gebhart/patrepeval huggingface dataset:
[Studies on the combined effect of fosfomycin with sulbactam/cefoperazone on methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa]. (1994)

We studied the combined effect of fosfomycin (FOM) with sulbactam/cefoperazone (SBT/CPZ) on clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA, 246 strains) and Pseudomonas aeruginosa (190 strains) in vitro. In ratio of mixed serum concentration of antibiotics at three hours after intravenous administration, the combination of FOM with SBT/CPZ and alone of arbekacin showed over 90% in cumulative percentage of MIC against MRSA and P. aeruginosa. The effect of the combination of FOM and SBT/CPZ was observed in MRSA strains of > 16 micrograms/ml of SBT/CPZ MIC and > 256 micrograms/ml FOM MIC. As well as in P. aeruginosa strains, the effect of the combination of FOM and SBT/CPZ was observed in strains of > 16 micrograms/ml of SBT/CPZ MIC and < 256 micrograms/ml FOM MIC, but it was not remarkable in strains of > 256 micrograms/ml FOM MIC. These results suggests that the combination treatment of FOM and SBT/CPZ may be effective for mixed infection of MRSA and P. aeruginosa.
Camptothecin-resistant mutants of Chinese hamster ovary cells containing a resistant form of topoisomerase I. (1988)

In Chinese hamster ovary cells, stable mutants that exhibit 250- to 350-fold resistance to camptothecin (CptR mutants) have been isolated from mutagen-treated cultures. The CptR mutants exhibited no cross-resistance towards drugs such as colchicine, vinblastine, taxol, or puromycin but showed slightly (2- to 3-fold) enhanced sensitivity towards various drugs that inhibit DNA topoisomerase II (namely teniposide, etoposide, doxorubicin, mitoxantrone, amsacrine, ellipticine), suggesting that the genetic lesion in these mutants was highly specific. In contrast to the wild-type cells, the CptR line was resistant to camptothecin-induced DNA strand breaks as measured by alkaline elution. Biochemical studies revealed that in CptR mutants the cellular activity as well as protein content of DNA topoisomerase I were reduced to about 40-50% of the level in wild-type cells. Normal levels of activity and content were observed for the related enzyme DNA topoisomerase II. Studies with DNA topoisomerase I purified from the wild-type and the mutant cells showed that the enzyme from the CptR cells was markedly resistant to camptothecin as assayed by the drug's effects either on relaxation of supercoiled DNA or on stabilization of the covalent enzyme-DNA intermediate. The presence of a camptothecin-resistant form of DNA topoisomerase I in the mutant cells provides further evidence that this enzyme is the cellular target of camptothecin. Cell hybridization studies between the CptR and CptS cells showed that the hybrids formed between these two cell lines were sensitive to camptothecin. The recessive behavior of the CptR mutation provides a plausible explanation for the reduced topoisomerase I content (about one-half of wild-type cells) of the mutant cells and also for their enhanced sensitivity towards inhibitors of topoisomerase II.
The yopM gene of Yersinia pestis encodes a released protein having homology with the human platelet surface protein GPIb alpha (1989)

In Yersinia pestis KIM, there are 11 Yops (yersinial outer membrane proteins) encoded by the low-Ca2+ response virulence plasmid pCD1. Only Yops M and N are found in easily detectable amounts in the culture medium. In this study, we located and characterized the yopM gene to obtain clues about its role in the virulence of Y. pestis. Rabbit antibody was raised against Yops M and H, copurified from the supernatant of Y. pseudotuberculosis 43(pGW600, pCD1 yopE::Mu dI1[Apr lac]). This antiserum was adsorbed with an Escherichia coli clone that strongly expressed YopH. The resulting YopM-specific antibody was used to screen a HindIII library of pCD1. HindIII-F and several subclones from it expressed YopM in E. coli minicells. A DNA fragment of 1.39 kilobases from HindIII-F was sequenced and found to contain a 367-amino-acid open reading frame capable of encoding a protein with molecular mass (41,566 daltons) and isoelectric point (4.06) similar to those of YopM. The +1 site of the yopM gene was determined by primer extension. The DNA sequence contained repeating structures: 11 pairs of exact direct repeats, two exact inverted repeats, and three palindromes, ranging from 10 to 42 bases in size. One consensus 14-amino-acid sequence was repeated six times in the predicted protein sequence. The YopM sequence shares some significant homology with the von Willebrand factor- and thrombin-binding domain of the alpha chain of human platelet membrane glycoprotein Ib. These findings suggested a testable hypothesis for the function of YopM.
Hardware Trojans - Prevention, Detection, Countermeasures (A Literature Review) (2011)

Abstract : A Hardware Trojan is a malicious, undesired, intentional modification of an electronic circuit or design, resulting in the incorrect behaviour of an electronic device when in operation - a back-door that can be inserted into hardware. A Hardware Trojan may be able to defeat any and all security mechanisms (software or hardware-based) and subvert or augment the normal operation of an infected device. This may result in modifications to the functionality or specification of the hardware, the leaking of sensitive information, or a Denial of Service (DoS) attack. Understanding Hardware Trojans is vital when developing next generation defensive mechanisms for the development and deployment of electronics in the presence of the Hardware Trojan threat. Research over the past five years has primarily focussed on detecting the presence of Hardware Trojans in infected devices. This report reviews the state-of-the-art in Hardware Trojans, from the threats they pose through to modern prevention, detection and countermeasure techniques.
Protein Kinase C δ (δPKC)-Annexin V Interaction (2006)

Protein kinase C (PKC) plays a critical role in diseases such as cancer, stroke, and cardiac ischemia, and participates in a variety of signal transduction pathways such as apoptosis, cell proliferation, and tumor suppression. Though much is known about PKC downstream signaling events, the mechanisms of regulation of PKC activation and subsequent translocation have not been elucidated. Protein-protein interactions regulate and determine the specificity of many cellular signaling events. Such a specific protein-protein interaction is described here between deltaPKC and annexin V. We demonstrate, at physiologically relevant conditions, that a transient interaction between annexin V and deltaPKC occurs in cells after deltaPKC stimulation, but before deltaPKC translocates to the particulate fraction. Evidence of deltaPKC-annexin V binding is provided also by FRET and by in vitro binding studies. Dissociation of the deltaPKC-annexin V complex requires ATP and microtubule integrity. Furthermore, depletion of endogenous annexin V, but not annexin IV, with siRNA inhibits deltaPKC translocation following PKC stimulation. A rationally designed eight amino acid peptide, corresponding to the interaction site for deltaPKC on annexin V, inhibits deltaPKC translocation and deltaPKC-mediated function as evidenced by its protective effect in a model of myocardial infarction. Our data indicate that translocation of deltaPKC is not simply a diffusion-driven process, but is instead a multi-step event regulated by protein-protein interactions. We show that following cell activation, deltaPKC-annexin V binding is a transient and an essential step in the function of deltaPKC, thus identifying a new role for annexin V in PKC signaling and a new step in PKC activation.
Enzyme-polyelectrolyte complex: Salt effects on the reaction of urease with polyallylamine (2009)

The effects of inorganic mono- and divalent salts of different types on how the cation polyelectrolyte polyallylamine hydrochloride (PAA) binds with the oligomer enzyme urease were studied. It was shown that in solutions of the monovalent salts NaCl, KCl, and NH4Cl, polyelectrolyte-protein complexes formed by electrostatic interactions, which decreased monotonically as the salt concentrations increased according to the classic law of statistical physics, correlating the Debye radius with the ionic strength of the solution. In solutions of the divalent salts Na2SO4 and (NH4)2SO4, the efficiency of the formation of the polyelectrolyte-protein complexes changed abruptly (the enzyme was drastically activated) at low salt concentrations (∼0.6–0.8 mM), which was not consistent with the classic theory of charge interactions in solutions with different ionic strengths. Turbidimetric titration at different salt concentrations in the given range revealed a high aggregative ability for sulfates and low ability for chlorides. It was concluded that the anomalies in the concentration dependence of the enzyme activity and aggregative ability were related to the formation of stable bonds PAA to the divalent SO 4 2− anion, which increased drastically when the ratio of anion concentration to the number of positively charged PAA monomers in solution reached 1: 2.
Skin, immunity and the nervous system (1997)

Connections between nerve fibres and cutaneous cells have been studied using confocal and electron microscopy. In the skin, nerve fibres may secrete neuromediators, i.e. substance P, vasoactive intestinal peptide, somatostatin, calcitonin-gene-related peptide, gastrin-releasing peptide, neuropeptide Y, peptide histidine-isoleucine, neurotensin, neurokinins A and B, bradykinin, acetylcholine, catecholamines, endorphins and enkephalins. Neurohormones such as prolactin, melanocyte-stimulating hormone and adrenocorticotrophic hormone are also expressed in the skin. Neuromediators and neurohormones may be secreted by cutaneous cells, which also express receptors. Functions of epidermal and dermal cells are modulated by these substances. Immune cells transiently present in the skin (e.g. macrophages and lymphocytes) are modulated by neuromediators through receptors. During the course of skin disorders, especially inflammatory reactions, the neuroimmunocutaneous system is destabilized. This is particularly true in psoriasis. This destabilization may be secondary, although evidence shows it can also be responsible for the induction and maintenance of the inflammatory process. The skin, the nervous system and immunity are not independent systems but are closely associated and use the same language of cytokines and neurotransmitters. A new concept is suggested: the neuroimmunocutaneous system.
Direct, Catalytic Monofluorination of sp3 C–H Bonds: A Radical-Based Mechanism with Ionic Selectivity (2014)

Recently, our group unveiled a system in which an unusual interplay between copper(I) and Selectfluor effects mild, catalytic sp(3) C-H fluorination. Herein, we report a detailed reaction mechanism based on exhaustive EPR, (19)F NMR, UV-vis, electrochemical, kinetic, synthetic, and computational studies that, to our surprise, was revealed to be a radical chain mechanism in which copper acts as an initiator. Furthermore, we offer an explanation for the notable but curious preference for monofluorination by ascribing an ionic character to the transition state.
[Basic studies on enzyme therapy of immune complex diseases]. (1985)

Several in vitro investigations and animal experiments are described which may be used as experimental basis for the enzymatic treatment of rheumatoid arthritis and, possibly, also other immune complex diseases. Demonstration of absorption of unaltered orally-administered radiolabelled enzymes is shown in guinea pigs and rabbits. In vitro experiments with 4 types of soluble immune complexes which were incubated with gradually increasing amounts of enzymes showed dose-dependent cleavage of complexes. Antigen-induced experimental arthritis of rabbits, fed different amounts of a therapeutically used mixture of enzymes at different times, could be inhibited by this treatment, in dependence of dosage and time of feeding. With respect to the therapeutic applications of this study, the results favour the use of a high dosage repeated daily administration, since duration of effect seems limited.
Using antibody catalysis to study the outcome of multiple evolutionary trials of a chemical task (2000)

Catalytic aldolase antibodies generated by immunization with two different, but structurally related, beta-diketone haptens were cloned and sequenced to study similarities and differences between independently evolved catalysts. Kinetic and sequence analysis coupled with mutagenesis, structural, and modeling studies reveal that the defining event in the evolution of these catalysts was a somatic mutation that placed a lysine residue in a deep, yet otherwise unrefined, hydrophobic pocket. We suggest that covalent chemistries may be as readily selected from the immune repertoire as the traditional noncovalent interactions that have formed the basis of immunochemistry until this time. Further, we believe that these experiments recapitulate the defining events in the evolution of nature's enzymes, particularly as they relate to chemical mechanism, catalytic promiscuity, and gene duplication.
Sequential Immunization with V3 Peptides from Primary Human Immunodeficiency Virus Type 1 Produces Cross-Neutralizing Antibodies against Primary Isolates with a Matching Narrow-Neutralization Sequence Motif (2006)

An antibody response capable of neutralizing not only homologous but also heterologous forms of the CXCR4-tropic human immunodeficiency virus type 1 (HIV-1) MNp and CCR5-tropic primary isolate HIV-1 JR-CSF was achieved through sequential immunization with a combination of synthetic peptides representing HIV-1 Env V3 sequences from field and laboratory HIV-1 clade B isolates. In contrast, repeated immunization with a single V3 peptide generated antibodies that neutralized only type-specific laboratory-adapted homologous viruses. To determine whether the cross-neutralization response could be attributed to a cross-reactive antibody in the immunized animals, we isolated a monoclonal antibody, C25, which neutralized the heterologous primary viruses of HIV-1 clade B. Furthermore, we generated a humanized monoclonal antibody, KD-247, by transferring the genes of the complementary determining region of C25 into genes of the human V region of the antibody. KD-247 bound with high affinity to the "PGR" motif within the HIV-1 Env V3 tip region, and, among the established reference antibodies, it most effectively neutralized primary HIV-1 field isolates possessing the matching neutralization sequence motif, suggesting its promise for clinical applications involving passive immunizations. These results demonstrate that sequential immunization with B-cell epitope peptides may contribute to a humoral immune-based HIV vaccine strategy. Indeed, they help lay the groundwork for the development of HIV-1 vaccine strategies that use sequential immunization with biologically relevant peptides to overcome difficulties associated with otherwise poorly immunogenic epitopes.
Identification of an Inhibitor of Neovascularization from Cartilage (1990)

Certain tissues such as cartilage are resistant to vascular invasion, yet no single tissue-derived molecule that can inhibit angiogenesis has been reported. A protein derived from cartilage was purified that inhibits angiogenesis in vivo and capillary endothelial cell proliferation and migration in vitro in three separate bioassays. This protein is also an inhibitor of mammalian collagenase. These findings may help elucidate the mechanisms by which neovascularization is controlled in both normal and pathological states.
Nonlinear two-dimensional elastic inversion of multioffset seismic data (1987)

Abstract The treatment of multioffset seismic data as an acoustic wave field is becoming increasingly disturbing to many geophysicists who see a multitude of wave phenomena, such as amplitude-offset variations and shear-wave events, which can only be explained by using the more correct elastic wave equation. Not only are such phenomena ignored by acoustic theory, but they are also treated as undesirable noise when they should be used to provide extra information, such as S-wave velocity, about the subsurface. The problems of using the conventional acoustic wave equation approach can be eliminated via an elastic approach. In this paper, equations have been derived to perform an inversion for P-wave velocity, S-wave velocity, and density as well as the P-wave impedance, S-wave impedance, and density. These are better resolved than the Lame parameters. The inversion is based on nonlinear least squares and proceeds by iteratively updating the earth parameters until a good fit is achieved between the observed data and the modeled data corresponding to these earth parameters. The iterations are based on the preconditioned conjugate gradient algorithm. The fundamental requirement of such a least-squares algorithm is the gradient direction which tells how to update the model parameters. The gradient direction can be derived directly from the wave equation and it may be computed by several wave propagations. Although in principle any scheme could be chosen to perform the wave propagations, the elastic finite-difference method is used because it directly simulates the elastic wave equation and can handle complex, and thus realistic, distributions of elastic parameters. This method of inversion is costly since it is similar to an iterative prestack shot-profile migration. However, it has greater power than any migration since it solves for the P-wave velocity, S-wave velocity, and density and can handle very general situations including transmission problems. Three main weaknesses of this technique are that it requires fairly accurate a priori knowledge of the low-wavenumber velocity model, it assumes Gaussian model statistics, and it is very computer-intensive. All these problems seem surmountable. The low-wavenumber information can be obtained either by a prior tomographic step, by the conventional normal-moveout method, by a priori knowledge and empirical relationships, or by adding an additional inversion step for low wavenumbers to each iteration. The Gaussian statistics can be altered by preconditioning the gradient direction, perhaps to make the solution blocky in appearance like well logs, or by using large model variances in the inversion to reduce the effect of the Gaussian model constraints. Moreover, with some improvements to the algorithm and more parallel computers, it is hoped the technique will soon become routinely feasible.
Treatment of Leg Telangiectasias Using a Long-Pulse Frequency-doubled Neodymium:YAG Laser at 532 nm (1998)

The VersaPulse variable pulse width laser appears to be an effective modality for the treatment of leg telangiectasias. The relative lack of patient discomfort combined with a high degree of patient satisfaction may indicate a fairly high level of patient acceptance of this new form of therapy for the treatment of leg telangiectasias.
Three-dimensional optical coherence tomography of the embryonic murine cardiovascular system (2006)

Optical coherence tomography (OCT) is an emerging high-resolution real-time biomedical imaging technology that has potential as a novel investigational tool in developmental biology and functional genomics. In this study, murine embryos and embryonic hearts are visualized with an OCT system capable of 2-microm axial and 15-microm lateral resolution and with real-time acquisition rates. We present, to our knowledge, the first sets of high-resolution 2- and 3-D OCT images that reveal the internal structures of the mammalian (murine) embryo (E10.5) and embryonic (E14.5 and E17.5) cardiovascular system. Strong correlations are observed between OCT images and corresponding hematoxylin- and eosin-stained histological sections. Real-time in vivo embryonic (E10.5) heart activity is captured by spectral-domain optical coherence tomography, processed, and displayed at a continuous rate of five frames per second. With the ability to obtain not only high-resolution anatomical data but also functional information during cardiovascular development, the OCT technology has the potential to visualize and quantify changes in murine development and in congenital and induced heart disease, as well as enable a wide range of basic in vitro and in vivo research studies in functional genomics.
Artificial miRNAs Targeting Mutant Huntingtin Show Preferential Silencing In Vitro and In Vivo (2015)

Huntington's disease (HD) is a dominantly inherited neurodegenerative disease caused by CAG repeat expansion in exon 1 of huntingtin (HTT). Studies in mouse models of HD with a regulated mutant transgene show that continuous mutant allele expression is required for behavioral and pathological signs; when mutant HTT expression declined, neuronal degeneration improved. To date, it is unknown whether neural cells in the adult human brain can tolerate reduction in both normal and mutant alleles. Thus, it may be important to develop allele-specific silencing approaches. Several siRNA sequences targeting the CAG expanded motif or prevalent single-nucleotide polymorphisms (SNPs) in linkage disequilibrium with the mutant allele have been designed and their selectivity demonstrated in vitro. However, it is unknown whether these allele-specific siRNAs will retain their specificity when expressed from artificial RNAi platforms. Here, we designed CAG- and SNP- targeting artificial miRNAs and demonstrate that some, but not all, retained their selectivity in vitro using an allele-specific reporter system and in vivo in a transgenic mouse model developed to express normal and mutant human HTT alleles.
Insights into the antigenic advancement of influenza A(H3N2) viruses, 2011–2018 (2019)

Influenza A(H3N2) viruses evade human immunity primarily by acquiring antigenic changes in the haemagglutinin (HA). HA receptor-binding features of contemporary A(H3N2) viruses hinder traditional antigenic characterization using haemagglutination inhibition and promote selection of HA mutants. Thus, alternative approaches are needed to reliably assess antigenic relatedness between circulating viruses and vaccines. We developed a high content imaging-based neutralization test (HINT) to reduce antigenic mischaracterization resulting from virus adaptation to cell culture. Ferret reference antisera were raised using clinical specimens containing viruses representing recent vaccine strains. Analysis of viruses circulating during 2011-2018 showed that gain of an N158-linked glycosylation in HA was a molecular determinant of antigenic distancing between A/Hong Kong/4801/2014-like (clade 3C.2a) and A/Texas/50/2012-like viruses (clade 3C.1), while multiple evolutionary HA F193S substitution were linked to antigenic distancing from A/Switzerland/97152963/2013-like (clade 3C.3a) and further antigenic distancing from A/Texas/50/2012-like viruses. Additionally, a few viruses carrying HA T135K and/or I192T showed reduced neutralization by A/Hong Kong/4801/2014-like antiserum. Notably, this technique elucidated the antigenic characteristics of clinical specimens, enabling direct characterization of viruses produced in vivo, and eliminating in vitro culture, which rapidly alters the genotype/phenotype. HINT is a valuable new antigenic analysis tool for vaccine strain selection.