gebhart/patrepeval huggingface dataset:
The human GINS complex associates with Cdc45 and MCM and is essential for DNA replication (2009)

The GINS complex, originally discovered in Saccharomyces cerevisiae and Xenopus laevis, binds to DNA replication origins shortly before the onset of S phase and travels with the replication forks after initiation. In this study we present a detailed characterization of the human GINS (hGINS) homolog. Using new antibodies that allow the detection of endogenous hGINS in cells and tissues, we have examined its expression, abundance, subcellular localization and association with other DNA replication proteins. Expression of hGINS is restricted to actively proliferating cells. During the S phase, hGINS becomes part of a Cdc45-MCM-GINS (CMG) complex that is assembled on chromatin. Down-regulation of hGINS destabilizes CMG, causes a G1-S arrest and slows down ongoing DNA replication, effectively blocking cell proliferation. Our data support the notion that hGINS is an essential component of the human replisome.
ALK in Neuroblastoma: Biological and Therapeutic Implications (2018)

Neuroblastoma (NB) is the most common and deadly solid tumour in children. Despite the development of new treatment options for high-risk NB, over half of patients relapse and five-year survival remains at 40-50%. Therefore, novel treatment strategies aimed at providing long-term disease remission are urgently sought. <i>ALK</i>, encoding the anaplastic lymphoma kinase receptor, is altered by gain-of-function point mutations in around 14% of high-risk NB and represents an ideal therapeutic target given its low or absent expression in healthy tissue postnatally. Small-molecule inhibitors of Anaplastic Lymphoma Kinase (ALK) approved in ALK fusion-positive lung cancer are currently undergoing clinical assessment in patients with ALK-mutant NB. Parallel pre-clinical studies are demonstrating the efficacy of ALK inhibitors against common ALK variants in NB; however, a complex picture of therapeutic resistance is emerging. It is anticipated that long-term use of these compounds will require combinatorial targeting of pathways downstream of ALK, functionally-related 'bypass' mechanisms and concomitant oncogenic pathways.
Prophage Genomics (2003)

The majority of the bacterial genome sequences deposited in the National Center for Biotechnology Information database contain prophage sequences. Analysis of the prophages suggested that after being integrated into bacterial genomes, they undergo a complex decay process consisting of inactivating point mutations, genome rearrangements, modular exchanges, invasion by further mobile DNA elements, and massive DNA deletion. We review the technical difficulties in defining such altered prophage sequences in bacterial genomes and discuss theoretical frameworks for the phage-bacterium interaction at the genomic level. The published genome sequences from three groups of eubacteria (low- and high-G+C gram-positive bacteria and gamma-proteobacteria) were screened for prophage sequences. The prophages from Streptococcus pyogenes served as test case for theoretical predictions of the role of prophages in the evolution of pathogenic bacteria. The genomes from further human, animal, and plant pathogens, as well as commensal and free-living bacteria, were included in the analysis to see whether the same principles of prophage genomics apply for bacteria living in different ecological niches and coming from distinct phylogenetical affinities. The effect of selection pressure on the host bacterium is apparently an important force shaping the prophage genomes in low-G+C gram-positive bacteria and gamma-proteobacteria.
Signal acquisition and tracking with adaptive arrays in the digital mobile radio system IS-54 with flat fading (1993)

The author considers the dynamic performance of adaptive arrays in wireless communication systems. With an adaptive array, the signals received by multiple antennas are weighted and combined to suppress interference and combat desired signal fading. In these systems, the weight adaptation algorithm must acquire and track the weights even with rapid fading. The author considers the performance of the least-mean-square (LMS) and direct matrix inversion (DMI) algorithms in the North American digital mobile radio system IS-54. He shows that implementation of these algorithms permits the use of coherent detection, which improves performance by 1 dB over differential detection. Results for two base station antennas with flat Rayleigh fading show that the LMS algorithm has large tracking loss for vehicle speeds above 20 mph, but the DMI algorithm can acquire and track the weights to combat desired signal fading at vehicle speeds up to 60 mph with less than 0.2 dB degradation from ideal performance with differential detection. Similarly, interference is also suppressed with performance gains over maximal ratio combining within 0.5 dB of the predicted ideal gain.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Glioma Surgery: Technological Advances to Achieve a Maximal Safe Resection. (2015)

Glioblastoma multiforme (GBM) is the most frequent primary central nervous system (CNS) tumor. Despite the best treatment and advances in therapy, prognosis remains poor. One of the mainstays of therapy in GBM is surgical excision. Several studies have confirmed that the extent of resection (EOR) positively influences overall survival (OS) in patients with high-grade gliomas (HGGs). A literature search was performed using PubMed to assess the useful neurosurgical tools to achieve the best neurosurgical performance. In order to achieve the major extent of resection, preserving neurological function, many tools are now available, especially neuronavigation, intraoperative fluorescence, intraoperative ultrasound, and neuromonitoring. In addition to the maximal excision of tumor, the neurosurgeon can use photodynamic therapy (PTD) and local drug delivery (LDD) to improve the local control and bridge conventional radio and chemotherapy. EOR improves OS in patients with HGGs. There are technological possibilities for achieving a complete resection preserving neurological function, and it is not acceptable to perform only biopsy of these lesions.
The synthesis, discovery, and development of a highly promising class of microtubule stabilization agents: Curative effects of desoxyepothilones B and F against human tumor xenografts in nude mice (2001)

We have evaluated two synthetic epothilone analogues lacking the 12,13-epoxide functionality, 12,13-desoxyepothilone B (dEpoB), and 12,13-desoxyepothilone F (dEpoF). The concentrations required for 50% growth inhibition (IC(50)) for a variety of anticancer agents were measured in CCRF-CEM/VBL1000 cells (2,048-fold resistance to vinblastine). By using dEpoB, dEpoF, aza-EpoB, and paclitaxel, the IC(50) values were 0.029, 0.092, 2.99, and 5.17 microM, respectively. These values represent 4-, 33.5-, 1,423- and 3,133-fold resistance, respectively, when compared with the corresponding IC(50) in the parent [nonmultiple drug-resistant (MDR)] CCRF-CEM cells. We then produced MDR human lung carcinoma A549 cells by continuous exposure of the tumor cells to sublethal concentrations of dEpoB (1.8 yr), vinblastine (1.2 yr), and paclitaxel (1.8 yr). This continued exposure led to the development of 2.1-, 4,848-, and 2,553-fold resistance to each drug, respectively. The therapeutic effect of dEpoB and paclitaxel was also compared in vivo in a mouse model by using various tumor xenografts. dEpoB is much more effective in reducing tumor sizes in all MDR tumors tested. Analysis of dEpoF, an analog possessing greater aqueous solubility than dEpoB, showed curative effects similar to dEpoB against K562, CCRF-CEM, and MX-1 xenografts. These results indicate that dEpoB and dEpoF are efficacious antitumor agents with both a broad chemotherapeutic spectrum and wide safety margins.
Processing and properties of centimeter-long, in-fiber, crystalline-selenium filaments (2010)

We report on the fabrication and characterization of globally ordered crystalline selenium filaments with diameters about 200 nm and aspect ratios upwards of 105. Amorphous Se filaments are fabricated by a recently developed approach in which a thin film evolves into an ordered array of filaments in fiber. Single-crystal and polycrystalline filaments are attained with a postdrawing annealing procedure. Arrays of two-cm-long crystalline nanowires, electrically contacted to external circuitry through the fiber end facets, exhibit a two-orders-of-magnitude change in conductivity between dark and illuminated states. These results hold promise for the fabrication of filament-detector arrays that may be integrated with large-area electronics.
Recent developments in our understanding of the plant cuticle as a barrier to the foliar uptake of pesticides† (1999)

The plant cuticle is a highly complex membrane which forms the outer surface of the aerial portion of plants. The nature of the plant cuticle is reviewed with particular regard to its action as a potential barrier to the penetration of pesticide molecules; the role of the cuticular waxes is highlighted. The physicochemical properties of the cuticle influence the behaviour of spray droplets and, in turn, may affect the rate and efficiency of cuticle penetration. The permeation of active ingredients is influenced by their solubility characteristics as indicated by octanol/water (log Kow) and cuticle/water (Kcw) partition coefficients. Penetration of hydrophilic compounds (low log Kow) may be enhanced by hydration of the cuticle, while transcuticular transport of non-polar solutes (high log Kow) is increased by factors which reduce wax viscosity. The use of in-vitro models involving isolated cuticle membranes, isolated cuticle waxes, or isolated leaves has helped to focus on the activities of the cuticle in the absence of other physiological factors. Using these systems, the role of the waxes as a transport-limiting barrier has been identified and the factors influencing sorption, permeance and desorption examined. The action of surfactants, in vitro and in vivo, has been briefly addressed in regard to their role in facilitating cuticle penetration; other steps involving surfactant/solute/cuticle are complex, and synergy appears to depend on a number of factors including test species, concentration of active ingredient, surfactant type and concentration. Adjuvants may greatly influence the surface properties of the droplet, predispose the cuticle to solute transport, and enhance pesticide activity. The nature of these complex inter-relationships is discussed. © 1999 Society of Chemical Industry
New Inhibitors of Scrapie-Associated Prion Protein Formation in a Library of 2,000 Drugs and Natural Products (2003)

Transmissible spongiform encephalopathies (TSEs) are fatal, untreatable neurodegenerative diseases associated with the accumulation of a disease-specific form of prion protein (PrP) in the brain. One approach to TSE therapeutics is the inhibition of PrP accumulation. Indeed, many inhibitors of the accumulation of PrP associated with scrapie (PrP(Sc)) in scrapie-infected mouse neuroblastoma cells (ScN(2)a) also have antiscrapie activity in rodents. To expedite the search for potential TSE therapeutic agents, we have developed a high-throughput screening assay for PrP(Sc) inhibitors using ScN(2)a cells in a 96-well format. A library of 2000 drugs and natural products was screened in ScN(2)a cells infected with scrapie strain RML (Chandler) or 22L. Forty compounds were found to have concentrations causing 50% inhibition (IC(50)s) of PrP(Sc) accumulation of <or=10 microM against both strains. Seventeen had IC(50)s of <or=1 microM against both strains. Several classes of compounds were represented in the 17 most potent inhibitors, including naturally occurring polyphenols (e.g., tannic acid and tea extracts), phenothiazines, antihistamines, statins, and antimalarial compounds. These 17 compounds were also evaluated in a solid-phase cell-free hamster PrP conversion assay. Only the polyphenols inhibited the cell-free reaction, and their IC(50)s were near 100 nM. Several of the new PrP(Sc) inhibitors cross the blood-brain barrier and thus have potential to be effective after TSE infection reaches the brain. The fact that many are either approved human drugs or edible natural products should facilitate their use in animal testing and clinical trials.
Differential effects of CD40 stimulation on normal and neoplastic cell growth. (2000)

CD40 is a molecule in the tumor necrosis factor receptor/nerve growth factor receptor (TNFR/NGFR) family that is present on both normal and neoplastic B lineage cells. It is also expressed on carcinoma and melanoma cells and can be augmented with interferon gamma. CD40 stimulation in normal B cells has been demonstrated to promote normal B cell differentiation and growth in vitro. In contrast to these effects, CD40 stimulation by either anti-CD40 antibodies or a recombinant soluble CD40 ligand can inhibit the growth of human breast carcinomas and aggressive histology B lymphomas in vitro and in vivo. This is believed to occur by activation-induced cell death (AICD) in which stimuli that promote the growth of normal cell types inhibit the growth of neoplastic counterparts. This occurs through the induction of apoptosis, necrosis and/or cell cycle arrest. Thus, CD40 stimulation may be of potential clinical use in the treatment of carcinomas and B cell lymphomas. This review shall provide an overview of the various effects of CD40 stimulation on both normal and neoplastic cell types.
Sequential expression of new gene programs in inducer T-cell clones. (1983)

We have prepared a cDNA probe that detects genes that are rapidly and abundantly expressed after exposure of inducer T-lymphocyte clones to antigen or mitogen. All inducer cells tested express a characteristic set of new mRNA, and these mRNAs are not expressed after activation of other lymphocytes. This initial burst of mRNA synthesis is paralleled by synthesis and secretion of a family of polypeptides that mediate inducer cell activity, including T- and B-cell growth factors, interferon, and molecules that bind to antigen. Expression of this initial genetic program precedes mitosis and is replaced within 74 hr by a different genetic program, which may control further cell division. The action of these sequential sets of genetic programs defines two stages of the cell's differentiation and accounts for altered expression of the cell's immunological functions.
A Single-Step Affinity Column for Purification of Serotype-5 Based Adeno-associated Viral Vectors (2001)

Here we describe a single-step affinity column for purification of vectors based on adeno-associated virus type 5 (AAV5). A sialic-acid-rich protein called mucin was covalently attached to Sepharose and was found to bind AAV5 vectors. Elution with high salt efficiently recovered highly active vectors of greater purity than what is achieved with CsCl(2) sedimentation.
Enhanced Gas Sensing by Individual SnO2 Nanowires and Nanobelts Functionalized with Pd Catalyst Particles (2005)

The sensing ability of individual SnO(2) nanowires and nanobelts configured as gas sensors was measured before and after functionalization with Pd catalyst particles. In situ deposition of Pd in the same reaction chamber in which the sensing measurements were carried out ensured that the observed modification in behavior was due to the Pd functionalization rather than the variation in properties from one nanowire to another. Changes in the conductance in the early stages of metal deposition (i.e., before metal percolation) indicated that the Pd nanoparticles on the nanowire surface created Schottky barrier-type junctions resulting in the formation of electron depletion regions within the nanowire, constricting the effective conduction channel and reducing the conductance. Pd-functionalized nanostructures exhibited a dramatic improvement in sensitivity toward oxygen and hydrogen due to the enhanced catalytic dissociation of the molecular adsorbate on the Pd nanoparticle surfaces and the subsequent diffusion of the resultant atomic species to the oxide surface.
In vitro characterization of Ro 46‐2005, a novel synthetic non‐peptide endothelin antagonist of ETA and ETB receptors (1993)

Ro 46-2005 is a new synthetic non-peptide endothelin (ET) receptor antagonist. In binding experiments, Ro 46-2005 proved to be equipotent (IC50 200-500 nM) for inhibition of [125]ET-1 binding on the two known ET receptor subtypes (ETA and ETB). Scatchard analysis was consistent with a competitive binding mode. Ro 46-2005 also inhibited the functional consequences of ET-1 stimulation: the ET-1 induced release of arachidonic acid from rat mesangial cells was inhibited with an IC50 of 1.8 microM.
Peroxidases in chemistry and biology (1990)

The second of two relatively independent volumes on the chemistry and biology of peroxidases. Volumes 2 covers the peroxidases isolated from plants and microorganisms, and includes detailed discussions of some of the unique reactions catalyzed by these enzymes. Volume one covered the peroxidases iso
Cytokine and chemokine expression in the central nervous system associated with protective cell-mediated immunity againstCryptococcus neoformans (2004)

Cryptococcus neoformans is a yeast that causes cryptococcosis, a life-threatening disease that develops following inhalation and dissemination of the organisms. C. neoformans has a predilection for the central nervous system (CNS) and mortality is most frequently associated with meningoencephalitis. Susceptibility to cryptococcosis is increased in patients with deficiencies in cell-mediated immunity (CMI). Because cryptococcal CNS infections are associated with mortality and diagnosis of cryptococcosis is often not made until after dissemination to the CNS, a better understanding of host defense mechanisms against C. neoformans in the CNS is needed to design improved therapies for immunocompromised individuals suffering from cryptococcosis. Using a mouse model, we previously described a protective cell-mediated immune response induced in the periphery that limited the growth of C. neoformans in the CNS. In the current investigation, we examined cytokine and chemokine expression in the CNS to identify factors important in achieving protective immunity. We observed increased expression of IL-1beta, TNF-alpha, IFN-gamma, MCP-1, RANTES, and IP-10 in C. neoformans-infected brains of immune mice compared to control mice suggesting that these cytokines and chemokines are associated with the protective immune response. Furthermore, the Th1-type cytokines TNF-alpha and IFN-gamma, but not the Th2 cytokines IL-4 and IL-5, were secreted at significantly higher levels in C. neoformans-infected brains of immune mice compared to control mice. Our results demonstrate that cytokines and chemokines associated with CMI are produced following infection in the CNS of immunized mice, and the expression of these factors correlates with protection against C. neoformans in the CNS.
Site-Specific Glycosylation of Secretory Immunoglobulin A from Human Colostrum (2015)

Secretory immunoglobulin A (sIgA) is a major glycoprotein in milk and plays a key role in mediating immune protection of the gut mucosa. Although it is a highly glycosylated protein, its site-specific glycosylation and associated glycan micro-heterogeneity have still not been fully elucidated. In this study, the site-specific glycosylation of sIgA isolated from human colostrum (n = 3) was analyzed using a combination of LC-MS and LC-MS/MS and in-house software (Glycopeptide Finder). The majority of the glycans found are biantennary structures with one or more acidic Neu5Ac residues; however, a large fraction belonged to truncated complex structures with terminal GlcNAc. Multiple glycosites were identified with nearly 30 glycan compositions located at seven sites on the secretory component, six compositions at a single site on the J chain, and 16 compositions at five sites on the IgA heavy (H) chain. Site-specific heterogeneity and relative quantitation of each composition and the extent of occupation at each site were determined using nonspecific proteases. Additionally, 54 O-linked glycan compositions located at the IgA1 hinge region (HR) were identified by comparison against a theoretical O-glycopeptide library. This represents the most comprehensive report to date detailing the complexity of glycan micro-heterogeneity with relative quantitation of glycoforms for each glycosylation site on milk sIgA. This strategy further provides a general method for determining site-specific glycosylation in large protein complexes.
Fatty Acid Compositions of Oil Species Affect the 5 Basic Taste Perceptions (2002)

ABSTRACT: To elucidate the effects of oils, particularly tuna oil, on taste perception, we conducted sensory analysis employing an oil‐in‐water emulsion prepared with basic taste substances and 3 oil species. Each type of oil extended perception retention, and did not affect sweetness or saltiness, but suppressed sourness and bitterness. Bitterness suppression was highest in tuna oil. Tuna oil also enhanced umami intensity. The results of individual fatty acid addition test were in good agreement with these effects of tuna oil. Thus, we proposed that tuna oil's specific fatty acid composition resulted in the specific taste effects of tuna oil.
General purpose multichannel micro-dispensing device (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTGeneral purpose multichannel micro-dispensing deviceMurray. Kahl, Gerald I. Kaufman, and John M. WiltCite this: Anal. Chem. 1976, 48, 4, 789–790Publication Date (Print):April 1, 1976Publication History Published online1 May 2002Published inissue 1 April 1976https://pubs.acs.org/doi/10.1021/ac60368a001https://doi.org/10.1021/ac60368a001research-articleACS PublicationsRequest reuse permissionsArticle Views24Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
A facile synthesis of 5H‐1‐thia‐3,5,6,8‐tetraazaacenaphthylenes (1995)

Abstract Ethyl 5‐substituted 7‐(methylthio)‐5 H ‐1‐thia‐3,5,6,8‐ tetra‐azaacenaphthylene‐2‐carboxylates ( 5a‐f ) representing a new heterocyclic system were prepared by acid‐catalyzed cyclocondensation of ethyl 5‐amino‐4‐(substituted amino)‐2‐(methylthio)thieno[2,3‐ d ]pyrimidine‐6‐carboxylates ( 3a‐f ) with triethyl orthoformate. Compounds 3 were obtained by aminolysis of 4,6‐dichloro‐2‐(methylthio)pyrimidine‐5‐carbonitrile ( 1 ) affording 2 followed by base‐promoted cyclization with sodium ethyl thioglycolate.