gebhart/patrepeval huggingface dataset:
Cellular targets and mechanisms of nitros(yl)ation: An insight into their nature and kinetics in vivo (2004)

There is mounting evidence that the established paradigm of nitric oxide (NO) biochemistry, from formation through NO synthases, over interaction with soluble guanylyl cyclase, to eventual disposal as nitrite/nitrate, represents only part of a richer chemistry through which NO elicits biological signaling. Additional pathways have been suggested that include interaction of NO-derived metabolites with thiols and metals to form S-nitrosothiols (RSNOs) and metal nitrosyls. Despite the overwhelming attention paid in this regard to RSNOs, little is known about the stability of these species, their significance outside the circulation, and whether other nitros(yl)ation products are of equal importance. We here show that N-nitrosation and heme-nitrosylation are indeed as ubiquitous as S-nitrosation in vivo and that the products of these reactions are constitutively present throughout the organ system. Our study further reveals that all NO-derived products are highly dynamic, have fairly short lifetimes, and are linked to tissue oxygenation and redox state. Experimental evidence further suggests that nitroso formation occurs substantially by means of oxidative nitrosylation rather than NO autoxidation, explaining why S-nitrosation can compete effectively with nitrosylation. Moreover, tissue nitrite can serve as a significant extravascular pool of NO during brief periods of hypoxia, and tissue nitrate/nitrite ratios can serve as indicators of the balance between local oxidative and nitrosative stress. These findings vastly expand our understanding of the fate of NO in vivo and provide a framework for further exploration of the significance of nitrosative events in redox sensing and signaling. The findings also raise the intriguing possibility that N-nitrosation is directly involved in the modulation of protein function.
Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults (2016)

Clonal haematopoiesis is thought to be a rare condition that increases in frequency with age and predisposes individuals to haematological malignancy. Recent studies, utilizing next-generation sequencing (NGS), observed haematopoietic clones in 10% of 70-year olds and rarely in younger individuals. However, these studies could only detect common haematopoietic clones->0.02 variant allele fraction (VAF)-due to the error rate of NGS. To identify and characterize clonal mutations below this threshold, here we develop methods for targeted error-corrected sequencing, which enable the accurate detection of clonal mutations as rare as 0.0003 VAF. We apply these methods to study serially banked peripheral blood samples from healthy 50-60-year-old participants in the Nurses' Health Study. We observe clonal haematopoiesis, frequently harbouring mutations in DNMT3A and TET2, in 95% of individuals studied. These clonal mutations are often stable longitudinally and present in multiple haematopoietic compartments, suggesting a long-lived haematopoietic stem and progenitor cell of origin.
Acoustoelectric Effects in Carbon Nanotubes (2000)

We report observations of acoustoelectric effects in carbon nanotubes. We excite sound in &mgr;m long ropes of single walled carbon nanotubes suspended between two metallic contacts by applying radio-frequency electric field. The sound is detected by measuring either the dc resistance of the tubes in a region of strong temperature dependence (in the vicinity of superconducting or metal-insulator transition), or their critical current. We show that, depending on the excitation power, the vibrations produce either electron heating or phase coherence breaking.
Morphology Development of Mesoporous Materials:  a Colloidal Phase Separation Mechanism (2004)

Synthetic conditions such as temperature, stirring rate, ionic strength, acidity, and reactant ratios that affect the mesostructures and macrostructures of mesoporous materials have been extensively studied in the nonionic block copolymer templating system. Highly ordered SBA-15 materials with ∼100% rodlike morphologies (∼1−2 μm long) have been obtained in the presence of inorganic salts. Synthesis conditions such as low temperature, low acidity, and low ionic strength that increase the induction time give rise to the morphologies of mesoporous silica with increased curvatures. The particle growth process of rodlike SBA-15 materials from solutions has been examined by directly observing the morphologies of particles as a function of time. A colloidal phase separation mechanism (CPSM) for the formation of mesoporous materials is proposed. It is suggested that the formation process of mesoporous materials involves three stages: (1) cooperative self-assembly of inorganic/organic composites; (2) formation of a new crystal-like phase rich in aggregates of block copolymer/silica species; and (3) phase separation of this liquid crystal-like phase from the solution and further growth of solid mesostructures driven by further condensation of silica species. The morphologies of mesoporous materials are developed after the phase separation stage and influenced by the competition mainly between the free energy of mesostructure self-assembly (ΔG) and the colloidal surface free energy (F), as well as other interactions such as the shearing force. When the phase separation stage occurs early, ΔG is dominant and the macrostructure of mesoporous materials is developed together with the formation of mesostructure; therefore, mesoporous materials with crystal-like morphologies can be generated. The role of inorganic salts is well explained based on the CPSM by taking into account the colloidal interaction enhanced by inorganic salts. Cubic (Im3̄m) mesoporous single crystals have been obtained with exclusively rhombdodecahedron shapes (1−2 μm in size). Ultrathin microtoming TEM measurements confirm that such polyhedral particles are perfect single crystals. The different influences of hydrothermal treatments upon the mesostructures and macrostructures have been discussed in the hexagonal and cubic synthesis systems. By employing the CPSM, hexagonal mesoporous single crystals have been obtained in the absence of inorganic salts; the size limitation (∼1−2 μm) of mesoporous single crystals has also been discussed. Such understandings may be useful in the fabrication of mesoporous materials with well-defined, crystal-like morphologies.
Effect of Electrode Size, Shape, and Placement During Electrical Stimulation (2004)

Objective: The effect of electrode size, shape, and placement during electrical stimulation of the biceps, quadriceps, and tibialis anterior muscles were studied to assess what current is required during current-controlled electrical stimulation (ES I ) to reach a set muscle force, as well as to evaluate patient comfort.
Role of the "Helix Clamp" in HIV-1 Reverse Transcriptase Catalytic Cycling as Revealed by Alanine-scanning Mutagenesis (1996)

Residues 259-284 of HIV-1 reverse transcriptase exhibit sequence homology with other nucleic acid polymerases and have been termed the "helix clamp" (Hermann, T., Meier, T., Gotte, M., and Heumann, H. (1994) Nucleic Acids Res. 22, 4625-4633), since crystallographic evidence indicates these residues are part of two alpha-helices (alpha H and alpha I) that interact with DNA. Alanine-scanning mutagenesis has previously demonstrated that several residues in alpha H make important interactions with nucleic acid and influence frameshift fidelity. To define the role of alpha I (residues 278-286) during catalytic cycling, we performed systematic site-directed mutagenesis from position 277 through position 287 by changing each residue, one by one, to alanine. Each mutant protein was expressed and, except for L283A and T286A, was soluble. The soluble mutant enzymes were purified and characterized. In contrast to alanine mutants of alpha H, alanine substitution in alpha I did not have a significant effect on template.primer (T.P) binding as revealed by a lack of an effect on Km, T.P, Ki for 3'-azido-2',3'-dideoxythymidine 5'-triphosphate, koff, T.P and processivity. Consistent with these observations, the fidelity of the mutant enzymes was not influenced. However, alanine mutagenesis of alpha I lowered the apparent activity of every mutant relative to wild-type enzyme. Titration of two mutants exhibiting the lowest activity with T.P (L282A and R284A) demonstrated that these mutant enzymes could bind T.P stoichiometrically and tightly. In contrast, active site concentrations determined from "burst" experiments suggest that the lower activity is due to a smaller populations of enzyme bound productively to T.P. The putative electrostatic interactions between the basic side chains of the helix clamp and the DNA backbone are either very weak or kinetically silent. In contrast, interactions between several residues of alpha H and the DNA minor groove, 3-5 nucleotides from the 3'-primer terminus, are suggested to be critical for DNA binding and fidelity.
Derivation of Human Embryonic Stem Cell Lines in Serum Replacement Medium Using Postnatal Human Fibroblasts as Feeder Cells (2005)

Derivation and culture of human embryonic stem cells (hESCs) without animal-derived material would be optimal for cell transplantation. We derived two new hES (HS293 and HS306) and 10 early cell lines using serum replacement (SR) medium instead of conventional fetal calf serum and human foreskin fibroblasts as feeder cells. Line HS293 has been in continuous culture, with a passage time of 5-8 days, since October 2003 and is at passage level 56. Line HS306 has been cultured since February 2004, now at passage 41. The lines express markers of pluripotent hESCs (Oct-4, SSEA-4, TRA-1-60, TRA-1-81, GCTM-2, and alkaline phosphatase). The pluripotency has been shown in embryoid bodies in vitro, and the pluripotency of line 293 has also been shown in vivo by teratoma formation in severe combined immunodeficiency/beige mice. The karyotype of HS293 is 46,XY, and that of HS306 is 46,XX. Ten more early lines have been derived under similar conditions since September 2004. We conclude that hESC lines can be successfully derived using SR medium and postnatal human fibroblasts as feeder cells. This is a step toward xeno-free conditions and facilitates the use of these cells in transplantation.
Rho/ROCK Pathway Contributes to the Activation of Extracellular Signal-regulated Kinase/GATA-4 during Myocardial Cell Hypertrophy (2002)

The low molecular weight GTPase Rho mediates a variety of cytoskeleton-dependent cell functions and stretch- and G(q) protein-induced hypertrophic responses in cardiac myocytes. Although ROCK, one of Rho's effectors, has been suggested to mediate hypertrophic signals, the relationship of Rho/ROCK with downstream signals is unknown. A zinc finger transcription factor, GATA-4, is activated by extracellular signal-regulated kinase 1/2 and is required for the up-regulation of the endothelin-1 gene during myocardial cell hypertrophy. However, it is unknown whether Rho/ROCK signals are linked to downstream GATA-4. By transient transfection assays using a dominant-negative mutant and an activated derivative of ROCK-I, we showed that ROCK-I participates in GATA-4-dependent endothelin-1 transcription. Inhibition of the Rho/ROCK pathway by Y-27632, a selective inhibitor of ROCK, suppressed phenylephrine-stimulated phosphorylation of extracellular signal-regulated kinase 1/2 and increased the DNA binding activity of cardiac GATA-4. Interestingly, latrunculin B, which inhibits actin polymerization, also prevents phenylephrine-induced responses. These findings demonstrate that the Rho/ROCK pathway is linked to downstream GATA-4 via the activation of extracellular signal-regulated kinases during myocardial cell hypertrophy. The results also suggest that changes in actin dynamics provide a convergence point for Rho/ROCK to the downstream signals during this process.
Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments (2009)

Th17 cells play an active role in autoimmune diseases. However, the nature of Th17 cells is poorly understood in cancer patients. We studied Th17 cells, the associated mechanisms, and clinical significance in 201 ovarian cancer patients. Tumor-infiltrating Th17 cells exhibit a polyfunctional effector T-cell phenotype, are positively associated with effector cells, and are negatively associated with tumor-infiltrating regulatory T cells. Tumor-associated macrophages promote Th17 cells through interleukin-1beta (IL-1beta), whereas tumor-infiltrating regulatory T cells inhibit Th17 cells through an adenosinergic pathway. Furthermore, through synergistic action between IL-17 and interferon-gamma, Th17 cells stimulate CXCL9 and CXCL10 production to recruit effector T cells to the tumor microenvironment. The levels of CXCL9 and CXCL10 are associated with tumor-infiltrating effector T cells. The levels of tumor-infiltrating Th17 cells and the levels of ascites IL-17 are reduced in more advanced diseases and positively predict patient outcome. Altogether, Th17 cells may contribute to protective human tumor immunity through inducing Th1-type chemokines and recruiting effector cells to the tumor microenvironment. Inhibition of Th17 cells represents a novel immune evasion mechanism. This study thus provides scientific and clinical rationale for developing novel immune-boosting strategies based on promoting the Th17 cell population in cancer patients.
Synthesis and Hybridization Properties of Oligonucleotides Containing Polyamines at the C-2 Position of Purines: A Pre-synthetic Approach for the Incorporation of Spermine into Oligodeoxynucleotides Containing 2-(4,9,13-Triazatridecyl)-2′-deoxyguanosine (2000)

We have developed a synthesis of spermine-containing oligonucleotides (ODN-sper) which allows incorporation of multiple polyamine residues. This approach was based on the pertrifluoroacetylated 5'DMT-dGsper phosphoramidite synthon. Its coupling yield with resin-bound ODN decreased dramatically when close to the 3'-end. Optimization of the coupling conditions allowed 22-mer ODNs containing up to six spermine residues to be synthesized. Several ODNs of different sequences with 1-4 pendent spermines could be purified and their hybridization properties were evaluated. Duplex melting temperatures increased linearly with the number of polyamine residues (deltaTm/sper = 3.0 +/- 0.2 degrees C in 100mM NaCl). This compares very favorably with values reported for duplexes of similar initial stability containing other cation-substituted bases. Moreover, the stability increase was neither sequence nor position-dependent, and even contiguous spermine residues did not cross-talk. Extrapolation based on these findings leads to the conclusion that a duplex formed with a 22-mer oligonucleotide containing seven spermine residues would be as stable as genomic DNA, which highlights its potential for DNA strand invasion.
Analysis of the mammalian gadd45 gene and its response to DNA damage. (1993)

The gadd45 gene is transcriptionally activated through at least two different mechanisms; one following treatment with base-damaging agents such as methylmethane sulfonate and UV radiation and the other following ionizing radiation. To investigate the sequences involved in induction of gadd45 by agents producing high levels of base damage, the hamster, human, and mouse genes were sequenced. Comparison of these sequences revealed a high level of conservation between species of 1500 base pairs of the proximal promoter and 700 base pairs within the third intron. However, in the promoter regions, there was no conservation between species of any transcription factor binding sites known to confer DNA damage responsiveness. The promoter of the hamster gene was inducible by base-damaging agents in both rodent and human cell lines and the human gene was inducible in a rodent cell line. This indicates that both sequence elements in the gadd45 promoter and factors binding to these sites are conserved in mammalian cells. Deletion analysis of the hamster promoter did not reveal any specific sequence which conferred damage inducibility and the maximal response required a large portion of the promoter. The hamster promoter was not inducible by ionizing radiation, suggesting that sequences outside the promoter region used, such as a p53 binding site in the third intron, are necessary. The human GADD45 gene was mapped to chromosome 1p31.1-31.2.
Está nevando en la Ciudad de los Reyes (1986)

?Por que tenia que sonar con mis muertes y millones de muertos y mujeres con punales en la mano? ?a que se debia todo eso? ?y la sangre que me empapaba la camisa? ?no siento que esta empapada de sangre? ?mi mano tambien no esta ensangrentada? ?no es chocante ver la sangre de uno encharcada en la cama? y aquella increible vision de encontrarme en un mundo sonado donde todo se sucedia a velocidad luz puesto que no habia forma de detener las fugaces imagenes que corrian por mi mente me despertaba los ojos del alma y ya sentia que una especie de energia penetraba mi cuerpo dormido (dos veces lo senti tan claramente que me entraron ganas de despertarme pero aquel poderoso halo me lo impedia) trasladandome a otros sitios desconocidos y asi viajaba y vi a un hombre sin poder distinguirle el rostro y vi paginas amarillas isi pudiera parar una sola de las imagenes de las miles que se deslizan por mi craneo de seguro que descubriria un mundo distinto al que conozco! ?como seria ese mundo desconocido aun el cual solo me mostraba destellos de su contorno? ?que clase de criaturas habria alli? ?de que material estaria hecho su habitat? y por alli pasa una oleada de imagenes nuevamente que me marean y estaba nevando en la Ciudad de los Reyes en el mes de diciembre toda la madrugada
Privacy and authentication for wireless local area networks (1994)

Wireless networks are being driven by the need for providing network access to mobile or nomadic computing devices. Although the need for wireless access to a network is evident, new problems are inherent in the wireless medium itself. Specifically, the wireless medium introduces new opportunities for eavesdropping on wireless data communications. Anyone with an appropriate wireless receiver can eavesdrop, and this kind of eavesdropping is virtually undetectable. Furthermore, since the wireless medium cannot be contained by the usual physical constraints of walls and doors, active intrusions through the wireless medium are also made easier. In order to prevent this unauthorized access to the network, the authors present the design of a secure communication protocol that provides for both the privacy of wireless data communications and the authenticity of communicating parties. The placement of the protocol in the overall protocol stack and issues relevant to wireless links and mobile computing devices are discussed. They also present proof of the security of the protocol using the logic of authentication formalism developed by Burrows, Abadi, and Needham (1990).< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Expression Cloning and Regulation of Steroid 5α-Reductase, an Enzyme Essential for Male Sexual Differentiation (1989)

The conversion of testosterone into the more potent androgen, dihydrotestosterone, catalyzed by the enzyme steroid 5 alpha-reductase, is required for the differentiation of male external genitalia. Here, we report the isolation of cDNA clones encoding the rat steroid 5 alpha-reductase using expression cloning in Xenopus oocytes. DNA sequence analysis demonstrates that the liver and ventral prostate forms of steroid 5 alpha-reductases are identical hydrophobic proteins of 29 kDa. The amount of steroid 5 alpha-reductase mRNA in liver increased in response to castration, but remained unchanged in the prostate. Testosterone administration to castrates induced expression of mRNA in the prostate but had no effect on liver. The data suggest that the steroid 5 alpha-reductase gene is differentially regulated by testosterone in androgen-responsive versus non-responsive tissues.
Apatite Formation Induced by Silica Gel in a Simulated Body Fluid (1992)

It has been confirmed that the essential condition for glasses and glass‐ceramics to bond to living bone is the formation of an apatite layer on their surfaces in the body. It has been proposed that a hydrated silica formed on the surfaces of these materials in the body plays an important role in forming the surface apatite layer, but this has not yet been proved. In the present study, it is shown experimentally that a pure hydrated silica gel can induce apatite formation on its surface in a simulated body fluid when its starting pH is increased from 7.2 to 7.4.
Ischemic Preconditioning in Humans (1999)

Ischemic preconditioning, a powerful form of endogenous protection against myocardial infarction, has been demonstrated in several animal species and, recently, in isolated human cardiomyocytes. For both logistic and ethical reasons, no clinical study can meet the strict conditions of experimental studies on preconditioning with infarct size as the end-point. Nevertheless, the demonstration of adaptation to ischemia observed during in vitro studies on human atrial trabeculae, in patients in the setting of coronary bypass surgery, and in the setting of coronary angioplasty in the absence of collateral vessel recruitment strongly suggests that ischemic preconditioning occurs in humans. This notion is further supported by the observation that in these human models, the adaptation to ischemia is influenced by drugs acting on K(ATP) channels and on purinergic and alpha-adrenergic receptors, similar to what is observed in accepted experimental models of ischemic preconditioning. This important form of myocardial endogenous protection may also play a role in the warm-up phenomenon and in mediating the beneficial effects of preinfarction angina. The demonstration of ischemic preconditioning in humans and the identification of some of its mediators suggests that in patients at high risk for myocardial infarction, drugs known to block this endogenous form of protection should be used with caution, whereas drugs known to elicit preconditioning might have a relevant therapeutic role.
Modification of the physical and optical properties of the frustule of the diatomCoscinodiscus wailesiiby nickel sulfate (2007)

In this paper we demonstrate how the photonic properties of a diatom can be altered by growth with a metal pollutant. Both the optical and physical properties of the silica frustule of the diatom Coscinodiscus wailesii were affected by the presence of nickel sulfate in sea water. It was found that a sublethal concentration of the metal both significantly modified the size of the pores of the valves and quenched the intrinsic PL of the amorphous silica. Since cytoplasmic structures may be involved in determining the frustule architecture, we also present TEMs of nickel-grown diatoms and show the affected organelles. The ability to modify the properties of the frustule shows that mechanisms exist for the alteration of existing structures in nature to optimize specific characteristics for exploitation in biotechnological applications.
Melatonin and the pineal gland, from basic science to clinical application : proceedings of the International Symposium on Melatonin and the Pineal Gland: From Basic Science to Clinical Application, Paris, 6-9 September 1992 (1993)

Biochemistry, Molecular Biology and Mechanisms of Action (10 papers). Melatonin Receptors (10 papers). Melatonin Analogs (5 papers). Rhythm Entrainment and Response to Light (20 papers). Melatonin Effects and Pharmacology (12 papers). Immune System and Cancer (4 papers). Clinical Perspectives (14 papers). Index of Authors.