gebhart/patrepeval huggingface dataset:
Characterization of the Self Association of Avian Sarcoma Virus Integrase by Analytical Ultracentrifugation (1999)

Retroviral integration protein (IN) has been shown to be both necessary and sufficient for the integration of reverse-transcribed retroviral DNA into the host cell DNA. It has been demonstrated that self-assembly of IN is essential for proper function. Analytical ultracentrifugation was used to determine the stoichiometry and free energy of self-association of a full-length IN in various solvents at 23.3 degrees C. Below 8% glycerol, an association stoichiometry of monomer-dimer-tetramer is observed. At salt concentrations above 500 mM, dimer is the dominant species over a wide range of protein concentrations. However, as physiological salt concentrations are approached, tetramer formation is favored. The addition of glycerol to 500 mM NaCl, 20 mM Tris (pH 8.4), 2 mM beta-mercaptoethanol significantly enhances dimer formation with little effect on tetramer formation. Furthermore, as electrostatic shielding is increased by increasing the ionic strength or decreasing the cation size, dimer formation is strengthened while tetramer formation is weakened. Taken together, the data support a model in which dimer formation includes favorable buried surface interactions which are opposed by charge-charge repulsion, while favorable electrostatic interactions contribute significantly to tetramer formation.
The Alzheimer's disease Beta-secretase enzyme, BACE1 (2007)

The pathogenesis of Alzheimer's disease is highly complex. While several pathologies characterize this disease, amyloid plaques, composed of the beta-amyloid peptide are hallmark neuropathological lesions in Alzheimer's disease brain. Indeed, a wealth of evidence suggests that beta-amyloid is central to the pathophysiology of AD and is likely to play an early role in this intractable neurodegenerative disorder. The BACE1 enzyme is essential for the generation of beta-amyloid. BACE1 knockout mice do not produce beta-amyloid and are free from Alzheimer's associated pathologies including neuronal loss and certain memory deficits. The fact that BACE1 initiates the formation of beta-amyloid, and the observation that BACE1 levels are elevated in this disease provide direct and compelling reasons to develop therapies directed at BACE1 inhibition thus reducing beta-amyloid and its associated toxicities. However, new data indicates that complete abolishment of BACE1 may be associated with specific behavioral and physiological alterations. Recently a number of non-APP BACE1 substrates have been identified. It is plausible that failure to process certain BACE1 substrates may underlie some of the reported abnormalities in the BACE1-deficient mice. Here we review BACE1 biology, covering aspects ranging from the initial identification and characterization of this enzyme to recent data detailing the apparent dysregulation of BACE1 in Alzheimer's disease. We pay special attention to the putative function of BACE1 during healthy conditions and discuss in detail the relationship that exists between key risk factors for AD, such as vascular disease (and downstream cellular consequences), and the pathogenic alterations in BACE1 that are observed in the diseased state.
Fiber tracking: principles and strategies – a technical review (2002)

The state of the art of reconstruction of the axonal tracts in the central nervous system (CNS) using diffusion tensor imaging (DTI) is reviewed. This relatively new technique has generated much enthusiasm and high expectations because it presently is the only approach available to non-invasively study the three-dimensional architecture of white matter tracts. While there is no doubt that DTI fiber tracking is providing exciting new opportunities to study CNS anatomy, it is very important to understand its limitations. In this review we therefore assess the basic principles and the assumptions that need to be made for each step of the study, including both data acquisition and the elaborate fiber reconstruction algorithms. Special attention is paid to situations where complications may arise, and possible solutions are reviewed. Validation issues and potential future directions and improvements are also discussed.
Organization, structure, and polymorphisms of the human profilaggrin gene (1990)

Profilaggrin is a major protein component of the keratohyalin granules of mammalian epidermis. It is initially expressed as a large polyprotein precursor and is subsequently proteolytically processed into individual functional filaggrin molecules. We have isolated genomic DNA and cDNA clones encoding the 5'- and 3'-ends of the human gene and mRNA. The data reveal the presence of likely "CAT" and "TATA" sequences, an intron in the 5'-untranslated region, and several potential regulatory sequences. While all repeats are of the same length (972 bp, 324 amino acids), sequences display considerable variation (10-15%) between repeats on the same clone and between different clones. Most variations are attributable to single-base changes, but many also involve changes in charge. Thus, human filaggrin consists of a heterogeneous population of molecules of different sizes, charges, and sequences. However, amino acid sequences encoding the amino and carboxyl termini are more conserved, as are the 5' and 3' DNA sequences flanking the coding portions of the gene. The presence of unique restriction enzyme sites in these conserved flanking sequences has enabled calculations on the size of the full-length gene and the numbers of repeats in it: depending on the source of genomic DNA, the gene contains 10, 11, or 12 filaggrin repeats that segregate in kindred families by normal Mendelian genetic mechanisms. This means that the human profilaggrin gene system is also polymorphic with respect to size due to simple allelic differences between different individuals. The amino- and carboxyl-terminal sequences of profilaggrin contain partial or truncated repeats with unusual un-filaggrin-like sequences on the termini.(ABSTRACT TRUNCATED AT 250 WORDS)
Affordable, Real-Time, 3-D Avian Radar Networks For Centralized North American Bird Advisory Systems (2005)

Affordable avian radar systems are being developed for Natural Resource Management (NRM) and bird aircraft strike hazard (BASH) applications. Recently [I], the authors have reported on mobile avian radar system requirements and on a system design that is state-of-the-art. In the present paper, the system design of a single avian radar is expanded in scope to address 3-D avian radar networks. These are essential to fully realize an affordable yet high-performance North American bird advisory system. The proposed avian radar network design includes antenna, transceiver and signal processor designs for the avian radar sensor, network design, sensor integration, and system operation and control from an operations center.
Transcriptional Activation of the Cyclin A Gene by the Architectural Transcription Factor HMGA2 (2003)

The HMGA2 protein belongs to the HMGA family of architectural transcription factors, which play an important role in chromatin organization. HMGA proteins are overexpressed in several experimental and human tumors and have been implicated in the process of neoplastic transformation. Hmga2 knockout results in the pygmy phenotype in mice and in a decreased growth rate of embryonic fibroblasts, thus indicating a role for HMGA2 in cell proliferation. Here we show that HMGA2 associates with the E1A-regulated transcriptional repressor p120(E4F), interfering with p120(E4F) binding to the cyclin A promoter. Ectopic expression of HMGA2 results in the activation of the cyclin A promoter and induction of the endogenous cyclin A gene. In addition, chromatin immunoprecipitation experiments show that HMGA2 associates with the cyclin A promoter only when the gene is transcriptionally activated. These data identify the cyclin A gene as a cellular target for HMGA2 and, for the first time, suggest a mechanism for HMGA2-dependent cell cycle regulation.
Recent advances in ruthenium-based olefin metathesis (2018)

Ruthenium-based olefin metathesis catalysts, known for their functional group tolerance and broad applicability in organic synthesis and polymer science, continue to evolve as an enabling technology in these areas. A discussion of recent mechanistic investigations is followed by an overview of selected applications.
Pfam: multiple sequence alignments and HMM-profiles of protein domains (1998)

Pfam contains multiple alignments and hidden Markov model based profiles (HMM-profiles) of complete protein domains. The definition of domain boundaries, family members and alignment is done semi-automatically based on expert knowledge, sequence similarity, other protein family databases and the ability of HMM-profiles to correctly identify and align the members. Release 2.0 of Pfam contains 527 manually verified families which are available for browsing and on-line searching via the World Wide Web in the UK at http://www.sanger.ac.uk/Pfam/ and in the US at http://genome.wustl. edu/Pfam/ Pfam 2.0 matches one or more domains in 50% of Swissprot-34 sequences, and 25% of a large sample of predicted proteins from the Caenorhabditis elegans genome.
Simian immunodeficiency virus RNA is efficiently encapsidated by human immunodeficiency virus type 1 particles (1993)

Packaging of retroviral RNA is attained through the specific recognition of a cis-acting encapsidation site (located near the 5' end of the viral RNA) by components of the Gag precursor protein. Human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) are two lentiviruses that lack apparent sequence similarity in their putative encapsidation regions. We used SIV vectors to determine whether HIV-1 particles can recognize the SIV encapsidation site and functionally propagate SIV nucleic acid. SIV nucleic acid was replicated by HIV-1 proteins. Thus, efficient lentivirus pseudotyping can take place at the RNA level. Direct examination of the RNA contents of virus particles indicated that encapsidation of this heterologous RNA is efficient. Characterization of deletion mutants in the untranslated leader region of SIV RNA indicates that only a very short region at the 5' end of the SIV RNA is needed for packaging. Comparison of this region with the corresponding region of HIV-1 reveals that both are marked by secondary structures that are likely to be similar. Thus, it is likely that a similar higher-order RNA structure is required for encapsidation.
High‐frequency electrical conduction block of mammalian peripheral motor nerve (2005)

Abstract A quick‐acting, quick‐reversing method for blocking action potentials in peripheral nerves could be used in the treatment of muscle spasticity and pain. A high‐frequency alternating‐current (HFAC) sinusoidal waveform is one possible means for providing this type of block. HFAC was used to block peripheral motor nerve activity in an in vivo mammalian model. Frequencies from 10 to 30 kH Z at amplitudes of between 2 and 10 V were investigated. A complete and reversible motor block was obtained at all frequencies. The block threshold amplitudes showed a linear relationship with frequency, the lowest threshold being at 10 kH Z . HFAC block has three phases: an onset response; a period of asynchronous firing; and a steady state of complete or partial block. The onset response and the asynchronous firing can be minimized by using an optimal frequency–amplitude combination. In general, the onset response was lowest for the combination of 30 kH Z and 10 V. Muscle Nerve, 2005
Identification of a peroxisomal targeting signal at the carboxy terminus of firefly luciferase. (1987)

Translocation of proteins across membranes of the endoplasmic reticulum, mitochondrion, and chloroplast has been shown to be mediated by targeting signals present in the transported proteins. To test whether the transport of proteins into peroxisomes is also mediated by a peptide targeting signal, we have studied the firefly luciferase gene that encodes a protein transported to peroxisomes in both insect and mammalian cells. We have identified two regions of luciferase which are necessary for transport of this protein into peroxisomes. We demonstrate that one of these, region II, represents a peroxisomal targeting signal because it is both necessary and sufficient for directing cytosolic proteins to peroxisomes. The signal is no more than twelve amino acids long and is located at the extreme carboxy-terminus of luciferase. The location of the targeting signal for translocation across the peroxisomal membrane therefore differs from the predominantly amino-terminal location of signals responsible for transport across the membranes of the endoplasmic reticulum, chloroplast, or mitochondrion.
Studies with a PNMT inhibitor (1979)

DCTQ (SK&F 64139) is a potent inhibitor of both adrenal and central nervous system (CNS) phenylethanolamine N-methyltransferase (PNMT). In animal studies, a plasma level of 0.35 microgram/ml was associated with 50% inhibition of both adrenal and central PNMT. We performed single-dose phase I studies with DCTQ in man. Plasma drug levels up to 6.26 microgram/ml were readily obtained. There were few subjective and no objective clinical changes. DCTQ did not alter blood pressure or cause CNS symptoms in man. Furthermore, resting plasma and urinary catecholamines did not change after DCTQ. The study suggests that acute inhibition of PNMT under resting conditions is without significant clinical effect.
In vitro and in vivo properties of a dimeric bispecific single‐chain antibody IgG‐fusion protein for depletion of CCR2+ target cells in mice (2005)

The chemokine receptor CCR2 is highly expressed on leukocytes in several inflammatory diseases of both mice and men. Apart from blockade of CCR2 to prevent chemokine-dependent cell migration, depletion of CCR2(+) cells might be a promising strategy for treatment of inflammatory diseases. We therefore designed a bispecific antibody construct with the ability to deplete CCR2(+) target cells in vitro and in vivo. The bispecific antibody construct consists of two single-chain antibody variable fragments (scFv) - one recognizing murine CD3epsilon and the other recognizing murine CCR2 - joined by a short linker and fused to a modified hinge region and the C(H)2 and C(H)3 domains of murine IgG1 for dimerization. The protein was expressed in mammalian cells and purified via its C-terminal histidine tail. In vitro this construct leads to efficient antigen-specific and costimulation-independent activation of T cells and strong lysis of CCR2(+) target cells. In vivo the construct induces an almost complete depletion of CCR2(+)CD11b(+) monocytes from the peripheral blood and spleens of BALB/c mice within 24 h. This recombinant protein construct is a dimeric, bispecific antibody with markedly improved serum levels compared to conventional bispecific single-chain antibodies and the ability to deplete CCR2(+)CD11b(+) monocytes in vivo.
Bioeffects induced by exposure to microwaves are mitigated by superposition of ELF noise (1997)

We have previously demonstrated that microwave fields, amplitude modulated (AM) by an extremely low-frequency (ELF) sine wave, can induce a nearly twofold enhancement in the activity of ornithine decarboxylase (ODC) in L929 cells at SAR levels of the order of 2.5 W/kg. Similar, although less pronounced, effects were also observed from exposure to a typical digital cellular phone test signal of the same power level, burst modulated at 50 Hz. We have also shown that ODC enhancement in L929 cells produced by exposure to ELF fields can be inhibited by superposition of ELF noise. In the present study, we explore the possibility that similar inhibition techniques can be used to suppress the microwave response. We concurrently exposed L929 cells to 60 Hz AM microwave fields or a 50 Hz burst-modulated DAMPS (Digital Advanced Mobile Phone System) digital cellular phone field at levels known to produce ODC enhancement, together with band-limited 30-100 Hz ELF noise with root mean square amplitude of up to 10 microT. All exposures were carried out for 8 h, which was previously found to yield the peak microwave response. In both cases, the ODC enhancement was found to decrease exponentially as a function of the noise root mean square amplitude. With 60 Hz AM microwaves, complete inhibition was obtained with noise levels at or above 2 microT. With the DAMPS digital cellular phone signal, complete inhibition occurred with noise levels at or above 5 microT. These results suggest a possible practical means to inhibit biological effects from exposure to both ELF and microwave fields.
Characterization of phosphoproteins from electrophoretic gels by nanoscale Fe(III) affinity chromatography with off-line mass spectrometry analysis (2001)

Detailed characterization of phosphoproteins as well as other post-translationally modified proteins is required to fully understand protein function and regulatory events in cells and organisms. Here we present a mass spectrometry (MS) based experimental strategy for the identification and mapping of phosphorylation site(s) using only low-picomole amounts of phosphoprotein starting material. Miniaturized sample preparation methods for MS facilitated localization of phosphorylation sites in phosphoproteins isolated by polyacrylamide gel electrophoresis. Custom made, nanoscale immobilized Fe(III) affinity chromatography (Fe(III)-IMAC) columns were employed for enrichment of phosphorylated peptides from crude peptide mixtures prior to off-line analysis by matrix-assisted laser desorption/ionization (MALDI) MS or nanoelectrospray tandem mass spectrometry (MS/MS). An optimized and sensitive procedure for alkaline phosphatase treatment of peptide mixtures was implemented, which in combination with nano-scale Fe(III)-IMAC and MALDI-MS allowed unambiguous identification of phosphopeptides by observation of 80 Da mass shifts. Nanoelectrospray MS/MS was used for phosphopeptide sequencing for exact determination of phosphorylation sites. The advantages and limitations of the experimental strategy was demonstrated by enrichment, identification and sequencing of phosphopeptides from the model proteins ovalbumin and bovine beta-casein isolated by gel electrophoresis. Furthermore, an autophosphorylation site at Ser-3 in recombinant human casein kinase-2 beta subunit was determined. The potential of miniaturized Fe(III)-IMAC and MALDI-MS for characterization of in vivo phosphorylated proteins was demonstrated by identification of tryptic phosphopeptides derived from the human p47/phox phosphoprotein isolated by two-dimensional gel electrophoresis.
Conversion dependence of the structural units and the degree of branching of a hyperbranched polyester based on 4,4-bis-(4′-hydroxyphenyl)pentanoic acid determined by NMR spectroscopy (1999)

The hyperbranched polyester based on 4,4-bis-(4′-hydroxyphenyl)pentanoic acid was synthesized with different DP's. A complete 1H and 13C NMR assignment of the oligomers was carried out. Six different structural units were quantified by NMR analysis. The conversion dependence of the content of these structural units and of the degree of branching DB follows the theoretically derived equations. Furthermore, six different diads were quantified by 13C NMR spectroscopy. The conversion dependence of the diads was calculated and again the measured data agree well with the theory. The good fit between theoretical and measured data proves that the polycondensation of the 4,4-bis-(4′-hydroxyphenyl)pentanoic acid follows a random growth of the different units with equal reaction rates of all reaction steps. Finally, spin-lattice relaxation times (T1C) and nuclear Overhauser enhancements (NOE) were determined and discussed.
Cas13b is a Type VI-B CRISPR-associated RNA-Guided RNase differentially regulated by accessory proteins Csx27 and Csx28 (2016)

CRISPR-Cas adaptive immune systems defend microbes against foreign nucleic acids via RNA-guided endonucleases. Using a computational sequence database mining approach, we identify two Class 2 CRISPR-Cas systems (subtype VI-B) that lack Cas1 and Cas2 and encompass a single large effector protein, Cas13b, along with one of two previously uncharacterized associated proteins, Csx27 or Csx28. We establish that these CRISPR-Cas systems can achieve RNA interference when heterologously expressed. Through a combination of biochemical and genetic experiments, we show that Cas13b processes its own CRISPR array with short and long direct repeats, cleaves target RNA, and exhibits collateral RNase activity. Using an E. coli essential gene screen, we demonstrate that Cas13b has a double-sided protospacer-flanking sequence and elucidate RNA secondary structure requirements for targeting. We also find that Csx27 represses, whereas Csx28 enhances, Cas13b-mediated RNA interference. Characterization of these CRISPR systems creates opportunities to develop tools to manipulate and monitor cellular transcripts.
Modes of action of interferon and analogues of 2-5A, a mediator of interferon action (1984)

In the last few years, several different interferons have been described, cloned, sequenced, expressed in heterologous systems and purified to homogeneity (Weissmann et al., 1982; Kingsman & Kingsman, 1983). In particular for human interferons there exists at least thirteen subtypes of IFN-α, one IFN-β and one IFN-γ. All these molecular species and some of their recombinant hybrids show a number of common biological properties but also distinctive antiviral (Weck et al., 1981; Kingsman & Kingsman, 1983) and other activities (Rehberg et al., 1982; Pestka et al., 1983b). Recombinant DNA technology has substantially contributed to the study of the mechanism of action of interferon and will probably continue to do so in the future by allowing a detailed analysis of the regulation and site-directed mutagenesis of IFN-induced proteins.
Advertising: Is IT A Necessary Evil or A Flawed Blessing? (2015)

Advertising clutter and consumer apathy has been discussed at length in many research papers. The inspiration for the present research paper has come from the innovative and strategic use of advertisement money by Virgin Group (USA) for better promotion and placement of their products; against giant international competitors well entrenched in their own markets. This success must inspire companies to fight temptation to add to the clutter and waste a lot of corporate and mostly public funds with no tangible evidence of increasing their company sales and profitability. If we can dispassionately look at some of the recent TV commercials; For example tooth paste products; some brands claim different benefits for their own marginally different versions and others invent newer benefits and previously unheard of virtues and health benefits: the point of concern is-does the advertisement really pays off? OR can such big money be used for better products or customer service? This paper attempts to critically evaluate the efficacy of advertisements in the present crowded environment of advertisement space. Still some companies pursue an aggressive advertising plan-is it really paying? These questions will be increasingly relevant where corporate profits are continuously under pressure and global organizations are trying to figure a way out of this unhealthy and unprofitable advertisement race.
Neuropathic Pain Features in Patients With Bone Metastases Referred for Palliative Radiotherapy (2010)

Some patients with bone metastases manifest bone pain with distinguishable neuropathic features, and these patients reported greater pain intensity. Additional work is required to validate the S-LANSS against clinical criteria for neuropathic pain in this context and to explore the unmet pain management needs in this population.
Animal-assisted therapy for the homebound elderly (1993)

Harris, Marilyn D. RN, MSN; Rinehart, Joan M. RN, PhD; Gerstman, Jody MSW Author Information