gebhart/patrepeval huggingface dataset:
Functional analysis of phosphorylation sites in human lamin A controlling lamin disassembly, nuclear transport and assembly. (1993)

We have constructed point mutations in human lamin A cDNA at conserved serine and threonine residues, some of which were shown to be phosphorylated in vitro by cdc2-kinase and protein kinase C and in vivo. Using a functional in vivo assay system, we identified three categories of mutant phenotypes. (i) Dominant negative phenotypes in mitosis result from mutation of Thr-19 and Ser-22 within the amino-terminal cdc2-kinase motif of lamin A. An increase of aberrant mitotic phenotypes in the double mutants Thr-19/Ser-392 and Ser-22/Ser-392 suggests that concomitant phosphorylation of the three residues regulates mitotic lamin A disassembly. (ii) Mutation of both Ser-403/Ser-404 within a PKC motif flanking the nuclear localization signal inhibits transport of mutant lamin A to the nucleus in 64% of the cells. It is proposed that phosphorylation of the motif in vivo positively regulates nuclear localization together with the nuclear localization sequence. (iii) The assembly of lamin A into the perinuclear lamina is disturbed by mutation of the carboxy-terminal Ser-525, previously shown to be interphase-specifically phosphorylated (Eggert et al., Eur. J. Biochem. 213, 659-671 (1993)). The phenotype shows discontinuous and patch-like aggregates of the mutant protein in the nucleus. We suggest that phosphorylation of the site either regulates lamina assembly or lamina-chromatin interaction in interphase.
Role of Protease-activated Receptor-2 in Idiopathic Pulmonary Fibrosis (2011)

The PAR-2/TF/FVIIa axis may contribute to the development of pulmonary fibrosis; thus, interference with this pathway confers novel therapeutic potential for the treatment of IPF.
Femtosecond-picosecond laser photolysis studies on the mechanisms of fluorescence quenching induced by hydrogen-bonding interactions - 1-pyrenol-pyridine systems (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFemtosecond-picosecond laser photolysis studies on the mechanisms of fluorescence quenching induced by hydrogen-bonding interactions - 1-pyrenol-pyridine systemsHiroshi Miyasaka, Akihiro Tabata, Seishi Ojima, Noriaki Ikeda, and Noboru MatagaCite this: J. Phys. Chem. 1993, 97, 31, 8222–8228Publication Date (Print):August 1, 1993Publication History Published online1 May 2002Published inissue 1 August 1993https://pubs.acs.org/doi/10.1021/j100133a017https://doi.org/10.1021/j100133a017research-articleACS PublicationsRequest reuse permissionsArticle Views271Altmetric-Citations53LEARN 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 options Get e-Alerts
An Orthogonally Multiplexed QAM System Using the Discrete Fourier Transform (1981)

An orthogonally multiplexed QAM (O-QAM) system is a multichannel system with a baud rate spacing between adjacent carrier frequencies; this property is desirable to digitally implement the system using the discrete Fourier transformation (DFT). This paper provides a novel digital signal processing method based on an <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">N</tex> /2-point DFT processing in the O-QAM system. A complexity comparison between a digital O-QAM system and a digital singlechannel QAM system shows that the digital O-QAM system using the new method is more economical than the digitally implemented conventional single-channel data transmission system.
The polypeptide composition of bovine epidermal α-keratin (1975)

1. The polypedtide chains that comprise the subunits of the tonofilaments, or the α-keratin component, of bovine epidermis were fractionated by combination of chromatography on DEAE-cellulose and preparative polyacrylamide-gel electrophoresis. 2. The seve polypeptide chains investigated had generalyy similar properties; all contained two residues per molecule of tryptophan and N-acetylserine was the common N-terminal amino acid residue. 3. On the basis of close similarities in α-helix content and amino acid composition, the polypeptide chains were classified into three distinct groups. Each group contained approximately one-third of the total polypeptides on a molar basis. The groups and designated polypeptides chain numbers were: group one, polypeptides 1a and 1b, which had moleculae weights of 58,000, contained about 25% α-helix, 86 glutamic acid and 8 cysteine residues per molecule, but which differed in net charge, extinction coefficients and tyrosine contents; group two, polypeptides 2, 3, and 4, which hadmolecular weights within thewithin the range of 52,00-56,000, contained about 48% α-helix, 54 glutamic acid and 6 cysteine residues per molecule, but which differed in extinction coefficients and tryosine contents; and group, polypeptides 5 and 6, which had molecular weights of 47000-48000, contained about 56% α-helix, 64 glutamic acid and 4 cysteine residues per molecule, but which differed in extinction coefficients and tyrosine contents, it is suggested that none of the chains is a precursor or a degradation product of other polypeptidc chains. 5. It is concluded that bovine epidermal α-keratin consists of a heterogeneous group of similar polypeptide chains.
Multiple-Peptide Conjugates for Binding β-Amyloid Plaques of Alzheimer's Disease (2002)

Formation of beta-amyloid plaques in Alzheimer's disease is initiated by intermolecular contact of the 5-amino acid sequence, KLVFF, in beta-amyloid peptides ranging in size from 40 to 43 residues. Through optimization of binding avidity using structure/function studies, we have found that the retro-inverso peptide, ffvlk, binds artificial fibrils made from Abeta(1)(-)(40) with moderate affinity (K(d) = 5 x 10(-)(7) M). Conjugates having two copies of this peptide, whether connected by a long poly(ethylene glycol) (PEG) spacer or just two amino acids, display about 100-fold greater affinity for fibrils. Placing six copies of ffvlk on a branched PEG resulted in a 10 000-fold greater affinity (K(d) = 1 x 10(-)(10) M) than the monomer peptide. This increased affinity was accompanied by more effective inhibition of the thioflavin T fluorescence signal, which correlates with neurotoxicity of plaques and fibrils. We propose that conjugates bearing several copies of ffvlk may be useful as diagnostic and therapeutic agents for Alzheimer's disease.
Engineered Salmonella enterica serovar Typhimurium overcomes limitations of anti-bacterial immunity in bacteria-mediated tumor therapy (2017)

Cancer is one of the leading causes of death in the industrialized world and represents a tremendous social and economic burden. As conventional therapies fail to provide a sustainable cure for most cancer patients, the emerging unique immune therapeutic approach of bacteria-mediated tumor therapy (BMTT) is marching towards a feasible solution. Although promising results have been obtained with BMTT using various preclinical tumor models, for advancement a major concern is immunity against the bacterial vector itself. Pre-exposure to the therapeutic agent under field conditions is a reasonable expectation and may limit the therapeutic efficacy of BMTT. In the present study, we investigated the therapeutic potential of <i>Salmonella</i> and <i>E. coli</i> vector strains in naïve and immunized tumor bearing mice. Pre-exposure to the therapeutic agent caused a significant aberrant phenotype of the microenvironment of colonized tumors and limited the <i>in vivo</i> efficacy of established BMTT vector strains <i>Salmonella</i> SL7207 and <i>E. coli</i> Symbioflor-2. Using targeted genetic engineering, we generated the optimized auxotrophic <i>Salmonella</i> vector strain SF200 (<i>ΔlpxR9 ΔpagL7 ΔpagP8 ΔaroA ΔydiV ΔfliF</i>) harboring modifications in Lipid A and flagella synthesis. This combination of mutations resulted in an increased immune-stimulatory capacity and as such the strain was able to overcome the efficacy-limiting effects of pre-exposure. Thus, we conclude that any limitations of BMTT concerning anti-bacterial immunity may be countered by strategies that optimize the immune-stimulatory capacity of the attenuated vector strains.
Biomarkers in pulmonary hypertension (2008)

There have been significant recent advances in the understanding of the pathophysiology of pulmonary hypertension, and a growing number of therapeutic agents have become available to the treating physician. Traditional methods of diagnosing and monitoring this condition have comprised echocardiography and right heart catheterisation, in addition to functional measures, such as estimation of functional class and the 6-min walk test. An increasing number of biomarkers have been described that are elevated in pulmonary hypertension and which may assist the clinician in diagnosis and in the assessment of disease severity and response to treatment. The present article details the more important biomarkers, their potential applications and the evidence supporting their use.
Anatomic dissociation between HIV-1 and its endogenous inhibitor in mucosal tissues. (1997)

The rarity of oral transmission of human immunodeficiency virus (HIV)-1 by saliva suggests the absence of HIV-1 in the oral cavity and/or the presence of viral inhibitory molecules. We analyzed salivary gland tissues from 55 individuals with acquired immune deficiency syndrome (AIDS) for the presence of HIV-1 by in situ hybridization and detected the virus in more than 30% of these salivary glands. These data, together with previous demonstrations of HIV-1 in oral secretions, implicate a key role for an anti-viral molecule(s) in suppressing transmission. Thus, we focused on the characterization and localization of the endogenous antiviral molecule secretory leukocyte protease inhibitor (SLPI), which inhibits HIV-1 infection in vitro. Expression of SLPI transcripts was evident in submandibular, parotid, and minor salivary glands from both HIV-1-infected and seronegative subjects. Gene expression was reflected by similar levels of SLPI protein by immunohistochemical analysis in the tissues and by enzyme-linked immunosorbent assay in the saliva. However, although SLPI accumulated in acinar cells or ductal epithelium, HIV-1 transcripts did not, and these viral transcripts were identified only in mononuclear cells within the salivary gland stroma. By in situ hybridization, we found no evidence of productive HIV-1 infection of salivary gland epithelium. Thus, HIV-1 was frequently identified in salivary gland tissue, but the virus was found in interstitial mononuclear cells only and did not co-localize with SLPI. Once within the oral cavity, HIV-1 exposure to antiviral levels of SLPI may impede infection of additional target cells, contributing to the virtual absence of oral transmission of HIV-1 by saliva. These studies emphasize the importance of innate, endogenous inhibitors of HIV-1, particularly SLPI, as effective inhibitors of HIV-1 transmission.
Mixed Protein Carriers for Modulating DNA Release (2009)

Aqueous mixtures of oppositely charged polyelectrolytes undergo associative phase separation, resulting in coacervation, gelation, or precipitation. This phenomenon has been exploited in forming DNA gel particles by interfacial diffusion. We report here the formation of DNA gel particles by mixing solutions of double-stranded DNA with aqueous solutions containing two cationic proteins, lysozyme and protamine sulfate. The effect of the lysozyme/protamine ratio on the degree of DNA entrapment, surface morphology, swelling-deswelling behavior, and kinetics of DNA release has been investigated. By mixing the two proteins, we obtain particles that display higher loading efficiency and loading capacity values, in comparison to those obtained in single-protein systems. Examination of the release profiles has shown that in mixed protein particles, complex, dual-stage release kinetics is obtained. The overall release profile is dependent on the lysozyme/protamine ratio. The obtained profiles, or segments of them, are accuratelly fitted using the zero-order and first-order models, and the Weibull function. Fluorescence microscopy studies have suggested that the formation of these particles is associated with the conservation of the secondary structure of DNA. This study presents a new platform for controlled release of DNA from DNA gel particles formed by interfacial diffusion.
Film Morphology and Thin Film Transistor Performance of Solution-Processed Oligothiophenes (2004)

The relationship between film morphology and thin film transistor (TFT) performance was investigated for two symmetrical α,ω-substituted sexithiophene derivatives containing thermally removable solubilizing groups. Solution deposition methods such as spin-coating, dip-casting, and inkjet-printing were optimized for solvent and annealing temperatures, and several substrate surface treatments were explored. The resulting thin films were characterized with AFM and the observed semiconductor performance was found to correlate with the morphology of the films, with the most crystalline films exhibiting the highest performance. Devices showed overall mobilities as high as 0.07 cm2/V s with on/off ratios > 108, which are among the highest reported values for oligothiophenes solution cast at room temperature.
Connective tissue growth factor binds vascular endothelial growth factor (VEGF) and inhibits VEGF‐induced angiogenesis (2001)

Vascular endothelial growth factor (VEGF) is a strong angiogenic mitogen and plays important roles in angiogenesis under various pathophysiological conditions. The in vivo angiogenic activity of secreted VEGF may be regulated by extracellular inhibitors, because it is also produced in avascular tissues such as the cartilage. To seek the binding inhibitors against VEGF, we screened the chondrocyte cDNA library by a yeast two-hybrid system by using VEGF165 as bait and identified connective tissue growth factor (CTGF) as a candidate. The complex formation of VEGF165 with CTGF was first established by immunoprecipitation from the cells overexpressing both binding partners. A competitive affinity-binding assay also demonstrated that CTGF binds specifically to VEGF165 with two classes of binding sites (Kd = 26 +/- 11 nM and 125 +/- 38 nM). Binding assay using deletion mutants of CTGF indicated that the thrombospondin type-1 repeat (TSP-1) domain of CTGF binds to the exon 7-coded region of VEGF165 and that the COOH-terminal domain preserves the affinity to both VEGF165 and VEGF121. The interaction of VEGF165 with CTGF inhibited the binding of VEGF165 to the endothelial cells and the immobilized KDR/IgG Fc; that is, a recombinant protein for VEGF165 receptor. By in vitro tube formation assay of endothelial cells, full-length CTGF and the deletion mutant possessing the TSP-1 domain inhibited VEGF165-induced angiogenesis significantly in the complex form. This antiangiogenic activity of CTGF was demonstrated further by in vivo angiogenesis assay by using Matrigel injection model in mice. These data demonstrate for the first time that VEGF165 binds to CTGF through a protein-to-protein interaction and suggest that the angiogenic activity of VEGF165 is regulated negatively by CTGF in the extracellular environment.
Assessment of medical treatments for menorrhagia (1994)

Although usually not life-threatening, dysfunctional uterine bleeding (DUB) can cause discomfort and disruption to life for many women. It has been poorly researched in the past, primarily because of difficulties in trying to accurately measure blood loss and response to treatment. There are several different therapies currently available but, for many, actual evidence of their efficacy is lacking from scientific data. Progestogens are the most frequently prescribed drugs for the treatment of DUB. Data support their use in anovulatory women but a number of comparative trials have shown that an overall reduction in blood loss of only 20% is achieved in ovulatory women. Their use, therefore, must be questioned as the first line of treatment. Combined oral contraceptives were at one time popular but whether the low-dose, current generation pills are equally effective awaits appropriate trials. Prostaglandin synthetase inhibitors can be useful, with up to a third of women with menorrhagia benefiting from a reduction of between 25% and 35% in blood loss. A proportionally greater reduction is seen in women with more excessive bleeding. Antifibrinolytic drugs have been shown to reduce menstrual blood loss in DUB by 50% and would be useful in women in whom oestrogens are contraindicated. Gonadotrophin-releasing hormone analogues are highly effective because of their ability to induce amenorrhoea, but long-term use is contraindicated because of their hypo-oestrogenic effects. One other effective therapy for menorrhagia has been danazol.(ABSTRACT TRUNCATED AT 250 WORDS)
The inhibition of incorporation of leucine into protein of cell-free systems from rat liver and Escherichia coli by chlortetracycline (1963)

Gale & Folkes (1953) found that chlortetracycline inhibited protein synthesis in bacterial cultures whereas nucleic acid synthesis was apparently stimulated. Nikolov & Ilkov (1961) found that it reduced the incorporation in vivo of methionine into the proteins of a number of tissues in the rabbit, suggesting that the drug may also interfere with protein synthesis in the aniimal. Although much attention has been paid in recent years to the inhibition of protein biosynthesis by puromycin, chloramphenicol and streptomycin, there appears to be little information on the mode of action of chlortetracycline in inhibiting protein biosynthesis. The present work concerns the action of this drug on the incorporation of [14C]leucine into the various fractions of cell-free preparations from rat liver and Escherichia coli.
Cloning and partial nucleotide sequence of human immunoglobulin mu chain cDNA from B cells and mouse-human hybridomas. (1980)

Purified mRNAs coding for mu and kappa human immunoglobulin polypeptides were translated in vitro and their products were characterized. The mu-specific mRNAs, derived from both human lymphoblastoid cells (GM607) and from a mouse-human somatic cell hybrid secreting human mu chains (alpha D5-H11-BC11), were copied into cDNAs and inserted into the plasmid pBR322. Several recombinant cDNAs that were obtained were identified by a combination of colony hybridization with labeled probes, in vitro translation of plasmid-selected mu mRNAs, and DNA nucleotide sequence determination. One recombinant DNA, for which the sequence has been partially determined, contains the codons for part of the C3 constant region domain through the carboxy-terminal piece (155 amino acids total) as well as the entire 3' noncoding sequence up to the poly(A) site of the human mu mRNA. The sequence A-A-U-A-A occurs 12 nucleotides prior to the poly(A) addition site in the human mu mRNA. Considerable sequence homology is observed in the mouse and human mu mRNA 3' coding and noncoding sequences.
Involvement of phosphatidylinositol 3-kinase in stromal cell-derived factor-1 alpha-induced lymphocyte polarization and chemotaxis. (1999)

The role of phosphatidylinositol 3-kinase (PI3-kinase), an important enzyme involved in signal transduction events, has been studied in the polarization and chemotaxis of lymphocytes induced by the chemokine stromal cell-derived factor-1 alpha (SDF-1 alpha). This chemokine was able to directly activate p85/p110 PI3-kinase in whole human PBL and to induce the association of PI3-kinase to the SDF-1 alpha receptor, CXCR4, in a pertussis toxin-sensitive manner. Two unrelated chemical inhibitors of PI3-kinase, wortmannin and Ly294002, prevented ICAM-3 and ERM protein moesin polarization as well as the chemotaxis of PBL in response to SDF-1 alpha. However, they did not interfere with the reorganization of either tubulin or the actin cytoskeleton. Moreover, the transient expression of a dominant negative form of the PI3-kinase 85-kDa regulatory subunit in the constitutively polarized Peer T cell line inhibited ICAM-3 polarization and markedly reduced SDF-1 alpha-induced chemotaxis. Conversely, overexpression of a constitutively activated mutant of the PI3-kinase 110-kDa catalytic subunit in the round-shaped PM-1 T cell line induced ICAM-3 polarization. These results underline the role of PI3-kinase in the regulation of lymphocyte polarization and motility and indicate that PI3-kinase plays a selective role in the regulation of adhesion and ERM proteins redistribution in the plasma membrane of lymphocytes.
Two Distinct Subtypes of Human Respiratory Syncytial Virus (1985)

Antigenic variation of human respiratory syncytial (RS) virus strains was analysed using a collection of nine, six, six, nine and one monoclonal antibodies respectively directed against the large glycoprotein (G), fusion protein (F), matrix protein (M), nucleoprotein (NP) and phosphoprotein (P) components of the Long strain of RS virus. A comparison was made with seven other strains isolated during different years in radioimmune precipitation analyses and immune fluorescence tests. Two different subtypes of the virus were demonstrable. Subtype A included the prototype strains Long and A2 and virus isolates from 1973, 1983 and 1984; subtype B included four virus strains isolated in successive years from 1979 to 1982. Subtype A viruses reacted with all the antibodies, whereas subtype B viruses showed different epitope characteristics in four structural components. The number of altered epitopes were 5/6, 1/2, 2/6 and 1/6 in the G, F, M and NP components, respectively. It is concluded that the two subtypes have evolved separately. The finding of two subtypes may explain previously observed strain variations in neutralization tests, and gives a new perspective on the immunobiology of RS virus.
The FB-RED algorithm for TCP over ATM (2002)

We present the FB-RED (fair-buffering random early detection) algorithm, a new congestion control scheme for TCP over ATM connections which takes advantage of ATM to improve the fairness characteristics of the RED gateway algorithm. Utilizing the fact that ATM is connection-oriented and the ABR explicit rate control mechanism, the FB-RED algorithm calculates the bandwidth-delay product of each connection and based on this value it ensures fair drop probabilities. Two variants of the FB-RED algorithm are presented. The first one weighs the drop probabilities of the original RED algorithm relative to each connection's bandwidth-delay product, while the second one changes the original RED algorithm to ensure that the drop probabilities of each connection roughly equals the optimal drop probability. Both variants are shown to markedly improve the fairness as compared to the original RED algorithm in various simulation topologies.