gebhart/patrepeval huggingface dataset:
Anchoring Hairpin Ribozymes to Long Target RNAs by Loop–Loop RNA Interactions (2002)

Efficient ribozyme-mediated gene silencing requires the effective binding of a ribozyme to its specific target sequence. Stable stem-loop domains are key elements for efficiency of natural antisense RNAs. This work tests the possibility of using such naturally existing structural motifs for anchoring hairpin ribozymes when targeting long RNAs. Assays were performed with four catalytic antisense RNAs, based on the hairpin ribozyme (HP), that carried a stable stem-loop motif at their 3' end. Extensions consisted of one of the following motifs: the stem-loop II of the natural antisense RNA-CopA, its natural target in CopT, the TAR-RNA motif, or its complementary sequence alphaTAR. Interestingly, the presence of any of these antisense motifs resulted in an enhancement of catalytic performance against the ribozyme's 14-nucleotide-long target RNA (Swt). A series of artificial, long RNA substrates containing the Swt sequence and the natural TAR-RNA stem-loop were constructed and challenged with a catalytic antisense RNA carrying the TAR-complementary stem-loop. This cleaves each of these substrates significantly more efficiently than HP. The deletion of the TAR domain in the substrate, or its substitution by its complementary counterpart alphaTAR, abolishes the positive effect. These results suggest that the enhancement is owed to the interaction of both complementary stem-loop domains. Moreover, they demonstrate that the TAR domain can be used as an anchoring site to facilitate the access of hairpin ribozymes to their specific target sequences within TAR-containing RNAs.
Changes in Aβ Non-Nociceptive Primary Sensory Neurons in a Rat Model of Osteoarthritis Pain (2010)

Thus, at one month after induction of the OA model Abeta-fiber low threshold mechanoreceptors but not C- or Adelta-fiber nociceptors had undergone changes in electrophysiological properties. If these changes reflect a change in functional role of these neurons in primary afferent sensory processing, then Abeta-fiber non-nociceptive primary sensory neurons may be involved in the pathogenesis of OA pain. Further, it is important to point out that the patterns of the changes we observed are consistent with observations in models of peripheral neuropathy but not models of peripheral inflammation.
Monophosphoryl lipid A as an adjuvant. Past experiences and new directions. (1995)

The current era of vaccinology has resulted in antigens produced by synthetic chemistry and by genetic engineering techniques; these may provide more effective and safe vaccines. Many of these antigens can be produced in large quantities and in relatively pure form. However, inherent in their simplified, defined structures is a lack of immunogenicity and they require an immunostimulant or adjuvant to elicit appropriate immunity. It has been the purpose of this chapter to document the potential use of MPL as a vaccine adjuvant. In this regard, it has been demonstrated that (1) MPL has retained the useful immunostimulating activities of the parent LPS molecule, but has greatly attenuated toxicity; (2) MPL produces diverse effects on the cellular elements of the immune system, including macrophage activation and T and B cell interaction, with concomitant cytokine and lymphokine release; (3) MPL has proven adjuvant activity, in both the cellular and humoral effector arms of immunity; (4) MPL has adjuvant activity when used alone, or in combination with other immunostimulants and delivery vehicles; and (5) MPL has been administered safely to humans in various clinical vaccine trials. Thus, MPL is emerging as a promising new adjuvant for use in human vaccines.
Static (Isometric) Exercise and the Heart: Physiological and Clinical Considerations (1974)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Process optimization and characterization of device worthy sol-gel based PZT for ferroelectric memories (1990)

The purpose of this work is to develop and characterize an optimized sol-gel PZT process to be used in ferroelectric memories. A review of the sol-gel process is given, including discussions on hydrolysis under acidic and basic conditions. Application of the sol-gel process to thin films is then discussed. Topics such as removal of solvents, stresses in the thin film and how this relates to cracking are mentioned. A review of different synthesis methods of sol-gel PZT is then conducted in order to help determine a device worthy sol-gel PZT process. Methods of controlling the pore size by hydrolysis and different heat treatments at various stages during the drying and annealing cycles are then used. The quality of thin film PZT on Pt is characterized by using dispersive X-ray and X-ray diffraction analyses. Electrical results yield Pr ranging from 7.9-21.9 μC/cm2Ec ranging from 29.1 -92.3 kV/cm and switching times as fast as 56 ns, using a capacitor area of 1 × 104 μm2. However, these results depend on the stoichiometry and method of measurement used. Fatigue curves show a single time constant switching charge decay which may be indicative of a single type of defect domain interaction.
The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T cell receptor transgenic mice. (1992)

To study the factors that determine whether CD4+ T cells produce interleukin 4 (IL-4) or interferon gamma (IFN-gamma) upon stimulation we used a system allowing naive T cells to be primed in vitro by specific antigen. Dense CD4+ T cells were purified from mice that expressed transgenes encoding a T cell receptor specific for pigeon cytochrome C peptide 88-104 in association with I-Ek. These T cells produced very limited amounts of IL-4 and IFN-gamma upon immediate challenge with 88-104 and antigen-presenting cells (APC). However, after an initial "priming" culture in which they were incubated for 4 d in the presence of 88-104, APC, and 1,000 U/ml IL-4, the T cells acquired the capacity to produce substantial amounts of IL-4 upon rechallenge but made very little IFN-gamma. Cells primed in the absence of IL-4 produced IFN-gamma upon rechallenge but virtually no IL-4. The inhibitory effect of IL-4 on IFN-gamma production did not appear to be mediated by the induction of IL-10 production since IL-10 addition to initial cultures did not suppress priming for IFN-gamma production, nor did anti-IL-10 block the inhibitory effect of IL-4. IFN-gamma itself did not increase priming for IFN-gamma production, nor did anti-IFN-gamma reduce such priming. IFN-gamma did, however, diminish priming for IL-4 production when limiting amounts of IL-4 (100 U/ml) were used in the initial culture. The dominant effect of IL-4 in determining the lymphokine-producing phenotype of primed cells was observed with dendritic cells (DC), activated B cells, and I-Ek-transfected fibroblasts as APC. However, the different APC did vary in their potency, with DC being superior to activated B cells, which were superior to transfected fibroblasts.
Targeted Deletion of Thioredoxin-Interacting Protein Regulates Cardiac Dysfunction in Response to Pressure Overload (2007)

Biomechanical overload induces cardiac hypertrophy and heart failure, and reactive oxygen species (ROS) play a role in both processes. Thioredoxin-Interacting Protein (Txnip) is encoded by a mechanically-regulated gene that controls cell growth and apoptosis in part through interaction with the endogenous dithiol antioxidant thioredoxin. Here we show that Txnip is a critical regulator of the cardiac response to pressure overload. We generated inducible cardiomyocyte-specific and systemic Txnip-null mice (Txnip-KO) using Flp/frt and Cre/loxP technologies. Compared with littermate controls, Txnip-KO hearts had attenuated cardiac hypertrophy and preserved left ventricular (LV) contractile reserve through 4 weeks of pressure overload; however, the beneficial effects were not sustained and Txnip deletion ultimately led to maladaptive LV remodeling at 8 weeks of pressure overload. Interestingly, these effects of Txnip deletion on cardiac performance were not accompanied by global changes in thioredoxin activity or ROS; instead, Txnip-KO hearts had a robust increase in myocardial glucose uptake. Thus, deletion of Txnip plays an unanticipated role in myocardial energy homeostasis rather than redox regulation. These results support the emerging concept that the function of Txnip is not as a simple thioredoxin inhibitor but as a metabolic control protein.
A 0.7V MOSFET-only switched-opamp ΣΔ modulator (2003)

A 0.7V MOSFET-only switched-opamp /spl Sigma//spl Delta/ modulator for speech applications achieves 67dB SNDR, and 75dB dynamic range. The circuit, occupying 0.08mm/sup 2/ in 0.18/spl mu/m CMOS, does not use voltage boosting or low-V/sub T/ devices. All capacitors are compensated MOS devices.
Cello‐Oligosaccharide Hydrolysis by Cellobiohydrolase II from Trichoderma Reesei (1996)

The hydrolysis of soluble cello-oligosaccharides, with a degree of polymerisation of 4-6, catalysed by cellobiohydrolase II from Trichoderma reesei was studied using 1H-NMR spectroscopy and HPLC. The experimental progress curves were analysed by fitting numerically integrated kinetic equations, which provided cleavage patterns and kinetic constants for each oligosaccharide. This analysis procedure accounts for product inhibition and avoids the initial slope approximation. No glucose was detected at the beginning of the reaction indicating that only the internal glycosidic linkages are attacked. For cellotetraose only the second glycosidic linkage was cleaved. For cellopentaose and cellohexaose the second and the third glycosidic linkage from the non-reducing end were cleaved with approximately equal probability. The degradation rates of these cello-oligosaccharides, 1-12 s-1 at 27 degrees C, are about 10-100 times faster than for the 4-methylumbelliferyl substituted analogs or for collotriose. No intermediate products larger than cellotriose were released. The degradation rate for cellotetraose were higher than its off-rate, which accounts for the processive degradation of cellohexaose. A high cellohexaose/enzyme ratio caused slow reversible inactivation of the enzyme.
254. New Chimeric Gene Therapy Vectors Based on Four Different Mammalian Bocaviruses (2016)

Parvoviruses have long been developed as safe, efficient and versatile DNA delivery vectors for gene therapy applications. In particular adeno-associated viral (AAV) vectors have emerged as lead candidates owing to their apathogenicity and amenability to genetic modifications. Yet, a drawback is their limited cargo capacity of 4.9 kb, which is insufficient to accommodate larger genes. Intriguingly, it was shown recently that oversized single-stranded AAV genomes can be packaged into capsids of human bocavirus 1 (HboV1, also a parvovirus), yielding HboV1/AAV chimeras that specifically and efficiently transduce human airway epithelia (HAE). Motivated by this pioneering work, we aimed to expand the repertoire of HboV/AAV chimeras by vectorizing four additional primate bocaviruses known to infect the gastrointestinal (GI) tract. We thus assembled and cloned the VP1/VP2 ORFs from three human variants (HboV2-4) and gorilla bocavirus into a helper plasmid derived from HboV1, carrying the genes required for HboV1 replication and packaging. To assess viral particle assembly, HEK293T cells were transfected with three plasmids: (i) one of our new HboV helpers; (ii) a self-complementary AAV-YFP vector; and (iii) pDG, a plasmid encoding all genes for AAV packaging and replication. In all cases, correct expression of VP1/VP2 proteins was confirmed by Western blot analyses of cell lysates. Also, following large-scale production and iodixanol gradient purification, qPCR analyses of the 40% phase showed the presence of DNase-resistant particles for all five bocaviral serotypes. Most importantly, titration of these particles revealed comparable quantities, demonstrating that expression of NS and NP1 proteins from HboV1 supports assembly of the four other bocaviruses. Analysis in primary HAE showed YFP transgene expression for all chimeric vectors except for HboV2/AAV, congruent with prior detection of the cognate wild-type viruses in nasopharyngeal aspirates. Further in line with epidemiological data, we noted a marked difference in infectivity, from 15% for HboV1, to below 1% for the others. In looming experiments, the new vectors will be studied in primary epithelial cells from the GI tract, which are the putative natural target cells for HboV2-4 and gorilla bocavirus. Interestingly, infectivity of all chimeras could be boosted by adding proteasome inhibitors, reminiscent of data with AAV. Hence, to enhance escape from the proteasome degradation pathway and improve transduction, we mutated surface tyrosines in the VP2 protein of HboV1. Functional assessment of the resulting mutants is currently ongoing. Collectively, the large capacity, unique cell specificities and ability to cross-package AAV DNA make this novel vector set highly attractive for human gene therapy applications. In the future, it should be moreover rewarding to attempt molecular evolution of bocavirus capsids, taking advantage of the profound experience with AAV vectors.
A New Method for Modulating Traumatic Brain Injury With Mechanical Tissue Resuscitation (2011)

Mechanical tissue resuscitation with controlled subatmospheric pressure can significantly modulate levels of excitatory amino acids and lactate in traumatic brain injury, decrease the water content and volume of injured brain, improve neuronal survival, and speed functional recovery.
Omacetaxine: A Protein Translation Inhibitor for Treatment of Chronic Myelogenous Leukemia (2014)

Chronic myelogenous leukemia (CML) is driven by the Bcr-Abl fusion protein, which is a result of a (9;22) chromosomal translocation. Imatinib, dasatinib, and nilotinib (tyrosine kinase inhibitors, TKI) have revolutionized how CML is treated. Although the majority of patients respond to these kinase inhibitors, a subset becomes resistant to these therapeutics. Synribo (omacetaxine mepesuccinate) was recently approved by the U.S. Food and Drug Administration for Philadelphia-positive CML either in the chronic or the accelerated phase whose disease failed two prior TKIs. With omacetaxine 1.25 mg/m(2) twice daily for 14 days during induction and for 7 days during maintenance, a major cytogenetic response occurred in 20% of patients in the chronic phase and major hematologic response in 27% of patients in the accelerated phase. Laboratory investigations unraveled the mechanism of action and effectiveness of this agent. Bcr-Abl protein is intrinsically programmed to turn over with a short half-life that makes it susceptible to protein translation inhibitors. Omacetaxine (homoharringtonine) inhibits total protein biosynthesis by binding to A-site cleft of ribosomes. As a corollary to this action, there is a diminution of short-lived proteins, such as Bcr-Abl, followed by cell death. Approval of this first-in-class protein translation inhibitor opens up new avenues for its use in other diseases as well as mechanism-based combinations.
Broadband High-Efficiency Half-Wave Plate: A Supercell-Based Plasmonic Metasurface Approach (2015)

We design, fabricate, and experimentally demonstrate an ultrathin, broadband half-wave plate in the near-infrared range using a plasmonic metasurface. The simulated results show that the linear polarization conversion efficiency is over 97% with over 90% reflectance across an 800 nm bandwidth. Moreover, simulated and experimental results indicate that such broadband and high-efficiency performance is also sustained over a wide range of incident angles. To further obtain a background-free half-wave plate, we arrange such a plate as a periodic array of integrated supercells made of several plasmonic antennas with high linear polarization conversion efficiency, consequently achieving a reflection-phase gradient for the cross-polarized beam. In this design, the anomalous (cross-polarized) and the normal (copolarized) reflected beams become spatially separated, hence enabling highly efficient and robust, background-free polarization conversion along with broadband operation. Our results provide strategies for creating compact, integrated, and high-performance plasmonic circuits and devices.
The Luminosity of Spectrometers with Prisms, Gratings, or Fabry-Perot Etalons (1954)

Formulas have been established which express the flux given by a spectrometer as a function of the effective resolving power and of the dimension of the dispersive system (area of the base of the prism, or area of the grating, or area of the plates of the étalon). It is thus possible to compare the luminosities of the three types of instruments with, in each case, equal resolving power and equal dimension. This comparison reveals a great superiority of the grating over the prism for all regions of wavelengths, and a great superiority of the étalon over the grating. In the case of the étalon, the overlapping may be overcome by the use of several étalons in series.
A Controlled Trial of Arthroscopic Surgery for Osteoarthritis of the Knee (2002)

Arthroscopic surgery for osteoarthritis of the knee provides no additional benefit to optimized physical and medical therapy. (ClinicalTrials.gov number, NCT00158431.)
Amygdala activity at encoding correlated with long-term, free recall of emotional information. (1996)

Positron emission tomography of cerebral glucose metabolism in adult human subjects was used to investigate amygdaloid complex (AC) activity associated with the storage of long-term memory for emotionally arousing events. Subjects viewed two videos (one in each of two separate positron emission tomography sessions, separated by 3-7 days) consisting either of 12 emotionally arousing film clips ("E" film session) or of 12 relatively emotionally neutral film clips ("N" film session), and rated their emotional reaction to each film clip immediately after viewing it. Three weeks after the second session, memory for the videos was assessed in a free recall test. As expected, the subjects' average emotional reaction to the E films was higher than that for the N films. In addition, the subjects recalled significantly more E films than N films. Glucose metabolic rate of the right AC while viewing the E films was highly correlated with the number of E films recalled. AC activity was not significantly correlated with the number of N films recalled. The findings support the view derived from both animal and human investigations that the AC is selectively involved with the formation of enhanced long-term memory associated with emotionally arousing events.
Kinetic and Stoichiometric Relationships of the Energy and Carbon Metabolism in the Culture of Microalgae (2003)

Some microalgae can grow metabolizing inorganic and organic carbon sources, which might occur simultaneously and independently, while energy is supplied by light and/or an organic carbon source. In this context, the contribution of each metabolism to total growth can be determined by quantitative analysis. The illumination of microalgal cells growing in the presence of organic substances, might cause an effect which can drive the carbon metabolism in different ways. When analyzing the growth of different strains of microalgae, some differences could be distinguished , between additive or inhibitory effect of light on heterotrophi c metabolism in mixotrophic or photoheterotrophic growth. This manuscript proposes, the integration of a kinetic and stoichiometric metabolic model which explains the differences of carbon and energy utilization modes between mixotrophic and photoheterotrophic growth in microalgae. This model presumably discloses relevant independent facts between the mechanisms of photosynthesi s and the oxidative metabolism of organi c compounds, such as glucose and the importance of these differences on the production of biomass and secondary metabolites.
Molecular Analysis of Putative Pneumococcal Virulence Proteins (1997)

Although the polysaccharide capsule has been recognized as a sine qua non of virulence, recent attention has focused on the role of pneumococcal proteins in pathogenesis, particularly in view of their potential as vaccine antigens. The contribution of pneumolysin, two distinct neuraminidases, autolysin, hyaluronidase, and the 37 kDa pneumococcal surface adhesin A has been examined by specifically mutagenizing the respective genes in the pneumococcal chromosome and examining the impact on virulence in animal models. The vaccine potential of these proteins has also been assessed by immunization of mice with purified antigens, followed by challenge with virulent pneumococci.
Purification of mRNA guanylyltransferase and mRNA (guanine-7-) methyltransferase from vaccinia virions. (1975)

A purified enzyme system isolated from vaccinia virus cores has been shown to modify the 5' termini of viral mRNA and synthetic poly(A) and poly(G) to form the structures m7G(5')pppA- and m7G(5')pppG-. The enzyme system has both guanylyltransferase and methyltransferase activities. The GTP:mRNA guanylyltransferase activity incorporates GMP into the 5' terminus via a 5'-5' triphosphate bond. The properties of this reaction are: (a) of the four nucleoside triphosphates only GTP is a donor, (b) mRNA with two phosphates at the 5' terminus is an acceptor while RNA with a single 5'-terminal phosphate is not, (c) Mg2+ is required, (d) the pH optimum is 7.8, (e) PP1 is a strong inhibitor, and (f) the reverse reaction, namely the formation of GTP from PP1 and RNA containing the 5'-terminal structure G(5')pppN-, readily occurs. The S-adenosylmethionine:mRNA(guanine-7-)methyltransferase activity catalyzes the methylation of the 5'-terminal guanosine. This reaction exhibits the following characteristics: (a) mRNA with the 5'-terminal sequences G(5')pppA- and G(5')pppG- are acceptors, (b) only position 7 of the terminal guanosine is methylated; internal or conventional 5'-terminal guanosine residues are not methylated, (c) the reaction is not dependent upon GTP or divalent cations, (d) optimal activity is observed in a broad pH range around neutrality, (e) the reaction is inhibited by S-adenosylhomocysteine. Both the guanylyltransferase and methyltransferase reactions exhibit bisubstrate kinetics and proceed via a sequential mechanism. The reactions may be summarized: (see article).
Comparatively Assessing different Shapes of Lithium-ion Battery Cells (2017)

Different shapes of lithium-ion batteries (LIB) are competing as energy storages for the automobile application. The shapes can be divided into cylindrical and prismatic, whereas the prismatic shape can be further divided in regard to the housing stability in Hard-Case and Pouch. Within this paper, the differences in manufacturing costs and efforts as well as the shape related advantages and disadvantages for an automobile application are discussed. Additionally, the process steps for manufacturing the prismatic hard-case and the pouch cell are analyzed in terms of their individual value contribution to the manufacturing costs. Within the analysis, manufacturing errors can be allocated to specific process steps and economically quantified.