gebhart/patrepeval huggingface dataset:
The Long-Term Stability of the Human Gut Microbiota (2013)

A low-error 16S ribosomal RNA amplicon sequencing method, in combination with whole-genome sequencing of >500 cultured isolates, was used to characterize bacterial strain composition in the fecal microbiota of 37 U.S. adults sampled for up to 5 years. Microbiota stability followed a power-law function, which when extrapolated suggests that most strains in an individual are residents for decades. Shared strains were recovered from family members but not from unrelated individuals. Sampling of individuals who consumed a monotonous liquid diet for up to 32 weeks indicated that changes in strain composition were better predicted by changes in weight than by differences in sampling interval. This combination of stability and responsiveness to physiologic change confirms the potential of the gut microbiota as a diagnostic tool and therapeutic target.
Identification of an essential serine residue in glucagon: implication for an active site triad. (1994)

Several glucagon analogs containing substitutions for serine have been synthesized to assess the role of the four serine residues in the hormone. The strategic importance of His1 has been confirmed, and we have previously identified an aspartic acid critical for activity at position 9. While these findings have led to a series of pure glucagon antagonists, the details of specific glucagon-receptor interactions that switch on the ensuing signaling events are still not readily apparent. The requirement for serine was tested by the chemical synthesis of a series of analogs containing substitutions for the hydrophilic hydroxyl group in each of the highly conserved serine residues at positions 2, 8, 11, and 16 of glucagon. The resulting analogs were analyzed in rat hepatocyte membranes for their receptor-binding affinities as well as their abilities to stimulate adenylate cyclase. Positions 2 and 8 were the most sensitive to modification, where both binding and activity were adversely affected. This is consistent with the notion that although the sequence responsible for transduction lies in the amino-terminal half of glucagon, some residues at that end also contribute to binding affinity. Modifications at position 11 generated high-binding-affinity derivatives that were full or moderate agonists. In contrast, position 16 replacement analogs maintained significant receptor binding affinities while the agonist properties were almost completely lost, thus separating binding and transduction functions. Therefore, Ser16 is a third critical residue that determines glucagon activity. It is postulated, but not proven, that a serine residue, together with His1 and Asp9, may participate in the putative active center of glucagon, which, upon initial recognition and binding to receptor, leads to transduction of the biological signal. A dependence of the glucagon action on a three-residue cooperative mechanism might be analogous to the charge-relay scheme of serine proteases. It is suggested that, after binding to its receptor, glucagon becomes activated and functions like a coenzyme in catalyzing the specific hydrolysis of a peptide bond in the receptor, generating new amino and carboxyl end groups, and that one of these exposed chains may contact the GTP-binding protein and activate it for further interaction with adenylate cyclase. This idea was supported by inhibition experiments with 4-amidinophenylmethanesulfonyl fluoride (APMSF), a specific and irreversible inhibitor of serine proteases, which at a concentration of 5 mM completely suppressed cAMP formation by glucagon in liver membranes. cAMP formation was not affected if either glucagon or membranes were separately pretreated with APMSF and then assayed.
Therapeutic photobiomodulation: nitric oxide and a novel function of mitochondrial cytochrome c oxidase. (2011)

Currently, light therapies are widely used in both human and veterinarian medicine. The application of light to clinical therapeutics includes: photodynamic therapy, used to kill cancer cells; UVA therapies, used to treat a variety of skin diseases; and photobiomodulation, used to promote cell growth and recovery from injury. Photobiomodu-lation uses light emitting diodes (LEDs) or low energy lasers, which emit light in the visible red to near infrared range. Light in this range penetrates tissue reasonably well, lacks the carcinogenic/mutagenic properties of UV light, and acts on an endogenous photoreceptor which likely acts to initiate light-altered signaling pathways. Although early studies identified mitochondrial cytochrome c oxidase as an endogenous photoreceptor for photobiomodulation, the cellular and molecular mechanisms underlying photobiomodulation have not been clear. Three recent findings provide important new insight. First, nitric oxide has been implicated. Second, cytochrome c oxidase, an enzyme known to reduce oxygen to water at the end of the mitochondrial respiratory chain, has been shown to have a new enzymatic activity--the reduction of nitrite to nitric oxide. This nitrite reductase activity is elevated under hypoxic conditions but also occurs under normoxia. And third, low intensity light enhances nitric oxide synthesis by cytochrome c oxidase without altering its ability to reduce oxygen. From these findings, we propose that cytochrome c oxidase functions in photobiomodulation by producing nitric oxide, a signaling molecule which can then function in both intra- and extracellular signaling pathways. We also propose that the effectiveness of photobiomodulation is under the control of tissue oxygen and nitrite levels.
Bell Inequality Violation with Two Remote Atomic Qubits (2008)

We observe violation of a Bell inequality between the quantum states of two remote Yb+ ions separated by a distance of about 1 m with the detection loophole closed. The heralded entanglement of two ions is established via interference and joint detection of two emitted photons, whose polarization is entangled with each ion. The entanglement of remote qubits is also characterized by full quantum state tomography.
Synthesis and anti-HIV activity of carbocyclic 2',3'-didehydro-2',3'-dideoxy 2,6-disubstituted purine nucleosides (1990)

(+-)-cis-[4-[(2,5-Diamino-6-chloropyrimidinyl)amino]-2- cyclopentenyl]carbinol (5a) was synthesized from 2-amino-4,6-dichloropyrimidine and cis-4-(hydroxymethyl)cyclopentenylamine (2a) by subsequent preparation of the 5-[(4-chlorophenyl)azo] derivative of the resulting pyrimidine (3a) and reduction of the azo moiety with zinc and acetic acid. The carbocyclic analogue of 2',3'-didehydro-2',3'-dideoxy 2-amino-6-chloropurine (6a) and the corresponding 8-azapurine (9a) were prepared from 5a. The carbocyclic 2',3'-didehydro-2',3'-dideoxy analogues of guanine (7a) and 2,6-diaminopurine (8a), and 8-azaguanine (10a) and 8-aza-2,6-diaminopurine (11a) were prepared from 6a and 9a, respectively. The corresponding 2',3'-saturated series of 2-amino-6-substituted-purine carbocyclic nucleosides was prepared following the same scheme starting with cis-4-(hydroxymethyl)cyclopentylamine (2b). Carbocyclic 2',3'-didehydro-2',3'-dideoxyguanosine (carbovir, 7a) emerged as a potent and selective anti-HIV agent. Its hydrolytic stability and its ability to inhibit the infectivity and replication of HIV in T-cells at concentrations of approximately 200-400-fold below toxic concentrations make carbovir an excellent candidate for development as a potential antiretroviral agent.
Down-regulation of NF-κB transcriptional activity in HIV-associated kidney disease by BRD4 inhibition. (2012)

VOLUME 287 (2012) PAGES 28840–28851 PAGE 28849: Due to an error during the production process, an incorrect version of Fig. 5C was originally published in the above article. The corrected figure appears below.
Development of a positive genetic selection system for inhibition of protein splicing using mycobacterial inteins in Escherichia coli DNA gyrase subunit A. (2002)

An intein-based positive genetic selection system was developed to study protein splicing and to provide a selection system with the potential for finding splicing inhibitors. Inteins can be novel antimicrobial targets when present in essential proteins since blocking splicing would kill the organism. For example, pathogenic mycobacteria encode inteins that interrupt DNA gyrase. The gyrase selection system exploits (1) splicing of inteins out of Gyrase A and (2) the dominant lethal effect of quinolone poisoning of DNA gyrase, which in turn blocks replication. The system was adapted for whole-cell high-throughput screening using green fluorescent protein as an automatable readout of viability. To demonstrate the efficacy of this system, mutations that blocked splicing of the Mycobacterium xenopi Gyrase A intein were isolated. Splicing was then assayed at a second temperature to identify inteins with a temperature-sensitive splicing phenotype. Mutations were mapped onto a structure-based sequence alignment, which led to the rational prediction of a temperature-sensitive splicing mutation. GyrA intein subdomain relationships also provided insight into intein evolution.
Helicons-the early years (1997)

Helicon waves are right-hand polarized (RHP) waves which propagate in radially confined magnetized plasmas for frequencies /spl omega//sub ci//spl Lt//spl omega//spl Lt//spl omega//sub ce/ where /spl omega//sub ci/ is the ion cyclotron frequency and /spl omega//sub ce/ is the electron cyclotron frequency. They are part of a much larger family of waves which can propagate down to zero frequency and constitute a very rich field for studying complex propagation characteristics and wave-particle interactions. This paper gives a historical perspective of the waves and their relationship to plasma source development up to the mid 1980s, presents a simple description of their propagation characteristics in free and bounded plasmas, and finishes with their first reported use in plasma processing experiments.
A planar filter-lens array for millimeter-wave applications (2004)

The novel concept of filter-lens array (FLA) is introduced in this paper. Measured results for a Ka-band design show that a typical FLA can meet system requirements for a wide range of applications. FLAs present a compact and simple means of focusing and filtering at millimeter-wave frequencies, and can replace the standard combinations of dielectric lenses and bandpass filters. They are expected to find application in power combining, medium-angle beam-steering, and millimeter-wave (mm-wave) imaging systems.
The Star-Nosed Mole Reveals Clues to the Molecular Basis of Mammalian Touch (2013)

Little is known about the molecular mechanisms underlying mammalian touch transduction. To identify novel candidate transducers, we examined the molecular and cellular basis of touch in one of the most sensitive tactile organs in the animal kingdom, the star of the star-nosed mole. Our findings demonstrate that the trigeminal ganglia innervating the star are enriched in tactile-sensitive neurons, resulting in a higher proportion of light touch fibers and lower proportion of nociceptors compared to the dorsal root ganglia innervating the rest of the body. We exploit this difference using transcriptome analysis of the star-nosed mole sensory ganglia to identify novel candidate mammalian touch and pain transducers. The most enriched candidates are also expressed in mouse somatosesensory ganglia, suggesting they may mediate transduction in diverse species and are not unique to moles. These findings highlight the utility of examining diverse and specialized species to address fundamental questions in mammalian biology.
Relationship between carbohydrate-induced hypertriglyceridemia and fatty acid synthesis in lean and obese subjects (2000)

We previously reported that a eucaloric, low fat, liquid formula diet enriched in simple carbohydrate markedly increased the synthesis of fatty acids in lean volunteers. To examine the diet sensitivity of obese subjects, 7 obese and 12 lean volunteers were given two eucaloric low fat solid food diets enriched in simple sugars for 2 weeks each in a random-order, cross-over design (10% fat, 75% carbohydrate vs. 30% fat, 55% carbohydrate, ratio of sugar to starch 60:40). The fatty acid compositions of both diets were matched to the composition of each subject's adipose tissue and fatty acid synthesis measured by the method of linoleate dilution in plasma VLDL triglyceride. In all subjects, the maximum % de novo synthesized fatty acids in VLDL triglyceride 3;-9 h after the last meal was higher on the 10% versus the 30% fat diet. There was no significant difference between the dietary effects on lean (43+/-13 vs. 12+/-13%) and obese (37+/-15 vs. 6+/-6%) subjects, despite 2-fold elevated levels of insulin and reduced glucagon levels in the obese. Similar results were obtained for de novo palmitate synthesis in VLDL triglyceride measured by mass isotopomer distribution analysis after infusion of [(13)C]acetate. On the 10% fat diet, plasma triglycerides (fasting and 24 h) were increased and correlated with fatty acid synthesis. Triglycerides were higher when fatty acid synthesis was constantly elevated rather than having diurnal variation.Thus, eucaloric, solid food diets which are very low in fat and high in simple sugars markedly stimulate fatty acid synthesis from carbohydrate, and plasma triglycerides increase in proportion to the amount of fatty acid synthesis. However, this dietary effect is not related to body mass index, insulin, or glucagon levels.
Formation and Characterization of Epitaxial TiO2 and BaTiO3/TiO2 Films on Si Substrate (1995)

Rutile-phase TiO 2 films were epitaxially grown on Si(100) substrates by oxidizing epitaxial TiN films grown by KrF pulsed excimer laser deposition. The TiO 2 film was (110)-oriented and composed of two domains perpendicular to each other in the plane. The electrical resistivity at 2.5 V and the dielectric constant at 1 MHz of the film were 1.1×10 10 Ω· cm and 49, respectively. This film could be used as a buffer layer for the growth of epitaxial BaTiO 3 film on Si. The BaTiO 3 (260 nm)/TiO 2 (230 nm) double-layered film showed a high dielectric constant ( ε r =91) and a very low leakage current of 5×10 -8 A/cm 2 at 10 V.
Importance of the Membrane-Proximal Extracellular Domains for Activation of the Signal Transducer Glycoprotein 130 (2000)

The transmembrane glycoprotein gp130 is the common signal transducing receptor subunit of the IL-6-type cytokines. The gp130 extracellular part is predicted to consist of six individual domains. Whereas the role of the three membrane-distal domains (D1-D3) in binding of IL-6 and IL-11 is well established, the function of the membrane-proximal domains (D4-D6) is unclear. Mapping of a neutralizing mAb to the membrane-proximal part of gp130 suggests a functional role of D4-D6 in receptor activation. Individual deletion of these three domains differentially interferes with ligand binding of the soluble and membrane-bound receptors. All deletion mutants do not signal in response to IL-6 and IL-11. The deletion mutants Delta4 and, to a lesser extent, Delta6 are still activated by agonistic monoclonal gp130 Abs, whereas the deletion mutant Delta5 does not respond. Because membrane-bound Delta5 binds IL-6/soluble IL-6R as does wild-type gp130, but does not transduce a signal in response to various stimuli, this domain plays a prominent role in coupling of ligand binding and signal transduction. Replacement of the fifth domain of gp130 by the corresponding domain of the homologous G-CSF receptor leads to constitutive activation of the chimera upon overexpression in COS-7 cells. In HepG2 cells this mutant responds to IL-6 comparable to wild-type gp130. Our findings suggest a functional role of the membrane-proximal domains of gp130 in receptor activation. Thus, within the hematopoietic receptor family the mechanism of receptor activation critically depends on the architecture of the receptor ectodomain.
Clinical Impact of Molecular Diagnostics in Endocrinology (2002)

Genetic defects in genes encoding hormones, hormone receptors or polypeptides of the signaling pathways usually cause complex disease manifestations characterized by the involvement of several tissues and variable expression. Genetic aberrations, like chromosome aneuploidy, gene translocations or mutations in key regulatory proteins (even if not directly affecting genes of the endocrine system) often lead to clinical symptoms, including central endocrine functions like sexual differentiation or metabolic disturbances, like diabetes mellitus. But also minor genetic alterations like point mutations can affect the function of gene products to cause endocrine diseases. If the underlying molecular defects of endocrinopathies are known, direct molecular diagnosis can be performed. This is particularly useful if it helps to solve difficult differential diagnosis problems or if there exist effective preventive therapeutic options. The present paper presents examples for endocrine diseases in which molecular testing significantly increases the specificity and sensitivity of diagnostics and demonstrates the benefits for the patients and the healthcare system. In multiple endocrine neoplasia type 2, an unambiguous identification of gene carriers in affected families can be achieved by genetic testing. As a preventive measure to avoid medullary thyroid carcinoma, prophylactic thyroidectomy is recommended for individuals carrying the disease causing mutation. In adrenogenital syndrome, sequence analysis of the steroid 21-hydroxylase gene has become an important tool to confirm or exclude suspected late-onset forms of the disease, where hormone measurements are not informative. The major benefit, however, lies in identifying heterozygous carriers and providing a reliable prenatal test for couples carrying a defect in the 21-hydroxylase gene. Today, prenatal treatment with dexamethasone, which prevents the virilization in female fetuses, should always be based on results from molecular diagnosis performed from chorionic villus samples.
Selective cooling of biological tissues: application for thermally mediated therapeutic procedures (1995)

The ability to control the degree and spatial distribution of cooling in biological tissues during a thermally mediated therapeutic procedure would be useful for several biomedical applications of lasers. We present a theory based on the solution of the heat conduction equation that demonstrates the feasibility of selectively cooling biological tissues. Model predictions are compared with infrared thermal measurements of in vivo human skin in response to cooling by a cryogen spurt. The presence of a boundary layer, undergoing a liquid-vapour phase transition, is associated with a relatively large thermal convection coefficient (approximately 40 kW m-2 K-1), which gives rise to the observed surface temperature reductions (30-40 degrees C). The degree and the spatial-temporal distribution of cooling are shown to be directly related to the cryogen spurt duration.
3-Aryl-2-methyl serines. II. Inversions at carbon 3 (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT3-Aryl-2-methyl serines. II. Inversions at carbon 3Seemon H. Pines, Sandor Karady, Matthew A. Kozlowski, and Meyer SletzingerCite this: J. Org. Chem. 1968, 33, 5, 1762–1767Publication Date (Print):May 1, 1968Publication History Published online1 May 2002Published inissue 1 May 1968https://pubs.acs.org/doi/10.1021/jo01269a013https://doi.org/10.1021/jo01269a013research-articleACS PublicationsRequest reuse permissionsArticle Views70Altmetric-Citations10LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Nanoparticle Pseudocrosslinked Micellar Fluids: Optimal Solution for Fluid-Loss Control With Internal Breaking (2010)

Abstract Micellar fluids with viscoelastic behavior, or viscoelastic surfactant fluids, are used in the oil industry as completion and stimulation fluids. The viscoelastic (i.e. viscous and elastic) behavior of these fluids is based on the overlap and entanglement of very long worm-like-micelles. High fluid leak-off has, however, limited their application for hydraulic fracturing and frac-packing applications. Recent developments have found that micellar fluids can have wall-building leak-off control similar to crosslinked-polymer fluids (CPF) by the addition of a small amount of inorganic crystals that are less than 100 nanometers in size (i.e. nanoparticle). This paper will investigate the mechanism of fluid loss control for the particle-micellar fluid system. The tiny particles have high surface force, including van der Waals and electrostatic forces. The nanoparticle surface forces pseudo-crosslink the elongated micelles, which is similar to crosslinking polymers. The unique pseudo-crosslinking of surfactant micelles and particles has demonstrated improved viscosity, the formation of a filter cake, and enhanced thermal stability. Laboratory tests show the development of a filter cake significantly reduces the rate of fluid loss and demonstrates wall-building rather than viscosity-dependant leak-off control. Two models of static fluid loss control for particle-polymer fluid system will be reviewed. Fluid leakoff characteristics will be compared between the particle-micellar fluid system and particle-polymer fluid system. Uniqueness of this system is that the fluid loss control was achieved without compromising the internal breaking efficacy. Ordinarily additives 'plasticize' the micellar or colloidal aggregates. However, through our patented processes, we were able to successfully place the internal breakers inside the elongated micelles so as to not interfere with particles' pseudo-crosslinking. When internal breakers are activated by temperature, the elongated micelle structure collapses thereby significantly reducing the fluid viscosity and thus breaking down the filter cake into tiny particles. This results in clean breaking gel with reduced damage to formation permeability and fracture conductivity.
Cellular Mechanisms of Immunologic Tolerance (1983)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More