gebhart/patrepeval huggingface dataset:
Loss of CABLES1, a Cyclin-dependent Kinase-interacting Protein that Inhibits Cell Cycle Progression, Results in Germline Expansion at the Expense of Oocyte Quality in Adult Female Mice (2007)

Recent studies have shown that cell cycle inhibitors encoded by the Ink4a gene locus constrain the self-renewing activity of adult stem cells of the hematopoietic and nervous systems. Here we report that knockout (KO) of the Cables1 [cyclin-dependent kinase (CDK)-5 and ABL enzyme substrate 1] cell cycle-regulatory gene in mice has minimal to no effect on hematopoietic stem cell (HSC) dynamics. However, female Cables1-null mice exhibit a significant expansion of germ cell (oocyte) numbers throughout adulthood. This is accompanied by a dramatic elevation in the number of atretic immature oocytes within the ovaries and an increase in the incidence of degenerating oocytes retrieved following superovulation of CABLES1-deficient females. These outcomes are not observed in mice lacking p16INK4a alone or both p16INK4a and p19ARF. These data support recent reports that adult female mice can generate new oocytes and follicles but the enhancement of postnatal oogenesis by Cables1 KO appears offset by a reduction in oocyte quality, as reflected by increased elimination of these additional germ cells via apoptosis. This work also reveals cell lineage specificity with respect to the role that specific CDK-interacting proteins play in restraining the activity of adult germline versus somatic stem cells.
Novel Mycophenolic Adenine Bis(phosphonate) Analogues As Potential Differentiation Agents against Human Leukemia (2002)

Novel mycophenolic adenine dinucleotide (MAD) analogues have been prepared as potential inhibitors of inosine monophosphate dehydrogenase (IMPDH). MAD analogues resemble nicotinamide adenine dinucleotide binding at the cofactor binding domain of IMPDH; however, they cannot participate in hydride transfer and therefore inhibit the enzyme. The methylenebis(phosphonate) analogues C2-MAD and C4-MAD were obtained by coupling 2',3'-O-isopropylideneadenosine 5'-methylenebis(phosphonate) (22) with mycophenolic alcohols 20 and 21 in the presence of diisopropylcarbodiimide followed by deprotection. C2-MAD was also prepared by coupling of mycophenolic methylenebis(phosphonate) derivative 30 with 2',3'-O-isopropylideneadenosine. Compound 30 was conveniently synthesized by the treatment of benzyl-protected mycophenolic alcohol 27 with a commercially available methylenebis(phosphonic dichloride) under Yoshikawa's reaction conditions. C2-MAD and C4-MAD were found to inhibit the growth of K562 cells (IC(50) = 0.7 microM and IC(50) = 0.1 microM, respectively) as potently as mycophenolic acid (IC(50) = 0.3 microM). In addition, C2-MAD and C4-MAD triggered vigorous differentiation of K562 cells an order of magnitude more potently than tiazofurin, and MAD analogues were resistant to glucuronidation in vitro. These results show that C2-MAD and C4-MAD may be of therapeutic interest in the treatment of human leukemias.
Sex‐Sorting Mammalian Sperm: Concept to Application in Animals (2001)

Sperm sexing can be used to produce sexed offspring with 85%-95% accuracy (Amann, 1999; Johnson and Seidel, 1999; Seidel et al 1999a). On September 1, 2000, the sale of sexed bovine sperm commented in the United Kingdom. It will be interesting to see to what degree sexed sperm penetrate the semen market. This verified sexed product sets the stage for commercialization around the world in major animal producing countries. This commercialization of sexed sperm occurred nearly 20 years after technology for accurately determining the proportion of X and Y sperm in semen was first developed at Lawrence Livermore National Laboratory. It came about due to advances in both the hardware and the software componenets of computer science, biophysic, cell biology and applied reproductive physiology plus efforts of innovative scientist. Many individuals have contributed in making semen sexing in animals a commercial reality since the research team of Bart Gledhill, Dan Pinkel, Duane Garner, Susan Lake, and Larry Johnson began following up on the first flow cytometric studies on human sperm by Friedrich Otto, Wolfgang Göhde, and Marvin Meistrich. There was also major input from personnel at USDA Beltsville Agricultural Research Center as well as scientists at Cambridge University, Atlantic Breeders Cooperative, Colorado State University and XY Inc. These include Chuck Allen, Rupert Amann, David Cran, Patrick Doyle, Mike Evans, Lisa Herickhoff, Mervyn Jacobson, Kehuan Lu, Chris Polge, Wim Rens, John Schenk, George Seidel, Glenn Welch, and many others.
Perspective on Potential Clinical Applications of Recombinant Human Interleukin‐7 (2009)

Interleukin-7 has critical and nonredundant roles in T cell development, hematopoiesis, and postdevelopmental immune functions as a prototypic homeostatic cytokine. Based on a large body of preclinical evidence, it may have multiple therapeutic applications in immunodeficiency states, either physiologic (immuno-senescence), pathologic (HIV) or iatrogenic (postchemotherapy and posthematopoietic stem cell transplant) and may have roles in immune reconstitution or enhancement of immunotherapy. Early clinical development trials in humans show that, within a short time, rhIL-7 administration results in a marked preferential expansion of both naive and memory CD4 and CD8 T cell pools with a tendency toward enhanced CD8 expansion. As a result, lymphopenic or normal older hosts develop an expanded circulating T cell pool with a profile that resembles that seen earlier in life with increased T cell repertoire diversity. These results, along with a favorable toxicity profile, open a wide perspective of potential future clinical applications.
Subnanosecond pulses from a KrF laser pumped SF&lt;inf&gt;6&lt;/inf&gt;Brillouin amplifier (1985)

Experimental measurements are presented of pulse compression in a backward Brillouin amplifier using SF <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</inf> gas pumped by 0.9 GHz linewidth KrF laser radiation. Average pulse durations of 390 ps and energy extraction effieiencies of 40 percent from 24 ns pump pulses have been demonstrated at pressures of 15.3 and 12.6 atm, respectively.
Notch Signals Inhibit the Development of Erythroid/Megakaryocytic Cells by Suppressing GATA-1 Activity through the Induction of HES1 (2004)

The effects of Notch signals on the erythroid/megakaryocytic differentiation of hematopoietic cells were examined. Activation of Notch signals by the intracellular Notch1 or an estradiol-inducible form of Notch1/ER suppressed the expression of the erythroid marker glycophorin A in an erythroid/megakaryocytic cell line K562. Although Mock-transfected K562 cells underwent megakaryocytic differentiation in response to 12-O-tetradecanoylphorbol-13-acetate (TPA), estradiol-activated Notch1/ER induced apoptosis during TPA treatment in the transfectant, which was accompanied by the reduced expression of an antiapoptotic molecule Bcl-XL. Even when apoptosis was prevented by the overexpression of Bcl-XL, activated Notch signals still inhibited TPA-induced megakaryocytic differentiation. As for this mechanism, Notch1/recombination signal binding protein J-kappa-induced HES1 but not HES5 was found to inhibit the function of an erythroid/megakaryocytic lineage-specific transcription factor GATA-1. Although HES1 did not affect the DNA binding activity of GATA-1 in gel shift and chromatin immunoprecipitation assays, it directly bound to GATA-1 and dissociated a critical transcriptional cofactor, p300, from GATA-1. Furthermore, overexpressed HES1 inhibited the development of erythroid and megakaryocytic cells in colony assays. Also, the Notch ligand Jagged1 expressed on NIH3T3 cells suppressed the development of erythroid and megakaryocytic cells from cocultured Lin-Sca-1+ hematopoietic stem/progenitor cells. These results suggest that Notch1 inhibits the development of erythroid/megakaryocytic cells by suppressing GATA-1 activity through HES1.
Structural and stereochemical studies of potent inhibitors of glucosylceramide synthase and tumor cell growth. (1995)

Analogs and homologs of PDMP were synthesized, based on its structure (D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol). This compound had previously been found to block the synthesis of GlcCer (glucosylceramide). Increasing the acyl chain length from 10 to 16 carbon atoms greatly enhanced the efficacy of the enzyme inhibitor, as did the use of a less polar cyclic amine, especially a pyrrolidine instead of a morpholine ring. Replacement of the phenyl ring by a chain corresponding to sphingosine also yielded a strongly inhibitory material. By using a chiral synthetic route, we showed that the isomers active against GlcCer synthase had the R,R-(D-threo)-configuration. However, strong inhibition of the growth of human cancer cells in plastico was produced by both the threo and erythro racemic compounds, showing involvement of an additional factor (beyond simple depletion of cell glycosphingolipids by blockage of GlcCer synthesis). The growth arresting effects could be correlated with increases in cellular ceramide and diglyceride levels. The aliphatic pyrrolidino compound was strongly inhibitory toward the glucosyltransferase and produced almost complete depletion of glycolipids, but did not inhibit growth or cause an accumulation of ceramide. Attempts were made to see whether the differences in growth effects could be attributed to the influence of the inhibitors on related enzymes (ceramide and sphingomyelin synthase and ceramidase and sphingomyelinase). While some stimulation of enzyme activity was noted, particularly at high inhibitor concentrations (50 microM), these findings did not explain the differing effects of the different inhibitors. The best inhibitors of GlcCer synthase compared favorably in efficacy with some cancer chemotherapeutic drugs in current use when tested with a battery of human cancer cells.
Continuum Solvent Studies of the Stability of RNA Hairpin Loops and Helices (1998)

We apply continuum solvent models to investigate the relative stability of various conformational forms for two RNA sequences, GGAC(UUCG)GUCC and GGUG(UGAA)CACC. In the first part, we compare alternate hairpin conformations to explore the reliability of these models to discriminate between different local conformations. A second part looks at the hairpin-duplex conversion for the UUCG sequence, identifying major contributors to the thermodynamics of a much large scale transition. Structures were taken as snapshots from multi-nanosecond molecular dynamics simulations computed in a consistent fashion using explicit solvent and with long-range electrostatics accounted for using the Particle-Mesh Ewald procedure. The electrostatic contribution to solvation energies were computed using both a finite-difference Poisson-Boltzmann (PB) model and a pairwise Generalized Born model; non-electrostatic contributions were estimated with a surface-area dependent term. To these solvation free energies were added the mean solute internal energies (determined from a molecular mechanics potential) and estimates of the solute entropy (from a harmonic analysis). Consistent with experiment and with earlier solvated molecular dynamics simulations, the UUCG hairpin was found to prefer conformers close to a recent NMR structure determination in preference to those from an earlier NMR study. Similarly, results for the UGAA hairpin favored an NMR-derived structure over that to be expected for a generic GNRA hairpin loop. Experimental free energies are not known for the hairpin/duplex conversion, but must be close to zero since hairpins are seen in solution and duplexes in crystals; out calculations find a value near zero and illustrate the expected interplay of solvation, salt effects and entropy in affecting this equilibrium.
Circuit design for multi-body interactions in superconducting quantum annealing systems with applications to a scalable architecture (2017)

Quantum annealing provides a way of solving optimization problems by encoding them as Ising spin models which are implemented using physical qubits. The solution of the optimization problem then corresponds to the ground state of the system. Quantum tunneling is harnessed to enable the system to move to the ground state in a potentially high non-convex energy landscape. A major difficulty in encoding optimization problems in physical quantum annealing devices is the fact that many real world optimization problems require interactions of higher connectivity, as well as multi-body terms beyond the limitations of the physical hardware. In this work we address the question of how to implement multi-body interactions using hardware which natively only provides two-body interactions. The main result is an efficient circuit design of such multi-body terms using superconducting flux qubits in which effective N-body interactions are implemented using N ancilla qubits and only two inductive couplers. It is then shown how this circuit can be used as the unit cell of a scalable architecture by applying it to a recently proposed embedding technique for constructing an architecture of logical qubits with arbitrary connectivity using physical qubits which have nearest-neighbor four-body interactions. It is further shown that this design is robust to non-linear effects in the coupling loops, as well as mismatches in some of the circuit parameters.
Direct covalent mercuration of nucleotides and polynucleotides (1975)

Nucleotides of cytosine and uracil are readily mercurated by heating at 37-50 degrees in buffered aqueous solutions (pH 5.0-8.0) containing mercuric acetate. Proton magnetic resonance, elemental, electrophoretic, and chromatographic analyses have shown the products to be 5-mercuricytosine and 5-mercuriuracil derivatives, where the mercury atom is covalently bonded. Polynucleotides can be mercurated under similar conditions. Cytosine and uracil bases are modified in RNA while only cytosine residues in DNA are substituted. There is little, if any, reaction with adenine, thymine, or guanine bases. The rate of polymer mercuration is, unlike that of mononucleotides, markedly influenced by the ionic strength of the reaction mixture: the lower the ionic strength the faster the reaction rate. Pyrimidine residues in single- and double-stranded polymers react at essentially the same rate. Although most polynucleotides can be extensively mercurated at pH 7.0 in sodium or Trisacetate buffers, tRNA undergoes only limited substitution in Tris buffers. The mild reaction conditions give minimal single-strand breakage and, unlike direct iodination procedures, do not produce pyrimidine hydrates. Mercurated polynucleotides can be exploited in a variety of ways, particularly by crystallographic and electron microscopic techniques, as tools for studying polynucleotide structure.
NOBEL LECTURE: The Molecular Biology of Memory Storage: A Dialog Between Genes and Synapses (2001)

The biology of learning, and short-term and long-term memory, as revealed by Aplysia and other organisms, is reviewed.
A bio-adhesive formulation for the delivery of anti-fungal agents to the oesophagus (2005)

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Spectrum resource allocation for wireless packet access with application to advanced cellular Internet service (1998)

The advanced cellular Internet service (ACIS) is targeted for applications such as Web browsing with a peak downlink transmission rate on the order of 1-2 Mbits/s using a wide-area cellular infrastructure. In order to provide bandwidth on demand using scarce radio spectrum, the medium-access control (MAC) protocol must: 1) handle dynamic and diverse traffic with high throughput, and 2) efficiently reuse limited spectrum with high peak rates and good quality. Most of the existing approaches do not sufficiently address the second aspect. This paper proposes a dynamic packet assignment (DPA) scheme which, without coordinating base stations, allocates spectrum on demand with no collisions and low interference to provide high downlink throughput. Interference sensing and priority ordering are employed to reduce interference probability. A staggered frame assignment schedule is also proposed to prevent adjacent base stations from allocating the same channel to multiple mobiles at the same time. Simulation results based on a packet data traffic model derived from wide-area network traffic statistics, which exhibit a "self-similar" property when aggregating multiple sources, confirm that this method is able to reuse spectrum efficiently in a large cellular system having many users with short active periods. Distributed iterative power control further enhances spectrum efficiency such that the same channel can be simultaneously reused in every base station.
Characterization of the interaction between the A2 subunit and A1/A3-C1-C2 dimer in human factor VIIIa. (1992)

Factor VIIIa is a heterotrimer of the factor VIII heavy chain-derived A1 and A2 subunits plus the factor VIII light chain-derived A3-C1-C2 subunit. While the A1 and A3-C1-C2 subunits can be isolated as a stable dimer, the A2 subunit is weakly associated with the dimer. In the human protein, the association of A2 with dimer is reversible and governed by a pH-dependent dissociation constant. Using the specific activity of factor VIIIa as an indicator of trimer concentration, the Kd (pH 6.0) was determined to be 28 nM whereas at the more physiologic pH (pH 7.4) this value was approximately 260 nM. Results from pH shift experiments confirmed the reversible binding of A2 to dimer as did the capacity for high levels of exogenous A2 subunit to inhibit the spontaneous decay of factor VIIIa activity. A2 subunit associated with the A1 subunit in the A1/A3-C1-C2 dimer based upon the capacity for free A1 subunit to inhibit the reconstitution of factor VIIIa from A2 subunit and dimer. These results indicate that the primary mechanism for the spontaneous decay of human factor VIIIa is the reversible dissociation of A2 subunit from the A1 subunit of the A1/A3-C1-C2 dimer.
An Investigation of Desferrithiocin Metabolism (1994)

The hydrolyses of (S)-desferrithiocin (DFT, 1), (R)-desmethyl-DFT (2), and (R)-desazadesmethyl-DFT (3) were studied at pH 2.5 and 7.2 in order to access the stability of the thiazolines at the pH of the stomach and the serum. At 37 degrees C and pH 2.5, DFT (1) (t1/2 = 18.6 h), desmethyl-DFT (2) (t1/2 = 8.74 h), and desazadesmethyl-DFT (3) (t1/2 = 31.7 h) were shown to open principally to the thiol amides with trace amounts of the corresponding thioesters, < or = 2%. The thiazolines were resistant to hydrolysis at pH 7.2. Iron(III) stabilized significantly the thiazolines in the complexes 16a/b of 3 in regard to hydrolysis at pH 2.5 (t1/2 > 20 days). The iron(III) complexes 16a/b were shown to be stable at pH 7.2. While the thiol amides 13 and 14 of 1 and 2 were isolated from the hydrolysis of the parent desferrithiocins, the thioester 4 and the thiol amide 5 of 3 were synthesized and their stability in aqueous solution, iron-clearance properties, and toxicity were evaluated. Thioester 4 was shown to rearrange to thiol amide 5 at pH 2.5 and 37 degrees C with a half-life of 4.18 h and instantaneously at pH 7.2. Thiol amide 5 is in equilibrium with 4 (5/4 = 49:1) at pH 2.5 and was shown to be stable at pH 7.2. Thioester 4 and thiol amide 5 demonstrated neither iron-clearance activity in iron-overloaded rats nor toxic side effects in mice. Hydrolysis products of the drug, which might be generated in the stomach, seem unlikely to be the source of the drug's toxicity or iron-clearing properties.
Purification and properties of a translation inhibitor from wheat germ (1979)

A translation inhibitor from wheat germ has been purified more than 400-fold to apparent homogeneity. The inhibitor is a basic protein with a molecular weight of 30 000. This protein effectively blocks protein synthesis in animal cell-free extracts but does not affect protein synthesis in intact cells. Inhibition occurs at a ribosome to inhibitor molar ratio of 100:1, indicating an enzymic mechanism of action. The wheat germ protein inhibits the translation of endogenous mRNA, exogenous mRNA, and poly(uridylic acid) at a step in polypeptide chain elongation and without breakdown of the polysomes. Neither the aminoacylation reaction nor mRNA degradation is affected by the inhibitor. An interesting feature of the inhibition reaction is that it requires, in addition to the wheat germ inhibitor, both ATP and tRNA. The function of these two compounds in the inhibition is presently unknown since neither the hydrolysis of the beta,gamma-pyrophosphate bond of ATP nor a modification of the tRNA can be demonstrated during the reaction.
Characterization of suppressive oligodeoxynucleotides that inhibit Toll‐like receptor‐9‐mediated activation of innate immunity (2007)

Summary Synthetic oligodeoxynucleotides containing unmethylated CpG sequences (CpG‐ODNs) stimulate Toll‐like receptor‐9 (TLR‐9), thereby activating innate immunity. Stimulatory CpG‐ODNs have been shown to be valuable in modifying immune responses in allergy, infection and cancer. Recently, it has been reported that the stimulation of TLR‐9 by endogenous DNA might contribute to the pathogenesis of autoimmune diseases. We here report the identification of a suppressive, guanosine‐rich ODN (G‐ODN) that inhibited the activation of TLR‐9 by stimulatory CpG‐ODNs. The G‐ODN was suppressive in murine macrophages and dendritic cells as well as in human plasmacytoid dendritic cells in vitro . G‐ODN blocked the secretion of tumour necrosis factor‐α (TNF‐α) and interleukin‐12p40 and interfered with the up‐regulation of major histocompatibility complex (MHC) class II and costimulatory molecules. G‐ODN was inhibitory even at a molar ratio of 1 : 10 (G‐ODN:CpG‐ODN) and when administered up to 7 hr after stimulation with CpG. G‐ODN specifically inhibited TLR‐9 but not other TLRs. Inhibition was dependent on a string of five guanosines. G‐ODN was also inhibitory in an in vivo model of CpG/galactosamin (GalN) lethal shock. G‐ODN interfered with upstream TLR‐9 signalling. However, by extensive analysis we can exclude that G‐ODN acts at the stage of cellular uptake. G‐ODN therefore represents a class of suppressive ODNs that could be of therapeutic use in situations with pathologic TLR‐9 activation, as has been proposed for certain autoimmune diseases.
BRISK: Binary Robust invariant scalable keypoints (2011)

Effective and efficient generation of keypoints from an image is a well-studied problem in the literature and forms the basis of numerous Computer Vision applications. Established leaders in the field are the SIFT and SURF algorithms which exhibit great performance under a variety of image transformations, with SURF in particular considered as the most computationally efficient amongst the high-performance methods to date. In this paper we propose BRISK <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sup> , a novel method for keypoint detection, description and matching. A comprehensive evaluation on benchmark datasets reveals BRISK's adaptive, high quality performance as in state-of-the-art algorithms, albeit at a dramatically lower computational cost (an order of magnitude faster than SURF in cases). The key to speed lies in the application of a novel scale-space FAST-based detector in combination with the assembly of a bit-string descriptor from intensity comparisons retrieved by dedicated sampling of each keypoint neighborhood.