gebhart/patrepeval huggingface dataset:
High-temperature protein G is essential for activity of the Escherichia coli clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system (2011)

Prokaryotic DNA arrays arranged as clustered regularly interspaced short palindromic repeats (CRISPR), along with their associated proteins, provide prokaryotes with adaptive immunity by RNA-mediated targeting of alien DNA or RNA matching the sequences between the repeats. Here, we present a thorough screening system for the identification of bacterial proteins participating in immunity conferred by the Escherichia coli CRISPR system. We describe the identification of one such protein, high-temperature protein G (HtpG), a homolog of the eukaryotic chaperone heat-shock protein 90. We demonstrate that in the absence of htpG, the E. coli CRISPR system loses its suicidal activity against λ prophage and its ability to provide immunity from lysogenization. Transcomplementation of htpG restores CRISPR activity. We further show that inactivity of the CRISPR system attributable to htpG deficiency can be suppressed by expression of Cas3, a protein that is essential for its activity. Accordingly, we also find that the steady-state level of overexpressed Cas3 is significantly enhanced following HtpG expression. We conclude that HtpG is a newly identified positive modulator of the CRISPR system that is essential for maintaining functional levels of Cas3.
Simultaneous analysis of monoterpenes and diterpenoids of conifer oleoresin (1993)

Abstract A simple and rapid procedure for the simultaneous determination of monoterpenes and diterpenoid resin acids of conifer stem oleoresin is described; it involves tissue extraction with methyl tert ‐butyl ether and methylation of the resin acids with CH 2 N 2 . The resin acid methyl esters and the monoterpenes are then analysed in a single gas chromatographic step. Enantiomer composition of the major monoterpene constituents is determined, after preliminary purification by thin layer chromatography, by capillary gas chromatography on a cyclodextrin column. The method is applicable to conifer species of high resin content (Iodgepole pine) and low resin content (grand fir).
Uptake of Protoporphyrin and Violet Light Photodestruction of Propionibacterium acnes (1987)

The uptake of protoporphyrin IX by Propionibacterium acnes in suspension has been studied by fluorescence spectroscopy. Protoporphyrin, after it was injected into a cell suspension, was firstly bound to receptors on the cell surface and in this state protoporphyrin was non-fluorescent. Subsequently, probably as a result of lateral diffusion in the cell wall, these protoporphyrin-receptor complexes formed dimers. The final step in the overall uptake process of protoporphyrin by the cells from the surroundings consisted in a jump of such dimers from waterlike to lipidlike compartments in the cell membrane where protoporphyrin became fluorescent. The lipidlike compartments in the cells had a limited binding capacity of protoporphyrin. The fraction of surviving cells versus light dose has also been studied for varying amounts of protoporphyrin added to the cell suspensions. The survival curves were exponentially decaying with the irradiation time and there was a direct proportionality between the inverse slope of the survival curves and the intensity of protoporphyrin fluorescence form the lipidlike compartments. The relevance of these results to the therapy of Acne vulgaris is also discussed.
Quantitative SLM-based differential interference contrast imaging (2010)

We describe the implementation of quantitative Differential Interference Contrast (DIC) Microscopy using a spatial light modulator (SLM) as a flexible Fourier filter in the optical path. The experimental arrangement allows for the all-electronic acquisition of multiple phase shifted DIC-images at video rates which are analyzed to yield the optical path length variation of the sample. The resolution of the technique is analyzed by retrieving the phase profiles of polystyrene spheres in immersion oil, and the method is then applied for quantitative imaging of biological samples. By reprogramming the diffractive structure displayed at the SLM it is possible to record the whole set of phase shifted DIC images simultaneously in different areas of the same camera chip. This allows for quantitative snap-shot imaging of a sample, which has applications for the investigation of dynamic processes.
Pharos neurovascular intracranial stent: Elective use for a symptomatic stenosis refractory to medical therapy (2009)

The Warfarin-Aspirin Symptomatic Intracranial Disease study investigators demonstrated that medically managed patients with symptomatic intracranial stenosis experience a 7-11% annual stroke risk. Early treatment efforts utilized balloon-mounted coronary stents, which provided excellent angiographic results (postprocedure stenoses <10%), versus percutaneous transluminal angioplasty (PTA) alone (40%). However, the rigidity of balloon-mounted coronary stents provided limited access to the tortuous cerebrovasculature. Self-expanding stents became available for intracranial stenosis treatment in 2002. With increased flexibility, immediate results were encouraging (approximately 30% residual stenosis). However, midterm results have demonstrated disappointingly high rates of restenosis. To address these issues, the Pharos Neurovascular Stent System (Pharos, Micrus Endovascular, San Jose, CA) was developed. The Pharos is a balloon-expandable stent mounted on a rapid-exchange PTA catheter especially designed for intracranial endovascular applications. Utilizing the Pharos, we obtained an outstanding angiographic result (0% residual stenosis), with no associated morbidity. The patient was discharged home on postprocedure day 1 and remained symptom-free, with no in-stent stenosis, 3 months later. Our experience with the Pharos supports early literature suggesting that this stent may be a valuable treatment option for patients with medically refractory intracranial stenosis.
Design, implementation, and evaluation of a Revision Control System (1982)

The Revision Control System (RCS) is a software tool that helps in managing multiple revisions of text. RCS automates the storing, retrieval, logging, identification, and merging of revisions, and provides access control. It is useful for text that is revised frequently, for example programs and documentation.This paper presents the design and implementation of RCS. Both design and implementation are evaluated by contrasting RCS with SCCS, a similar system. SCCS is implemented with forward, merged deltas, while RCS uses reverse, separate deltas. (Deltas are the differences between successive revisions.) It is shown that the latter technique improves run-time efficiency, while requiring almost no extra space.
Ribozyme suppression of endogenous thyroid hormone receptor activity in Xenopus laevis cells (2002)

Xenopus laevis is an excellent model for thyroid hormone (T3)-regulated gene expression. T3 initiates two drastically different pathways during metamorphosis: death of larval tissues and growth of adult tissues. The role that each T3 receptor (TR) isotype, alpha and beta, plays in metamorphosis is uncertain. The X.laevis tetraploid genome limits experiments to overexpression, misexpression and dominant negative studies. Ribozymes offer an alternative by suppressing gene activity through specific mRNA reduction. It has been suggested that ribozymes will not work in X.laevis because of the organism's intracellular environment and body temperature. In this study, we show that hammerhead ribozymes are active in vitro against transcribed TRbeta message and in vivo against a TRbeta-luciferase fusion protein. We next show that TRbeta-targeted ribozymes can inhibit T3-induced transcription of a reporter gene in cultured X.laevis cells, using T3 response elements from two T3-responsive transcription factor genes. One has early expression kinetics in response to T3 and is proposed to be TRalpha regulated whereas the other has intermediate induction kinetics and thus may be partially TRbeta regulated. Therefore, ribozymes are a potentially valuable tool for overcoming the limitations in this system for examining gene function in X.laevis.
Relationship between melanin content and superoxide dismutase (SOD) activity in the liver of various species of animals (1987)

The scavenger effect of melanin and of superoxide dismutase (SOD) activity on superoxide anion has been shown. In this work we show the relationship between melanin content and SOD activity in livers containing different quantities of melanin which were taken from various species of animals. The mitochondrial SOD activity disappears when the melanin content in the liver is very high; moreover it increases, in the liver of various species of animals examined, proportionally to the decrease of melanin content. No significant variation of the SOD activity localized in the soluble fraction has been detected when related to the melanin content. We think that in the pigmented liver the antioxidant activity of the melanin could mimic part of the function of SOD. The loss of Mn SOD activity could be mediated by a low intracellular level of superoxide anion due to the scavenger effect of melanin on superoxide anion; in fact, it is well known that the biosynthesis of Mn SOD is induced by intracellular levels of superoxide anion.
Ceramide Inhibits Inwardly Rectifying K+Currents via a Ras- and Raf-1-Dependent Pathway in Cultured Oligodendrocytes (1998)

Ceramide is a lipid mediator implicated in apoptosis induced by proinflammatory cytokines in many cell types, including oligodendrocytes (OLGs). To determine whether ceramide modulates transmembrane signaling events in OLGs, we studied its effect on intracellular Ca2+ (Cai), resting membrane potential and inwardly rectifying K+ currents (IKir) in cultured neonatal rat OLGs. We report here that (1) exposure to C2-ceramide (cer) rarely increases OLG Cai, whereas sphingosine elicits sustained increase in Cai; (2) cer causes OLG depolarization, an effect mimicked by sphingosine-1-phosphate but not by sphingosine; and (3) cer, but not its inactive analog dihydroceramide, inhibits OLG IKir. The cer effect is attenuated by Ras antibody Y13-259, by protein kinase C inhibitory peptide (19-36), and by suppression of c-Raf-1 expression with antisense raf-1 oligonucleotides. We conclude that cer-induced OLG depolarization is mediated via inhibition of IKir by a Ras- and raf-1-dependent pathway, which results in the phosphorylation of the inward rectifier K+ channel protein.
A chimeric mouse-human antibody that retains specificity for HIV gp120 and mediates the lysis of HIV-infected cells. (1989)

Murine mAb BAT123, which was made against the envelope glycoprotein gp120 of HTLV-IIIB strain of HIV type 1 (HIV-1), is capable of neutralizing HTLV-IIIB in vitro. It also inhibits the fusion between uninfected CD4+ cells and HIV-1-infected cells to form syncytia. As a step to explore the potential utility of the anti-HIV antibody in vivo, we have constructed a mouse-human chimeric antibody by rDNA techniques. The chimeric antibody, which bears the variable domains of mouse antibody BAT123 and constant domains Cr1 and C kappa of human Ig retains the Ag specificity of BAT123 as determined by its reactivity with HIV-1-infected H9 cells, gp120 in Western blot analysis, and the oligopeptide recognized by BAT123. The antiviral activities of the chimeric antibody in neutralizing HIV-1 infection as well as inhibiting the syncytia formation are also found identical to those of the parent murine antibody. Moreover, in the presence of human blood mononuclear cells, the chimeric antibody but not BAT123 (mouse IgG1) induces antibody-dependent cellular cytotoxicity. The findings point to the potential usefulness of the chimeric antibody in treating patients infected with HIV-1.
Frequent expression of IL-7 gene transcripts in tumor cells of classical Hodgkin's disease. (1995)

Interleukin-7 (IL-7) is a pleiotropic cytokine acting mainly on cells of the hematolymphoid system. In vitro studies have shown enhanced proliferation of acute lymphoblastic leukemia cells in response to IL-7. On the other hand, tumor cell lines transfected with a functioning IL-7 gene and subsequently transplanted into mice resulted in a prominent inflammatory infiltrate and reduced tumorigeneicity. These data suggest an important role of this cytokine in the pathophysiology of lymphoid neoplasms. Because little is known about the in vivo expression of this cytokine in various neoplastic and nonneoplastic lesions of the lymphoid system, we examined frozen and paraffin-embedded tissue samples of normal, reactive, and malignant lymphoid lesions using in situ hybridization with a 35S-labeled RNA probe specific for IL-7. Tumor cells of nodular sclerosing and mixed cellularity type of Hodgkin's disease displayed IL-7-specific signals in 24 of 31 cases. Among reactive lesions, only thymic tissue showed labeling within both cortex and medulla (4 of 7 cases), whereas in tonsils clear-cut IL-7-specific signals could not be found. Tissues infiltrated by B-type chronic lymphocytic leukemia or T- or B-type lymphoblastic lymphoma showed cytokine-specific signals in only one case of lymphoblastic lymphoma in rare reactive cells. In conjunction with the finding of elevated levels of IL-7 in the serum of many patients with Hodgkin's disease, our data suggest an important role of this cytokine in the pathogenesis of Hodgkin's disease. The prominent reactive infiltrate observed in most cases of Hodgkin's disease could be a consequence of elevated local levels of this cytokine as similar infiltrates are also observed in tumors in mice resulting from injection of tumor cell lines transfected with a functioning IL-7 gene.
The Yfe system of Yersinia pestis transports iron and manganese and is required for full virulence of plague (1999)

Iron acquisition in Yersinia pestis is fundamental to the success of plague pathogenesis. We have previously identified an approximately 5.6 kb region (yfe) of Y. pestis genomic DNA, capable of restoring iron-deficient growth but not siderophore production to an Escherichia coli mutant (SAB11) incapable of synthesizing the siderophore, enterobactin. The yfe locus of Y. pestis, found in both pigmented (Pgm+) and nonpigmented (Pgm-) strains, comprises five genes arranged in two distinct operons (yfeA-D and yfeE ). The larger of these, yfeABCD, encodes an ABC transport system, whose expression is iron and Fur regulated and is repressed in cells grown in the presence of manganese. Cells from a Pgm-, Yfe- (DeltayfeAB ) mutant strain of Y. pestis exhibited reduced transport of both 55Fe and 54Mn. Furthermore, cells containing an intact yfe locus showed reduced 55Fe uptake when competing amounts of MnCl2 or ZnCl2 were present, whereas 54Mn uptake was inhibited by FeCl3 but not by ZnCl2. Similarly, yfe mutants of Y. pestis exhibited growth defects on media supplemented with the iron chelators 2,2'-dipyridyl or conalbumin. These growth defects were not relieved by supplementation with MnCl2. A ybt-, DeltayfeAB mutant of Y. pestis was completely avirulent in mice infected intravenously (LD50 > 1.7 x 107 cfu) compared with its parental ybt-, yfe+ strain, which had an LD50 of < 12. In addition, compared with its ybt+, yfe+ parent, a ybt+, DeltayfeAB mutant of Y. pestis had an approximately 100-fold increase in the LD50 from a subcutaneous route of infection. These data suggest that the Yfe and Ybt systems may function effectively to accumulate iron during different stages of the infectious process of bubonic plague.
Lactation and a Reduced Risk of Premenopausal Breast Cancer (1994)

There is a reduction in the risk of breast cancer among premenopausal women who have lactated. No reduction in the risk of breast cancer occurred among postmenopausal women with a history of lactation.
An improved method for the synthesis of stabilized primary enamines and imines (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAn improved method for the synthesis of stabilized primary enamines and iminesJames A. Kloek and Kindrick L. LeschinskyCite this: J. Org. Chem. 1978, 43, 7, 1460–1462Publication Date (Print):March 1, 1978Publication History Published online1 May 2002Published inissue 1 March 1978https://pubs.acs.org/doi/10.1021/jo00401a037https://doi.org/10.1021/jo00401a037research-articleACS PublicationsRequest reuse permissionsArticle Views292Altmetric-Citations32LEARN 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
Global Reactivation of Epigenetically Silenced Genes in Prostate Cancer (2010)

Transcriptional silencing associated with aberrant promoter hypermethylation is a common mechanism of inactivation of tumor suppressor genes in cancer cells. To globally profile the genes silenced by hypermethylation in prostate cancer, we screened a whole genome expression microarray for genes reactivated in the LNCaP, DU-145, PC-3, and MDA2b prostate tumor cell lines after treatment with the demethylating drug 5-aza-2-deoxycytidine and the histone deacetylation-inhibiting drug trichostatin A. A total of 2,997 genes showed at least 2-fold upregulation of expression after drug treatment in at least one prostate tumor cell line. For validation, we examined the first 45 genes, ranked by upregulation of expression, which had a typical CpG island and were known to be expressed in the normal cell counterpart. Two important findings were, first, that several genes known to be frequently hypermethylated in prostate cancer were apparent, and, second, that validation studies revealed eight novel genes hypermethylated in the prostate tumor cell lines, four of which were unmethylated in normal prostate cells and hypermethylated in primary prostate tumors (SLC15A3, 66%; KRT7, 54%; TACSTD2, 17%; GADD45b, 3%). Thus, we established the utility of our screen for genes hypermethylated in prostate cancer cells. One of the novel genes was TACSTD2/TROP2, a marker of human prostate basal cells with stem cell characteristics. TACSTD2 was unmethylated in prostatic intraepithelial neoplasia and may have utility in emerging methylation-based prostate cancer tests. Further study of the hypermethylome will provide insight into the biology of the disease and facilitate translational studies in prostate cancer.
N‐Heterocyclic Carbene‐Mediated Enantioselective Addition of Phenols to Unsymmetrical Alkylarylketenes (2009)

Abstract Chiral N‐heterocyclic carbenes (NHCs) mediate the enantioselective addition of 2‐phenylphenol to unsymmetrical alkylarylketenes, delivering α‐alkyl‐α‐arylacetic acid derivatives with good levels of enantiocontrol (up to 84% ee ). Enantiodivergent stereochemical outcomes are observed using 2‐phenylphenol and benzhydrol in the NHC‐promoted esterification reaction using a triazolium precatalyst derived from pyroglutamic acid, consistent with distinct mechanistic pathways operating within these processes.
Overcoming mutation-based resistance to antiandrogens with rational drug design (2013)

The second-generation antiandrogen enzalutamide was recently approved for patients with castration-resistant prostate cancer. Despite its success, the duration of response is often limited. For previous antiandrogens, one mechanism of resistance is mutation of the androgen receptor (AR). To prospectively identify AR mutations that might confer resistance to enzalutamide, we performed a reporter-based mutagenesis screen and identified a novel mutation, F876L, which converted enzalutamide into an AR agonist. Ectopic expression of AR F876L rescued the growth inhibition of enzalutamide treatment. Molecular dynamics simulations performed on antiandrogen-AR complexes suggested a mechanism by which the F876L substitution alleviates antagonism through repositioning of the coactivator recruiting helix 12. This model then provided the rationale for a focused chemical screen which, based on existing antiandrogen scaffolds, identified three novel compounds that effectively antagonized AR F876L (and AR WT) to suppress the growth of prostate cancer cells resistant to enzalutamide. DOI:http://dx.doi.org/10.7554/eLife.00499.001.
NN-align. An artificial neural network-based alignment algorithm for MHC class II peptide binding prediction (2009)

The NN-align method is competitive with the state-of-the-art MHC class II peptide binding prediction algorithms. The method is publicly available at http://www.cbs.dtu.dk/services/NetMHCII-2.0.
Formation of Integral Asymmetric Membranes of AB Diblock and ABC Triblock Copolymers by Phase Inversion (2013)

The formation of integral asymmetric membranes from ABC triblock terpolymers by non-solvent-induced phase separation is shown. They are compared with the AB diblock copolymer precursors. Triblock terpolymers of polystyrene-block-poly(2-vinylpyridine)-block-poly(ethylene oxide) (PS-b-P2VP-b-PEO) with two compositions are investigated. The third block supports the formation of a membrane in a case, where the corresponding diblock copolymer does not form a good membrane. In addition, the hydrophilicity is increased by the third block and due to the hydroxyl group the possibility of post-functionalization is given. The morphologies are imaged by scanning electron microscopy. The influence of the PEO on the membrane properties is analyzed by water flux, retention, and dynamic contact angle measurements.
Zernike polynomials and aberration balancing (2003)

For small aberrations, the Strehl ratio of an imaging system depends on the aberration variance. If the aberration function is expanded in terms of a complete set of polynomials that are orthogonal over the system aperture, then the variance is given by the sum of the square of the aberration coefficients. One such set is that of Zernike polynomials, which are orthogonal over a circular pupil. Its advantage lies in the fact that Zernike polynomials can be identified with the classical aberrations that are balanced to yield minimum variance, and thus a maximum Strehl ratio. We discuss classical aberrations, balanced aberrations, and Zernike polynomials for systems with circular pupils. How these polynomials change for an annular or a Gaussian pupil are also discussed.