional surface structure (1997)

Natural rubber (cis-1,4-polyisoprene) is formed inside plant cells from allylic diphosphate initiators and isopentenyl diphosphate, and packaged in subcellular rubber particles. In addition to rubber. rubber particles contain proteins. which vary in size in different species. Rubber transferase [EC 2.5.1.20], the enzyme that catalyzes the cis-1,4 polymerization of isoprene into rubber, is particle bound. Since membrane lipids have been identified in extracts of Heivea brasiliensis rubber particles, it has been suggested that rubber particles are covered by a half-unit membrane. We have examined the fatty acid and lipid composition of rubber particles from four rubber producing species. H. brasiliensis, Parthenium argentatum, Ficus elastica, and Euphorbia lactiflua. We demonstrate that although rubber particles from all four species contain significant amounts of phospholipids, glycolipids and sterols. there appears to be insufficient membrane lipid to constitute a half-unit membrane. Our results suggest that the rubber particle surface is a mosaic of protein, conventional membrane lipids and other components. The lipid covering may be a remnant of the rubber particle's origin in a unit membrane, with the addition of non-conventional components. including a large amount of non-phospholipid phosphate containing material. possibly polyisoprene mono- or diphosphate.
Sperm from β1,4-galactosyltransferase-null mice are refractory to ZP3-induced acrosome reactions and penetrate the zona pellucida poorly (1997)

A variety of sperm surface components have been suggested to mediate gamete recognition by binding to glycoside ligands on the egg coat glycoprotein ZP3. The function of each of these candidate receptors is based upon varying degrees of circumstantial and direct evidence; however, the effects on fertilization of targeted mutations in any of these candidate receptors have not yet been reported. In this paper, we describe the effects of targeted mutations in beta1,4-galactosyltransferase, the best studied of the candidate receptors for ZP3. Surprisingly, galactosyltransferase-null (gt[-/-]) males are fertile; however, sperm from gt(-/-) males bind less radiolabeled ZP3 than wild-type sperm, and are unable to undergo the acrosome reaction in response to either ZP3 or anti-galactosyltransferase antibodies, as do wild-type sperm. In contrast, gt(-/-) sperm undergo the acrosome reaction normally in response to calcium ionophore, which bypasses the requirement for ZP3 binding. The inability of gt(-/-) sperm to undergo a ZP3-induced acrosome reaction renders them physiologically inferior to wild-type sperm, as assayed by their relative inability to penetrate the egg coat and fertilize the oocyte in vitro. Thus, although ZP3 binding and subsequent induction of the acrosome reaction are dispensable for fertilization, they impart a physiological advantage to the fertilizing sperm. A second strain of mice was created that is characterized by a loss of of the long galactosyltransferase isoform responsible for ZP3-dependent signal transduction, but which maintains normal levels of Golgi galactosylation. Sperm from these mice show that the defective sperm-egg interactions in gt(-/-) mice are due directly to a loss of the long galactosyltransferase isoform from the sperm surface and are independent of the state of intracellular galactosylation during spermatogenesis.
Solvent-Free Al(OTf)3-Catalyzed Aminolysis of 1,2-Epoxides by 2-Picolylamine:  A Key Step in the Synthesis of Ionic Liquids (2004)

Beta-Amino alcohols N-2'-pyridylmethyl substituted 3 have been prepared in excellent yields under mild conditions by the first Lewis acid-catalyzed aminolysis of 1,2-epoxides 1 with the bihaptic amine 2-picolylamine (2) with use of 5 mol % of Al(OTf)(3) under solvent-free conditions. As a representative of a new class of ionic liquids, cis-5-[(4'-methylphenyl)sulfonyl]-1,2,3,4,4a,5,6,11a-octahydropyrido[1,2-a]quinoxalin-11-ium methanesulfonate (6) and its chloride derivative 7 have been synthesized under environmentally friendly conditions by the one-pot aminolysis of cyclohexene oxide (1a) with 2 and intramolecular cyclization of the resulting 2-[(pyridin-2'-yl)methylamino]cyclohexanol (3a).