gebhart/patrepeval huggingface dataset:
An activity in rat tissues that modifies nitrotyrosine-containing proteins (1998)

Homogenates from rat spleen and lung could modify nitrotyrosine-containing BSA. With incubation, nitrotyrosine-containing BSA lost its epitope to a monoclonal antibody that selectively recognized nitrotyrosine-containing proteins. In the presence of protease inhibitors, the loss of the nitrotyrosine epitope occurred without protein degradation and hydrolysis. This activity was found in supernatant but not particulate fractions of spleen homogenates. The factor was heat labile, was sensitive to trypsin treatment, and was retained after passage through a membrane with a 10-kDa retention. The activity was time- and protein-concentration dependent. The activity increased about 2-fold in spleen extracts with endotoxin (bacterial lipopolysaccharide) treatment of animals, suggesting that the activity is inducible or regulatable. Other nitrotyrosine-containing proteins also served as substrates, while free nitrotyrosine and some endogenous nitrotyrosine-containing proteins in tissue extracts were poor substrates. Although the product and possible cofactors for this reaction have not yet been identified, this activity may be a "nitrotyrosine denitrase" that reverses protein nitration and, thus, decreases peroxynitrite toxicity. This activity was not observed in homogenates from rat liver or kidney, suggesting that there may also be some tissue specificity for the apparent denitrase activity.
Effects of magainins and cecropins on the sporogonic development of malaria parasites in mosquitoes (1989)

Magainins and cecropins are families of peptides with broad antimicrobial and antiparasitic activities derived respectively from the skin of frogs or from giant silk moths. In insects, cecropins function as part of an inducible immune system against a number of bacterial infections. When injected into anopheline mosquitoes previously infected with a variety of Plasmodium species, both magainins and cecropins disrupt sporogonic development by aborting the normal development of oocysts; sporozoites are not formed and the vector cannot transmit the parasite to another host. It may be possible to induce effective transmission-blocking immunity in the mosquito vector by the introduction and expression of genes coding for magainins, cecropins, or similarly acting parasiticidal peptides into the mosquito genome.
l-Ascorbic Acid Potentiates Nitric Oxide Synthesis in Endothelial Cells (1999)

Ascorbic acid has been shown to enhance impaired endothelium-dependent vasodilation in patients with atherosclerosis by a mechanism that is thought to involve protection of nitric oxide (NO) from inactivation by free oxygen radicals. The present study in human endothelial cells from umbilical veins and coronary arteries investigates whether L-ascorbic acid additionally affects cellular NO synthesis. Endothelial cells were incubated for 24 h with 0.1-100 microM ascorbic acid and were subsequently stimulated for 15 min with ionomycin (2 microM) or thrombin (1 unit/ml) in the absence of extracellular ascorbate. Ascorbate pretreatment led to a 3-fold increase of the cellular production of NO measured as the formation of its co-product citrulline and as the accumulation of its effector molecule cGMP. The effect was saturated at 100 microM and followed a similar kinetics as seen for the uptake of ascorbate into the cells. The investigation of the precursor molecule L-gulonolactone and of different ascorbic acid derivatives suggests that the enediol structure of ascorbate is essential for its effect on NO synthesis. Ascorbic acid did not induce the expression of the NO synthase (NOS) protein nor enhance the uptake of the NOS substrate L-arginine into endothelial cells. The ascorbic acid effect was minimal when the citrulline formation was measured in cell lysates from ascorbate-pretreated cells in the presence of known cofactors for NOS activity. However, when the cofactor tetrahydrobiopterin was omitted from the assay, a similar potentiating effect of ascorbate pretreatment as seen in intact cells was demonstrated, suggesting that ascorbic acid may either enhance the availability of tetrahydrobiopterin or increase its affinity for the endothelial NOS. Our data suggest that intracellular ascorbic acid enhances NO synthesis in endothelial cells and that this may explain, in part, the beneficial vascular effects of ascorbic acid.
A post-beamforming 2-D pseudoinverse filter for coarsely sampled ultrasound arrays (2009)

Beamforming artifacts due to coarse discretization of imaging apertures represent a significant barrier against the use of array probes in high-frequency applications. Nyquist sampling of array apertures dictates center-to-center spacing of lambda/2 for elimination of grating lobes in the array pattern. However, this requirement is hard to achieve using current transducer technologies, even at the lower end of high-frequency ultrasonic imaging (in the range 25-35 MHz). In this paper, we present a new design approach for 2-D regularized pseudoinverse (PIO) filters suitable for restoring imaging contrast in systems employing coarsely sampled arrays. The approach is based on a discretized 2-D imaging model for linear arrays assuming scattering from a Cartesian grid in the imaging field of view (FOV). We show that the discretized imaging operator can be represented with a block Toeplitz matrix with the blocks themselves being Toeplitz. With sufficiently large grid size in the axial and lateral directions, it is possible to replace this Toeplitz-block block Toeplitz (TBBT) operator with its circulant-block block circulant (CBBC) equivalent. This leads to a computationally efficient implementation of the regularized pseudoinverse filtering approach using the 2-D fast Fourier transform (FFT). The derivation of the filtering equation is shown in detail and the regularization procedure is fully described. Using FIELD, we present simulation data to show the 2-D point-spread functions (PSFs) for imaging systems employing linear arrays with fine and coarse sampling of the imaging aperture. PSFs are also computed for a coarsely sampled array with different levels of regularization to demonstrate the tradeoff between contrast and spatial resolution. These results demonstrate the well-behaved nature of the PSF with the variation in a single regularization parameter. Specifically, the 6 dB axial and lateral dimensions of the PSF increase gradually with increasing value of the regularization parameter. On the other hand, the peak grating lobe level decreases gradually with increasing value of the regularization parameter. The results are supported by image reconstructions from a simulated cyst phantom obtained using finely and coarsely sampled apertures with and without the application of the regularized 2-D PIO.
Password management (2002)

Problems of password selection and password management are discussed. Using a simple yet powerful model, the author describes ways to select passwords and identifies two techniques of hindering the compromise of a system by guarding the information and algorithms used to validate user passwords. It is pointed out that obtaining access to a system, or to resources on the system, is the first step in attacking the system. Penetration by obtaining, or guessing, a password is a time-honored, and extremely effective, technique for gaining such access; thus, a firm understanding of passwords, their uses, and techniques for password management are essential to the security of any computer system.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Synergistic Effects of Chemical Enhancers and Therapeutic Ultrasound on Transdermal Drug Delivery (1996)

The effects of (i) a series of chemical enhancers and (ii) the combination of these enhancers and therapeutic ultrasound (1 MHz, 1.4 W/cm2, continuous) on transdermal drug transport are investigated. A series of chemical enhancer formulations, including (i) polyethylene glycol 200 dilaurate (PEG), (ii) isopropyl myristate (IM), (iii) glycerol trioleate (GT), (iv) ethanol/pH 7.4 phosphate buffered saline in a 1:1 ratio (50% EtOH), (v) 50% EtOH saturated with linoleic acid (LA/EtOH), and (vi) phosphate buffered saline (PBS), as a control, are evaluated using corticosterone as a model drug. LA/EtOH is the most effective of these enhancers, increasing the corticosterone flux by 900-fold compared to that from PBS. Therapeutic ultrasound (1 MHz, 1.4 W/cm2, continuous) increases the corticosterone permeability from all of the enhancers examined by up to 14-fold (LA/EtOH) and increases the corticosterone flux from the saturated solutions by up to 13,000-fold (LA/EtOH), relative to that from PBS. Similar enhancements are obtained with LA/EtOH with and without ultrasound for four other model drugs, dexamethasone, estradiol, lidocaine, and testosterone. The permeability enhancements for all of these drugs resulting from the addition of linoleic acid to 50% EtOH increase with increasing drug molecular weight. Likewise, the permeability enhancement attained by ultrasound and LA/EtOH relative to passive EtOH exhibits a similar size dependence. A mechanistic explanation of this size dependence is provided. It is suggested that bilayer disordering agents, such as linoleic acid and ultrasound, transform the SC lipid bilayers into a fluid lipid bilayer phase or create a separate bulk oil phase. The difference in diffusivity of a given solute in SC bilayers and in either fluid bilayers or bulk oil is larger for larger solutes, thereby producing greater enhancements for larger solutes.
Recent advances in the fabrication and adhesion testing of biomimetic dry adhesives (2010)

In the past two years, there have been a large number of publications on the topic of biomimetic dry adhesives from modeling, fabrication and testing perspectives. We review and compare the most recent advances in fabrication and testing of these materials. While there is increased convergence and consensus as to what makes a good dry adhesive, the fabrication of these materials is still challenging, particularly for anisotropic or hierarchal designs. Although qualitative comparisons between different adhesive designs can be made, quantifying the exact performance and rating each design is significantly hampered by the lack of standardized testing methods. Manufacturing dry adhesives, which can reliably adhere to rough surfaces, show directional and self-cleaning behavior and are relatively simple to manufacture, is still very challenging—great strides by multiple research groups have however made these goals appear achievable within the next few years.
APR-246 potently inhibits tumour growth and overcomes chemoresistance in preclinical models of oesophageal adenocarcinoma (2015)

APR-246 has significant antitumour activity in OAC. Given that APR-246 is safe at therapeutic levels our study strongly suggests that APR-246 can be translated into improving the clinical outcomes for OAC patients.
Synthesis and biological activity of 5-substituted-2-amino-1,3,4-oxadiazole derivatives (2011)

Electrical energy offers numerous benefits for performing synthesis, including increased reaction rates, enhanced yields, and cleaner chemistries. 5-Substituted-2-amino-1,3,4-oxadiazoles were synthesized directly from the semicarbazone at a platinum electrode under controlled potential electrolysis in an undivided cell assembly in acetonitrile. The compounds were screened for antibacterial and antifungal activity against Staphylococcus aureus, Klebsiella pneumoniae, Pellicularia salmonicolor, and Macrophomina phaseolina.
Difference Confocal Scanning Microscopy (1984)

The properties of type I and confocal scanning microscopes are discussed. It is shown that an enhanced confocal image may be obtained by subtracting the type I from the confocal image. The resulting differential contrast image is found to be very sensitive to variations in object height.
Transcription of the Escherichia coli fliC gene is regulated by metal ions (1991)

luxAB gene fusions in the Escherichia coli genome were used to screen for clones displaying transcriptional changes in the presence of aluminum. One clone was found that contained a luciferase gene fusion in which transcription was increased in the presence of aluminum and which was subsequently shown to be induced by copper, iron, and nickel. Cloning of the metal-regulated gene, hybridization to the ordered phage lambda bank of the E. coli chromosome, and sequencing of DNA adjacent to the luxAB fusion revealed that the insertion occurred within the fliC (hag) gene of E. coli. This gene encodes flagellin, the filament subunit of the bacterial motility organ, and is under the control of several regulatory cascades. These results suggest that environmental metals may play a role in the regulation of the motility potential of E. coli and that this bioluminescent gene fusion clone (or derivatives thereof) may be used to prepare a biosensor for the rapid detection of metal contamination in water samples.
The California Verbal Learning Test – second edition: Test-retest reliability, practice effects, and reliable change indices for the standard and alternate forms (2006)

The California Verbal Learning Test - second edition (CVLT-II) is one of the most widely used neuropsychological tests in North America. The present study evaluated the 1-month test-retest reliability and practice effects associated with the standard and alternate forms of the CVLT-II in a sample of 195 healthy adults. Eighty participants underwent repeat assessment using the standard form of the CVLT-II on both occasions, whereas the remaining 115 individuals received the standard form at baseline and the alternate form at follow-up. Consistent with prior research, results revealed generally large test-retest correlation coefficients for the primary CVLT-II measures in both the standard/standard (range=0.80-0.84) and standard/alternate (range=0.61-0.73) cohorts. Despite exhibiting slightly lower test-retest reliability coefficients, participants in the alternate form group displayed notably smaller practice effects (Cohen's d range=-0.01 to 0.18) on the primary indices relative to individuals who received the standard form on both occasions (Cohen's d range=0.27-0.61). Reliable change indices were also generated and applied to primary CVLT-II variables to determine the base rates of significant improvements (range=2-10%), declines (range=0-7%), and stability (range=85-97%) in performance over time. Overall, findings from this study support the test-retest reliability of the standard and alternate forms of the CVLT-II in healthy adults and may enhance the usefulness of this test in longitudinal neuropsychological evaluations.
Activation of coagulation and angiogenesis in cancer: immunohistochemical localization in situ of clotting proteins and vascular endothelial growth factor in human cancer. (1998)

Thrombin-catalyzed, cross-linked fibrin (XLF) formation is a characteristic histopathological finding in many human and experimental tumors and is thought to be of importance in the local host defense response. Although the pathogenesis of tumor-associated fibrin deposition is not entirely clear, several tumor procoagulants have been described as likely primary stimuli for the generation of thrombin (and XLF) in the tumor microenvironment (TME). In a previous study of a variety of human tumors we have shown that tissue factor (TF) is the major procoagulant. However, the relative contribution to fibrin deposition in the TME of tumor cell TF and host cell TF (eg, macrophage-derived) was not established. In addition, recent evidence has implicated TF in the regulation of the synthesis of the pro-angiogenic factor vascular endothelial growth factor (VEGF) by tumor cells. In the current study we used in situ techniques to determine the cellular localization of XLF, TF, VEGF, and an alternative tumor procoagulant, so-called cancer procoagulant (CP), a cysteine protease that activates clotting factor X. In lung cancer we have found XLF localized predominantly to the surface of tumor-associated macrophages, as well as to some endothelial cells and perivascular fibroblasts in the stromal area of the tumors co-distributed with TF at the interface of the tumor and host cells. Cancer pro-coagulant was localized to tumor cells in several cases but not in conjunction with the deposition of XLF. TF and VEGF were co-localized in both lung cancer and breast cancer cells by in situ hybridization and immunohistochemical staining. Furthermore, a strong relationship was found between the synthesis of TF and VEGF levels in human breast cancer cell lines (r2 = 0.84; P < 0.0001). Taken together, these data are consistent with a highly complex interaction between tumor cells, macrophages, and endothelial cells in the TME leading to fibrin formation and tumor angiogenesis.
Antibody-directed fibrinolysis: a bispecific (Fab')2 that binds to fibrin and tissue plasminogen activator (1990)

A bispecific (Fab')2 molecule was constructed by linking the monovalent Fab' from an anti-fibrin monoclonal antibody to the Fab' from an anti tissue plasminogen activator (tPA, single chain) monoclonal antibody by means of inter-heavy-chain disulfide bonds. An immunochemical complex composed of the bispecific (Fab')2 molecule bound to tPA [tPA-bispecific (Fab')2 complex] was then generated and purified. Its molecular weight was 170 kDa [less than half the molecular weight of a previously described tPA-bispecific antibody complex containing the entire anti-fibrin and anti-tPA immunoglobulin molecules; Runge, M. S., et al. (1987) Trans. Assoc. Am. Phys. 100, 250-255]. The tPA-bispecific (Fab')2 complex was 8.6-fold more efficient in fibrinolysis than tPA alone and 94-fold more potent than urokinase. This enhancement in the fibrinolytic potency of tPA compares favorably with that observed for the bispecific whole-antibody complex. These results suggest that this smaller, less immunogenic molecule is capable of binding both fibrin and tPA with high affinity and of enhancing the thrombolytic efficiency of exogenous and, perhaps, endogenous tPA.
Convenient fluorometric assay for matrix metalloproteinase activity and its application in biological media (1996)

Matrix metalloproteinases (MMPs) are involved in physiological tissue remodeling and pathological conditions like tumour metastasis and joint destruction. Until now, no convenient and sensitive MMP-activity assay in crude media like synovial fluid has been available. Therefore, the highly soluble fluorogenic substrate TNO211 (Dabcyl-Gaba-Pro-Gln-Gly-Leu-Glu(EDANS)-Ala-Lys-NH2), containing the MMP cleavable Gly-Leu bond and EDANS/Dabcyl as fluorophore/quencer combination, was synthesized and characterized as an MMP specific substrate. We show that the fluorogenic assay using TNO211 is sensitive and can detect MMP activity in culture medium from endothelial cells and untreated synovial fluid (SF) from RA and OA patients, and control subjects. MMP activity in SF significantly increased in the order C < OA < RA, thus the frequent use of OA samples as control in studies on RA is debatable.
Identifying Breast Cancer Druggable Oncogenic Alterations: Lessons Learned and Future Targeted Options (2008)

Although the introduction of novel therapies and drug combinations has improved the prognosis of metastatic breast cancer, this disease remains incurable. It is therefore important to develop additional novel therapeutic strategies and agents. Increased understanding of the biology and the molecular alterations present in breast cancer is facilitating the design of targeted therapies directed to oncogenic proteins. Here, we review the signaling pathways and proteins that participate in breast cancer proliferation and survival, with special emphasis in those that are druggable. We will also comment on how the knowledge on the basic pathogenetic processes is translated into drug development strategies that are reaching the breast cancer clinic.
Safety Assessment of Chlorphenesin as Used in Cosmetics (2014)

Chlorphenesin functions as a biocide in cosmetics and is used at concentrations up to 0.32% in rinse-off products and up to 0.3% in leave-on products. The Cosmetic Ingredient Review Expert Panel (Panel) noted that chlorphenesin was well absorbed when applied to the skin of rats; however, any safety concern was minimized because available data demonstrated an absence of toxicity. The Panel concluded that chlorphenesin is safe in the present practices of use and concentration.
Isoproterenol potentiates synaptic transmission primarily by enhancing presynaptic calcium influx via P- and/or Q-type calcium channels in the rat amygdala (1996)

The effects of selective beta-adrenergic receptor agonist isoproterenol (Iso) on neuronal excitability and synaptic transmission were investigated in brain slices of rat amygdala. Iso (15 microM) produced a long-lasting enhancement of the EPSP that was not blocked by pretreatment with 20 microM D-2-amino-5-phosphonovalerate (D-APV) alone or D-APV in combination with kynuretic acid (1 mM). The sensitivity of postsynaptic neurons to the glutamate receptor agonist AMPA was unchanged by Iso pretreatment. Superfusion of Iso reversibly blocked the after-hyperpolarization (AHP) that followed a depolarizing current pulse and caused more action potential firing. Intracellular application of a selective inhibitor of the catalytic subunit of cAMP-dependent protein kinase A blocked the effect of Iso on the AHP, whereas Iso-induced potentiation was entirely normal in the same neuron. In addition, Iso decreased the magnitude of paired-pulse facilitation, which is consistent with a presynaptic mode of action. Substituting the Mg2+ for Ca2+ in the medium completely abolished the Iso-induced enhancement of the EPSP. The effect of Iso also was blocked by low concentrations of omega-agatoxin-IVA, but not by nifedipine or omega-conotoxin-GVIA. These results suggest that Iso enhances synaptic transmission in the amygdala via a presynaptic site of action: the mechanism underlying the potentiating effect likely is attributable to an increased Ca2+ influx through P- and/or Q-type Ca2+ channels.
The Genetic and Molecular Basis for Sunscreen Biosynthesis in Cyanobacteria (2010)

Ultraviolet UV-A and UV-B radiation is harmful to living systems, causing damage to biological macromolecules. An important strategy for dealing with UV exposure is the biosynthesis of small-molecule sunscreens. Among such metabolites, the mycosporine and mycosporine-like amino acids (MAAs) are remarkable for their wide phylogenetic distribution and their unique chemical structures. Here, we report the identification of a MAA biosynthetic gene cluster in a cyanobacterium and the discovery of analogous pathways in other sequenced organisms. We have expressed the cluster in a heterologous bacterial host and characterized all four biosynthetic enzymes in vitro. In addition to clarifying the origin of the MAAs, these efforts have revealed two unprecedented enzymatic strategies for imine formation.
Biopsy with Thermally‐Responsive Untethered Microtools (2012)

Thermally activated, untethered microgrippers can reach narrow conduits in the body and be used to excise tissue for diagnostic analyses. As depicted in the figure, the feasibility of an in vivo biopsy of the porcine bile duct using untethered microgrippers is demonstrated.