gebhart/patrepeval huggingface dataset:
Engineering and Evolution of Synthetic Adeno-Associated Virus (AAV) Gene Therapy Vectors via DNA Family Shuffling (2012)

Adeno-associated viral (AAV) vectors represent some of the most potent and promising vehicles for therapeutic human gene transfer due to a unique combination of beneficial properties(1). These include the apathogenicity of the underlying wildtype viruses and the highly advanced methodologies for production of high-titer, high-purity and clinical-grade recombinant vectors(2). A further particular advantage of the AAV system over other viruses is the availability of a wealth of naturally occurring serotypes which differ in essential properties yet can all be easily engineered as vectors using a common protocol(1,2). Moreover, a number of groups including our own have recently devised strategies to use these natural viruses as templates for the creation of synthetic vectors which either combine the assets of multiple input serotypes, or which enhance the properties of a single isolate. The respective technologies to achieve these goals are either DNA family shuffling(3), i.e. fragmentation of various AAV capsid genes followed by their re-assembly based on partial homologies (typically >80% for most AAV serotypes), or peptide display(4,5), i.e. insertion of usually seven amino acids into an exposed loop of the viral capsid where the peptide ideally mediates re-targeting to a desired cell type. For maximum success, both methods are applied in a high-throughput fashion whereby the protocols are up-scaled to yield libraries of around one million distinct capsid variants. Each clone is then comprised of a unique combination of numerous parental viruses (DNA shuffling approach) or contains a distinctive peptide within the same viral backbone (peptide display approach). The subsequent final step is iterative selection of such a library on target cells in order to enrich for individual capsids fulfilling most or ideally all requirements of the selection process. The latter preferably combines positive pressure, such as growth on a certain cell type of interest, with negative selection, for instance elimination of all capsids reacting with anti-AAV antibodies. This combination increases chances that synthetic capsids surviving the selection match the needs of the given application in a manner that would probably not have been found in any naturally occurring AAV isolate. Here, we focus on the DNA family shuffling method as the theoretically and experimentally more challenging of the two technologies. We describe and demonstrate all essential steps for the generation and selection of shuffled AAV libraries (Fig. 1), and then discuss the pitfalls and critical aspects of the protocols that one needs to be aware of in order to succeed with molecular AAV evolution.
Regional fat loss from the thigh in obese women after adrenergic modulation. (1987)

Beta-adrenergic stimulation and alpha 2-adrenergic inhibition increase lipolysis from fat cells. Twenty-eight obese women were placed on a calorie-restricted diet and one of five treatments was applied to one thigh three to five times per week for four weeks: (1) isoproterenol injections; (2) cream containing colforsin (forskolin), aminophylline, and yohimbine; (3) yohimbine cream; (4) colforsin cream; or (5) aminophylline cream. The opposite thigh was treated with a placebo (injection or cream). The treated thighs lost significantly more girth after treatment, both by injection and by cream. No adverse reactions were attributable to either the cream or the injections. It is concluded that local fat reduction from the thigh can be safely accomplished.
Effects of epidural anesthesia and postoperative epidural analgesia on immune function in esophageal carcinoma patients undergoing thoracic surgery (2014)

Thoracic epidural anesthesia (TEA) has been demonstrated to significantly reduce stress and immune dysfunction in trauma patients. In esophageal carcinoma patients undergoing thoracic surgery, TEA combined with general anesthesia during surgery and subsequent postoperative patient-controlled epidural analgesia (PCEA) may improve plasma cortisol (Cor), interleukin (IL)-6 and IL-17 levels and helper T-cell differentiation. A total of 60 esophageal carcinoma patients undergoing thoracic surgery were randomly allocated into groups I, II, III and I (n=15 per group). During surgery, groups I and II received total intravenous general anesthesia (TIVA), whereas groups III and IV received combined TEA and TIVA. Postoperatively, groups I and III received postoperative patient-controlled intravenous analgesia (PCIA), while groups II and IV received PCEA. The Cor, IL-6, IFN-γ, IL-4 and IL-17 levels were measured in peripheral blood samples collected prior to anesthesia (T0), at 2 h after incision (T1), at 4 h postoperatively (T2), at 24 h postoperatively (T3) and at 48 h postoperatively (T4). The plasma Cor, IL-17 and IL-6 levels increased significantly at the beginning of the operation in groups I, II and III, while in group IV there were no significant differences during the entire period, concurrent with enhanced Th0 to Th2 shift, contributing to a Th2-dominant Th1/Th2 ratio. General anesthesia with TEA more efficiently inhibited the onset of the Th2-dominant status and decreased the plasma levels of Cor and IL-6 compared to general anesthesia alone and PCEA inhibited the Th2-dominant status more efficiently compared to PCIA. Therefore, general anesthesia combined with TEA and sole administration of PCEA were demonstrated to inhibit the stress response and minimize immune dysfunction, generating most pronounced results upon combination TEA/PCEA treatment.
Noise performance of phase-insensitive multicasting in multi-stage parametric mixers (2013)

Noise properties of large-count spectral multicasting in a phase-insensitive parametric mixer were investigated. Scalable multicasting was achieved using two-tone continuous-wave seeded mixers capable of generating more than 20 frequency non-degenerate copies. The mixer was constructed using a multistage architecture to simultaneously manage high Figure-of-Merit frequency generation and suppress noise generation. The performance was characterized by measuring the conversion efficiency and noise figure of all signal copies. Minimum noise figure of 8.09dB was measured. Experimental findings confirm that noise of the multicasted signal does not grow linearly with copy count and that it can be suppressed below this limit.
Low-complexity Viterbi detection for a family of partial response systems (1992)

Viterbi detection combined with class IV partial response (PR) equalization has been used in commercial magnetic disk drive products. The use of PR models of the form (1-D) (1+D)/sup n/ where n>1 could potentially result in even higher storage densities. However, the computational complexity of the corresponding Viterbi decoders has hindered the use of such models in practice. The authors develop a novel decoding algorithm for PR systems of the above form which achieves near-optimal performance but requires less computation than Viterbi detection.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Observing Quantum State Diffusion by Heterodyne Detection of Fluorescence (2016)

A qubit can relax by fluorescence, which prompts the release of a photon into its electromagnetic environment. By counting the emitted photons, discrete quantum jumps of the qubit state can be observed. The succession of states occupied by the qubit in a single experiment, its quantum trajectory, depends in fact on the kind of detector. How are the quantum trajectories modified if one measures continuously the amplitude of the fluorescence field instead? Using a superconducting parametric amplifier, we perform heterodyne detection of the fluorescence of a superconducting qubit. For each realization of the measurement record, we can reconstruct a different quantum trajectory for the qubit. The observed evolution obeys quantum state diffusion, which is characteristic of quantum measurements subject to zeropoint fluctuations. Independent projective measurements of the qubit at various times provide a quantitative verification of the reconstructed trajectories. By exploring the statistics of quantum trajectories, we demonstrate that the qubit states span a deterministic surface in the Bloch sphere at each time in the evolution. Additionally, we show that when monitoring fluorescence field quadratures, coherent superpositions are generated during the decay from excited to ground state. Counterintuitively, measuring light emitted during relaxation can give rise to trajectories with increased excitation probability.
Physical and Functional Sensitivity of Zinc Finger Transcription Factors to Redox Change (1996)

Redox regulation of DNA-binding proteins through the reversible oxidation of key cysteine sulfhydryl groups has been demonstrated to occur in vitro for a range of transcription factors. The direct redox regulation of DNA binding has not been described in vivo, possibly because most protein thiol groups are strongly buffered against oxidation by the highly reduced intracellular environment mediated by glutathione, thioredoxin, and associated pathways. For this reason, only accessible protein thiol groups with high thiol-disulfide oxidation potentials are likely to be responsive to intracellular redox changes. In this article, we demonstrate that zinc finger DNA-binding proteins, in particular members of the Sp-1 family, appear to contain such redox-sensitive -SH groups. These proteins displayed a higher sensitivity to redox regulation than other redox-responsive factors both in vitro and in vivo. This effect was reflected in the hyperoxidative repression of transcription from promoters with essential Sp-1 binding sites, including the simian virus 40 early region, glycolytic enzyme, and dihydrofolate reductase genes. Promoter analyses implicated the Sp-1 sites in this repression. Non-Sp-1-dependent redox-regulated genes including metallothionein and heme oxygenase were induced by the same hyperoxic stress. The studies demonstrate that cellular redox changes can directly regulate gene expression in vivo by determining the level of occupancy of strategically positioned GC-binding sites.
A 13C NMR Determination of the Comonomer Sequence Distributions in Propylene-Butene-1 Copolymers (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA 13C NMR Determination of the Comonomer Sequence Distributions in Propylene-Butene-1 CopolymersJames C. RandallCite this: Macromolecules 1978, 11, 3, 592–597Publication Date (Print):May 1, 1978Publication History Published online1 May 2002Published inissue 1 May 1978https://pubs.acs.org/doi/10.1021/ma60063a032https://doi.org/10.1021/ma60063a032research-articleACS PublicationsRequest reuse permissionsArticle Views502Altmetric-Citations65LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Effect of nitric oxide and cell redox status on the regulation of endothelial cell xanthine dehydrogenase (1995)

We have previously reported that endothelial cell (EC) xanthine dehydrogenase/xanthine oxidase (XD/XO) activity correlates inversely with the O2 tension to which the cells are exposed. Whether this effect is related to the production of reactive O2 species is unclear. We exposed bovine pulmonary artery EC to various conditions that altered the redox status of the cells: 1) hypoxia (3% O2) and normoxia (20% O2); 2) menadione (MEN), known to generate O2 radicals; 3) catalase (CAT) and reduced glutathione (GSH), which detoxify H2O2; and 4) various NO-generating systems. Changes in intracellular XO and XO + XD activities were correlated with rates of extracellular H2O2 release from the same cells. Conditions that decreased extracellular H2O2 release (hypoxia, CAT, and GSH) produced significant and parallel increases in intracellular XO and XO + XD activities in a time-dependent fashion. MEN treatment increased extracellular release of H2O2 and subsequently reduced intracellular XO and XO + XD activities. NO-generating agents did not change extracellular release of H2O2 but significantly reduced XO and XO + XD activities. The latter effect was prevented by reduced hemoglobin. Scavengers of hydroxyl radicals reversed the inhibition of XO and XO + XD activities produced by MEN but not that produced by NO. While NO significantly inhibited XD/XO activity from rat epididymal fat pad, it did not affect XD/XO mRNA expression in these cells. We conclude that intracellular XD/XO activity is sensitive to changes in oxidant-generating and protective systems. Inhibition of XD/XO activity by NO may be mediated through direct binding of NO to the enzyme iron-sulfur moiety or to its sulfhydryl groups.(ABSTRACT TRUNCATED AT 250 WORDS)
<title>Fast multiplierless approximation of the DCT with the lifting scheme</title> (2000)

In this paper, we present a systematic approach to design two families of fast multiplierless approximations of the DCT with the lifting scheme, based on two kinds of factorizations of the DCT matrix with Givens rotations. A scaled lifting structure is proposed to reduce the complexity of the transform. Analytical values of all lifting parameters are derived, from which dyadic values with different accuracies can be obtained through finite-length approximations. This enables low-cost and fast implementations with only shift and addition operations. Besides, a sensitivity analysis is developed for the scaled lifting structure, which shows that for certain rotation angles, a permuted version of it is more robust to truncation errors. Numerous approximation examples with different complexities are presented for the 8-point and 16-point DCT. As the complexity increases, more accurate approximation of the floating DCT can be obtained in terms of coding gains, frequency responses, and mean square errors of DCT coefficients. Hence the lifting-based fast transform can be easily tailored to meet the demands of different applications, making it suitable for hardware and software implementations in real-time and mobile computing applications.
Low-temperature growth of piezoelectric AlN film by rf reactive planar magnetron sputtering (1980)

A single-crystalline aluminum nitride film is grown on a basal-plane sapphire substrate and the c-axis-oriented films are grown on glass and gold-film substrates at substrate temperatures as low as from 50 to 500 °C by using reactive rf planar magnetron sputtering. Surface acoustic waves are generated in both structures where interdigital transducers are located on the top of an aluminum nitride film and at the interface between the film and the substrate sapphire. The effective surface acoustic wave coupling factor k2 is 0.09 and 0.12%, respectively, for these interdigital transducer configurations. The aluminum nitride films sputtered on a gold film on a glass rod and on a glass sheet itself are also piezoelectric and used as bulk and surface acoustic wave transducers, respectively. These piezoelectric aluminum nitride films on glass and metal-film substrates have become available for the first time because film growth at low temperature has become possible in the present study.
Critical roles for mTORC2- and rapamycin-insensitive mTORC1-complexes in growth and survival of BCR-ABL-expressing leukemic cells (2010)

In recent years, there have been substantial research advances on the mechanisms by which BCR-ABL transforms hematopoietic cells and promotes leukemic cell growth and survival. Among the diverse signaling cascades activated by BCR-ABL, the mTOR pathway plays a critical role in mRNA translation of genes that promote leukemogenesis and mitogenic responses. We have recently shown that dual targeting of mTORC1 and mTORC2 complexes using a catalytic mTOR inhibitor, OSI-027, results in generation of potent antileukemic effects against BCR-ABL transformed cells. Such effects were also seen in cells expressing the T315I mutation, which is resistant to all currently approved BCR-ABL kinase inhibitors. Our studies also demonstrate that such dual catalytic inhibition of mTORC2 and mTORC1 complexes in BCR-ABL-expressing K562 cells results in induction of autophagy, and that inhibition of the autophagic process using chloroquine promotes apoptosis of these cells. Altogether, our studies suggest that autophagy may be a limiting factor for the induction of apoptosis during dual mTORC2-mTORC1 targeting, in at least some types of BCR-ABL-expressing cells and have raised the potential of combinations of catalytic inhibitors of mTOR with autophagy inhibitors for the treatment of refractory Ph(+) leukemias.
Range uncertainties in proton therapy and the role of Monte Carlo simulations (2012)

The main advantages of proton therapy are the reduced total energy deposited in the patient as compared to photon techniques and the finite range of the proton beam. The latter adds an additional degree of freedom to treatment planning. The range in tissue is associated with considerable uncertainties caused by imaging, patient setup, beam delivery and dose calculation. Reducing the uncertainties would allow a reduction of the treatment volume and thus allow a better utilization of the advantages of protons. This paper summarizes the role of Monte Carlo simulations when aiming at a reduction of range uncertainties in proton therapy. Differences in dose calculation when comparing Monte Carlo with analytical algorithms are analyzed as well as range uncertainties due to material constants and CT conversion. Range uncertainties due to biological effects and the role of Monte Carlo for in vivo range verification are discussed. Furthermore, the current range uncertainty recipes used at several proton therapy facilities are revisited. We conclude that a significant impact of Monte Carlo dose calculation can be expected in complex geometries where local range uncertainties due to multiple Coulomb scattering will reduce the accuracy of analytical algorithms. In these cases Monte Carlo techniques might reduce the range uncertainty by several mm.
Cyclic strain induces mouse embryonic stem cell differentiation into vascular smooth muscle cells by activating PDGF receptor β (2008)

Embryonic stem (ES) cells are exposed to fluid-mechanical forces, such as cyclic strain and shear stress, during the process of embryonic development but much remains to be elucidated concerning the role of fluid-mechanical forces in ES cell differentiation. Here, we show that cyclic strain induces vascular smooth muscle cell (VSMC) differentiation in murine ES cells. Flk-1-positive (Flk-1+) ES cells seeded on flexible silicone membranes were subjected to controlled levels of cyclic strain and examined for changes in cell proliferation and expression of various cell lineage markers. When exposed to cyclic strain (4-12% strain, 1 Hz, 24 h), the Flk-1+ ES cells significantly increased in cell number and became oriented perpendicular to the direction of strain. There were dose-dependent increases in the VSMC markers smooth muscle alpha-actin and smooth muscle-myosin heavy chain at both the protein and gene expression level in response to cyclic strain, whereas expression of the vascular endothelial cell marker Flk-1 decreased, and there were no changes in the other endothelial cell markers (Flt-1, VE-cadherin, and platelet endothelial cell adhesion molecule 1), the blood cell marker CD3, or the epithelial marker keratin. The PDGF receptor beta (PDGFR beta) kinase inhibitor AG-1296 completely blocked the cyclic strain-induced increase in cell number and VSMC marker expression. Cyclic strain immediately caused phosphorylation of PDGFR beta in a dose-dependent manner, but neutralizing antibody against PDGF-BB did not block the PDGFR beta phosphorylation. These results suggest that cyclic strain activates PDGFR beta in a ligand-independent manner and that the activation plays a critical role in VSMC differentiation from Flk-1+ ES cells.
Pleated Sheets and Turns ofβ-Peptides with Proteinogenic Side Chains (1999)

Components of a toolbox with predictable secondary structural elements: β-peptides. The β-peptide shown here with proteinogenic side chains adopts a parallel pleated sheet structure in the solid state upon incorporation of suitably configured β-amino acids. When a β-dipeptide turn segment is incorporated in the center, a hairpin is formed in solution.
AAV-mediated intramuscular delivery of myotubularin corrects the myotubular myopathy phenotype in targeted murine muscle and suggests a function in plasma membrane homeostasis (2008)

Myotubular myopathy (XLMTM, OMIM 310400) is a severe congenital muscular disease due to mutations in the myotubularin gene (MTM1) and characterized by the presence of small myofibers with frequent occurrence of central nuclei. Myotubularin is a ubiquitously expressed phosphoinositide phosphatase with a muscle-specific role in man and mouse that is poorly understood. No specific treatment exists to date for patients with myotubular myopathy. We have constructed an adeno-associated virus (AAV) vector expressing myotubularin in order to test its therapeutic potential in a XLMTM mouse model. We show that a single intramuscular injection of this vector in symptomatic Mtm1-deficient mice ameliorates the pathological phenotype in the targeted muscle. Myotubularin replacement in mice largely corrects nuclei and mitochondria positioning in myofibers and leads to a strong increase in muscle volume and recovery of the contractile force. In addition, we used this AAV vector to overexpress myotubularin in wild-type skeletal muscle and get insight into its localization and function. We show that a substantial proportion of myotubularin associates with the sarcolemma and I band, including triads. Myotubularin overexpression in muscle induces the accumulation of packed membrane saccules and presence of vacuoles that contain markers of sarcolemma and T-tubules, suggesting that myotubularin is involved in plasma membrane homeostasis of myofibers. This study provides a proof-of-principle that local delivery of an AAV vector expressing myotubularin can improve the motor capacities of XLMTM muscle and represents a novel approach to study myotubularin function in skeletal muscle.