gebhart/patrepeval huggingface dataset:
Fibrinogen is an important determinant of the metastatic potential of circulating tumor cells (2000)

Detailed studies of tumor cell-associated procoagulants and fibrinolytic factors have implied that local thrombin generation and fibrin deposition and dissolution may be important in tumor growth and dissemination. To directly determine whether fibrin(ogen) or plasmin(ogen) are determinants of the metastatic potential of circulating tumor cells, this study examined the impact of genetic deficits in each of these key hemostatic factors on the hematogenous pulmonary metastasis of 2 established murine tumors, Lewis lung carcinoma and the B16-BL6 melanoma. In both tumor models, fibrinogen deficiency strongly diminished, but did not prevent, the development of lung metastasis. The quantitative reduction in metastasis in fibrinogen-deficient mice was not due to any appreciable difference in tumor stroma formation or tumor growth. Rather, tumor cell fate studies indicated an important role for fibrin(ogen) in sustained adhesion and survival of tumor cells within the lung. The specific thrombin inhibitor, hirudin, further diminished the metastatic potential of circulating tumor cells in fibrinogen-deficient mice, although the inhibitor had no apparent effect on tumor cell proliferation in vitro. The absence of plasminogen and plasmin-mediated fibrinolysis had no significant impact on hematogenous metastasis. The authors concluded that fibrin(ogen) is a critical determinant of the metastatic potential of circulating tumor cells. Furthermore, thrombin appears to facilitate tumor dissemination through at least one fibrin(ogen)-independent mechanism. These findings suggest that therapeutic strategies focusing on multiple distinct hemostatic factors might be beneficial in the containment of tumor metastasis.
Evaluation of Different Photosensitizers for Use in Photochemical Gene Transfection¶ (2001)

Many potentially therapeutic macromolecules, e.g. transgenes used in gene therapy, are taken into the cells by endocytosis, and have to be liberated from endocytic vesicles in order to express a therapeutic function. To achieve this we have developed a new technology, named photochemical internalization (PCI), based on photochemical reactions inducing rupture of endocytic vesicles. The aim of this study was to clarify which properties of photosensitizers are important for obtaining the PCI effect improving gene transfection. The photochemical effect on transfection of human melanoma THX cells has been studied employing photosensitizers with different physicochemical properties and using two gene delivery vectors: the cationic polypeptide polylysine and the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). Photochemical treatment by photosensitizers that do not localize in endocytic vesicles (tetra[3-hydroxyphenyl]porphyrin and 5-aminolevulinic acid-induced protoporphyrin IX) do not stimulate transfection, irrespective of the gene delivery vector. In contrast, photosensitizers localized in endocytic vesicles stimulate polylysine-mediated transfection, and amphiphilic photosensitizers (disulfonated aluminium phthalocyanine [AlPcS2a] and meso-tetraphenylporphynes) show the strongest positive effect, inducing approximately 10-fold increase in transfection efficiency. In contrast, DOTAP-mediated transfection is inhibited by all photochemical treatments irrespective of the photosensitizer used. Neither AlPcS2a nor Photofrin affects the uptake of the transfecting DNA over the plasma membrane, therefore photochemical permeabilization of endocytic vesicles seems to be the most likely mechanism responsible for the positive PCI effect on gene transfection.
Pro-caspase-3 Is a Major Physiologic Target of Caspase-8 (1998)

The apoptotic signal triggered by ligation of members of the death receptor family is promoted by sequential activation of caspase zymogens. We show here that in a purified system, the initiator caspases-8 and -10 directly process the executioner pro-caspase-3 with activation rates (kcat/Km) of 8.7 x 10(5) and 2.8 x 10(5) M-1 s-1, respectively. These rates are of sufficient magnitude to indicate direct processing in vivo. Differentially processed forms of caspase-3 that accumulate during its activation have similar rates of activation, activities, and specificities. The pattern and rate of caspase-8 induced activation of pro-caspase-3 in cytosolic extracts was the same as in a purified system. Moreover, immunodepletion of a putative intermediary in the pathway to activation, pro-caspase-9, was without consequence. Taken together these data demonstrate that the initiator caspase-8 can directly activate pro-caspase-3 without the requirement for an accelerator. The in vitro data thus help to deconvolute previous in vivo transfection studies which have debated the role of a direct versus indirect transmission of the apoptotic signal generated by ligation of death receptors.
Osteocalcin promoter-based toxic gene therapy for the treatment of osteosarcoma in experimental models. (1996)

Osteocalcin (OC), a noncollagenous bone matrix protein, is expressed in high levels by osteoblasts. To determine whether the OC promoter mediates cell-specific gene expression in cells of osteoblast lineage, we constructed a recombinant adenovirus, Ad-OC-TK, which contains the OC promoter that drives the expression of herpes simplex virus thymidine kinase (TK). We tested the expression of TK by this virus in osteoblast cell lines as well as in non-osteoblastic cell lines by assessing the enzyme activity of TK in vitro. Whereas the OC promoter failed to drive the expression of the TK gene in several non-osteoblastic cell lines such as WH, a human bladder transitional carcinoma, and NIH 3T3, an embryonic mouse fibroblast cell line, the OC promoter mediated high levels of expression in osteoblast cell lines including murine ROS and human MG-63 cells. The addition of acyclovir (ACV), a pro-drug for the inhibition of cell proliferation, resulted in the induction of osteoblast-specific cell death in vitro. Intratumoral injection of Ad-OC-TK into murine ROS osteosarcoma abolished tumor growth in a host treated with subsequent i.p. ACV injection in vivo. The Ad-OC-TK virus plus ACV treatment appears to be highly selective in blocking the growth of both murine and human osteosarcoma cell lines in vitro and murine osteosarcoma in vivo.
The synthesis of 13C‐enriched α‐methyldopa (1974)

Abstract Alpha‐methyldopa hydrochloride, specifically labelled with 13 C in the benzylic position, was prepared for use in biotransformation studies. Carbonation of the lithio derivative of 3,4‐dibenzyloxybenzene with 13 CO 2 (64 atom percent) was followed by LiA1H 4 reduction of the resulting benzoic acid. Oxidation with CrO 3 provided the benzaldehyde which was condensed with nitroethane to form the phenylnitropropene, Reduction of this phenylnitropropene with Fe/HOAc gave the corresponding phenyl‐2‐propanone which was converted to its hydantoin derivative. Base hydrolysis of the hydantoin followed by debenzylation in concentrated hydrochloric acid gave the desired alpha‐methyldopa hydrochloride in 16% overall yield.
Prolonged inhibitory effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine against replication of Epstein-Barr virus (1984)

The effects of 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), a new antiviral drug, and acyclovir (ACV) [9-(2-hydroxyethoxymethyl)guanine] on the replication of Epstein-Barr virus (EBV) were compared. Both drugs inhibited EBV DNA replication in P3HR-1 cells and superinfected Raji cells, but neither inhibited replication of the plasmid form of the EBV genome in latently infected Raji cells. However, DHPG had a more prolonged inhibitory effect than ACV. Although the effect of the drugs is prompt, the kinetics of inhibition of EBV replication indicated that a drug exposure of 14 days was needed to reduce the EBV genome copy number to the residual plasmid level (30 copies per cell). The inhibitory effect of ACV was readily reversed within 11 days after removal of the drug, in contrast to the more prolonged effect exerted by DHPG, which persisted for more than 21 days. The 50% inhibitory doses for cell growth of ACV and DHPG were estimated to be 250 and 200 microM, respectively. The viral 50% and 90% effective doses of inhibition were, respectively, 0.3 and 9 microM for ACV and 0.05 and 3 microM for DHPG. The therapeutic indices (50% inhibitory dose/50% effective dose) for ACV and DHPG were 833 and 4,000, respectively. Synthesis of EBV-associated polypeptides was also affected. In superinfected Raji cells, ACV (100 microM) and DHPG (30 microM) inhibited synthesis of polypeptides with molecular weights of 145,000 and 140,000; in addition, synthesis of polypeptides with molecular weights of 110,000 and 85,000 was markedly reduced by DHPG but not by ACV. However, after drug removal, the inhibitory effect of ACV on polypeptide synthesis was abolished in contrast to the more persistent effect of DHPG.
Image Separation using Wavelets and Shearlets (2011)

In this paper, we present an image separation method for separating images into point- and curvelike parts by employing a combined dictionary consisting of wavelets and compactly supported shearlets utilizing the fact that they sparsely represent point and curvilinear singularities, respectively. Our methodology is based on the very recently introduced mathematical theory of geometric separation, which shows that highly precise separation of the morphologically distinct features of points and curves can be achieved by $\ell^1$ minimization. Finally, we present some experimental results showing the effectiveness of our algorithm, in particular, the ability to accurately separate points from curves even if the curvature is relatively large due to the excellent localization property of compactly supported shearlets.
Novel Transcription Coactivator Complex Containing Activating Signal Cointegrator 1 (2002)

Human activating signal cointegrator 1 (hASC-1) was originally isolated as a transcriptional coactivator of nuclear receptors. Here we report that ASC-1 exists as a steady-state complex associated with three polypeptides, P200, P100, and P50, in HeLa nuclei; stimulates transactivation by serum response factor (SRF), activating protein 1 (AP-1), and nuclear factor kappaB (NF-kappaB) through direct binding to SRF, c-Jun, p50, and p65; and relieves the previously described transrepression between nuclear receptors and either AP-1 or NF-kappaB. Interestingly, ectopic expression of Caenorhabditis elegans ASC-1 (ceASC-1), an ASC-1 homologue that binds P200 and P100, like hASC-1, while weakly interacting only with p65, in HeLa cells appears to replace endogenous hASC-1 from the hASC-1 complex and exerts potent dominant-negative effects on AP-1, NF-kappaB, and SRF transactivation. In addition, neutralization of endogenous P50 by single-cell microinjection of a P50 antibody inhibits AP-1 transactivation; the inhibition is relieved by coexpression of wild-type P50, but not of P50DeltaKH, a mutant form that does not interact with P200. Overall, these results suggest that the endogenous hASC-1 complex appears to play an essential role in AP-1, SRF, and NF-kappaB transactivation and to mediate the transrepression between nuclear receptors and either AP-1 or NF-kappaB in vivo.
Analytical Method of Estimating Chemometric Prediction Error (1997)

We present an analytical formula that estimates the uncertainty in concentrations predicted by linear multivariate calibration, particularly partial least-squares (PLS). We emphasize the analysis of spectroscopic data. The derivation addresses the important limit in which calibration error is negligible in comparison to noise in the prediction spectra. The formula is expressed in terms of standard PLS calibration parameters and the amplitude of spectral noise; it is therefore straightforward to evaluate. To test the formula, we performed PLS analysis upon simulated spectra and upon experimental Raman spectra of dissolved biological analytes in water. In each instance, the root-mean-squared error of prediction was compared to the estimate from the formula. Accurate uncertainty estimates were obtained in cases where calibration noise was lower than prediction noise, and surprisingly good estimates were obtained even when the noise levels were equal. By comparing measured and estimated uncertainties, we assessed the robustness of each PLS calibration model. The scaling of prediction uncertainty with the spectral signal-to-noise ratio is also discussed.
Identification of epigenetic modulators in human breast cancer by integrated analysis of DNA methylation and RNA-Seq data (2018)

Human tumors undergo massive changes in DNA methylation. Recent studies showed that site-specific methylation of CpG sites is determined by the DNA sequence context surrounding the CpG site, which alludes to a possible mechanism for site-specific aberrant DNA methylation in cancer through DNA-binding proteins. In this paper, DNA methylation data and RNA-Seq data of breast tumors and normal tissues in the database of The Cancer Genome Atlas (TCGA) were integrated with information of DNA motifs in seven databases to find DNA-binding proteins and their binding motifs that were involved in aberrant DNA methylation in breast cancer. A total of 42,850 differentially methylated regions (DMRs) that include 77,298 CpG sites were detected in breast cancer. One hundred eight DNA motifs were found to be enriched in DMRs, and 109 genes encoding proteins binding to these motifs were determined. Based on these motifs and genes, 63 methylation modulator genes were identified to regulate differentially methylated CpG sites in breast cancer. A network of these 63 modulator genes and 645 transcription factors was constructed, and 20 network modules were determined. A number of pathways and gene sets related to breast cancer were found to be enriched in these network modules. The 63 methylation modulator genes identified may play an important role in aberrant methylation of CpG sites in breast cancer. They may help to understand site-specific dysregulation of DNA methylation and provide epigenetic markers for breast cancer.
Identification of tetracycline antibiotics by electrospray ionization in a quadrupole ion trap (1998)

Tetracycline antibiotics, tetracycline, chlortetracycline, demeclocycline, doxycycline, minocycline, methacycline, oxytetracycline, and anhydrotetracycline, are examined by electrospray ionization in a quadrupole ion trap. Studies were undertaken to evaluate the use of metal complexation as an alternative to conventional proton attachment. A variety of metal cationization processes, including attachment of Na+, Mg2+, Ca2+, Co2+, Ni2+, and Cu2+ were probed. Infrared multiphoton photodissociation and collisionally activated dissociation (CAD) were compared for generation of diagnostic fragmentation patterns of protonated and metal cationized tetracyclines. The photodissociation spectra provide a more informative signature, including more low mass ions that are not observed upon CAD. The metal complexes dissociate by pathways that are similar to those observed for the protonated molecules.
Radiolysis to knock-on damage transition in zeolites under electron beam irradiation (2011)

The electron-beam-induced damage in a zeolite under 60--200 keV energy beam irradiation has both radiolitic and knock-on components and can be described by linear superposition of these two processes. Theoretical predictions supported by experiments at 60 keV suggest that for electron beam energies smaller than 70 keV, the damage to the specimen follows a radiolitic path. For energies larger than 200 keV, knock-on based sputtering of the material will dominate, while considerable radiolitic movement of the atoms will still be present.
Advancing the Boundaries of High-Connectivity Network Simulation with Distributed Computing (2005)

The availability of efficient and reliable simulation tools is one of the mission-critical technologies in the fast-moving field of computational neuroscience. Research indicates that higher brain functions emerge from large and complex cortical networks and their interactions. The large number of elements (neurons) combined with the high connectivity (synapses) of the biological network and the specific type of interactions impose severe constraints on the explorable system size that previously have been hard to overcome. Here we present a collection of new techniques combined to a coherent simulation tool removing the fundamental obstacle in the computational study of biological neural networks: the enormous number of synaptic contacts per neuron. Distributing an individual simulation over multiple computers enables the investigation of networks orders of magnitude larger than previously possible. The software scales excellently on a wide range of tested hardware, so it can be used in an interactive and iterative fashion for the development of ideas, and results can be produced quickly even for very large networks. In contrast to earlier approaches, a wide class of neuron models and synaptic dynamics can be represented.
Evidence that urodilatin, rather than ANP, regulates renal sodium excretion. (1990)

Urodilatin, a closely related member of the atrial peptide family, was discovered recently in human urine. Urodilatin (ANP 95-126) is believed to be produced within the kidney and is natriuretic; evidence indicates that most of the ANP-like immunoreactivity in the kidney elutes with urodilatin rather than with ANP. Moreover, urodilatin is little affected by renal enzymes that inactivate atriopeptin. To determine the relative importance of urodilatin versus ANP in the regulation of renal sodium excretion, we studied intact and cardiac-denervated conscious dogs under three experimental conditions: (1) spontaneous sodium excretion, (2) intravenous infusion of saline, and (3) left atrial distension. Urodilatin was measured in urine with a newly developed radioimmunoassay that selectively measures urodilatin without any cross-reactivity with alpha-human atrial natriuretic peptide (alpha-hANP); alpha-hANP was measured in plasma by radio-immunoassay because it is rapidly inactivated in the kidney by enzymatic activity. In each group of experiments, sodium excretion correlated better with urodilatin than it did with circulating alpha-hANP. The correlation coefficient (r value) between urodilatin excretion and renal sodium excretion exceeded 0.8 in 13 of 18 experiments and was below 0.6 in only 2 experiments. On the other hand, the correlation between circulating atriopeptin and sodium excretion exceeded 0.8 in only 3 of 18 experiments and was below 0.6 in 10 experiments. A negative correlation between plasma atriopeptin and renal sodium excretion was observed during left atrial distension in the cardiac-denervated dogs. These results and other considerations suggest that urodilatin, rather than atriopeptin, is the member of the ANP family that is primarily involved in the regulation of renal sodium excretion.
Characterization of a CPI-Lexitropsin Conjugate-Oligonucleotide Covalent Complex by 1H NMR and Restrained Molecular Dynamics Simulation (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCharacterization of a CPI-Lexitropsin Conjugate-Oligonucleotide Covalent Complex by 1H NMR and Restrained Molecular Dynamics SimulationNancy L. Fregeau, Yuqiang Wang, Richard T. Pon, William A. Wylie, and J. William LownCite this: J. Am. Chem. Soc. 1995, 117, 35, 8917–8925Publication Date (Print):September 1, 1995Publication History Published online1 May 2002Published inissue 1 September 1995https://pubs.acs.org/doi/10.1021/ja00140a004https://doi.org/10.1021/ja00140a004research-articleACS PublicationsRequest reuse permissionsArticle Views127Altmetric-Citations30LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Chromosome Replication and the Division Cycle of Escherichia coli B/r (1971)

The average amount of deoxyribonucleic acid (DNA) per cell was measured in steady-state cultures of Escherichia coli B/r grown at 37 C in glucose-limited chemostats or in batch cultures in the exponential growth phase as maintained with one of several carbon sources. Within experimental errors, DNA content was dependent only on growth rate and independent of the type of culture, the carbon source, or the addition of growth factors. The amount of DNA per cell increased continuously with growth rate over the range of 0.02 to 3 divisions per hour. The data over the entire range of growth rates are in agreement with a constant time for a single replication point to traverse the entire genome, 47 min, and with cell division following 25 min after termination of replication. The measured amount of DNA per genome was 4.2 x 10(-15) g (or 2.5 x 10(9) daltons).
Subunit dissociations in natural and recombinant hemoglobins (1996)

A precise and rapid procedure employing gel filtration on Superose-12 to measure the tetramer-dimer dissociation constants of some natural and recombinant hemoglobins in the oxy conformation is described. Natural sickle hemoglobin was chosen to verify the validity of the results by comparing the values with those reported using an independent method not based on gel filtration. Recombinant sickle hemoglobin, as well as a sickle double mutant with a substitution at the Val-6(beta) receptor site, had approximately the same dissociation constant as natural sickle hemoglobin. Of the two recombinant hemoglobins with amino acid replacements in the alpha 1 beta 2 subunit interface, one was found to be extensively dissociated and the other completely dissociated. In addition, the absence of an effect of the allosteric regulators DPG and IHP on the dissociation constant was demonstrated. Thus, a tetramer dissociation constant can now be determined readily and used together with other criteria for characterization of hemoglobins and their interaction with small regulatory molecules.
114 MFLOPS logarithmic number system arithmetic unit for DSP applications (1995)

An arithmetic core for DSP applications, comprising two multiplier/dividers and an adder/subtractor, using logarithmic number system (LNS) arithmetic, is described. For most operands, precision better than the worst-case precision of IEEE 754 is obtained. Three operations per cycle are performed using 69k transistors integrated in a 16 mm/sup 2/ core in 1.2 /spl mu/m CMOS, offering better performance than the best previous result in only 43% of the area. The use of a new interleaved memory ROM structure and a second-order function interpolator are the key techniques that result in reduced area. This modest area allows several core units to be integrated on a chip for high performance DSP applications.