gebhart/patrepeval huggingface dataset:
Teichomycins, new antibiotics from Actinoplanes teichomyceticus nov. sp. II. Extraction and chemical characterization. (1978)

The teichomycins are new antibiotics produced by Actinoplanes teichomyceticus nov. sp.Teichomycin A1 is a phosphorus-containing antibiotic, active in vitro and in vivo against gram-positive bacteria, and active only in vitro against gram-negative bacteria. Teichomycin A2 is a chlorine-containing antibiotic, active in vitro and in vivo against gram-positive bacteria. Isolation, purification and physical and chemical properties of the two antibiotics are reported. Teichomycin A1 is a member of the phosphoglycolipid class of antibiotics while teichomycin A2 is related to the group of the glycopeptide antibiotics.
GLFG and FxFG Nucleoporins Bind to Overlapping Sites on Importin-β (2002)

The interaction between nuclear pore proteins (nucleoporins) and transport factors is crucial for the translocation of macromolecules through nuclear pores. Many nucleoporins contain FG sequence repeats, and previous studies have demonstrated interactions between repeats containing FxFG or GLFG cores and transport factors. The crystal structure of residues 1-442 of importin-beta bound to a GLFG peptide indicates that this repeat core binds to the same primary site as FxFG cores. Importin-beta-I178D shows reduced binding to both FxFG and GLFG repeats, consistent with both binding to an overlapping site in the hydrophobic groove between the A-helices of HEAT repeats 5 and 6. Moreover, FxFG repeats can displace importin-beta or its S. cerevisiae homologue, Kap95, bound to GLFG repeats. Addition of soluble GLFG repeats decreases the rate of nuclear protein import in digitonin-permeabilized HeLa cells, indicating that this interaction has a role in the translocation of carrier-cargo complexes through nuclear pores. The binding of GLFG and FxFG repeats to overlapping sites on importin-beta indicates that functional differences between different repeats probably arise from differences in their spatial organization.
Strange bedfellows: polyadenylation factors at the promoter (2003)

ne of the more unexpected discoveries in the field of gene expression during the last few years has been the degree to which transcription of mRNA precursors is coupled to their subsequent processing into mature mRNAs. Much of this linkage involves the transcribing enzyme itself, RNA polymerase II (RNAP II), and specifically the repetitive C-terminal domain of its largest subunit (known simply as the CTD). A large body of evidence now indicates that the CTD has a significant role in enhancing the efficiency of all three of the major processing reactions—capping, splicing, and polyadenylation (for review, see Hirose and Manley 2000; Bentley 2002; Maniatis and Reed 2002; Proudfoot et al. 2002). This was initially surprising—all three reactions were known to occur just fine in vitro in the absence of transcription, or for that matter RNAP II and the CTD—but in retrospect it makes sense as a way to ensure accurate, efficient, and rapid processing of nascent pre-mRNAs. Precisely how the CTD functions is not entirely understood, especially in the more complex splicing and polyadenylation reactions, but a number of interactions with specific processing factors have been documented and these likely serve to help recruit the processing machinery to the pre-mRNA and then to stabilize or enhance the activity of these complexes.
Class IMHC molecules: assembly and antigen presentation (1999)

Several years ago, the only factor known to be necessary for the assembly and surface expression of class I MHC was beta 2m; even for beta 2m, it was unclear at what point in class I maturation its role was played. Recent experiments that employed attachment of an endoplasmic reticulum (ER) retention signal to beta 2m have shown that the point of time at which beta 2m is required is while the class I heavy chain is in the ER. Later association between beta 2m and class I is not vital in order for properly folded class I to be expressed at the cell surface. After crystallization of the first class I MHC molecule, it was realized that not only is antigen presented by class I, but that antigen is presented in the form of a peptide that stabilizes the class I structure and allows its transit to the cell surface. Class I allelic differences influence interactions with both peptide and beta 2m, with likely consequences for the ability of the class I heavy chains to present antigen through alternative pathways. Furthermore, it is now also clear that formation of appropriate disulfide bonds in the class I heavy chain is needed before class I can bind peptide antigen securely, a process that may be assisted by an ER chaperone. Many different proteins that are resident in the ER, such as calnexin, transporter associated with antigen processing (TAP), calreticulin, and tapasin, have been found to be integral to class I assembly. TAP, tapasin, and calreticulin bind preferentially to the open form of class I, which can be distinguished with the use of a monoclonal antibody specific for this form. Calreticulin and calnexin contrast in their interactions with class I, despite other similarities between these two chaperones. Overall, class I MHC assembly is now understood to involve the interplay of multiple intra- and intermolecular events in a defined chronological order which ensure continual reporting of cellular contents to cytotoxic T lymphocytes.
GLUT-2 gene transfer into insulinoma cells confers both low and high affinity glucose-stimulated insulin release. Relationship to glucokinase activity (1994)

The rat insulinoma cell line RIN 1046-38 loses glucose-stimulated insulin secretion as a function of time in culture. We found that the loss of glucose sensing in these cells was correlated with the loss of expression of GLUT-2 and glucokinase. Stable transfection of RIN cells with a plasmid containing the GLUT-2 cDNA conferred glucose-stimulated insulin release in intermediate but not high passage cells, with the near-maximal 3-fold increase occurring at 50 microM glucose. GLUT-2 expressing cells also exhibited a larger response to the combination of 5 mM glucose + 1 microM forskolin than untransfected cells (7.9 versus 1.6-2.7-fold, respectively). GLUT-2 expressing intermediate passage, but not high passage, RIN cells exhibited a 4-fold increase in glucokinase enzymatic activity relative to nonexpressing controls. Glucokinase activity was also increased by transfer of the GLUT-2 gene into intermediate passage RIN cells via recombinant adenovirus. Preincubation of GLUT-2 expressing intermediate passage RIN cells with 2-deoxyglucose to inhibit low Km hexokinases resulted in a glucose-stimulated insulin secretion response that was shifted toward the physiologic range. These studies indicate that GLUT-2 expression confers both a high and low affinity glucose-stimulated insulin secretion response to intermediate passage RIN cells.
CD101, a long-acting echinocandin, and comparator antifungal agents tested against a global collection of invasive fungal isolates in the SENTRY 2015 Antifungal Surveillance Program (2017)

CD101 is a novel echinocandin with exceptional chemical stability and long-acting pharmacokinetics. The activity of CD101 and comparators was evaluated using CLSI broth microdilution methods against 713 invasive fungal isolates, including 589 Candida spp. (6 species), 14 C. neoformans, 97 A. fumigatus and 13 A. flavus species complex collected worldwide during 2015. All C. tropicalis, C. krusei and C. dubliniensis, 99.7% of C. albicans and 98.3% of C. glabrata were inhibited by ≤0.12 µg/mL of CD101, and these isolates were susceptible/wild type to other echinocandins using CLSI clinical breakpoint and epidemiological cutoff value (ECV) interpretive criteria. C. parapsilosis displayed higher MIC values (range 0.25-2 µg/mL), but similar results were observed for other echinocandins. One C. glabrata and one C. albicans with CD101 MIC value at 1 and 0.25 µg/mL possessed F625S and S645P alterations on FKS1, respectively. These isolates also displayed elevated MIC values for at least one clinically available echinocandin. Fluconazole resistance was noted for 6.6% of C. glabrata and 3.6% C. parapsilosis. Echinocandins had limited activity against C. neoformans. CD101 activity against A. fumigatus and A. flavus (MEC ≤0.03 µg/mL) was comparable to other echinocandins (MEC ≤0.03 µg/mL). These moulds had MIC values below ECVs for the mould-active azoles. CD101 was as active as other echinocandins against common fungal organisms recovered from invasive fungal infections. The extended half-life profile is very desirable as less frequent dosing of this agent should facilitate shorter and more cost-effective hospital stays, improve compliance for outpatients, and provide more convenient outpatient prophylaxis.
Catalytic Hydroaminoalkylation of Alkenes (2009)

Hydroaminoalkylation of alkenes, where the α-C–H bonds of N-alkylamines are added to alkenes, is one of the unique strategies for functionalization of both amines and alkenes. This review introduces the recent developments of the catalytic, intra- or inter-molecular hydroaminoalkylation, as well as the mechanistic studies on that.
Rapid Attenuation of AP-1 Transcriptional Factors Associated with Nitric Oxide (NO)-mediated Neuronal Cell Death (1996)

Stimulation of glutamate receptors causes several intracellular reactions including activation of activator protein-1 (AP-1) production and nitric oxide (NO) generation. Exposing mouse cerebellar granule cells to N-methyl-D-aspartate or kainate (KA) in culture induced an increase of AP-1 DNA binding activity that was blocked by further addition of sodium nitroprusside (SNP), a typical NO donor. Immunoblotting using anti-c-Fos antiserum revealed the specific attenuation of AP-1, although total protein synthesis was not affected. Since the level of c-fos mRNA expression stimulated by KA remained constant even after exposure to SNP, the AP-1 attenuation can be post-transcriptionally induced. SNP did not affect the Ca2+ influx into the cells stimulated by KA. The involvement of NO in the AP-1 attenuation was supported by the fact that potassium ferrocyanide (K4Fe(CN)6), an analogue of SNP but devoid of NO, failed to inhibit the AP-1 DNA binding activity stimulated by KA. SNP alone induced neuronal cell death, which was blocked by the simultaneous addition of antioxidants, superoxide dismutase and catalase, and an NO scavenger, suggesting a direct role of peroxynitrite in the cell death. In good agreement with these effects, the AP-1 attenuation by SNP was also blocked by antioxidants. These results indicated that post-transcriptional attenuation of AP-1 is involved in the early processes of NO-mediated neuronal cell death.
Context Encoders: Feature Learning by Inpainting (2016)

We present an unsupervised visual feature learning algorithm driven by context-based pixel prediction. By analogy with auto-encoders, we propose Context Encoders - a convolutional neural network trained to generate the contents of an arbitrary image region conditioned on its surroundings. In order to succeed at this task, context encoders need to both understand the content of the entire image, as well as produce a plausible hypothesis for the missing part(s). When training context encoders, we have experimented with both a standard pixel-wise reconstruction loss, as well as a reconstruction plus an adversarial loss. The latter produces much sharper results because it can better handle multiple modes in the output. We found that a context encoder learns a representation that captures not just appearance but also the semantics of visual structures. We quantitatively demonstrate the effectiveness of our learned features for CNN pre-training on classification, detection, and segmentation tasks. Furthermore, context encoders can be used for semantic inpainting tasks, either stand-alone or as initialization for non-parametric methods.
Design and functionality of colloidal-crystal-templated materials—chemical applications of inverse opals (2012)

Templating with colloidal crystals composed of monodisperse spheres is a convenient chemical method to obtain porous materials with well-ordered periodicity and interconnected pore systems. The three-dimensionally ordered macroporous (3DOM) products or inverse opals are of interest for numerous applications, both for the optical properties related to structural color of these photonic crystal materials and because of their bicontinuous nanostructure, i.e., a continuous nanostructured skeleton with large interfacial area and a three-dimensionally interconnected pore system with low tortuosity. This review outlines various synthetic methods used to control the morphology of 3DOM materials with different compositions. It highlights aspects of the choice of colloidal particles, assembly of the colloidal crystal template, infiltration and processing, template removal, and other necessary modifications to enhance the functionality of the materials. It also considers syntheses within the confinement of 3DOM materials and summarizes characterization methods that are particularly useful in the analysis of 3DOM materials. The review then discusses chemical applications of 3DOM materials, namely sorption and controlled release, optical and electrochemical sensors, solar cells, lithium ion batteries, supercapacitors, fuel cells, and environmental and chemical fuel catalysis. A focus is on structural features and materials properties that enable these applications.
A proposed new convention for graphic presentation of molecular geometry and topography (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA proposed new convention for graphic presentation of molecular geometry and topographyHubert Maehr Cite this: J. Chem. Educ. 1985, 62, 2, 114Publication Date (Print):February 1, 1985Publication History Received3 August 2009Published online1 February 1985Published inissue 1 February 1985https://doi.org/10.1021/ed062p114RIGHTS & PERMISSIONSArticle Views756Altmetric-Citations29LEARN 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 InReddit PDF (5 MB) Get e-Alertsclose Get e-Alerts
Interactions between Bortezomib and Romidepsin and Belinostat in Chronic Lymphocytic Leukemia Cells (2008)

Coadministration of the clinically relevant HDACIs romidepsin or belinostat with bortezomib synergistically induces cell death in CLL cells, likely through mechanisms involving, among other factors, NF-kappaB inactivation and perturbation in the expression of proapoptotic and antiapoptotic proteins. A strategy combining HDAC with proteasome inhibition warrants further attention in CLL.
γ-Tocotrienol-induced autophagy in malignant mammary cancer cells (2013)

γ-Tocotrienol, a member of the vitamin E family of compounds, displays potent antiproliferative and cytotoxic effects in a variety of cancer cell types at treatment doses that have little or no effect on normal cell viability or growth. Autophagy is a tightly regulated lysosomal self-digested process that can either promote cell survival or programmed cell death, but the role of autophagy in mediating γ-tocotrienol-induced cytotoxicity in breast cancer is not presently completely understood. Mouse (+SA) and human (MCF-7 and MDA-MD-231) mammary tumor cells lines were exposed to 0-40 µmol/L γ-tocotrienol for a 24 h treatment period. γ-Tocotrienol treatment caused a relatively large increase in the accumulation of monodansylcadaverine (MDC)-labeled vacuoles, a marker of autophagosome formation, in all tumor cell lines. Results also showed that γ-tocotrienol treatment induced an increased conversion of microtubule-associated protein, 1A/1B-light chain 3, from its cytosolic form (LC3B-I) to its lipidated form (LC3B-II), increased Beclin-1 levels, and increased acridine orange staining as determined by flow cytometry analysis, providing further evidence of γ-tocotrienol-induced autophagy in these mammary cancer cell lines. In contrast, similar treatment with γ-tocotrienol was not found to increase autophagy marker expression in immortalized mouse (CL-S1) and human (MCF-10 A) normal mammary epithelial cell lines. Treatment with γ-tocotrienol also caused a reduction in PI3K/Akt/mTOR signaling and a corresponding increase in the Bax/Bcl-2 ratio, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase (PARP) levels in these cancer cell lines, suggesting that γ-tocotrienol-induced autophagy may be involved in the initiation of apoptosis. In summary, these findings demonstrate that the cytotoxic effects of γ-tocotrienol are associated with the induction of autophagy in a mouse and human mammary cancer cells.
Maximum likelihood estimation via the ECM algorithm: A general framework (1993)

Two major reasons for the popularity of the EM algorithm are that its maximum step involves only complete-data maximum likelihood estimation, which is often computationally simple, and that its convergence is stable, with each iteration increasing the likelihood. When the associated complete-data maximum likelihood estimation itself is complicated, EM is less attractive because the M-step is computationally unattractive. In many cases, however, complete-data maximum likelihood estimation is relatively simple when conditional on some function of the parameters being estimated. We introduce a class of generalized EM algorithms, which we call the ECM algorithm, for Expectation/Conditional Maximization (CM), that takes advantage of the simplicity of complete-data conditional maximum likelihood estimation by replacing a complicated M-step of EM with several computationally simpler CM-steps. We show that the ECM algorithm shares all the appealing convergence properties of EM, such as always increasing the likelihood, and present several illustrative examples.
Regulation of c-jun expression during induction of monocytic differentiation by okadaic acid. (1992)

The present work has examined the effects of okadaic acid, an inhibitor of type 1 and 2A protein phosphatases, on the regulation of c-jun expression during monocytic differentiation of U-937 leukemia cells. The results demonstrate that okadaic acid treatment is associated with induction of a differentiated monocyte phenotype characterized by: (a) growth arrest; (b) increases in Mac-1 cell surface antigen expression; (c) down-regulation of c-myc transcripts; and (d) induction of tumor necrosis factor gene expression. This induction of monocytic differentiation was associated with transient increases in c-jun mRNA levels, which were maximal at 6 h. Similar effects were obtained for the c-fos gene. Run-on analysis demonstrated detectable levels of c-jun transcription in U-937 cells and that this rate is increased approximately 40-fold following okadaic acid exposure. c-jun mRNA levels were superinduced in cells treated with both okadaic acid and cycloheximide, whereas inhibition of protein synthesis had little, if any, effect on okadaic acid-induced c-jun transcription. The half-life of c-jun mRNA was similar (45-50 min) in both untreated and okadaic acid-induced cells. In contrast, treatment with both okadaic acid and cycloheximide was associated with stabilization (t 1/2 = 90 min) of c-jun transcripts. Taken together, these findings indicate that the induction of c-jun transcription by okadaic acid is controlled primarily by a transcriptional mechanism. Since previous studies have demonstrated that the c-jun gene is autoinduced by Jun/AP-1, we also studied transcription of c-jun promoter (positions -132/+170)-reporter gene constructs with and without a mutated AP-1 element.(ABSTRACT TRUNCATED AT 250 WORDS)
Drug Induced Liver Injury: Review with a Focus on Genetic Factors, Tissue Diagnosis, and Treatment Options (2015)

Drug-induced liver injury (DILI) is a rare but potentially life threatening adverse drug reaction. DILI may mimic any morphologic characteristic of acute or chronic liver disease, and the histopathologic features of DILI may be indistinguishable from those of other causes of liver injury, such as acute viral hepatitis. In this review article, we provide an update on causative agents, clinical features, pathogenesis, diagnosis modalities, and outcomes of DILI. In addition, we review results of recently reported genetic studies and updates on pharmacological and invasive treatments.
Activation of Matrix-Degrading Metalloproteinases by Mast Cell Proteases in Atherosclerotic Plaques (1998)

Recent studies suggest that mast cell-derived neutral proteases can activate matrix-degrading metalloproteinases (MMPs). We have investigated the role of the mast cell proteases tryptase and chymase in the activation of MMPs in human carotid endarterectomy specimens (atherosclerotic, n=32) and postmortem carotid arteries (control, n=17). In vitro degranulation of mast cells in atherosclerotic carotid arteries by compound 48/80 caused a significant increase in MMP activity. Addition of the nonselective tryptase inhibitor antipain, the specific trypsinlike protease inhibitor 4-amidinophenylmethanesulfonyl fluoride, and the chymase inhibitor chymostatin reduced this increase in MMP activity by 30+/-6%, 23+/-6%, and 9+/-2%, respectively. Immunocytochemistry identified significantly higher numbers of tryptase-containing cells (mast cells) and cells expressing MMP-1 and MMP-3 in the "shoulder" regions of atherosclerotic artery lesions compared with the tunica media of control arteries. Dual immunocytochemistry showed collocation of MMP-1 and MMP-3 with mast cells in the shoulder regions. Degranulation was observed in 78+/-5% (mean+/-SEM) of mast cells in this area, whereas nonactivated mast cells were observed in all other areas. In situ zymography revealed caseinolytic and gelatinolytic activity in these areas. In conclusion, in vitro mast cell degranulation, which releases mast cell proteases, in carotid arteries increases MMP activity. Furthermore, elevated MMP-1 and MMP-3 expression is collocated with increased numbers of degranulated mast cells and with greater MMP activity in the shoulder regions of atherosclerotic plaques. Activation of MMPs by mast cell-derived proteases may be an important mechanism in atherosclerotic plaque destabilization.