gebhart/patrepeval huggingface dataset:
Characterization of mutations in aclacinomycin A-non-producing Streptomyces galilaeus strains with altered glycosylation patterns (2002)

In this study a set of Streptomyces galilaeus ATCC 31615 mutants was characterized, which are incapable of synthesizing some or all of the deoxyhexose sugars of aclacinomycin A. Complementation experiments with the the mutant strains H026, H038, H039, H054, H063, H065 and H075 were carried out with glycosylation genes previously derived from the wild-type S. galilaeus. Mutations in strains H038, H063 and H075 were complemented with single PCR-amplified genes. Furthermore, amplification and sequencing of the corresponding genes from the mutant strains revealed single point mutations in the sequences. First, in H038 a transition mutation in aknQ, encoding a putative dTDP-hexose 3-ketoreductase, causes an amino acid substitution from glycine to aspartate, suppressing the biosynthesis of both 2-deoxyfucose and rhodinose and thus leading to the accumulation of aclacinomycin T with rhodosamine as its only sugar. Second, in H063, which accumulates aklavinone without a sugar moiety, amino acid substitution occurs, with threonine being substituted by isoleucine in dTDP-glucose synthase, the first enzyme participating in deoxyhexose biosynthesis, encoded by aknY. Third, a nonsense mutation in aknP leads to truncated dTDP-hexose 3-dehydratase in H075, which is incapable of synthesizing rhodinose. In addition, mutants H054 and H065, which accumulate aclacinomycins without aminosugars, were complemented by a gene for an aminotransferase, aknZ. Characterization of the nature of the mutations adds to the usefulness and value of the mutants in the analysis of gene function and in the creation of novel compounds by combinatorial biosynthesis. Furthermore, these results strengthen the assignments of akn gene products and enlighten the biosynthetic pathway for deoxyhexoses.
Abstract 3366: <i>In vivo</i> efficacy of a PD-L1 targeted, antigen seeding engineered toxin body (2020)

Abstract Engineered toxin bodies (ETBs) comprised of a proprietarily engineered Shiga-like Toxin A subunit (SLTA) genetically fused to antibody-like binding domains work through novel mechanisms of action and can force internalization, self-route through intracellular compartments to the cytosol, and induce potent cell-kill via the enzymatic and permanent inactivation of ribosomes. Our PD-L1 targeted ETB, MT-6402, includes antigen seeding technology (AST), and additionally delivers a viral antigen for presentation in complex with MHC-I to resident viral-specific cytotoxic T lymphocytes (CTLs). The fusion protein provides a powerful, dual mechanism of action to specifically target and destroy PD-L1 positive tumor and inhibitory immune cells. In vitro testing of human tumor cell lines has demonstrated that cell surface PD-L1 expression is required for activity of the PD-L1 targeted ETBs. MT-6402 demonstrated effective depletion of PD-L1 expressing cells across a panel of immortalized cancer cell lines from multiple origins, including lung, skin, breast, and ovary. In a co-culture assay of PD-L1 target cells and antigen specific T-cells, PD-L1 targeted MT-6402 delivers a viral antigen to the target cells and can activate cytokine secretion and T-cell mediated killing. Additionally, MT-6402 treatment of human peripheral blood mononuclear cells (PBMCs) leads to selective depletion of PD-L1 positive cells (IFN-γ stimulated monocytes) in the absence of depletion of PD-L1 low/negative lymphocytes. Murine models, including patient derived xenografts, have demonstrated that the PD-L1 targeted ETBs are efficacious in vivo. Additional in vivo tumor models to further describe the effect of MT-6402 are being explored. Exploratory studies in a primate model have shown that MT-6402 can be tolerated at levels shown to induce T cell activation (type 1 cytokines). MT-6402 delivers a powerful and unique dual mechanism of action. The combination of a PD-L1 specific direct cell kill and redirection of a robust effector T cell response to the tumor has potential benefit in solid tumor indications, including in the relapsed setting, when disease has progressed after checkpoint and/or other therapies. Citation Format: Hilario J. Ramos, Brigitte Brieschke, Sara LeMar, Joseph D. Dekker, Aimee Iberg, Garrett L. Robinson, Asis Sarkar, Banmeet Anand, Melissa M. Singh, Jay Zhao, Jack P. Higgins, Erin K. Willert. In vivo efficacy of a PD-L1 targeted, antigen seeding engineered toxin body [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3366.
Structure2function studies of an engineered scaffold protein derived from Stefin A. II: Development and applications of the SQT variant (2011)

Lukas Kurt Josef Stadler1, Toni Hoffmann1,8, Darren Charles Tomlinson2, Qifeng Song1, Tracy Lee1, Michael Busby3, Yvonne Nyathi4, Elisenda Gendra4, Christian Tiede4, Keith Flanagan5, Simon J. Cockell6, Anil Wipat5, Colin Harwood7, Simon D. Wagner8, Margaret A. Knowles2, Jason J. Davis3, Neil Keegan9 and Paul Ko Ferrigno1,4,10 Section of Experimental Therapeutics, Leeds Institute of Molecular Medicine, St James’s University Hospital, Beckett St, Leeds LS9 7TF, UK, Section of Experimental Oncology, Leeds Institute of Molecular Medicine, St James’s University Hospital, Beckett St, Leeds LS9 7TF, UK, Chemical Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK, Aptuscan Ltd, Leeds Innovation Centre, Clarendon Road, Leeds, UK, Computing Science, University of Newcastle, Newcastle upon Tyne, UK, Bioinformatics Support Unit, University of Newcastle, Newcastle upon Tyne, UK, Institute for Cell and Molecular Biosciences, University of Newcastle, Newcastle upon Tyne, UK, MRC Toxicology Unit and Department of Cancer Studies and Molecular Medicine, Hodgkin Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK and Institute of Cellular Medicine, Diagnostic and Therapeutic Technologies, The Medical School, University of Newcastle, Newcastle upon Tyne, UK
PRODUCTION AND EVALUATION OF SUGAR CANE FIBER GEOTEXTILES (REPORT 2: FIELD TESTING) (1997)

Prior research involved the production and laboratory testing of sugar cane fiber geotextiles for soil erosion control. Comparative preliminary studies were conducted on test slopes to determine slope stability, in horticulture plots to determine grass propagation characteristics, and in the laboratory to characterize physical properties. Based upon satisfactory laboratory and germination results, a field test was designed to determine product performance in a natural environment. A field test was conducted in cooperation with the Louisiana Transportation Research Center and the Louisiana Department of Transportation and Development to compare the sugar cane fiber mats with commercially available natural fiber geotextiles of wood, coconut, and straw. Field test results indicated that protection provided for the seed bed during the vegetative establishment period and slope stabilization were satisfactory among all products. Further work will include a continuous process for sugar cane fiber mat formation and a spray-on application using bagasse fibers. Standardized product specifications need to be developed.
Enhancement of protein expression in insect cells by a lobster tropomyosin cDNA leader sequence (2002)

We describe a cis element that dramatically increases the expression levels of exogenous genes in baculovirus-infected insect cells. This 21 bp sequence element is derived from a 5' untranslated leader sequence of a lobster tropomyosin cDNA (L21). By using a transfer vector carrying L21, the expression levels of tropomyosin and luciferase were 20- and seven-fold higher with L21 than without L21, respectively. L21 has both the Kozak sequence and the A-rich sequence found in the polyhedrin leader sequence. We assume that both sequence elements are essential for the enhancement of protein expression in the baculovirus-based expression system.
Inversion Based Multibody Control: Launch Vehicle with Fuel Slosh (2005)

ics under consideration were fully actuated. The dynamics we consider in this paper, are that of a critically underactuated system. The dynamic inversion-based nonlinear control algorithm presented in this paper will account for the coupled dynamics of interconnected rigid bodies. Specifically, the controller regulates engine angle of a vehicle by operating on the engine gimbal torque in the presence of fuel slosh. The controller uses an estimate of the slosh dynamics provided by a reduced-order observer. We compare the performance / stability improvements offered by high-fidelity controllers (those designed for a multi-body vehicle including slosh) over low-fidelity controllers (those designed for a multi-body vehicle but without regard for slosh dynamics). We use the proposed design procedure to simulate a controller that can actively damp slosh using additional thrusts.
In-Situ Destruction of Chlorinated Hydrocarbons in Groundwater Using Catalytic Reductive Dehalogenation in a Reactive Well:  Testing and Operational Experiences (1999)

A groundwater treatment technology based on catalytic reductive dehalogenation has been developed to efficiently destroy chlorinated hydrocarbons in situ using a reactive well approach. The treatment process utilizes dissolved H2 as an electron donor, in the presence of a commercial palladium-on-alumina catalyst, to rapidly reduce common chlorinated aliphatics such as trichloroethylene and tetrachloroethylene into nonchlorinated hydrocarbons such as ethane. Rapid reaction rates permit the deployment of a treatment unit within a dual-screened well bore, allowing contaminated groundwater to be drawn from one water-bearing zone, treated within the well bore, and discharged to an adjacent zone with only one pass through the system. A demonstration groundwater treatment system based on this concept was evaluated in a chlorinated hydrocarbon contaminated aquifer at a major Superfund site. The system rapidly destroyed a variety of common contaminants such as TCE and PCE and maintained its performance for a test period of 1 year. Operation of the treatment system was optimized to maintain catalyst activity and to prevent formation of intermediate compounds.
Performance of a soft-output adaptive equalizer combined with soft-decision metrics generator based on differential detection (2002)

This paper proposes a soft-output adaptive equalizer combined with a novel soft-decision metrics generator based on differential detection, and assesses its performance by computer simulation and hardware experiments. The proposed soft-decision metrics generator performs differential detection by using the equalizer's soft-decision output and weights its results with the short-term average of squared errors in the equalizer. We confirm that the proposed scheme achieves good performance with lower complexity in generating the soft-decision metrics for Viterbi (1979) decoding compared with the conventional scheme.
Sensing Protein Surfaces with Targeted Fluorescent Receptors (2015)

Invited for the cover of this issue is the group of David Margulies at the Weizmann Institute of Science (Israel). The image highlights the analogy between fluorescent molecular sensors and a miniaturized camera that can capture changes that occur at the nanoscale and shed light on the structural state of proteins. Read the full text of the article at 10.1002/chem.201502069.
Potent, Metabolically Stable 2‐Alkyl‐8‐(2<i>H</i>‐1,2,3‐triazol‐2‐yl)‐9<i>H</i>‐adenines as Adenosine A<sub>2A</sub> Receptor Ligands (2015)

Inhibition of adenosine A2A receptors has been shown to elicit a therapeutic response in preclinical animal models of Parkinson's disease (PD). We previously identified the triazolo-9H-purine, ST1535, as a potent A(2A)R antagonist. Studies revealed that ST1535 is extensively hydroxylated at the ω-1 position of the butyl side chain. Here, we describe the synthesis and evaluation of derivatives in which the ω-1 position has been substituted (F, Me, OH) in order to block metabolism. The stability of the compounds was evaluated in human liver microsomes (HLM), and the affinity for A(2A)R was determined. Two compounds, (2-(3,3-dimethylbutyl)-9-methyl-8-(2H-1,2,3-triazol-2-yl)-9H-purin-6-amine (3 b) and 4-(6-amino-9-methyl-8-(2H-1,2,3-triazol-2-yl)-9H-purin-2-yl)-2-methylbutan-2-ol (3 c), exhibited good affinity against A(2A)R (Ki =0.4 nM and 2 nM, respectively) and high in vitro metabolic stability (89.5% and 95.3% recovery, respectively, after incubation with HLM for two hours).
Process for grinding coal or ores in a liquid medium. [in liquid plus anionic polyelectrolyte] (1979)

A process is described for grinding coal or ores containing metal values comprising carrying out the grinding in a liquid medium and with a grinding aid comprising an anionic polyelectrolyte derived from polyacrylic acid and dispersible in the liquid medium. The grinding aid is present in an amount effective to provide increased grinding efficiency.
Macrolactams Two novel homologous series of compounds produced by Actinomadura sp. SCC 1778. (1992)

Eight antifungal compounds were identified from the fermentation of Actinomadura sp. SCC 1778. This culture produces four homologous compounds (C22H42N2O5 approximately C25H48N2O5) containing the sugar, mycosamine, and four homologous compounds (C22H42N2O5 approximately C25H48N2O5) containing the sugar, 3,6-dideoxy-3-amino-L-talopyranose. Five of the compounds identified were novel macrolactams. All these compounds exhibit antifungal activity against Candida spp. with geometric mean MICs ranging from approximately 1.0 micrograms/ml for the higher homologs to 30 micrograms/ml for the lower homologs.
Temperature dependence of magnetoresistance and surface magnetization in ferromagnetic tunnel junctions (1998)

The temperature dependence of spin-polarized tunneling is investigated between 77 and 420 K for various ferromagnetic tunnel junctions. Both the junction resistance and the magnetoresistance decrease with increasing temperature $T.$ The experimental results are successfully described by a model that includes two current contributions. The dominant one is elastic, spin-polarized tunneling between the two ferromagnetic electrodes, each with an electron polarization $P$ that decreases with $T$ due to thermally excited spin waves according to $P\ensuremath{\propto}(1\ensuremath{-}\ensuremath{\alpha}{T}^{3/2}),$ i.e., in the same way as the surface magnetization. A smaller second conductance is due to assisted, spin-independent tunneling which we find to be proportional to ${T}^{1.35\ifmmode\pm\else\textpm\fi{}0.15}.$
Identification of Amino Acid Residues of the Matrix Metalloproteinase-2 Essential for Its Selective Inhibition by β-Amyloid Precursor Protein-derived Inhibitor (2008)

The extracellular domain of beta-amyloid precursor protein (APP) contains an inhibitor against matrix metalloproteinase-2 (MMP-2, gelatinase A). Our previous study ( Higashi, S. and Miyazaki, K. (2003) J Biol Chem 278, 14020-14028 ) demonstrated that the inhibitor is localized within the ISYGN-DALMP sequence of APP, and a synthetic decapeptide containing this sequence (named APP-derived inhibitory peptide, APP-IP) selectively inhibits the activity of MMP-2. To determine the region of interaction that correlates with the selective inhibition, we constructed various MMP-2 mutants. An MMP-2 mutant, which had the hemopexin-like domain and three fibronectin-like type II domains of MMP-2 deleted, and native MMP-2 showed similar affinities for APP-IP, suggesting that only the catalytic domain of MMP-2 is essential for the interaction. Studies of chimeric proteases, consisting of various parts of the MMP-2 catalytic domain and those of MMP-7 (matrilysin) or MMP-9 (gelatinase B), further revealed that Ala(88) and Gly(94) in the non-prime side and Tyr(145) and Thr(146) in the prime side of the substrate-binding cleft of MMP-2 contribute separately to the selective inhibition. Replacement of the amino acid residue at position 94 of a chimeric MMP mutant affected its interaction with the C-terminal Pro(10) of APP-IP, whereas that of residues 145-148 affected the interaction with Tyr(3) of the inhibitor, suggesting that the N to C direction of APP-IP relative to the substrate-binding cleft of MMP is analogous to that of propeptide in proMMP, and opposite to that of substrate. When the APP-IP sequence was added to the N terminus of the catalytic domain of MMP-2, the activity of the protease was intramolecularly inhibited. We speculate that the direction of interaction makes the active site-bound APP-IP resistant to cleavage, thereby supporting the inhibitory action of the peptide inhibitor.
Multiple Intravenous Administrations of Human Umbilical Cord Blood Cells Benefit in a Mouse Model of ALS (2012)

These results demonstrate that multiple injections of MNC hUCB cells, even beginning at the symptomatic disease stage, could benefit disease outcomes by protecting motor neurons from inflammatory effectors. This multiple cell infusion approach may promote future clinical studies.
Production of a Broad Spectrum Antimicrobial Substance by<i>Lactobacillus reuteri</i> (1989)

Lactobacillus reuteri resides in the gastrointestinal tract of humans, swine, poultry and other animals. Resting cells of this species convert glycerol into a potent, broad-spectrum antimicrobial substance termed reuterin. Reuterin is a low molecular weight, neutral, water soluble compound, capable of inhibiting growth of species representing all bacterial genera tested thus far, including: Escherichia, Salmonella, Shigella, Proteus, Pseudomonas, Clostridium and Staphylococcus. Also affected, but to a lesser degree, are lactic acid bacteria belonging to the genera Streptococcus, Pediococcus, Leuconostoc, and Lactobacillus. In this report we describe a method to screen lactobacilli for production of unique antimicrobial substances and the discovery of reuterin.
Native Intact Mass Determination of Antibodies Conjugated with Monomethyl Auristatin E and F at Interchain Cysteine Residues (2012)

We present here a method for the rapid determination of the intact mass of noncovalently associated antibody heavy chains (HC) and light chains (LC) which result from the attachment of drug conjugates to interchain cysteine residues. By analyzing the antibody-drug conjugate (ADC) using native desalting conditions, we maintain the intact bivalent structure of the ADC, which ordinarily would decompose as a consequence of denaturing chromatographic conditions typically used for liquid chromatographic-mass spectrometric (LC-MS) analysis. The mass of the desalted ADC is subsequently determined using standard desolvation and ionization conditions. Methods presented previously in the literature for analyzing interchain cysteinyl-linked ADCs are either not amenable to online mass spectrometry or result in the denaturing dissociation of conjugated HC and LC during chromatographic separation and subsequent mass measurement. We have avoided this outcome with our method and have successfully and routinely obtained intact mass measurement of IgG1 mAbs conjugated with maleimidocaproyl-monomethyl Auristatin F (mcMMAF) and valine-citrulline-monomethyl Auristatin E (vcMMAE) at interchain cysteine residues. Our results thus represent the first reported direct measurement of the intact mass of an ADC conjugated at interchain cysteine residues.
Distinct regulatory mechanism for p70 S6 kinase β from that for p70 S6 kinase α (2001)

These results indicate that p70beta is regulated by the mTOR- and PDK1-signalling pathways through a synergistic interaction between phosphorylated Thr241 and Thr401, while Ser383 plays minor role in their activation mechanism. Activated p70beta may be less sensitive to dephosphorylation mediated by putative phosphatases activated by rapamycin, amino acid withdrawal, and probably wortmannin.
Sandwich-type functionalized graphene sheet-sulfur nanocomposite for rechargeable lithium batteries (2011)

A functionalized graphene sheet-sulfur (FGSS) nanocomposite was synthesized as the cathode material for lithium-sulfur batteries. The structure has a layer of functionalized graphene sheets/stacks (FGS) and a layer of sulfur nanoparticles creating a three-dimensional sandwich-type architecture. This unique FGSS nanoscale layered composite has a high loading (70 wt%) of active material (S), a high tap density of ∼0.92 g cm(-3), and a reversible capacity of ∼505 mAh g(-1) (∼464 mAh cm(-3)) at a current density of 1680 mA g(-1) (1C). When coated with a thin layer of cation exchange Nafion film, the migration of dissolved polysulfide anions from the FGSS nanocomposite was effectively reduced, leading to a good cycling stability of 75% capacity retention over 100 cycles. This sandwich-structured composite conceptually provides a new strategy for designing electrodes in energy storage applications.
A Novel Multivalent, Single-Domain Antibody Targeting TcdA and TcdB Prevents Fulminant Clostridium difficile Infection in Mice (2014)

The incidence of Clostridium difficile infection (CDI) and associated mortality have increased rapidly worldwide in recent years. Therefore, it is critical to develop new therapies for CDI. In this study, we generated a novel, potently neutralizing, tetravalent, and bispecific antibody composed of 2 heavy-chain-only VH (VHH) binding domains against both TcdA and TcdB (designated "ABA") that reverses fulminant CDI in mice infected with an epidemic 027 strain after a single injection of the antibody. We demonstrated that ABA bound to both toxins simultaneously and displayed a significantly enhanced neutralizing activity both in vitro and in vivo. Additionally, ABA was able to broadly neutralize toxins from clinical C. difficile isolates that express both TcdA and TcdB but failed to neutralize the toxin from TcdA(-)TcdB(+) C. difficile strains. This study thus provides a rationale for the development of multivalent VHHs that target both toxins and are broadly neutralizing for treating severe CDI.
New Peroxide Curable Perfluoroelastomer for High Temperature Applications (2001)

Perfluoroelastomers are used in hostile environments due to their very high chemical and thermal resistance. Halogen containing perfluoroelastomers are cured by peroxide in presence of a curing agent. Commonly used curing agents, such as triallyl cyanurate and triallyl isocyanurate, show good thermal resistance only up to 220°C, thus restricting material application at higher temperatures. In this work, a new perfluoroelastomer for high temperature applications is presented. The polymer is synthesized with the so-called branching and pseudoliving technology and it is crosslinked with a new curing agent especially designed for high temperature resistance, namely a fluorinated di-olefin. The resulting polymer network exhibits by far improved thermal resistance, retaining its sealing ability and mechanical properties up to 300°C. Besides, the processability and the sealing properties of this di-olefin cured perfluoroelastomer are excellent. Based on this technology, a new peroxide curable perfluoroelastomer for high temperature applications has been obtained and developed at industrial scale. This material is today available from Ausimont S.p.A. with the trade name of “Tecnoflon ® PFR95”.