gebhart/patrepeval huggingface dataset:
High-Precision Timing of Millisecond Pulsars and Precision Astrometry (1995)

We present the technique of long-term, high-precision timing of millisecond pulsars as applied to precision astrometry. We provide a tutorial on pulsars and pulsar timing, as well as up-to-date results of long-term timing observations of two millisecond pulsars, PSRs B1855+09 and B1937+21. We consider the feasibility of tying the extragalactic and optical reference frames to that defined by solar system objects, and we conclude that precision astrometry from millisecond pulsar timing has a bright future.
MOLECULAR ORGANIZATION AND FUNCTION OF THE COMPLEMENT SYSTEM (1988)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Metabolic Engineering of a Novel Propionate-Independent Pathway for the Production of Poly(3-Hydroxybutyrate- co -3-Hydroxyvalerate) in Recombinant Salmonella enterica Serovar Typhimurium (2002)

A pathway was metabolically engineered to produce poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), a biodegradable thermoplastic with proven commercial applications, from a single, unrelated carbon source. An expression system was developed in which a prpC strain of Salmonella enterica serovar Typhimurium, with a mutation in the ability to metabolize propionyl coenzyme A (propionyl-CoA), served as the host for a plasmid harboring the Acinetobacter polyhydroxyalkanoate synthesis operon (phaBCA) and a second plasmid with the Escherichia coli sbm and ygfG genes under an independent promoter. The sbm and ygfG genes encode a novel (2R)-methylmalonyl-CoA mutase and a (2R)-methylmalonyl-CoA decarboxylase, respectively, which convert succinyl-CoA, derived from the tricarboxylic acid cycle, to propionyl-CoA, an essential precursor of 3-hydroxyvalerate (HV). The S. enterica system accumulated PHBV with significant HV incorporation when the organism was grown aerobically with glycerol as the sole carbon source. It was possible to vary the average HV fraction in the copolymer by adjusting the arabinose or cyanocobalamin (precursor of coenzyme B12) concentration in the medium.
Streptococcus pneumoniae endohexosaminidase D; feasibility of using N-glycan oxazoline donors for synthetic glycosylation of a GlcNAc-asparagine acceptor (2010)

Endohexosaminidase D, a family 85 glycoside hydrolase from S. pneumoniae and the first endohexosaminidase to be discovered, is found to be capable of catalysing the glycosylation of a glycosyl amino acid bearing a GlcNAc residue using a variety of N-glycan oxazoline donors. Although enzyme-catalysed oxazoline hydrolysis is a significant competing reaction that is not countered by the addition of organic co-solvents or variation of reaction pH, a high yielding synthetic process can be achieved by the sequential addition of multiple equivalents of oxazoline donor, demonstrating the synthetic potential of this enzyme as a biocatalyst for the synthesis of defined glycoconjugates. Notably Endo-D does not appear to hydrolyse the resulting products under the conditions used. The synthetic activity displayed by Endo D implies that other, as yet untested, family GH85 enzymes may display similar synthetic potential. Furthermore since Endo D is capable of cleaving N-glycans attached to monoclonal antibodies (mAbs), and also of cleaving glycans that are core-fucosylated, the development of Endo D as a useful biocatalyst for the synthesis of important defined homogeneous complex glycoconjugates may have significant future potential, provided that the limitation of direct oxazoline hydrolysis can be surmounted.
The Enzyme and the cDNA Sequence of a Thermolabile and Double-Strand Specific DNase from Northern Shrimps (Pandalus borealis) (2010)

The shrimp nuclease contains enzyme activity that may be controlled by temperature or buffer compositions. The double-stranded DNA specificity, as well as the thermolabile feature, strengthens its potential for in vitro applications.
Lachrymal Determinations: Methods and Updates on Biopharmaceutical and Clinical Applications (2004)

This article displays different procedures used to collect lachrymal fluid and describes some of its applications. Sampling tears represents the main difficulty to produce precise and reproducible results. The direct sampling procedure consists in collecting tears with capillary tubes and has the drawback of demanding previous stimulation that induces major dilution. The indirect method does not require preliminary stimulation but has been held responsible for altering epithelium and promoting leakage from plasma. Schirmer strips and sponges are classically required. Applications are numerous in biopharmaceutical and clinical fields. The determination of endogenous components has great potentiality as a diagnostic tool, but the use of tear as a substitute of plasma does not present clinical relevance. Levels of drugs like immunosuppressive or antibiotic agents are determined in tears to verify that pharmacological concentrations are reached and frequency of administration is deduced from kinetic fitting.
Vitamin D and multiple sclerosis (2008)

Vitamin D is a principal regulator of calcium homeostasis. However, recent evidence has indicated that vitamin D can have numerous other physiological functions including inhibition of proliferation of a number of malignant cells including breast and prostate cancer cells and protection against certain immune mediated disorders including multiple sclerosis (MS). The geographic incidence of MS indicates an increase in MS with a decrease in sunlight exposure. Since vitamin D is produced in the skin by solar or UV irradiation and high serum levels of 25-hydroxyvitamin D (25(OH)D) have been reported to correlate with a reduced risk of MS, a protective role of vitamin D is suggested. Mechanisms whereby the active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) may act to mediate this protective effect are reviewed. Due to its immunosuppressive actions, it has been suggested that 1,25(OH)(2)D(3) may prevent the induction of MS.
Cancer, the Mind, and the Problem of Self-blame (2006)

“Why me?” This question of causal attribution is pervasive among cancer patients—so pervasive, in fact, that it is the basis for the name of the largest national breast cancer patient support network. As work in the field of psychooncology has advanced, the emotional aspects of cancer have been publicized and have entered the minds of lay audiences everywhere. A 2001 survey by Stewart and colleagues of Canadian breast cancer survivors, recurrence free for an average of nearly 9 years, found that 42% of them believed that stress caused breast cancer—a belief that is without scientific foundation—while only 27% felt that genetics and 15% felt that diet were involved
The Role of Homophilic Binding in Anti-tumor Antibody R24 Recognition of Molecular Surfaces (1999)

The murine antibody R24 and mouse-human Fv-IgG1(kappa) chimeric antibody chR24 are specific for the cell-surface tumor antigen disialoganglioside GD3. X-ray diffraction and surface plasmon resonance experiments have been employed to study the mechanism of "homophilic binding," in which molecules of R24 recognize and bind to other molecules of R24 though their heavy chain variable domains. R24 exhibits strong binding to liposomes containing disialoganglioside GD3; however, the kinetics are unusual in that saturation of binding is not observed. The binding of chR24 to GD3-bearing liposomes is significantly weaker, suggesting that cooperative interactions involving antibody constant regions contribute to R24 binding of membrane-bound GD3. The crystal structures of the Fabs from R24 and chR24 reveal the mechanism for homophilic binding and confirm that the homophilic and antigen-binding idiotopes are distinct. The homophilic binding idiotope is formed largely by an anti-parallel beta-sheet dimerization between the H2 complementarity determining region (CDR) loops of two Fabs, while the antigen-binding idiotope is a pocket formed by the three CDR loops on the heavy chain. The formation of homophilic dimers requires the presence of a canonical conformation for the H2 CDR in conjunction with participation of side chains. The relative positions of the homophilic and antigen-binding sites allows for a lattice of GD3-specific antibodies to be constructed, which is stabilized by the presence of the cell membrane. This model provides for the selective recognition by R24 of cells that overexpress GD3 on the cell surface.
The Bruton's tyrosine kinase inhibitor ibrutinib exerts immunomodulatory effects through regulation of tumor-infiltrating macrophages (2017)

The Bruton's tyrosine kinase (Btk) inhibitor ibrutinib has demonstrated promising efficacy in a variety of hematologic malignancies. However, the precise mechanism of action of the drug remains to be fully elucidated. Tumor-infiltrating macrophages presented in the tumor microenvironment have been shown to promote development and progression of B-cell lymphomas through crosstalk mediated by secreted cytokines and chemokines. Because Btk has been implicated in Toll-like receptor (TLR) signaling pathways that regulate macrophage activation and production of proinflammatory cytokines, we investigated the immunomodulatory effects of Btk inhibitor on macrophages. Our results demonstrate that Btk inhibition efficiently suppresses production of CXCL12, CXCL13, CCL19, and VEGF by macrophages. Furthermore, attenuated secretion of homeostatic chemokines from Btk inhibitor-treated macrophages significantly compromise adhesion, invasion, and migration of lymphoid malignant cells and even those not driven by Btk expression. The supernatants from Btk inhibitor-treated macrophages also impair the ability of endothelial cells to undergo angiogenic tube formation. Mechanistic analysis revealed that Btk inhibitors treatment downregulates secretion of homeostatic chemokines and cytokines through inactivation of Btk signaling and the downstream transcription factors, NF-κB, STAT3, and AP-1. Taken together, these results suggest that the encouraging therapeutic efficacy of Btk inhibitor may be due to both direct cytotoxic effects on malignant B cells and immunomodulatory effects on macrophages present in the tumor microenvironment. This novel mechanism of action suggests that, in addition to B-cell lymphomas, Btk inhibitor may also have therapeutic value in lymphatic malignancies and solid tumors lacking Btk expression.
TP53 in hematological cancer: Low incidence of mutations with significant clinical relevance (2003)

Inactivation of the wild-type p53 gene (TP53) by various genetic alterations is a major event in human tumorigenesis. More than 60% of human primary tumors exhibit a mutation in the p53 gene. Hematological malignancies present a rather low incidence of genetic alterations in this gene (10-20%). Nevertheless, epidemiological studies of the hematological malignancies indicate that the prognosis of patients with a mutation in the p53 gene is worse than those expressing the wild-type p53 protein. Correlations between drug resistance, altered apoptosis, and mutations in the p53 gene are found in hematological malignancies and leukemias. These issues, as well as the possibility of exploiting p53 and its various functions for new therapeutic strategies, are discussed in the present review.
Positional reproducibility of protein spots in two‐dimensional polyacrylamide gel electrophoresis using immobilised pH gradient isoelectric focusing in the first dimension: An interlaboratory comparison (1994)

An intra- and interlaboratory comparison of positional reproducibility of protein spots in two-dimensional electrophoresis using immobilised pH gradients (IPG) in the first dimension (IPG-DALT) was made. Aliquots of two different samples, human cardiac and barley leaf proteins, were separated in two different laboratories (London and Munich), using 180 mm long IPG gel strips, pH 4-8, for the first dimension and homogeneous SDS-PAGE gels (12% T) for the second dimension. Subsets of 340 (cardiac) and 200 (barley) well-resolved spots distributed across the 2-D gel patterns were selected for computer analysis (PDQUEST) of positional reproducibility. The IPG-dimension was highly reproducible in each laboratory, with a mean standard deviation of about 1 mm for both types of sample. Interlaboratory comparisons revealed identical results for barley with a mean standard deviation along the x-axis of about 1 mm, whereas the cardiac matchset showed slightly more variability (mean standard deviation approximately 1.5 mm). Nevertheless, IPG-DALT provides significantly improved reproducibility of spot positions compared to conventional isoelectric focusing with synthetic carrier ampholytes.
Multiple access with time-hopping impulse modulation (2002)

A time-hopping modulation format employing impulse signal technology has several features which may make it attractive for multiple-access communications. These features are outlined, an estimate of the multiple-access capability of a communication system employing this format under ideal propagation conditions is presented, and emerging design issues are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Bioproduction of Human Enzymes in Transgenic Tobaccoa (1996)

Transgenic plants have significant potential in the bioproduction of complex human therapeutic proteins due to ease of genetic manipulation, lack of potential contamination with human pathogens, conservation of eukaryotic cell machinery mediating protein modification, and low cost of biomass production. Tobacco has been used as our initial transgenic system because Agrobacterium-mediated transformation is highly efficient, prolific seed production greatly facilitates biomass scale-up, and development of new "health-positive" uses for tobacco has significant regional support. We have targeted bioproduction of complex recombinant human proteins with commercial potential as human pharmaceuticals. Human protein C (hPC), a highly processed serum protease of the coagulation/anticoagulation cascade, was produced at low levels in transgenic tobacco leaves. Analogous to its processing in mammalian systems, tobacco-synthesized hPC appears to undergo multiple proteolytic cleavages, disulfide bond formation, and N-linked glycosylation. Although tobacco-derived hPC has not yet been tested for all posttranslational modifications or for enzymatic (anticlotting) activity, these results are promising and suggest considerable conservation of protein processing machinery between plants and animals. CropTech researchers have also produced the human lysosomal enzyme glucocerebrosidase (hGC) in transgenic tobacco. This glycoprotein has significant commercial potential as replacement therapy in patients with Gaucher's disease. Regular intravenous administration of modified glucocerebrosidase, derived from human placentae or CHO cells, has proven highly effective in reducing disease manifestations in patients with Gaucher's disease. However, the enzyme is expensive (dubbed the "world's most expensive drug" by the media), making it a dramatic model for evaluating the potential of plants to provide a safe, low-cost source of bioactive human enzymes. Transgenic tobacco plants were generated that contained the human glucocerebrosidase cDNA under the control of an inducible plant promoter. hGC expression was demonstrated in plant extracts by enzyme activity assay and immunologic cross-reactivity with anti-hGC antibodies. Tobacco-synthesized hGC comigrates with human placental-derived hGC during electrophoretic separations, is glycosylated, and, most significantly, is enzymatically active. Although expression levels vary depending on transformant and induction protocol, hGC production of > 1 mg/g fresh weight of leaf tissue has been attained in crude extracts. Our studies provide strong support for the utilization of tobacco for high-level production of active hGC for purification and eventual therapeutic use at potentially much reduced costs. Furthermore, this technology should be directly adaptable to the production of a variety of other complex human proteins of biologic and pharmaceutical interest.
Absorbable Polyglactin Mesh for Retropubic Sling Operations in Female Urinary Stress Incontinence (1983)

Mesh of absorbable polyglactin 910 instead of human tissues or nonabsorbable synthetic materials was utilized for retropubic sling procedures in 21 women with urinary stress incontinence. The patients have been observed for a period ranging from 4 to 14 months. 20 of them are continent while there was 1 relapse after 2 months. The postoperative complications were minimal, and there has been no instance of foreign body reaction.
Iterative Hard Thresholding and L0 Regularisation (2007)

Sparse signal approximations are approximations that use only a small number of elementary waveforms to describe a signal. In this paper we proof the convergence of an iterative hard thresholding algorithm and show, that the fixed points of that algorithm are local minima of the sparse approximation cost function, which measures both, the reconstruction error and the number of elements in the representation. Simulation results suggest that the algorithm is comparable in performance to a commonly used alternative method.
Agrobacterium tumefaciens -Mediated Transformation of Maize Embryos Using a Standard Binary Vector System (2002)

We have achieved routine transformation of maize (Zea mays) using an Agrobacterium tumefaciens standard binary (non-super binary) vector system. Immature zygotic embryos of the hybrid line Hi II were infected with A. tumefaciens strain EHA101 harboring a standard binary vector and cocultivated in the presence of 400 mg L-1 L-cysteine. Inclusion of L-cysteine in cocultivation medium lead to an improvement in transient beta-glucuronidase expression observed in targeted cells and a significant increase in stable transformation efficiency, but was associated with a decrease in embryo response after cocultivation. The average stable transformation efficiency (no. of bialaphos-resistant events recovered per 100 embryos infected) of the present protocol was 5.5%. Southern-blot and progeny analyses confirmed the integration, expression, and inheritance of the bar and gus transgenes in R0, R1, and R2 generations of transgenic events. To our knowledge, this represents the first report in which fertile, stable transgenic maize has been routinely produced using an A. tumefaciens standard binary vector system.
Gene expression profiling of tumours derived from rasV12/E1A-transformed mouse embryonic fibroblasts to identify genes required for tumour development. (2005)

Some of the genes identified in this work, whose expression is altered upon rasV12/E1A transformation of MEFs, could be new cancer therapeutic targets.
Mutant p53 Disrupts MCF-10A Cell Polarity in Three-dimensional Culture via Epithelial-to-mesenchymal Transitions (2011)

Mutant p53 is not only deficient in tumor suppression but also acquires additional activity, called gain of function. Mutant p53 gain of function is recapitulated in knock-in mice that carry one null allele and one mutant allele of the p53 gene. These knock-in mice develop aggressive tumors compared with p53-null mice. Recently, we and others showed that tumor cells carrying a mutant p53 are addicted to the mutant for cell survival and resistance to DNA damage. To further define mutant p53 gain of function, we used the MCF-10A three-dimensional model of mammary morphogenesis. MCF-10A cells in three-dimensional culture undergo a series of morphological changes and form polarized and growth-arrested spheroids with hollow lumen, which resembles normal glandular architectures in vivo. Here, we found that endogenous wild-type p53 in MCF-10A cells was not required for acinus formation, but knockdown of endogenous wild-type p53 (p53-KD) led to partial clearance of cells in the lumen due to decreased apoptosis. Consistent with this, p53-KD altered expression patterns of the cell adhesion molecule E-cadherin, the cytoskeletal marker β-catenin, and the extracellular matrix protein laminin V. We also found that ectopic expression of the mutant G245S led to a phenotype similar to p53-KD, whereas a combination of ectopic expression of siRNA-resistant G245S with p53-KD led to a less cleared lumen. In contrast, ectopic expression of mutant R248W, R175H, and R273H disrupted normal acinus architectures with filled lumen and led to formation of irregular and multiacinus structures regardless of p53-KD. In addition, these mutants altered normal expression patterns and/or levels of E-cadherin, β-catenin, laminin V, and tight junction marker ZO-1. Furthermore, epithelial-to-mesenchymal transitions (EMT) markers, Snail, Slug, and Twist, were highly induced by mutant p53 and/or p53-KD. Together, we postulate that EMT represents a mutant p53 gain of function and mutant p53 alters cell polarity via EMT.
Detection ofN6-methyladenosine based on the methyl-sensitivity of MazF RNA endonuclease (2017)

We found that Escherichia coli MazF toxin, an ACA-sequence-specific endoribonuclease, was sensitive to N<sup>6</sup>-methyladenosine (m6A), representing the first m6A-sensitive RNA cleavage enzyme. The methyl-sensitivity of MazF allowed simple analyses of both m6A demethylase and methyltransferase activity. Furthermore, the approach could be used for inhibitor screening.
Cloning, sequence, and expression of the lysostaphin gene from Staphylococcus simulans. (1987)

A 1.5-kilobase-pair fragment of DNA that contains the lysostaphin gene from Staphylococcus simulans and its flanking sequences has been cloned and completely sequenced. The gene encodes a preproenzyme of Mr 42,000. The NH2-terminal sequence of the preproenzyme is composed of a signal peptide followed by seven tandem repeats of a 13-amino acid sequence. Conversion of prolysostaphin to the mature enzyme occurs extracellularly in cultures of S. simulans and involves removal of the NH2-terminal portion of the proenzyme that contains the tandem repeats. The high degree of homology of the repeats suggests that they have arisen by duplication of a 39-base-pair sequence of DNA. In S. simulans, the lysostaphin gene is present on a large beta-lactamase plasmid.
Symptoms associated with impaired gastric emptying of solids and liquids in functional dyspepsia (2003)

Objectives
The relationship between functional dyspepsia and delayed gastric emptying of solids or liquids is still unclear. The aim of the present study was to investigate in dyspeptic patients the prevalence of delayed gastric emptying for solids or for liquids and to investigate the relationship to the dyspepsia symptom pattern.
A virtual prototype manufacturing software system for MEMS (2002)

In this paper we report on developments on a computer-aided design software system (IntelliCAD) for prototype development of microelectromechanical systems. The system is designed to fill gaps in micro-manufacturing know-how by linking performance modeling to manufacturing (machine) parameters. The architecture is self-contained, completely integrated and allows modification for user applications. IntelliCAD's integration is accomplished by an architecture different from a previously reported academic system (1990). The architecture has integrated mask layout, a material database, a fabrication database, process simulation, backward process parameter optimization at each fabrication step, a process debugger, a 3D solid modeler, and parametric electrostatic, mechanical, thermomechanical and electro-mechanical analysis.