gebhart/patrepeval huggingface dataset:
Potential Role of Rho-Associated Protein Kinase Inhibitors for Glaucoma Treatment (2012)

Rho kinase inhibitors are widely considered as a new treatment for glaucoma. Rho kinase inhibition has been shown in vitro and in vivo to lower intraocular pressure. Furthermore in the first clinical reports involving healthy human subjects, the results were quite promising. The potential of this new class of medicines is enormous in a field where there were not many developments lately. The inhibition of Rho kinase lowers the intraocular pressure by increasing the outflow through the trabecular meshwork. Increased blood flow to the optic nerve and a possible delay of optic nerve cell death has also been reported. As a consequence, the exploration of pharmacological inhibitors of Rho kinase signaling is actively being pursued by a number of pharmaceutical companies such as Senju Pharmaceuticals, Novartis, Kowa, Santen, Aerie, Inspire and others. In this article, we review the latest patents in this field, with their corresponding literature, regarding Rho kinase inhibitors for the treatment of intraocular pressure and summarize the many roles of Rho kinase signaling in the eye.
Cyclopalladated compounds as chemotherapeutic agents: Antitumor activity against a murine melanoma cell line (2003)

Palladacycle compounds obtained from N, N-dimethyl-1-phenethylamine (dmpa), phenyl-2-pyridinyl-acetylene and 1-phenyl-3-N, N-dimethylamine-propine, respectively, were complexed to 1, 2 ethanebis (diphenylphosphine) (dppe) ligand to synthesize antitumor cyclopalladated complexes that were tested in vitro and in vivo against syngeneic B16F10-Nex2 murine melanoma cells of low immunogenicity implanted subcutaneously in mice. Complexes were not toxic to mice injected 3 times i.p. with as much as 60 microM/animal/week. Of 3 cyclopalladated complexes that were inhibitory in vitro at low concentrations (<1.25 microM), complex 7a was the most active in vivo, delaying tumor growth and prolonging animal survival. In vitro, binucleate complex 7a caused a collapse of respiratory activity with an abrupt decrease of extracellular acidification on short incubation (up to 100 min), followed by DNA degradation after 24 hr. The apoptosis-like reaction to this Pd-complex was not accompanied by increased levels of caspases 1 and 3. Complex 7a bound to a bacterial plasmid DNA, causing late conformational changes after 24 hr. Two other complexes with different C, N-cycles were also apoptotic and 2 binucleated ones were inactive. These results introduce the palladacycle-dppe complexes as promising antitumor drugs with exquisite structural specificities and for action in vivo and in vitro.
The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease (2006)

Autosomal-dominant polycystic kidney disease (ADPKD) is a common genetic disorder that frequently leads to renal failure. Mutations in polycystin-1 (PC1) underlie most cases of ADPKD, but the function of PC1 has remained poorly understood. No preventive treatment for this disease is available. Here, we show that the cytoplasmic tail of PC1 interacts with tuberin, and the mTOR pathway is inappropriately activated in cyst-lining epithelial cells in human ADPKD patients and mouse models. Rapamycin, an inhibitor of mTOR, is highly effective in reducing renal cystogenesis in two independent mouse models of PKD. Treatment of human ADPKD transplant-recipient patients with rapamycin results in a significant reduction in native polycystic kidney size. These results indicate that PC1 has an important function in the regulation of the mTOR pathway and that this pathway provides a target for medical therapy of ADPKD.
Human recombinant lipocortin 1 has acute local anti-inflammatory properties in the rat paw edema test. (1989)

Human recombinant lipocortin 1 has been tested for anti-inflammatory activity in a conventional model of acute inflammation. Microgram amounts of the protein, locally administered, inhibited edema of the rat paw when induced by subplantar injections of carrageenin: the ED50 was 10-20 micrograms per paw, and inhibition (maximum of 60-70%) was not dependent upon an intact adrenal cortex. Doses of lipocortin that produced approximately 50% inhibition in the carrageenin test were inactive against edema elicited by bradykinin, serotonin, platelet-activating factor-acether, or dextran, whereas edema caused by Naja mocambique venom phospholipase A2 was strongly inhibited by lipocortin. The protein inhibited edema when rats were pretreated with agents that depleted mast-cell amines, kininogen, or polymorphonuclear leukocytes prior to initiation of the carrageenin edema but had no inhibitory action when rats were pretreated with the dual cyclooxygenase/lipoxygenase inhibitor BW 755C. These results demonstrate that human recombinant lipocortin has potent local anti-inflammatory activity, probably through selectively interfering with eicosanoid generation. Lipocortin is relatively ineffective against edema caused by mast-cell degranulation or kinins, except when degranulation is caused by phospholipase A2.
Candid covariance-free incremental principal component analysis (2003)

Appearance-based image analysis techniques require fast computation of principal components of high-dimensional image vectors. We introduce a fast incremental principal component analysis (IPCA) algorithm, called candid covariance-free IPCA (CCIPCA), used to compute the principal components of a sequence of samples incrementally without estimating the covariance matrix (so covariance-free). The new method is motivated by the concept of statistical efficiency (the estimate has the smallest variance given the observed data). To do this, it keeps the scale of observations and computes the mean of observations incrementally, which is an efficient estimate for some well known distributions (e.g., Gaussian), although the highest possible efficiency is not guaranteed in our case because of unknown sample distribution. The method is for real-time applications and, thus, it does not allow iterations. It converges very fast for high-dimensional image vectors. Some links between IPCA and the development of the cerebral cortex are also discussed.
The Capacitive Performance of Nitrogen-enriched Carbon in Different Electrolytes (2006)

Abstract not Available.
No Evidence for MLL/AF4 Expression in Normal Cord Blood Samples (1999)

To the Editor:

In a recent issue of Blood, Uckun et al[1][1] reported a high frequency of the MLL/AF4 expression not only among infant patients with acute lymphoblastic leukemia (ALL) but also among children older than 1 year (12 out of 127) at the diagnosis of the disease. This group with reverse
Cyclodextrin formation by the thermostable alpha-amylase of Thermoanaerobacterium thermosulfurigenes EM1 and reclassification of the enzyme as a cyclodextrin glycosyltransferase (1995)

Extensive characterization of the thermostable alpha-amylase of Clostridium thermosulfurogenes EM1, recently reclassified as Thermoanaerobacterium thermosulfurigenes, clearly demonstrated that the enzyme is a cyclodextrin glycosyltransferase (CGTase). Product analysis after incubation of the enzyme with starch revealed formation of alpha-, beta-, and gamma-cyclodextrins, as well as linear sugars. The specific activity for cyclization of this CGTase was similar to those of other CGTases, whereas the specific activity for hydrolysis was relatively high in comparison with other CGTases. Alignment of the amino acid sequence of the T. thermosulfurigenes enzyme with sequences from known bacterial CGTases showed high homology. The four consensus regions of carbohydrate-converting enzymes, as well as a C-terminal raw-starch binding motif, could be identified in the sequence.
La lumière, ses causes et ses effets. Effets de la lumière / par M. Edmond Becquerel,... (1868)

Quercetin suppresses TNF-alpha mediated stimulation of IL-8 and MCP-1 expression, at least in part, by inhibiting the activation of NF-kappa B.
Physical-Chemistry Characteristics and Biodistribution of Poly(ethylene glycol)-Coated Liposomes Using Poly(oxyethylene) Cholesteryl Ether. (1995)

Poly(ethylene glycol)-coated liposomes were prepared with poly(oxyethylene) cholesteryl ethers (mPEG-Chol). PEG unit numbers tested were 50, 100 and 200, of which the average molecular weights (m) of PEG were 2200, 4400 and 8800, respectively. Properties of both PEG-coated liposomes and PEG-Chol molecules were investigated. These liposomes exhibited a long circulation time in the blood after i.v. injection in rats, estimated by both the lipid membrane marker, L-alpha-dipalmitoylphosphatidylcholine [2-palmitoyl-9,10-3H](3H-DPPC), and an internal aqueous marker, 3H-inulin. Accumulation in the liver and spleen at 8h-post-injection was significantly reduced compared with conventional liposomes. The percentage of PEG-Chol incorporation in liposomal membranes was also investigated. Liposomes composed of egg yolk phosphatidylcholine (EPC)/PEG-Chol at various molar ratios were separated from free PEG-Chol molecules, which are not incorporated in liposomal membranes by chromatography over Sepharose CL-4B columns, PEG-Chol incorporation reached approx. 14 and 18 mol% of the total lipids with 25% PEG-Chol unit numbers of 200 and 50, respectively. The occupied area per molecule of PEG-Chol was larger than that of Chol, and the fluorescence anisotropy (r) of the initial 25 mol% (8800)PEG-Chol liposomes was smaller than that observed for 12.5 mol% Chol liposomes. PEG-coated liposomes containing calcein were incubated at 37 degrees C in heat-inactivated fetal bovine serum (FBS). In the presence of FBS, calcein leakage was increased with PEG-Chol percentage incorporation and an increase in FBS concentration. The amount released from PEG-coated liposomes represented 60% at maximum and was larger than that of the control liposomes. PEG-Chol molecules are interesting compounds since they can be easily synthesized in a large amount on an industrial scale. The basic physical-chemistry characteristics investigated in this article are critical to assess the pharmacological application of PEG-Chol liposomes as drug delivery systems.
Oligonucleotide N3′→P5′ Phosphoramidates and Thio‐Phoshoramidates as Potential Therapeutic Agents (2010)

Nucleic acids analogues, i.e., oligonucleotide N3'-->P5' phosphoramidates and N3'-->P5' thio-phosphoramidates, containing 3'-amino-3'-deoxy nucleosides with various 2'-substituents were synthesized and extensively studied. These compounds resist nuclease hydrolysis and form stable duplexes with complementary native phosphodiester DNA and, particularly, RNA strands. An increase in duplexes' melting temperature, DeltaT(m), relative to their phosphodiester counterparts, reaches 2.2-4.0 degrees per modified nucleoside. 2'-OH- (RNA-like), 2'-O-Me-, and 2'-ribo-F-nucleoside substitutions result in the highest degree of duplex stabilization. Moreover, under close to physiological salt and pH conditions, the 2'-deoxy- and 2'-fluoro-phosphoramidate compounds form extremely stable triple-stranded complexes with either single- or double-stranded phosphodiester DNA oligonucleotides. Melting temperature, T(m), of these triplexes exceeds T(m) values for the isosequential phosphodiester counterparts by up to 35 degrees . 2'-Deoxy-N3'-->P5' phosphoramidates adopt RNA-like C3'-endo or N-type nucleoside sugar-ring conformations and hence can be used as stable RNA mimetics. Duplexes formed by 2'-deoxy phosphoramidates with complementary RNA strands are not substrates for RNase H-mediated cleavage in vitro. Oligonucleotide phosphoramidates and especially thio-phosphoramidates conjugated with lipid groups are cell-permeable and demonstrate high biological target specific activity in vitro. In vivo, these compounds show good bioavailability and efficient biodistribution to all major organs, while exerting acceptable toxicity at therapeutically relevant doses. Short oligonucleotide N3'-->P5' thio-phosphoramidate conjugated to 5'-palmitoyl group, designated as GRN163L (Imetelstat), was recently introduced as a potent human telomerase inhibitor. GRN163L is not an antisense agent; it is a direct competitive inhibitor of human telomerase, which directly binds to the active site of the enzyme and thus inhibits its activity. This compound is currently in multiple Phase-I and Phase-I/II clinical trials as potential broad-spectrum anticancer agent.
recB recC-dependent processing of heteroduplex DNA stimulates recombination of an adjacent gene in Escherichia coli (1990)

The effect of DNA mismatched repair on the genetic recombination of a gene adjacent to the mismatch site (MS) was tested by using four mismatch configurations. An MS was constructed in a well-characterized plasmid recombination substrate, and recombination with a resident compatible plasmid was measured after transformation of the mismatched plasmid into Escherichia coli. The mismatched plasmids were constructed such that one of the DNA strands was methylated by the DNA adenine methylase (Dam), while the other strand was unmethylated. The processing of a hemimethylated single-base-pair mismatch had no effect on the recombination of the adjacent gene, suggesting that the most efficient (Dam-instructed) mismatch repair process does not secondarily promote genetic recombination. However, mismatches that could form an ordered secondary structure resembling a cruciform increased the recombination of this adjacent gene at least 20-fold. An identical mismatch that could not form an ordered secondary structure had no effect in this system. The increased frequency of recombination observed was found to require the recB or recC gene product or both. Furthermore, the recombination appeared unidirectional, in that the cruciform-containing plasmid did not produce stable transformants. Our results support a model in which the cruciform-containing plasmid can participate in recombination with the resident plasmid but is unable to produce stable transformant progeny. A proposed role for the RecBCD enzyme (ExoV) in this process is discussed.
GROWTH AND REPRODUCTION OF THE GIANT GLOSSIPHONIID LEECHHAEMENTERIA GHILIANII (1981)

A continuously breeding laboratory colony of the giant leech Haementeria ghilianii has been established from a few specimens collected in French Guyana. The leeches feed on live rabbits or bovine blood, which they draw from an artifical feeding device. Leech growth is saltatory, in that at each of four successive feedings, spaced over about half a year, the weight of each specimen increases 3- to 6-fold. The male reproductive system of this hermaphroditic leech matures first, at a body weight of 3-5 g. The female reproductive system matures after at least one more feeding, at a body weight of at least 8 g. Fecundity (number of eggs per laying) depends on the weight of the leech at the time of oviposition, increasing from 60 for the smallest mature individuals to 500 for the largest. These data on the growth and reproduction of H. ghilianii gathered under laboratory conditions are consistent with its probable life cycle in the native habitat.
Mechanical properties of silicones for MEMS (2008)

This paper focuses on the mechanical properties of polydimethylsiloxane (PDMS) relevant for microelectromechanical system (MEMS) applications. In view of the limited amount of published data, we analyzed the two products most commonly used in MEMS, namely RTV 615 from Bayer Silicones and Sylgard 184 from Dow Corning. With regard to mechanical properties, we focused on the dependence of the elastic modulus on the thinner concentration, temperature and strain rate. In addition, creep and thermal aging were analyzed. We conclude that the isotropic and constant elastic modulus has strong dependence on the hardening conditions. At high hardening temperatures and long hardening time, RTV 615 displays an elastic modulus of 1.91 MPa and Sylgard 184 of 2.60 MPa in a range up to 40% strain.
Free fatty acids stimulate the polymerization of tau and amyloid beta peptides. In vitro evidence for a common effector of pathogenesis in Alzheimer's disease. (1997)

Alzheimer's disease is a degenerative disorder of the central nervous system, characterized by the concomitant deposition of extracellular filaments composed of beta-amyloid peptides and intracellular filaments composed of the microtubule-associated protein tau. We have discovered that free fatty acids (FFAs) stimulate the assembly of both amyloid and tau filaments in vitro. The minimal concentration of arachidonic acid observed to stimulate tau assembly ranged from 10 to 20 mumol/L, depending on the source of the purified tau. Tau preparations that do not exhibit spontaneous assembly were among those induced to polymerize by arachidonic acid. All long-chain FFAs tested enhanced assembly to some extent, although greater stimulation was usually associated with unsaturated forms. Utilizing fluorescence spectroscopy, unsaturated FFAs were also demonstrated to induce beta-amyloid assembly. The minimal concentration of oleic or linoleic acid observed to stimulate the assembly of amyloid was 40 mumol/L. The filamentous nature of these thioflavin-binding amyloid polymers was verified by electron microscopy. These data define a new set of tools for examining the polymerization of amyloid and tau proteins and suggest that cortical elevations of FFAs may constitute a unifying stimulatory event driving the formation of two of the obvious pathogenetic lesions in Alzheimer's disease.
Recent Advances in Multimedia Information System Security (2009)

A multimedia communication system enables multimedia data&amp;apos;s generation, storage, management, distribution, receiving, consuming, editing, sharing, and so on. In such systems, there are various security issues, which must be considered such as eavesdropping, intrusion, forgery, piracy and privacy, etc. Until now, various security solutions for multimedia communication systems have been reported, while few works have surveyed the latest research advances. This paper gives a thorough review to multimedia information system security. It introduces a general architecture of multimedia information system, and investigates some security issues in multimedia information systems. It reviews the latest security solutions such as Digital Rights Management (DRM), confidentiality protection, ownership protection, traitor tracing, secure multimedia distribution based on watermarking, forgery detection, copy detection, privacy-preserving data mining, secure user interface, intrusion detection and prevention. Moreover, the paper presents some hot research topics such as Trusted Computing, steganography, security in network or service convergence, security of content sharing in social networks, privacy-preserving data processing, multimedia forensics and intelligent surveillance in multimedia information system security. It is expected to benefit readers by providing the latest research progress, advising some research directions and giving a list of references about multimedia system security. Povzetek: Prispevek podaja pregled novejših pristopov pri zagotavljanju varnosti multimedijskih informacijskih sistemov.
Highly Polymerized Procyanidins in Brown Soybean Seed Coat with a High Radical-Scavenging Activity (2001)

1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity of the 70% aqueous acetone extract from the seed coat of the brown soybean variety, Akita-Zairai, was investigated. The activity of the seed coat of Akita-Zairai was much higher than that of three other reddish-brown varieties, but lower than that of two black varieties, and was closely dependent on the content of phenolic compounds. In the LH20 column chromatography of Akita-Zairai, high DPPH radical-scavenging activities were detected in the fractions eluted with MeOH and 70% aqueous acetone. Proanthocyanidins were also detected in fractions showing high radical-scavenging activities. Matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry analysis showed that the degree of polymerization (DP) of the procyanidins contained in the brown or black soybean seed coat was as high as DP30.
Conservation of an intact human immunodeficiency virus type 1 vif gene in vitro and in vivo (1995)

Replication of vif-negative human immunodeficiency virus type 1 (HIV-1) is attenuated in certain cell lines and highly impaired in peripheral blood lymphocytes in vitro. To determine whether intact vif is positively selected during natural HIV-1 infection and to determine vif sequence variability, we employed PCR amplification, cloning, and sequencing to investigate the vif region of replicating virus in short-term-passage HIV-1 primary isolates from five asymptomatic individuals and from five persons with AIDS. A total of 46 vif clones were obtained and analyzed. Recombinant proviruses were constructed from selected vif clones from one patient and found to be fully infectious. We found that 38 of the 46 clones sequenced carried open vif reading frames and that there was a low degree of heterogeneity of vif genes within isolates from the same individual and among isolates from different donors. The cysteines previously found to be essential for vif protein function were conserved in all clones. A phylogenetic tree constructed from all available vif nucleotide sequences resulted in a virus grouping similar to those of gag and env. Direct sequencing of vif amplified by PCR from uncultured lymphocytes of 15 individuals at various stages of progression toward AIDS demonstrated vif open reading frames in 13 of 15 samples tested. There was no obvious correlation between disease status and the presence of an intact vif within this sample group at the time of sample procurement. The conservation of the vif open reading frame in vitro and in vivo and its limited variability following virus transmission in vitro are consistent with a role for vif in natural HIV-1 infection.
Novel pyrimidine and 1,3,5-triazine hypolipemic agents (1984)

New compounds were synthesized by changing the substituents of a trisubstituted pyrimidine, i.e., [[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]thio] acetic acid, a potent hypolipidemic agent, impaired, however, by a marked hepatomegaly-inducing effect. The structural variations led to the subsidence (14b, i.e., 4-chloro-2-(dimethylamino)-6-[(2,3-dimethylphenyl)amino]pyrimidine) or to the reduction (18b, [[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]amino] acetic acid) of said untoward effect but still maintained the hypolipidemic effect that, although markedly decreased, still proves significant for serum cholesterol and triglycerides (18b) or for serum triglycerides only (14b).