gebhart/patrepeval huggingface dataset:
Maintenance and differentiation in culture of pluripotential embryonic cell lines from pig blastocysts. (1990)

Cell lines were established from explanted blastocysts of domestic pigs; the cells could be maintained indefinitely when grown on mouse fibroblast feeder cell layers. They differentiate spontaneously at high densities, or when allowed to form aggregates when cultured on a non-adhesive substratum. Their appearance and differentiative behaviour resembles that of mouse embryonic stem cell lines. We are currently attempting to establish whether these cultures represent primary ectodermal lineages which would be of particular relevance to developmental and transgenic studies.
Interaction of the Vp3 Nuclear Localization Signal with the Importin α2/β Heterodimer Directs Nuclear Entry of Infecting Simian Virus 40 (2002)

For nuclear entry of large nucleoprotein complexes, it is thought that one key nuclear localization signal (NLS) of a protein component becomes exposed to mediate importin recognition. We show that the nuclear entry of simian virus 40 involves a dynamic interplay between two distinct interiorly situated capsid NLSs, the Vp1 NLS and the Vp3 NLS, and the selective exposure and importin recognition of the Vp3 NLS. The Vp3 NLS-null mutants assembled normally into virion-like particles (VLP) in mutant DNA-transfected cells. When used to infect a new host, the null VLP entered the cell normally but was impaired in viral DNA nuclear entry due to a lack of recognition by the importin alpha 2/beta heterodimer, leading to reduced viability. Both Vp3 and Vp1 NLSs directed importin interaction in vitro, but the Vp1 NLS, which overlaps the Vp1 DNA binding domain, did not bind importins in the presence of DNA. The results suggest that certain canonical NLSs within a nucleoprotein complex, such as the Vp1 NLS, can be masked from functioning by binding to the nucleic acid component and that the availability of an NLS that is not masked and can become exposed for importin binding, such as the Vp3 NLS, is a general feature of the nuclear entry of the nucleoprotein complexes, including those of other animal viruses.
The synthetic triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole blocks nuclear factor-κB activation through direct inhibition of IκB kinase β (2006)

The synthetic triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im) is a multifunctional agent with potent anti-inflammatory, antiproliferative, cytoprotective, and apoptotic activities, whose molecular targets are unknown. Using both cell-free and cellular assays, we show that CDDO-Im is a direct inhibitor of IkappaB kinase (IKK) beta and that it thereby inhibits binding of nuclear factor-kappaB to DNA and subsequent transcriptional activation. Pretreatment of cells with CDDO-Im prevents IkappaBalpha phosphorylation and degradation in response to tumor necrosis factor alpha. The kinetics of this inhibition by CDDO-Im are rapid and occur within 15 min. A biotinylated analogue of CDDO-Im showed that CDDO-Im binds to the IKK signalsome. Furthermore, we show that Cys(179) on IKK is a target for CDDO-Im. This is the first report to show that this novel synthetic triterpenoid binds to and inhibits IKKbeta directly.
Structure of an E6AP-UbcH7 Complex: Insights into Ubiquitination by the E2-E3 Enzyme Cascade (1999)

The E6AP ubiquitin-protein ligase (E3) mediates the human papillomavirus-induced degradation of the p53 tumor suppressor in cervical cancer and is mutated in Angelman syndrome, a neurological disorder. The crystal structure of the catalytic hect domain of E6AP reveals a bilobal structure with a broad catalytic cleft at the junction of the two lobes. The cleft consists of conserved residues whose mutation interferes with ubiquitin-thioester bond formation and is the site of Angelman syndrome mutations. The crystal structure of the E6AP hect domain bound to the UbcH7 ubiquitin-conjugating enzyme (E2) reveals the determinants of E2-E3 specificity and provides insights into the transfer of ubiquitin from the E2 to the E3.
Hyperdiploid (47-50) acute lymphoblastic leukemia in children (1992)

Among ploidy groups in childhood acute lymphoblastic leukemia (ALL), hyperdiploidy 47 to 50 is perhaps the least well known. From December 1979 to December 1990, we successfully studied banded karyotypes in 598 cases of newly diagnosed ALL, of which 86 (14.4%) had modal chromosome numbers of 47 to 50. In this group, the most frequently acquired numerical abnormalities were +21 (n = 34), +X (18), +8 (8), and +10 (7). The chromosomal regions most often affected by structural abnormalities were 1q (n = 13), 6q (12), 12p (18), and 19p (9). Analysis of event-free survival (EFS) for Studies X and XI among patients with hyperdiploid (47 to 50) ALL showed no significant differences in outcome according to the presence (n = 36) or absence (n = 35) of chromosomal translocations (P = .81) or the gain of specific chromosomes (P = .40). Patients with hyperdiploid (47 to 50) ALL treated in a contemporary program of multiagent chemotherapy had a significantly better outcome than did those in an earlier study using less intensive therapy (4-year EFS = 75% [95% confidence interval, 55% to 86%] v 41% [22% to 59%]; P = .006 by the logrank test). Our findings indicate that the adverse prognosis previously attributed to hyperdiploidy 47 to 50 improves significantly with more effective chemotherapy.
Expanded GAA repeats impair FXN gene expression and reposition the FXN locus to the nuclear lamina in single cells (2015)

Abnormally expanded DNA repeats are associated with several neurodegenerative diseases. In Friedreich's ataxia (FRDA), expanded GAA repeats in intron 1 of the frataxin gene (FXN) reduce FXN mRNA levels in averaged cell samples through a poorly understood mechanism. By visualizing FXN expression and nuclear localization in single cells, we show that GAA-expanded repeats decrease the number of FXN mRNA molecules, slow transcription, and increase FXN localization at the nuclear lamina (NL). Restoring histone acetylation reverses NL positioning. Expanded GAA-FXN loci in FRDA patient cells show increased NL localization with increased silencing of alleles and reduced transcription from alleles positioned peripherally. We also demonstrate inefficiencies in transcription initiation and elongation from the expanded GAA-FXN locus at single-cell resolution. We suggest that repressive epigenetic modifications at the expanded GAA-FXN locus may lead to NL relocation, where further repression may occur.
Screening for Defined Cystic Fibrosis Mutations by Solid-Phase Minisequencing (1992)

We have developed a rapid method for the quantitative detection of point mutations and deletions. In this minisequencing method, enzymatically amplified DNA, 5'-biotinylated in one strand, is bound to a solid phase and denatured. A detection primer, constructed to end immediately before the mutation, is annealed to the immobilized single-stranded template and elongated with a single, labeled deoxynucleoside residue. We have applied the solid-phase minisequencing method to the detection of the major mutation, delta F508, causing cystic fibrosis (CF). In the presence of the allele with the delta F508 mutation, [3H]dTTP is incorporated; with the nonmutated allele, [3H]dCTP is incorporated. Thus, samples from heterozygous individuals allow the incorporation of both labels. The method was evaluated by analyzing 59 coded DNA specimens collected from 20 Finnish CF patients and their parents. The ratio of [3H]C to [3H]T gave unambiguously the allele combination. The solid-phase minisequencing method was also applicable to the analysis of three CF mutations simultaneously, i.e., delta F508, G542X, and G551D. We conclude that the microtiter-plate-based minisequencing test is an accurate method for the screening of defined sequence alterations in the CF gene.
Quantitative effects of antihydrophobic agents on binding constants and solubilities in water. (1992)

The effects of urea and of guanidinium chloride on binding constants in water for 6-(4-tert-butylanilino)-naphthalene-2-sulfonate and of bis(p-tert-butylphenyl) phosphate binding to beta-cyclodextrin and to N,N'-bis(6-beta-cyclo-dextrinyl)imidazolium ion have been determined. Their effects on the water solubility of p-tert-butylbenzyl alcohol and p-methylbenzyl alcohol have also been examined. Quantitative correlations show that the effects of these additives, which diminish hydrophobic effects, are similar for release of a tert-butylphenyl group from a cyclodextrin cavity into water or for solubilizing such a group from a second phase. The effects of these agents on the binding constants for double-ended substrates binding to the bis(cyclodextrin) host are much larger than for a simple substrate binding to monomeric cyclodextrin, consistent with additivity of free-energy perturbations. Ethanol also decreases binding in these systems, and increases solubilities, but the quantitative correlations are less straightforward.
Structure-Activity Relationship of a New Class of Anti-Hepatitis B Virus Agents (2002)

N-Nonyl-deoxy-galactonojirimycin (N-nonyl-DGJ) has been shown to reduce the amount of hepatitis B virus (HBV) produced by tissue cultures under conditions where cell viability is not affected. We show here that the compound N-nonyl-DGJ was effective against lamivudine-resistant HBV mutants bearing the YMDD motif in the polymerase gene, consistent with the compound's activity being distinct from those of nucleoside inhibitors. To better understand the chemical structures that influence its antiviral activity, a series of imino sugar derivatives were made and tested for their antiviral activity against HBV. This work suggests that the antiviral activity of the alkovirs requires an alkyl chain length of at least eight carbons but that the galactose-based head group can be modified with little or no loss in activity.
Characterization of conserved human immunodeficiency virus type 1 gp120 neutralization epitopes exposed upon gp120-CD4 binding (1993)

Interaction with the CD4 receptor enhances the exposure on the human immunodeficiency type 1 gp120 exterior envelope glycoprotein of conserved, conformation-dependent epitopes recognized by the 17b and 48d neutralizing monoclonal antibodies. The 17b and 48d antibodies compete with anti-CD4 binding antibodies such as 15e or 21h, which recognize discontinuous gp120 sequences near the CD4 binding region. To characterize the 17b and 48d epitopes, a panel of human immunodeficiency virus type 1 gp120 mutants was tested for recognition by these antibodies in the absence or presence of soluble CD4. Single amino acid changes in five discontinuous, conserved, and generally hydrophobic regions of the gp120 glycoprotein resulted in decreased recognition and neutralization by the 17b and 48d antibodies. Some of these regions overlap those previously shown to be important for binding of the 15e and 21h antibodies or for CD4 binding. These results suggest that discontinuous, conserved epitopes proximal to the binding sites for both CD4 and anti-CD4 binding antibodies become better exposed upon CD4 binding and can serve as targets for neutralizing antibodies.
Aborigines, sharks and Australian accents on Australian writing (2011)

At last year's Adelaide Writers Festival, during a session on The Macquarie Anthology of Australian Literature, an impassioned argument broke out on the subject of Australian writing. Robert Dessaix declared that, in our current age of globalisation, where national identities and national cultures are harder to define, there is no longer any such thing as Australian writing. 'Do any of us write as Australian writers?' he asked his fellow panellists Chloe Hooper, Michelle de Kretser and Malcolm Knox. 'I know I don't. I write as moi. I don't write about Aborigines and sharks.'...
Chain conformation in two-dimensional dense state (2004)

In an effort to provide evidence concerning the conformation of many chains in strict two-dimensional (2D) dense state, we synthesized polymer chains of diameter of nanometers through an anionic polymerization process. The conformational characteristics of the long chain molecules in films of thickness h corresponding to the chain diameter a were directly obtained from atomic force microscopy observations. In 2D dispersed state, the conformations of the long chain molecules were typical Gaussian. However, in 2D dense state the long chain molecules were strongly interpenetrated. Their conformations were largely perturbed by the presence of neighbor chains and were not Gaussian. This result was in contradiction with the segregated globule model predicted by de Gennes. The central reason is that 2D space cannot be filled to normal density with 2D Gaussian globules; either the area must be greatly increased with consequently large voids, or the globule conformation must be expanded by allowing chains to interpenetrate each other.
Homocysteine, vitamin B 6 , and vascular disease in AD patients (2002)

Elevated plasma homocysteine in patients with AD appears related to vascular disease and not AD pathology. In addition, low vitamin B(6) status is prevalent in patients with AD. It remains to be determined if elevated plasma homocysteine or low vitamin B(6) status directly influences AD pathogenesis or progression.
Universal characteristics of chemical synthesis and property optimization (2011)

A common goal in chemistry is to optimize a synthesis yield or the properties of a synthesis product by searching over a suitable set of variables (e.g., reagents, solvents, reaction temperature, etc.). Synthesis and property optimizations are regularly performed, yet simple reasoning implies that meeting these goals should be exceedingly difficult due to the large numbers of possible variable combinations that may be tested. This paper resolves this conundrum by showing that the explanation lies in the inherent attractive topology of the fitness landscape specifying the synthesis yield or property value as a function of the variables. Under simple physical assumptions, the landscape is shown to contain no suboptimal local extrema that could act as traps on the way to the optimal outcome. The literature contains broad evidence supporting this “OptiChem” theory. OptiChem theory implies that increasing the number of variables employed should result in more efficient and effective optimization, contrary to intuition.
DMA repair mechanisms associated with cellular resistance to antitumor drugs (1998)

The 1990s have already heralded an enormous expansion of our knowledge of DNA repair. Gene by gene, protein by protein, each partner in the molecular processes of DNA repair is being identified and characterized, not only in bacteria and yeast, but also in mammalian cellular systems. Several distinctive mechanisms are now explained at a molecular level, even if certain specific parts still remain to be elucidated fully. The techniques used to study DNA repair have also profited from this progress with a plethora of novel in vitro assays, specific antibodies, together with DNA or RNA probes becoming available. The increased use of these tools has permitted a multiplicity of studies on DNA repair which are now not exclusively mechanistically based. Thus, certain studies have now implicated DNA repair processes as likely to be involved in the multifactorial phenomenon of drug resistance to anticancer drugs. Under these circumstances, DNA repair mechanisms should provide useful pharmacological targets to attack with novel inhibitors, with the aim of reducing and/or sensitizing tumor cells to anticancer drugs which damage DNA. Our increased knowledge of the molecular mechanisms associated with DNA repair permits us now to consider such new pharmacological targeting. In this article, we review the present status of these DNA-repair-related pharmacological studies, and discuss both the likely and possible approaches which might have potential therapeutic applications.
Tumor microenvironment as a target of malignant gliomas treatment (2015)

Microglial cells in malignant gliomas closely interact with tumor cells. Microenvironment provides local immunosuppression, which promotes escape of tumors from immune system control. Numerous cytokines secreted by microenvironment support survival, nutrition, growth, proliferation and invasion of tumor cells. Microenvironment-targeted therapy is no less important than the traditional cytostatic therapy. Seem promising therapies aimed at reducing the recruitment of immune cells and their amounts in the tumor tissue, at neutralizationof the immunosuppressive properties of microglia and / or inversion of its suppressive phenotype, as well as disinhibition and stimulation of antineoplastic functions of microenvironment.
Relationship between Ballistocardiographic Forces and Certain Events in the Cardiac Cycle (1952)

The temporal relationships of the various waves of the ballistocardiogram have been studied by means of simultaneously recorded electrocardiograms, femoral pulses, and electrokymograms of the great vessels and heart chambers. A modification of the Dock type of electromagnetic, undamped, direct ballistocardiograph has been employed in this study of 23 normal individuals. The total duration of mechanical systole in the great vessels has been found to correspond closely to the H-L interval. The HIJKL complex of the ballistocardiogram appears to be entirely related to the events of ventricular systole. The M, N and O waves represent after-waves occurring during diastole.
Laboratory Diagnostic Systems for Ebola and Marburg Hemorrhagic Fevers Developed with Recombinant Proteins (2006)

Ebola virus and Marburg virus (EBOV and MARV, respectively) of the family Filoviridae cause hemorrhagic fever with high mortality rates, sometimes reaching 50 to 90% of infected individuals, in humans and nonhuman primates (10,16,47).EBOV consists of four species, Zaire EBOV, Sudan EBOV, Ivory Coast EBOV, and Reston EBOV, which were first isolated in the Democratic Republic of Congo, Sudan, Ivory Coast, and the Philippines, respectively (47).MARV consists of one species, Lake Victoria MARV.Public health concerns about filovirus infection have increased in recent years.First, there have recently been large outbreaks of hemorrhagic fevers caused by EBOV (Ebola hemorrhagic fever [EHF]) and MARV (Marburg hemorrhagic fever [MHF]) in Africa; EHF outbreaks occurred in the Democratic Republic of Congo and Uganda in 1995 and 2000, respectively, and MHF outbreaks occurred in the Democratic Republic of Congo in 1998 -1999 and in Angola in 2004 -2005 (1, 7, 27, 56, 58-60) (1, 7, 27, 56, 58-60).Second, there is a possibility that filoviruses may be used as bioweapons.In this regard, filoviruses are classified as category A warfare agents by the U.S. government and are considered to pose a great risk to international security, along with anthrax, botulism, tularemia, and smallpox (2).As the magnitude of international trade and travel is continuously increasing, there is a significant risk that the hemorrhagic fever viruses could be introduced to virus-free countries from areas where they are endemic.Therefore, the development of laboratory diagnostic systems for EHF and MHF is an important subject even in countries without viral hemorrhagic fevers.Manipulation of infectious hemorrhagic fever viruses such as EBOV, MARV, Crimean-Congo hemorrhagic fever virus, and Lassa virus requires a biosafety level 4 (BSL-4) laboratory, which is designed for work with dangerous and exotic agents that pose a high risk of laboratory infection and life-threatening disease.However, BSL-4 laboratories are only available in a limited group of countries, such as the United States, Canada, France, the United Kingdom, Germany, South Africa, Sweden, and Russia.To get around the need for BSL-4 laboratories, recombinant viral antigens are used for immunodiagnostics.The recombi-nant proteins of these viruses have been expressed, and serological diagnostic methods have been developed using the recombinant proteins.Antigen detection systems have also been developed using recombinant antigens.In this article, recent progress in the development of diagnostic methods for EHF and MHF is reviewed.
p32 Protein, a Splicing Factor 2-associated Protein, Is Localized in Mitochondrial Matrix and Is Functionally Important in Maintaining Oxidative Phosphorylation (1997)

Human p32, originally cloned as a splicing factor 2-associated protein, has been reported to interact with a variety of molecules including human immunodeficiency virus Tat and complement 1q (C1q). p32 protein is supposed to be in the nucleus and on the plasma membrane for the association with human immunodeficiency virus Tat and C1q, respectively. None of the interactions, however, is proven to have a physiological role. To investigate the physiological function of p32, we determined the intracellular localization of p32. The fractionation of cells, fluorescent immunocytochemistry, and electron microscopic immunostaining show that p32 is exclusively localized in the mitochondrial matrix. We cloned a Saccharomyces cerevisiae homologue of human p32 gene, referred to yeast p30 gene. The yeast p30 protein is also localized in the mitochondrial matrix. The disruption of the p30 gene caused the growth retardation of yeast cells in a glycerol medium but not in a glucose medium, i.e. the impairment of the mitochondrial ATP synthesis. The growth impairment was restored by the introduction of the human p32 cDNA, indicating that p30 is a functional yeast counterpart of human p32. Taken together, both p32 and p30 reside in mitochondrial matrix and play an important role in maintaining mitochondrial oxidative phosphorylation.
Protection by iron salts against sporidesmin intoxication in sheep (1989)

A number of iron compounds have been shown to protect sheep against the harmful effects of the facial eczema toxin, sporidesmin. Various salts were found to be effective; the oxidation state of the metal was not important although water-solubility did appear to be a prerequisite for prophylactic activity. The effect of iron salts was additive with that of zinc, and it is suggested that the protective action of these compounds results from their ability to inhibit the absorption of copper, consistent with the previously-proposed free-radical mechanism for sporidesmin toxicity.
Alignable liftoff transfer of device arrays via a single polymeric carrier membrane (1993)

The Letter reports epitaxial liftoff and direct bonding of GaAs/AlxGa1−xAs heterostructure device arrays and continuous films, using a single transparent polymer membrane to support the material during etch of the sacrificial layer and to manipulate it into position for bonding. Au–Sn eutectic alloy bonding leads to a metallurgical bond in minutes. Photoluminescence and current–voltage characteristics show that material quality is not substantially degraded in the transfer process.