gebhart/patrepeval huggingface dataset:
Amino poly(glycerol methacrylate)s for oligonucleic acid delivery with enhanced transfection efficiency and low cytotoxicity (2011)

To improve the transfection activity and reduce cell cytotoxicity of polycations with antisense oligonucleotide (AON), poly(glycidyl methacrylate)s (PGMAs) were modified with different amines, i.e., methylethylamine (MEA), 2-amino-1-butanol (2-ABO) and 4-amino-1-butanol (4-ABO). The structures of resulting polymers were well characterized and their thermal properties were studied by differential scanning calorimetry (DSC). The amino PGMA could self-assemble with AON in a Tris buffer solution, resulting in narrowly distributed polymer/AON complexes with a size of 0.1–0.3 μm at an amine-group-of-polymer/phosphate-group-of-nucleotide ratio (N/P ratio) of 0.5–3. Spherical nanoparticles of the complexes were visualized using atomic force microscopy (AFM), and the gel electrophoresis and zeta potential assay evidenced the formation of complexes at relatively low N/P ratios. Stability of the complexes towards dissociation was tested using ethidium bromide displacement assay. Protection of the incorporated AON against DNase I degradation was also evaluated. An increased charge ratio and a synergistic effect of hydrogen bonding in this system contributed to the increased stability of the complex, which prevents the incorporated AON from nuclease degradation. In vitro cytotoxicity experiments on COS-7 cells showed that all amino PGMAs displayed lower toxicity compared to the control PEI25k, except for the polymers with a relatively high molecular weight (30 kDa). In addition, the MEA modified linear and star-shaped PGMA (Mn in the range of 15–20 kDa) as well as 4-ABO modified linear PGMA complexes exhibited higher transfection efficiencies in vitro, compared to PEI25k. These results demonstrated that amino PGMAs with suitable amine groups and molecular weight can be used as safe and efficient AON delivery polymers.
Synthese von 2α‐Methoxycarbonyl‐A‐nor‐lupan (1968)

Abstract 2α‐Methoxycarbonyl‐A‐nor‐lupan ( 1b ) wurde aus Lupeol synthetisiert. Einige Verbindungen, die mehr als eine Sauerstoff‐Funktion im Ring A von Lupan tragen, wurden ebenfalls dargestellt.
Baculovirus-mediated Gene Delivery and RNAi Applications (2015)

Baculoviruses are widely encountered in nature and a great deal of data is available about their safety and biology. Recently, these versatile, insect-specific viruses have demonstrated their usefulness in various biotechnological applications including protein production and gene transfer. Multiple in vitro and in vivo studies exist and support their use as gene delivery vehicles in vertebrate cells. Recently, baculoviruses have also demonstrated high potential in RNAi applications in which several advantages of the virus make it a promising tool for RNA gene transfer with high safety and wide tropism.
Wavelet Steerability and the Higher-Order Riesz Transform (2010)

Our main goal in this paper is to set the foundations of a general continuous-domain framework for designing steerable, reversible signal transformations (a.k.a. frames) in multiple dimensions ( d >or= 2). To that end, we introduce a self-reversible, Nth-order extension of the Riesz transform. We prove that this generalized transform has the following remarkable properties: shift-invariance, scale-invariance, inner-product preservation, and steerability. The pleasing consequence is that the transform maps any primary wavelet frame (or basis) of [Formula: see text] into another "steerable" wavelet frame, while preserving the frame bounds. The concept provides a functional counterpart to Simoncelli's steerable pyramid whose construction was primarily based on filterbank design. The proposed mechanism allows for the specification of wavelets with any order of steerability in any number of dimensions; it also yields a perfect reconstruction filterbank algorithm. We illustrate the method with the design of a novel family of multidimensional Riesz-Laplace wavelets that essentially behave like the N th-order partial derivatives of an isotropic Gaussian kernel.
A Trans-Acting Factor that Binds to a GT-motif in a Phytochrome Gene Promoter (1990)

The regulatory photoreceptor, phytochrome, controls the expression of numerous genes, including its own phyA genes, which are transcriptionally repressed in response to light. Functional analysis of a rice phyA gene promoter, by means of microprojectile-mediated gene transfer, indicates that a GT motif, GCGGTAATT, closely related to elements in the promoters of a number of other light-regulated genes, is critical for expression. Partial complementary DNA clones have been obtained for a rice nuclear protein, designated GT-2, that binds in a highly sequence-specific fashion to this motif. Mutational analysis shows that the paired G's are most crucial to binding. GT-2 has domains related to certain other transcription factors. Northern blot analysis shows that GT-2 messenger RNA levels decline in white light although red and far red light pulses are ineffective.
Activation of the Ras/Mitogen-Activated Protein Kinase Pathway by Kinase-Defective Epidermal Growth Factor Receptors Results in Cell Survival but Not Proliferation (1998)

Signalling by the epidermal growth factor (EGF) receptor (EGFR) has been studied intensively, but for most cell types the analysis is complicated by the fact that EGFR not only homodimerizes but can also form heterodimers with other EGFR family members. Heterodimerization is a particular problem in the study of EGFR mutants, where the true phenotype of the mutants is confounded by the contribution of the heterodimer partner to signal transduction. We have made use of the murine hemopoietic cell line BaF/3, which does not express EGFR family members, to express wild-type (WT) EGFR, three kinase-defective EGFR mutants (V741G, Y740F, and K721R), or a C-terminally truncated EGFR (CT957) and have measured their responses to EGF. We found that under the appropriate conditions EGF can stimulate cell proliferation of BaF/3 cells expressing WT or CT957 EGFRs but not that of cells expressing the kinase-defective mutants. However, EGF promotes the survival of BaF/3 cells expressing either of the kinase-defective receptors (V741G and Y740F), indicating that these receptors can still transmit a survival signal. Analysis of the early signalling events by the WT, V741G, and Y740F mutant EGF receptors indicated that EGF stimulates comparable levels of Shc phosphorylation, Shc-GRB-2 association, and activation of Ras, B-Raf, and Erk-1. Blocking the mitogen-activated protein kinase (MAPK) signalling pathway with the specific inhibitor PD98059 abrogates completely the EGF-dependent survival of cells expressing the kinase-defective EGFR mutants but has no effect on the EGF-dependent proliferation mediated by WT and CT957 EGFRs. Similarly, the Src family kinase inhibitor PP1 abrogates EGF-dependent survival without affecting proliferation. However blocking phosphatidylinositol-3-kinase or JAK-2 kinase with specific inhibitors does arrest growth factor-dependent cell proliferation. Thus, EGFR-mediated mitogenic signalling in BaF/3 cells requires an intact EGFR tyrosine kinase activity and appears to depend on the activation of both the JAK-2 and PI-3 kinase pathways. Activation of the Src family of kinases or of the Ras/MAPK pathway can, however, be initiated by a kinase-impaired EGFR and is linked to survival.
Experimental Protection of Mice against Lethal Staphylococcus aureus Infection by Novel Bacteriophage φMR11 (2003)

The protective effects of bacteriophages were assessed against experimental Staphylococcus aureus infection in mice. Of the S. aureus phages isolated in the study, phi MR11 was representatively used for all testing, because its host range was the most broad and it carries no genes for known toxins or antibiotic resistance. Intraperitoneal injections (8 x 10(8) cells) of S. aureus, including methicillin-resistant bacteria, caused bacteremia and eventual death in mice. In contrast, subsequent intraperitoneal administration of purified phi MR11 (MOI > or = 0.1) suppressed S. aureus-induced lethality. This lifesaving effect coincided with the rapid appearance of phi MR11 in the circulation, which remained at substantial levels until the bacteria were eradicated. Inoculation with high-dose phi MR11 alone produced no adverse effects attributable to the phage. These results uphold the efficacy of phage therapy against pernicious S. aureus infections in humans and suggest that phi MR11 may be a potential prototype for gene-modified, advanced therapeutic S. aureus phages.
Identification of TNF-LT blocking factor(s) in the serum and ultrafiltrates of human cancer patients. (1990)

Human serum ultrafiltrate (UFS) obtained from cancer patients contains material(s) which inhibit the cytolytic activity of tumor necrosis factor (TNF-alpha) and lymphotoxin (LT-TNF-beta) in vitro. These factors are found in UFS from patients with different types of cancers and are not detected in the sera of normal donors. Results from molecular sizing studies demonstrated that their molecular weights are over 30 kD. They appear to block by interfering with the early stages of cell lysis. It is not clear whether or not these TNF-LT blocking factor(s) are the same molecules. These factors may have adverse effects on the biological activities of TNF and LT in cancer patients.
Photochemistry of refractive index structures in poly(methyl methacrylate) by femtosecond laser irradiation (2006)

Femtosecond, subablation threshold photomodification of poly(methyl methacrylate) (PMMA) at 387 nm is explored to enable fabrication of optical components. Volatile fragment analysis (thermal desorption gas chromatography-mass spectrometry) and molecular weight distribution monitoring (size exclusion chromatography) suggest photochemical modification, involving direct cleavage of the polymer backbone and propagation via chain unzipping under formation of monomers, similar to the pyrolytic degradation of PMMA. Waveguides were produced in undoped, clinical-grade PMMA, showing an increased refractive index in the laser focal region (Dnmax=4x10(-3)).
Bladder Surface Glycosaminoglycans: An Epithelial Permeability Barrier (1990)

Sulfated polysaccharide's ability to modulate the movement of small molecules was examined both in vivo and in vitro. For the in vivo test, the rabbit bladder was utilized and C-14 labeled urea 45-Ca, or 3H2O was placed into the lumen of control bladders, bladders pretreated with protamine sulfate (20 mg./cc) and bladders pretreated with protamine sulfate (20 mg./cc) plus pentosanpoly-sulfate (PPS), 10 mg./cc. After 45 minutes, the controls absorbed 21% of the urea, 16% of the calcium, and 38% of the 3H2O; the protamine treated group 40% urea, 23% calcium, and 51% H2O; the PPS only group 22% urea and the protamine plus PPS group absorbed 24% of urea, 18% calcium, and 44% water. Differences between the control and protamine groups were statistically significant, p less than 0.01 for urea 45-Ca and 3H2O. The bladder mucosa contained a significantly higher concentration of urea and calcium after protamine treatment which were both reversed by PPS (p less than 0.01) while 3H2O content went down significantly (p = 0.03), reflecting a loss of the hydrophilic effect of bladder GAG. The control mucosas had 250 cpm/mg. tissue urea for Ca 64 cpm/mg. and water 262 cpm/mg., the protamine group urea 498 cpm/mg., Ca 190 cpm/mg., and H2O 139 cpm/mg.; the protamine plus PPS group urea 344 cpm/mg., Ca 129 cpm/mg., and water 168 cpm/mg. For the in vitro studies, an Ussing chamber was employed. Normal rabbit bladder membranes were placed in the chambers and the potential difference was zeroed across the membrane. There were three groups, membranes that were treated only with the irrigating solution, membranes pretreated with protamine, and membranes pretreated with protamine plus PPS. At the end of 40 minutes, there was an approximately 1.2% movement of urea across the control membrane, a 3.5% movement across the protamine treated membrane (a significant increase p less than 0.001) and a 1.1% movement across the protamine plus PPS treated membrane. It would appear that the surface polysaccharide may play an important role as a bladder permeability barrier in modulating both charged and uncharged small molecule movement in that its ability to impair such movement can be inhibited by protamine and this protamine effect can be reversed by a treatment with an exogenous sulfated polysaccharide.
Scalable synthesis of sequence-defined, unimolecular macromolecules by Flow-IEG (2015)

We report a semiautomated synthesis of sequence and architecturally defined, unimolecular macromolecules through a marriage of multistep flow synthesis and iterative exponential growth (Flow-IEG). The Flow-IEG system performs three reactions and an in-line purification in a total residence time of under 10 min, effectively doubling the molecular weight of an oligomeric species in an uninterrupted reaction sequence. Further iterations using the Flow-IEG system enable an exponential increase in molecular weight. Incorporating a variety of monomer structures and branching units provides control over polymer sequence and architecture. The synthesis of a uniform macromolecule with a molecular weight of 4,023 g/mol is demonstrated. The user-friendly nature, scalability, and modularity of Flow-IEG provide a general strategy for the automated synthesis of sequence-defined, unimolecular macromolecules. Flow-IEG is thus an enabling tool for theory validation, structure-property studies, and advanced applications in biotechnology and materials science.
Prevention of rejection of murine islet allografts by pretreatment with anti-dendritic cell antibody. (1984)

Previously we have demonstrated that islets of Langerhans treated with donor-specific anti-Ia serum and complement survive when transplanted across the major histocompatibility complex of the mouse. In this study, using immunofluorescence, we demonstrate two morphologically distinct populations of Ia-positive cells scattered within the Ia-negative islet tissue. A large irregularly shaped Ia-positive subset of cells were identified as dendritic cells by using the 33D1 antibody specific for a mouse dendritic cell antigen. The other small, round Ia-positive subset was 33D1 negative. Islets pretreated with anti-dendritic cell antibody and complement prior to transplantation survived in their histoincompatible recipients for greater than 200 days. Rejection of stable islet allografts promptly occurred when transplant recipients were challenged with 1 X 10(5) donor dendritic cells 60 days after transplantation. These results demonstrate an important in vivo role for donor dendritic cells in the stimulation of allograft rejection.
The effect of heat setting on the structure and mechanical properties of poly(ethylene terephthalate) fiber. II. The elastic modulus and its dependence on structure (1981)

Abstract The effects of temperature, time of heat setting, and rate of cooling on the elastic modulus of free‐and taut‐annealed poly(ethylene terephthalate) (PET) fibers were determined at different time scales using Instron, Rheovibron, and pulse propagation meter. The correlation of the elastic modulus with structure is critically examined in terms of the widely used simple one‐phase and two‐phase models for fiber modulus. It is concluded that these simple models are not universally applicable.
Inhibition by Eicosapentaenoic Acid of Oxidized-LDL- and Lysophosphatidylcholine-Induced Human Coronary Artery Smooth Muscle Cell Production of Endothelin (2001)

The objectives of the present study were (1) to determine whether oxidized low-density lipoprotein (LDL) and lysophosphatidylcholine (lyso-PC), a major phospholipid component of oxidized LDL, stimulate the production of endothelin-1 (ET)-1 in cultured human coronary artery smooth muscle cells (SMCs), and (2) to examine the possible effect of an antiatherogenic agent, eicosapentaenoic acid (EPA), on oxidized-LDL- and lyso-PC-stimulated ET-1 production in these cells. Oxidized LDL (10-50 microg/ml) and lyso-PC (10(-7) to 10(-5) mol/l) stimulated ET-1 production in a concentration-dependent manner. By contrast, the effects of native LDL and phosphatidylcholine were modest or absent. Lyso-PC (10(-7) to 10(-5) mol/l) and oxidized LDL (10-50 microg/ml) significantly induced particulate protein kinase C (PKC) activation. Lyso-PC- and oxidized-LDL-stimulated ET-1 production was significantly inhibited by PKC inhibitor, PKC (19-36). EPA (80-160 micromol/l) clearly suppressed ET-1 production stimulated by oxidized LDL and lyso-PC in a concentration-dependent manner. Furthermore, EPA (160 micromol/l) significantly inhibited lyso-PC (10(-5) mol/l)- and oxidized LDL (50 microg/ml)-induced particulate PKC activation. Results suggest that oxidized LDL and lyso-PC stimulate ET-1 production by a mechanism involving activation of PKC, and that EPA suppresses ET-1 production stimulated by lyso-PC as well as oxidized LDL probably through the modulation of PKC in human coronary artery SMCs. EPA may exert an antiatherosclerotic effect, in part, through these mechanisms.
The cytoskeletal linking proteins, moesin and radixin, are upregulated by platelet-derived growth factor, but not basic fibroblast growth factor in experimental mesangial proliferative glomerulonephritis. (1996)

The expression of the two cytoskeletal linking proteins, moesin and radixin, was examined in experimental mesangial proliferative nephritis in rats (anti-Thy1 model). Moesin and radixin mRNA and protein are constitutively expressed in all cell types of normal rat glomeruli, except podocytes. In the anti-Thy1 model the expression of moesin and radixin was increased in infiltrating macrophages and in activated, alpha-smooth muscle actin-positive mesangial cells and was concentrated in the cellular extensions of mesangial cells in areas of glomerular remodelling. Studies using neutralizing antibodies demonstrated that the increase in moesin and radixin expression by mesangial cells is mediated by PDGF, but not bFGF. The increase in these cytoskeletal proteins appears to be regulated primarily (radixin) or partially (moesin) posttranscriptionally. The data suggest that PDGF mediated upregulation of the cytoskeletal proteins, moesin and radixin, is important for cell migration and other changes that accompany the coordinated restoration of glomerular architecture after injury.
Clinical experience with flupirtine in the U.S. (1987)

Flupirtine, a chemically unique, orally effective, non-narcotic, centrally acting analgesic was evaluated for efficacy and safety in five parallel, double-blind randomized clinical trials which included both placebo and active control comparisons. Flupirtine was given in oral doses of 100 to 300 mg, with a maximum daily dose of 600 mg to patients with pain resulting from episiotomy, surgical or dental procedures. Patients rated pain intensity, pain relief and adverse experiences at regular intervals up to 6 hours following medication. Assessments of efficacy included measures of the sum of pain intensity differences (SPID), total pain relief (TOPAR) and peak analgesia (PPID). More than 1300 patients have been evaluated at 26 study sites in the United States. More than 170 of them received flupirtine 100 mg, 250 received 200 mg and 50 received 300 mg. An additional 415 patients received positive control medications (paracetamol 650 mg, codeine 60 mg, pentazocine 50 mg or oxycodone 10 mg plus paracetamol 650 mg). All doses of flupirtine produced analgesia after a single dose. Pharmacokinetic evaluations have shown linear kinetics for flupirtine and a 100 mg t.i.d. dosage schedule produces average steady-state blood levels equivalent to the peak response for a single 200 mg dose. Adverse experiences occurring in flupirtine clinical studies have been minimal in incidence, nature and degree, with drowsiness being the most frequently reported reaction (approximately 10%).
Clinical Evaluation of Two Methods for Genotyping Hepatitis C Virus Based on Analysis of the 5′ Noncoding Region (2003)

We compared the performance characteristics of a standardized direct sequencing method (TRUGENE HCV 5'NC; Visible Genetics Inc., Toronto, Ontario, Canada) and a reverse hybridization line probe assay (INNO-LiPA HCV II; Bayer Corp., Tarrytown, N.Y.) for genotyping of hepatitis C virus (HCV). Both methods are based on detection of sequence heterogeneity in the 5' noncoding (5'NC) region. Concordance between the genotyping methods was assessed by testing 172 samples representing the six major genotypes. Sequence analysis of the more phylogenetically informative nonstructural 5B (NS5B) region was also done with 148 (86%) samples to confirm the accuracy of and resolve discrepancies between the 5'NC genotyping results. The sensitivities of the methods were assessed by using the 5'NC amplicon from both the qualitative and quantitative AMPLICOR HCV tests (Roche Diagnostics Corp., Indianapolis, Ind.). The ability of the methods to detect mixed-genotype infections was determined with mixtures of two different genotypes at relative concentrations ranging from 1 to 50%. Both 5'NC methods were able to genotype 99.4% of the samples with type agreement for 99.5% and subtype agreement for 68.2% of the samples. No or ambiguous subtype results were found by the line probe assay for 16.5% and by the TRUGENE 5'NC test for 17.1% of the samples. Discrepancies occurred between the line probe assay and NS5B results at the type level for 1.4% of the samples and at the subtype level for 14.2% of the samples. Discrepancies also occurred between the TRUGENE 5'NC and NS5B results at the type level for 2% of the samples and at the subtype level for 8.1% of the samples. We also found two distinct strains of HCV classified as type 2 by analysis of the 5'NC region that were type 1 by analysis of the NS5B region. The sensitivities of the two 5'NC genotyping methods were comparable and dependent on the amplification test used ( approximately 10(3) IU/ml with the qualitative HCV RNA tests and approximately 10(5) IU/ml with the quantitative HCV RNA tests). Genotype mixtures were successfully identified at a relative concentration of 5% by the line probe assay and 10% by the TRUGENE 5'NC test. In conclusion, the performance characteristics of the 5'NC methods were similar and both methods produced accurate results at the genotype level but neither method should be used for subtyping.
Assessing amino acid uptake by phototrophic nanoflagellates in nonaxenic cultures using flow cytometric sorting (2009)

Biologically available concentrations of individual dissolved amino acids in the open ocean are generally <1 nM. Despite this, the microbial turnover of amino acids is usually measured in hours indicating high demand. It is thought that the majority of uptake is due to bacterioplankton, although protists, particularly phototrophic protists, are also expected to take up amino acids. In order to assess the ability of protists to compete with prokaryotes for amino acids at subnanomolar concentrations, we examined the direct uptake of (3)H-leucine by phototrophic nanoflagellates (prasinophytes, pelagophytes and trebouxiophytes) and by associated bacteria using flow cytometric cell sorting. In contrast to (3)H-leucine-assimilating bacterial copopulations, none of the six studied nanoflagellates showed measurable direct uptake of (3)H-leucine, suggesting that the studied phototrophic protists were unable to utilize dissolved (3)H-leucine at natural oceanic concentrations. More practically, the flow-sorting technique allowed rapid and unequivocal differentiation of organic nitrogen uptake between prokaryotic cells and eukaryotic cells in mixed microbial populations, reducing the need to establish and maintain axenic algal cultures.