gebhart/patrepeval huggingface dataset:
Conversion of CTLA-4 from Inhibitor to Activator of T Cells with a Bispecific Tandem Single-Chain Fv Ligand (2004)

Abs or their recombinant fragments against surface receptors of the Ig superfamily can induce or block the receptors' native function depending on whether they induce or prevent the assembly of signalosomes on their cytoplasmic tails. In this study, we introduce a novel paradigm based on the observation that a bispecific tandem single-chain variable region fragment ligand of CTLA-4 by itself converts this inhibitory receptor into an activating receptor for primary human T lymphocytes. This reversal of function results from increased recruitment of the serine/threonine phosphatase 2A to the cytoplasmic tail of CTLA-4, consistent with a role of this phosphatase in the regulation of CTLA-4 function, and assembly of a distinct signalosome that activates an lck-dependent signaling cascade and induces IL-2 production. Our data demonstrate that the cytoplasmic domain of CTLA-4 has an inherent plasticity for signaling that can be exploited therapeutically with recombinant ligands for this receptor.
Tyrosyl radical generated by myeloperoxidase catalyzes the oxidative cross-linking of proteins. (1993)

Phagocytes generate H2O2 for use by a secreted heme enzyme, myeloperoxidase, to kill invading bacteria, viruses, and fungi. We have explored the possibility that myeloperoxidase might also convert L-tyrosine to a radical catalyst that cross-links proteins. Protein-bound tyrosyl residues exposed to myeloperoxidase, H2O2, and L-tyrosine were oxidized to o,o'-dityrosine, a stable product of the tyrosyl radical. The cross-linking reaction required L-tyrosine but was independent of halide and free transition metal ions; the heme poisons azide and aminotriazole were inhibitory. Activated neutrophils likewise converted polypeptide tyrosines to dityrosine. The pathway for oxidation of peptide tyrosyl residues was dependent upon L-tyrosine and was inhibited by heme poisons and catalase. Dityrosine synthesis was little affected by plasma concentrations of Cl- and amino acids, suggesting that the reaction pathway might be physiologically relevant. The requirement for free L-tyrosine and H2O2 for dityrosine formation and the inhibition by heme poisons support the hypothesis that myeloperoxidase catalyzes the cross-linking of proteins by a peroxidative mechanism involving tyrosyl radical. In striking contrast to the pathways generally used to study protein oxidation in vitro, the reaction does not require free metal ions. We speculate that protein dityrosine cross-linking by myeloperoxidase may play a role in bacterial killing or injuring normal tissue. The intense fluorescence and stability of biphenolic compounds may allow dityrosine to act as a marker for proteins oxidatively damaged by myeloperoxidase in phagocyte-rich inflammatory lesions.
Polyisobutylene‐containing block polymers by sequential monomer addition. X. Synthesis of poly(α‐methylstyrene‐b‐isobutylene‐b‐α‐methylstyrene) thermoplastic elastomers (1994)

Abstract Preparatory to triblock synthesis experiments, the cationic polymerization of α‐methylstyrene (αMeSt) was investigated using the 2‐chloro‐2,4,4‐trimethylpentane (TMPCI)/TiCl 4 initiating system in the presence of triethylamine (Et 3 N) as electron donor (ED) and CH 3 Cl/ n ‐hexane mixed solvent in the −80 to −40°C range. Conversions are influenced by temperature, [TiCl 4 ], [Et 3 N], and [αMeSt]. The polymerization of αMeSt is living at −80°C: Both termination and chain transfer to monomer are frozen out, however, initiation is slow relative to propagation. Highly syndiotactic (&gt;94%) Pα Mest was obtained. At−60deg;C initiator efficiency is ca. 100%, but termination becomes evident. Et 3 N may act both as Ed and as proton scavenger. Novel poly(α‐methystyrene‐b‐isobutylene‐b‐α‐methylstyrene) (PαMeSt‐PIB‐PαMeSt) triblocks have been synthesized by adding αMeSt to biliving polyisobutylene carbocations (⊕PIB⊕) in the −80 to −40°C range. The effects of temperature, solvent polarity, and [Et 3 N] on the block copolymerization have been investigated. At −80°C, the rate of crossover from ⊕PIB⊕ to αMeSt is lower than that of propagation of PαMeSt⊕, so that the triblock is contaminated by PIB and PIB‐b‐PαMeSt. At −60°C, crossover occurs preferentially. The rate of propagation relative to that of crossover is also reduced by lowering the solvent polarity and increasing the [Et 3 N]. High crossover efficiency and blocking efficiency can be obtained under optimum blocking conditions. The triblocks are novel thermoplastic elastomers (TPEs). © 1994 John Wiley &amp; Sons, Inc.
Chemosynthetic sulphur-oxidizing symbionts of marine invertebrate animals are capable of nitrogen fixation (2016)

Chemosynthetic symbioses are partnerships between invertebrate animals and chemosynthetic bacteria. The latter are the primary producers, providing most of the organic carbon needed for the animal host's nutrition. We sequenced genomes of the chemosynthetic symbionts from the lucinid bivalve Loripes lucinalis and the stilbonematid nematode Laxus oneistus. The symbionts of both host species encoded nitrogen fixation genes. This is remarkable as no marine chemosynthetic symbiont was previously known to be capable of nitrogen fixation. We detected nitrogenase expression by the symbionts of lucinid clams at the transcriptomic and proteomic level. Mean stable nitrogen isotope values of Loripes lucinalis were within the range expected for fixed atmospheric nitrogen, further suggesting active nitrogen fixation by the symbionts. The ability to fix nitrogen may be widespread among chemosynthetic symbioses in oligotrophic habitats, where nitrogen availability often limits primary productivity.
An implantable multielectrode array with on-chip signal processing (1986)

This active probe can be used for the long-term recording of extracellular neural biopotentials and as a basis for closed-loop neural prostheses. The probe incorporates on-chip circuitry for amplifying, multiplexing, and buffering neural signals recorded from ten recording electrodes spaced 100-/spl mu/m apart. It requires only three leads and operates from a single 5-V supply. On-chip self-test circuitry for testing electrode impedance levels is provided. The on-chip circuitry is fabricated in a die area of 1.3 mm/SUP 2/ using 6-/spl mu/m LOCOS enhancement-depletion NMOS technology, and dissipates 5 mW of power. The probe is 4.7 mm long and 15 /spl mu/m thick, and has a shank which tapers from 160 /spl mu/m near the base to less than 15 /spl mu/m near the tip.
An integrated approach utilizing proteomics and bioinformatics to detect ovarian cancer (2005)

The combination of SELDI with bioinformatics tools could find new biomarkers and establish patterns with high sensitivity and specificity for the detection of ovarian cancer.
Intracellular traffic of the MHC class I-like IgG Fc receptor, FcRn, expressed in epithelial MDCK cells (1999)

Transfer of passive immunity from mother to the fetus or newborn involves the transport of IgG across several epithelia. Depending on the species, IgG is transported prenatally across the placenta and yolk sac or is absorbed from colostrum and milk by the small intestine of the suckling newborn. In both cases apical to basolateral transepithelial transport of IgG is thought to be mediated by FcRn, an IgG Fc receptor with homology to MHC class I antigens. We have now expressed the human FcRn in polarized MDCK cells and analyzed the intracellular routing of the receptor. FcRn showed a predominant intracellular localization at steady state. Newly synthesized FcRn was delivered in a non-vectorial fashion to both the apical and basolateral surfaces of MDCK cell monolayers. Following internalization from the apical or basolateral domain, the receptor transcytosed to the opposite surface. These findings provide direct evidence for the transepithelial transport function of FcRn and indicate that the receptor undergoes multiple rounds of transcytosis.
Control of auxin-regulated root development by the Arabidopsis thaliana SHY2/IAA3 gene (1999)

The plant hormone auxin controls many aspects of development and acts in part by inducing expression of various genes. Arabidopsis thaliana semidominant shy2 (short hypocotyl) mutations cause leaf formation in dark-grown plants, suggesting that SHY2 has an important role in regulating development. Here we show that the SHY2 gene encodes IAA3, a previously known member of the Aux/IAA family of auxin-induced genes. Dominant shy2 mutations cause amino acid changes in domain II, conserved among all members of this family. We isolated loss-of-function shy2 alleles including a putative null mutation. Gain-of-function and loss-of-function shy2 mutations affect auxin-dependent root growth, lateral root formation, and timing of gravitropism, indicating that SHY2/IAA3 regulates multiple auxin responses in roots. The phenotypes suggest that SHY2/IAA3 may activate some auxin responses and repress others. Models invoking tissue-specificity, feedback regulation, or control of auxin transport may explain these results.
Sputum microRNA Biomarkers for Identifying Lung Cancer in Indeterminate Solitary Pulmonary Nodules (2015)

Sputum miRNA biomarkers may improve LDCT screening for lung cancer in heavy smokers by preoperatively diagnosing malignant SPNs. Nevertheless, a prospective study in a large population to validate the biomarkers is needed.
Carbon Metal Fluoride Nanocomposites (2003)

The structure and electrochemistry of -based carbon metal fluoride nanocomposites (CMFNCs) was investigated in detail from 4.5 to 1.5 V, revealing a reversible metal fluoride conversion process. These are the first reported examples of a high-capacity reversible conversion process for positive electrodes. A reversible specific capacity of approximately 600 mAh/g of CMFNCs was realized at 70°C. Approximately one-third of the capacity evolved in a reaction between 3.5 and 2.8 V related to the cathodic reduction reaction of to The remainder of the specific capacity occurred in a two-phase conversion reaction at 2 V resulting in the formation of a finer Fe:LiF nanocomposite. Upon oxidation, selective area electron diffraction characterization revealed the reformation of a metal fluoride. Evidence presented suggested that the metal fluoride is related to in structure. A pseudocapacitive reaction is proposed as a possible mechanism for the subsequent oxidation reaction. Preliminary results of and CMFNCs were used in the discussion of the electrochemical properties of the reconverted metal fluoride. © 2003 The Electrochemical Society. All rights reserved.
High-Voltage FET Amplifiers for Satellite and Phased-Array Applications (2005)

The high-voltage FET amplifier (HVFA) configuration for power amplifier applications in satellite communications and phased-array systems can offer substantial improvement in DC-to-RF conversion efficiency. A proof-of-concept experiment, design considerations, and the RF results of MIC implementation at C- and X-band are reported. An X-band MMIC HVFA design is also presented.
Guided Bone Regeneration in Calvarial Bone Defects Using Polytetrafluoroethylene Membranes (1995)

Guided bone regeneration is defined as controlled stimulation of new bone formation in a bony defect, either by osteogenesis, osteoinduction, or osteoconduction, re-establishing both structural and functional characteristics. Bony defects may be found as a result of congenital anomalies, trauma, neoplasms, or infectious conditions. Such conditions are often associated with severe functional and esthetic problems. Corrective treatment is often complicated by limitations in tissue adaptations. The aim of the investigation was to compare histologically the amount of bone formed in an experimentally created parietal bone defect protected with one or two polytetrafluoroethylene membranes with a contralateral control defect. A bony defect was created bilaterally in the parietal bone lateral to the sagittal suture in 29 6-month-old male Wistar rats. The animals were divided into two groups: (1) In the double membrane group (n = 9), the left experimental bone defect was protected by an outer polytetrafluoroethylene membrane under the periosteum and parietal muscles and an inner membrane between the dura mater and the parietal bone. (2) In the single membrane group (n = 20), only the outer membrane was placed. The right defect was not covered with any membrane and served as control. The animals were killed after 30 days. None of the control defects demonstrated complete or partial bone regeneration. In the single membrane group, the experimental site did not regenerate in 15 animals, partially in four, and completely in one. In the double membrane group, six of the experimental defects had complete closure with bone, two had partial closure, and one no closure.(ABSTRACT TRUNCATED AT 250 WORDS)
Intravitreal VEGF and bFGF produce florid retinal neovascularization and hemorrhage in the rabbit (2001)

These results demonstrate that retinal vascular changes leading to hemorrhaging is produced rapidly in the rabbit by simultaneous intravitreal release of both VEGF and bFGF. Understanding how these growth factors induce retinal NV may suggest novel therapeutic treatment strategies.
Caspase-cleaved Tau Expression Induces Mitochondrial Dysfunction in Immortalized Cortical Neurons (2009)

In Alzheimer disease (AD) mitochondrial abnormalities occur early in the pathogenic process and likely play a significant role in disease progression. Tau is a microtubule-associated protein that is abnormally processed in AD, and a connection between tau pathology and mitochondrial impairment has been proposed. However, few studies have examined the relationship between pathological forms of tau and mitochondrial dysfunction. We recently demonstrated that inducible expression of tau truncated at Asp-421 to mimic caspase cleavage (T4C3) was toxic to immortalized cortical neurons compared with a full-length tau isoform (T4). In this study we investigated the effects of T4C3 on mitochondrial function. Expression of T4C3 induced mitochondrial fragmentation and elevated oxidative stress levels in comparison with T4-expressing cells. Thapsigargin treatment of T4 or T4C3 cells, which causes an increase in intracellular calcium levels, resulted in a significant decrease in mitochondrial potential and loss of mitochondrial membrane integrity in T4C3 cells when compared with cells expressing T4. The mitochondrial fragmentation and mitochondrial membrane damage were ameliorated in T4C3 cells by pretreatment with cyclosporine A or FK506, implicating the calcium-dependent phosphatase calcineurin in these pathogenic events. Increased calcineurin activity has been reported in AD brain, and thus, inhibition of this phosphatase may provide a therapeutic target for the treatment of AD.
Engineering and Preclinical Evaluation of Attenuated Nontyphoidal Salmonella Strains Serving as Live Oral Vaccines and as Reagent Strains (2011)

While nontyphoidal Salmonella (NTS) has long been recognized as a cause of self-limited gastroenteritis, it is becoming increasingly evident that multiple-antibiotic-resistant strains are also emerging as important causes of invasive bacteremia and focal infections, resulting in hospitalizations and deaths. We have constructed attenuated Salmonella enterica serovar Typhimurium and Salmonella enterica serovar Enteritidis strains that can serve as live oral vaccines and as "reagent strains" for subunit vaccine production in a safe and economical manner. Prototype attenuated vaccine strains CVD 1921 and CVD 1941, derived from the invasive wild-type strains S. Typhimurium I77 and S. Enteritidis R11, respectively, were constructed by deleting guaBA, encoding guanine biosynthesis, and clpP, encoding a master protease regulator. The clpP mutation resulted in a hyperflagellation phenotype. An additional deletion in fliD yielded reagent strains CVD 1923 and CVD 1943, respectively, which export flagellin monomers. Oral 50% lethal dose (LD₅₀) analyses showed that the NTS vaccine strains were all highly attenuated in mice. Oral immunization with CVD 1921 or CVD 1923 protected mice against lethal challenge with wild-type S. Typhimurium I77. Immunization with CVD 1941 but not CVD 1943 protected mice against lethal infection with S. Enteritidis R11. Immune responses induced by these strains included high levels of serum IgG anti-lipopolysaccharide (LPS) and anti-flagellum antibodies, with titers increasing progressively during the immunization schedule. Since S. Typhimurium and S. Enteritidis are the most common NTS serovars associated with invasive disease, these findings can pave the way for development of a highly effective, broad-spectrum vaccine against invasive NTS.
Complex Target SELEX (2008)

Aptamers are non-naturally occurring structured oligonucleotides that may bind to small molecules, peptides, and proteins. Typically, aptamers are generated by an in vitro selection process referred to as SELEX (systematic evolution of ligands by exponential enrichment). Aptamers that bind with high affinity and specificity to proteins that reside on the cell surface have potential utility as therapeutic antagonists, agonists, and diagnostic agents. When the target protein requires the presence of the cell membrane (e.g., G-protein-coupled receptors, ion channels) or a co-receptor to fold properly, it is difficult or impossible to program the SELEX experiment with purified, soluble protein target. Recent advances in which the useful range of SELEX has been extended from comparatively simple purified forms of soluble proteins to complex mixtures of proteins in membrane preparations or in situ on the surfaces of living cells offer the potential to discover aptamers against previously intractable targets. Additionally, in cases in which a cell-type specific diagnostic is sought, the most desirable target on the cell surface may not be known. Successful application of aptamer selection techniques to complex protein mixtures can be performed even in the absence of detailed target knowledge and characterization. This Account presents a review of recent work in which membrane preparations or whole cells have been utilized to generate aptamers to cell surface targets. SELEX experiments utilizing a range of target "scaffolds" are described, including cell fragments, parasites and bacteria, viruses, and a variety of human cell types including adult mesenchymal stem cells and tumor lines. Complex target SELEX can enable isolation of potent and selective aptamers directed against a variety of cell-surface proteins, including receptors and markers of cellular differentiation, as well as determinants of disease in pathogenic organisms, and as such should have wide therapeutic and diagnostic utility.
Gas turbine NO{sub x} emissions approaching zero -- Is it worth the price? (1999)

The requirement for gas turbines to meet ever lower NO{sub x} emission levels results from a regulatory approach developed before combustion systems existed that are capable of achieving single digit NO{sub x}. Dry low NO{sub x} (DLN) combustors for GE Frame 7FAs, 7EAs and 6Bs are now demonstrating 9 ppm NO{sub x}. This paper compares the energy, environmental and economic impacts of requiring add-on emission controls to achieve a lower level of NO{sub x}, with a gas turbine combustion system that is already capable of achieving single digit NO{sub x}. The conclusion reached is that ratcheting NO{sub x} down to lower and lower levels through the use of add-on emission controls reaches the point of diminishing return when the gas turbine combustion system is capable of achieving single digit NO{sub x}. The cost of add-on emission controls to achieve a lower NO{sub x} level becomes excessive, the heat rate increases and the overall environmental impacts are actually worsened. The recommendation is made for the U.S. EPA to amend the regulatory process to allow permit authorities to consider conflicting environmental, energy and economic impacts in nonattainment areas, as they now can in attainment areas, in cases where add-on emission controls willmore » result in only a small reduction in emissions.« less
ChemInform Abstract: A Convenient Synthesis of 3‐ and 3,4‐Substituted 4,5‐Dihydroisoxazole‐ 5‐acetic Acids. (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
High-Level Vancomycin-Resistant Staphylococcus aureus Isolates Associated with a Polymicrobial Biofilm (2006)

Glycopeptides such as vancomycin are the treatment of choice for infections due to methicillin-resistant Staphylococcus aureus. This study describes the identification of high-level vancomycin-resistant S. aureus (VRSA) isolates in a polymicrobial biofilm within an indwelling nephrostomy tube in a patient in New York. S. aureus, Enterococcus faecalis, Enterococcus faecium, Micrococcus species, Morganella morganii, and Pseudomonas aeruginosa were isolated from the biofilm. For VRSA isolates, vancomycin MICs ranged from 32 to >128 microg/ml. VRSA isolates were also resistant to aminoglycosides, fluoroquinolones, macrolides, penicillin, and tetracycline but remained susceptible to chloramphenicol, linezolid, rifampin, and trimethoprim-sulfamethoxazole. The vanA gene was localized to a plasmid of approximately 100 kb in VRSA and E. faecium isolates from the biofilm. Plasmid analysis revealed that the VRSA isolate acquired the 100-kb E. faecium plasmid, which was then maintained without integration into the MRSA plasmid. The tetracycline resistance genes tet(U) and tet(S), not previously detected in S. aureus isolates, were identified in the VRSA isolates. Additional resistance elements in the VRSA isolate included a multiresistance gene cluster, ermB-aadE-sat4-aphA-3, msrA (macrolide efflux), and the bifunctional aminoglycoside resistance gene aac(6')-aph(2")-Ia. Multiple combinations of resistance genes among the various isolates of staphylococci and enterococci, including vanA, tet(S), and tet(U), illustrate the dynamic nature of gene acquisition and loss within and between bacterial species throughout the course of infection. The potential for interspecies transfer of antimicrobial resistance genes, including resistance to vancomycin, may be enhanced by the microenvironment of a biofilm.
CCCLXXXII.—The action of highly concentrated hydrochloric acid on cellulose and on some derivatives of glucose and of xylose (1923)

E. L. Hirst and D. R. Morrison, J. Chem. Soc., Trans., 1923, 123, 3226 DOI: 10.1039/CT9232303226
RNA-guided editing of bacterial genomes using CRISPR-Cas systems (2013)

Here we use the clustered, regularly interspaced, short palindromic repeats (CRISPR)–associated Cas9 endonuclease complexed with dual-RNAs to introduce precise mutations in the genomes of Streptococcus pneumoniae and Escherichia coli. The approach relies on dual-RNA:Cas9-directed cleavage at the targeted genomic site to kill unmutated cells and circumvents the need for selectable markers or counter-selection systems. We reprogram dual-RNA:Cas9 specificity by changing the sequence of short CRISPR RNA (crRNA) to make single- and multinucleotide changes carried on editing templates. Simultaneous use of two crRNAs enables multiplex mutagenesis. In S. pneumoniae, nearly 100% of cells that were recovered using our approach contained the desired mutation, and in E. coli, 65% that were recovered contained the mutation, when the approach was used in combination with recombineering. We exhaustively analyze dual-RNA:Cas9 target requirements to define the range of targetable sequences and show strategies for editing sites that do not meet these requirements, suggesting the versatility of this technique for bacterial genome engineering.