gebhart/patrepeval huggingface dataset:
[Gene therapy of cardiovascular disorders]. (1999)

More than 300 protocols have been developed for human gene therapy, but, it has not yet been proved to be a successful therapeutic strategy. One of the most important barriers to success is the development of efficient gene delivery systems. We have developed HVJ-liposomes by combining fusion proteins of HVJ (Hemagglutinating virus of Japan; Sendai virus) with liposomes containing DNA. This vector system has been very effective for in vivo gene delivery, especially in cardiovascular systems. Using HVJ-liposomes, we have reported successful gene therapy experiments such as prevention of restenosis after balloon injury, suppression of dysfunction of vein graft, and experimental ischemic disorders. Indeed, the success in the treatment of arteriosclerosis obliterance by VEGF (vascular endothelial growth factor) gene transfer was reported recently. These cardiovascular gene therapy strategies appear to be very promising therapeutics in future.
ChemInform Abstract: anti‐HIV Phosphotriester Pronucleotides: Basis for the Rational Design of Biolabile Phosphate Protecting Groups (2000)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Functionalized Lineage Tracing Can Enable the Development of Homogenization-Based Therapeutic Strategies in Cancer (2022)

The therapeutic landscape across many cancers has dramatically improved since the introduction of potent targeted agents and immunotherapy. Nonetheless, success of these approaches is too often challenged by the emergence of therapeutic resistance, fueled by intratumoral heterogeneity and the immense evolutionary capacity inherent to cancers. To date, therapeutic strategies have attempted to outpace the evolutionary tempo of cancer but frequently fail, resulting in lack of tumor response and/or relapse. This realization motivates the development of novel therapeutic approaches which constrain evolutionary capacity by reducing the degree of intratumoral heterogeneity prior to treatment. Systematic development of such approaches first requires the ability to comprehensively characterize heterogeneous populations over the course of a perturbation, such as cancer treatment. Within this context, recent advances in functionalized lineage tracing approaches now afford the opportunity to efficiently measure multimodal features of clones within a tumor at single cell resolution, enabling the linkage of these features to clonal fitness over the course of tumor progression and treatment. Collectively, these measurements provide insights into the dynamic and heterogeneous nature of tumors and can thus guide the design of homogenization strategies which aim to funnel heterogeneous cancer cells into known, targetable phenotypic states. We anticipate the development of homogenization therapeutic strategies to better allow for cancer eradication and improved clinical outcomes.
Direct and Combined Revascularization in Pediatric Moyamoya Disease (1999)

Surgical revascularization by direct anastomosis in pediatric patients is technically feasible, is well tolerated, and can improve the progressive natural history, the angiographic appearance, and the cerebral blood flow abnormalities associated with the disease. Direct revascularization has the advantage of providing immediate and high-flow revascularization and is particularly useful for patients who have experienced failure of previous indirect revascularization procedures.
Potential Environmental Impacts and Antimicrobial Efficacy of Silver- and Nanosilver-Containing Textiles (2016)

For textiles containing nanosilver, we assessed benefit (antimicrobial efficacy) in parallel with potential to release nanosilver (impact) during multiple life cycle stages. The silver loading and method of silver attachment to the textile highly influenced the silver release during washing. Multiple sequential simulated household washing experiments for fabric swatches in deionized water with or without detergent showed a range of silver release. The toxicity of washing experiment supernatants to zebrafish (Danio rerio) embryos was negligible, with the exception of the very highest Ag releases (∼1 mg/L Ag). In fact, toxicity tests indicated that residual detergent exhibited greater adverse response than the released silver. Although washing the fabrics did release silver, it did not affect their antimicrobial efficacy, as demonstrated by >99.9% inhibition of E. coli growth on the textiles, even for textiles that retained as little as 2 μg/g Ag after washing. This suggests that very little nanosilver is required to control bacterial growth in textiles. Visible light irradiation of the fabrics reduced the extent of Ag release for textiles during subsequent washings. End-of-life experiments using simulated landfill conditions showed that silver remaining on the textile is likely to continue leaching from textiles after disposal in a landfill.
CD3‐induced apoptosis of CD4+CD8+ thymocytes in the absence of clonotypic T cell antigen receptor (1996)

Abstract Clonal selection of T cells mediated through the T cell antigen receptor (TCR) mostly occurs at the CD4 + CD8 + double positive thymocyte stage. Immature CD4 + CD8 + thymocytes expressing self‐reactive TCR are induced to die upon clonotypic engagement of TCR by self antigens. CD3 engagement by antibody of the surface TCR‐CD3 complex is known to induce apoptosis of CD4 + CD8 + thymocytes, a process that is generally thought to represent antigen‐induced negative selection in the thymus. The present study shows that the CD3‐induced apoptosis of CD4 + CD8 + thymocytes can occur even in TCRα − mutant mice which do not express the TCRαβ/CD3 antigen receptor. Anti‐CD3 antibody induces death of CD4 + CD8 + thymocytes in TCRα − mice either in cell cultures or upon administration in vivo . Interestingly, most surface CD3 chains expressed on CD4 + CD8 + thymocytes from TCRα − mice are not associated with clonotypic TCR chains, including TCRβ. Thus, apoptosis of CD4 + CD8 + thymocytes appear to be induced through the CD3 complex even in the absence of clonotypic antigen receptor chains. These results shed light on previously unknown functions of the clonotype‐independent CD3 complex expressed on CD4 + CD8 + thymocytes, and suggest its function as an apoptotic receptor inducing elimination of developing thymocytes.
Poly(triacetylene) Oligomers: Synthesis, Characterization, and Estimation of the Effective Conjugation Length by Electrochemical, UV/Vis, and Nonlinear Optical Methods (1997)

Abstract Poly(triacetylene)s [PTAs, (CCCRCRCC) n –] are a new class of linearly conjugated polymers with a nonaromatic all‐carbon backbone. To explore structure–property relationships in PTAs, we prepared a series of monodisperse oligomers ranging from monomer to hexamer by oxidative Glaser–Hay coupling of a bifunctional („chain‐forming”︁) ( E )‐hex‐3‐ene‐1,5‐diyne in the presence of an endcapping unit. All six oligomers are amazingly stable towards exposure to light, air, and temperatures beyond their melting points. They have been fully characterized and are readily soluble in a wide range of solvents. The conjugated rods are reversibly reduced in one‐electron transfer steps and cannot be oxidized below +1.23 V vs. Fc/Fc + . The effective conjugation length in PTAs was estimated from the electronic absorption (UV/Vis) data, and various evaluation methods yielded convergence of the optical properties in the range of 7 to 10 monomer units. The nonresonant second‐order molecular hyperpolarizability γ was measured in CHCl 3 by means of the third harmonic generation (THG) at Δ = 1.907 μm. A plot of γ/ n vs. n revealed a power law γ ≈ n a for γ with a fitted exponent a = 2.5 ∓ 0.1. From the THG measurements, an effective conjugation length of about 10 monomer units was found, in surprisingly good agreement with the value obtained from UV/Vis spectroscopy data.
Polyphenylene ether based thin-film nonlinear optical materials having high chromophore densities and alignment stability [Erratum to document cited in CA112(14):119567m] (1990)

The structures of the dimethylphenol and its derivatives in Scheme I should be the 2,6 isomers.
IL-33 isoforms: their future as vaccine adjuvants? (2015)

The identification and characterization of cytokine isoforms is likely to provide critical important new insight into immunobiology. Cytokine isoforms can provide additional diversity to their complex biological effects that participate in control and protection against different foreign pathogens. Recently, IL-33 has been identified as a proinflammatory cytokine having several different biologically active isoform products. Originally associated with Th2 immunity, new evidence now supports the role of two IL-33 isoforms to facilitate the generation of protective Th1 and CD8 T cell immunity against specific pathogens. Therefore, a better understanding of the IL-33 isoforms will inform us on how to utilize them to facilitate their development as tools as vaccine adjuvants for immune therapy.
Control Strategy for Long-Term Station-Keeping on Near-Rectilinear Halo Orbits (2020)

This work considers the control of a spacecraft in indefinite near-rectilinear halo orbit about the Earth-Moon L2. For indefinite station-keeping, it is important to minimize fuel consumption, while allowing for occasional transfer to a new orbit. The control scheme therefore consists of two components: the first component is the tracking of the nominal NRHO and the second component is an orbit correction maneuver between NRHO trajectories. The nominal NRHO is computed using a multiple-shooting technique that takes into account all forces on the spacecraft whose magnitude is larger than the dominant disturbance forces caused by navigational error. The tracking component is a linear-quadratic regulation scheme that rejects disturbances caused by orbit determination error, using a Lyapunov sublevel set that models the state covariance generated using sequential Kalman filter. The orbit correction maneuver is computed to minimize fuel costs.
microRNA expression profiling identifies molecular signatures associated with anaplastic large cell lymphoma (2013)

Anaplastic large-cell lymphomas (ALCLs) encompass at least 2 systemic diseases distinguished by the presence or absence of anaplastic lymphoma kinase (ALK) expression. We performed genome-wide microRNA (miRNA) profiling on 33 ALK-positive (ALK[+]) ALCLs, 25 ALK-negative (ALK[-]) ALCLs, 9 angioimmunoblastic T-cell lymphomas, 11 peripheral T-cell lymphomas not otherwise specified (PTCLNOS), and normal T cells, and demonstrated that ALCLs express many of the miRNAs that are highly expressed in normal T cells with the prominent exception of miR-146a. Unsupervised hierarchical clustering demonstrated distinct clustering of ALCL, PTCL-NOS, and the AITL subtype of PTCL. Cases of ALK(+) ALCL and ALK(-) ALCL were interspersed in unsupervised analysis, suggesting a close relationship at the molecular level. We identified an miRNA signature of 7 miRNAs (5 upregulated: miR-512-3p, miR-886-5p, miR-886-3p, miR-708, miR-135b; 2 downregulated: miR-146a, miR-155) significantly associated with ALK(+) ALCL cases. In addition, we derived an 11-miRNA signature (4 upregulated: miR-210, miR-197, miR-191, miR-512-3p; 7 downregulated: miR-451, miR-146a, miR-22, miR-455-3p, miR-455-5p, miR-143, miR-494) that differentiates ALK(-) ALCL from other PTCLs. Our in vitro studies identified a set of 32 miRNAs associated with ALK expression. Of these, the miR-17∼92 cluster and its paralogues were also highly expressed in ALK(+) ALCL and may represent important downstream effectors of the ALK oncogenic pathway.
H{sub 2}O{sub 2} enhanced thermal oxidation of n-heptane and chlorobenzene (1995)

The destruction of certain volatile organic compounds (VOCs) by incineration requires high temperatures and long residence times. The oxidation process occurs by a complex series of reactions initiated and propagated by free radicals. It was postulated that the addition of hydrogen peroxide to a heated stream of VOCs in air would enhance the kinetics of thermal oxidation. In this work, the VOCs studied include n-heptane and chlorobenzene. Results show that H{sub 2}O, is effective in enhancing the thermal destruction of both compounds. Computer kinetic modeling was done using the Chemkin II program package and the predicted products of incomplete combustion (PICs) were compared with those found experimentally using GC and GC-MS analysis. Although the model does not accurately predict PICs for both parent compounds, the experimental data for further adjustments of the model and a better understanding of what reactions may be of importance in the proposed mechanisms.
CpG oligodeoxynucleotides induce cyclooxygenase‐2 and prostaglandin synthesis in human B lymphocytes: Implications for antibody production and innate immunity. (2008)

Many chronic inflammatory diseases are characterized by infiltrates of B cells and plasma cells coupled with high prostaglandin (PG) levels. B cells were not previously thought to express cyclooxygenase‐2 (Cox‐2) and PGs. Interest in CpG oligodeoxynucleotides (ODN) is fueled by clinical trials that show CpG ODN enhance antibody production and act as adjuvants. Since antibodies play a key role in fighting infections, it is important to understand how CpG ODN affect human B cells and influence antibody production. We recently demonstrated that activated human B cells highly express Cox‐2 and that Cox‐2 activity is crucial for optimal antibody production ( J. Immunology , 177:7811, 2006). Herein, we tested the hypothesis that CpG ODNs induce human B cell Cox‐2 and that Cox‐2 activity is important for optimal antibody production. Exposure of human B lymphocytes to synthetic CpG ODN sequences increased steady‐state Cox‐2 mRNA levels and induced Cox‐2 protein. Importantly, CpG‐induced IgM and IgG production was attenuated following inhibition of Cox‐2 activity by selective drug inhibitors. CpG motifs therefore enhance antibody production by directly stimulating B cells and by inducing Cox‐2. These findings support the concept that drugs that attenuate Cox‐2 activity can reduce optimal antibody response to adjuvants/vaccination.
Implementation of auto-rectification and depth estimation of stereo video in a real-time smart camera system (2008)

In this paper, we present a real-time, low power, and wireless embedded stereo vision system. The system consists of WiCa board (Wireless Camera board) and the methods developed using a smart camera processor, IC3D. IC3D is an SIMD video-analysis processor that has 320 processor elements. The proposed auto-rectification method is suitable for a parallel stereo system like WiCa. It is based on the matching of a planar background. After rectification, the two images of the background are coincident with each other, i.e., both the vertical and horizontal disparity of the background plane is removed. Then a dense matching method is implemented to achieve the depth map of the foreground object. Left-to-right checking and reliability checking is applied to reduce the error of the estimated depth. The system runs at 30fps and handles disparity up to 37 pixels in CIF (320×240 pixels) mode.
Kienböck's disease. Results of treatment with ulnar lengthening. (1984)

Further experience with ulnar lengthening in the treatment of 22 patients with Kienböck's disease confirms the efficacy of this procedure as observed in a previous series of 20 patients. In this procedure, the joint compressive force is removed from the trabeculae of the convex portion of the body of the lunate that is weakened by avascular necrosis. Subchondral fractures were present in at least 13 of the 22 patients. The technique of ulnar osteotomy, with interposition bone graft supported by a slotted bone plate applied prior to completion of the osteotomy, seems well established. Three patients were lost to follow-up and one required a secondary lunate excision for continuing pain. The remainder of the patients were well satisfied with the procedure.
Thyroxine induces cyclosporin A‐insensitive, Ca2+‐dependent reversible permeability transition pore in rat liver mitochondria (1997)

The effect of thyroxine on Ca2+-dependent mitochondrial permeability transition has been examined. It is shown that 40 microM thyroxine induces high amplitude swelling and decrease in membrane potential in Ca2+-loaded rat liver mitochondria, both in the presence and absence of cyclosporin A. Thyroxine-induced decrease in membrane potential is partially or completely reversed by addition of EGTA into the incubation medium. Nigericin and ADP are shown to prevent, or significantly delay, the effects of thyroxine on both mitochondrial swelling and membrane potential, whereas nicotinamide potentiates the permeabilisation of mitochondria. It is suggested that thyroxine induced reversible, cyclosporin A-insensitive permeability transition pore (PTP) opening in the inner mitochondrial membrane.
2'-C-Methyladenosine and 2'-C-methyluridine 5'-diphosphates are mechanism-based inhibitors of ribonucleoside diphosphate reductase from Corynebacterium nephridii (1993)

The interaction of the adenyosylcobalamin-dependent ribonucleoside diphosphate reductase of Cornyebacterium nephridii with 2'-C-methyladenosine 5'-diphosphate (2'-MeADP) and 2'-C-methyluridine 5'-diphosphate (2'-MeUDP) has been investigated. The nucleotide analogs are converted to adenine and uracil, respectively, suggesting that they may be mechanism-based inhibitors. In addition, both analogs generate nucleotides with properties expected for the 2'-deoxy-2'-C-methylnucleotides. The nucleoside obtained after enzymatic dephosphorylation of the product formed from 2'-MeADP has been identified as 2'-deoxy-2'-C-methyladenosine by 1H NMR and mass spectroscopies. Adenine is the major product derived from 2'-MeADP, indicating that the degradation pathway predominates. During the reaction, the carbon-cobalt bond of the coenzyme is cleaved irreversibly to yield 5'-deoxyadenosine and cob(II)alamin. 2'-MeADP is a potent competitive inhibitor of the reduction of the purine nucleotides ADP and GDP, while 2'-MeUDP competitively inhibits the reduction of the pyrimidine nucleotides UDP and CDP. 2'-MeADP is a very effective promoter of the tritium exchange reaction between [5'-3H2]adenosylcobalamin and the solvent, indicating that the exchange reaction is an integral part of the overall reduction. All these observations are consistent with the reaction mechanism proposed by Stubbe and co-workers [Harris, G., Ashley, G. W., Robins, M. J., Tolman, R. L., & Stubbe, J. (1987) Biochemistry 26, 1895-1902 (1987); Stubbe, J. (1990) J. Biol. Chem. 265, 5329-5332] in which they suggest that the partitioning between reduction and inactivation occurs at the level of the 2'-deoxy-3'-ketoribonucleotide intermediate.
Macromol. React. Eng. 1/2017 (2017)

Front Cover: Alkylaluminums such as trialkylaluminum (TOA) perform multiple functions during olefin polymerization using borates and metallocene catalysts, such as scavenging catalyst poisons, alkylating transition metal–chloride bonds, deactivation of the catalyst sites and chain transfer reactions. The figures show how alkylation reaction, deactivation of the catalyst sites and chain transfer by TOA can be manifested by recording monomer profiles, kinetic modeling and molecular weight measurement. (Fig A labels on the right indicate TOA concentration in the reactor in μmol/L). More details can be found in article, number 1600044, by Saeid Mehdiabadi, João B. P. Soares,* Jeffrey Brinen.
Aging-induced dielectric relaxation in barium titanate ceramics (2007)

In this letter the authors report on the aging effect on the phase transitions and dielectric properties of 1mol% Mn-doped BaTiO3 ceramics. Aging the ceramics in the ferroelectric state stimulates a resistance for the orthorhombic-tetragonal and tetragonal-cubic phase transitions, which leads to stabilization of the tetragonal phase over a wider temperature range. The dielectric constant of the aged sample shows dispersion, associated with a dielectric loss relaxation peak near the 100kHz frequency region, in contrast to the unaged one. The present results are discussed in light of the existing models for ferroelectric domain stabilization.
Metabolism of benzo(a)pyrene by human epithelial cells in vitro. (1975)

Primary cell cultures derived from human skin epithelium metabolized benzo(a)pyrene to three classes of compounds: phenols, quinones, and dihydrodiols. The relative proportions of metabolites varied according to the skin donor but differed from the pattern of metabolites in rat liver microsome preparations. While appreciable amounts of 7,8- and 9,10-dihydrodiol; 1,6-, 3,6-, and 6,12-quinone; and 3- and 9-hydroxy derivatives were found in the medium, no 4,5 (K-region)-dihydrodiol or epoxide was detected. Reduced amounts of quinones were produced when the cultures were pretreated with hydrocortisone before exposure to the hydrocarbon. The cultures did not require a period of enzyme induction for efficient metabolism of the hydrocarbon. Cultures of fibroblasts derived from the same skin samples as the epithelial cells metabolized the hydrocarbon but to a much different extent. Preexposure of the epithelial cell cultures to mixtures of polycyclic hydrocarbons resulted in a decrease in the amounts of carcinogen metabolized to phenols and dihydrodiols. These findings suggest that the prevalence of carcinomatous disease in humans is due to the differential capacity of the epithelial cells to metabolize potential carcinogens to active forms, a capacity reduced in fibroblasts or other nonepithelial cells. This suggestion is supported by the observations that supposedly normal prostate cells also efficiently metabolize polycyclic hydrocarbons in a manner similar to that of epidermal cells. No evidence of neoplastic transformation was seen in cytological preparations of cells exfoliated into the medium.
Selective inhibition of intestinal guanosine 3′,5′-cyclic monophosphate signaling by small-molecule protein kinase inhibitors (2018)

The guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinase II (cGKII) serine/threonine kinase relays signaling through guanylyl cyclase C (GCC) to control intestinal fluid homeostasis. Here, we report the discovery of small-molecule inhibitors of cGKII. These inhibitors were imidazole-aminopyrimidines, which blocked recombinant human cGKII at submicromolar concentrations but exhibited comparatively little activity toward the phylogenetically related protein kinases cGKI and cAMP-dependent protein kinase (PKA). Whereas aminopyrimidyl motifs are common in protein kinase inhibitors, molecular modeling of these imidazole-aminopyrimidines in the ATP-binding pocket of cGKII indicated an unconventional binding mode that directs their amine substituent into a narrow pocket delineated by hydrophobic residues of the hinge and the αC-helix. Crucially, this set of residues included the Leu-530 gatekeeper, which is not conserved in cGKI and PKA. In intestinal organoids, these compounds blocked cGKII-dependent phosphorylation of the vasodilator-stimulated phosphoprotein (VASP). In mouse small intestinal tissue, cGKII inhibition significantly attenuated the anion secretory response provoked by the GCC-activating bacterial heat-stable toxin (STa), a frequent cause of infectious secretory diarrhea. In contrast, both PKA-dependent VASP phosphorylation and intestinal anion secretion were unaffected by treatment with these compounds, whereas experiments with T84 cells indicated that they weakly inhibit the activity of cAMP-hydrolyzing phosphodiesterases. As these protein kinase inhibitors are the first to display selective inhibition of cGKII, they may expedite research on cGMP signaling and may aid future development of therapeutics for managing diarrheal disease and other pathogenic syndromes that involve cGKII.