gebhart/patrepeval huggingface dataset:
Hepatitis C virus internal ribosome entry site RNA contains a tertiary structural element in a functional domain of stem-loop II (2001)

The internal ribosome entry site (IRES) of hepatitis C virus (HCV) RNA contains >300 bases of highly conserved 5'-terminal sequence, most of it in the uncapped 5'-untranslated region (5'-UTR) upstream from the single AUG initiator triplet at which translation of the HCV polyprotein begins. Although progress has been made in defining singularities like the RNA pseudoknot near this AUG, the sequence and structural features of the HCV IRES which stimulate accurate and efficient initiation of protein synthesis are only partially defined. Here we report that a region further upstream from the AUG, stem-loop II of the HCV IRES, also contains an element of local tertiary structure which we have detected using RNase H cleavage and have mapped using the singular ability of two bases therein to undergo covalent intra-chain crosslinking stimulated by UV light. This pre-existing element maps to two non-contiguous stretches of the HCV IRES sequence, residues 53-68 and 103-117. Several earlier studies have shown that the correct sequence between bases 45 and 70 of the HCV IRES stem-loop II domain is required for initiation of protein synthesis. Because features of local tertiary structure like the one we report here are often associated with protein binding, we propose that the HCV stem-loop II element is directly involved in IRES action.
Information on Polydispersity and Branching from Combined Quasi-Elastic and Intergrated Scattering (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInformation on Polydispersity and Branching from Combined Quasi-Elastic and Intergrated ScatteringW. Burchard, M. Schmidt, and W. H. StockmayerCite this: Macromolecules 1980, 13, 5, 1265–1272Publication Date (Print):September 1, 1980Publication History Published online1 May 2002Published inissue 1 September 1980https://pubs.acs.org/doi/10.1021/ma60077a045https://doi.org/10.1021/ma60077a045research-articleACS PublicationsRequest reuse permissionsArticle Views1423Altmetric-Citations301LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Truncated atrial natriuretic peptide analogs. Comparison between receptor binding and stimulation of cyclic GMP accumulation in cultured vascular smooth muscle cells. (1986)

A series of truncated atrial natriuretic peptide analogs were examined as a means of defining the structural requirements for receptor occupancy and stimulation of cyclic GMP accumulation in bovine aortic smooth muscle cells. It was determined that deletion of amino acids from the carboxyl and/or amino termini of the peptides diminished their ability to increase cyclic GMP levels. Deletion of amino acids from the carboxyl terminus had the greatest effect, and atrial natriuretic peptide analogs lacking the carboxyl-terminal phenylalanyl-arginyl-tyrosine tripeptide were 100-1000-fold less active than parent compounds in stimulating intracellular cyclic GMP accumulation. In marked contrast to the cyclic GMP effects, deletion of amino- and/or carboxyl-terminal amino acids had only minor effects on the affinity of the peptides for specific smooth muscle cell-associated receptors. Peptide analogs lacking the phenylalanyl-arginyl-tyrosine tripeptide bound to receptors with an affinity only 1.1-5-fold weaker than the parent compounds. Thus, there was no correlation between apparent receptor binding affinity of atrial natriuretic peptide analogs and potency of these same peptides for stimulating intracellular cyclic GMP accumulation. Furthermore, analogs that bound to receptors and failed to elicit significant cyclic GMP responses did not antagonize or modulate increases in cyclic GMP induced by parent compounds. These data are most consistent with the existence of multiple subpopulations of atrial natriuretic peptide receptors on aortic smooth muscle cells.
Transduction of cytosine deaminase gene makes rat glioma cells highly sensitive to 5-fluorocytosine (1997)

To investigate the potential use of E. coli cytosine deaminase (CD) gene instead of the commonly used HSV-TK gene in the gene therapy of brain tumors, we constructed a retrovirus vector carrying the CD gene. We then transduced a rat glioma cell line C6 with CD gene by the retrovirus vector. Transduction of the CD gene made C6 cells become highly sensitive to the anti-fungi drug 5-fluorocytosine (5FC). IC50 for 5FC was 6,000 microM in CD-negative cells, while it was 3 microM in CD-positive cells. Mixed cellular assay showed that CD-positive cells had a strong "bystander effect" on CD-negative cells when exposed to 5FC. Significant anti-tumor effects were observed in nude mice bearing s.c. tumors derived from CD-positive cells when these animals were given 250 mg/kg 5FC twice a day for 20 consecutive days. A marked decrease in tumor weight occurred when a mixture containing 50% CD-positive and 50% CD-negative C6 cells was injected s.c., followed by 5FC treatment, suggesting the bystander effect in vivo. Concerning the pharmacokinetics of 5FC, especially its high oral bio-availability and good penetration into cerebrospinal fluid, we suppose that the combination of CD-gene transfer and 5FC oral administration may have potential use in the gene therapy of brain tumors.
pADPRT‐2: a novel mammalian polymerizing(ADP‐ribosyl)transferase gene related to truncated pADPRT homologues in plants and Caenorhabditis elegans1 (1999)

Until recently, poly(ADP-ribosyl)ation was supposed to be confined only to polymerizing(ADP-ribosyl)transferase/(ADP-ribose)polymerase (E.C. 2.4.2.30). Here, we present novel polymerizing(ADP-ribosyl)transferase homologues from mouse and man that lack all of the N-terminal DNA binding and BRCA1 C-terminus domains and will be designated polymerizing(ADP-ribosyl)transferase-2 as distinguished from the classical polymerizing(ADP-ribosyl)transferase (polymerizing(ADP-ribosyl)transferase-1). The murine polymerizing(ADP-ribosyl)transferase-2 gene shares three identical intron positions with its Caenorhabditis elegans (EMBL nucleotide sequence database Z47075) and one with the Arabidopsis thaliana homologue ('APP', GenBank database AF069298). Expression of the murine polymerizing(ADP-ribosyl)transferase-2 gene was elevated in spleen, thymus and testis and the corresponding poly(ADP-ribosyl)ation activity might account for most of the residual poly(ADP-ribosyl)ation observed in polymerizing(ADP-ribosyl)transferase-1(-/-) mice.
Novel cis -Acting Replication Element in the Adeno-Associated Virus Type 2 Genome Is Involved in Amplification of Integrated rep-cap Sequences (2001)

This study identifies a region of the adeno-associated virus type 2 (AAV-2) rep gene (nucleotides 190 to 540 of wild-type AAV-2) as a cis-acting Rep-dependent element able to promote the replication of transiently transfected plasmids. This viral element is also shown to be involved in the amplification of integrated sequences in the presence of adenovirus and Rep proteins.
Inverse scattering: an iterative numerical method for electromagnetic imaging (1991)

The authors propose a spatial iterative algorithm for electromagnetic imaging based on a Newton-Kantorovich procedure for the reconstruction of the complex permittivity of inhomogeneous lossy dielectric objects with arbitrary shape. Starting from integral representation of the electric field and using the moment method, this technique has been developed for 2-D (for TM and TE polarization cases) objects as well as for 3-D objects. Its performance has been compared with spectral techniques of classical diffraction tomography, the modified Newton method, and the pseudo-inverse method.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Endocytic trafficking of glycosphingolipids in sphingolipid storage diseases (2003)

In this review, recent studies of membrane lipid transport in sphingolipid (SL) storage disease (SLSD) fibroblasts are summarized. Several fluorescent glycosphingolipid (GSL) analogues are internalized from the plasma membrane via caveolae and are subsequently transported to the Golgi complex of normal fibroblasts, while in 10 different SLSD cell types, these lipids accumulate in endosomes and lysosomes. Additional studies have shown that cholesterol homeostasis is perturbed in multiple SLSDs secondary to accumulation of endogenous SLs, and that mis-targeting of the GSLs is regulated by cellular cholesterol. Golgi targeting of GSLs internalized via caveolae is dependent on microtubules and phosphoinositide 3-kinase(s) and is inhibited by expression of dominant-negative rab7 and rab9 constructs. Overexpression of wild-type rab7 or rab9 (but not rab11) in Niemann-Pick C fibroblasts results in correction of lipid trafficking defects, including restoration of Golgi targeting of fluorescent lactosylceramide and endogenous GM1 ganglioside (monitored by the transport of fluorescent cholera toxin), and a dramatic reduction in accumulation of intracellular cholesterol. These results suggest an approach for restoring normal lipid trafficking in this, and perhaps other, SLSD cell types, and may provide a basis for future therapy of these diseases.
Synthesis and Characterization of High-Molecular Mass Polyethylene Glycol-Conjugated Oligonucleotides (1997)

The use of synthetic oligonucleotides as possible drugs for human therapy is usually hampered by their low in vivo stability and capacity to achieve high concentrations at their cellular targets. To overcome this, it has been suggested that they be modified chemically. Among the various options, conjugation with short- and long-chain polyethylene glycols (PEGs) has several advantages: PEG is nontoxic and very soluble, reduces immunogenic reactions, and increases the stability of the conjugated molecules. PEG is generally joined to oligonucleotides while bound to the insoluble solid-phase supports, after their synthesis, which does not allow for their being easy scaled up. The use of the liquid-phase approach as an alternative synthetic process, utilizing the PEG polymer both as a soluble, inert synthetic support and a stabilizing agent of the oligonucleotide, is proposed. A new protocol has been set up, characterized by a stable phosphate bond between the support and the oligonucleotide. This method has been tested on a 12mer previously investigated as an antisense agent against HIV. The PEG-conjugated 12mer was efficiently synthesized and purified. It was found that the high-molecular mass PEG chain results in enzymatic stability and does not interfere with the formation of the duplex with its nucleic acid target.
Perturbation of hepcidin expression by BMP type I receptor deletion induces iron overload in mice (2011)

Bone morphogenetic protein (BMP) signaling induces hepatic expression of the peptide hormone hepcidin. Hepcidin reduces serum iron levels by promoting degradation of the iron exporter ferroportin. A relative deficiency of hepcidin underlies the pathophysiology of many of the genetically distinct iron overload disorders, collectively termed hereditary hemochromatosis. Conversely, chronic inflammatory conditions and neoplastic diseases can induce high hepcidin levels, leading to impaired mobilization of iron stores and the anemia of chronic disease. Two BMP type I receptors, Alk2 (Acvr1) and Alk3 (Bmpr1a), are expressed in murine hepatocytes. We report that liver-specific deletion of either Alk2 or Alk3 causes iron overload in mice. The iron overload phenotype was more marked in Alk3- than in Alk2-deficient mice, and Alk3 deficiency was associated with a nearly complete ablation of basal BMP signaling and hepcidin expression. Both Alk2 and Alk3 were required for induction of hepcidin gene expression by BMP2 in cultured hepatocytes or by iron challenge in vivo. These observations demonstrate that one type I BMP receptor, Alk3, is critically responsible for basal hepcidin expression, whereas 2 type I BMP receptors, Alk2 and Alk3, are required for regulation of hepcidin gene expression in response to iron and BMP signaling.
Effects of Human Growth Hormone on Body Composition in Elderly Men (1991)

Body composition changes progressively in mid and late adulthood. Lean body mass in men over 50 years old contracts at an average rate of -0.6% per year. Body weight tends to remain stable because of a reciprocal expansion of adipose mass. The shrinkage of the lean body mass reflects the atrophy of skeletal muscles, skin and visceral organs. Because growth hormone causes expansion of the lean body mass and contraction of the adipose mass, and because growth hormone secretion tends to diminish in late adulthood, it has been postulated that geriatric hyposomatotropism is a contributory cause to the body composition changes described above. The authors have tested this hypothesis by recruiting 45 independent men over 61 years old with plasma somatomedin C level below 0.35 U/ml, indicating little or no detectable growth hormone secretion. The 21-month protocol was as follows: baseline period 0-6 months, experimental period 6-18 months and post-experimental period 18-21 months. During the experimental period, 26 men (group I) received approximately 0.03 mg/kg of biosynthetic human growth hormone (hGH) subcutaneously 3 times a week, while 19 men (group II) received no treatment. Plasma somatomedin C was measured monthly. The following outcome variables were measured at 0, 6, 12 and 18 months: lean body mass, adipose mass, skin thickness (dermis plus epidermis), sizes of the liver, spleen and kidneys, the cross sectional areas of ten muscle groups, and bone density at 9 skeletal sites. Lean body mass and adipose mass were also measured at 21 months. In group I, hGH treatment raised the plasma somatomedin C level and maintained it in the range 0.5-1.5 U/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
An iterative method for the identification of nonlinear systems using a Hammerstein model (1966)

An iterative method is proposed for the identification of nonlinear systems from samples of inputs and outputs in the presence of noise. The model used for the identification consists of a no-memory gain (of an assumed polynomial form) followed by a linear discrete system. The parameters of the pulse transfer function of the linear system and the coefficients of the polynomial non-linearity are alternately adjusted to minimize a mean square error criterion. Digital computer simulations are included to demonstrate the feasibility of the technique.
Left atrial appendage function in patients with atrial flutter. (1997)

Left atrial appendage function is depressed and spontaneous echo contrast more frequent in patients with atrial flutter and intermittent atrial fibrillation, as opposed to patients with pure atrial flutter. These data support the concept that patients with atrial flutter and intermittent atrial fibrillation have an increased risk of thromboembolic events and should therefore receive adequate anticoagulant treatment.
Model calibration and validation for pre-production EUVL (2012)

As Extreme Ultraviolet Lithography (EUVL) enters the pre-production phase, the need to qualify the Electronic Design Automation (EDA) infrastructure is pressing. In fact, it is clear that EUV will require optical proximity correction (OPC), having its introduction shifted to more advanced technology nodes. The introduction of off-axis illumination will enlarge the optical proximity effects, and EUV-specific effects such as flare and shadowing have to be fully integrated in the correction flow and tested. We have performed a model calibration exercise on the ASML NXE:3100 pre-production EUVL scanner using Brion's Tachyon NXE EUV system. A model calibration mask has been designed, manufactured and characterized. The mask has different flare levels, as well as model calibration structures through CDs and pitch. The flare modulation through the mask is obtained by varying tiling densities. The generation of full-chip flare maps has been qualified against experimental results. The model was set up and calibrated on an intermediate flare level, and validated in the full flare range. Wafer data have been collected and were used as input for model calibration and validation. Two-dimensional structures through CD and pitch were used for model calibration and verification. We discuss in detail the EUV model, and analyze its various components, with particular emphasis to EUV-specific phenomena such as flare and shadowing.
7-Hydroxycoumarin−Hemicyanine Hybrids: A New Class of Far-Red Emitting Fluorogenic Dyes (2008)

The design and synthesis of novel water-soluble far-red emitting phenol-based fluorophores derived from 7-hydroxycoumarin are described. These hemicyanine-coumarin hybrids display promising spectroscopic features such as large apparent Stokes shift (ranging from 60 to 140 nm) and fluorescence emission maxima between 620 and 720 nm in physiological conditions. Their utility was then illustrated by the preparation of an original fluorogenic probe of penicillin G acylase (PGA) whose fluorescence is unveiled through an enzyme-initiated domino reaction.
Living Bacterial Cell Array for Genotoxin Monitoring (2004)

A biosensor composed of a high-density living bacterial cell array was fabricated by inserting bacteria into a microwell array formed on one end of an imaging fiber bundle. The size of each microwell allows only one cell to occupy each well. In this biosensor, E. coli cells carrying a recA::gfp fusion were used as sensing components for genotoxin detection. Each fiber in the array has its own light pathway, enabling thousands of individual cell responses to be monitored simultaneously with both spatial and temporal resolution. The biosensor was capable of performing cell-based functional sensing of a genotoxin with high sensitivity and short incubation times (1 ng/mL mitomycin C after 90 min). Dose-response curves for several genotoxins were obtained. The biosensors demonstrated an active sensing lifetime of more than 6 h and a shelf lifetime of two weeks.
Harmonin-b, an actin-binding scaffold protein, is involved in the adaptation of mechanoelectrical transduction by sensory hair cells (2009)

We assessed the involvement of harmonin-b, a submembranous protein containing PDZ domains, in the mechanoelectrical transduction machinery of inner ear hair cells. Harmonin-b is located in the region of the upper insertion point of the tip link that joins adjacent stereocilia from different rows and that is believed to gate transducer channel(s) located in the region of the tip link's lower insertion point. In Ush1c (dfcr-2J/dfcr-2J) mutant mice defective for harmonin-b, step deflections of the hair bundle evoked transduction currents with altered speed and extent of adaptation. In utricular hair cells, hair bundle morphology and maximal transduction currents were similar to those observed in wild-type mice, but adaptation was faster and more complete. Cochlear outer hair cells displayed reduced maximal transduction currents, which may be the consequence of moderate structural anomalies of their hair bundles. Their adaptation was slower and displayed a variable extent. The latter was positively correlated with the magnitude of the maximal transduction current, but the cells that showed the largest currents could be either hyperadaptive or hypoadaptive. To interpret our observations, we used a theoretical description of mechanoelectrical transduction based on the gating spring theory and a motor model of adaptation. Simulations could account for the characteristics of transduction currents in wild-type and mutant hair cells, both vestibular and cochlear. They led us to conclude that harmonin-b operates as an intracellular link that limits adaptation and engages adaptation motors, a dual role consistent with the scaffolding property of the protein and its binding to both actin filaments and the tip link component cadherin-23.
Functional inhibitory human leucocyte antigen class I receptors on natural killer (NK) cells in patients with chronic NK lymphocytosis (2003)

Chronic natural killer (NK) lymphocytosis is a rare disorder characterized by an indolent clinical course. Despite high NK cell numbers, many patients present with only mild clinical symptoms, and are often asymptomatic. NK cells are equipped with a range of receptors that bind human leucocyte antigen (HLA)-class I molecules. The killer immunoglobulin-like receptors (KIR, CD158) bind groups of HLA alleles, the CD94/NKG2 receptors bind HLA-E, and the CD85j (ILT2, LIR-1) receptor binds to the relatively non-polymorphic alpha3 domain of HLA molecules. Inhibitory HLA class I receptors silence NK cells against cells expressing normal levels of HLA class I. Analysis of NK cells in six patients with chronic NK lymphocytosis revealed a high level of the inhibitory CD94/NKG2A receptor on all NK cells. In four patients, KIR were absent, in one patient a single KIR was expressed in the absence of self-ligand, and in one patient CD85j and multiple KIR were expressed. Cytotoxicity assays demonstrated that all HLA class I receptors were functional. The ability of monoclonal antibodies to block the receptors and allow killing of autologous target cells established that both receptor and ligand expression were adequate for inhibitory function. We propose that the silent behaviour of NK cells in patients with chronic NK lymphocytosis is due to effective inhibitory HLA class I receptors.