gebhart/patrepeval huggingface dataset:
BRD4 Profiling Identifies Critical Chronic Lymphocytic Leukemia Oncogenic Circuits and Reveals Sensitivity to PLX51107, a Novel Structurally Distinct BET Inhibitor (2018)

Bromodomain and extra-terminal (BET) family proteins are key regulators of gene expression in cancer. Herein, we utilize BRD4 profiling to identify critical pathways involved in pathogenesis of chronic lymphocytic leukemia (CLL). BRD4 is overexpressed in CLL and is enriched proximal to genes upregulated or <i>de novo</i> expressed in CLL with known functions in disease pathogenesis and progression. These genes, including key members of the B-cell receptor (BCR) signaling pathway, provide a rationale for this therapeutic approach to identify new targets in alternative types of cancer. Additionally, we describe PLX51107, a structurally distinct BET inhibitor with novel <i>in vitro</i> and <i>in vivo</i> pharmacologic properties that emulates or exceeds the efficacy of BCR signaling agents in preclinical models of CLL. Herein, the discovery of the involvement of BRD4 in the core CLL transcriptional program provides a compelling rationale for clinical investigation of PLX51107 as epigenetic therapy in CLL and application of BRD4 profiling in other cancers.<b>Significance:</b> To date, functional studies of BRD4 in CLL are lacking. Through integrated genomic, functional, and pharmacologic analyses, we uncover the existence of BRD4-regulated core CLL transcriptional programs and present preclinical proof-of-concept studies validating BET inhibition as an epigenetic approach to target BCR signaling in CLL. <i>Cancer Discov; 8(4); 458-77. ©2018 AACR.</i><i>This article is highlighted in the In This Issue feature, p. 371</i>.
A Structurally Diverse Library of Polycyclic Lactams Resulting from Systematic Placement of Proximal Functional Groups (2006)

A short, linear sequence for the synthesis of complex small polycyclic lactams (see picture) is presented. The sequence, which is applied to the synthesis of a library of 529 compounds, is based on a catalytic, enantioselective cycloaddition between an oxazole and an aldehyde, so that the resultant compounds are enantiomerically pure and readily prepared in either stereochemical series. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z503341_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Bacteriophage based probes for pathogen detection (2012)

Rapid and specific detection of pathogenic bacteria is important for the proper treatment, containment and prevention of human, animal and plant diseases. Identifying unique biological probes to achieve a high degree of specificity and minimize false positives has therefore garnered much interest in recent years. Bacteriophages are obligate intracellular parasites that subvert bacterial cell resources for their own multiplication and production of disseminative new virions, which repeat the cycle by binding specifically to the host surface receptors and injecting genetic material into the bacterial cells. The precision of host recognition in phages is imparted by the receptor binding proteins (RBPs) that are often located in the tail-spike or tail fiber protein assemblies of the virions. Phage host recognition specificity has been traditionally exploited for bacterial typing using laborious and time consuming bacterial growth assays. At the same time this feature makes phage virions or RBPs an excellent choice for the development of probes capable of selectively capturing bacteria on solid surfaces with subsequent quick and automatic detection of the binding event. This review focuses on the description of pathogen detection approaches based on immobilized phage virions as well as pure recombinant RBPs. Specific advantages of RBP-based molecular probes are also discussed.
Preferential Interaction of Sentrin with a Ubiquitin-conjugating Enzyme, Ubc9 (1997)

Sentrin is a ubiquitin-like molecule that has been shown to interact with the death domains of Fas and tumor necrosis factor receptor 1 (TNFR1), PML, Rad51, Rad52, and RanGAP1. We have reported previously that sentrin can be conjugated to other proteins in a manner analogous to protein ubiquitination (Kamitani, T., Nguyen, H. P., and Yeh, E. T. H. (1997) J. Biol. Chem. 272, 14001-14004). Furthermore, the conserved C-terminal Gly-Gly residues are required for sentrinization to occur. To identify enzymes which play a role in sentrinization, the yeast two-hybrid system was used to screen a human placenta cDNA library using sentrin as bait. A strong positive interacting clone was found to contain a cDNA insert encoding the ubiquitin-conjugating enzyme, Ubc9. The interaction between sentrin and Ubc9 required the ubiquitin domain and the C-terminal Gly-Gly residues of sentrin. This interaction appears to be specific because sentrin could only interact weakly with UbcH5B, but could not interact with HHR6B, UbcH6 nor E2-EPF. In vitro translated sentrin could be precipitated by a GST-Ubc9 fusion protein, but not by glutathione S-transferase. A beta-mercaptoethanol-sensitive Ubc9-sentrin conjugate could also be identified in the in vitro binding assay. Substitution of the conserved cysteine residue of Ubc9 by serine abolished the formation of the Ubc9-sentrin conjugate. Taken together, Ubc9 is a strong candidate to be the key conjugating enzyme in the sentrinization pathway.
Risk Factors for Stroke During Surgery for Carotid Body Tumors (2011)

Internal carotid artery manipulation, including reconstruction, ligation, and repair of injury, significantly increased the incidence of stroke. For uncomplicated CBT resection, careful preoperative planning, especially for patients with class II and III tumors, is mandatory to avoid inadvertent ICA manipulation necessitated by bleeding. Early ECA division during the operation rather than preoperative percutaneous embolization in patients with class II and III tumors was significantly effective in reducing the stroke rate.
11.8 Integrated ultrasonic system for measuring body-fat composition (2015)

An accurate, low-power, and highly integrateci solution for accurate assessment of body fat is presented that addresses a growing consumer interest in economical and easy-to-use solutions for monitoring personal health and fitness. Unlike the prevalent present solution that estimates body fat percentage from an impedance measurement integrated in a weight scale and gives only a global index with accuracy compromised by a host of factors including skin moisture and metabolic activity, the reported approach uses ultrasound for an accurate measure of the actual thickness of the fat and muscle layers [1].
Diagnosis of specialized intestinal metaplasia of the esophagus with optical coherence tomography (2001)

Summary form only given. The purpose of this study was to acquire a large series of biopsy-correlated OCT images to establish and validate objective OCT image criteria for specialized intestinal metaplasia and prospectively determine the sensitivity and specificity of these criteria.
Single Amino Acids Determine Specificity of Binding of Protein Kinase A Regulatory Subunits by Protein Kinase A Anchoring Proteins (1999)

Cyclic AMP-dependent protein kinase is tethered to protein kinase A anchoring proteins (AKAPs) through regulatory subunits (R) by RIalpha-specific, RIIalpha-specific, or RIalpha/RIIalpha dual-specific binding. Ala- and Val-scanning mutagenesis determined that hydrophobic amino acids at three homologous positions are required for binding of RIalpha to FSC1/AKAP82 domain B and RIIalpha to AKAP Ht31. A mutation at the middle position reversed the binding specificity of both AKAPs, and mutations at this same position of the dual-specific domain A of FSC1/AKAP82 converted it into either an RIalpha or RIIalpha binding domain. This suggests that hydrophobic amino acids at three conserved positions within the primary sequence and an amphipathic helix of AKAPs are required for cyclic AMP-dependent protein kinase binding, with the size of the aliphatic side chain at the middle position determining RIalpha or RIIalpha binding specificity.
Wash-free magnetic immunoassay of the PSA cancer marker using SERS and droplet microfluidics (2016)

We report a novel wash-free magnetic immunoassay technique for prostate-specific antigen (PSA) that uses a surface-enhanced Raman scattering (SERS)-based microdroplet sensor. The magnetic bar embedded in a droplet-based microfluidic system segregates the free and bound SERS tags by splitting the droplets into two smaller parts. The presence of PSA targets leads more SERS tags to immunocomplex in one droplet so that fewer SERS tags remain in another supernatant solution droplet. Thus, SERS signal measurement enables the quantitative evaluation of PSA markers. This approach can provide a rapid and sensitive assay that is applicable for PSA cancer markers in serum without any washing. Specifically, SERS signals were measured at 174 droplets per minute and averaged for quantitative evaluation of PSA. The limit of detection (LOD) determined by our SERS-based microdroplet sensor was estimated to be below 0.1 ng mL(-1), which is significantly below the clinical cut-off value for the diagnosis of prostate cancer. In addition, because the entire assay can be carried out automatically, only a minimal amount of sample is needed. Accordingly, the approach is expected to be useful as a potential clinical tool for the early diagnosis of prostate cancer.
Localization of Bacillus subtilis sacU(Hy) mutations to two linked genes with similarities to the conserved procaryotic family of two-component signalling systems (1988)

Mutations in the sacU region have a pleiotropic phenotype. Certain mutations designated sacU(Hy), for example, express degradative enzymes at high levels, are able to sporulate in the presence of glucose, have severely reduced transformation efficiencies, and are nonmotile. We isolated and sequenced the sacU gene region of Bacillus subtilis. Two open reading frames were found in the sacU region, and sacU(Hy) mutations were localized to both of these open reading frames. The two open reading frames have similarities to two widespread families of proteins that mediate responses to environmental stimuli.
Transition-metal nitro-nitrosyl redox couple: catalytic oxidation of olefins to ketones (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTransition-metal nitro-nitrosyl redox couple: catalytic oxidation of olefins to ketonesMark A. Andrews and Kevin P. KellyCite this: J. Am. Chem. Soc. 1981, 103, 10, 2894–2896Publication Date (Print):May 1, 1981Publication History Published online1 May 2002Published inissue 1 May 1981https://doi.org/10.1021/ja00400a081RIGHTS & PERMISSIONSArticle Views565Altmetric-Citations70LEARN 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 (441 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
A Helix-Loop-Helix Peptide at the Upper Lip of the Active Site Cleft of Lysozyme Confers Potent Antimicrobial Activity with Membrane Permeabilization Action (2001)

Recently, we have found that partially unfolded lysozyme exerts broad spectrum antimicrobial action in vitro against Gram-negative and Gram-positive bacteria independent of its catalytic activity. In parallel, an internal peptide (residues 98-112) of hen egg white lysozyme, obtained after digestion with clostripain, possessed broad spectrum antimicrobial action in vitro. This internal peptide is part of a helix-loop-helix domain (87-114 sequence of hen lysozyme) located at the upper lip of the active site cleft of lysozyme. The helix-loop-helix (HLH) structures are known motifs commonly found in membrane-active and DNA-binding proteins. To evaluate the contribution of the HLH peptide to the antimicrobial properties of lysozyme, the HLH sequence and its secondary structure derivatives of chicken and human lysozyme were synthesized and tested for antimicrobial activity against several bacterial strains. We found that the full HLH peptide of both chicken and human lysozymes was potently microbicidal against both Gram-positive and Gram-negative bacteria and the fungus Candida albicans. The N-terminal helix of HLH was specifically bactericidal to Gram-positive bacteria, whereas the C-terminal helix was bactericidal to all tested strains. Outer and inner membrane permeabilization studies, as well as measurements of transmembrane electrochemical potentials, provided evidence that HLH peptide and its C-terminal helix domain kill Gram-negative bacteria by crossing the outer membrane via self-promoted uptake and causing damage to the inner membrane through channel formation. The results are discussed in terms of proposed mechanisms for the catalytically independent antimicrobial activity of lysozyme that offer a new strategy for the design of potential antimicrobial drugs in the treatment of infectious diseases.
Distributed Video Coding (2004)

Distributed coding is a new paradigm for video compression, based on Slepian and Wolf's and Wyner and Ziv's information-theoretic results from the 1970s. This paper reviews the recent development of practical distributed video coding schemes. Wyner-Ziv coding, i.e., lossy compression with receiver side information, enables low-complexity video encoding where the bulk of the computation is shifted to the decoder. Since the interframe dependence of the video sequence is exploited only at the decoder, an intraframe encoder can be combined with an interframe decoder. The rate-distortion performance is superior to conventional intraframe coding, but there is still a gap relative to conventional motion-compensated interframe coding. Wyner-Ziv coding is naturally robust against transmission errors and can be used for joint source-channel coding. A Wyner-Ziv MPEG encoder that protects the video waveform rather than the compressed bit stream achieves graceful degradation under deteriorating channel conditions without a layered signal representation.
Chemical Reaction Engineering (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommentaryNEXTChemical Reaction EngineeringOctave LevenspielView Author Information Chemical Engineering Department Oregon State University Corvallis, Oregon 97331Cite this: Ind. Eng. Chem. Res. 1999, 38, 11, 4140–4143Publication Date (Web):September 11, 1999Publication History Published online11 September 1999Published inissue 1 November 1999https://pubs.acs.org/doi/10.1021/ie990488ghttps://doi.org/10.1021/ie990488gbrief-reportACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views23019Altmetric-Citations1239LEARN 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 SUBJECTS:Kinetic modeling,Kinetics,Order,Reaction engineering,Surface reactions Get e-Alerts
Multiple C-Terminal Lysine Residues Target p53 for Ubiquitin-Proteasome-Mediated Degradation (2000)

In normal cells, p53 is maintained at a low level by ubiquitin-mediated proteolysis, but after genotoxic insult this process is inhibited and p53 levels rise dramatically. Ubiquitination of p53 requires the ubiquitin-activating enzyme Ubc5 as a ubiquitin conjugation enzyme and Mdm2, which acts as a ubiquitin protein ligase. In addition to the N-terminal region, which is required for interaction with Mdm2, the C-terminal domain of p53 modulates the susceptibility of p53 to Mdm2-mediated degradation. To analyze the role of the C-terminal domain in p53 ubiquitination, we have generated p53 molecules containing single and multiple lysine-to-arginine changes between residues 370 and 386. Although wild-type (WT) and mutant molecules show similar subcellular distributions, the mutants display a higher transcriptional activity than WT p53. Simultaneous mutation of lysine residues 370, 372, 373, 381, 382, and 386 to arginine residues (6KR p53 mutant) generates a p53 molecule with potent transcriptional activity that is resistant to Mdm2-induced degradation and is refractory to Mdm2-mediated ubiquitination. In contrast to WT p53, transcriptional activity directed by the 6KR p53 mutant fails to be negatively regulated by Mdm2. Those differences are also manifest in HeLa cells which express the human papillomavirus E6 protein, suggesting that p53 C-terminal lysine residues are also implicated in E6-AP-mediated ubiquitination. These data suggest that p53 C-terminal lysine residues are the main sites of ubiquitin ligation, which target p53 for proteasome-mediated degradation.
A method for constructing single-copy lac fusions in Salmonella typhimurium and its application to the hemA-prfA operon (1992)

This report describes a set of Escherichia coli and Salmonella typhimurium strains that permits the reversible transfer of lac fusions between a plasmid and either bacterial chromosome. The system relies on homologous recombination in an E. coli recD host for transfer from plasmid to chromosome. This E. coli strain carries the S. typhimurium put operon inserted into trp, and the resulting fusions are of the form trp::put::[Kanr-X-lac], where X is the promoter or gene fragment under study. The put homology flanks the lac fusion segment, so that fusions can be transduced into S. typhimurium, replacing the resident put operon. Subsequent transduction into an S. typhimurium strain with a large chromosomal deletion covering put allows selection for recombinants that inherit the fusion on a plasmid. A transposable version of the put operon was constructed and used to direct lac fusions to novel locations, including the F plasmid and the ara locus. Transductional crosses between strains with fusions bearing different segments of the hemA-prfA operon were used to determine the contribution of the hemA promoter region to expression of the prfA gene and other genes downstream of hemA in S. typhimurium.
Mucopolysaccharidosis type VI: Structural and clinical implications of mutations in N-acetylgalactosamine-4-sulfatase (2001)

Mucopolysaccharidosis type VI (MPS-VI) is an autosomal recessive lysosomal storage disorder caused by the deficiency of N-acetylgalactosamine-4-sulfatase (4S; or ARSB). Mutations in the 4S gene are responsible for 4S deficiency, which leads to the intralysosomal storage of partially degraded glycosaminoglycans, dermatan sulfate, and chondroitin 4-sulfate. To date, a total of 45 clinically relevant mutations have been identified in the human 4S gene. Missense mutations are the largest group, with 31 identified mutations. Nonsense mutations and small insertions or deletions comprise the remainder, with seven mutations each. Six polymorphisms have also been reported: two amino acid substitutions and four silent transitions. Mapping of the missense mutations onto the 4S structure shows that they are distributed throughout the three subunits of the mature 4S polypeptide. Mutations have been identified in active site residues, in residues adjacent to the active site, in potential substrate binding residues, in residues exposed on the surface, and in residues buried within the protein core. Missense mutations have also been identified in disulfide crosslinks. Molecular modeling of MPS-VI mutations onto the 4S structure suggests that the majority cause 4S deficiency via destabilization and the consequent reduction of 4S protein concentration. The vast majority of MPS-VI mutant alleles are either unique to a patient or are present in a small number of patients. So far, no common mutations have been described. Therefore, screening of the general population for MPS-VI alleles will be difficult.
Structure‐Tuned Lead Halide Perovskite Nanocrystals (2015)

Colloidally stable suspensions of lead halide perovskite nanocrystals are prepared from high-quality lead halide nanocrystal seeds. Perovskite nanocrystals with different layered crystal structures are reported. These systems are well suited for investigations of the intrinsic photophysics and spectroscopy of organic-inorganic metal halide perovskites.
Novel 5-HT3 antagonists: indol-3-ylspiro(azabicycloalkane-3,5'(4'H)oxazoles) (1992)

The synthesis and biochemical evaluation of a series of spirofused indole oxazoline 5-HT3 antagonists is described in which the oxazoline ring acts as a bioisosteric replacement for esters and amides. The effect of substitution about the indole ring has shown the steric limitations of the aromatic binding site. Incorporation of a variety of azabicyclic systems within the rigid spirofused framework has allowed the definition of a binding model which incorporates a number of known antagonists and agonists. In this model steric constraints limit substitution around the indole ring although there is some bulk tolerance at the 1- and 2-positions. The importance of constraining the basic nitrogen within an azabicyclic system is underlined by comparison with the monocyclic piperidine. The highest affinity was observed for those compounds in which the basic nitrogen occupies a bridgehead position, the most potent analogue in this group being the azabicyclic [3.3.1] system (pIC50 = 8.95), suggesting lipophilic interactions may play a role in increasing affinity. A suggested model for agonist binding is included in which the basic nitrogens are superimposed and the 5-hydroxyl group of 5-HT is superimposed on the H-bond-accepting atom of the heterocyclic linking group.