gebhart/patrepeval huggingface dataset:
Function and Protective Capacity ofTreponema pallidumsubsp.pallidumGlycerophosphodiester Phosphodiesterase (1998)

Infectious syphilis, caused by the spirochete bacterium Treponema pallidum subsp. pallidum, remains a public health concern worldwide. The immune-response evasion mechanisms employed by T. pallidum are poorly understood, and prior attempts to identify immunoprotective antigens for subsequent vaccine design have been unsuccessful. Previous investigations conducted in our laboratory identified the T. pallidum glycerophosphodiester phosphodiesterase as a potential immunoprotective antigen by using a differential immunologic expression library screen. In studies reported here, heterologous expression of the T. pallidum glycerophosphodiester phosphodiesterase in Escherichia coli yielded a full-length, enzymatically active protein. Characterization of the recombinant molecule showed it to be bifunctional, in that it exhibited specific binding to human immunoglobulin A (IgA), IgD, and IgG in addition to possessing enzymatic activity. IgG fractionation studies revealed specific binding of the recombinant enzyme to the Fc fragment of human IgG, a characteristic that may play a role in enabling the syphilis spirochete to evade the host immune response. In further investigations, immunization with the recombinant enzyme significantly protected rabbits from subsequent T. pallidum challenge, altering lesion development at the sites of challenge. In all cases, animals immunized with the recombinant molecule developed atypical pale, flat, slightly indurated, and nonulcerative reactions at the challenge sites that resolved before lesions appeared in the control animals. Although protection in the immunized rabbits was incomplete, as demonstrated by the presence of T. pallidum in the rabbit infectivity test, glycerophosphodiester phosphodiesterase nevertheless represents a significantly immunoprotective T. pallidum antigen and thus may be useful for inclusion in an antigen cocktail vaccine for syphilis.
Clostridium difficileToxins: Mechanism of Action and Role in Disease (2005)

As the leading cause of hospital-acquired diarrhea, Clostridium difficile colonizes the large bowel of patients undergoing antibiotic therapy and produces two toxins, which cause notable disease pathologies. These two toxins, TcdA and TcdB, are encoded on a pathogenicity locus along with negative and positive regulators of their expression. Following expression and release from the bacterium, TcdA and TcdB translocate to the cytosol of target cells and inactivate small GTP-binding proteins, which include Rho, Rac, and Cdc42. Inactivation of these substrates occurs through monoglucosylation of a single reactive threonine, which lies within the effector-binding loop and coordinates a divalent cation critical to binding GTP. By glucosylating small GTPases, TcdA and TcdB cause actin condensation and cell rounding, which is followed by death of the cell. TcdA elicits effects primarily within the intestinal epithelium, while TcdB has a broader cell tropism. Important advances in the study of these toxins have been made in the past 15 years, and these are detailed in this review. The domains, subdomains, and residues of these toxins important for receptor binding and enzymatic activity have been elegantly studied and are highlighted herein. Furthermore, there have been major advances in defining the role of these toxins in modulating the inflammatory events involving the disruption of cell junctions, neuronal activation, cytokine production, and infiltration by polymorphonuclear cells. Collectively, the present review provides a comprehensive update on TcdA and TcdB's mechanism of action as well as the role of these toxins in disease.
Use of the P Gene to Genotype Human Metapneumovirus Identifies 4 Viral Subtypes (2004)

This study, conducted during 2001-2003, undertook the screening of patients with acute infectious respiratory-tract disease. A random selection of positive specimens was used for sequencing studies of the human metapneumovirus (hMPV) nucleoprotein gene and the phosphoprotein (P) gene. Australian and international sequences were compared, and a global classification scheme was developed. The hMPV P gene was an ideal molecular target for the detection and genotyping of hMPV. The region contained conserved sequences for reverse-transcriptase-polymerase chain-reaction primers and adequate variability to permit the accurate genotyping of the virus into 2 main lineages and 4 sublineages. Establishing viral identity is essential for the linking of genotype and disease severity.
Implication of RNA structure on antisense oligonucleotide hybridization kinetics (1992)

A 47-nucleotide transcript of the activated Ha-ras gene was prepared and determined, by enzymatic structure mapping, to form a stable hairpin structure. Six antisense decaribonucleotides were designed, and association constants (Ka) for the hairpin- and length-matched complements were measured. Two of the antisense oligonucleotides targeted to the loop had nearly equal affinity for the transcript compared to the complement. The others, including one oligonucleotide complementary to the 3' side of the single-stranded loop, bound 10(5)-10(6)-fold less tightly to the transcript than to the short complement. We propose the difference in affinity is due to the target structure, both the secondary structure of the stem and the structure in the loop. Measurement of the bimolecular association rate constant, k1, and the dissociation rate constant, k-1, for these oligonucleotides indicates the observed relationship between affinity and structure is primarily due to k1.
Specificity of anti-phospholipid antibodies in infectious mononucleosis: a role for anti-cofactor protein antibodies (2000)

SUMMARY The antigen specificity of anti-phospholipid antibodies in infectious mononucleosis (IM) was studied using ELISA for the detection of anti-β2-glycoprotein I (β2-GPI), anti-annexin V, anti-protein S and anti-prothrombin antibodies and TLC immunostaining for the detection of anti-phospholipid antibodies. This technique enabled us to look at antibodies reacting to ‘pure’ phospholipid antigens in the absence of protein contamination. Sera from 46 patients with IM, 18 with systemic lupus erythematosus (SLE), 21 with primary anti-phospholipid antibody syndrome (PAPS), 50 with Helicobacter pylori infection and 30 healthy blood donors were tested. This study highlights anti-phospholipid antibodies in patients with IM as specific ‘pure’ anti-cardiolipin antibodies, while in PAPS and SLE patients anti-phosphatidylserine and anti-phosphatidylethanolamine antibodies were also found. This investigation also shows that the anti-cardiolipin antibodies found in IM can be present with anti-cofactor protein antibodies. The higher prevalence of anti-cofactor antibodies found in IM sera than in Helicobacter pylori sera may be due to the immunostimulatory effect and/or the polyclonal activation often observed in course of Epstein–Barr virus infection. However, anti-β2-GPI and, to a lesser extent, anti-prothrombin antibodies occur with a significantly lower prevalence in IM than in PAPS patients. This finding suggests that these antibodies should be regarded as the expression of the broad autoimmune syndrome involving the phospholipid-binding plasma proteins.
Tandem Ligation of Multipartite Peptides with Cell-Permeable Activity (2002)

To prepare multipartite peptides with several functional cargoes including a cell-permeable sequence or transportant for intracellular delivery, tandem ligation of peptides is a convenient convergent approach with the fewest synthetic steps. It links three or four unprotected segments forming two or more regiospecific bonds consecutively without a deprotection step. This paper describes a tandem ligation strategy to prepare multipartite peptides with normal and branched architectures carrying a novel transportant peptide that is rich in arginine and proline to permit their cargoes to be translocated across membranes to affect their biological functions in cytoplasm. Our strategy consists of three ligation methods specific for amino terminal cysteine (Cys), serine/threonine (Ser/Thr), and N(alpha)-chloroacetylated amine to afford Xaa-Cys, Xaa-OPro (oxaproline) and Xaa-psiGly (pseudoglycine) at the ligation sites, respectively. Assembly of single-chain peptides from three different segments was achieved by the tandem Cys/OPro ligation to form two amide bonds, an Xaa-Cys and then an Xaa-OPro. Assembly of two- and three-chain peptides with branched architectures from four different segments was accomplished by tandem Cys/psiGly/OPro ligation. These NT-specific tandem ligation strategies were successful in generating cell-permeable multipartite peptides with one-, two-, and three-chain architectures, ranging in size from 52 to 75 residues and without the need of a protection or deprotection step. In addition, our results show that there is considerable flexibility in architectural design to obtain cell-permeable multipartite peptides containing a transportant sequence.
Steric and hydrophobic determinants of the solubilities of recombinant sickle cell hemoglobins (1992)

Models for the structure of the fibers of deoxy sickle cell hemoglobin (Hb Hb S, beta 6 Glu-->Val) have been obtained from X-ray and electron microscopic studies. Recent molecular dynamics calculations of polymer formation give new insights on the various specific interactions between monomers. Site-directed mutagenesis with expression of the Hb S beta subunits in Escherichia coli provides the experimental tools to test these models. For Hb S, the beta 6 Val residue is intimately involved in a specific lateral contact, at the donor site, that interacts with the acceptor site of an adjacent molecule composed predominantly of the hydrophobic residues Phe 85 and Leu 88. Comparing natural and artificial mutants indicates that the solubility of deoxyHb decreases in relation to the surface hydrophobicity of the residue at the beta 6 position with Ile > Val > Ala. We also tested the role of the stereospecific adjustment between the donor and acceptor sites by substituting Trp for Glu at the beta 6 location. Among these hydrophobic substitutions and under our experimental conditions, only Val and Ile were observed to induce polymer formation. The interactions for the Ala mutant are too weak whereas a Trp residue inhibits aggregation through steric hindrance at the acceptor site of the lateral contact. Increasing the hydrophobicity at the axial contact between tetramers of the same strand also contributes to the stability of the double strand. This is demonstrated by associating the beta 23 Val-->Ile mutation at the axial contact with either the beta 6 Glu-->Val or beta 6 Glu-->Ile substitution in the same beta subunit.(ABSTRACT TRUNCATED AT 250 WORDS)
Cannabinoids as therapeutic agents in cancer: current status and future implications (2014)

The pharmacological importance of cannabinoids has been in study for several years. Cannabinoids comprise of (a) the active compounds of the Cannabis sativa plant, (b) endogenous as well as (c) synthetic cannabinoids. Though cannabinoids are clinically used for anti-palliative effects, recent studies open a promising possibility as anti-cancer agents. They have been shown to possess anti-proliferative and anti-angiogenic effects in vitro as well as in vivo in different cancer models. Cannabinoids regulate key cell signaling pathways that are involved in cell survival, invasion, angiogenesis, metastasis, etc. There is more focus on CB1 and CB2, the two cannabinoid receptors which are activated by most of the cannabinoids. In this review article, we will focus on a broad range of cannabinoids, their receptor dependent and receptor independent functional roles against various cancer types with respect to growth, metastasis, energy metabolism, immune environment, stemness and future perspectives in exploring new possible therapeutic opportunities.
A CMOS channel-select filter for a direct-conversion wireless receiver (1997)

A highly selective and linear switched-capacitor channel-select filter is fabricated in 1-/spl mu/m CMOS for a direct-conversion wireless receiver operating in the 902-928 MHz ISM band. The filter selects a 230-kHz wide channel and attenuates by at least 50 dB from 320 kHz to 57 MHz. The input IP3 is +30 dBm, the input-referred noise in the passband is 70 nV//spl radic/Hz, and the circuit takes 4.6 mA from a 3.3 V supply. Direct subsampling of the 915 MHz RF input signal by the filter front-end is also demonstrated with only a small degradation in linearity. The input noise voltage is halved in a redesign while keeping the current drain unchanged.
Efficient and Selective P‐nitrophenyl‐ester‐hydrolyzing Antibodies Elicited by a P‐nitrobenzyl Phosphonate Hapten (1997)

A number of monoclonal antibodies elicited against a nitrobenzyl (Nbzl)-phosphonate transition-state analogue (TSA), and which were selected for the hydrolysis of the corresponding Nbzl-ester, were also found to catalyze the hydrolysis of the analogous p-nitrophenyl(Np) ester with notable efficiency and specificity. The activity towards the Np-ester is higher in terms of rates (k(cat); as expected from the higher intrinsic reactivity of Np-esters); however, the rate acceleration (k(cat)/k(uncat)) is close to or lower than that observed with the Nbzl-ester. Unexpectedly, the affinity to the Np-ester substrate (1/K(M)) and therefore k(cat)/K(M) are significantly higher. The best example is antibody D2.4 having a k(cat)/K(M) value of 64 s(-1) x M(-1) with the Nbzl-ester and 9400 s(-1) x M(-1) with the Np-ester. Moreover, due to a lower product inhibition by p-nitrophenol relative to p-nitrobenzyl alcohol, these antibodies exhibit more than 1000 turnovers with the Np-ester. The differential affinity of these antibodies to the Nbzl-phosphonate TSA versus the Nbzl-ester substrate (K(S)/K(TSA) or K(M)/K(i)) correlates well with the observed rate enhancement (k(cat)/k(uncat)). For the Np-ester, however, stabilisation of the transition state (as reflected by K(S)/K(TSA) and by the catalytic proficiencies, k(cat)/K(M)/k(uncat)) does not fully account for the catalytic power (k(cat)/k(uncat)), indicating a more complex catalytic mechanism than simply transition-state stabilization. A comparison of the kinetic parameters of D2.4 with other Np-ester-hydrolyzing antibodies raised against Np-phosphonate haptens emphasizes the marked advantage of this antibody which was elicited against an Nbzl-phosphonate hapten. These results appear to be general: anti-(Nbzl-phosphonate TSA) antibodies obtained from other mouse strains and using different immunization protocols are also efficient Np-esterases. They demonstrate the use of an expanded TSA-hapten, where a spacer (a methylene group) mimics bonds that are partially cleaved in the transition state of the catalyzed reaction.
Fluorescence‐activated cell sorting purification of pancreatic progenitor cells (2008)

Here we review progress on isolation and characterization of progenitor cells in the pancreas. We discuss advantages and current limitations of experiments with purified pancreatic cells, and areas where future growth in our understanding is needed to advance experiments in pancreas biology based on cell purification.
A Barcode Screen for Epigenetic Regulators Reveals a Role for the NuB4/HAT-B Histone Acetyltransferase Complex in Histone Turnover (2011)

Dynamic modification of histone proteins plays a key role in regulating gene expression. However, histones themselves can also be dynamic, which potentially affects the stability of histone modifications. To determine the molecular mechanisms of histone turnover, we developed a parallel screening method for epigenetic regulators by analyzing chromatin states on DNA barcodes. Histone turnover was quantified by employing a genetic pulse-chase technique called RITE, which was combined with chromatin immunoprecipitation and high-throughput sequencing. In this screen, the NuB4/HAT-B complex, containing the conserved type B histone acetyltransferase Hat1, was found to promote histone turnover. Unexpectedly, the three members of this complex could be functionally separated from each other as well as from the known interacting factor and histone chaperone Asf1. Thus, systematic and direct interrogation of chromatin structure on DNA barcodes can lead to the discovery of genes and pathways involved in chromatin modification and dynamics.
Stick and slip actuators: design, control, performances and applications (2002)

This paper describes stick and slip actuators, which can be included into the family of inertial drives. We propose several configurations and a modeling of these actuators. Stick and slip actuators present the advantage of allowing long displacements (several centimeters or even more) at high speed (several mm/s) with ultrahigh resolution (<5 mn). Moreover, they are simple, compact and have high stiffness. They are therefore well adapted to challenging applications such as micromanipulation. Long displacements are obtained by stepping motion (stepping mode), each step being typically 400 mm, while fine displacements with high resolution are made possible by a scanning-mode. A simple controller, combining stepping- and scanning-modes, has been designed. The excellent performance of a 1-degree-of-freedom (1-DOF) actuator is demonstrated. An innovative concept, the so called "monolithic piezoceramics flexible structures" allowing to design extremely simple micromanipulators, is also reported. Four prototypes are presented: a 1-DOF actuator, a 6-DOF platform and two 3-DOF mobile microrobots. The authors also describe briefly four applications where stick and slip actuators have been used successfully, namely: a sample holder for AFM (tilt), a micro-EDM machine, a microassembly system and a micro-telemanipulation system for biological specimens.
Beam-Beam Simulations with GUINEA-PIG (1998)

While the bunches in a linear collider cross only once, due to their small size they experience a strong beam-beam effect. GUINEA-PIG is a code to simulate the impact of this effect on luminosity and back ground. A short overview of the program is given with examples of its application to the back ground strudies for TESLA, the top quark threshold scan and a possible luminosity monitor, as well as some results for CLIC.
Three‐dimensional extracellular matrix engineering in the nervous system (1998)

Growing neurites are guided through their environment during development and regeneration via different cellular and extracellular matrix (ECM) molecular cues. To mimic cell–matrix interactions, a three-dimensional (3D) hydrogel-based ECM equivalent containing a covalently immobilized laminin oligopeptide sequence was designed to facilitate nerve regeneration. This study illustrates that the oligopeptide domain CDPGYIGSR covalently linked to an agarose gel as a bioartificial 3D substrate successfully supports neurite outgrowth from dorsal root ganglia (DRG) in vitro. The specificity of the neurite promoting activity was illustrated through the inhibition of neurite outgrowth from DRG in a CDPGYIGSR-derivatized gel in the presence of solubilized CDPGYIGSR peptide. Gels derivatized with CDPGYIGSK and CDPGRGSYI peptides stimulated a smaller increase of neurite outgrowth. In vivo experiments revealed the capability of a CDPGYIGSR-derivatized gel to enhance nerve regeneration in a transected rat dorsal root model compared to an underivatized gel, a CDPGRGSYI gel, and saline-filled nerve guidance channels. These data suggest the feasibility of a 3D hydrogel-based ECM equivalent capable of enhancing neurite outgrowth in vitro and in vivo. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 392–400, 1998.
Intramolecular [4+3] Cycloadditions. Studies of Relative Asymmetric Induction (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIntramolecular [4+3] Cycloadditions. Studies of Relative Asymmetric InductionMichael Harmata, Chandra B. Gamlath, Charles L. Barnes, and Darin E. JonesCite this: J. Org. Chem. 1995, 60, 16, 5077–5092Publication Date (Print):August 1, 1995Publication History Published online1 May 2002Published inissue 1 August 1995https://pubs.acs.org/doi/10.1021/jo00121a028https://doi.org/10.1021/jo00121a028research-articleACS PublicationsRequest reuse permissionsArticle Views554Altmetric-Citations35LEARN 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 (3)»Supporting Information Supporting Information Get e-Alerts
Experience with colonic volvulus (1989)

Fifty-eight cases of colonic volvulus were reviewed including 30 cases of sigmoid volvulus, 27 cases of cecal volvulus, and 1 of transverse colon volvulus. Decompression procedures were attempted in 31 instances of sigmoid volvulus in 27 patients and were successful 25 times (81 percent). Seven patients with sigmoid volvulus did not undergo surgery and of those, two died of unrelated causes, one was lost to follow-up, one was well, and three had recurrent volvulus. Twenty-four operations were performed on 23 patients and there were three deaths (13 percent mortality). There was one recurrence in two patients who underwent simple detorsion. Chronic large-bowel motility disturbances were a persistent problem in 9 of 20 (45 percent) surgical survivors. Among 27 instances of cecal volvulus, one was reduced by contrast enema and ten endoscopic attempts at decompression were unsuccessful. Twenty-six operations were done and there were four operative deaths (15 percent mortality). There were no recurrences. Large-bowel motility disorders were noted in follow-up in 3 of 22 patients (14 percent). Overall there were 10 deaths in 58 patients for a 17 percent mortality rate. These data support the importance of endoscopic decompression for sigmoid volvulus but not for cecal volvulus. Definitive treatment of both forms of volvulus should include assessment of colonic motility.
30.3: Invited Paper : AMOLED Manufacturing – Challenges and Solutions from a Material Makers Perspective (2014)

Abstract The paper describes fundamental material properties required for modern day evaporation based AMOLED manufacturing and shows how material manufacturers have to adapt their products developments to those needs.
Nanoparticle–aptamer bioconjugates for cancer targeting (2006)

The combination of targeted drug delivery and controlled-release technology may pave the road for more effective yet safer chemotherapeutic options for cancer therapy. Drug-encapsulated polymeric nanoparticle-aptamer bioconjugates represent an emerging technology that can facilitate the delivery of chemotherapeutics to primary and metastatic tumours. Aptamers are short nucleic acid molecules with binding properties and biochemical characteristics that may make them suitable for use as targeting molecules. The goal of this review is to summarise the key components that are required for creating effective cancer targeting nanoparticle-aptamer bioconjugates. The field of controlled release and the structure and properties of aptamers, as well as the criteria for constructing effective conjugates, will be discussed.