gebhart/patrepeval huggingface dataset:
Evaluation of synergism among Bacillus thuringiensis toxins (1992)

A simple test for synergism among toxins is described and applied to previously reported data on independent and joint toxicities of insecticidal proteins from Bacillus thuringiensis. The analysis shows synergism between a 27-kDa (CytA) toxin and 130- or 65-kDa (CryIV) toxins from B. thuringiensis subsp. israelensis against Aedes aegypti larvae. No positive synergism between 130- and 65-kDa toxins or among three CryIA toxins tested against seven species of Lepidoptera occurred. Comparisons with the original interpretations of these data show one case in which synergism occurred but was reported previously as absent and two cases that were not synergistic but were reported previously as suggestive of synergism. These results show that lack of an appropriate test for synergism can produce misleading conclusions. The methods described here can be used to test for synergistic effects of any poisons.
Effects of Interleukin-13 Blockade on Allergen-induced Airway Responses in Mild Atopic Asthma (2010)

IL-13 has a role in allergen-induced airway responses in humans. Further study is required to determine whether anti-IL-13 monoclonal antibodies will be beneficial clinically.
Leukemia-Associated Somatic Mutations Drive Distinct Patterns of Age-Related Clonal Hemopoiesis (2015)

Clonal hemopoiesis driven by leukemia-associated gene mutations can occur without evidence of a blood disorder. To investigate this phenomenon, we interrogated 15 mutation hot spots in blood DNA from 4,219 individuals using ultra-deep sequencing. Using only the hot spots studied, we identified clonal hemopoiesis in 0.8% of individuals under 60, rising to 19.5% of those ≥90 years, thus predicting that clonal hemopoiesis is much more prevalent than previously realized. DNMT3A-R882 mutations were most common and, although their prevalence increased with age, were found in individuals as young as 25 years. By contrast, mutations affecting spliceosome genes SF3B1 and SRSF2, closely associated with the myelodysplastic syndromes, were identified only in those aged >70 years, with several individuals harboring more than one such mutation. This indicates that spliceosome gene mutations drive clonal expansion under selection pressures particular to the aging hemopoietic system and explains the high incidence of clonal disorders associated with these mutations in advanced old age.
Synergistic growth inhibition by Iressa and Rapamycin is modulated by VHL mutations in renal cell carcinoma (2005)

Epidermal growth factor receptor (EGFR) and tumour growth factor alpha (TGFalpha) are frequently overexpressed in renal cell carcinoma (RCC) yet responses to single-agent EGFR inhibitors are uncommon. Although von Hippel-Lindau (VHL) mutations are predominant, RCC also develops in individuals with tuberous sclerosis (TSC). Tuberous sclerosis mutations activate mammalian target of rapamycin (mTOR) and biochemically resemble VHL alterations. We found that RCC cell lines expressed EGFR mRNA in the near-absence of other ErbB family members. Combined EGFR and mTOR inhibition synergistically impaired growth in a VHL-dependent manner. Iressa blocked ERK1/2 phosphorylation specifically in wt-VHL cells, whereas rapamycin inhibited phospho-RPS6 and 4E-BP1 irrespective of VHL. In contrast, phospho-AKT was resistant to these agents and MYC translation initiation (polysome binding) was similarly unaffected unless AKT was inhibited. Primary RCCs vs cell lines contained similar amounts of phospho-ERK1/2, much higher levels of ErbB-3, less phospho-AKT, and no evidence of phospho-RPS6, suggesting that mTOR activity was reduced. A subset of tumours and cell lines expressed elevated eIF4E in the absence of upstream activation. Despite similar amounts of EGFR mRNA, cell lines (vs tumours) overexpressed EGFR protein. In the paired cell lines, PRC3 and WT8, EGFR protein was elevated post-transcriptionally in the VHL mutant and EGF-stimulated phosphorylation was prolonged. We propose that combined EGFR and mTOR inhibitors may be useful in the subset of RCCs with wt-VHL. However, apparent differences between primary tumours and cell lines require further investigation.
Synthesis, Film-Forming, and Electronic Properties of o-Phenylenediamine Copolymers Displaying An Uncommon Tricolor (2007)

Novel electrochromic copolymers from o-phenylenediamine (oPD) with aniline (ANi) were facilely synthesized by a chemical oxidative polymerization. The synthesis, structure, and properties of the copolymers were systematically studied by changing oPD content and polymerization temperature. The dependence of the polymerization yield at 70 °C on the oPD content is quite different from that at 17 °C, indicating that the copolymerization between the oPD and ANi comonomers varies significantly with polymerization temperature, whereas the conductivity and solubility of the copolymers obtained at 17 and 70 °C demonstrate similar dependency of the oPD content. The reactivity ratios, roPD and rANi, of oPD and ANi were found to be 9.70 and 2.74, respectively, implying a stronger homopolymerization tendency than copolymerization between them. The copolymers exhibit stronger formability and uniformity of the film, much higher electroactivity, and better tricolor electrochromism than oPD and ANi homopolymers. The copolymer film, containing 50 mol % oPD unit is red at −0.5 to 0 V vs SCE, turns to green at 0 to +0.6 V vs SCE, and blue at +0.6 to +1.35 V vs SCE. Possible assignments of the macromolecular structures of the copolymers in different potential ranges are proposed. The difficulty of synthesizing electrochromic oPD/ANi copolymers could be overcome to some extent by the oxidative polymerization at 70 °C. Particularly, the copolymer has an uncommon combination of strong film formability, high electroactivity, and unique tricolor electrochromism, which could not be achieved by both homopolymers themselves.
Surface micromachined structures fabricated with silicon fusion bonding (2002)

A surface micromachining technique has been developed which makes use of silicon fusion bonding. Many of the same types of micromechanical devices previously fabricated from polycrystalline have been fabricated from single-crystal silicon. Bridges and beams suspended near the substrate surface, complex thermally isolated designs, diaphragms suspended over shallow vacuum cavities, vertically and laterally resonant structures, fluid control devices, and fully released components have been created. It is concluded that this novel surface micromachining process is a powerful and versatile technology for a new generation of micromechanical inventions.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Molecular Recognition between Genetically Engineered Streptavidin and Surface-Bound Biotin (1999)

This study examines the binding of wild-type streptavidin and streptavidin mutants to biotin-terminated self-assembled monolayers (SAMs) as a model of biomolecular recognition at solid−liquid interfaces. The types of streptavidin proteins employed in this work were wild-type, Tyr43Ala (Y43A), and Trp120Ala (W120A), which have biotin-binding affinities that span several orders of magnitude (Ka varies from ∼1013 M-1 for wild-type to 107 M-1 for W120A). Two types of biotin-terminated monolayers were examined: those formed by chemisorption of 11-mercaptoundecanoic-(8-biotinoylamido-3,6-dioxaoctyl) amide (1) and those formed from mixtures of 12-mercaptododecanoic-(8-biotinoylamido-3,6-dioxaoctyl) amide (2) and 11-mercapto undecanol (3). Our findings support two previously published studies that found that 1 forms monolayers on gold that are disordered, while 2 and mixtures of 2 and 3 form closely packed, well-organized SAMs. The kinetics of binding and desorption of wild-type streptavidin and the mutants to and from these monolayers were measured using surface plasmon resonance spectroscopy. Adsorption of the proteins was found to occur at a diffusion-limited rate and to saturate at different surface coverages depending on their biotin-binding affinity. On disordered monolayers formed from 1, only a fraction of the bound mutants could be dissociated by exposure to free biotin. The fraction of undissociated mutants correlated with the biotin-binding affinity, suggesting that the formation of nonspecific interactions depends on the residence time of the protein on the surface. On mixed SAMs formed from 2 and 3, complete dissociation of the proteins occurred upon exposure to free biotin in solution. The kinetics of desorption of streptavidin from mixed SAMs was analyzed using a model that included the possibility of bivalent protein binding to the SAM at high surface concentrations of biotin. It was found that rate constants of dissociation were larger for the dissociation of a streptavidin−biotin bond on the surface than in solution. On biotinylated SAMs, the kinetic constants of dissociation were dependent on the surface concentration of biotin. Slow dissociation rates at higher surface coverage result from attractive protein−protein interactions. The results demonstrate the importance of the preparation and the structure of the solid surface and the complexity of biomolecular recognition at solid−liquid interfaces. Molecular recognition is affected by interactions between the adsorbed proteins and the surface and also by interactions among adsorbed proteins. These conclusions have important implications for the development of reversible biosensors.
Short Antimicrobial Lipo‐α/γ‐AA Hybrid Peptides (2014)

The last two decades have seen the rise of antimicrobial peptides (AMPs) to combat emerging antibiotic resistance. Herein we report the solid-phase synthesis of short lipidated α/γ-AA hybrid peptides. This family of lipo-chimeric peptidomimetics displays potent and broad-spectrum antimicrobial activity against a range of multi-drug resistant Gram-positive and Gram-negative bacteria. These lipo-α/γ-AA hybrid peptides also demonstrate high biological specificity, with no hemolytic activity towards red blood cells. Fluorescence microscopy suggests that these lipo-α/γ-AA chimeric peptides can mimic the mode of action of AMPs and kill bacterial pathogens via membrane disintegration. As the composition of these chimeric peptides is simple, therapeutic development could be economically feasible and amenable for a variety of antimicrobial applications.
T Cell Dysfunction by Hepatitis C Virus Core Protein Involves PD-1/PDL-1 Signaling (2007)

Reports have shown that a negative T cell costimulatory pathway mediated by PD-1 (programmed death-1) and PDL-1 (programmed death ligand-1) is associated with T cell exhaustion and persistent viral infection. Persistent hepatitis C virus (HCV) infection in humans is also characterized by impaired T lymphocyte function, but the role of the PD-1 and PDL-1 pathway in HCV infection is unknown. Here we report that T cells isolated from chronically HCV-infected patients express significantly higher levels of PD-1 when compared with healthy donors. In addition, PD-1 and PDL-1 expression is upregulated on healthy donor T cells exposed to HCV core, a nucleocapsid protein that is immunosuppressive; upregulation of PD-1 is mediated through interaction of HCV core with the complement receptor, gC1qR. Importantly, T cell functions that are dysregulated by HCV core, including T cell activation, proliferation, and apoptosis, can be restored by blocking PD-1 and PDL-1 engagement. Our results indicate that HCV core can upregulate a key negative T cell signaling pathway associated with viral persistence and highly expressed on the T cells of persistently infected individuals. This upregulation of the PD-1 and PDL-1 pathway in humans represents a novel and perhaps common mechanism by which a virus usurps host machinery to facilitate persistence.
The elderberry (Sambucus nigra L.) bark lectin recognizes the Neu5Ac(alpha 2-6)Gal/GalNAc sequence. (1987)

Carbohydrate binding properties of a new plant lectin isolated from elderberry (Sambucus nigra L.) (SNA) bark were studied using the techniques of quantitative precipitation, hapten inhibition, and equilibrium dialysis. Purified SNA precipitates highly sialylated glycoproteins such as fetuin, orosomucoid, and ovine submaxillary mucin, but not their asialo derivatives. Hapten inhibition experiments showed that both D-Gal and D-GalNAc are weak inhibitors of SNA-glycophorin precipitation, but neither New5Ac nor Neu5Gc is an inhibitor. A series of oligosaccharides which contain the terminal Neu5Ac(alpha 2-6)Gal sequence showed an extremely high inhibitory potency (1,600-10,000 times more inhibitory than Gal). On the other hand, oligosaccharides with the Neu5Ac(alpha 2-3)Gal linkage were only 30-80 times more inhibitory than Gal, thus showing a marked preference for the 2,6-linked isomer. Hapten inhibition with Gal and its epimers suggested that the equatorial OH at C-3 and the axial OH at C-4 of the D-pyranose ring are strict requirements for binding. Conversion of the Neu5Ac residue to its 7-carbon analogue by selective periodate oxidation of its glyceryl side chain, followed by NaBH4 reduction, completely destroyed the ability of fetuin and orosomucoid to precipitate with SNA. Moreover, the same treatment of Neu5Ac(alpha 2-3)lactitol also abolished its ability to inhibit the precipitation reaction, suggesting that the glyceryl side chain of NBu5Ac (especially the C-8 and/or C-9 portion) is an important determinant for SNA. The increased inhibitory potency of various glycosides with beta-linked nonpolar aglycons suggested the presence of a hydrophibic interacting region adjacent to the carbohydrate binding site. The results of equilibrium dialysis using [3H] Neu5Ac(alpha 2-6)lactitol as ligand showed the presence of two equivalent, noninteracting carbohydrate binding sites in this tetrameric glycoprotein lectin (Ka = 3.9 X 10(5) M-1).
The utilization efficiency of hydrogen peroxide on the removal of volatile organic acids in sand columns (1996)

Effects of hydrogen peroxide (H2O2) on the removal of volatile organic acids were studied with a series of sand columns. Hydrogen peroxide was used as an alternative oxygen source to enhance the removal of volatile organic acids. In the presence of microorganisms, H2O2 was readily decomposed to increase the dissolved oxygen concentrations (DO) in waters. The microorganisms used in this study could tolerate the toxicity of H2O2, even if its concentration reached 450 mg/L. The volatile organic acids used in this study were not chemically oxidized by H2O2. The results indicated that the concentrations of H2O2 required to remove volatile organic acids were higher than those calculated from the theoretical stoichiometry equation. Hydrogen peroxide was not effectively utilized, especially when the concentrations of H2O2 were relatively high. When the concentration of H2O2 was high, oxygen produced from the decomposition of H2O2 might not be effectively utilized by microorganisms and might escape from waters in gaseous form. The ratio of the amount of the volatile organic acid removed to the amount of H2O2 added decreased with an increase in the concentrations of H2O2. Multi-point injection of H2O2 can be used to improve its utilization efficiency, if a higher concentration of H2O2 was required.
518. The influence of substituent groups on ring scission. Part I. The ring scission of some unsymmetrically substituted glutaric anhydrides (1951)

J. C. Roberts and K. Selby, J. Chem. Soc., 1951, 2335 DOI: 10.1039/JR9510002335
Dual Vectors Expressing Murine Factor VIII Result in Sustained Correction of Hemophilia A Mice (2003)

Hemophilia A is a sex-linked disorder that results from a deficiency of functional factor VIII and is currently treated by protein replacement therapies. Within the past decade, gene therapy efforts have come to the forefront of novel therapeutics. In this work, a dual-vector approach was employed in which recombinant adeno-associated viral (rAAV) vectors expressing the heavy and light chains of the murine factor VIII gene were delivered either intramuscularly or intravenously to a mouse model of hemophilia A. From in vitro work, it was determined that coinfection with both vectors is required as heterodimerization of the heavy and light chains occurs intracellularly. In vivo, therapeutic levels of factor VIII expression were achieved throughout the duration of the study (22 weeks). Intravenous and intramuscular delivery resulted in a maximal average expression of 31.4 +/- 6.4 and 29 +/- 6.5% of normal murine factor VIII levels, respectively. Western blots of cryoprecipitate as well as immunostaining of injection sites with an anti-murine factor VIII light chain antibody also confirmed the expression of factor VIII. Because the murine form of the gene was used in the mouse model, less than 1 Bethesda unit of inhibitors was noted. This work demonstrates the feasibility of using rAAV vectors for the long-term treatment of hemophilia A.
Micro-RNA speciation in fetal, adult and Alzheimer's disease hippocampus (2007)

Micro-RNAs constitute a family of small noncoding ribonucleic acids that are posttranscriptional regulators of messenger RNA activity. Although micro-RNAs are known to be dynamically regulated during neural development, the role of micro-RNAs in brain aging and neurodegeneration is not known. This study examined micro-RNA abundance in the hippocampal region of fetal, adult and Alzheimer's disease brain. The data indicate that micro-RNAs encoding miR-9, miR-124a, miR-125b, miR-128, miR-132 and miR-219 are abundantly represented in fetal hippocampus, are differentially regulated in aged brain, and an alteration in specific micro-RNA complexity occurs in Alzheimer hippocampus. These data are consistent with the idea that altered micro-RNA-mediated processing of messenger RNA populations may contribute to atypical mRNA abundance and neural dysfunction in Alzheimer's disease brain.
Frequent inactivation of PTEN/MMAC1 in primary prostate cancer. (1997)

Sporadic prostate carcinoma is the most common male cancer in the Western world, yet many of the major genetic events involved in the progression of this often fatal cancer remain to be elucidated. Numerous cytogenetic and allelotype studies have reported frequent loss of heterozygosity on chromosomal arm 10q in sporadic prostate cancer. Deletion mapping studies have unambiguously identified a region of chromosome 10q23 to be the minimal area of loss. A new tumor suppressor gene, PTEN/MMAC1, was isolated recently at this region of chromosome 10q23 and found to be inactivated by mutation in three prostate cancer cell lines. We screened 80 prostate tumors by microsatellite analysis and found chromosome 10q23 to be deleted in 23 cases. We then proceeded with sequence analysis of the entire PTEN/MMAC1 coding region and tested for homozygous deletion with new intragenic markers in these 23 cases with 10q23 loss of heterozygosity. The identification of the second mutational event in 10 (43%) tumors establishes PTEN/MMAC1 as a main inactivation target of 10q loss in sporadic prostate cancer.
Thl epitope repertoire on the a subunit of human muscle acetylcholine receptor in myasthenia gravis (1997)

In myasthenia gravis (MG), CD4+ T helper cells recognize the muscle acetylcholine receptor (AChR) alpha subunit. We investigated the epitope repertoire of anti-AChR blood CD4+ Th1 cells from 13 myasthenic patients and three healthy controls, using overlapping synthetic peptides screening the alpha subunit sequence and an enzyme-linked immunospot (ELISPOT) assay that detects antigen-induced interferon-gamma secretion of individual Th1 cells. All patients recognized a pool of the alpha subunit peptides. All but one patient recognized numerous peptides. Each patient had an individual pattern of peptide recognition, but most or all patients recognized four sequences (residues 48-67, 101-137, 304-322, and 403-437) that stimulated relatively large numbers of Th1 cells. They include previously identified "immunodominant" sequences recognized by AChR-specific CD4+ T cell lines from myasthenic patients. Peptide 1-14 was also recognized frequently. The controls recognized, with a low precursor frequency, the peptide pool and a few peptides that frequently included the immunodominant sequences described above. The present results demonstrate that Th1 cells are involved in the anti-AChR response in MG and that their epitope repertoire is very complex. This indicates that when MG is clinically evident, the AChR itself is the sensitizing antigen and the target of the autoimmune Th1 cells, although it does not exclude that molecular mimicry between one AChR epitope and a microbial structure may have triggered this autoimmune response. Although the complexity of the Th1 repertoire suggests that development of specific immunosuppressive treatments targeted on epitopes recognized by autoimmune T cells will be difficult, the existence of immunodominant T epitope sequences might facilitate that task.
Full-wafer technology-A new approach to large-scale laser fabrication and integration (1991)

A concept for full-wafer processing (FWP) and full-wafer testing (FWT) for semiconductor laser fabrication in the AlGaAs-GaAs material system is presented. The approach is based on chemically assisted ion beam etching for the laser-mirror formation. Record values for mirror scattering, optimum mirror reflectivity, and equivalence to cleaved mirrors in terms of laser threshold and efficiency have been achieved. Promising results for uniformity and reproducibility for major laser diode characteristics on processed 2-in wafers have been found. The FWP technology has been extensively used for designing test sites to determine various materials, process, and laser parameters, such as sheet resistance, ridge dimensions, lithographic alignment errors, mirror surface leakage, etc.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Neuronal properties and trophic activities of immortalized hippocampal cells from embryonic and young adult mice (1990)

The hippocampal formation elaborates trophic factors such as nerve growth factor (NGF) to support the cholinergic innervation it receives from the septal region. To further study the trophic interactions of this pathway, hippocampal cells from embryonic day 18 and postnatal day 21 mice were immortalized via somatic cell fusion to N18TG2 neuroblastoma cells. The hippocampal cell lines exhibit morphological and cytoskeletal features which are typical of their neuronal parents but which are not expressed by the neuroblastoma parent. When differentiated with retinoic acid, the hippocampal cell lines exhibit electrophysiological features similar to cultured hippocampal neurons. Many of the lines constitutively express high levels of NGF, and at least one cell line exerts a non-NGF trophic effect on the expression of choline acetyltransferase by septal neurons in vitro. These cell lines are potentially useful for investigating the neurochemical and excitable properties of hippocampal neurons and identifying novel trophic activities that promote the development and maintenance of the septohippocampal pathway.
Confocal microscopy of single molecules of the green fluorescent protein (1998)

Single molecule detection has been extended into life sciences by use of strongly fluorescent labels. The green fluorescent protein (GFP) as a self-fluorescent biomolecule has attracted considerable attention. Here, single molecules of the GFP-mutant Glu222Gln are immobilized in a polyvinylalcohol matrix and detected by confocal fluorescence microscopy. Although this mutant stabilizes one of both conformers of the wild-type GFP, the investigation of its fluorescence dynamics reveals strong signal fluctuations. This fluorescence behaviour is—at least partly—caused by reversible photochemical changes of the protein framework, that can relax into the fluorescent state on different timescales. Thus, this protein appears particularly appropriate for studying the microheterogeneity of the macromolecule GFP on a single molecule level.