gebhart/patrepeval huggingface dataset:
2'-O-methyl RNA oligonucleotides identify two functional elements in the trypanosome spliced leader ribonucleoprotein particle (1993)

Using permeable trypanosomes as an in vivo model system for trans-splicing, we have searched for functional elements in the Trypanosoma brucei spliced leader (SL) RNA by masking various regions of the molecule with short antisense 2'-O-methyl RNA oligomers. Initial probing of the structure of newly synthesized SL RNA by deoxyoligonucleotide-directed ribonuclease (RNase) H cleavage revealed three accessible regions: the 5' end, sequences downstream of the 5' splice site, and a putative single-stranded sequence between stem-loops II and III, which is thought to be analogous to the mammalian Sm-binding site of U small nuclear RNAs. Using antisense 2'-O-methyl RNA oligomers, two functional elements of the SL RNA became apparent. Masking of positions 1-18 inhibited modification of the cap 4 structure of newly synthesized SL RNA and, thereby, blocked utilization of the SL RNA in trans-splicing. In addition, nucleotides +1 to +4 relative to the 5' splice site, which include the invariant GU dinucleotide were accessible to oligomer binding in the SL ribonucleoprotein particle, and their blockade resulted in complete inhibition of trans-splicing. In contrast, RNA oligomer binding to the single-stranded region between stem-loop II and III of the SL RNA had no detectable effect on trans-splicing activity of the SL RNA.
Characterization of frequent deletions causing steroid 21-hydroxylase deficiency. (1988)

Steroid 21-hydroxylase deficiency is caused by mutations in the CYP21B gene. This gene and a highly homologous pseudogene, CYP21A, alternate with the C4A and C4B genes encoding the fourth component of complement. Classical deficiency alleles are frequently caused by deletions of CYP21B or by gene conversions that transfer deleterious mutations from the CYP21A pseudogene to CYP21B. Gene conversions involving restriction enzyme sites that distinguish CYP21A [e.g., 3.2-kilobase (kb) Taq I fragment] and CYP21B (3.7-kb Taq I fragment) might be confused with actual deletions of CYP21B. To determine the incidence of this type of gene conversion, 15 chromosomes (in 13 families) with absent 3.7-kb Taq I fragments were studied. When hybridized with a 21-hydroxylase probe, all of these chromosomes were associated with absent 2.9-kb Kpn I fragments, 14 of 15 were associated with absent 2.4-kb Bgl II/EcoRI fragments, and 13 of 15 were associated with absent 10-kb Bgl II/EcoRI and 12-kb EcoRI fragments. Thirteen of 15 chromsomes had absent 6.0- or 5.4-kb Taq I fragments when hybridized with a C4 probe. Thus, 2 of 15 chromosomes do not carry deletions and may represent gene conversions; 13 of 15 chromosomes studied have a deletion of approximately equal to 30 kb, leaving behind the C4A gene and a single CYP21A-like gene. Hybridization with specific oligonucleotide probes showed that in all 13 cases this remaining CYP21 gene carried an 8-base-pair deletion, typical of CYP21A, that prevents synthesis of a functional protein. Thus, gene conversions are rarely confused with deletions as a cause of 21-hydroxylase deficiency.
Transduction of CLL cells by CD40 ligand enhances an antigen-specific immune recognition by autologous T cells (2005)

Several features of chronic lymphocytic leukemia (CLL) suggest that immune-based strategies may have therapeutic potential. A promising approach is provided by the transduction of CLL cells with CD40 ligand (CD40L) by viral vectors to enhance their immunogenicity. We compared the antigen-presenting capacity of CD40L-transduced CLL cells with mock-transduced or CD40L-stimulated CLL cells (CD40-CLL). A significantly higher number of T cells could be expanded using CD40L-transduced CLL cells as antigen-presenting cells (APCs) compared with the control group (P = .008). Using 5 different CLL-associated tumor antigens, including fibromodulin, MDM2 (murine double minute 2), survivin, p53, and KW-13, we show in interferon-gamma (IFN-gamma) enzyme-linked immunospot (ELISPOT) assays after 35 days of in vitro culture that the number of antigen-specific autologous T cells was also significantly higher when CD40L-transduced CLL cells were used as APCs (P < .001). Thus, CD40L-transduced CLL cells are able to induce an antigen-specific T-cell response and might be superior to CD40-CLL cells for immune-based therapeutic strategies in CLL.
Cooperative Effect of Two Surface Amino Acid Mutations (Q252L and E170K) in Glucose Dehydrogenase from <i>Bacillus megaterium</i> IWG3 on Stabilization of Its Oligomeric State (2005)

A thermostable glucose dehydrogenase (GlcDH) mutant of Bacillus megaterium IWG3 harboring the Q252L substitution (Y. Makino, S. Negoro, I. Urabe, and H. Okada, J. Biol. Chem. 264:6381-6385, 1989) is stable at pH values above 9, but only in the presence of 2 M NaCl. Another GlcDH mutant exhibiting increased stability at an alkaline pH in the absence of NaCl has been isolated previously (S.-H. Baik, T. Ide, H. Yoshida, O. Kagami, and S. Harayama, Appl. Microbiol. Biotechnol. 61:329-335, 2003). This mutant had two amino acid substitutions, Q252L and E170K. In the present study, we characterized three GlcDH mutants harboring the substitutions Q252L, E170K, and Q252L/E170K under low-salt conditions. The GlcDH mutant harboring two substitutions, Q252L/E170K, was stable, but mutants harboring a single substitution, either Q252L or E170K, were unstable at an alkaline pH. Gel filtration chromatography analyses demonstrated that the oligomeric state of the Q252/E170K enzyme was stable, while the tetramers of the enzymes harboring a single substitution (Q252L or E170K) dissociated into dimers at an alkaline pH. These results indicated that the Q252L and E170K substitutions synergistically strengthened the interaction at the dimer-dimer interface. The crystal structure of the E170K/Q252L mutant, determined at 2.0-angstroms resolution, showed that residues 170 and 252 are located in a hydrophobic cavity at the subunit-subunit interface. We concluded that these residues in the wild-type enzyme have thermodynamically unfavorable effects, while the Q252L and E170K substitutions increase the subunit-subunit interactions by stabilizing the hydrophobic cavity.
An Efficient Protocol for the Preparation of Primary Alcohols Bearing a β-Chiral Center via an Oxazolidinone Auxiliary Mediated Resolution, and Application to the Synthesis of 4,4-Disubstituted Piperidine Substance P Antagonists (2000)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTAn Efficient Protocol for the Preparation of Primary Alcohols Bearing a β-Chiral Center via an Oxazolidinone Auxiliary Mediated Resolution, and Application to the Synthesis of 4,4-Disubstituted Piperidine Substance P AntagonistsRichard T. Lewis, Tamara Ladduwahetty, Kevin J. Merchant, Linda E. Keown, Laure Hitzel, Hugh Verrier, Graeme I. Stevenson, and Angus M. MacLeodView Author Information Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK Cite this: J. Org. Chem. 2000, 65, 8, 2615–2618Publication Date (Web):March 25, 2000Publication History Received29 November 1999Published online25 March 2000Published inissue 1 April 2000https://pubs.acs.org/doi/10.1021/jo9918246https://doi.org/10.1021/jo9918246brief-reportACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views291Altmetric-Citations6LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Alcohols,Chromatography,Molecular structure,Organic compounds,Redox reactions Get e-Alerts
Influenza Vaccine Prepared by Photodynamic Inactivation of Virus (1963)

Summary and Conclusions Influenza virus (108 EID50/ml, PR-8 strain of type A) in the presence of 10-5.5 M toluidine blue was photodynamically inactivated by visible light. Although all detectable infectivity was destroyed, the immunizing and hemagglutinating antigens were preserved. The photosensitive influenza-dye complex is readily dissociable, since virus-dye mixtures passed through cation resins yielded dye-free virus that regained its photoresistance. Although the infectivity of virus in infected allantoic fluid could be photodynamically destroyed, the hemagglutinin was not affected. However, upon removal of certain constituents of allantoic fluid by dialysis or by erythrocyte purification of the virus, the viral hemagglutinin became photosensitive in the presence of toluidine blue. The results with the purified hemagglutinin are similar to those found with the mature poliovirus particle, for here also, purification was required for the infective moiety to become photosensitive (9). Influenza virus vaccines inactivated by photodynamic action and by formalin were compared for antigenicity in mice. With the photodynamically inactivated vaccine, the immunologic response in mice was found to be equal to that produced by formalin-inactivated vaccine but somewhat less than that produced by injection of live virus. Such a photodynamically inactivated vaccine might prove advantageous for use with strains that have antigens particularly sensitive to formalin.
Information-Driven Dynamic Sensor Collaboration for Tracking Applications (2002)

This article overviews the information-driven approach to in ad hoc networks. The main idea is for a network to determine participants in a sensor collaboration by dynamically optimizing the information utility of data for a given cost of communication and computation. A definition of information utility is introduced, and several approximate measures of the information utility are developed for reasons of computational tractability. We illustrate the use of this approach using examples drawn from tracking applications.
A Balance between B Cell Receptor and Inhibitory Receptor Signaling Controls Plasma Cell Differentiation by Maintaining Optimal Ets1 Levels (2014)

Signaling through the BCR can drive B cell activation and contribute to B cell differentiation into Ab-secreting plasma cells. The positive BCR signal is counterbalanced by a number of membrane-localized inhibitory receptors that limit B cell activation and plasma cell differentiation. Deficiencies in these negative signaling pathways may cause autoantibody generation and autoimmune disease in both animal models and human patients. We have previously shown that the transcription factor Ets1 can restrain B cell differentiation into plasma cells. In this study, we tested the roles of the BCR and inhibitory receptors in controlling the expression of Ets1 in mouse B cells. We found that Ets1 is downregulated in B cells by BCR or TLR signaling through a pathway dependent on PI3K, Btk, IKK2, and JNK. Deficiencies in inhibitory pathways, such as a loss of the tyrosine kinase Lyn, the phosphatase Src homology region 2 domain-containing phosphatase 1 (SHP1) or membrane receptors CD22 and/or Siglec-G, result in enhanced BCR signaling and decreased Ets1 expression. Restoring Ets1 expression in Lyn- or SHP1-deficient B cells inhibits their enhanced plasma cell differentiation. Our findings indicate that downregulation of Ets1 occurs in response to B cell activation via either BCR or TLR signaling, thereby allowing B cell differentiation and that the maintenance of Ets1 expression is an important function of the inhibitory Lyn → CD22/SiglecG → SHP1 pathway in B cells.
Proinflammatory and Th2-Derived Cytokines Modulate CD40-Mediated Expression of Inflammatory Mediators in Airway Epithelia: Implications for the Role of Epithelial CD40 in Airway Inflammation (2000)

Cytokines produced by activated macrophages and Th2 cells within the lung play a key role in asthma-associated airway inflammation. Additionally, recent studies suggest that the molecule CD40 modulates lung immune responses. Because airway epithelial cells can act as immune effector cells through the expression of inflammatory mediators, the epithelium is now considered important in the generation of asthma-associated inflammation. Therefore, the goal of the present study was to examine the effects of proinflammatory and Th2-derived cytokines on the function of CD40 in airway epithelia. The results show that airway epithelial cells express CD40 and that engagement of epithelial CD40 induces a significant increase in expression of the chemokines RANTES, monocyte chemoattractant protein (MCP-1), and IL-8 and the adhesion molecule ICAM-1. Cross-linking epithelial CD40 had no effect on expression of the adhesion molecule VCAM-1. The proinflammatory cytokines TNF-alpha and IL-1beta and the Th2-derived cytokines IL-4 and IL-13 modulated the positive effects of CD40 engagement on inflammatory mediator expression in airway epithelial cells. Importantly, CD40 ligation enhanced the sensitivity of airway epithelial cells to the effects of TNF-alpha and/or IL-1beta on expression of RANTES, MCP-1, IL-8, and VCAM-1. In contrast, neither IL-4 nor IL-13 modified the effects of CD40 engagement on the expression of RANTES, MCP-1, IL-8, or VCAM-1; however, both IL-4 and IL-13 attenuated the effects of CD40 cross-linking on ICAM-1 expression. Together, these findings suggest that interactions between CD40-responsive airway epithelial cells and CD40 ligand+ leukocytes, such as activated T cells, eosinophils, and mast cells, modulate asthma-associated airway inflammation.
Alternative Architectures of SOI MOSFET for Improving DC and Microwave Characteristics (2001)

DC and high frequency characteristics of innovative SOI MOSFET's such as graded channel and dynamic threshold voltage MOS are presented in this paper. These architectures are very promising for high frequency low power low voltage analog applications.
A high sensitive fiber SERS probe based on silver nanorod arrays (2007)

A portable fiber SERS probe has been developed based on Ag nanorod array fabricated by oblique angle deposition. The incoming laser beam was designed to focus onto the Raman substrate at 45 degrees incident angle in order to maximize surface enhanced Raman scattering signal. With a fiber Raman system, a detection sensitivity of 10(-17) moles for trans-1, 2- bis(4-pyridyl)ethane molecules has been demonstrated. This Raman probe can also be used for in situ measurement for samples in aqueous solution. Such a fiber probe has great potential as a portable and remote sensor for on-site biological or chemical detection.
SAFE-OPS: An approach to embedded software security (2005)

The new-found ubiquity of embedded processors in consumer and industrial applications brings with it an intensified focus on security, as a strong level of trust in the system software is crucial to their widespread deployment. The growing area of software protection attempts to address the key steps used by hackers in attacking a software system. In this paper, we introduce a unique approach to embedded software protection that utilizes a hardware/software codesign methodology. Results demonstrate that this framework can be the successful basis for the development of embedded applications that meet a wide range of security and performance requirements.
Differential regulation of action potential firing in adult murine thalamocortical neurons by Kv3.2, Kv1, and SK potassium and N‐type calcium channels (2007)

Sensory signals of widely differing dynamic range and intensity are transformed into a common firing rate code by thalamocortical neurons. While a great deal is known about the ionic currents, far less is known about the specific channel subtypes regulating thalamic firing rates. We hypothesized that different K(+) and Ca(2+) channel subtypes control different stimulus-response curve properties. To define the channels, we measured firing rate while pharmacologically or genetically modulating specific channel subtypes. Inhibiting Kv3.2 K(+) channels strongly suppressed maximum firing rate by impairing membrane potential repolarization, while playing no role in the firing response to threshold stimuli. By contrast, inhibiting Kv1 channels with alpha-dendrotoxin or maurotoxin strongly increased firing rates to threshold stimuli by reducing the membrane potential where action potentials fire (V(th)). Inhibiting SK Ca(2+)-activated K(+) channels with apamin robustly increased gain (slope of the stimulus-response curve) and maximum firing rate, with minimum effects on threshold responses. Inhibiting N-type Ca(2+) channels with omega-conotoxin GVIA or omega-conotoxin MVIIC partially mimicked apamin, while inhibiting L-type and P/Q-type Ca(2+) channels had small or no effects. EPSC-like current injections closely mimicked the results from tonic currents. Our results show that Kv3.2, Kv1, SK potassium and N-type calcium channels strongly regulate thalamic relay neuron sensory transmission and that each channel subtype controls a different stimulus-response curve property. Differential regulation of threshold, gain and maximum firing rate may help vary the stimulus-response properties across and within thalamic nuclei, normalize responses to diverse sensory inputs, and underlie sensory perception disorders.
A Microfluidic Love-Wave Biosensing Device for PSA Detection Based on an Aptamer Beacon Probe (2015)

A label-free and selective aptamer beacon-based Love-wave biosensing device was developed for prostate specific antigen (PSA) detection. The device consists of the following parts: LiTaO3 substrate with SiO2 film as wave guide layer, two set of inter-digital transducers (IDT), gold film for immobilization of the biorecongniton layer and a polydimethylsiloxane (PDMS) microfluidic channels. DNA aptamer, or "artificial antibody", was used as the specific biorecognition probe for PSA capture. Some nucleotides were added to the 3'-end of the aptamer to form a duplex with the 3'-end, turning the aptamer into an aptamer-beacon. Taking advantage of the selective target-induced assembly changes arising from the "aptamer beacon", highly selective and specific detection of PSA was achieved. Furthermore, PDMS microfluidic channels were designed and fabricated to realize automated quantitative sample injection. After optimization of the experimental conditions, the established device showed good performance for PSA detection between 10 ng/mL to 1 μg/mL, with a detection limit of 10 ng/mL. The proposed sensor might be a promising alternative for point of care diagnostics.
Clinical and Bacteriologic Features of Chronic Sinusitis in Children (1989)

The clinical and bacteriologic aspects of chronic sinusitis in childhood were studied. Of 35 children who underwent surgical procedures for chronic sinusitis, 22 had positive bacteriologic cultures of aspirates from the sinus. The most common organisms isolated were Haemophilus influenzae, Streptococcus pneumoniae, and Branhamella catarrhalis. Five of eight S pneumoniae strains were relatively resistant to penicillin and resistant to sulfamethoxazole-trimethoprim. All of the B catarrhalis and 20% of the H influenzae organisms were beta-lactamase positive. Overall, 14 of 28 of the bacteria were penicillin resistant. In addition, all 12 children 2 years of age or younger had a positive bacterial culture as compared with much lower rates in older children. Although the incidence of S pneumoniae strains that are relatively resistant seems to be rising, to our knowledge we report the first description of these organisms as significant pathogens in chronic childhood sinusitis. These results indicate that chronic, difficult to manage sinusitis in very young children is frequently bacterial in origin, especially if the patient is 2 years old or younger. In light of the frequent failure of antibiotic therapy and considering the incidence of relatively resistant S pneumoniae strains, puncture of the sinus should be considered early in the course of chronic sinusitis to isolate pathogenic organisms and determine appropriate antimicrobial therapy.
DNA vaccines: Vector design, delivery, and antigen presentation (1998)

Inoculations with antigen-expressing plasmid DNAs (DNA vaccines) in the production of protective immune responses. Since the initial development of DNA vaccines more than 5 years ago, major strides have been made in the design of efficient vaccine vectors and in the process of vaccine delivery. However, many questions remain regarding the mechanism of cellular transfection and in the development of immune responses. This review addresses functional aspects of DNA vaccines, including vector design and delivery, as well as cellular transfection and antigen presentation. J. Cell. Biochem. Suppls. 30/31:304–311, 1998. © 1998 Wiley-Liss, Inc.
Solvent Triggering between Conformational States in Amphiphilic Shape-Persistent Macrocycles (2002)

The amphiphilic shape-persistent macrocycle 1 containing four phenol-OH groups as polar side groups and four hexyloxy groups as nonpolar side groups in an adaptable arrangement was recrystallized from solvents of different polarity. X-ray crystallography reveals that the conformation of the macrocycle is solvent dependent such that in the pyridine solvate only two of the nonpolar side groups point outward while in the THF solvate all four of them point outward. Moreover, in the latter case the three-dimensional packing leads to the formation of a supramolecular channel structure with a large pore size.
A review of mobile location privacy in the Internet of Things (2012)

The goal of Internet of Things (IoT) research is to extend computing and connectivity to anything, anyone, anywhere and anytime. While there are apparent benefits in using IoT systems, the convergence of technologies has begun to challenge the privacy of users. Powered by location based services, these systems have the potential to enable a systematic mass surveillance and to impinge on the personal privacy of users, especially their location privacy. This paper overviews some of the existing location privacy issues found on mobile devices. Particular attention is paid to the current access permission mechanism used on the Android, iPhone and Windows Mobile platforms. It is anticipated that the current privacy issues in mobile platforms are more likely to be inherited if not magnified in the IoT.
Catalytic Asymmetric Synthesis of Esters from Ketenes (2005)

By building on elementary principles of Brønsted acid−base chemistry, a nucleophile-catalyzed method for the asymmetric synthesis of esters from ketenes has been transformed into a much more versatile and effective Brønsted acid-catalyzed process. The product aryl esters can be converted into useful derivatives, such as enantioenriched alcohols and carboxylic acids.
Recursive map displacement field estimation and its applications (2002)

We briefly describe some of our work on the use of stochastic models to describe the displacement vector field (DVF) in an image sequence. Specifically, autoregressive models are used which describe the abrupt transitions in the DVF with the use of a line process, but also result in spatio-temporally recursive structures. The use of such models in developing maximum a posteriori estimators for the DVF and the line process is subsequently described. Finally, the extension and application of the resulting estimator to the problems of object tracking, video compression and restoration of video sequences is reviewed.