gebhart/patrepeval huggingface dataset:
Ultrasound enhancement of rabbit femoral artery thrombolysis (1997)

Experiments were conducted to evaluate the potential of low-intensity, externally applied ultrasound to accelerate arterial thrombolysis in an animal model and to characterize potential effects of ultrasound exposure on vessel wall morphology. The femoral arteries of 32 rabbits were exposed, a flowprobe was positioned around the vessel, and a stenosis produced with two circumferential silk sutures to reduce flow by 50%. Thrombosis was achieved by injecting thrombin through the cannulated superficial epigastric branch into a 1-cm segment of femoral artery which was isolated for 20 min. Streptokinase was administered intravenously as a 15,000 U/kg bolus followed by an infusion of 15,000 U/kg per h. Ultrasound (1 MHz, 2 W/cm2) was delivered to the thrombosed vessel during streptokinase administration in 17 animals, and 15 control animals received sham ultrasound only. Thrombolysis occurred in nine of 17 (53%) animals receiving both streptokinase and ultrasound, and this was significantly greater than the rate in animals receiving streptokinase alone (2/15, 13%; P=0.025). Ultrasound caused a mean temperature elevation of 4 degrees C in exposed tissues. Light and electron microscopy demonstrated increased platelet accumulation on thrombi in ultrasound-treated vessels compared with controls. Endothelial cell vacuolation was seen by electron microscopy in ultrasound-exposed vessels. The results indicate that externally applied, low-intensity ultrasound can significantly enhance thrombolysis in a rabbit arterial model. Possible adverse effects are minor and include platelet accumulation, temperature elevation and minor endothelial changes. Externally applied ultrasound has potential value as an adjunct to thrombolytic therapy.
The Secreted Hepatitis B Precore Antigen Can Modulate the Immune Response to the Nucleocapsid: A Mechanism for Persistence (1998)

Abstract The hepatitis B precore Ag (HBeAg) is a secreted nonparticulate version of the viral nucleocapsid hepatitis B core Ag (HBcAg), and its function is unknown. A proportion of HBeAg-specific Th cells evade deletion/anergy in HBeAg-transgenic (Tg) mice and mediate anti-HBe “autoantibody” (autoAb) production after in vivo activation with the appropriate Th cell peptide. This model system was used to determine how secretory HBeAg may effect deletion of Th cells in the periphery. For this purpose, HBeAg-Tg mice were bred with Fas and Fas ligand (FasL)-defective lpr/lpr and gld/gld mutant mice. Fas-FasL interactions mediate activation-induced apoptosis in the periphery. In HBeAg-Tg/+ mice, high-titrated anti-HBe autoAb was produced that was exclusively composed of the IgG1 isotype (i.e., Th2-like profile). In contrast, HBeAg-Tg/lpr and HBeAg-Tg/gld mice produced significantly less anti-HBe autoAb, and the IgG isotype patterns were broadened to include IgG2a, IgG2b and IgG3 as well as IgG1 (i.e., mixed Th1/Th2-like profile). These results suggest that HBeAg-specific Th1 cells are preferentially depleted by Fas-FasL-mediated interactions. The effect of circulating HBeAg on HBcAg-specific Th1 cells was also examined by transferring HBe/HBcAg-specific Th cells into dual HBeAg- and HBcAg-expressing Tg recipient mice. The presence of serum HBeAg ablated the expected Th1-mediated anti-HBc Ab response and shifted it toward a Th2 phenotype. These results suggest that in the context of a hepatitis B viral infection, circulating HBeAg has the potential to preferentially deplete inflammatory HBeAg- and HBcAg-specific Th1 cells that are necessary for viral clearance, thereby promoting hepatitis B virus persistence.
[Interferon-alpha therapy]. (2001)

Interferon-alpha (IFN alpha) with or without Ara-C is a choice of therapy for patients with CML who cannot receive allogeneic stem cell transplantation and gives those better prognosis than a conventional chemotherapy, although it has a variety of adverse effects. Especially, in a certain population(about 20%) of CML patients, IFN alpha can induce complete cytogenetic response in spite of persistant minimal residual disease. The basis of IFN alpha activity against CML is still unknown, but the contribution of immune-mediated mechanism is expected.
Contracting over the quality aspect of security in software product markets (2006)

Secure software development has gained momentum during the past couple of years and improvements have been made. Buyers have started to demand secure software and contractual practices for taking security into consideration in the software purchasing context have been developed. Software houses naturally are very keen to providing what their potential customers' desire with respect to security and quality of their products. This study analyses the capacity of private bargaining to incite secure software development and suggests methods for improvement.I argue that without appropriate regulatory intervention the level of security will not improve to meet the needs of the network society as a whole. There are not appropriate incentives for secure development in the market for software products. The software houses do not have to bear the costs resulting from vulnerabilities in their software and the buyers' capability to separate a secure product from an insecure one is limited.
The role of side chain conformational flexibility in surface recognition by Tenebrio molitor antifreeze protein (2003)

Two-dimensional nuclear magnetic resonance spectroscopy was used to investigate the flexibility of the threonine side chains in the beta-helical Tenebrio molitor antifreeze protein (TmAFP) at low temperatures. From measurement of the (3)J(alphabeta) (1)H-(1)H scalar coupling constants, the chi(1) angles and preferred rotamer populations can be calculated. It was determined that the threonines on the ice-binding face of the protein adopt a preferred rotameric conformation at near freezing temperatures, whereas the threonines not on the ice-binding face sample many rotameric states. This suggests that TmAFP maintains a preformed ice-binding conformation in solution, wherein the rigid array of threonines that form the AFP-ice interface matches the ice crystal lattice. A key factor in binding to the ice surface and inhibition of ice crystal growth appears to be the close surface-to-surface complementarity between the AFP and crystalline ice, and the lack of an entropic penalty associated with freezing out motions in a flexible ligand.
Chemical Modification of Natural Human Tumor Necrosis Factor‐α with Polyethylene Glycol Increases Its Anti‐tumor Potency (1994)

Natural human tumor necrosis factor-alpha (TNF-alpha) was chemically modified with an active ester of monomethoxy polyethylene glycol (PEG). The molecular weight of PEG-modified TNF-alpha depended on the reaction time as well as the initial molar ratio of PEG to TNF-alpha. The specific activity of modified TNF-alpha was gradually reduced with increase in the degree of PEG-modification, but the plasma half-life of TNF-alpha was increased by up to 40-fold. Modified TNF-alpha showed approximately 100 times greater anti-tumor potency than unmodified TNF-alpha. Covalent attachment of PEG to TNF-alpha thus increased the bioavailability of TNF-alpha, and may facilitate its potential therapeutic use.
Normal Prenatal but Arrested Postnatal Sexual Development of Luteinizing Hormone Receptor Knockout (LuRKO) Mice (2001)

To study further the role of gonadotropins in reproductive functions, we generated mice with LH receptor (LHR) knockout (LuRKO) by inactivating, through homologous recombination, exon 11 on the LHR gene. LuRKO males and females were born phenotypically normal, with testes, ovaries, and genital structures indistinguishable from their wild-type (WT) littermates. Postnatally, testicular growth and descent, and external genital and accessory sex organ maturation, were blocked in LuRKO males, and their spermatogenesis was arrested at the round spermatid stage. The number and size of Leydig cells were dramatically reduced. LuRKO females also displayed underdeveloped external genitalia and uteri postnatally, and their age of vaginal opening was delayed by 5-7 days. The (-/-) ovaries were smaller, and histological analysis revealed follicles up to the early antral stage, but no preovulatory follicles or corpora lutea. Reduced gonadal sex hormone production was found in each sex, as was also reflected by the suppressed accessory sex organ weights and elevated gonadotropin levels. Completion of meiosis of testicular germ cells in the LuRKO males differs from other hypogonadotropic/cryptorchid mouse models, suggesting a role for FSH in this process. In females, FSH appears to stimulate developing follicles from the preantral to early antral stage, and LH is the stimulus beyond this stage. Hence, in each sex, the intrauterine sex differentiation is independent of LH action, but it has a crucial role postnatally for attaining sexual maturity. The LuRKO mouse is a close phenocopy of recently characterized human patients with inactivating LHR mutations, although the lack of pseudohermaphroditism in LuRKO males suggests that the intrauterine sex differentiation in this species is not dependent on LH action.
In Vitro Evaluation of an Active Heat-and-Moisture Exchanger: The Hygrovent Gold (2010)

The passive Hygrovent Gold provided adequate heat and moisture in normothermia, but the active Hygrovent Gold provided the highest humidity, in both normothermia and hypothermia.
ENaC Degradation in A6 Cells by the Ubiquitin-Proteosome Proteolytic Pathway (2001)

Amiloride-sensitive epithelial Na(+) channels (ENaC) are responsible for trans-epithelial Na(+) transport in the kidney, lung, and colon. The channel consists of three subunits (alpha, beta, gamma) each containing a proline rich region (PPXY) in their carboxyl-terminal end. Mutations in this PPXY domain cause Liddle's syndrome, an autosomal dominant, salt-sensitive hypertension, by preventing the channel's interactions with the ubiquitin ligase Neural precursor cell-expressed developmentally down-regulated protein (Nedd4). It is postulated that this results in defective endocytosis and lysosomal degradation of ENaC leading to an increase in ENaC activity. To show the pathway that degrades ENaC in epithelial cells that express functioning ENaC channels, we used inhibitors of the proteosome and measured sodium channel activity. We found that the inhibitor, MG-132, increases amiloride-sensitive trans-epithelial current in Xenopus distal nephron A6 cells. There also is an increase of total cellular as well as membrane-associated ENaC subunit molecules by Western blotting. MG-132-treated cells also have increased channel density in patch clamp experiments. Inhibitors of lysosomal function did not reproduce these findings. Our results suggest that in native renal cells the proteosomal pathway is an important regulator of ENaC function.
Abstract 2495: Pharmacodynamic Profile of a Novel Chimeric Natriuretic Peptide, CD-NP, as Compared to C-Type Natriuretic Peptide (2007)

Background: C-type natriuretic peptide (CNP), a 22-amino-acid peptide and a ligand of the natriuretic peptide receptor-B (NPR-B), exhibits venodilating, anti-fibrotic, and vascular-regenerating properties but limited renal actions. A Mayo-designed chimeric peptide, CD-NP, which consists of CNP and the C-terminus of Dendroaspis NP, was synthesized to test the hypothesis that CD-NP would possess CNP-like properties with an improved pharmacodynamic profile. Methods: Normal anesthetized dogs were given CD-NP 50 ng/kg/min (n = 10) or an equimolar dose of CNP 29.3 ng/kg/min (n = 9) i.v. for 75 min. Hemodynamic, renal, and hormonal data were obtained pre-infusion (pre-I), at 30 and 60 min I, and post-I, and were compared both within group vs pre-I (mean ± SE, P&lt; 0.05*, &lt; 0.01 † ) and between groups ( P &lt; 0.05 ‡ , &lt; 0.01 § , &lt; 0.001 ¶ ). Plasma BNP was measured by radioimmunoassay. Results: CD-NP resulted in greater increases in plasma cGMP (7±.4 to 25±3 †¶ to 36±3 †¶ to 23±3 †¶ pmol/ml), urinary cGMP excretion (978±145, 3170±205 †¶ , 5919±616 †¶ , 3077±298 †¶ pmol/min) vs CNP (8±.8, 10±.6 † , 11±.7 † , 8±.5 pmol/ml; 976±110, 1104±115, 1317±103, 998±101 pmol/min, respectively). CD-NP also increased urine Na + excretion (19±4, 168±24 †§ , 237±26 †¶ , 96±12 † μEq/min), urine flow (0.2±.1, 1.3±.2 † , 1.8±.3 † , 0.8±.2 † ml/min), and GFR (37±2 ‡ , 48±3 † , 51±3 † , 53±4 † ml/min) vs CNP (36±12, 68±10, 85±26, 81±25 μEq/min; 0.4±.1, 0.9±.2, 1.2±.3*, 0.9±.3 ml/min; 52±5, 53±7, 50±4, 49±6 ml/min, respectively). CD-NP reduced PCWP (5.7±.7, 4.1±1*, 3.2±.7 † , 4.3±.8 mmHg), RAP (1.8±.4, 1.1±.4 † , 0.9±.5 †§ , 1.3±.5 § mmHg), PAP (12±.6, 10±.4*, 10±.6, 11±.7 mmHg) vs CNP (6±.6, 5±.8, 6±.8, 7±.9 † mmHg; 2.6±.3, 2.5±.3 to 2.9±.3 to 3.5±.5 † mmHg; 13±1, 12±1, 12±1, 13±1 mmHg, respectively). Mean blood pressure was unchanged in either group. CD-NP increased circulating BNP during infusion vs CNP (40±4 vs 18±2 pg/ml, P&lt;0.001). Conclusion: This study demonstrates the successful transformation of CNP to a CNP-like peptide with enhanced natriuretic, diuretic, GFR-enhancing, and cardiac-unloading actions. CD-NP may also promote increases in plasma BNP which via the NPR-A receptor may contribute to its biological actions. The therapeutic potential of CD-NP in heart failure warrants further studies.
Protein dissociation from DNA in model systems and chromatin (1978)

Salt induced dissociation of protamine, poly(L-lysine) and poly(L-arginine) from DNA was measured by relative light scattering at theta = 90 degrees and/or centrifugation. Dissociation of histones from DNA was studied using relative light scattering and intrinsic tyrosine fluorescence. Protamine was dissociated from DNA at 0.15 M MgCl2 (ionic strength mu = 0.45) or 0.53 M NaCl (mu = 0.53) based on light scattering data and at approximately 0.2 M MgCl2 (mu = 0.6) or 0.6 M NaCl based on centrifugation data. NaCl induced dissociation of poly(Lys) or poly(Arg) from natural DNAs measured by light scattering did not depend on the guanine plus cytosine content. To dissociate poly(Arg) from DNA higher ionic strength using NaCl, MgCl2, or CaCl2, similar ionic strength using NaClo4, and lower ionic strength using Na2SO4 was needed then to dissociated poly(Lys). Both the decrease in light scattering and the enhancement of tyrosine fluorescence of chromatin occurred between 0.5 and 1.5 M NaCl when histones were dissociated.
High‐Performance Integrated ZnO Nanowire UV Sensors on Rigid and Flexible Substrates (2011)

Abstract Due to the large surface area‐to‐volume ratio and high quality crystal structure, single nanowire (NW)‐based UV sensors exhibit very high on/off ratios between photoresponse current and dark current. Practical applications require a large‐scale and low‐cost integration, compatibility to flexible electronics, as well as reasonably high photoresponse current that can be detected without high‐precision measurement systems. In this paper, NW‐based UV sensors were fabricated in large‐scale by integrating multiple NWs connected in parallel via the contact printing method. Linear scaling of the photoresponse current with the number of NWs is demonstrated. Integrated ZnO NW UV sensors were fabricated on rigid glass and flexible polyester (PET) substrates at the macroscopic scale. The flexible and rigid sensors performed comparably, exhibiting on/off current ratios approximately three orders of magnitude higher than sensors made from polycrystalline ZnO thin films. Under UV irradiance of 4.5 mW cm −2 and 3 V bias, photoresponse currents and on/off current ratios for the rigid and flexible UV sensors reached 12.22 mA and 82 000, and 14.1 mA and 120 000, respectively. This result suggests that lateral integration of semiconductor NWs is an effective approach to large‐scale fabrication of flexible NW sensors that inherit the merits of single‐NW‐based systems with unaffected performance compared to using rigid substrate.
A Randomized Trial of Three Antipneumocystis Agents in Patients with Advanced Human Immunodeficiency Virus Infection (1995)

In patients with advanced HIV infection, the three treatment strategies we examined have similar effectiveness in preventing P. carinii pneumonia. Strategies that start with trimethoprim-sulfamethoxazole or with high-dose dapsone, rather than aerosolized pentamidine, are superior in patients with fewer than 100 CD4+ lymphocytes per cubic millimeter.
Suppression of Spruce Beetle Attacks by MCH Released from Bubble Caps (1989)

Abstract The attack density of the spruce beetle, Dendroctonus rufipennis (Kirby), was reduced to 10-25% of that on untreated felled Engelmann spruce (Picea engelmannii) trees, when the trees were treated with 9-15 bubble cap release devices, each releasing the aggregation inhibitor MCH at 1-3 mg/24 h at 20°C. In the first experiment, deterioration of many release devices reduced the suppression effect. In the second experiment, MCH reduced attacks by 85%, and total brood production by 79-88%. The attacks on the MCH treated trees occurred late, as evidenced by the early stage of development of galleries and brood on these trees. Semiochemical-baited traps at untreated, or MCH-treated, felled trees caught few beetles, and had no effect on the attack density. The results show that manually applied MCH can be used operationally to reduce attacks by the spruce beetle on small groups of wind thrown trees. Mass trapping of spruce beetles is not feasible with currently known semiochemicals. West. J. Appl. For. 4(2):49-52, April 1989.
Investigation of the morphology and surface properties of crosslinked poly(urethane-ester-siloxane)s (2012)

Two series of crosslinked poly(urethane-ester-siloxane)s were synthesized from ?,?-dihydroxy-(ethylene oxide-poly(dimethylsiloxane)-ethylene oxide) (EO-PDMS-EO), 4,4?-methylenediphenyl diisocyanate and Boltorn? hyperbranched polyesters of the second and third pseudo generation, by a two-step polymerization in solution. The effect of the EO-PDMS-EO content and functionality of the applied crosslinking agent on the morphology and surface properties of the prepared poly(urethane-ester-siloxane)s was investigated by FTIR spectroscopy, small-angle X-ray scattering (SAXS), atomic force microscopy (AFM), scanning electron microscopy (SEM) and water absorption measurement. Different techniques (FTIR peak deconvolution, SAXS and AFM) revealed that decrease of the crosslinking agent functionality and EO-PDMS-EO content promotes microphase separation in the synthesized poly(urethane-ester-siloxane)s. SEM analysis and water absorption experiments showed that due to the hydrophobic character of EO-PDMS-EO and its ability to migrate to the surface of poly(urethane-ester-siloxane)s, samples synthesized with higher EO-PDMS-EO content and crosslinking agent of lower functionality have more hydrophobic surface and better waterproof performances. The obtained results indicate that the synthesis of poly(urethane-ester-siloxane)s based on EO-PDMS-EO and Boltorn? hyperbranched polyesters leads to the creation of networks with interesting morphological and surface properties, which can be easily tailored by changing the content of EO-PDMS-EO segment or functionality of hyperbranched polyester.
Targeting DMPK with Antisense Oligonucleotide Improves Muscle Strength in Myotonic Dystrophy Type 1 Mice (2017)

Myotonic dystrophy type 1 (DM1), a dominant hereditary muscular dystrophy, is caused by an abnormal expansion of a (CTG)<sub>n</sub> trinucleotide repeat in the 3' UTR of the human dystrophia myotonica protein kinase (DMPK) gene. As a consequence, mutant transcripts containing expanded CUG repeats are retained in nuclear foci and alter the function of splicing regulatory factors members of the MBNL and CELF families, resulting in alternative splicing misregulation of specific transcripts in affected DM1 tissues. In the present study, we treated DMSXL mice systemically with a 2'-4'-constrained, ethyl-modified (ISIS 486178) antisense oligonucleotide (ASO) targeted to the 3' UTR of the DMPK gene, which led to a 70% reduction in CUG<sup>exp</sup> RNA abundance and foci in different skeletal muscles and a 30% reduction in the heart. Furthermore, treatment with ISIS 486178 ASO improved body weight, muscle strength, and muscle histology, whereas no overt toxicity was detected. This is evidence that the reduction of CUG<sup>exp</sup> RNA improves muscle strength in DM1, suggesting that muscle weakness in DM1 patients may be improved following elimination of toxic RNAs.
The Cytoplasmic Tyrosine Motifs in Full-Length Glycoprotein 130 Have Different Roles in IL-6 Signal Transduction (2000)

The function of the signal-transducing receptor subunit glycoprotein 130 (gp130) in the IL-6-receptor complex has previously been studied using carboxyl-terminal deletion mutants or a truncated molecule of approximately 60 membrane-proximal amino acids (containing box 1 and box 2) linked to the individual gp130 tyrosine motifs. However, the redundancy of the tyrosine motifs within the cytoplasmic part of gp130 has been neglected. Here we describe the analysis of the function of the individual cytoplasmic tyrosine residues of gp130 in the context of the full-length receptor protein in IL-6 signaling as measured by STAT activation, acute phase protein induction, and stimulation of proliferation. Add-back receptor mutants containing only one cytoplasmic tyrosine have been generated and tested for their efficiency in IL-6 signal transduction. Our studies revealed that tyrosine motifs which have been described to recruit STAT proteins are not equivalent with respect to their potential to activate STAT factors and acute phase protein gene promoters: the two distal tyrosines, Tyr905 and Tyr915, of gp130 were more potent than Tyr767 and Tyr814. Surprisingly, Tyr905 and Tyr915 mediate acute phase protein gene promoter activation stronger than the wild-type receptor containing all six cytoplasmic tyrosine residues. In contrast, Ba/F3 cells stably transfected with add-back receptors containing Tyr767 or Tyr905 were more sensitive to IL-6-induced proliferation than cells expressing the other add-back receptor mutants. Thus, the tyrosine residues in the cytoplasmic part of gp130 were found to contribute differentially to IL-6 signal transduction in the full- length gp130 protein.
Processing of gene expression data generated by quantitative real-time RT-PCR. (2002)

Quantitative real-time PCR represents a highly sensitive and powerful technique for the quantitation of nucleic acids. It has a tremendous potential for the high-throughput analysis of gene expression in research and routine diagnostics. However, the major hurdle is not the practical performance of the experiments themselves but rather the efficient evaluation and the mathematical and statistical analysis of the enormous amount of data gained by this technology, as these functions are not included in the software provided by the manufacturers of the detection systems. In this work, we focus on the mathematical evaluation and analysis of the data generated by quantitative real-time PCR, the calculation of the final results, the propagation of experimental variation of the measured values to the final results, and the statistical analysis. We developed a Microsoft Excel-based software application coded in Visual Basic for Applications, called Q-Gene, which addresses these points. Q-Gene manages and expedites the planning, performance, and evaluation of quantitative real-time PCR experiments, as well as the mathematical and statistical analysis, storage, and graphical presentation of the data. The Q-Gene software application is a tool to cope with complex quantitative real-time PCR experiments at a high-throughput scale and considerably expedites and rationalizes the experimental setup, data analysis, and data management while ensuring highest reproducibility.