gebhart/patrepeval huggingface dataset:
Epigenetic Modification of Transgenes under the Control of the Mouse Mammary Tumor Virus LTR: Tissue-Dependent Influence on Transcription of the Transgenes (1996)

Transgenic mice expressing human urokinase, as well as animals expressing human urokinase receptor under the control of the murine mammary tumor virus (MMTV) long terminal repeat, were established. In the vast majority of the founder animals and their descendants, the transgene was completely methylated, corresponding to down-regulation of transgene expression in the mammary gland. Two lineages with human urokinase receptor as the transgene with mixed methylation of the transgenes were analyzed in more detail. We show here for the first time that the methylation status of the transgene is identical in different organs of an animal, but may differ from animal to animal among the descendents. In the mammary gland, complete methylation of the transgene was incompatible with expression; unmethylated and mixed methylation transgenes gave rise to expression at the RNA as well as at the protein level. The methylation observed was not the consequence of an imprinting process. Surprisingly, in organs other than the mammary gland, such as liver, kidney and spleen, weak expression of the transgene was noted independent of the methylation status of the MMTV promoter. With respect to the molecular mechanism it is unresolved whether the human growth hormone sequence of the transgene harbors a methylation inducing element responsible for the observed methylation pattern.
Assembly of Cell Regulatory Systems Through Protein Interaction Domains (2003)

The sequencing of complete genomes provides a list that includes the proteins responsible for cellular regulation. However, this does not immediately reveal what these proteins do, nor how they are assembled into the molecular machines and functional networks that control cellular behavior. The regulation of many different cellular processes requires the use of protein interaction domains to direct the association of polypeptides with one another and with phospholipids, small molecules, or nucleic acids. The modular nature of these domains, and the flexibility of their binding properties, have likely facilitated the evolution of cellular pathways. Conversely, aberrant interactions can induce abnormal cellular behavior and disease. The fundamental properties of protein interaction domains are discussed in this review and in detailed reviews on individual domains at Science's STKE at http://www.sciencemag.org/cgi/content/full/300/5618/445/DC1.
Estimation of Mechanical Properties of Al/Cu Compound Layer Formed by Impact Welding (2005)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
Cognate peptide-induced destruction of CD8+ cytotoxic T lymphocytes is due to fratricide. (1993)

In the absence of other cells, cloned CTL in culture can undergo massive destruction upon the addition of a peptide that is recognized, in association with the CTL's class I MHC proteins, by the CTL's Ag-specific TCR. To determine whether the destruction is a result of the individual CTL's recognition via its own TCR of peptide-MHC-I complexes on its own surface ("suicide"), or to cytolytic attack by some CTL on others in the same culture ("fratricide"), we compared the rate of peptide-induced cell death in conventional cultures, where CTL are free to establish cell-cell contacts, with other cultures in which individual CTL were prevented from forming cell-cell contacts by encasing them individually in agarose gel microdrops. The differences were dramatic: in the presence of high concentrations of peptide (10 millionfold greater than is necessary to support 50% lysis of conventional target cells by these CTL) cell death was linear over 0 to 8 h in conventional cultures, at a rate of about 10% per hour, whereas in the presence of the same high concentration of peptide over the same time course, no death was detected among the cells encased in agarose gel microdroplets. The results demonstrate an absolute requirement for cell-cell contact in the destruction of cloned CTL in culture with their cognate peptides at high concentration. Using an increase of intracellular calcium ion concentration ([Ca2+]i) as a measure of T-cell activation, we also found that peptide-dependent activation of CTL likewise depends upon cell-cell contact.
Elevated globotriaosylsphingosine is a hallmark of Fabry disease (2008)

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of alpha-galactosidase A that affects males and shows disease expression in heterozygotes. The characteristic progressive renal insufficiency, cardiac involvement, and neuropathology usually are ascribed to globotriaosylceramide accumulation in the endothelium. However, no direct correlation exists between lipid storage and clinical manifestations, and treatment of patients with recombinant enzymes does not reverse several key signs despite clearance of lipid from the endothelium. We therefore investigated the possibility that globotriaosylceramide metabolites are a missing link in the pathogenesis. We report that deacylated globotriaosylceramide, globotriaosylsphingosine, and a minor additional metabolite are dramatically increased in plasma of classically affected male Fabry patients and plasma and tissues of Fabry mice. Plasma globotriaosylceramide levels are reduced by therapy. We show that globotriaosylsphingosine is an inhibitor of alpha-galactosidase A activity. Furthermore, exposure of smooth muscle cells, but not fibroblasts, to globotriaosylsphingosine at concentrations observed in plasma of patients promotes proliferation. The increased intima-media thickness in Fabry patients therefore may be related to the presence of this metabolite. Our findings suggest that measurement of circulating globotriaosylsphingosine will be useful to monitor Fabry disease and may contribute to a better understanding of the disorder.
Physicochemical Foundations and Structural Design of Hydrogels in Medicine and Biology (2000)

Hydrogels are cross-linked hydrophilic polymers that can imbibe water or biological fluids. Their biomedical and pharmaceutical applications include a very wide range of systems and processes that utilize several molecular design characteristics. This review discusses the molecular structure, dynamic behavior, and structural modifications of hydrogels as well as the various applications of these biohydrogels. Recent advances in the preparation of three-dimensional structures with exact chain conformations, as well as tethering of functional groups, allow for the preparation of promising new hydrogels. Meanwhile, intelligent biohydrogels with pH- or temperature-sensitivity continue to be important materials in medical applications.
Optimal estimation for error concealment in scalable video coding (2002)

This work is concerned with scalable video coding and, specifically, with error concealment for the mitigation of damage caused by packet loss at the enhancement layer. We propose a frequency-domain error concealment scheme that makes full use of the information available at the decoder from both the current base layer, and prior enhancement layer frames. It employs a statistical model for the evolution of transform coefficients from frame to frame and implements the optimal estimate of the reconstructed coefficient. Moreover, the ideas underlying the proposed approach allow detection and correction of blocks that suffer from significant error propagation from past losses. Substantial PSNR gains are observed in the experiments.
Impact of Pre-Existing Immunity on Gene Transfer to Nonhuman Primate Liver with Adeno-Associated Virus 8 Vectors (2011)

Vectors based on the primate-derived adeno-associated virus serotype 8 (AAV8) are being evaluated in preclinical and clinical models. Natural infections with related AAVs activate memory B cells that produce antibodies capable of modulating the efficacy and safety of the vector. We have evaluated the biology of AAV8 gene transfer in macaque liver, with a focus on assessing the impact of pre-existing humoral immunity. Twenty-one macaques with various levels of AAV neutralizing antibody (NAb) were injected intravenously with AAV8 vector expressing green fluorescent protein. Pre-existing antibody titers in excess of 1:10 substantially diminished hepatocyte transduction that, in the absence of NAbs, was highly efficient. Vector-specific NAb diminished liver deposition of genomes and unexpectedly increased genome distribution to the spleen. The majority of animals showed high-level and stable sequestration of vector capsid protein by follicular dendritic cells of splenic germinal centers. These studies illustrate how natural immunity to a virus that is related to a vector can impact the efficacy and potential safety of in vivo gene therapy. We propose to use the in vitro transduction inhibition assay to evaluate research subjects before gene therapy and to preclude from systemic AAV8 trials those that have titers in excess of 1:10.
Nucleoside syntheses, XXII1) Nucleoside synthesis with trimethylsilyl triflate and perchlorate as catalysts (1981)

Abstract The novel Lewis acids (CH 3 ) 3 SiOSO 2 CF 3 ( 3 ), (CH 3 ) 5 SiOSO 2 C 4 F 9 ( 6 ), and (CH 3 ) 3 SiClO 4 ( 4 ) are highly selective and efficient Friedel‐Crafts catalysts for nucleoside formation form silylated heterocycles and peracylated sugars as well as for rearrangements of persilylated protected nucleosides. With basic silylated heterocycles these new catalysts give much higher yields of the natural N ‐1‐nucleosides than with SnCl 4 .
Abstract 167: Targeting non-coding RNAs with the CRISPR/Cas9 system in human cell lines (2015)

Abstract The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system (CRISPR/Cas) has been recently shown to be a powerful genome-editing tool in a variety of organisms. However, these studies are mainly focused on protein-coding genes. The present study aims to determine whether this technology can be applied to non-coding genes. One of the challenges for knockout of non-coding genes is that a small deletion or insertion generated by the standard CRISPR/Cas system may not necessarily lead to functional loss of a given non-coding gene because of lacking an open reading frame, especially in polyploidy human cell lines. To overcome this challenge, we adopt a selection system that allows for marker genes to integrate into the genome through homologous recombination (HR). Moreover, we construct a dual guide RNA vector that can make two cuts simultaneously at designated sites such that a large fragment can be deleted. With these approaches, we are able to successfully generate knockouts for miR-21, miR-29a, lncRNA-21A, UCA1 and AK023948 in various human cell lines. Finally, we show that the HR-mediated targeting efficiency can be further improved by suppression of the non-homologous end joining pathway. Together, these results demonstrate the feasibility of knockout for non-coding genes by the CRISPR/Cas system in human cell lines. Citation Format: Tsui-Ting Ho, Nanjiang Zhou, Jianguo Huang, Pratirodh Koirala, Min Xu, Roland Fung, Fangting Wu, Yin-Yuan Mo. Targeting non-coding RNAs with the CRISPR/Cas9 system in human cell lines. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 167. doi:10.1158/1538-7445.AM2015-167
Syntax and semantics in a word-sequence recognition system (2005)

A recognizer of meaningful sequences of isolated words spoken in the Italian language is presented. The system has been designed in a modular fashion and the current version has been obtained by adding the syntactic and semantic levels to the isolated-word recognizer previously developed by the same authors. The lexical, syntactic and semantic levels are integrated into a hierarchical knowledge source represented by a transition network grammar. The parsing is directed by the control unit and is performed by means of a combined strategy of bottom-up and top-down techniques, using a modified version of the Earley algorithm. Lexical hypotheses are verified at the phonemic level assigning them a score based on a distance measure evaluated by an error-correcting parsing algorithm. The protocol used in the preliminary experi - ments is a robot command language.
Biomaterials to Spatially Regulate Cell Fate (2002)

Cell fate can be directed by material-derived signals and an appropriate combination of signals can direct distinct cell fates. Adhesive ligands promote the multiplication of cells in direct contact with the signal, while the calcium gradient resulting from its release spatially regulates the ability of cells to differentiate (see Figure for an example of myoblasts that have formed muscle tissue).
Stereoselective hydroxyalkylations of (S)‐2‐azetidinecarboxylic acid (1990)

Abstract The enolate generated from S ‐phenyl ( S )‐1‐benzyl‐2‐azetidinecarbothioate is converted into racemic products 2 by treatment with electrophiles. The bicyclic oxazolidinone derivative 12 has been prepared from trimethylsilyl ( S )‐1‐(trimethylsilyl)‐2‐azetidinecarboxylate ( 11 ) and pivalaldehyde without racemization. Addition of 12 to aldehydes and hydrolysis gives the products 13 a‐h . The structure of the adduct 13 h from 4‐pyridinecarbaldehyde was determined by X‐ray crystal structure analysis, proving that the trigonal centers of the bicyclic enolate and of the aldehyde have combined with relative topicity unlike . Thus, the reaction resembles that of the homologous proline derivative described previously, and the novel products are formally D ‐ allo ‐threonines with an ethylene bridge between the nitrogen and the adjacent carbon atoms (Scheme 4) and with absolute configuration R , R . The mechanism of the C  C bond‐forming reaction is discussed.
Atomic force microscopy of DNA molecules (1992)

DNA-cytochrome c complexes adsorbed on carbon-coated mica surfaces were directly imaged by atomic force microscopy in air using commercially available cantilevers, with a routine resolution of 6 nm. Images of M13 phage DNA and M13-DNA polymerase complex are also shown.
Towards a Memetic Feature Selection Paradigm [Application Notes (2010)

Feature selection has become the focus of many real-world application oriented developments and applied research in recent years. With the rapid advancement of computer and database technologies, problems "with hundreds and thousands of variables or features are now ubiquitous in pattern recognition, data mining, and machine learning [1], [2]. In this article, we consider two real-world feature selection applications: gene selection in cancer classification based on microarray data and band selection for pixel classification using hyperspectral imagery data.
Purification and characterization of CMP-N-acetylneuraminic acid:lactosylceramide (alpha 2-3) sialyltransferase (GM3-synthase) from rat brain. (1993)

CMP-N-acetylneuraminic acid:lactosylceramide (alpha 2-3) sialyltransferase (GM3-synthase) was purified to homogeneity from a Triton CF-54 extract of young rat brain. The enzyme was separated by affinity chromatography on CDP-Sepharose column and resolved by linear NaCl gradient elution from the same adsorbent. Final purification of GM3-synthase was achieved by chromatography on a "lactosylceramide acid"-Sepharose column and specific elution with lactosylceramide. The enzyme activity was highest at pH 6.5 and required the presence of Triton CF-54 (0.15%) and Mn2+ (10 mM) for its full activity. The product of the reaction catalyzed by the enzyme was identified as GM3 based on its mobility on thin layer chromatographic plates using two different solvent systems. Comparison with several glycolipid substrates showed high specificity of GM3-synthase for lactosylceramide. The apparent Km value for lactosylceramide and CMP-N-acetylneuraminic acid were 80 and 210 microM, respectively. The apparent molecular mass of the enzyme determined on SDS-polyacrylamide gel electrophoresis was 76 kDa.
Experience in Acid Diversion in High Permeability Deep Water Formations Using Visco-Elastic-Surfactant (2001)

Abstract It is a great challenge to divert acid into untreated zones in a thick, heterogeneous, and high permeability sandstone formation. The heterogeneity can be created by hydraulic fracturing, acidizing, or the nature of the reservoir. Common diverting agents do not work well in these situations. In high permeability porous media, foam has the tendency to segregate, gaseous phase will occupy smaller pores while the aqueous phase occupies the larger pores1. Due to the relative permeability effect, the higher permeability streaks becomes the preferable path for acid treatment fluids2. Therefore, limited effective diversion can be achieved by foam. Other diverting agents rely on particulate matter or polymer solution to plug off thief zones temporarily. However, the invasion of the undissolved particles and polymer residue can cause further formation damage. Owing to its rheological properties, and its lack of solids, Visco-Elastic-Surfactant diverting agents (VESDA) have been proven to be effective for acid diversion in carbonate formations3, where large flow channels are generated due to acid-rock reaction. This current study extends the application into diversion in high permeability, highly heterogeneous sandstone formations. Throughout this paper, the term VESDA is used to refer to the VES diverting agent. Laboratory tests have shown that VES is capable of increasing the flow resistance in the high permeability rock (simulated by a proppant pack) and will divert treatment fluid into the low permeability sandstone matrix. The process was more efficient if multiple stages of alternating VES and acid were used. Field case histories in Gulf of Mexico are also presented in this study to demonstrate the effectiveness of the VES material for acid diversion in the highly permeable and heterogeneous sandstone reservoirs.
Vibrational circular dichroism of N-acetyl-l-cysteine protected gold nanoparticles (2005)

Vibrational circular dichroism is used to determine the conformation of a thiol adsorbed on gold nanoparticles.
Antibodies against Vascular Endothelial Growth Factor Improve Early Renal Dysfunction in Experimental Diabetes (2001)

Vascular endothelial growth factor (VEGF) is a cytokine that potently stimulates angiogenesis, microvascular hyperpermeability, and endothelium-dependent vasodilation, effects that are largely mediated by endothelial nitric oxide synthase (eNOS). The expression of VEGF is pronounced in glomerular visceral epithelial cells, but its function in renal physiology and pathophysiology is unknown. VEGF expression is upregulated by high ambient glucose concentrations in several cell types in vitro and in glomeruli of diabetic rats. To assess the role of VEGF in the pathophysiology of early renal dysfunction in diabetes, monoclonal anti-VEGF antibodies (Ab) were administered to control and streptozotocin-induced diabetic rats for 6 wk after induction of diabetes. Based on in vitro binding studies, an adequate serum VEGF inhibitory activity was achieved during the entire course of anti-VEGF Ab administration. Anti-VEGF Ab treatment but not administration of isotype-matched control Ab decreased hyperfiltration, albuminuria, and glomerular hypertrophy in diabetic rats. VEGF blockade also prevented the upregulation of eNOS expression in glomerular capillary endothelial cells of diabetic rats. Antagonism of VEGF had no effect on GFR and glomerular volume in control rats. These results identify VEGF as a pathogenetic link between hyperglycemia and early renal dysfunction in diabetes. Targeting VEGF may prove useful as a therapeutic strategy for the treatment of early diabetic nephropathy.
Cleavage of IgGs by proteases associated with invasive diseases (2010)

The effective functioning of immunoglobulins and IgG mAbs in removing pathological cells requires that the antigen binding regions and the Fc (effector) domain act in concert. The hinge region that connects these domains itself presents motifs that engage Fc receptors on immune effector cells to achieve cell lysis. In addition, sequences in the lower hinge/CH2 and further down the CH2 region are involved in C1q binding and complement-mediated cell killing. Proteolytic enzymes of little relevance to human physiology were successfully used for decades to generate fragments of IgGs for reagent and therapeutic use. It was subsequently noted that tumor-related and microbial proteases also cleaved human IgG specifically in the hinge region. We have shown previously that the "nick" of just one of the lower hinge heavy chains of IgG unexpectedly prevented many effector functions without impacting antigen binding. Of interest, related single-cleaved IgG breakdown products were detected in breast carcinoma extracts. This suggested a pathway by which tumors might avoid host immune surveillance under a cloak of proteolytically-generated, dysfunctional antibodies that block competent IgG binding. The host immune system cannot be blind to this pathway since there exists a widespread, low-titer incidence of anti-hinge (cleavage-site) antibodies in the healthy population. The prevalence of anti-hinge reactivity may reflect an ongoing immune recognition of normal IgG catabolism. Tumor growth and bacterial infections potentially generate hostile proteolytic environments that may pose harsh challenges to host immunity. Recent findings involving physiologically-relevant proteases suggest that the potential loss of key effector functions of host IgGs may result from subtle and limited proteolytic cleavage of IgGs and that such events may facilitate the incursion of invasive cells in local proteolytic settings.
Using an AMACR (P504S)/34βE12/p63 Cocktail for the Detection of Small Focal Prostate Carcinoma in Needle Biopsy Specimens (2005)

We assessed the usefulness of immunohistochemical analysis with a 3-antibody cocktail (alpha-methylacyl coenzyme A racemase [AMACR, or P504S], 34betaE12, p63) and a double-chromogen reaction for detection of limited prostate cancer in 138 needle biopsy specimens, including 82 with small foci of prostatic adenocarcinoma and 56 benign prostates. When carcinoma was present, red cytoplasmic granular staining (AMACR) in the malignant glands and cells and dark brown nuclear (p63) and cytoplasmic (34betaE12) staining in basal cells of adjacent nonmalignant glands were found. Of 82 cases of small foci of prostatic adenocarcinoma, 78 (95%) expressed AMACR; all malignant glands were negative for basal cell staining. All benign glands adjacent to malignant glands were recognized easily by basal cell marker positivity and little or no AMACR expression. No benign glands were simultaneously positive for AMACR and negative for basal cell markers (specificity, 100%). There were no differences in intensity and numbers of positive glands with double-chromogen staining compared with using 1-color staining. Our results indicate that immunohistochemistry with a 3-antibody cocktail and double chromogen is a simple and easy assay that can be used as a routine test, which overcomes the problems of studying small lesions in prostate needle biopsies with multiple immunohistochemical stains.