gebhart/patrepeval huggingface dataset:
In vitro and in vivo targeting of immunoliposomal doxorubicin to human B-cell lymphoma. (1998)

The ability to selectively target liposomal anticancer drugs via specific ligands against antigens expressed on malignant cells could improve the therapeutic effectiveness of the liposomal preparations as well as reduce adverse side effects associated with chemotherapy. Long-circulating formulations of liposomes containing lipid derivatives of poly(ethyleneglycol) [sterically stabilized liposomes (SLs)] have been described previously, and new techniques have recently been developed for coupling monoclonal antibodies (Abs) at the poly(ethyleneglycol) terminus of these liposomes. Ab-targeted SLs [immunoliposomes (SILs)] containing entrapped anticancer drugs are predicted to be useful in the treatment of hematological malignancies such as B-cell lymphomas or multiple myeloma, in which the target cells are present in the vasculature. The specific binding, in vitro cytotoxicity, and in vivo antineoplastic activity of doxorubicin (DXR) encapsulated in SILs coupled to monoclonal Ab anti-CD19 (SIL[anti-CD19]) were investigated against malignant B cells expressing CD19 surface antigens. Binding experiments with SIL[anti-CD19] resulted in a 3-fold higher association of the SILs with a human CD19+ B lymphoma cell line (Namalwa) in comparison with nontargeted SLs. Using flow cytometry, fluorescently labeled SIL[anti-CD19] bound to B cells with no recognition of T cells in a mixture of B cells and T cells in culture. Nontargeted SLs demonstrated significantly lower recognition of either B cells or T cells. Targeted DXR-SIL[anti-CD19] displayed a higher cytotoxicity to B cells relative to DXR entrapped in nontargeted SLs. Therapeutic experiments in severe combined immunodeficient mice implanted with Namalwa cells by the i.v. or i.p. routes resulted in significantly increased effectiveness of DXR-SIL[anti-CD19] compared to similar amounts of free DXR, DXR-SL (no Ab), or isotype-matched nonspecific Abs attached to DXR-SL. Single doses (3 mg/kg) of DXR-SIL[anti-CD19] administered i.v. resulted in a significantly improved therapeutic benefit, including some long-term survivors. From our results, we infer that targeted anti-CD19 liposomes containing the anticancer drug DXR may be selectively cytotoxic for B cells and may be useful in the selective elimination of circulating malignant B cells in vivo.
Thermally Irreversible Photochromic Systems. Photoreaction of Diarylethene Derivatives with Imidazo[1,2-a]pyridine Rings (1991)

Abstract A non-symmetrical diarylethene with imidazo[1,2-a]pyridine ring on one end and thiophene ring on the other end, 1,2-dicyano-1-(2-methylimidazo[1,2-a]pyridin-3-y1)-2-(2,4,5-trimetyl-3-thieny1)ethene 2Z underwent a hexatriene-cyclohexadiene type reversible ring-closure reaction by photoirradiation, while an only Z–E isomerization was observed for a symmetrical diarylenthene with two imidazo[1,2-a]pyridine rings, 1,2-dicyano-1,2-bis(2-methylimidazo[1,2-a]pyridin-3-yl)ethene 1Z. The ring-closure reaction was not discerned. The photogenerated closed-ring form 2C had the absorption band at 535 nm, which is 23 nm longer wavelengths than that of the corresponding dithienylethene, and kept the absorption intensity constant for more than 24 h at 80 °C. The quantum yield close to unity was observed for the photochemical ring-opening reaction of 2C with 546 nm light.
Nonlinear system modeling based on the Wiener theory (1981)

This paper is a tutorial of nonlinear system modeling methods which are based on the Wiener theory of nonlinear systems. The basic concepts that underlie the Wiener theory are discussed and illustrated. Various modeling methods are presented by which a non-linear system can be modeled using either white Gaussian, nonwhite Gaussian, or certain non-Gaussian inputs. The experimental error in determining the Wiener model is discussed in terms of a new concept called measurement stability. Since attempts are being made to apply these modeling methods to diverse areas of study, this paper is written to be comprehensible by nonspecialists in system theory
Cell surface labeling of glucose transporter isoform GLUT4 by bis-mannose photolabel. Correlation with stimulation of glucose transport in rat adipose cells by insulin and phorbol ester. (1990)

A new impermeant photoaffinity label has been used for identifying cell surface glucose transporters in isolated rat adipose cells. This compound is 2-N-4(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis(D-mannos-4- yloxy)-2- propylamine. We have used this reagent in combination with immunoprecipitation by specific antibodies against the GLUT4 and GLUT1 glucose transporter isoforms to estimate the relative abundance of these two transporters on the surface of the intact adipose cell following stimulation by insulin and phorbol 12-myristate 13-acetate (PMA). In the basal state, GLUT4 and GLUT1 are both present at the cell surface but GLUT4 is more abundant than GLUT1. In response to insulin, GLUT4 increases 15-20-fold and GLUT1 increases approximately 5-fold while 3-O-methyl-D-glucose transport is stimulated 20-30-fold. By contrast, PMA only induces a approximately 4-fold increase in GLUT4 while GLUT1 increases approximately 5-fold to the same level as seen with insulin. In addition, PMA stimulates 3-O-methyl-D-glucose transport approximately 3-fold to only 13% of the insulin-stimulated state. Thus GLUT4 is the major glucose transporter isoform under all conditions, and it is selectively and markedly enriched in response to insulin but not PMA which increases GLUT1 and GLUT4 equally. Furthermore, stimulation of glucose transport activity correlates closely with the appearance of GLUT4 on the cell surface in response to both insulin and PMA but does not correlate with the sum of GLUT1 and GLUT4 appearance. These results suggest that GLUT4 may be inherently more active than GLUT1 due to a higher TK (turnover/Km).
Quarterly Quiz Bell-Shaped Tones (1994)

Quarterly Quiz Bell-Shaped Tones Get access M. OWEN LEE M. OWEN LEE Search for other works by this author on: Oxford Academic Google Scholar The Opera Quarterly, Volume 10, Issue 4, summer 1994, Pages 91–94, https://doi.org/10.1093/oq/10.4.91 Published: 01 July 1994
Inflammation, a Key Event in Cancer Development (2006)

Several recent studies have identified nuclear factor-kappaB as a key modulator in driving inflammation to cancers. Besides this transcription factor, essential in regulating inflammation and cancer development, an inflammatory microenvironment inhabiting various inflammatory cells and a network of signaling molecules are also indispensable for the malignant progression of transformed cells, which is attributed to the mutagenic predisposition of persistent infection-fighting agents at sites of chronic inflammation. As a subverted host response to inflammation-induced tumors, the inflammatory cells and regulators may facilitate angiogenesis and promote the growth, invasion, and metastasis of tumor cells. Thus far, research regarding inflammation-associated cancer development has focused on cytokines and chemokines as well as their downstream targets in linking inflammation and cancer. Moreover, other proteins with extensive roles in inflammation and cancer, such as signal transducers and activators of transcription, Nrf2, and nuclear factor of activated T cells, are also proposed to be promising targets for future studies. The elucidation of their specific effects and interactions will accelerate the development of novel therapeutic interventions against cancer development triggered by inflammation.
In vitro modulation of the apolipoprotein composition of high density lipoprotein. Displacement of apolipoprotein A-I from high density lipoprotein by apolipoprotein A-II. (1980)

To gain an understanding on the role of apolipoprotein A-11 (apo A-II) in high density lipoprotein (HDL) structure, preparations of canine HDL known to contain essentially only apolipoprotein A-I (apo A-I) and no apo A-11 were incubated with lipid-free human apo A-11 as a function of time, temperature, ionic strength, and at different stoichiometric ratios.Analysis of the products isolated by density gradient ultracentrifugation demonstrated the uptake of apo A-11 by canine HDL.Uptake was independent of ionic strength (p = 0.15 to 3.0 M) and was attended by a linear release of apo A-I from the HDL particles with no loss of lipids.Two apo A-11 molecules (Mr = 17,400 each) displaced 1 apo A-I molecule (Mr = 28,000) from HDL until human apo A-11 was the only apolipoprotein component of canine HDL.The 3 apo A-I molecules in HDL could be replaced by six human apo A-11 molecules.All of the hybrid particles retained physiochemical properties of native canine HDL.To determine the time course and temperature dependence of apolipoprotein replacement, single bilayer lecithin-cholesterol vesicles (molar ratio, 4:l) were added to each incubation mixture at variable time periods to trap any free protein in solution.Uptake of apo A-I1 by HDL and the associated release of apo A-I were complete in less than 1 min and independent of the temperature (4°C and 23°C).The results indicate that apo A-11 can rapidly displace apo A-I from HDL without significantly affecting the overall structural properties of this lipoprotein.This displacement process appears to be related to a difference in the affinity of these two apolipoproteins for the HDL surface and is probably of physiological importance.The demonstration that HDL particles of varying apolipoprotein composition can be readily produced in vitro offers novel approaches for investigating the structural and functional properties of high density lipoproteins.Human high density lipoproteins contain two major apolipoproteins, apolipoprotein A-I and apolipoprotein A-11, In contrast, animals such as the dog, cow, pig, and chicken have
2‐(4‐Methoxyphenoxy)‐5‐nitro‐N‐(4‐sulfamoylphenyl)benzamide Activates Kir6.2/SUR1 KATP Channels. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Cryptochromes: Blue Light Receptors for Plants and Animals (1999)

Cryptochromes are blue, ultraviolet-A photoreceptors. They were first characterized for Arabidopsis and are also found in ferns and algae; they appear to be ubiquitous in the plant kingdom. They are flavoproteins similar in sequence to photolyases, their presumptive evolutionary ancestors. Cryptochromes mediate a variety of light responses, including entrainment of circadian rhythms in Arabidopsis, Drosophila, and mammals. Sequence comparison indicates that the plant and animal cryptochrome families have distinct evolutionary histories, with the plant cryptochromes being of ancient evolutionary origin and the animal cryptochromes having evolved relatively recently. This process of repeated evolution may have coincided with the origin in animals of a modified circadian clock based on the PERIOD, TIMELESS, CLOCK, and CYCLE proteins.
Statistical Associating Fluid Theory Equation of State with Lennard-Jones Reference Applied to Pure and Binary n-Alkane Systems (1998)

A prototype equation of state, developed on the basis of thermodynamic perturbation theory of the first order (TPT1), using the Lennard-Jones potential for the reference fluid, is found to represent pure-fluid and binary phase equilibria in the systems of small chain molecules, such as normal alkanes.
The antibody-mediated targeted delivery of interleukin-10 inhibits endometriosis in a syngeneic mouse model (2011)

The F8 antibody targets endometriotic lesions in vivo in a mouse model of endometriosis and may be used for the non-invasive imaging of the disease and for the pharmacodelivery of anti-inflammatory cytokines, such as IL10.
The 1-aminocyclopropane-1-carboxylate synthase gene family of Arabidopsis thaliana. (1992)

Genomic sequences encoding five divergent 1-aminocyclopropane-1-carboxylic acid (ACC) synthase polypeptides (ACC1, ACC2, ACC3, ACC4, and ACC5) have been isolated from Arabidopsis thaliana by using heterologous cDNAs and PCR fragments amplified from genomic DNA with degenerate oligonucleotide primers. Each gene is located on a different chromosome in the Arabidopsis genome. The genes are differentially expressed during development and in response to environmental stimuli. Protein-synthesis inhibition derepresses the expression of all genes but most dramatically derepresses that of ACC2, suggesting that their expression may be under negative control. The sequence of ACC2 was determined, and its transcription initiation site was defined. Authenticity of the polypeptide encoded by the gene was confirmed by expression experiments in Escherichia coli. The predicted size of the protein is 55,623 Da, and it contains the 11 invariant amino acid residues conserved between aminotransferases and ACC synthases from various plant species. Comparative analysis of structural and expression characteristics of ACC synthase genes from Arabidopsis and other plant species suggests that the sequence divergence of the ACC synthase genes and possibly the distinct regulatory networks governing the expression of ACC synthase subfamilies arose early in plant evolution and before the divergence of monocots and dicots.
Treatment of refractory non-Hodgkin's lymphoma with radiolabeled MB-1 (anti-CD37) antibody. (1989)

The biodistribution, toxicity, and therapeutic potential of anti-CD37 monoclonal antibody (MoAb) MB-1 labeled with iodine 131 (131I) was evaluated in ten patients with advanced-, low- or intermediate-grade non-Hodgkin's lymphomas who failed conventional treatment. Sequential dosimetric studies were performed with escalating amounts of antibody MB-1 (0.5, 2.5, 10 mg/kg) trace-labeled with 5 to 10 mCi 131I. Serial tumor biopsies and gamma camera imaging showed that the 10 mg/kg MoAb dose yielded the best MoAb biodistribution in the ten patients studied. Biodistribution studies in the five patients with splenomegaly and tumor burdens greater than 1 kg indicated that not all tumor sites would receive more radiation than normal organs, and these patients were therefore not treated with high-dose radioimmunotherapy. The other five patients did not have splenomegaly and had tumor burdens less than 0.5 kg; all five patients in this group showed preferential localization and retention of MoAb at tumor sites. Four of these patients have been treated with 131I (232 to 608 mCi) conjugated to anti-CD37 MoAb MB-1, delivering 850 to 4,260 Gy to tumor sites. Each of these four patients attained a complete tumor remission (lasting 4, 6, 11+, and 8+ months). A fifth patient, whose tumor did not express the CD37 antigen, was treated with 131I-labeled anti-CD20 MoAb 1F5 and achieved a partial response. Myelosuppression occurred 3 to 5 weeks after treatment in all cases, but there were no other significant acute toxicities. Normal B cells were transiently depleted from the bloodstream, but immunoglobulin (Ig) levels were not affected, and no serious infections occurred. Two patients required reinfusion of previously stored autologous, purged bone marrow. Two patients developed asymptomatic hypothyroidism 1 year after therapy. The tolerable toxicity and encouraging efficacy warrant further dose escalation in this phase I trial.
The Tie2-agonist Vasculotide rescues mice from influenza virus infection (2015)

Seasonal influenza virus infections cause hundreds of thousands of deaths annually while viral mutation raises the threat of a novel pandemic strain. Antiviral drugs exhibit limited efficacy unless administered early and may induce viral resistance. Thus, targeting the host response directly has been proposed as a novel therapeutic strategy with the added potential benefit of not eliciting viral resistance. Severe influenza virus infections are complicated by respiratory failure due to the development of lung microvascular leak and acute lung injury. We hypothesized that enhancing lung endothelial barrier integrity could improve the outcome. Here we demonstrate that the Tie2-agonist tetrameric peptide Vasculotide improves survival in murine models of severe influenza, even if administered as late as 72 hours after infection; the benefit was observed using three strains of the virus and two strains of mice. The effect required Tie2, was independent of viral replication and did not impair lung neutrophil recruitment. Administration of the drug decreased lung edema, arterial hypoxemia and lung endothelial apoptosis; importantly, Vasculotide is inexpensive to produce, is chemically stable and is unrelated to any Tie2 ligands. Thus, Vasculotide may represent a novel and practical therapy for severe infections with influenza.
Enhanced survival of adriamycin-treated Chinese hamster cells by 2-deoxy-D-glucose and 2,4-dinitrophenol. (1982)

Abstract The purpose of this work was to determine the role of metabolic energy [adenosine triphosphate (ATP)] in the expression of cytotoxicity of the antitumor drug, Adriamycin (ADRM), in Chinese hamster fibroblasts. When ADRM-sensitive V79 cells or an ADRM-resistant variant, 77A, were pretreated with either 6 mm 2-deoxy-d-glucose or 0.2 mm 2,4-dinitrophenol for 18 hr and then exposed to ADRM for 1 hr at 37°, we observed a substantial increase in cellular survival. In the case of V79 cells pretreated with deoxyglucose, as much as a 1000-fold increase in survival was measured. The maximum dose of ADRM for V79 cells was 3 µg/ml, and for 77A cells it was 15 µg/ml. The effects of metabolic inhibitors on intracellular ATP content, ADRM uptake, mitotic indices, cellular multiplication, and plating efficiency were measured in untreated as well as in inhibitor-treated cells. The same concentrations of deoxyglucose (6 mm) and dinitrophenol (0.2 mm) that were used for cytotoxicity studies were also used in the biochemical studies. Under conditions of pretreatment with metabolic inhibitors which increased the survival of cells, a lowering of ATP content and a concomitant slight enhancement of drug uptake were observed. Plating efficiency was not affected. We also have observed a partial inhibition of growth after pretreatment with metabolic inhibitors as shown by lowered mitotic indices and by cell counts. We conclude that the increase in survival of both ADRM-sensitive and resistant cells is not due to decreased intracellular accumulation of the drug. Flow microfluorimetric analysis of V79 cells pretreated with deoxyglucose showed no reduction in the numbers of cells in the S phase of the cell cycle, the most sensitive compartment for ADRM, while pretreatment with dinitrophenol, on the other hand, significantly reduced the number of cells in S phase. When inhibitors were removed, and the cells were rinsed, refed complete growth medium, and then exposed to a single dose of drug (1.5 µg/ml for V79; 10 µg/ml for 77A) at various times up to 7 hr, cellular survival decreased while ATP content increased as a function of time. We conclude that the effects of the metabolic inhibitors are reversible and that cells slowly regain their sensitivity to ADRM. As intracellular levels of ATP increase, sensitivity to ADRM increases. Thus, metabolic energy may be important for cytotoxic damage by ADRM. However, the enhancement in cellular survival may also be partly related to slower cell cycle progression.
Intravenous Neridronate in Adults With Osteogenesis Imperfecta (2003)

Osteogenesis imperfecta (OI) is a heritable disease of connective tissue, characterized by increased bone fragility. Bisphosphonates currently seems to be the most promising therapy, at least in children. We tested IV neridronate, an amino-bisphosphonate structurally similar to alendronate and pamidronate in adults with OI. Twenty-three men and 23 premenopausal women with OI were randomized to either iv neridronate (100 mg infused intravenously for 30 minutes every 3 months) or no treatment with a ratio of 2 to 1. Control patients were given the same bisphosphonate therapy at the end of the first year. Clinical evaluation included bone densitometry measurements using dual energy X-ray absorptiometry (DXA), fasting serum and urinary biochemistry every 6 months, and radiographs of the spine taken at baseline and after 12 and 24 months of follow-up. Spine and hip bone mineral density rose by 3.0 +/- 4.6% (SD) and by 4.3 +/- 3.9%, respectively, within the first 12 months of treatment, whereas small insignificant changes were observed in the control group. During the second year of follow-up, additional 3.91% and 1.49% increases were observed at the spine and hip, respectively. Markers of skeletal turnover significantly fell during neridronate treatment. Fracture incidence during neridronate treatment was significantly lower than before therapy and compared with controls. Neridronate iv infusions, administered quarterly, significantly increase bone mineral density and lowered the risk of clinical fracture in adults with OI. Bisphosphonate therapy seems to provide clinical benefits, not only to children with OI, but also to adult patients.
Diarylmethylene-bridged 4,4′-(bis(9-carbazolyl))biphenyl: morphological stable host material for highly efficient electrophosphorescence (2009)

A novel compound (BCBP) based on the modification of a well-known host material 4,4′-(bis(9-carbazolyl))biphenyl (CBP) through arylmethylene bridge linkage was synthesized, and fully characterized. Its thermal, electrochemical, electronic absorption and photoluminescent properties were studied. A high glass transition temperature (Tg) of 173 °C is observed for BCBP due to the introduction of the bridged structure, remarkably contrasting with a low Tg of 62 °C for CBP. Furthermore, the bridged structure enhances the conjugation and raises the HOMO energy, thus facilitating hole-injection and leading to a low turn-on voltage in an electroluminescent device. With the device structure of ITO/MoO3/NPB/Ir complex: BCBP/BCP/Alq3/LiF/Al, maximum power efficiencies of 41.3 lm/W and 6.3 lm/W for green- and blue-emitting OLED were achieved, respectively.
Human Herpesvirus 8-Encoded vGPCR Activates Nuclear Factor of Activated T Cells and Collaborates with Human Immunodeficiency Virus Type 1 Tat (2003)

Human herpesvirus 8 (HHV-8), the etiologic agent of Kaposi's sarcoma (KS), encodes a chemokine receptor homologue, the viral G protein-coupled receptor (vGPCR), that has been implicated in KS pathogenesis. Expression of vGPCR constitutively activates several signaling pathways, including NF-kappa B, and induces the expression of proinflammatory and angiogenic factors, consistent with the inflammatory hyperproliferative nature of KS lesions. Here we show that vGPCR also constitutively activates the nuclear factor of activated T cells (NF-AT), another transcription factor important in regulation of the expression of inflammatory cytokines and related factors. NF-AT activation by vGPCR depended upon signaling through the phosphatidylinositol 3-kinase-Akt-glycogen synthetase kinase 3 (PI3-K/Akt/GSK-3) pathway and resulted in increased expression of NF-AT-dependent cell surface molecules (CD25, CD29, Fas ligand), proinflammatory cytokines (interleukin-2 [IL-2], IL-4), and proangiogenic factors (granulocyte-macrophage colony-stimulating factor GMCSF and TNF alpha). vGPCR expression also increased endothelial cell-T-cell adhesion. Although infection with HHV-8 is necessary to cause KS, coinfection with human immunodeficiency virus type 1 (HIV-1), in the absence of antiretroviral suppressive therapy, increases the risk of KS by many orders of magnitude. NF-AT and NF-kappa B activation by vGPCR was greatly increased by the HIV-1 Tat protein, although Tat alone had little effect on NF-AT. The enhancement of NF-AT by Tat appears to be mediated through collaborative stimulation of the PI3-K/Akt/GSK-3 pathway by vGPCR and Tat. Our data further support the idea that vGPCR contributes to the pathogenesis of KS by a paracrine mechanism and, in addition, provide the first evidence of collaboration between an HIV-1 protein and an HHV-8 protein.