gebhart/patrepeval huggingface dataset:
Lipoprotein-associated phospholipase A2, platelet-activating factor acetylhydrolase, generates two bioactive products during the oxidation of low-density lipoprotein: use of a novel inhibitor (1999)

A novel and potent azetidinone inhibitor of the lipoprotein-associated phospholipase A2 (Lp-PLA2), i.e. platelet-activating factor acetylhydrolase, is described for the first time. This inhibitor, SB-222657 (Ki = 40±3 nM, kobs/[I] = 6.6×105 M-1·s-1), is inactive against paraoxonase, is a poor inhibitor of lecithin:cholesterol acyltransferase and has been used to investigate the role of Lp-PLA2 in the oxidative modification of lipoproteins. Although pretreatment with SB-222657 did not affect the kinetics of low-density lipoprotein (LDL) oxidation by Cu2+ or an azo free-radical generator as determined by assay of lipid hydroperoxides (LOOHs), conjugated dienes and thiobarbituric acid-reacting substances, in both cases it inhibited the elevation in lysophosphatidylcholine content. Moreover, the significantly increased monocyte chemoattractant activity found in a non-esterified fatty acid fraction from LDL oxidized by Cu2+ was also prevented by pretreatment with SB-222657, with an IC50 value of 5.0±0.4 nM. The less potent diastereoisomer of SB-222657, SB-223777 (Ki = 6.3±0.5 µM, kobs/[I] = 1.6×104 M-1·s-1), was found to be significantly less active in both assays. Thus, in addition to generating lysophosphatidylcholine, a known biologically active lipid, these results demonstrate that Lp-PLA2 is capable of generating oxidized non-esterified fatty acid moieties that are also bioactive. These findings are consistent with our proposal that Lp-PLA2 has a predominantly pro-inflammatory role in atherogenesis. Finally, similar studies have demonstrated that a different situation exists during the oxidation of high-density lipoprotein, with enzyme(s) other than Lp-PLA2 apparently being responsible for generating lysophosphatidylcholine.
Nutrient absorption (2001)

Some interesting advances in mechanisms and regulation of nutrient absorption were reported last year. Further evidence was obtained that the rate-limiting step in triacylglycerol absorption, especially with large doses of lipid, is transport of prechylomicrons from the endoplasmic reticulum to the Golgi apparatus. Targeted disruption of the adenosine triphosphate-binding cassette transporter in mice produced changes similar to human Tangier disease and suggested that this mouse may be a model for studying intestinal high-density lipoprotein assembly and secretion. A new mechanism for carbohydrate malabsorption was discovered: in sucrase-isomaltase deficiency, the enzyme fails to anchor in the brush border membrane and so is secreted into the lumen, where it is ineffective. Glycosylating insulin at B1 phenylalanine permitted it to bind to the brush border membrane and greatly enhanced its hypoglycemic activity when given orally. CaCo-2 cells and normal human enterocytes were shown to have two variants of the human sodium-dependent vitamin C transporter, hSVCT1; one is active and the other is an inactive splice variant. In rats, the divalent metal ion transporter, DMT1, appeared to be important for regulation of both absorption of iron and its movement into the liver.
Auto-coding implementation of Model Predictive Control with application to flight control (2009)

This paper describes an implementation of Model Predictive Control (MPC) in Simulink, using only built-in blocks. This enables the use of Matlab's Real-Time Workshop automatically to generate implementation code for an embedded processor. Experimental results are presented using MPC for control of an aircraft model in a wind tunnel. The blocks-only implementation is achieved by expressing an interior-point optimisation as a sequence of operations on a stored solution. A limitation of existing MPC implementations is that the on-line optimisation demands a complex, sometimes nondeterministic algorithm, making it impossible to verify the resulting software for safety critical applications such as flight control. The approach introduced in this paper permits automatic code generation and a route to verifiable MPC software.
Tris‐Cyclometalated Iridium(III) Complexes of Carbazole(fluorenyl)pyridine Ligands: Synthesis, Redox and Photophysical Properties, and Electrophosphorescent Light‐Emitting Diodes (2006)

Using ligands synthesized by Suzuki cross-coupling methodology, new phosphorescent homoleptic tris-cyclometalated complexes have been obtained, namely fac-[Ir(Cz-2-Fl(n)Py)(3)] (1 d-f) and fac-[Ir(Cz-3-Fl(n)Py)(3)] (2 d-f), which are solution-processible triplet emitters (Cz denotes N-hexylcarbazole, n is the number of 9,9'-dihexylfluorene (Fl) units (n=0,1,2) and Py is pyridine). In all cases, Py and Fl are substituted at the 2- and 2,7-positions, respectively, and Cz moieties are substituted by either Py or Fl at the 2- or 3-positions, in series 1 and 2, respectively. The oxidation potential of 1 d studied by cyclic voltammetry ({E{{{\rm ox}\hfill \atop 1/2\hfill}}}=0.14 V, versus Ag/AgNO(3), CH(2)Cl(2)) is less positive (i.e. raised HOMO level) compared to that of the isomer 2 d ({E{{{\rm ox}\hfill \atop 1/2\hfill}}}=0.30 V), where the Cz-nitrogen is meta to the Ir center. Ligand-centered oxidations occur at more positive potentials, leading to 7+ oxidation states with good chemical reversibility and electrochemical quasi-reversibility, for example, for 2 f {E{{{\rm ox}\hfill \atop {\rm pa}\hfill}}} =0.45 (1e), 0.95 (3e), 1.24 V (3e). Striking differences are seen in the solution-state photophysical data between complexes [Ir(Cz-2-Py)(3)] (1 d) and [Ir(Cz-3-Py)(3)] (2 d), in which the Cz moiety is bonded directly to the metal center: for the latter there is an 85 nm blue-shift in emission, a decrease in the luminescence lifetime and an increase in the PLQY value. Organic light emitting devices were made by spin-coating using polyspirobifluorene:bis(triphenyl)diamine (PSBF:TAD) copolymer as host and the complexes 1 d or 2 d as dopants. Turn-on voltages are low (3-4 V). With 1 d orange light is emitted at lambda(max)=590 nm with an EQE of 1.3 % (at 7.5 mA cm(-2)) and an emission intensity (luminance) of 4354 cd m(-2) (at 267 mA m(-2)). The green emission from 2 d devices (lambda(max)=500 nm) is due to the reduced electron-donating ability of the carbazole unit in 2 d. Recording the EL spectra of the 1 d device at 6 V (current density, 100 mA cm(-2)) established that the time to half brightness was about 9 h under continuous operation with no change in the spectral profile, confirming the high chemical stability of the complex.
Estradiol and Tamoxifen Regulate Endostatin Generation via Matrix Metalloproteinase Activity in Breast CancerIn vivo (2006)

Matrix metalloproteinases (MMP) are important regulators of tumor progression and angiogenesis. MMPs generate both proangiogenic and antiangiogenic fragments, such as vascular endothelial growth factor and endostatin. The in vivo activation of MMPs and endostatin generation occur mainly in the extracellular environment by interactions of different cell types. Therefore, these processes are necessary to study in the extracellular space in vivo. Sex steroids play a dominant role in breast carcinogenesis, by largely unknown mechanisms. In the present study, we used in vivo microdialysis to directly quantify MMP-2 and MMP-9 activity and sample endostatin from both stroma (murine) and tumor (human) cells in vivo in solid MCF-7 tumors in nude mice. We found that tamoxifen in combination with estradiol increased tumor MMP-2/MMP-9 in vivo activity, endostatin levels, and decreased tumor vascularization compared with estradiol treatment only. The stroma-derived endostatin was three to five times higher than cancer cell-generated endostatin. After inhibition of MMP-2/MMP-9, endostatin levels decreased, providing evidence that these proteases are highly involved in the generation of endostatin. Our results support the previously reported concept that MMPs may serve as negative regulators of angiogenesis. The regulation of endostatin generation by modulation of MMP-2/MMP-9 activities suggests a previously unrecognized mechanism of estradiol and tamoxifen, which may have implications for the pathogenesis of breast cancer.
Alterations of the PPP1R3 gene in human cancer. (1999)

Recently, the PTEN/MMAC1 gene encoding a protein phosphatase (PP) and the PPP2R1B gene encoding a regulatory subunit of PP2A have been identified as being genetically altered in several types of human cancers, indicating that aberrations of intracellular signaling pathways via PPs are involved in human carcinogenesis. Here we report genetic alterations of the PPP1R3 gene located at chromosome 7q31, which encodes regulatory subunit 3 of PP1, in various types of human cancers. Mutations of the PPP1R3 gene were detected in 5 of 33 (15%) non-small cell lung cancer cell lines and 2 of 38 (5%) primary non-small cell lung cancers and were also observed in cell lines derived from a small cell lung cancer, an ovarian cancer, a colorectal cancer, and a gastric cancer. Mutations were widely dispersed in the coding region of the PPP1R3 gene. Three of the 11 detected mutations were nonsense mutations, whereas the remaining ones were missense mutations, most of which caused substitutions of evolutionarily conserved amino acids. These findings suggest that PPP1R3 alteration plays a role in the development of human cancers and that PPP1R3 could act as a tumor suppressor gene.
Combining TRAIL with PI3 Kinase or HSP90 inhibitors enhances apoptosis in colorectal cancer cells via suppression of survival signaling (2013)

TRAIL has been shown to induce apoptosis in cancer cells, but in some cases they fail to respond to this ligand. We explored the ability of representative phosphatidylinositol-3-kinase (PI3 Kinase)/mTOR and HSP90 inhibitors to overcome TRAIL resistance by increasing apoptosis in colorectal cancer models. We determined the sensitivity of 27 human colorectal cancer and 2 non-transformed colon epithelial cell lines to TRAIL treatment. A subset of the cancer cell lines with a range of responses to TRAIL was selected from the panel for treatment with TRAIL combined with the PI3 Kinase/mTOR inhibitor PI-103 or the HSP90 inhibitor 17-AAG (tanespimycin). Two TRAIL-resistant cell lines were selected for in vivo combination studies with TRAIL and 17-AAG. We found that 13 colorectal cancer cell lines and the 2 non-transformed colon epithelial cell lines were resistant to TRAIL. We demonstrated that co-treatment of TRAIL and PI-103 or 17-AAG was synergistic or additive and significantly enhanced apoptosis in colorectal cancer cells. This was associated with decreased expression or activity of survival protein biomarkers such as ERBB2, AKT, IKKα and XIAP. In contrast, the effect of the combination treatments in non-transformed colon cells was minimal. We show here for the first time that co-treatment in vivo with TRAIL and 17-AAG in two TRAIL-resistant human colorectal cancer xenograft models resulted in significantly greater tumor growth inhibition compared to single treatments. We propose that combining TRAIL with PI3 Kinase/mTOR or HSP90 inhibitors has therapeutic potential in the treatment of TRAIL-resistant colorectal cancers.
Closed-form solutions for feedback control with terminal constraints (1985)

The problem of closed-loop control of maneuvers between two states for linear dynamical systems, subject to an arbitrarily specified terminal state, is considered. The feedback controller design is based on finite-time quadratic regulator theory. Closed-form expressions for the optimal control law are developed. Solutions are presented for both conventional and smoothed control profiles with fixed and/or free end condition problems. In the maneuvers using control-rate penalties, smooth profiles are generated throughout the maneuvers in the sense that the initial condition jump discontinuities have been eliminated. Several examples involving large-angle maneuvers of a spacecraft are demonstrated. Results include control maneuvers from one state to another, such as rest to rest and spin to rest, which effectively justify the solutions developed in this paper.
Impact of Age on the Relationships of Brown Adipose Tissue With Sex and Adiposity in Humans (2010)

Our data corroborate that, in general, BAT activity and BAT mass are elevated in female subjects and in younger people. Importantly, we provide novel evidence that the impact of BAT activity and BAT mass on adiposity appears to decline with aging only in male subjects. Furthermore, while BAT activity and BAT mass only moderately decline with increasing age in female subjects, a much stronger effect is found in male subjects.
Interaction between the Elastin Peptide VGVAPG and Human Elastin Binding Protein (2012)

The elastin binding protein (EBP), a spliced variant of lysosomal β-galactosidase, is the primary receptor of elastin peptides that have been linked to emphysema, aneurysm and cancer progression. The sequences recognized by EBP share the XGXXPG consensus pattern found in numerous matrix proteins, notably in elastin where the VGVAPG motif is repeated. To delineate the elastin binding site of human EBP, we built a homology model of this protein and docked VGVAPG on its surface. Analysis of this model suggested that Gln-97 and Asp-98 were required for interaction with VGVAPG because they contribute to the definition of a pocket thought to represent the elastin binding site of EBP. Additionally, we proposed that Leu-103, Arg-107, and Glu-137 were essential residues because they could interact with VGVAPG itself. Site-directed mutagenesis experiments at these key positions validated our model. This work therefore provides the first structural data concerning the interaction of the VGVAPG with its cognate receptor. The present structural data should now allow the development of EBP-specific antagonists.
부모교육 프로그램 개발과 수행에 관한 연구 경향 분석-최근 10년간 국내 연구를 중심으로- (2003)

The purpose of this study is to analyze the research trends in the development and implement of parent education programs. This study reviews 137 researches which were conducted during 1993-2003. Among 137 researches, 107 researches are unpublished master or Doctoral Dissertations, and 30 researches are papers published at Periodical Journals. The result of reviews shows that 66 researches are found to survey only the needs and desires for parent education program without implementing. However, among 71 researches, some researches are found to focus only on the implementing parent education program without the survey of the n~ds for program, or others are found to focus on both the survey of the needs for parent education program and the implement of program. In addition, the result of implementing parent education programs is found to be highly effective to· improve parent-child relationships. The implications for future studies are discussed in the. context of development and implement of parent education programs.
Forced IDO1 expression in dendritic cells restores immunoregulatory signalling in autoimmune diabetes (2014)

Indoleamine 2,3-dioxygenase (IDO1), a tryptophan catabolizing enzyme, is recognized as an authentic regulator of immunity in several physiopathologic conditions. We have recently demonstrated that IDO1 does not merely degrade tryptophan and produce immunoregulatory kynurenines, but it also acts as a signal-transducing molecule, independently of its enzymic function. IDO1 signalling activity is triggered in plasmacytoid dendritic cells (pDCs) by transforming growth factor-β (TGF-β), an event that requires the non-canonical NF-κB pathway and induces long-lasting IDO1 expression and autocrine TGF-β production in a positive feedback loop, thus sustaining a stably regulatory phenotype in pDCs. IDO1 expression and catalytic function are defective in pDCs from non-obese diabetic (NOD) mice, a prototypic model of autoimmune diabetes. In the present study, we found that TGF-β failed to activate IDO1 signalling function as well as up-regulate IDO1 expression in NOD pDCs. Moreover, TGF-β-treated pDCs failed to exert immunosuppressive properties in vivo. Nevertheless, transfection of NOD pDCs with Ido1 prior to TGF-β treatment resulted in activation of the Ido1 promoter and induction of non-canonical NF-κB and TGF-β, as well as decreased production of the pro-inflammatory cytokines, interleukin 6 (IL-6) and tumour necrosis factor-α (TNF-α). Overexpression of IDO1 in TGF-β-treated NOD pDCs also resulted in pDC ability to suppress the in vivo presentation of a pancreatic β-cell auto-antigen. Thus, our data suggest that a correction of IDO1 expression may restore its dual function and thus represent a proper therapeutic manoeuvre in this autoimmune setting.
Synthesis, properties, and biological activity of some nucleoside cyclic phosphoramidates (1984)

Reaction of the appropriate nucleoside with phosphoryl trichloride and then with N-methylethanolamine gave 2′,3′-O-isopropylidene-5′-O-(3″-methyl-1″-oxa-3″-aza-2″-phosphacyclopentan-2″-yl)uridine 2″-oxide (4), 5′-O-(3″-methyl-1″-oxa-3″-aza-2″-phosphacyclopentan-2″-yl)thymidine 2″-oxide (5), and 2′-deoxy-5-fluoro-5′-O-(3″-methyl-1″-oxa-3″-aza-2″-phosphacyclopentan-2″-yl)uridine 2″-oxide (6). A similar sequence of reactions, but using N,N′-dimethylethylenediamine, gave 5′-O-(1″,3″-dimethyl-1″,3″-diaza-2″-phosphacyclopentan-2″-yl)thymidine 2″-oxide (7) and 2′-deoxy-5′-O-(1″,3″-dimethyl-1″,3″-diaza-2″-phosphacyclopentan-2″-yl)-5-fluorouridine 2″-oxide (8).Compounds (4)–(8) were hydrolysed readily in the pH range 6.0–7.0 at 25 °C, the kinetics being first order in hydrogen ions and in substrate. The 1-oxa-3-aza-2-phospha derivatives were hydrolysed more readily than the 1,3-diaza-2-phospha derivatives and the 2′-deoxy-5-fluorouridine derivatives more rapidly than the thymidine derivatives. In each case hydrolysis resulted in the fission of one P–N bond.Compound (8) inhibited the growth of leukemia L1210 cells. It acted as a thymidylate synthetase inhibitor in the cell culture, but itself was not a substrate for the isolated, purified enzyme.
Proteomic Analysis of the Mode of Antibacterial Action of Silver Nanoparticles (2006)

Silver nanoparticles (nano-Ag) are potent and broad-spectrum antimicrobial agents. In this study, spherical nano-Ag (average diameter = 9.3 nm) particles were synthesized using a borohydride reduction method and the mode of their antibacterial action against E. coli was investigated by proteomic approaches (2-DE and MS identification), conducted in parallel to analyses involving solutions of Ag(+) ions. The proteomic data revealed that a short exposure of E. coli cells to antibacterial concentrations of nano-Ag resulted in an accumulation of envelope protein precursors, indicative of the dissipation of proton motive force. Consistent with these proteomic findings, nano-Ag were shown to destabilize the outer membrane, collapse the plasma membrane potential and deplete the levels of intracellular ATP. The mode of action of nano-Ag was also found to be similar to that of Ag(+) ions (e.g., Dibrov, P. et al, Antimicrob. Agents Chemother. 2002, 46, 2668-2670); however, the effective concentrations of nano-Ag and Ag(+) ions were at nanomolar and micromolar levels, respectively. Nano-Ag appear to be an efficient physicochemical system conferring antimicrobial silver activities.
New Xenograft Model of Multiple Myeloma and Efficacy of a Humanized Antibody Against Human Interleukin-6 Receptor (1997)

A new xenograft model of multiple myeloma (MM), where growth is strongly regulated by interleukin-6 (IL-6), was established in severe combined immunodeficiency (SCID) mice. In this model, endogenous IL-6 from SCID mice was ineffective at eliciting growth of the established human MM cell line KPMM2; these cells achieved autonomous growth through their autocrine secretion of IL-6. The etiopathology in this disease model is consistent with that of human MM. When greater than 3 × 106 KPMM2 cells were injected intravenously (IV), tumors developed in all mice and were predominantly localized in their bone marrow. Tumors were also apparent in the lymph nodes, but absent from other organs. Immunostaining of cell surface antigen (CD38) showed that more than 40% of bone marrow cells in femur were of myeloma origin in the advanced stage of tumor progression (day 37). Histologic analysis of these mice show that bone marrow was largely occupied by plasmablastic cells and bones had developed osteolytic lesions at multiple sites. Concurrently, there was a decrease in bone density throughout the body and a significant increase in ionized plasma calcium. M-protein was detected in the serum within 10 days after transplantation, which correlated with the tumor progression. Between 30 and 40 days after the transplantation, mice presented with a rapid and severe loss of body weight, hind leg paralysis, and fatigue. Subsequently, the mice died within a week. A single IV injection of 0.2 mg humanized anti–IL-6 receptor antibody (hPM1) into mice on the day after tumor transplantation substantially suppressed the elevation of serum M-protein and development of the tumor-associated abnormalities and significantly increased in the life span of tumor-bearing mice. Our data show the usefulness of this model to analyze the pathologic role of IL-6 in MM and the efficacy of targeting the IL-6 receptor in IL-6–dependent KPMM2 cells.
Validation and Utility of a Self-report Version of PRIME-MD<SUBTITLE>The PHQ Primary Care Study</SUBTITLE> (1999)

Our study suggests that the PHQ has diagnostic validity comparable to the original clinician-administered PRIME-MD, and is more efficient to use.
Usage of an intronic promoter for stable gene expression in Saccharomyces cerevisiae (2005)

This is the first report detailing the use of an intronic promoter in the construction of stable expression vectors and the novel system could serve as a model of expression vectors for fermentation or other purposes.
MICROGLIA AS MEDIATORS OF INFLAMMATORY AND DEGENERATIVE DISEASES (1999)

Microglia are the principal immune cells in the central nervous system (CNS) and have a critical role in host defense against invading microorganisms and neoplastic cells. However, as with immune cells in other organs, microglia may play a dual role, amplifying the effects of inflammation and mediating cellular degeneration as well as protecting the CNS. In entities like human immunodeficiency virus (HIV) infection of the nervous system, microglia are also critical to viral persistence. In this review we discuss the role of microglia in three diseases in which their activity is at least partially deleterious: HIV, multiple sclerosis, and Alzheimer's disease.
Effects on intact femora of dogs of the application and removal of metal plates. A metabolic and structural study comparing stiffer and more flexible plates. (1978)

Studies of flexible plates made of plastic have shown that less osteoporosis develops beneath them than beneath rigid metal plates. However, to date plastic plates of appropriate physical properties and biocompatibility are not available for use in humans. To determine if a similar beneficial effect could be obtained using metal plates, the effects of thick chromium cobalt plates were contrasted in experiments in dogs with the effects of thinner plates of similar design made of titanium, 6-aluminum, 4-vandium. A significant reduction in the osteoporosis was obtained by use of the more flexible plates. Following plate application a delayed, massive, transient stimulus to bone formation occurred endosteally, periosteally, and intracortically. Despite this, a substantial decrease in bone mass occurred, primarily mediated by endosteal bone resorption. Intracortical porosity played little or no role in net bone loss. The major effects subsided by six months. Recovery after plate removal was predominantly the result of endosteal new-bone formation.