gebhart/patrepeval huggingface dataset:
Leukocytes Utilize Myeloperoxidase-Generated Nitrating Intermediates as Physiological Catalysts for the Generation of Biologically Active Oxidized Lipids and Sterols in Serum (1999)

The initiation of lipid peroxidation and the concomitant formation of biologically active oxidized lipids and sterols is believed to play a central role in the pathogenesis of inflammatory and vascular disorders. Here we explore the role of neutrophil- and myeloperoxidase (MPO)-generated nitrating intermediates as a physiological catalyst for the initiation of lipid peroxidation and the formation of biologically active oxidized lipids and sterols. Activation of human neutrophils in media containing physiologically relevant levels of nitrite (NO(2)(-)), a major end product of nitric oxide (nitrogen monoxide, NO) metabolism, generated an oxidant capable of initiating peroxidation of lipids. Formation of hydroxy- and hydroperoxyoctadecadienoic acids [H(P)ODEs], hydroxy- and hydroperoxyeicosatetraenoic acids [H(P)ETEs], F(2)-isoprostanes, and a variety of oxysterols was confirmed using on-line reverse phase HPLC tandem mass spectrometry (LC/MS/MS). Lipid oxidation by neutrophils required cell activation and NO(2)(-), occurred in the presence of metal chelators and superoxide dismutase, and was inhibited by catalase, heme poisons, and free radical scavengers. LC/MS/MS studies demonstrated formation of additional biologically active lipid and sterol oxidation products known to be enriched in vascular lesions, such as 1-hexadecanoyl-2-oxovalaryl-sn-glycero-3-phosphocholine, which induces upregulation of endothelial cell adhesion and chemoattractant proteins, and 5-cholesten-3beta-ol 7beta-hydroperoxide, a potent cytotoxic oxysterol. In contrast to the oxidant formed during free metal ion-catalyzed reactions, the oxidant formed during MPO-catalyzed oxidation of NO(2)(-) readily promoted lipid peroxidation in the presence of serum constituents. Collectively, these results suggest that phagocytes may employ MPO-generated reactive nitrogen intermediates as a physiological pathway for initiating lipid peroxidation and forming biologically active lipid and sterol oxidation products in vivo.
Photoregulation of Mass Transport through a Photoresponsive Azobenzene-Modified Nanoporous Membrane (2004)

Photoresponsive nanoporous membranes, composed of monosized pores modified with azobenzene ligands, were prepared on an ITO working electrode using an evaporation-induced self-assembly procedure. They exhibited the size-selective photoregulated mass transport of two ferrocene-based molecular probes through the membrane to the electrode surface as determined using a chronoamperometry technique. The measured oxidative current increased and decreased in response to alternating UV and visible light exposure correlating strongly with the photoisomerization state of the azobenzene ligands. This indicates that the optically switchable conformation (trans or cis) of azobenzene ligands controls the effective pore size and, correspondingly, transport behavior on the nanoscale.
Metabolism-based herbicide resistance: regulationby safeners (2004)

Abstract Safeners are chemical agents that reduce the phytotoxicity of herbicides to crop plants by a physiological or molecular mechanism, without compromising weed control efficacy. Commercialized safeners are used for the protection of large-seeded grass crops, such as corn, grain sorghum, and wet-sown rice, against preplant-incorporated or preemergence-applied herbicides of the thiocarbamate and chloroacetanilide families. Safeners also have been developed to protect winter cereal crops such as wheat against postemergence applications of aryloxyphenoxypropionate and sulfonylurea herbicides. The use of safeners for the protection of corn and rice against sulfonylurea, imidazolinone, cyclohexanedione, isoxazole, and triketone herbicides also is well established. A safener-induced enhancement of herbicide detoxification in safened plants is widely accepted as the major mechanism involved in safener action. Safeners induce cofactors such as glutathione and herbicide-detoxifying enzymes such as glutathione S-transferases, cytochrome P450 monooxygenases, and glucosyl transferases. In addition, safeners enhance the vacuolar transport of glutathione or glucose conjugates of selected herbicides. The safener-mediated induction of herbicide-detoxifying enzymes appears to be part of a general stress response. Nomenclature: Corn, Zea mays L.; grain sorghum, Sorghum bicolor (L.) Moench; rice, Oryza sativa L.; wheat, Triticum aestivum L.
Temperature-compensated optical-fiber Bragg gratings (1995)

Optical-fiber Bragg gratings1 are expected to be important components in wavelength-division-multiplexed optical-communication systems. For this application, wavelength stability over the range of operating temperatures is vital. We present passive mounts that compensate the temperature dependence of the resonant wavelength λB by changing the strain in the fiber. The shift in λB over a 60°C range was reduced by a factor of 13, to only 0.04 nm.
Red microalga exopolysaccharides: 2. Study of the rheology, morphology and thermal gelation of aqueous preparations (1998)

Porphyridium sp (P.sp) is a red marine microalga which is encapsulated within a charged polysaccharide envelope. The external part of this envelope dissolves in the growth medium. This mucilaginous polymeric material harvested from the medium is an anionic heteropolysaccharide containing both carboxyl and half-ester sulfate groups. Aqueous preparations of P.sp polysaccharide yield highly viscous samples with unique rheological properties which may be of commercial value. Rheological studies of aqueous preparations have been combined with X-ray diffraction studies of oriented fibers in order to investigate the conformation and interactions of the macromolecules. The X-ray fiber diffraction suggests the presence of an oriented single two-fold helical structure of pitch 1.6 nm, indicating that the P.sp. polysaccharide contains extended regions with a regular chemical repeat. Aqueous preparations exhibit relatively high viscosity at low polymer concentrations. Within the investigated concentration range the preparations show marked shear thinning behavior with no evidence for a Newto-nian plateau. Small deformation mechanical studies of 1% show evidence for elastic behaviour indicative of a weak gel network. An unusual feature of these samples is a reversible sharp transition upon heating from a weak to a strong elastic network.
Caveolin-1 regulates expression of junction-associated proteins in brain microvascular endothelial cells (2006)

Recent evidence from this laboratory indicated that reduced expression of caveolin-1 accompanied the diminished expression of tight junction (TJ)-associated proteins occludin and zonula occludens-1 (ZO-1) following stimulation of brain microvascular endothelial cells (BMECs) with the chemokine CCL2 (formerly called MCP-1). Because attenuated caveolin-1 levels have also been correlated with heightened permeability of other endothelia, the objective of this study was to test the hypothesis that reduced caveolin-1 expression is causally linked to the action of CCL2 on BMEC junctional protein expression and barrier integrity. This was achieved using adenovirus to nondestructively deliver caveolin-1 siRNA (Ad-siCav-1) to BMEC monolayers, which model the blood-brain barrier (BBB). Treatment with siRNA reduced the caveolin-1 protein level as well as occludin and ZO-1. Additionally, occludin exhibited dissociation from the cytoskeletal framework. These changes were attended by comparable alterations in adherens junction (AJ)-associated proteins, VE-cadherin and beta-catenin, increased BMEC paracellular permeability, and facilitated the ability of CCL2 to stimulate monocytic transendothelial migration. Furthermore, treating BMECs with cavtratin, a synthetic cell-permeable peptide encoding the caveolin-1 scaffolding domain, antagonized effects of both Ad-siCav-1 and CCL2. These results collectively highlight caveolin-1 loss as a critical step in CCL2-induced modulation of BMEC junctional protein expression and integrity, and possibly serve a crucial role in regulating inflammation at the BBB.
Transgenic animals and drug development: A review (2011)

Pharmaceutical companies face the challenge that only ten percent of compounds tested in clinical trials eventually make it to the market and out of these, only a few will succeed to generate profit. Utilization of genetically altered animals (transgenic animals) in the pharmaceutical industry provides important insights into the function and interaction of particular gene products. Now, with the help of advanced technology numerous transgenic animals have been produced. The advent of transgenic animals has influenced the attrition rate in pharmaceutical research and development by increasing the quality of both targets and compounds. As with any experimental animal model, transgenic animals also have certain limitations but still they provide a powerful tool for the advancement of drugs in the pharmaceutical industry.
Interleukin-10 deficiency impairs regulatory T cell-derived neuropilin-1 functions and promotes Th1 and Th17 immunity (2016)

Regulatory T cells (Tregs) expand in peripheral lymphoid organs and can produce immunosuppressive cytokines to support tumor growth. IL-10 abrogation efficiently induces Treg formation but dampens tumoral neuropilin-1 (Nrp-1) Treg signaling, which simultaneously augments Th1 and Th17 immunity. These effects are associated with the plasticity and stability of Tregs and effector T cell functions that can limit tumorigenesis. Within the tumor microenvironment, there appears to be a "mutual antagonism" between immunoenhancement and immunosuppression mechanisms, eventually leading to decreased metastasis. In contrast, tumor progression is paralleled by a reduction in Nrp-1-producing Tregs controlled by the IL-10 and TGF-β1 levels. However, Th1, Th17 and Treg immunity is primarily regulated by IL-10 or Nrp-1 and not TGF-β1 except when combined with IL-10. These results emphasize the important implications for the therapeutic use of Tregs. The number of Treg cells must be maintained in a healthy and dynamic homeostatic range to prevent malignant diseases. Moreover, Treg-mediated immunosuppression can be limited by reducing tumor-derived Treg Nrp-1 levels.
Site-specific and photo-induced alkylation of DNA by a dimethylanthraquinone-oligodeoxynucleotide conjugate (1996)

A dialkyl-substituted anthraquinone derivative was synthesized and ligated to a sequence-directing oligodeoxynucleotide to examine its efficiency and specificity for cross-linking to complementary sequences of DNA. The anthraquinone appendage stabilized spontaneous hybridization of the target and probe sequences through non-covalent interactions, as indicated by thermal denaturation studies. Covalent modification of the target was induced by exposure to near UV light (lambda > 335 nm) to generate cross-linked duplexes in yields as great as 45%. Reaction was dependent on the first unpaired nucleotide extended beyond the duplex formed by association of the target and probe. A specificity of C > T > A = G was determined for modification at this position. The overall site and nucleotide selectivity seems to originate from the chemical requirements of cross-linking and does not likely reflect the dominant solution structure of the complex prior to irradiation.
Dual Probes for the Dopamine Transporter and σ1 Receptors:  Novel Piperazinyl Alkyl-bis(4‘-fluorophenyl)amine Analogues as Potential Cocaine-Abuse Therapeutic Agents (2003)

Both dopamine uptake inhibitors and sigma(1) receptor antagonists have been implicated as potential pharmacotherapeutics for the treatment of cocaine abuse. While the dopamine uptake inhibitors may share with cocaine neurochemical mechanisms underlying reinforcing properties, sigma(1) antagonists have been shown to attenuate some behavioral actions and toxic side effects associated with cocaine overdose. Rimcazole, a sigma(1) receptor antagonist that binds to the DAT (K(i) = 224 nM), is not behaviorally cocaine-like and attenuates some of the behavioral actions of cocaine. To determine the roles of both DAT and sigma(1) receptors in the behavioral actions of rimcazole, a series of analogues was synthesized. Initial studies identified two analogues (1 and 4) that showed high to moderate affinities for both DAT and sigma(1) receptors and failed to show cocaine-like discriminative stimulus (DS) effects. A second series of bis(4'-fluorophenyl)amine analogues have now been prepared in which the most potent DAT compound, 19 (K(i) = 8.5 nM), was selective over serotonin transporter (SERT/DAT = 94), norepinephrine transporter (NET/DAT = 63), and sigma(1) receptor binding (sigma(1)/DAT = 44). In addition, two other analogues 10 and 17 showed superior selectivity for DAT over SERT (170- and 140-fold, respectively) and DAT over NET (219- and 190-fold, respectively) but were essentially equipotent at DAT and sigma(1) receptors (10; K(i) = 77 and 124 nM, respectively, 17; K(i) = 28 and 13 nM, respectively). CoMFA studies at both DAT and sigma(1) receptors were performed to examine structural requirements for optimal binding at these two targets as well as to assess differences between them. Behavioral evaluation of analogues with varying affinities for both DAT and sigma(1) receptors may provide a novel approach toward designing medications for cocaine abuse.
Notochord repression of endodermal Sonic hedgehog permits pancreas development (1998)

Notochord signals to the endoderm are required for development of the chick dorsal pancreas. Sonic hedgehog (SHH) is normally absent from pancreatic endoderm, and we provide evidence that notochord, in contrast to its effects on adjacent neuroectoderm where SHH expression is induced, represses SHH expression in adjacent nascent pancreatic endoderm. We identify activin-betaB and FGF2 as notochord factors that can repress endodermal SHH and thereby permit expression of pancreas genes including Pdx1 and insulin. Endoderm treatment with antibodies that block hedgehog activity also results in pancreatic gene expression. Prevention of SHH expression in prepancreatic dorsal endoderm by intercellular signals, like activin and FGF, may be critical for permitting early steps of chick pancreatic development.
The Fidelity of 3′ Misinsertion and Mispair Extension During DNA Synthesis Exhibited by two Drug‐Resistant Mutants of the Reverse Transcriptase of Human Immunodeficiency Virus Type 1 with Leu74→Val and Glu89→Gly (1997)

The relatively low fidelity of DNA synthesis characteristic to the reverse transcriptases (RTs) of the AIDS-causing viruses, human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2, respectively) was implicated as a dominant factor that contributes to the genetic hypervariability of these viruses. The formation of 3'-mispaired DNA and the subsequent extension of this DNA were shown to be key determinants that lead to the error proneness of these RTs. As part of our goal to study the structure/function relationship in HIV-1 RT, we have conducted mutational studies aimed at identifying amino-acid residues involved in affecting the fidelity of DNA synthesis by the enzyme. We have recently found that two mutants of HIV-1 RT, which show resistance to nucleoside analog inhibitors ([Leu184]RT and [Phe183]RT), exhibit in vitro error proneness of DNA synthesis lower than that of wild-type enzyme [Bakhanshvili, M., Avidan, O. & Hizi, A. (1996) Mutational studies of human immunodeficiency virus type 1 reverse transcriptase: the involvement of residues 183 and 184 in the fidelity of DNA synthesis, FEBS Lett. 391, 257-262]. Using both criteria, the current comparative study suggests that these two mutant RTs display a substantially enhanced fidelity of DNA synthesis relative to the wild-type RT counterpart. In the current study we have analyzed two additional drug-resistant mutants of HIV-1 RT, [Val74]RT and [Gly89]RT, for their in vitro fidelity of DNA synthesis using two parameters of DNA synthesis: 3' mispair formation and elongation of 3'-mismatched DNA. The current comparative study suggests that these two mutant RTs display a substantially enhanced fidelity of DNA synthesis relative to the wild-type RT counterpart, using both criteria. Analysis of the relative frequencies of misinsertion and mispair extension indicates that the overall error proneness of DNA synthesis in HIV-1 RT is wild-type > [Val74]RT > [Gly89]RT mutant. The results further support the possible linkage between the capacity of an enzyme to incorporate a nucleoside analog instead of the correct dNTP (leading to drug sensitivity) and the ability to incorporate and extend a wrong nucleotide (resulting in mutagenesis). Our results may bear on the potential use of selecting and maintaining HIV virions with high fidelity and drug-resistant RTs to suppress the subsequent appearance of virions resistant to other drugs.
The Escherichia coli hemolysin secretion apparatus--a versatile antigen delivery system in attenuated Salmonella. (1994)

The E. coli hemolysin (HlyA) secretion apparatus represents a type I secretion system that is fully functional in Salmonella. The system which consists of the two specific membrane proteins HlyB and HlyD and the outer membrane protein TolC, recognizes on HlyA a C-terminally located signal sequence of about 60 amino acids. Fusion proteins to which this signal sequence is covalently linked at the C-terminus are also recognized by this secretion apparatus. The efficiency of secretion is dependent on the rate of folding of the reporter protein. Secretion-competent regions of a given reporter protein that is not secretable as entire protein can be screened by a recently constructed transposon TnhlyAs which allows the insertion of the secretion signal into any region of the reporter protein. The genetic information for antigens of any source ranging in size between 10 and 1000 amino acids can be easily inserted into a recently constructed secretion vector which will allow the secretion of the fused antigen(s) in attenuated Salmonella typhimurium strains and in other attenuated Enterobacteriaceae. By manipulation of the Hly secretion system the antigen can be either completely secreted into the environment, fixed on the outer membrane or arrested in the cytoplasm of the used carrier strain. By the use of appropriate attenuated Salmonella strains the antigen is delivered in isolated compartments or to the cytosolic compartment. The extracellular delivery of such antigens is also possible with the help of appropriate carrier strains. The immunological consequences of the different display of the processed antigen will be discussed in the paper by Hess et al in this volume. With a similar antigen delivery system the easy identification and molecular characterization of unknown antigens recognized by the immune system in an infection is also feasible.
The spinach plasma membrane Ca2+ pump is a 120‐kDa polypeptide regulated by calmodulin‐binding to a terminal region (1998)

The spinach ( Spinacia oleracea L.) leaf plasma membrane Ca 2+ ‐ATPase is regulated by calmodulin (3‐fold stimulation) and limited proteolysis (trypsin; 4‐fold stimulation). The plasma membrane Ca 2+ ‐ATPase was identified as a 120‐kDa polypeptide on western immunoblots using two different antibodies. During trypsin treatment the 120‐kDa band diminished and a new band appeared at 109 kDa. The appearance of the 109‐kDa band correlated with the increase in enzyme activity following trypsin treatment. The stimulations by calmodulin and trypsin were not additive, suggesting that the 109‐kDa polypeptide represents a Ca 2+ ‐ATPase lackin a terminal fragment involved in calmodulin regulation. This was confirmed by 125 I‐calmodulin overlay studies where calmodulin labeled the 120‐kDa band in the presence of Ca 2+ , while the 109‐kDa band did not bind calmodulin. The effects of calmodulin and limited proteolysis on ATP‐dependent accumulation of 45 Ca 2+ in isolated inside‐out plasma membrane vesicles were studied, and kinetical analyses performed with respect to Ca 2+ and ATP. Calmodulin increased the V max. for Ca 2+ pumping 3‐fold, and reduced K m for Ca 2+ from 1.6 to 0.9 µ M . The K m for ATP (11 µ M ) was not affected by calmodulin. The effects of limited proteolysis on the affinities for Ca 2+ and ATP were similar to those obtained with calmodulin. Notably, however, limited proteolysis increased the V max. for Ca 2+ pumping to a higher extent than calmodulin, indicating incomplete calmodulin activation, or removal of an additional inhibitory site by trypsin.
Tensor Analyzers (2013)

Factor Analysis is a statistical method that seeks to explain linear variations in data by using unobserved latent variables. Due to its additive nature, it is not suitable for modeling data that is generated by multiple groups of latent factors which interact multiplicatively. In this paper, we introduce Tensor Analyzers which are a multilinear generalization of Factor Analyzers. We describe an efficient way of sampling from the posterior distribution over factor values and we demonstrate that these samples can be used in the EM algorithm for learning interesting mixture models of natural image patches. Tensor Analyzers can also accurately recognize a face under significant pose and illumination variations when given only one previous image of that face. We also show that Tensor Analyzers can be trained in an unsupervised, semi-supervised, or fully supervised settings.
Identification of histidyl and cysteinyl residues essential for catalysis by 5′‐nucleotidase (1984)

Inactivation of both cytosolic 5'-nucleotidase and ecto-5'-nucleotidase by diethylpyrocarbonate indicated the presence of an essential histidyl residue which in the cytosolic enzyme was conclusively located at the active site. Inactivation by thiol reagents indicated the presence of an essential cysteinyl residue in both enzymes. The data suggest that both 5'-nucleotidases belong to a group of histidine phosphatases which also includes glucose-6-phosphatase and acid phosphatase. A working hypothesis for the catalytic mechanism of these enzymes is proposed.
A defucosylated anti‐CD317 antibody exhibited enhanced antibody‐dependent cellular cytotoxicity against primary myeloma cells in the presence of effectors from patients (2010)

The humanized monoclonal antibody (mAb) against CD317 antigen (anti-HM1.24 antibody; AHM), which is highly expressed on multiple myeloma (MM), induces antibody-dependent cellular cytotoxicity (ADCC). However, the antitumor activity of AHM in the clinical setting has not been clearly demonstrated. In this study, we produced defucosylated AHM and evaluated its potency for clinical application by performing autologous ADCC assays against primary MM cells from patients. Defucosylated AHM that was produced in rat myeloma YB2/0 cells expressing a low level of fucosyltransferase (FUT8) showed significant ADCC activity against three out of six primary MM cells in the presence of autologous PBMC, whereas conventional AHM did not. The results indicate that the potency of AHM to induce ADCC against primary MM cells was insufficient, but was significantly augmented by defucosylation. To generate more homogenous defucosylated monoclonal antibodies (mAb) for fermentation, we disrupted the GFT gene that encodes a GDP-fucose transporter in a CHO/DXB11 cell line by sequential homologous recombination. Analysis of the N-linked oligosaccharide in the defucosylated AHM produced by the established GFT(-/-)CHO cell line showed that a majority (93.4%) of the oligosaccharide was fucose free. The GFT(-/-) cells stably produced defucosylated mAb over passages. These results demonstrate that GTF(-/-)CHO-produced defucosylated AHM (GFTKO-AHM) will be a promising new therapeutic antibody against MM in the clinical setting.