gebhart/patrepeval huggingface dataset:
The human papillomavirus type 18 (HPV18) E2 gene product is a repressor of the HPV18 regulatory region in human keratinocytes (1989)

The human papillomavirus type 18 (HPV18) long control region (LCR) harbors transcriptional promoter and enhancer elements. Recombinant plasmids bearing all or part of the HPV18 LCR cloned in enhancer or promoter configuration upstream of the chloramphenicol acetyltransferase (CAT) gene were transfected into human fibroblasts and keratinocytes. Although the HPV18 enhancer can function in the absence of E2 gene products in both fibroblasts and keratinocytes, the promoter activity of the HPV18 LCR is detectable in keratinocytes but not in fibroblasts, suggesting that it is tissue specific. This promoter activity was repressed in human keratinocytes not only by the bovine papillomavirus type 1 E2 gene product but also by the homologous HPV18 E2 gene product. The promoter involved in the HPV18 E2 repression is located within a 230-base-pair domain directly upstream of the E6 open reading frame of the HPV18 LCR and is probably the previously identified E6 promoter. Although one cannot rule out the possibility that this repressing effect is mediated by a truncated form of HPV18 E2 protein, as was previously demonstrated for bovine papillomavirus type 1, a more likely explanation would be that the full-length HPV18 E2 protein behaves as a repressor. Indeed, at the same doses at which it inhibits transcription from the homologous HPV18 LCR, the HPV18 E2 gene product activates transcription from constructs bearing E2-binding palindromes cloned in enhancer configuration upstream of a heterologous promoter. The fact that the homologous HPV18 E2 gene product acts as a transcriptional repressor of the HPV18 LCR suggests a possible explanation for the overexpression of E6 and E7 open reading frames in cervical carcinoma cells and in cell lines derived from them.
Structural and functional analysis of the ligand specificity of the HtrA2/Omi PDZ domain (2007)

The mitochondrial serine protease HtrA2/Omi helps to maintain mitochondrial function by handling misfolded proteins in the intermembrane space. In addition, HtrA2/Omi has been implicated as a proapoptotic factor upon release into the cytoplasm during the cell death cascade. The protein contains a C-terminal PDZ domain that packs against the protease active site and inhibits proteolytic activity. Engagement of the PDZ domain by peptide ligands has been shown to activate the protease and also has been proposed to mediate substrate recognition. We report a detailed structural and functional analysis of the human HtrA2/Omi PDZ domain using peptide libraries and affinity assays to define specificity, X-ray crystallography to view molecular details of PDZ-ligand interactions, and alanine-scanning mutagenesis to probe the peptide-binding groove. We show that the HtrA2/Omi PDZ domain recognizes both C-terminal and internal stretches of extended, hydrophobic polypeptides. High-affinity ligand recognition requires contacts with up to five hydrophobic side chains by distinct sites on the PDZ domain. However, no particular residue type is absolutely required at any position, and thus, the HtrA2/Omi PDZ domain appears to be a promiscuous module adapted to recognize unstructured, hydrophobic polypeptides. This type of specificity is consistent with the biological role of HtrA2/Omi in mitochondria, which requires the recognition of diverse, exposed stretches of hydrophobic sequences in misfolded proteins. The findings are less consistent with, but do not exclude, a role for the PDZ domain in targeting the protease to specific substrates during apoptosis.
Sonication Power for Length Control of Single-Walled Carbon Nanotubes in Aqueous Suspensions Used for 2-Dimensional Network Formation (2010)

Control over the average length of single-walled carbon nanotubes (SWNTs) in suspension is of critical importance to characterizing and developing flexible, transparent thin films that use percolative transport to achieve reproducibility in electronic properties. This paper demonstrates how the average length of SWNTs in aqueous suspensions can be controlled by the conditions used to form (sonication) and purify (low-G centrifugation) the dispersions. The effect of ultrasonic probe sonication, which was used to disperse SWNT bundles into suspension, on the length and extent of defects on the nanotubes was investigated via atomic force microscopy (AFM) and confocal Raman spectroscopy, respectively. Quantitative information about the suspension concentration and the effect of sonication power on unbundling the SWNTs was obtained via UV−vis and near-IR spectroscopy, respectively. To obtain a clear understanding of the effect of sonication power on SWNT suspensions, repeated low-G centrifugation cycles were used to remove impurities such as bundles of SWNTs, amorphous carbon, and catalyst nanoparticles. This nonoxidizing purification method, which was performed prior to all analyses, allows direct determination of the effect of sonication power on defect formation.
Enzyme histochemistry and immunohistochemistry on biopsy specimens of pathologic human bone marrow (1981)

We have systematically investigated a variety of fixation and plastic embedding procedures and arrived at a method that allows processing of approximately 2-micron sections of bone marrow biopsies for examination by light microscopy. More importantly, this method permits the use of enzyme histochemical and immunohistochemical procedures that are rapidly becoming mandatory in the diagnosis of hematologic malignancies. Over 200 full-length bone marrow biopsy specimens were fixed in a mixture of paraformaldehyde, glutaraldehyde, and acrolein, dehydrated in acetone, and embedded in a mixture of methyl and glycolmethacrylate. All procedures were carried out at 4 degrees C. Decalcification was unnecessary. Sections 2-micron thick were cut and incubated for peroxidase, naphthol AS-D chloroacetate esterase, alpha- naphthyl butyrate esterase, acid phosphatase (with and without tartrate), or alkaline phosphatase and then examined by light microscopy. Specimens could be prepared for examination within 48 hr. This approach, which provides definitive markers for various hematopoietic cell lines in intact tissues, is invaluable when aspirated material is unavailable. It is also useful in the analysis of focal lesions of bone marrow due to inflammation or neoplasia and shows potential as an investigative tool. For example, we have discovered that early myelofibrosis is accompanied by a marked increase in the number of alkaline-phosphatase-positive reticulum cells.
PortraitSketch (2014)

We present PortraitSketch, an interactive drawing system that helps novices create pleasing, recognizable face sketches without requiring prior artistic training. As the user traces over a source portrait photograph, PortraitSketch automatically adjusts the geometry and stroke parameters (thickness, opacity, etc.) to improve the aesthetic quality of the sketch. We present algorithms for adjusting both outlines and shading strokes based on important features of the underlying source image. In contrast to automatic stylization systems, PortraitSketch is designed to encourage a sense of ownership and accomplishment in the user. To this end, all adjustments are performed in real-time, and the user ends up directly drawing all strokes on the canvas. The findings from our user study suggest that users prefer drawing with some automatic assistance, thereby producing better drawings, and that assistance does not decrease the perceived level of involvement in the creative process.
Immunodominance in Virus-Induced CD8 + T-Cell Responses Is Dramatically Modified by DNA Immunization and Is Regulated by Gamma Interferon (2002)

The phenomenon whereby the host immune system responds to only a few of the many possible epitopes in a foreign protein is termed immunodominance. Immunodominance occurs not only during microbial infection but also following vaccination, and clarification of the underlying mechanism may permit the rational design of vaccines which can circumvent immunodominance, thereby inducing responses to all epitopes, dominant and subdominant. Here, we show that immunodominance affects DNA vaccines and that the effects can be avoided by the simple expedient of epitope separation. DNA vaccines encoding isolated dominant and subdominant epitopes induce equivalent responses, confirming a previous demonstration that coexpression of dominant and subdominant epitopes on the same antigen-presenting cell (APC) is central to immunodominance. We conclude that multiepitope DNA vaccines should comprise a cocktail of plasmids, each with its own epitope, to allow maximal epitope dispersal among APCs. In addition, we demonstrate that subdominant responses are actively suppressed by dominant CD8(+) T-cell responses and that gamma interferon (IFN-gamma) is required for this suppression. Furthermore, priming of CD8(+) T cells to a single dominant epitope results in strong suppression of responses to other normally dominant epitopes in immunocompetent mice, in effect rendering these epitopes subdominant; however, responses to these epitopes are increased 6- to 20-fold in mice lacking IFN-gamma. We suggest that, in agreement with our previous observations, IFN-gamma secretion by CD8(+) T cells is highly localized, and we propose that its immunosuppressive effect is focused on the APC with which the dominant CD8(+) T cell is in contact.
Interaction of heparin with fibronectin and isolated fibronectin domains (1990)

Fluorescence polarization, gel exclusion chromatography and affinity chromatography were used to characterize the interaction of heparins of different size with human plasma fibronectin (Fn) and several of its isolated domains. The fluid-phase interaction of Fn with heparin was dominated by the 30 kDa and 40 kDa Hep-2 domains located near the C-terminal ends of the A and B chains respectively. The 30 kDa Hep-2A domain from the heavy chain was indistinguishable from the 40 kDa Hep-2B domain in this respect; the presence of an additional type III homology unit in the latter had no effect on the binding. Evidence was provided that each Hep-2 domain has two binding sites for heparin. The N-terminal Hep-1 domain reacted weakly in fluid phase even though it binds strongly to immobilized heparin. Fn and Hep-2 fragments were rather undiscriminating in their reaction with fluoresceinamine-labelled heparins of different sizes. However, oligosaccharides smaller than the tetradecasaccharide (14-mer) bound Fn with a 5-10-fold lower affinity. These results suggest that the Hep-2 domains of Fn are able to recognize a broad spectrum of oligosaccharides that presumably vary significantly with respect to the amount and spatial distribution of charge.
Molecular Pharmacology of Botulinum Toxin and Tetanus Toxin (1986)

Botulinum toxin is a term that has been used to describe eight different substances designated types A, B, Cb C2, D, E, F, and G. For many years it was assumed that these eight substances acted at the neuromuscular junction to block acetylcholine release. It is now known that this assumption is not entirely correct. Seven Of the substances do act at cholinergic junctions (types A, B, C b D, E, F, and G), and they are properly referred to as botulinum neurotoxins. The eighth substance (type C2) is unique in its structure and pharmacological actions. It is called the botulinum binary toxin. Tetanus toxin is a term that has been used to describe a single substance that acts mainly in the central nervous system to block inhibitory transmission. There are many similarities between tetanus toxin and botulinum neurotoxin, including a common origin, a closely related structure, and perhaps the same subcellular mechanism of action. The similarities between tetanus toxin and the botulinum binary toxin are less clear. The purpose of the present review is to discuss the proposed mechanism( s) of action of the three groups of clostridial toxins. Recent findings suggest that research is moving quickly toward a full determination of the cellular and subcellular actions of these substances. This is an encouraging tum of events, because the clostridial toxins are generally regarded as the most poisonous substances known to mankind.
A New Phosphodiesterase Forming Nucleoside 5'-Monophosphate from Rat Liver (1967)

Abstract A new phosphodiesterase forming nucleoside 5'-monophosphate from oligonucleotide has been purified 200-fold from a rat liver homogenate. This phosphodiesterase hydrolyzes p-nitrophenyl esters of nucleoside 5'-monophosphate and various oligonucleotides at approximately the same rapid rates, whereas it hydrolyzes DNA and RNA very slowly. The degradation products are all nucleoside 5'-monophosphates, showing no base specificity. Evidence is given that the initial site of attack is at the 3'-hydroxyl end of the oligonucleotide. The phosphodiesterase also hydrolyzes NAD and a new polymer synthesized from NAD (27–30) by isolated rat liver nuclei. The phosphodiesterase has an optimum pH at around 10. It is heat-labile and sensitive to ethylenediaminetetraacetic acid.
Chromosomal DNA patterns and gene stability of Pichia pastoris (1998)

We have clearly resolved four chromosomal bands from four Pichia pastoris (Komagataella pastoris) strains by using contour-clamped homogeneous electric field gel electrophoresis. The size of the P. pastoris chromosomal bands ranged from 1·7 Mb to 3·5 Mb and total genome size was estimated to be 9·5 Mb to 9·8 Mb; however, chromosome-length polymorphisms existed among four strains. Thirteen cloned genes isolated from strain GTS115 were assigned to the separated chromosomes, revealing that different hybridization patterns were observed in the AOX2 and URA3 genes among strains. P. pastoris is frequently used as an efficient host for heterologous gene expressions. We analysed chromosomal stability of strain GTS115-derived recombinant cell expressing human serum albumin during serial cultivation under the condition of vegetative and non-selective growth. No chromosomal rearrangements were observed and the expression constructs integrated into the his4 locus on chromosome I were very stable even at 83 generations, suggesting that stable expression would be carried out even in large-scale fermentation. © 1998 John Wiley & Sons, Ltd.
Antiviral Agents and Viral Diseases of Man (1990)

The recent explosion of research concerning the human immunodeficiency virus has advanced the understanding of a variety of viral infections and spurred the development of new antiviral agents. Drs Galasso, Whitley, and Merigan have made significant changes in their text, which was last revised in 1984. This new edition succeeds in incorporating the latest understanding of viral diseases and their therapy into one volume.
Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate Autoimmune Enteropathy Independently of Regulatory T Cells (2008)

Cell-based tolerogenic therapy is a relatively new approach for the treatment of autoimmune diseases. Mesenchymal stem cells (MSCs) have been shown to be potent immunomodulatory agents in a number of experimental and clinical scenarios; however, their use in various autoimmune diseases is undefined. Herein, we report the efficacy of MSC transplantation in a multiorgan autoimmunity model. Mice with defective peripheral tolerance caused by a deficiency in regulatory T cells were used as a testbed for therapy. After screening multiple target tissues of autoimmune attack, we observed an MSC-specific improvement in the histopathology of the distal ileum of treated mice. We then showed that MSCs can reduce mesenteric lymph node (MLN) cellularity in autoimmune mice during active disease and decrease activated T-cell populations in the MLN. Trafficking studies using enhanced green fluorescent protein (eGFP)-reporter MSCs revealed no appreciable engraftment in the intestine, but it did reveal the presence of eGFP+ cells organized in clusters within the MLN, as well as ancillary nodes. Semiquantitative analysis showed no difference in the number of clusters; however, eGFP+ cells in MLNs compared with ancillary nodes had distinct fibroblastoid morphology and formed a network with neighboring eGFP+ cells. Finally, we show evidence that transplantation of MSCs caused global immunosuppression, as measured by increased CD4+ CD8+ thymocyte production and serum interleukin-10 and decreased serum interferon-gamma. These data implicate the intestine as a new site of MSC tolerance induction and should motivate additional studies evaluating the use of MSCs as a treatment for autoimmune enteropathies.
A Low-Power Single-Weight-Combiner 802.11abg SoC in 0.13 µm CMOS for Embedded Applications Utilizing An Area and Power Efficient Cartesian Phase Shifter and Mixer Circuit (2008)

A low-power 802.11abg SoC which achieves the best reported sensitivity as well as lowest reported power consumption and utilizes an extensive array of auto calibrations is reported. This SoC utilizes a two-antenna array receiver to build a single weight combiner (SWC) system. A new signal-path Cartesian phase generation and combination technique is proposed that shifts the RF signal in 22.5deg phase steps. A 3 dB improvement in received SNR is achieved in comparison to the single path receiver. The radio and AFE occupy 10 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> of area in a digital 0.13 mum CMOS process of which 0.29 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> is occupied by the SWC RF receiver. The radio+AFE consume 85 mW of power in active Rx mode of which 30 mW is utilized by the SWC RF front-end.
Bcr-Abl Exerts Its Antiapoptotic Effect Against Diverse Apoptotic Stimuli Through Blockage of Mitochondrial Release of Cytochrome C and Activation of Caspase-3 (1998)

Bcr-Abl expression in leukemic cells is known to exert a potent effect against apoptosis due to antileukemic drugs, but its mechanism has not been elucidated. Recent reports have indicated that a variety of apoptotic stimuli cause the preapoptotic mitochondrial release of cytochrome c (cyt c) into cytosol, which mediates the cleavage and activity of caspase-3 involved in the execution of apoptosis. Whether Bcr-Abl exerts its antiapoptotic effect upstream to the cleavage and activation of caspase-3 or acts downstream by blocking the ensuing degradation of substrates resulting in apoptosis, has been the focus of the present studies. In these, we used (1) the human acute myelogenous leukemia (AML) HL-60 cells that are stably transfected with thebcr-abl gene (HL-60/Bcr-Abl) and express p185 Bcr-Abl; and (2) the chronic myelogenous leukemia (CML)-blast crisis K562 cells, which have endogenous expression of p210 Bcr-Abl. Exposure of the control AML HL-60 cells to high-dose Ara-C (HIDAC), etoposide, or sphingoid bases (including C2 ceramide, sphingosine, or sphinganine) caused the accumulation of cyt c in the cytosol, loss of mitochondrial membrane potential (MMP), and increase in the reactive oxygen species (ROS). These preapoptotic events were associated with the cleavage and activity of caspase-3, resulting in the degradation of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) and DNA fragmentation factor (DFF), internucleosomal DNA fragmentation, and morphologic features of apoptosis. In contrast, in HL-60/Bcr-Abl and K562 cells, these apoptotic stimuli failed to cause the cytosolic accumulation of cyt c and other associated mitochondrial perturbations, as well as the failure to induce the activation of caspase-3 and apoptosis. While the control HL-60 cells showed high levels of Bcl-2 and barely detectable Bcl-xL, HL-60/Bcr-Abl cells expressed high levels of Bcl-xL and undetectable levels of Bcl-2, a pattern of expression similar to the one in K562 cells. Bax and caspase-3 expressions were not significantly different between HL-60/Bcr-Abl or K562 versus HL-60 cells. These findings indicate that Bcr-Abl expression blocks apoptosis due to diverse apoptotic stimuli upstream by preventing the cytosolic accumulation of cyt c and other preapoptotic mitochondrial perturbations, thereby inhibiting the activation of caspase-3 and execution of apoptosis.
Centromere structure and function in budding and fission yeasts. (1990)

Functional centromeric DNAs have now been isolated and characterized from both budding (Saccharomyces cerevisiae) and fission (Schizosaccharomyces pombe) yeasts. Artificial chromosomes containing these centromere DNA sequences segregate faithfully in both mitotic and meiotic cell divisions, but only in the parent organism. Structure-function analyses have revealed surprising fundamental differences between these two centromere classes. In the budding yeast centromeres, a 125-bp consensus DNA sequence contains all the information needed in cis to provide proper chromosome segregation. In contrast, the fission yeast centromeres each contain a long run (40 to 100 kb) of untranscribed repetitive DNA sequences arranged into a large inverted repeat, most of which is required for full centromere function. The fission yeast centromere-kinetochore appears to be a highly relevant experimental model for analysis of the mechanism of chromosome segregation in higher eukaryotes, in which the centromere regions often contain megabases of transcriptionally silent repetitive DNA sequences of unknown function.
Modulation of human natural killer T cell ligands on TLR-mediated antigen-presenting cell activation (2007)

Invariant natural killer T (iNKT) cells are a subset of nonconventional T cells recognizing endogenous and/or exogenous glycolipid antigens in the context of CD1d molecules. It remains unclear whether innate stimuli can modify the profile of endogenous lipids recognized by iNKT cells on the surface of antigen-presenting cells (APCs). We report that activation of human APCs by Toll-like receptor ligands (TLR-L) modulates the lipid biosynthetic pathway, resulting in enhanced recognition of CD1d-associated lipids by iNKT cells, as defined by IFN-gamma secretion. APC-derived soluble factors further increase CD1d-restricted iNKT cell activation. Finally, using soluble tetrameric iNKT T cell receptors (TCR) as a staining reagent, we demonstrate specific up-regulation of CD1d-bound ligand(s) on TLR-mediated APC maturation. The ability of innate stimuli to modulate the lipid profile of APCs resulting in iNKT cell activation and APC maturation underscores the role of iNKT cells in assisting priming of antigen-specific immune responses.
The recoverability limit for superresolution via sparsity (2015)

We consider the problem of robustly recovering a $k$-sparse coefficient vector from the Fourier series that it generates, restricted to the interval $[- Ω, Ω]$. The difficulty of this problem is linked to the superresolution factor SRF, equal to the ratio of the Rayleigh length (inverse of $Ω$) by the spacing of the grid supporting the sparse vector. In the presence of additive deterministic noise of norm $σ$, we show upper and lower bounds on the minimax error rate that both scale like $(SRF)^{2k-1} σ$, providing a partial answer to a question posed by Donoho in 1992. The scaling arises from comparing the noise level to a restricted isometry constant at sparsity $2k$, or equivalently from comparing $2k$ to the so-called $σ$-spark of the Fourier system. The proof involves new bounds on the singular values of restricted Fourier matrices, obtained in part from old techniques in complex analysis.