gebhart/patrepeval huggingface dataset:
Genomic Integrity and the Genetics of Cancer (1994)

One method of maintaining genomic integrity involves the action of cell cycle checkpoint genes. These genes integrate proper sensing of environmental signals and appropriate cellular responses. Recent work suggests that p53 performs such an integrator function in mammalian cells. In this paper, we describe how, in mortal cells, the E6 and E7 viral oncoproteins of type 16 human papillomavirus (HPV) each disrupts the integration of these signals in its own unique way, resulting in two distinct types of genomic alterations and cell death as the cells respond to negative growth signals. Furthermore, these alterations in response to negative growth signals can precede any overt phenotypes displayed by the oncoprotein-expressing cells and suggest a novel way to examine cells from individuals that are predisposed to malignancy. These studies implicate loss of cell cycle control in tumor progression.
AMINO ACID BIOSYNTHESIS INHIBITORS AS HERBICIDES (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
Texture and microstructure evolution in single-phase TixTa1−xN alloys of rocksalt structure (2011)

The mechanisms controlling the structural and morphological features (texture and microstructure) of ternary transition metal nitride thin films of the TixTa1−xN system, grown by various physical vapor deposition techniques, are reported. Films deposited by pulsed laser deposition, dual cathode magnetron sputtering, and dual ion beam sputtering have been investigated by means of x-ray diffraction in various geometries and scanning electron microscopy. We studied the effects of composition, energetic, and kinetics in the evolution of the microstructure and texture of the films. We obtain films with single and mixed texture as well as films with columnar “zone-T” and globular type morphology. The results have shown that the texture evolution of ternary transition metal nitrides as well as the microstructural features of such films can be well understood in the framework of the kinetic mechanisms proposed for their binary counterparts, thus giving these mechanisms a global application.
Integration of large-area metallic nanohole arrays with multimode optical fibers for surface plasmon resonance sensing (2013)

Here, we report an implementation of enhanced surface plasmon resonance sensing on optical fibers through integration of large-area metallic nanohole arrays on the endfaces of multimode optical fibers by a template transfer method. The Au nanohole array integrated optical fiber sensors show a high refractive index sensitivity 559 nm per refractive index unit, narrow resonant peak width less than 10 nm in aqueous solution, and consistent optical responses with peak position variation less than 0.5 nm for various core diameters of optical fibers at same dielectric conditions. These specifications demonstrates that the nanohole array based optical fibers can serve as a high-performance, portable and lensless plasmonic platform with superior robustness and accessibility for surface plasmon resonance sensing.
The Effects of IL-20 Subfamily Cytokines on Reconstituted Human Epidermis Suggest Potential Roles in Cutaneous Innate Defense and Pathogenic Adaptive Immunity in Psoriasis (2007)

IL-19, IL-20, IL-22, IL-24, and IL-26 are members of the IL-10 family of cytokines that have been shown to be up-regulated in psoriatic skin. Contrary to IL-10, these cytokines signal using receptor complex R1 subunits that are preferentially expressed on cells of epithelial origin; thus, we henceforth refer to them as the IL-20 subfamily cytokines. In this study, we show that primary human keratinocytes (KCs) express receptors for these cytokines and that IL-19, IL-20, IL-22, and IL-24 induce acanthosis in reconstituted human epidermis (RHE) in a dose-dependent manner. These cytokines also induce expression of the psoriasis-associated protein S100A7 and keratin 16 in RHE and cause persistent activation of Stat3 with nuclear localization. IL-22 had the most pronounced effects on KC proliferation and on the differentiation of KCs in RHE, inducing a decrease in the granular cell layer (hypogranulosis). Furthermore, gene expression analysis performed on cultured RHE treated with these cytokines showed that IL-19, IL-20, IL-22, and IL-24 regulate many of these same genes to variable degrees, inducing a gene expression profile consistent with inflammatory responses, wound healing re-epithelialization, and altered differentiation. Many of these genes have also been found to be up-regulated in psoriatic skin, including several chemokines, beta-defensins, S100 family proteins, and kallikreins. These results confirm that IL-20 subfamily cytokines are important regulators of epidermal KC biology with potentially pivotal roles in the immunopathology of psoriasis.
Density-Based Clustering over an Evolving Data Stream with Noise (2006)

Clustering is an important task in mining evolving data streams. Beside the limited memory and one-pass constraints, the nature of evolving data streams implies the following requirements for stream clustering: no assumption on the number of clusters, discovery of clusters with arbitrary shape and ability to handle outliers. While a lot of clustering algorithms for data streams have been proposed, they offer no solution to the combination of these requirements. In this paper, we present DenStream, a new approach for discovering clusters in an evolving data stream. The “dense” micro-cluster (named core-micro-cluster) is introduced to summarize the clusters with arbitrary shape, while the potential core-micro-cluster and outlier micro-cluster structures are proposed to maintain and distinguish the potential clusters and outliers. A novel pruning strategy is designed based on these concepts, which guarantees the precision of the weights of the micro-clusters with limited memory. Our performance study over a number of real and synthetic data sets demonstrates the effectiveness and efficiency of our method.
Performance of a Nd:YVO_4 microchip laser with continuous-wave pumping at wavelengths between 741 and 825 nm (1993)

We report the performance of a Nd:YVO(4) laser, which uses cw Ti:sapphire pumping, for a range of pumping wavelengths, polarizations, and crystal temperatures.
Efficient transfection of chicken cells by lipofection, and introduction of transfected blastodermal cells into the embryo (1991)

Chicken blastodermal cells (CBCs) and primary chicken fibroblasts (PCFs) have been lipofected with a variety of lacZ constructs encoding Escherichia coli beta-galactosidase (beta-gal). A reporter construct (phspPTlacZpA) containing a mouse heat-shock protein 68 gene (hsp 68) promoter was used to establish conditions for efficient lipofection. The construct, in circular or linear plasmid form or as reporter sequences alone, was transferred efficiently by incubating the cells for 3.5 h in a mixture of 6.2 micrograms Lipofectin (a cationic liposome preparation from Bethesda Research Laboratories) and 1.55-3.1 micrograms DNA per mL DMEM. These lipofection conditions were used to transfer a reporter construct (pCBcMtlacZ) containing a Zn(2+)-inducible chicken metallothionein (cMt) promoter, and constructs showing constitutive expression due to Rous sarcoma virus plus chicken beta-actin (pmiwZ) or cytomegalovirus (pMaori3) promoters. Endogenous chicken beta-gal and transferred bacterial beta-gal activity could be distinguished clearly by incubating the cells with the substrate, Xgal, at pH 4.3 or 7.4, respectively. Expression of phspPTlacZpA in chicken cells did not appear to require specific induction of the mouse hsp68 promoter, whereas expression of pCBcMtlacZ required treatment of the cells for 6-12 h with 150 microM ZnCl2. Bacterial beta-gal activity was observed following lipofection of CBCs that were cultured in suspension or plated. The efficiency of lipofection was at least 1 in 25 for CBCs, judging by the proportion of cells shown to have beta-gal activity 16-24 h after lipofection treatment began; these events could represent transient or stable incorporation of the construct.(ABSTRACT TRUNCATED AT 250 WORDS)
NADPH-Cytochrome P450 Oxidoreductase (2001)

NADPH-cytochrome P450 oxidoreductase catalyzes transfer of electrons from NADPH, via two flavin cofactors, to various cytochrome P450s. The crystal structure of the rat reductase complexed with NADP(+) has revealed that nicotinamide access to FAD is blocked by an aromatic residue (Trp-677), which stacks against the re-face of the isoalloxazine ring of the flavin. To investigate the nature of interactions between the nicotinamide, FAD, and Trp-677 during the catalytic cycle, three mutant proteins were studied by crystallography. The first mutant, W677X, has the last two C-terminal residues, Trp-677 and Ser-678, removed; the second mutant, W677G, retains the C-terminal serine residue. The third mutant has the following three catalytic residues substituted: S457A, C630A, and D675N. In the W677X and W677G structures, the nicotinamide moiety of NADP(+) lies against the FAD isoalloxazine ring with a tilt of approximately 30 degrees between the planes of the two rings. These results, together with the S457A/C630A/D675N structure, allow us to propose a mechanism for hydride transfer regulated by changes in hydrogen bonding and pi-pi interactions between the isoalloxazine ring and either the nicotinamide ring or Trp-677 indole ring. Superimposition of the mutant and wild-type structures shows significant mobility between the two flavin domains of the enzyme. This, together with the high degree of disorder observed in the FMN domain of all three mutant structures, suggests that conformational changes occur during catalysis.
Selective object stabilization for home video consumers (2005)

This paper describes a unified approach for video stabilization. The essential goal is to stabilize image sequences that consist of moving foreground objects, which appear frequently in today's home videos captured by hand-held consumer cameras. Our proposed techniques mainly rely on the analysis of motion content. Three major components are: initialization, segmentation and stabilization. In motion initialization, we propose a novel algorithm to efficiently search for the best possible frame in a sequence to start segmentation. Our segmentation algorithm is based on expectation-maximization (EM) framework which provides the mechanism for simultaneous estimation of motion models and their layers of support. Based on the framework of Kalman filter and EM motion estimation, our proposed algorithm has the flexibility of allowing selective stabilization with respect to background or/and foreground objects, subject to the preferences of customers.
Magnetically Actuated Nanorod Arrays as Biomimetic Cilia (2007)

We present a procedure for producing high-aspect-ratio cantilevered micro- and nanorod arrays of a PDMS-ferrofluid composite material. The rods have been produced with diameters ranging from 200 nm to 1 mum and aspect ratios as high as 125. We demonstrate actuation of these superparamagnetic rod arrays with an externally applied magnetic field from a permanent magnet and compare this actuation with a theoretical energy-minimization model. The structures produced by these methods may be useful in microfluidics, photonic, and sensing applications.
The Propeptide Binding Site of the Bovine γ-Glutamyl Carboxylase (1997)

gamma-Glutamyl carboxylase is an integral membrane protein required for the posttranslational modification of vitamin K-dependent proteins. The main recognition between the enzyme and its substrates is through an 18-amino acid propeptide. It has been reported that this binding site resides in the amino-terminal third of the gamma-glutamyl carboxylase molecule (Yamada, M., Kuliopulos, A., Nelson, N. P., Roth, D. A., Furie, B., Furie, B. C., and Walsh, C. T. (1995) Biochemistry 34, 481-489). In contrast, we found the binding site in the carboxyl half of the gamma-glutamyl carboxylase. We show that the carboxylase may be cleaved by trypsin into an amino-terminal 30-kDa and a carboxyl-terminal 60-kDa fragment joined by a disulfide bond(s), and the propeptide binds to the 60-kDa fragment. The sequence of the amino terminus of the 60-kDa fragment reveals that the primary trypsin-sensitive sites are at residues 349 and 351. Furthermore, the tryptic fragment that cross-links to the propeptide also reacts with an antibody specific to the carboxyl portion of the gamma-glutamyl carboxylase. In addition, cyanogen bromide cleavage of bovine gamma-glutamyl carboxylase cross-linked to the peptide comprising residues TVFLDHENANKILNRPKRY of human factor IX yields a cross-linked fragment of 16 kDa from the carboxyl half of the molecule, the amino-terminal sequence of which begins at residue 438. Thus, the propeptide binding site lies carboxyl-terminal to residue 438 and is predicted to be in the lumen of the endoplasmic reticulum.
Molecular cloning of a novel G protein‐coupled receptor that may belong to the neuropeptide receptor family (1990)

A novel cDNA encoding a putative G protein-coupled receptor was isolated from a rat forebrain cDNA library by homology screening. Sequence comparison demonstrates that the encoded polypeptide containing seven transmembrane domains shows highest homology with tachykinin receptors, particularly in the transmembrane domains and the first intracellular loop. The mRNA for this new receptor seems specifically expressed in brain and is prominently localized in specific nuclei of the rat brain, including thalamus, cerebral cortex and hippocampus. We speculate that a neuropeptide may be the natural ligand of this novel G protein-coupled receptor.
Human White/Murine ABC8 mRNA Levels Are Highly Induced in Lipid-loaded Macrophages (2000)

To identify genes that are transcriptionally activated when human macrophages accumulate excess lipids, we employed the mRNA differential display technique using RNA isolated from human monocyte-macrophages incubated in the absence or presence of acetylated low density lipoprotein and sterols (cholesterol and 25-hydroxycholesterol). These studies identified a mRNA whose levels were highly induced in lipid-loaded macrophages. The mRNA encoded the human White protein, a member of the ATP-binding cassette (ABC) transporter superfamily of proteins. The mRNA levels of ABC8, the murine homolog of the human white gene, were also induced when a murine macrophage cell line, RAW264.7, was incubated with acetylated low density lipoprotein and sterols. Additional studies demonstrated that white/ABC8 mRNA levels were induced by specific oxysterols that included 25-, 20(S)-, and 22(R)-hydroxycholesterol, and by a retinoid X receptor-specific ligand. Furthermore, the oxysterol-mediated induction of ABC8 expression in mouse peritoneal macrophages was dependent on the presence of the nuclear oxysterol receptors, liver X receptors (LXRs). Macrophages derived from mice lacking both LXRalpha and LXRbeta failed to up-regulate the expression of ABC8 following incubation with 22(R)-hydroxycholesterol. Oxysterol-dependent induction of white/ABC8 mRNA was blocked by actinomycin D but not by cycloheximide treatment of cells. We conclude that the white and ABC8 genes are primary response genes that are transcriptionally activated by specific oxysterols and that this induction is mediated by the LXR subfamily of nuclear hormone receptors. These data strongly support the hypothesis that white/ABC8 has a role in cellular sterol homeostasis.
Gene Synthesis by Serial Cloning of Oligonucleotides (1988)

A rapid and simple method of gene synthesis is presented. A gene is constructed by serial additions of individual gene fragments in the 5'----3' direction. The vector used as the synthesis vehicle contains a unique Bsm I site at the amino terminus of the lacZ gene. Plasmid linearized with Bsm I is recircularized in vivo by oligonucleotide-directed double-strand break repair. The synthetic oligonucleotide used to "bridge" the double-strand break carries a 70- to 100-nucleotide insert which constitutes a portion of the gene along with a BsmI site at the 3' end that regenerates the site and allows for another consecutive round of mutagenesis to extend the gene sequence. The process is repeated until the entire gene is assembled. The method uses the beta-galactosidase color assay as a means of screening for correct insert lengths. The only in vitro enzymatic step necessary is a single Bsm I restriction digest of plasmid DNA. No ligation reactions are required. Only one strand of a gene sequence needs to be synthesized chemically. The gene synthesis method presented here was used to construct the human anaphylatoxin complement factor C3a gene.
Distinct mechanisms for N-acetylcysteine inhibition of cytokine-induced E-selectin and VCAM-1 expression (1997)

We have examined the effects of N-acetyl-L-cysteine (NAC), a well-characterized, thiol-containing antioxidant, on agonist-induced monocytic cell adhesion to endothelial cells (EC). NAC inhibited interleukin-1 (IL-1 beta)-induced, but not basal, adhesion with 50% inhibition at approximately 20 mM. Monocytic cell adhesion to EC in response to tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), alpha-thrombin, or phorbol 12-myristate 13-acetate (PMA) was similarly inhibited by NAC. Unlike published studies with pyrrolidinedithiocarbamate, which specifically inhibited vascular cell adhesion molecule 1 (VCAM-1), NAC inhibited IL-1 beta-induced mRNA and cell surface expression of both E-selectin and VCAM-1. NAC had no effect on the half-life of E-selectin or VCAM-1 mRNA. Although NAC reduced nuclear factor-kappa B (NF-kappa B) activation in EC as measured by gel-shift assays using an oligonucleotide probe corresponding to the consensus NF-kappa B binding sites of the VCAM-1 gene (VCAM-NF-kappa B), the antioxidant had no appreciable effect when an oligomer corresponding to the consensus NF-kappa B binding site of the E-selectin gene (E-selectin-NF-kappa B) was used. Because NF-kappa B has been reported to be redox sensitive, we studied the effects of NAC on the EC redox environment. NAC caused an expected dramatic increase in the reduced glutathione (GSH) levels in EC. In vitro studies demonstrated that whereas the binding affinity of NF-kappa B to the VCAM-NF-kappa B oligomer peaked at a GSH-to-oxidized glutathione (GSSG) ratio of approximately 200 and decreased at higher ratios, the binding to the E-selectin-NF-kappa B oligomer appeared relatively unaffected even at ratios > 400, i.e., those achieved in EC treated with 40 mM NAC. These results suggest that NF-kappa B binding to its consensus sequences in the VCAM-1 and E-selectin gene exhibits marked differences in redox sensitivity, allowing for differential gene expression regulated by the same transcription factor. Our data also demonstrate that NAC increases the GSH-to-GSSG ratio within the EC suggesting one possible mechanism through which this antioxidant inhibits agonist-induced monocyte adhesion to EC.
VEZF1 Elements Mediate Protection from DNA Methylation (2010)

There is growing consensus that genome organization and long-range gene regulation involves partitioning of the genome into domains of distinct epigenetic chromatin states. Chromatin insulator or barrier elements are key components of these processes as they can establish boundaries between chromatin states. The ability of elements such as the paradigm beta-globin HS4 insulator to block the range of enhancers or the spread of repressive histone modifications is well established. Here we have addressed the hypothesis that a barrier element in vertebrates should be capable of defending a gene from silencing by DNA methylation. Using an established stable reporter gene system, we find that HS4 acts specifically to protect a gene promoter from de novo DNA methylation. Notably, protection from methylation can occur in the absence of histone acetylation or transcription. There is a division of labor at HS4; the sequences that mediate protection from methylation are separable from those that mediate CTCF-dependent enhancer blocking and USF-dependent histone modification recruitment. The zinc finger protein VEZF1 was purified as the factor that specifically interacts with the methylation protection elements. VEZF1 is a candidate CpG island protection factor as the G-rich sequences bound by VEZF1 are frequently found at CpG island promoters. Indeed, we show that VEZF1 elements are sufficient to mediate demethylation and protection of the APRT CpG island promoter from DNA methylation. We propose that many barrier elements in vertebrates will prevent DNA methylation in addition to blocking the propagation of repressive histone modifications, as either process is sufficient to direct the establishment of an epigenetically stable silent chromatin state.
Generation of BDDs from hardware algorithm descriptions (1996)

We propose a new method for generating BDDs from hardware algorithm descriptions written in a programming language. Our system can deal with control structures, such as conditional branches (if-then-else) and data dependent loops (while-end). Once BDDs are generated, we can immediately check the equivalence of two different algorithm descriptions just by comparing BDDs. This method can also be applied to verification between algorithm-level and gate-level designs. Another interesting application is to synthesize loop-free logic circuits from algorithm descriptions. We show the experimental results for some practical examples, such as Greatest Common Divisor (GCD) calculation. Although our method has a limitation in size of problems, it is very practical and useful for actual design verification.
Radioimmunoassay of type I collagen that mainly detects degradation products in serum: application to patients with liver diseases (1990)

This radioimmunoassay for type I collagen mainly detects degradation products of the molecule in human serum samples. Type I collagen antigenicity in serum can be separated into two peaks by gel-filtration chromatography. The larger form represents collagen molecules (as shown by immunoblotting experiments), and (or) type I collagen with aminoterminal propeptide or intact procollagen molecules. The smaller form, the exact nature of which is not known, is quantitatively the principal antigenic form and is derived from degradation of type I collagen. The concentration of type I collagen in serum is increased mainly in cirrhotic patients, with or without active liver disease, but also somewhat in alcoholic patients without cirrhosis.
The Waiter at the Party: A Parable of Ecosystem Management in the Everglades (2006)

Adaptive management has emerged as a response to the complexity of environmental policy implementation. Development, regulatory advances, and shortcomings, and other contextual nuances all conspire to complicate policymaking. In this Article, the author explores how to adapt to changing circumstances by adopting more flexible management strategies. He explains how horizontal, intergovernmental networks may facilitate policy implementation more efficiently and effectively than traditional legal or hierarchical structures. Using a case study of the Florida Everglades, he illustrates the inevitability of surprise and the importance of adaptive management for achieving results.