gebhart/patrepeval huggingface dataset:
Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in human invasive breast carcinomas. (1997)

Activation of the zymogen of matrix metalloproteinase 2 (proMMP-2, progelatinase A) possibly is one of the key steps in invasion and metastasis of various human carcinomas. Three different membrane-type MMPs (MT-MMPs), MT1-, MT2-, and MT3-MMPs are thought to be activators of proMMP-2 in the tissues. MT4-MMP is structurally different from the other three enzymes, and its function as proMMP-2 activator is uncertain. In the present study of human invasive breast carcinomas, we examined a correlation between the expression of MT1-, MT2-, and MT3-MMPs, immunolocalization of MT1- and MT2-MMPs, and proMMP-2 activation. Northern blot analysis demonstrated the predominant expression of MT1-MMP mRNA in carcinoma tissues (20 of 20 cases), whereas MT2-MMP was detected in only 25% of the cases (5 of 20 cases), and no detectable expression of MT3-MMP was observed. The expression levels of MT1-MMP but not MT2-MMP correlated well with the presence of lymph node and distant metastases, clinical stages, and size of tumors. Immunohistochemically, MT1-MMP was localized predominantly in the carcinoma cells in all of the samples (32 of 32 cases). Immunostaining of MT2-MMP in the carcinoma cells was observed in only 38% of the cases (12 of 32 cases). Immunoblot analysis of tumor homogenates confirmed the presence of these MT-MMPs. Activation of proMMP-2 was significantly higher in the carcinoma samples with lymph node or distant metastasis compared to carcinoma without metastasis, normal control, or fibrocystic disease (P < 0.05). An increase in the activation ratio of proMMP-2 correlated directly with the expression of MT1-MMP but not MT2-MMP, as measured by either Northern blot analysis or immunostaining. These results suggest that MT1-MMP may play a key role in human breast carcinoma invasion and metastasis by being predominantly responsible for activation of proMMP-2.
Mutational analysis of the virulence region of an Agrobacterium tumefaciens Ti plasmid (1983)

Forty-nine Tn3 and Tn5 transposition insertion mutations were introduced into the virulence region of the pTiA6NC plasmid of Agrobacterium tumefaciens. Five Tn5 transposition mutations from an earlier study (D. Garfinkel and E. Nester, J. Bacteriol. 144:732-743, 1980) were also mapped more accurately. These mutations defined five separate loci within the virulence region. Two Tn3 insertions into one of these loci, virA, result in a strain which is only weakly virulent; however, a Tn5 insertion into this locus eliminates virulence. One Tn5 insertion into another locus, virC, results in a strain which is weakly virulent. Two additional Tn5 insertions into this locus eliminate virulence. Insertions into the remaining three loci eliminate virulence entirely.
Inheritance of P element and reporter gene sequences in zebrafish. (1994)

We have established 15 separate lines of zebrafish transgenic for two plasmid DNAs containing Drosophila P element sequences and either the reporter genes chloramphenicol acetyltransferase (CAT), neomycin phosphotransferase (NPT), and beta-galactosidase (BGAL) or the reporter gene hygromycin phosphotransferase (HPT). Transient expression of CAT, but not NPT or BGAL, could be measured in the G0 (microinjected) generation, while expression in subsequent generations was below the limit of detection for CAT and NPT. All 15 lines contain stable low copy number integrations of between one and five transgene copies per cell with characteristic Southern blot "junction fragments" and have shown Mendelian inheritance after the G1 generation. The transgenes in 13 of 15 of the lines were originally inherited by about 10% or less of the G1 fish, suggesting a mosaic integration into the germline. Of 14 tested lines, none is associated with an embryonic recessive lethal phenotype as scored in the G3 generation.
18F-Fluorobenzoate–Labeled Cystine Knot Peptides for PET Imaging of Integrin αvβ6 (2013)

These cystine knot peptide tracers, in particular (18)F-fluorobenzoate-R01, show translational promise for molecular imaging of integrin αvβ6 overexpression in pancreatic and other cancers.
Inhibitory effects of humic acid on insoluble glucan synthesis and cellular adherence of Streptococcus mutans (sobrinus) 6715. (1989)

Humic acid/
Increasing Hyperpolarized Spin Lifetimes Through True Singlet Eigenstates (2009)

The sensitivity limitations for magnetic resonance imaging of organic molecules have recently been addressed by hyperpolarization methods, which prepare excess nuclear spin polarization. This approach can increase sensitivity by orders of magnitude, but the enhanced signal relaxes away in tens of seconds, even in favorable cases. Here we show theoretically that singlet states between strongly coupled spins in molecules can be used to store and retrieve population in very-long-lived disconnected eigenstates, as long as the coupling between the spins substantially exceeds both the couplings to other spins and the resonance frequency difference between them. Experimentally, 2,3-carbon-13-labeled diacetyl has a disconnected eigenstate that can store population for minutes and is read out by hydration to make the two spins inequivalent.
Functional Assays for Protein C Activity and Protein C Inhibitor Activity in Plasma (1989)

An assay system for protein C (PC) activity and PC-inhibitor in plasma was developed. The assay was based on: (1) binding of PC to wells of a microtiter plate coated with a murine monoclonal anti-PC antibody (C3) that did not interfere with the activity or activation of PC; (2) activation of immobilized PC with Protac C; (3) incubation with or without a source of activated PC inhibitor; and (4) measurement of amidolytic activity using the substrate S-2366. The activity assay was specific for PC and sensitive to less than 1 microliter of plasma or 4 ng PC. Inhibition of activated PC by plasma followed pseudo first order kinetics. Heparin caused a dose dependent increase in the inhibition rate with half maximal stimulation at approximately 3 U/ml and maximal stimulation at heparin concentrations greater than or equal to 10 U/ml. This assay is suitable not only for determination of functional plasma levels of PC and PC inhibitor activities but also for kinetic studies of inhibition of activated PC in complex systems, such as plasma. Studies showed that urokinase interfered with the inhibition of APC by plasma inhibitor(s).
VpsR, a Member of the Response Regulators of the Two-Component Regulatory Systems, Is Required for Expression of vps Biosynthesis Genes and EPS ETr -Associated Phenotypes in Vibrio cholerae O1 El Tor (2001)

The rugose colonial variant of Vibrio cholerae O1 El Tor produces an exopolysaccharide (EPS(ETr)) that enables the organism to form a biofilm and to resist oxidative stress and the bactericidal action of chlorine. Transposon mutagenesis of the rugose variant led to the identification of vpsR, which codes for a homologue of the NtrC subclass of response regulators. Targeted disruption of vpsR in the rugose colony genetic background yielded a nonreverting smooth-colony morphotype that produced no detectable EPS(ETr) and did not form an architecturally mature biofilm. Analysis of two genes, vpsA and vpsL, within the vps cluster of EPS(ETr) biosynthesis genes revealed that their expression is induced above basal levels in the rugose variant, compared to the smooth colonial variant, and requires vpsR. These results show that VpsR functions as a positive regulator of vpsA and vpsL and thus acts to positively regulate EPS(ETr) production and biofilm formation.
Strategies and Approaches of Targeting STAT3 for Cancer Treatment (2016)

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that regulates the expression of genes related to cell cycle, cell survival, and immune response associated with cancer progression and malignancy in a number of cancer types. Once activated, STAT3 forms a homodimer and translocates to the nucleus where it binds DNA promoting the translation of target genes associated with antiapoptosis, angiogenesis, and invasion/migration. In normal cells, levels of activated STAT3 remain transient; however, STAT3 remains constitutively active in approximately 70% of human solid tumors. The pivotal role of STAT3 in tumor progression has promoted a campaign in drug discovery to identify small molecules that disrupt the function of STAT3. A range of approaches have been used to identify novel small molecule inhibitors of STAT3, including high-throughput screening of chemical libraries, computational-based virtual screening, and fragment-based design strategies. The most common approaches in targeting STAT3 activity are either via the inhibition of tyrosine kinases capable of phosphorylating and thereby activating STAT3 or by preventing the formation of functional STAT3 dimers through disruption of the SH2 domains. However, the targeting of the STAT3 DNA-binding domain and disruption of binding of STAT3 to its DNA promoter have not been thoroughly examined, mainly due to the lack of adequate assay systems. This review summarizes the development of STAT3 inhibitors organized by the approach used to inhibit STAT3, the current inhibitors of each class, and the assay systems used to evaluate STAT3 inhibition and offers an insight into future approaches for small molecule STAT3 inhibitor development.
Multichannel Electrocardiogram Decomposition Using Periodic Component Analysis (2008)

In this letter, we propose the application of the generalized eigenvalue decomposition for the decomposition of multichannel electrocardiogram (ECG) recordings. The proposed method uses a modified version of a previously presented measure of periodicity and a phase-wrapping of the RR-interval, for extracting the "most periodic" linear mixtures of a recorded dataset. It is shown that the method is an improved extension of conventional source separation techniques, specifically customized for ECG signals. The method is therefore of special interest for the decomposition and compression of multichannel ECG, and for the removal of maternal ECG artifacts from fetal ECG recordings.
Linking Antibody Fc Domain to Endostatin Significantly Improves Endostatin Half-life and Efficacy (2008)

Fc-endostatin is a superior molecule to the original clinical endostatin. Due to its long half-life, the amount of protein required is substantially reduced compared with the clinically tested endostatin. Furthermore, in view of the U-shaped curve of efficacy observed for endostatin, we estimate that the requirement for Fc-endostatin is approximately 700-fold less than endostatin alone. The half-life of endostatin is similar to that of vascular endothelial growth factor-Trap and Avastin, two other antiangiogenic reagents. We conclude that a new clinical trial of endostatin, incorporating Fc, may benefit cancer patients.
Posteruptive changes in human dental fluorosis--a histological and ultrastructural study. (1991)

The aim of the present study was to describe the structural features characterizing the severe grades of human fluorotic enamel (TF scores 5-9) with particular emphasis on the posteruptive changes in severely fluorosed teeth. Dental fluorosis is a subsurface hypomineralized lesion deep to a well-mineralized outer enamel surface, which in severe cases breaks apart shortly after eruption. Early signs of posteruptive changes comprise small defects corresponding to the opening of striae of Retzius. The enamel pits which develop after eruption in more severe cases exhibit an increase in mineral content at their base which correspond to the exposed subsurface hypomineralized lesions. Likewise, the extensive removal of surface enamel in the most severe cases of human fluorosis results in a highly varying uptake of mineral into the exposed subsurface hypomineralized lesions. The uptake varies greatly within apparently similar degrees of hypomineralized lesions. In approximal abrasion facets, however, where the subsurface lesions are also exposed, no evidence of mineral uptake was found. At the ultrastructural level, the well-mineralized surface zone consists of large hexagonal enamel crystals separated by rather large intercrystalline spaces in which numerous irregular small crystals are observed. Moreover, the large crystals may exhibit central and peripheral dissolution. In addition, mineral appeared to be deposited into such defects as well as along the side of the crystals, often with the lattices being continuous from the original crystal into the apparently posteruptive formed crystal material. It is concluded that a substantial mineral uptake can take place in exposed porous hypomineralized fluorotic enamel after eruption, but is most likely to be associated with the presence of microbial deposits, the metabolic activity of which may play a keyrole in mineral exchange.
Characterization of iron-sulfur clusters in lysine 2,3-aminomutase by electron paramagnetic resonance spectroscopy (1992)

Lysine 2,3-aminomutase from Clostridia catalyzes the interconversion of L-alpha-lysine with L-beta-lysine. The purified enzyme contains iron-sulfur ([Fe-S]) clusters, pyridoxal phosphate, and Co(II) [Petrovich, R. M., Ruzicka, F. J., Reed, G. H., & Frey, P. A. (1991) J. Biol. Chem. 266, 7656-7660]. Enzymatic activity depends upon the presence and integrity of these cofactors. In addition, the enzyme is activated by S-adenosylmethionine, which participates in the transfer of a substrate hydrogen atom between carbon-3 of lysine and carbon-2 of beta-lysine [Moss, M., & Frey, P. A. (1987) J. Biol. Chem. 262, 14859-14862]. This paper describes the electron paramagnetic resonance (EPR) properties of the [Fe-S] clusters. Purified samples of the enzyme also contain low and variable levels of a stable radical. The radical spectrum is centered at g = 2.006 and is subject to inhomogeneous broadening at 10 K, with a p1/2 value of 550 +/- 100 microW. The low-temperature EPR spectrum of the [Fe-S] cluster is centered at g = 2.007 and undergoes power saturation at 10 K in a homogeneous manner, with a p1/2 of 15 +/- 2 mW. The signals are consistent with the formulation [4Fe-4S] and are adequately simulated by a rhombic spectrum, in which gxx = 2.027, gyy = 2.007, and gzz = 1.99. Treatment of the enzyme with reducing agents converts the cluster into an EPR-silent form. Oxidation of the purified enzyme by air or ferricyanide converts the [Fe-S] complex into a species with an EPR spectrum that is consistent with the formulation [3Fe-4S].(ABSTRACT TRUNCATED AT 250 WORDS)
A Case of Dissociative amnesia with Conversion disorder -By using psychotherapy- (2003)

Our meta-analysis underscores the intricate equilibrium between functional efficacy and safety in the evaluation of DEVT and BT for ACS-LVO. Fundamentally, while BT appears more efficacious, concerns about safety arise due to the superior safety profile demonstrated by DEVT. Individualized treatment decisions are imperative, and further trials are warranted to enhance precision in clinical guidance.
Paralysis of phagocyte migration due to an artificial blood substitute (1984)

We investigated the effect of a candidate artificial blood substitute, Fluosol-DA (FDA), on human neutrophil function in a serum-free medium. In a 50% (vol/vol) mixture with polymorphonuclear cells (PMN), FDA had no effect on PMN viability, phagocytosis, superoxide anion generation, degranulation, or bactericidal activity. In striking contrast, the random migration and chemotaxis of PMN to both f-Met-Leu-Phe (fMLP) and activated serum were inhibited by 98% +/- 2%, 95% +/- 2%, and 88% +/- 6%, respectively. Inhibition of chemotaxis by FDA required no preincubation, was dose-dependent (50% inhibition [ID50] with a 14% vol/vol mixture with FDA), and was fully reversible by washing PMN free of FDA after one hour but not after 18 hours of incubation (32% +/- 11% inhibition of chemotaxis). FDA itself was not chemotactic and did not impair either the chemotactic activity or binding of fMLP to PMN. FDA also inhibited PMN adhesion (ID50, 9 +/- 1 vol/vol%). The inhibitory component of FDA was found to be its detergent additive, Pluronic F-68, which inhibited random migration, chemotaxis, and adhesion with ID50s of 1.4, 2.4, and 2.9 mg/mL, respectively (equivalent to FDA concentrations of 5, 9, and 11 vol/vol%, respectively). All the other components of FDA were noninhibitory. Plasma samples from humans injected with 8 mL/kg FDA and plasma samples from rabbits injected with 16 mL/kg FDA or an equivalent concentration of Pluronic F-68, when mixed with autologous PMN, also severely inhibited PMN chemotaxis. We conclude that exposure of PMN to clinically relevant concentrations of FDA inhibits PMN migration, presumably due to inhibition of adhesion. The inhibitory effect is entirely due to the detergent, Pluronic F-68. Artificial blood substitutes containing Pluronic F-68 may compromise the ability of PMN to prevent or effectively control microbial infections.
Role of Gut Barrier Function in the Pathogenesis of Nonalcoholic Fatty Liver Disease (2015)

Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease, and its incidence is increasing year by year. Many efforts have been made to investigate the pathogenesis of this disease. Since 1998 when Marshall proposed the conception of "gut-liver axis," more and more researchers have paid close attention to the role of gut barrier function in the pathogenesis of NAFLD. The four aspects of gut barrier function, including physical, chemical, biological, and immunological barriers, are interrelated closely and related to NAFLD. In this paper, we present a summary of research findings on the relationship between gut barrier dysfunction and the development of NAFLD, aiming at illustrating the role of gut barrier function in the pathogenesis of this disease.
Quantitative cerebrospinal fluid cytology in patients receiving intracavitary chemotherapy (1993)

Cytological evaluation of cerebrospinal fluid (CSF) is an important means of following response to intracavitary chemotherapy for leptomeningeal malignancy. We studied the feasibility of quantitative cytological evaluation by retrospective analysis of serial CSF specimens from 7 patients receiving phase I intracavitary chemotherapy for leptomeningeal malignancy who had persistent malignant cytology. Three to 34 CSF specimens per patient obtained over a 3- to 48-week period were reviewed. Significant (five- to 10-fold or greater) reductions in numbers of malignant cells in CSF during treatment could be identified in specimens otherwise diagnosed as positive. Quantitative CSF cytological evaluation is neither overly time consuming nor tedious to perform and may provide useful clinical information.
p34 Cdc28 -Mediated Control of Cln3 Cyclin Degradation (1995)

Cln3 cyclin of the budding yeast Saccharomyces cerevisiae is a key regulator of Start, a cell cycle event in G1 phase at which cells become committed to division. The time of Start is sensitive to Cln3 levels, which in turn depend on the balance between synthesis and rapid degradation. Here we report that the breakdown of Cln3 is ubiquitin dependent and involves the ubiquitin-conjugating enzyme Cdc34 (Ubc3). The C-terminal tail of Cln3 functions as a transferable signal for degradation. Sequences important for Cln3 degradation are spread throughout the tail and consist largely of PEST elements, which have been previously suggested to target certain proteins for rapid turnover. The Cln3 tail also appears to contain multiple phosphorylation sites, and both phosphorylation and degradation of Cln3 are deficient in a cdc28ts mutant at the nonpermissive temperature. A point mutation at Ser-468, which lies within a Cdc28 kinase consensus site, causes approximately fivefold stabilization of a Cln3-beta-galactosidase fusion protein that contains a portion of the Cln3 tail and strongly reduces the phosphorylation of this protein. These data indicate that the degradation of Cln3 involves CDC28-dependent phosphorylation events.
Measuring the Induced Membrane Voltage with Di-8-ANEPPS (2009)

Placement of a cell into an external electric field causes a local charge redistribution inside and outside of the cell in the vicinity of the cell membrane, resulting in a voltage across the membrane. This voltage, termed the induced membrane voltage (also induced transmembrane voltage, or induced transmembrane potential difference) and denoted by DeltaPhi, exists only as long as the external field is present. If the resting voltage is present on the membrane, the induced voltage superimposes (adds) onto it. By using one of the potentiometric fluorescent dyes, such as di-8-ANEPPS, it is possible to observe the variations of DeltaPhi on the cell membrane and to measure its value noninvasively. di-8-ANEPPS becomes strongly fluorescent when bound to the lipid bilayer of the cell membrane, with the change of the fluorescence intensity proportional to the change of DeltaPhi. This video shows the protocol for measuring DeltaPhi using di-8-ANEPPS and also demonstrates the influence of cell shape on the amplitude and spatial distribution of DeltaPhi.
Edge-respecting brushes (2008)

Digital paint is one of the more successful interactive applications of computing. Brushes that apply various effects to an image have been central to this success. Current painting techniques ignore the underlying image. By considering that image we can help the user paint more effectively. There are algorithms that assist in selecting regions to paint including flood fill, intelligent scissors and graph cut. Selected regions and the algorithms to create them introduce conceptual layers between the user and the painting task. We propose a series of "edge-respecting brushes" that spread paint or other effects according to the edges and texture of the image being modified. This restores the simple painting metaphor while providing assistance in working with the shapes already in the image. Our most successful fill brush algorithm uses competing least-cost-paths to identify what should be selected and what should not.
Conical refraction as a tool for polarization metrology (2013)

A method for polarization metrology based on the conical refraction (CR) phenomenon, occurring in biaxial crystals, is reported. CR transforms an input Gaussian beam into a light ring whose intensity distribution is linked to the incoming polarization. We present the design of a division-of-amplitude complete polarimeter composed of two biaxial crystals, whose measurement principle is based on the CR phenomenon. This design corresponds to a static polarimeter, that is, without mechanical movements or electrical signal addressing. Only one division-of-amplitude device is required, besides the two biaxial crystals, to completely characterize any state of polarization, including partially polarized and unpolarized states. In addition, a mathematical model describing the system is included. Experimental images of the intensity distribution related to different input polarization states are provided. These intensity patterns are compared with simulated values, proving the potential of polarimeters based on biaxial crystals.