gebhart/patrepeval huggingface dataset:
A Variable Bin Width Histogram Based Image Clustering Algorithm (2010)

In image clustering, digital images can be represented with a large number of visual features corresponding to a high dimensional data space. Traditional clustering algorithms have difficulty in processing image dataset because of the curse of dimensionality. Moreover, similarity between images is measured by the values of partial features. To discover clusters existing in different subspace is known as the projective clustering problem. In this paper, we propose a novel projective clustering algorithm that utilizes dense area detection in variable bin width histograms to form the description of potential cluster candidates. Those candidates with sufficient number of data objects are treated as description of clusters. Relative entropy is used as a density threshold in order to iteratively detect dense areas in each histogram. The construction of variable bin width histogram is automatic. Compared with fixed bin width histogram used in previous projective clustering algorithms, such as EPCH (an Efficient Projective Clustering technique by Histogram construction), variable bin width histogram keeps a nice tradeoff between accurately approximating the underlying distribution and clustering efficiency. Fewer input parameters are required in our proposed algorithm, and the only input parameter required is more robust to variations of other factors such as bin width and is more interpretable to general users. Experiments on an image segmentation dataset show that our algorithm has a better clustering quality than EPCH according to V-Measure.
Reversible prevention of platelet activation by (E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide (ajoene) in dogs under extracorporeal circulation. (1988)

Ajoene ((E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide), an organosulfur compound derived from garlic inhibits platelet activation induced ex vivo by all known agonists. The effect of ajoene on the thrombocytopenia associated with the circulation of blood through extracorporeal devices such as dialyzers or oxygenators was studied under the following conditions: Ex vivo using fresh, heparinized human blood, circulating through a dialyzer or oxygenator, and in vivo, in dogs subjected to extracorporeal circulation. In both experimental conditions ajoene proved very efficacious in preventing platelet loss (60-65% loss in controls vs. 15-20% loss in the presence of ajoene, p less than 0.01). Moreover, recuperation of platelet function was achieved after 3-4 h in the in vivo experiments.
Intracellular Signaling Mechanisms Activated by Cholecystokinin-Regulating Synthesis and Secretion of Digestive Enzymes in Pancreatic Acinar Cells (2001)

The intracellular signaling mechanisms by which cholecystokinin (CCK) and other secretagogues regulate pancreatic acinar function are more complex than originally realized. CCK couples through heterotrimeric G proteins of the Gq family to lead to an increase in intracellular free Ca2+, which shows spatial and temporal patterns of signaling. The actions of Ca2+ are mediated in part by activation of a number of Ca2+-activated protein kinases and the protein phosphatase calcineurin. By the process of exocytosis the intracellular messengers Ca2+, diacylglycerol, and cAMP activate the release of the zymogen granule content in a manner that is poorly understood. This fusion event most likely involves SNARE and Rab proteins present on zymogen granules and cellular membrane domains. More likely related to nonsecretory aspects of cell function, CCK also activates three MAPK cascades leading to activation of ERKs, JNKs, and p38 MAPK. Although the function of these pathways is not well understood, ERKs are probably related to cell growth, and through phosphorylation of hsp27, p38 can affect the actin cytoskeleton. The PI3K (phosphatidylinositol 3-kinase)-mTOR (mammalian target of rapamycin) pathway is important for regulation of acinar cell protein synthesis because it leads to both activation of p70S6K and regulation of the availability of eIF4E in response to CCK. CCK also activates a number of tyrosyl phosphorylation events including that of p125FAK and other proteins associated with focal adhesions.
Automated segmentation by pixel classification of retinal layers in ophthalmic OCT images (2011)

Current OCT devices provide three-dimensional (3D) in-vivo images of the human retina. The resulting very large data sets are difficult to manually assess. Automated segmentation is required to automatically process the data and produce images that are clinically useful and easy to interpret. In this paper, we present a method to segment the retinal layers in these images. Instead of using complex heuristics to define each layer, simple features are defined and machine learning classifiers are trained based on manually labeled examples. When applied to new data, these classifiers produce labels for every pixel. After regularization of the 3D labeled volume to produce a surface, this results in consistent, three-dimensionally segmented layers that match known retinal morphology. Six labels were defined, corresponding to the following layers: Vitreous, retinal nerve fiber layer (RNFL), ganglion cell layer & inner plexiform layer, inner nuclear layer & outer plexiform layer, photoreceptors & retinal pigment epithelium and choroid. For both normal and glaucomatous eyes that were imaged with a Spectralis (Heidelberg Engineering) OCT system, the five resulting interfaces were compared between automatic and manual segmentation. RMS errors for the top and bottom of the retina were between 4 and 6 μm, while the errors for intra-retinal interfaces were between 6 and 15 μm. The resulting total retinal thickness maps corresponded with known retinal morphology. RNFL thickness maps were compared to GDx (Carl Zeiss Meditec) thickness maps. Both maps were mostly consistent but local defects were better visualized in OCT-derived thickness maps.
Characterization of a Dominant Negative Mutant of the Cell Cycle Ubiquitin-conjugating Enzyme Cdc34 (1995)

The yeast Saccharomyces cerevisiae CDC34 gene encodes a ubiquitin-conjugating enzyme that is required for the cell cycle G1/S transition. We show here that a dominant negative Cdc34 protein is generated by simultaneously replacing both Cys95 and Leu99 with Ser residues. Cys95 is an essential catalytic residue that forms a transient thiol ester with ubiquitin during catalysis, and Leu99 is highly conserved among all known ubiquitin-conjugating enzymes. Mutants that encode either an alanine or a serine at one or both of these two positions are inactive. Of these eight mutants, overexpression of CDC34-C95S,L99S in wild type strains was found to block cell growth. Although cells overexpressing Cdc34-C95S,L99S do not exhibit the characteristic multibudded phenotype of cdc34 temperature-sensitive or null mutants, this blockade is relieved by simultaneous overxpression of wild type Cdc34. Purified Cdc34-C95S,L99S protein can be shown to inhibit in vitro ubiquitination of the Cdc34-specific substrate, Cln2 protein. We suggest that Cdc34-C95S,L99S selectively sequesters a subset of Cdc34 substrates or regulators. These findings have implications for the structure/function relationships of ubiquitin-conjugating enzymes, and suggest a general method for identifying components and substrates of specific ubiquitination pathways of eukaryotes.
Relationships Between Lyrics And Melody In Popular Music. (2009)

[TODO] Add abstract here.
Determinants and effects of option listings: evidence from ADRs (2013)

Purpose In this paper, the authors aim to test the assertion that options act as a substitute for short sales by allowing investors an alternative way to act on bearish sentiment. An empirical test of this assertion requires a researcher to observe both types of firm – those that weren’t short sale constrained, as well as those that were. The authors examine the ability of options to alleviate the short sales constraint directly – in an environment where the constraint is likely to differ across firms in a systematic fashion, namely the market for American Depository Receipts (ADRs). Design/methodology/approach The authors examine 190 option introductions on ADRs over the period of 1982 to 2006. The question of how ADRs are chosen for options listing, and whether those criteria differ from those found using purely domestic options, is addressed using logistic regressions. The authors use the event study methods of Brown and Warner to examine the price effect of the listing. They use OLS regression to identify determinants of the cumulative abnormal return upon option listing. Independent variables are those indicated by existing literature that examines option listing on domestic securities. Findings In an environment where the effective short sale constraint varies across firms, the authors find support for the contention that US option listings reduce the effect of the short sales constraint, providing relief for investors who have negative sentiment about the stock and are subject to a short sale constraint. However, it does not appear that option listing entities seek out companies for which short sale constraints are stronger. Originality/value The authors’ hypotheses are similar to those of Mayhew and Mihov and of Danielson and Sorescu, but the authors assert that the ADR market is a more robust environment in which to test the hypotheses. This is due to the potentially large variation in the effective short sale constraints that results from the differences in their underlying home market legal and regulatory environments. In addition to relative short interest and the change in relative short interest, this environment allows the authors to use indicator variables to directly test the ability of options to substitute for short sales.
The allosteric ATP‐inhibition of cytochrome c oxidase activity is reversibly switched on by cAMP‐dependent phosphorylation (2000)

In previous studies the allosteric inhibition of cytochrome c oxidase at high intramitochondrial ATP/ADP-ratios via binding of the nucleotides to the matrix domain of subunit IV was demonstrated. Here we show that the allosteric ATP-inhibition of the isolated bovine heart enzyme is switched on by cAMP-dependent phosphorylation with protein kinase A of subunits II (and/or III) and Vb, and switched off by subsequent incubation with protein phosphatase 1. It is suggested that after cAMP-dependent phosphorylation of cytochrome c oxidase mitochondrial respiration is controlled by the ATP/ADP-ratio keeping the proton motive force Deltap low, and the efficiency of energy transduction high. After Ca(2+)-induced dephosphorylation this control is lost, accompanied by increase of Deltap, slip of proton pumping (decreased H(+)/e(-) stoichiometry), and increase of the rate of respiration and ATP-synthesis at a decreased efficiency of energy transduction.
Alzheimer s disease and heparan sulfate proteoglycan (1998)

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder. Cardinal histopathologic changes of AD are neurofibrillary tangles (NFTs) and deposits of beta-amyloid protein (A-beta) in the form of neuritic plaques (NPs). Several different mutations found in patients with familial AD have been demonstrated to increase A-beta production, resulting in a common pathological cascade of beta-amyloidosis in the brain. Heparan sulfate proteoglycan (HSPG) has been co-localized with both A-beta in the NPs and NFTs. The proteoglycans are a family of complex macromolecules consisting of a protein core to which glycosaminoglycan (GAG) chains are covalently attached. HSPG has been shown to bind to A-beta, accelerate its fibril formation, and maintain its fibril stability. In AD and other neurodegenerative disorders, tau becomes hyperphosphorylated hence it is unable to bind to microtubules which results in the production of paired helical filaments, a building unit of NFTs. It has been shown in vitro that sulfated GAGs induce the formation of paired helical-like filaments under physiological conditions from tau. Furthermore, an interaction between HSPG and apolipoprotein E (a potent risk factor of AD) has been shown to be involved in neurodegeneration. Thus, substantial evidence exists to underscore important roles of HSPG in the etiology of AD.
Recent Advances in Antimicrobial Dendrimers (2000)

Recent progress in antimicrobial dendrimers is reviewed. Both specific interactions and non-specific interactions can be utilized to design multifunctional (polyvalent) antimicrobial agents, which might be more potent than their mono-functional counterparts. Dendrimers or hyperbranched polymers can also be used to design novel drug delivery systems
Electrophilic opening of the thiazolidine ring in penicillins (1971)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectrophilic opening of the thiazolidine ring in penicillinsStjepan Kukolja and Lilly Res. Lab.Cite this: J. Am. Chem. Soc. 1971, 93, 23, 6267–6269Publication Date (Print):November 1, 1971Publication History Published online1 May 2002Published inissue 1 November 1971https://pubs.acs.org/doi/10.1021/ja00752a046https://doi.org/10.1021/ja00752a046research-articleACS PublicationsRequest reuse permissionsArticle Views169Altmetric-Citations25LEARN 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
Enhancement of antineoplastic action of 5-aza-2???-deoxycytidine by zebularine on L1210 leukemia (2005)

Tumor suppressor genes that have been silenced by aberrant DNA methylation are potential targets for reactivation by novel chemotherapeutic agents. The potent inhibitor of DNA methylation and antileukemic agent, 5-aza-2'-deoxycytidine (5-AZA-CdR, Decitabine), can reactivate silent tumor suppressor genes. One hindrance to the curative potential of 5-AZA-CdR is its rapid in vivo inactivation by cytidine deaminase (CD). An approach to overcome this obstacle is to use 5-AZA-CdR in combination with zebularine (Zeb), a potent inhibitor of CD. Zeb also possesses independent antineoplastic activity due to its inhibition of DNA methylation. We tested the capacity of 5-AZA-CdR and Zeb alone and in combination to inhibit growth and colony formation of different leukemic cell lines. 5-AZA-CdR and Zeb in combination produced a greater inhibition of growth against murine L1210 lymphoid leukemic cells, and a greater reduction in colony formation by L1210 and human HL-60 myeloid leukemic cells, than either agent alone. The ability of these agents to reactivate the tumor suppressor gene, p57KIP2, was also tested using RT-PCR. The combination produced a synergistic reactivation of p57KIP2 in HL-60 leukemic cells. A methylation-specific PCR assay showed that this combination also induced a significantly greater demethylation level of the p57KIP2 promoter than either drug alone. The in vivo antineoplastic activity of the agents was evaluated in mice with L1210 leukemia. A greater increase in survival time of mice with L1210 leukemia was observed with the combination than with either agent alone using three different dose schedules. The enhanced activity observed with 5-AZA-CdR plus Zeb in both murine and human leukemic cells lines provides a rationale for the clinical investigation of these drugs in patients with advanced leukemia. The probable mechanism of this drug interaction involves inhibition of CD by Zeb and the complementary inhibition of DNA methylation by both agents.
Sleep and neuromuscular disease: bilevel positive airway pressure by nasal mask as a treatment for sleep disordered breathing in patients with neuromuscular disease (1998)

Bilevel positive airway pressure delivered by nasal mask may be used successfully to treat sleep disordered breathing associated with neuromuscular disease. This device can be employed to assist nocturnal ventilation by either the spontaneous or timed mode. In the United States it is less expensive and easier to institute than volume controlled NIPPV and may be as efficacious as this mode if close surveillance and regular reevaluation of the patient's status is maintained.
Decreased metabolism and viability of Mycoplasma hominis induced by monoclonal antibody-mediated agglutination (1992)

Monoclonal antibodies (MAbs) were generated against lysates of clinical Mycoplasma hominis isolates. Three of these, designated BG2, BA10, and FE6, recognized an integral membrane protein of M. hominis with an apparent molecular weight of 50,000 (p50). Electron microscopy studies demonstrated that this protein is distributed evenly over the cell surface. These anti-p50 MAbs were species specific for M. hominis; they reacted with 42% of 126 tested clinical M. hominis isolates and showed no reactivity to heterologous mycoplasma species. Immunoblot analysis after limited proteolysis of purified p50 demonstrated that the three MAbs reacted with different epitopes of the protein. Unlike BA10 and FE6, MAb BG2 induced a decrease in arginine metabolism and a reduction of CFU in metabolic inhibition tests. F(ab)2 fragments of MAb BG2 showed the same inhibitory effect as the intact MAb molecule, while Fab and Fc fragments had no influence on vital functions. Preincubation of the mycoplasmas with MAb BG2 followed by trypsin treatment yielded the same amount of CFU as the control without antibodies. In conclusion, the cell aggregates were resolved by the trypsin treatment. These experiments and tests with the antibody fragments led to the conclusion that only the intact MAb structure or the F(ab)2 structure had metabolic inhibition potential and that the observed metabolism inhibition as well as the apparent decrease in viability were a result of agglutination by MAb BG2.
Replacement of the H-Ras Farnesyl Group by Lipid Analogues:  Implications for Downstream Processing and Effector Activation in Xenopus Oocytes (1997)

Ras proteins must undergo a series of posttranslational lipidation steps before they become biologically functional. While the fact that farnesylation is required for subsequent processing steps and indispensable for Ras function has been established, the significance of the isoprenoid structure per se in the context of fully processed Ras is unknown. Here, we describe a novel approach for studying the isoprenoid structure-function relationship in vivo by replacing the H-Ras farnesyl group with synthetic analogues and analyzing their biological functions following microinjection into Xenopus oocytes. We show that the H-Ras farnesyl group can be stripped of most of its isoprenoid features that distinguish it from a fatty acid without any apparent effect on its ability to induce oocyte maturation and activation of mitogen-activated protein kinase. In contrast, replacement by the less hydrophobic isoprenoid geranyl causes severely delayed oocyte activation. Analysis of posttranslational processing reveals a striking correlation between the kinetics of processing, membrane binding, and the onset of biological activity regardless of lipid structure and suggests that slow C-terminal proteolysis and/or methylation can become rate-limiting for H-Ras function. Thus, while our results suggest no stringent requirement for the H-Ras farnesyl structure for effector activation in Xenopus oocytes, they reveal an important role for the lipid present at the farnesylation site in promoting efficient proteolysis and/or methylation which allows rapid palmitoylation, membrane localization, and biological activity. Xenopus oocytes provide a useful in vivo system for the kinetic analysis of the function of the protein of interest present at the physiological dose, which is required for accurate determination of structure-function relationships.
Viral liposomes released from insect cells infected with recombinant baculovirus expressing the matrix protein of vesicular stomatitis virus (1993)

The matrix (M) protein of vesicular stomatitis virus (VSV) has been found to promote assembly and budding of virions as well as down-regulating of VSV transcription. Large quantities of M protein can be produced in insect cells infected with recombinant baculovirus expressing the VSV M gene under control of the polyhedrin promoter. Analysis by pulse-chase experiments and density gradient centrifugation revealed that the [35S]methionine-labeled M protein synthesized in insect cells is released into the extracellular medium in association with lipid vesicles (liposomes). Electron microscopy and immunogold labeling showed that M protein expressed in insect cells induced the formation on plasma membrane of vesicles containing M protein, which are released from the cell surface in the form of liposomes. The baculovirus vector itself or recombinants expressing VSV glycoprotein (G) or nucleocapsid (N) protein did not produce the formation of vesicles in infected cells. The baculovirus-expressed M protein retains biological activity as demonstrated by its capacity to inhibit transcription when reconstituted with VSV nucleocapsids in vitro. These data suggest that M protein has the capacity to associate with the plasma membrane of infected cells and, in so doing, causes evagination of the membrane to form a vesicle which is released from the cell. This observation leads to the postulate, which requires further proof, that the VSV M protein can induce the formation and budding of liposomes from the cell membrane surface.
Preferred translation of human hepatitis B virus polymerase from core protein- but not from precore protein-specific transcript (1990)

In the human hepatitis B virus (HBV) genome, the 5' end of the polymerase coding sequence overlaps with the 3' end of the core protein coding sequence. Recent results obtained from genetic studies have suggested that translation of HBV polymerase initiates from the first ATG codon of the polymerase reading frame and is not a result of frameshift translation from the core protein reading frame, as in the case of retroviruses. By using in vitro-synthesized SP6 RNA transcripts, we now demonstrate that HBV core protein-specific mRNA can direct the synthesis of polymerase from the internal polymerase ATG codon in rabbit reticulocyte lysates and Xenopus oocytes. A related message with an additional 60 nucleotides at the 5' end (pre-core protein mRNA) was not as efficient as the core protein mRNA for translation of polymerase. Furthermore, translation of polymerase from the core protein mRNA was not inhibited by the cap analog m7GpppG. This result, together with the results described above, indicates that translation of HBV polymerase occurs in a novel, cap-independent manner.