gebhart/patrepeval huggingface dataset:
Antitumor Activity of Hyaluronic Acid Synthesis Inhibitor 4-Methylumbelliferone in Prostate Cancer Cells (2010)

4-Methylumbelliferone (4-MU) is a hyaluronic acid (HA) synthesis inhibitor with anticancer properties; the mechanism of its anticancer effects is unknown. We evaluated the effects of 4-MU on prostate cancer cells. 4-MU inhibited proliferation, motility, and invasion of DU145, PC3-ML, LNCaP, C4-2B, and/or LAPC-4 cells. At IC(50) for HA synthesis (0.4 mmol/L), 4-MU induced >3-fold apoptosis in prostate cancer cells, which could be prevented by the addition of HA. 4-MU induced caspase-8, caspase-9, and caspase-3 activation, PARP cleavage, upregulation of Fas-L, Fas, FADD and DR4, and downregulation of bcl-2, phosphorylated bad, bcl-XL, phosphorylated Akt, phosphorylated IKB, phosphorylated ErbB2, and phosphorylated epidermal growth factor receptor. At IC(50), 4-MU also caused >90% inhibition of NF-kappaB reporter activity, which was prevented partially by the addition of HA. With the exception of caveolin-1, HA reversed the 4-MU-induced downregulation of HA receptors (CD44 and RHAMM), matrix-degrading enzymes (MMP-2 and MMP-9), interleukin-8, and chemokine receptors (CXCR1, CXCR4, and CXCR7) at the protein and mRNA levels. Expression of myristoylated-Akt rescued 4-MU-induced apoptosis and inhibition of cell growth and interleukin-8, RHAMM, HAS2, CD44, and MMP-9 expression. Oral administration of 4-MU significantly decreased PC3-ML tumor growth (>3-fold) when treatment was started either on the day of tumor cell injection or after the tumors became palpable, without organ toxicity, changes in serum chemistry, or body weight. Tumors from 4-MU-treated animals showed reduced microvessel density ( approximately 3-fold) and HA expression but increased terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells and expression of apoptosis-related molecules. Therefore, the anticancer effects of 4-MU, an orally bioavailable and relatively nontoxic agent, are primarily mediated by inhibition of HA signaling.
A temporal filter approach for detection and reconstruction of curbs and road surfaces based on Conditional Random Fields (2011)

A temporal filter approach for real-time detection and reconstruction of curbs and road surfaces from 3D point clouds is presented. Instead of local thresholding, as used in many other approaches, a 3D curb model is extracted from the point cloud. The 3D points are classified to different parts of the model (i.e. road and sidewalk) using a temporally integrated Conditional Random Field (CRF). The parameters of curb and road surface are then estimated from the respectively assigned points, providing a temporal connection via a Kalman filter.
Monoamine oxidase A knockout mice exhibit impaired nicotine preference but normal responses to novel stimuli (2006)

Nicotine is thought to act on brain monoamine systems that normally mediate diverse motivational behaviors. How monoamine-related genes contribute to behavioral traits (e.g. responses to novel stimuli) comorbid with the susceptibility to nicotine addiction is still poorly understood. We examined the impact of constitutive monoamine oxidase A (MAOA) deficiency in mice on nicotine reward and responses to novel stimuli. Age-matched, male Maoa-knockout (KO) mice and wild-type (WT) littermates were tested for nicotine-induced conditioned place preference (CPP); voluntary oral nicotine preference/intake; spontaneous locomotor activity in a novel, inescapable open field; and novelty place preference. Nicotine preference in WT mice was reduced in Maoa-KO mice in the CPP and oral preference/intake tests. Control experiments showed that these phenotypes were not due to abnormalities in nicotine metabolism, fluid intake or response to taste. In contrast, Maoa-KO mice were normal in their behavioral response to a novel, inescapable open field and in their preference for a novel place. The observed phenotypes suggest that a constitutive deficiency of MAOA reduces the rewarding effects of nicotine without altering behavioral responses to novel stimuli in mice. Constitutive MAOA activity levels are likely to contribute to the vulnerability or resiliency to nicotine addiction by altering the rewarding effects of nicotine.
Catalytic synthesis of N-heterocycles and alpha-alkylated amines by hydroamination and hydroaminoalkylation (2017)

The research presented in this thesis emphasizes the versatility and utility of N,O-chelated early transition metals for the catalytic synthesis of -alkylated amines. Two major transformations were studied extensively in this work, hydroamination and hydroaminoalkylation. For both reactions, the synthetic utility and substrate scope has been expanded by the work presented herein. In the field of hydroamination, N-heterocycles with more than one heteroatom can now be synthesized using early transition metal catalysts from prochiral substrates. Hydroamination with a bis(amidate)bis(amido) complex of titanium of ether-containing aminoalkyne substrates yield cyclic imines, which are subsequently reduced via asymmetric transfer hydrogenation using the Noyori-Ikariya catalyst, RuCl [(S,S)-Ts-DPEN] (η⁶-p-cymene). 3-Substituted morpholines are synthesized using a one-pot sequential catalysis protocol, in good yields and high enantiomeric excesses. Substrate scope investigations reveal that high enantioselectivities in the asymmetric transfer hydrogenation reaction arise from key hydrogen bonding interactions between the oxygen heteroatom of the ether-containing cyclic imine and the [(S,S)-Ts-DPEN] ligand of Noyori-Ikariya catalyst. This mechanistic insight informed the proposal that this synthetic strategy can be extended to other substrates containing functional groups with hydrogen bond acceptors. As such, 3-substituted piperazines are also prepared with high enantioselectivities using this one-pot protocol. Advances to the hydroaminoalkylation transformation have also been made with the first reported example of room temperature reactivity observed using a phosphoramidate-tantalum complex. The preparation and characterization of a series of N,O-chelated phosphoramidate-tantalum complexes is described. These complexes were easily synthesized from either Ta(NMe₂)₅ by protonolysis or a simple organometallic precursor, TaMe₃Cl₂, by salt metathesis. Reactivity towards catalytic hydroaminoalkylation was explored and the results highlight that the choice of tantalum starting material dramatically affects the reaction temperatures required for catalytic turnover. N,O-chelated phosphoramidate dimethylamido tantalum complexes showed reactivity occurred only at elevated temperatures (≥ 90 °C), whereas phosphoramidate-tantalum complexes derived from TaMe₃Cl₂ exhibited unprecedented catalytic activity at room temperature. Preliminary efforts indicate that there is potential for an asymmetric version of hydroaminoalkylation at room temperature. Chiral phosphoramidate-tantalum complexes were prepared and studied as the first examples of asymmetric hydroaminoalkylation reactions at room temperature.
Volumizing effects of a smooth, highly cohesive, viscous 20-mg/mL hyaluronic acid volumizing filler: prospective European study (2009)

The 20-mg/mL smooth, highly cohesive, viscous, volumizing HA filler was effective, well tolerated, and easy to use in current clinical practice. Participants were very likely to recommend this product to colleagues and friends, and patients would be very or quite likely to request this product for future treatments.
‘Click’ Chemistry in Polymer and Materials Science (2007)

Abstract The modification of polymers after the successful achievement of a polymerization process represents an important task in macromolecular science. Cycloaddition reactions, among them the metal catalyzed azide/alkyne ‘click’ reaction (a variation of the Huisgen 1,3‐dipolar cycloaddition reaction between terminal acetylenes and azides) represents an important contribution towards this endeavor. They combine high efficiency (usually above 95%) with a high tolerance of functional groups and solvents, as well as moderate reaction temperatures (25–70 °C). The present review assembles recent literature for applications of this reaction in the field of polymer science (linear polymers, dendrimers, gels) as well as the use of this and related reactions for surface modification on carbon nanotubes, fullerenes, and on solid substrates, and includes the authors own publications in this field. A number of references (&gt;100) are included. magnified image
Akt inactivation is a key event in indole-3-carbinol-induced apoptosis in PC-3 cells. (2002)

Indole-3-carbinol (I3C) is a bioactive compound present in Brassica vegetables that shows an antitumor activity in experimental animals and inhibits the growth of human cancer cells in vitro. In recent years, studies on prostate cancer (PCa) chemoprevention have been intensified, because there is a long latency for the development of clinical PCa, which makes the PCa a better target for chemoprevention. We have shown previously that I3C induces cell growth inhibition by G(1) cell cycle arrest and induces apoptosis in a dose- and time-dependent manner in PC-3 PCa cells; however, the mechanism(s) by which I3C induces apoptosis in PC-3 cells is still not clear. A cell survival pathway involving phosphatidylinositol 3'-kinase (PI3K) and Akt is known to play an important role in inhibiting apoptosis in response to growth factor signaling, which prompted us to investigate whether this pathway plays any role in I3C-induced apoptosis in PCa cells. Here we report that I3C inhibits the phosphorylation and subsequent activation of Akt kinase. In addition, I3C abrogated epidermal growth factor (EGF)-induced activation of Akt in PC-3 cells. Western blot analyses of EGF receptor showed that I3C down-regulates the EGF receptor levels and its autophosphorylation. This was also accompanied by the inhibition of EGF-induced phosphorylation of PI3K by I3C treatment. Furthermore, the known downstream modulators of the Akt/PI3K cell survival pathway, Bcl-x(L), and BAD proteins showed decreased expression after I3C treatment. From these results, we conclude that I3C-induced apoptosis is partly mediated by the inhibition of Akt activation, resulting in the alterations in the downstream regulatory molecules of Akt activation in PC-3 cells. However, further in-depth investigation is needed to establish a cause-and-effect relationship between Akt pathway and I3C effect.
Tissue culture demyelination by normal human serum (1984)

Abstract Serum from all of 20 normal individuals induced some degree of demyelination when applied to well‐myelinated mouse cerebellum cultures. An intact complement sequence through C5 is required. Demyelinating activity was heat labile at 56°C for 30 minutes but was not destroyed at 50°C for 30 minutes (which inhibits properdin factor B and alternate complement pathway activation, but not the classic complement pathway). Sera from patients with agammaglobulinemia, C4 deficiency, or C6 deficiency all induced demyelination. Our results suggest that tissue culture demyelination results from nonimmunoglobulin activation of the alternate complement pathway and is not limited to sera from patients with neurological disease.
Distributed space-time codes in wireless relay networks (2005)

We apply the idea of space-time coding devised for multiple antenna systems to the communication over a wireless relay network. We use a two stage protocol, where in one stage the transmitter sends information and in the other, the relay nodes encode their received signals into a "distributed" linear dispersion code, and then transmit the coded signals to the receiver. We show that for high SNR the pairwise error probability (PEP) behaves as (log P/P)/sup min{T,R}/ with T the coherence interval, R the number of relay nodes and P the total transmit power. Thus, apart from the log P factor and assuming T/spl ges/R, the system has the same diversity as a multi-antenna system with R transmit antennas, which is the same as assuming that the R relay nodes can fully cooperate and have full knowledge of the transmitted signal. We further show that for a fixed total transmit power across the entire network, the optimal power allocation is for the transmitter to expend half the power and for the relays to collectively expend the other half. We also show that at low and high SNR, the coding gain is the same as that of a multi-antenna system with R antennas. At intermediate SNR, it can be quite different, which has implications for the design of distributed space-time codes.
NMR characterization of altered lignins extracted from tobacco plants down-regulated for lignification enzymes cinnamylalcohol dehydrogenase and cinnamoyl-CoA reductase (1998)

Homologous antisense constructs were used to down-regulate tobacco cinnamyl-alcohol dehydrogenase (CAD; EC 1.1.1.195) and cinnamoyl-CoA reductase (CCR; EC 1.2.1.44) activities in the lignin monomer biosynthetic pathway. CCR converts activated cinnamic acids (hydroxycinnamoyl-SCoAs) to cinnamaldehydes; cinnamaldehydes are then reduced to cinnamyl alcohols by CAD. The transformations caused the incorporation of nontraditional components into the extractable tobacco lignins, as evidenced by NMR. Isolated lignin of antisense-CAD tobacco contained fewer coniferyl and sinapyl alcohol-derived units that were compensated for by elevated levels of benzaldehydes and cinnamaldehydes. Products from radical coupling of cinnamaldehydes, particularly sinapaldehyde, which were barely discernible in normal tobacco, were major components of the antisense-CAD tobacco lignin. Lignin content was reduced in antisense-CCR tobacco, which displayed a markedly reduced vigor. That lignin contained fewer coniferyl alcohol-derived units and significant levels of tyramine ferulate. Tyramine ferulate is a sink for the anticipated build-up of feruloyl-SCoA, and may be up-regulated in response to a deficit of coniferyl alcohol. Although it is not yet clear whether the modified lignins are true structural components of the cell wall, the findings provide further indications of the metabolic plasticity of plant lignification. An ability to produce lignin from alternative monomers would open new avenues for manipulation of lignin by genetic biotechnologies.
Evidence for time-dependent activation of monocytes in the systemic circulation in unstable angina but not in acute myocardial infarction or in stable angina. (1994)

A time-dependent activation of systemic monocytes and a time-dependent increase in fibrinogen levels occurs in unstable angina but not in myocardial infarction. These findings provide further evidence that a specific inflammatory process occurs in unstable angina. Further studies are required to determine whether monocyte activation is a cause or a consequence of plaque instability in patients with unstable angina and to clarify the interrelations between platelet and monocyte activation in these circumstances.
Quantum simulation of spin models on an arbitrary lattice with trapped ions (2012)

A collection of trapped atomic ions represents one of the most attractive platforms for the quantum simulation of interacting spin networks and quantum magnetism. Spin-dependent optical dipole forces applied to an ion crystal create long-range effective spin-spin interactions and allow the simulation of spin Hamiltonians that possess nontrivial phases and dynamics. Here we show how appropriate design of laser fields can provide for arbitrary multidimensional spin-spin interaction graphs even for the case of a linear spatial array of ions. This scheme uses currently existing trap technology and is scalable to levels where classical methods of simulation are intractable.
Lipids revert inert Aβ amyloid fibrils to neurotoxic protofibrils that affect learning in mice (2007)

Although soluble oligomeric and protofibrillar assemblies of Abeta-amyloid peptide cause synaptotoxicity and potentially contribute to Alzheimer's disease (AD), the role of mature Abeta-fibrils in the amyloid plaques remains controversial. A widely held view in the field suggests that the fibrillization reaction proceeds 'forward' in a near-irreversible manner from the monomeric Abeta peptide through toxic protofibrillar intermediates, which subsequently mature into biologically inert amyloid fibrils that are found in plaques. Here, we show that natural lipids destabilize and rapidly resolubilize mature Abeta amyloid fibers. Interestingly, the equilibrium is not reversed toward monomeric Abeta but rather toward soluble amyloid protofibrils. We characterized these 'backward' Abeta protofibrils generated from mature Abeta fibers and compared them with previously identified 'forward' Abeta protofibrils obtained from the aggregation of fresh Abeta monomers. We find that backward protofibrils are biochemically and biophysically very similar to forward protofibrils: they consist of a wide range of molecular masses, are toxic to primary neurons and cause memory impairment and tau phosphorylation in mouse. In addition, they diffuse rapidly through the brain into areas relevant to AD. Our findings imply that amyloid plaques are potentially major sources of soluble toxic Abeta-aggregates that could readily be activated by exposure to biological lipids.
Capillary permeability is increased in normo‐ and microalbuminuric Type 1 diabetic patients: amelioration by ACE‐inhibition (1999)

Capillary permeability, as determined by NaF leakage, is elevated in normoalbuminuric Type 1 diabetic patients with long-standing disease, and the excess elevation in microalbuminuric Type 1 diabetic patients is ameliorated by ACE-inhibition. Skin NaF videodensitometry seems a useful tool to document capillary permeability in intervention studies.
Stability Order in Metal Chelate Compounds. II. 5-(p-Sulfophenylazo)-salicylate Complexes (1964)

Abstract The interaction of 5-(p-sulfophenylazo)-salicylic acid with zinc(II), copper(II), nickel-(II), cobalt(II), manganese(II), magnesium(II), calcium(II) and iron(III) has been investigated in aqueous media at 25.0±0.1°C and the ionic strength of 0.10 m. The stability constants for the 1 : 1 and 2 : 1 (ligand to metal) chelates of nickel, cobalt, manganese and magnesium, and for the 1 : 1 calcium chelate, as well as for the 2 : 1 ferric chelate, have been evaluated, and the resulting stability order with respect to the bivalent metals has been found to follow the sequence: calcium(II)&amp;lt;magnesium(II)&amp;lt;manganese(II)&amp;lt;(zinc(II))&amp;lt;copper(II)&amp;lt;nickel(II)&amp;lt;copper(II). The stability sequence, zinc(II)&amp;lt;nickel (II), is contrary to that observed for the catechol chelates. A p-sulfophenylazo group demonstrated an electron-withdrawing effect, the magnitude of which was slightly greater than that of a sulfonate group. However, the effect of the former group on the chelate-stability has been found to be comparable with that of the latter. The present salicylate derivative is also a good chelating agent for iron (III) ion, even though the chelate system somehow becomes involved in a higher pH range.
Rapid accumulation of hydrogen peroxide in cucumber roots due to exposure to low temperature appears to mediate decreases in water transport (2004)

Water transport across root systems of young cucumber (Cucumis sativus L.) seedlings was measured following exposure to low temperature (LT, 8-13 degrees C) for varying periods of time. In addition, the amount of water transported through the stems was evaluated using a heat-balance sap-flow gauge. Following LT treatment, hydrogen peroxide was localized cytochemically in root tissue by the oxidation of cerium (III) chloride. The effects of hydrogen peroxide on the hydraulic conductivity of single cells (Lp) in root tissues, and on the H+-ATPase activity of isolated root plasma membrane, have been worked out. Cytochemical evidence suggested that exposure of roots to LT stress caused a release of hydrogen peroxide in the millimolar range in the vicinity of plasma membranes. In response to a low root temperature (8 degrees C), the hydraulic conductivity of the root (Lp(r)) decreased by a factor of 4, and the half-times of water exchange increased by a factor of 5-6. Decreasing root temperatures from 25-13 degrees C increased the half-times of water exchange in a cell by a factor of 6-9. The measurement of axial water transport with a heat-balance sap-flow gauge showed that only a small amount of water was transported when 8 degrees C was imposed on cucumber roots. Lp and the H+-ATPase activity of the isolated root plasma membrane were very sensitive to externally applied hydrogen peroxide at a concentration of 1-16 mM. These observations suggest that the accumulation of hydrogen peroxide appears to mediate decreases in water transport in cucumber roots under low temperature.
Regional specificity of alterations in NGF, BDNF and NT-3 levels in Alzheimerʼs disease (1996)

USING two-site enzyme immunoassays (EIAs), we measured the levels of neurotrophins, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) simultaneously in three brain regions (motor cortex, dentate gyrus and entorhinal cortex) of patients with Alzheimer's disease (AD) and control individuals. Significant differences between the neurotrophin levels of these two groups were found in the different brain regions depending on the neurotrophin. The NGF level in the dentate gyrus of AD patients was higher, whereas the BDNF level in the entorhinal cortex and the NT-3 level in the motor cortex were lower than the corresponding control levels. These results indicate that protein levels of individual neurotrophins in different brain regions are affected differently by AD, and such differential changes may contribute to the complex pathology of AD.
The pathogenesis of bleomycin-induced pulmonary fibrosis in mice. (1974)

Administration of 0.5 mg bleomycin to mice twice weekly for 4 weeks induced pulmonary fibrosis. The initial site of injury was the intima of pulmonary arteries and veins where endothelial cells became edematous and were separated from the underlying basement membrane by large blebs. These lesions occurred after 2 weeks and were associated with infiltration of perivascular spaces by lymphocytes and plasma cells. Capillary endothelial blebbing and interstitial edema were observed after 4 weeks, when multifocal necrosis of type 1 alveolar epithelial cells was accompanied by fibrinous exudation into the alveoli. The process of repair was characterized by proliferation and metaplasia of type 2 epithelial cells, fibroblastic organization of alveolar fibrin and fibrosis of the interstitium within 8 to 12 weeks. The consistent induction of changes similar to those of diffuse pulmonary fibrosis or fibrosing alveolitis in man suggests that bleomycin-induced injury may provide a suitable model for the investigation of this ill-defined group of diseases.