gebhart/patrepeval huggingface dataset:
Ruthenium Complexes as Protein Kinase Inhibitors (2004)

[reaction: see text] Replacing complex natural products with simple metal complexes could lead to a new class of metallopharmaceuticals in which the metal center plays mainly a structural role. A strategy is introduced for the creation of ruthenium complex-based protein kinase inhibitors 1 (X = CO or CH(2)), morphed out of the class of indolocarbazole inhibitors with the alkaloid staurosporine as its most prominent member.
Tunable compensation of channel degrading effects using nonlinearly chirped passive fiber Bragg gratings (1999)

Several channel-degrading effects are present in nonstatic and dynamically reconfigurable wavelength-division-multiplexed systems and networks due to various types of dispersion in the optical transmission fiber. These effects must be addressed by tunable methods so that data signals do not fade with time. The relevant effects for which we demonstrate tunable compensation include: chromatic dispersion accumulated in a single channel and in multiple channels, polarization mode dispersion, and periodic RF power fading. We utilize a nonlinearly chirped fiber Bragg grating that provides a dispersive function that can be varied continuously by tuning a single mechanical stretching element.
Distinct CpG DNA and Polyinosinic-Polycytidylic Acid Double-Stranded RNA, Respectively, Stimulate CD11c− Type 2 Dendritic Cell Precursors and CD11c+ Dendritic Cells to Produce Type I IFN (2001)

Two classes of nucleic acids, bacterial DNA containing unmethylated CpG motifs and dsRNA in viruses, induce the production of type I IFN that contributes to the immunostimulatory effects of these microbial molecules. Thus, it is important to determine which cells produce type I IFN in response to CpG DNA and dsRNA. CD4(+)CD11c(-) type 2 dendritic cell precursors (pre-DC2) were identified as the main producers of type I IFN in human blood in response to viruses. Here we asked whether pre-DC2 also produce type I IFN in response to CpG DNA and dsRNA. Oligodeoxynucleotides containing particular palindromic CpG motifs induced pre-DC2, but not CD11c(+) blood DC or monocytes, to produce IFN-alpha. In contrast, a synthetic dsRNA, polyinosinic polycytidylic-acid, induced CD11c(+) DC, but not pre-DC2 or monocytes, to produce IFN-alphabeta. These data indicate that CpG DNA and polyinosinic-polycytidylic acid stimulate different types of cells to produce type I IFN and that it is important to select oligodeoxynucleotides containing particular CpG motifs to induce pre-DC2 to produce type I IFN, which may play a key role in the strong adjuvant effects of CpG DNA.
Identification and Characterization of the Dystrophin Anchoring Site on β-Dystroglycan (1995)

Dystrophin, the product of the Duchenne muscular dystrophy gene, is tightly associated with the sarcolemmal membrane to a large glycoprotein complex. One function of the dystrophin-glycoprotein complex is to link the cytoskeleton to the extracellular matrix in skeletal muscle. However, the molecular interactions of dystrophin with the membrane components of the dystrophin-glycoprotein complex are still elusive. Here, we demonstrate and characterize a specific interaction between beta-dystroglycan and dystrophin. We show that skeletal muscle and brain dystrophin as well as brain dystrophin isoforms specifically bind to beta-dystroglycan. To localize and characterize the dystrophin and beta-dystroglycan interaction domains, we reconstituted the interaction in vitro using dystrophin fusion proteins and in vitro translated beta-dystroglycan. We demonstrated that the 15 C-terminal amino acids of beta-dystroglycan constituted a unique binding site for the second half of the hinge 4 and the cysteine-rich domain of dystrophin (amino acids 3054-3271). This dystrophin binding site is located in a proline-rich environment of beta-dystroglycan within amino acids 880-895. The identification of the interaction sites in dystrophin and beta-dystroglycan provides further insight into the structure and the molecular organization of the dystrophin-glycoprotein complex at the sarcolemma membrane and will be helpful for studying the pathogenesis of Duchenne muscular dystrophy.
Quantitative model of diffuse speckle contrast analysis for flow measurement (2017)

Diffuse speckle contrast analysis (DSCA) is a noninvasive optical technique capable of monitoring deep tissue blood flow. However, a detailed study of the speckle contrast model for DSCA has yet to be presented. We deduced the theoretical relationship between speckle contrast and exposure time and further simplified it to a linear approximation model. The feasibility of this linear model was validated by the liquid phantoms which demonstrated that the slope of this linear approximation was able to rapidly determine the Brownian diffusion coefficient of the turbid media at multiple distances using multiexposure speckle imaging. Furthermore, we have theoretically quantified the influence of optical property on the measurements of the Brownian diffusion coefficient which was a consequence of the fact that the slope of this linear approximation was demonstrated to be equal to the inverse of correlation time of the speckle.
Molecular Recognition at Adenine Nucleotide (P2) Receptors in Platelets (2005)

Transmembrane signaling through P2Y receptors for extracellular nucleotides controls a diverse array of cellular processes, including thrombosis. Selective agonists and antagonists of the two P2Y receptors present on the platelet surface-the G (q)-coupled P2Y (1) subtype and the G (i)-coupled P2Y (12) subtype-are now known. High-affinity antagonists of each have been developed from nucleotide structures. The (N)-methanocarba bisphosphate derivatives MRS2279 and MRS2500 are potent and selective P2Y (1) receptor antagonists. The carbocyclic nucleoside AZD6140 is an uncharged, orally active P2Y (12) receptor antagonist of nM affinity. Another nucleotide receptor on the platelet surface, the P2X (1) receptor, the activation of which may also be proaggregatory, especially under conditions of high shear stress, has high-affinity ligands, although high selectivity has not yet been achieved. Although alpha,beta-methylene-adenosine triphosphate (ATP) is the classic agonist for the P2X (1) receptor, where it causes rapid desensitization, the agonist BzATP is among the most potent in activating this subtype. The aromatic sulfonates NF279 and NF449 are potent antagonists of the P2X (1) receptor. The structures of the two platelet P2Y receptors have been modeled, based on a rhodopsin template, to explain the basis for nucleotide recognition within the putative transmembrane binding sites. The P2Y (1) receptor model, especially, has been exploited in the design and optimization of antagonists targeted to interact selectively with that subtype.
Schistosoma mansoni Fatty Acid Binding Protein:  Specificity and Functional Control as Revealed by Crystallographic Structure, (2004)

Schistosoma mansoni fatty acid binding protein (Sm14) was crystallized with bound oleic acid (OLA) and arachidonic acid (ACD), and their structures were solved at 1.85 and 2.4 A resolution, respectively. Sm14 is a vaccine target for schistosomiasis, the second most prevalent parasitic disease in humans. The parasite is unable to synthesize fatty acids depending on the host for these nutrients. Moreover, arachidonic acid (ACD) is required to synthesize prostaglandins employed by schistosomes to evade the host's immune defenses. In the complex, the hydrocarbon tail of bound OLA assumes two conformations, whereas ACD adopts a unique hairpin-looped structure. ACD establishes more specific interactions with the protein, among which the most important is a pi-cation bond between Arg78 and the double bond at C8. Comparison with homologous fatty acid binding proteins suggests that the binding site of Sm14 is optimized to fit ACD. To test the functional implications of our structural data, the affinity of Sm14 for 1,8-anilinonaphthalenesulfonic acid (ANS) has been measured; moreover the binding constants of six different fatty acids were determined from their ability to displace ANS. OLA and ACD exhibited the highest affinities. To determine the rates of fatty acid binding and dissociation we carried out stopped flow kinetic experiments monitoring displacement by (and of) ANS. The binding rate constant of ligands is controlled by a slow pH dependent conformational change, which we propose to have physiological relevance.
P-Chiral Bis(trialkylphosphine) Ligands and Their Use in Highly Enantioselective Hydrogenation Reactions (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTP-Chiral Bis(trialkylphosphine) Ligands and Their Use in Highly Enantioselective Hydrogenation ReactionsTsuneo Imamoto, Junko Watanabe, Yoshiyuki Wada, Hideki Masuda, Hironari Yamada, Hideyuki Tsuruta, Satoru Matsukawa, and Kentaro YamaguchiView Author Information Department of Chemistry, Faculty of Science and Chemical Analysis Center, Chiba University Yayoi-cho, Inage-ku, Chiba 263-8522, Japan Material R & D Laboratories, Ogawa and Co., Ltd. Shoo-cho, Katsuta, Okayama 709-4321, Japan Cite this: J. Am. Chem. Soc. 1998, 120, 7, 1635–1636Publication Date (Web):February 6, 1998Publication History Received1 October 1997Published online6 February 1998Published inissue 1 February 1998https://pubs.acs.org/doi/10.1021/ja973423ihttps://doi.org/10.1021/ja973423irapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views3716Altmetric-Citations329LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Alkyls,Catalysts,Group 15 compounds,Ligands,Reaction products Get e-Alerts
Pulse radiolytic studies of the reaction of perhydroxyl/superoxide O2- with iron(II)/iron(III) ions. The reactivity of HO2/O2- with ferric ions and its implication on the occurrence of the Haber-Weiss reaction (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPulse radiolytic studies of the reaction of perhydroxyl/superoxide O2- with iron(II)/iron(III) ions. The reactivity of HO2/O2- with ferric ions and its implication on the occurrence of the Haber-Weiss reactionJames D. Rush and Benon H. J. BielskiCite this: J. Phys. Chem. 1985, 89, 23, 5062–5066Publication Date (Print):November 1, 1985Publication History Published online1 May 2002Published inissue 1 November 1985https://pubs.acs.org/doi/10.1021/j100269a035https://doi.org/10.1021/j100269a035research-articleACS PublicationsRequest reuse permissionsArticle Views935Altmetric-Citations286LEARN 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 options Get e-Alerts
Imparting Catalyst Control upon Classical Palladium-Catalyzed Alkenyl C–H Bond Functionalization Reactions (2011)

The functional group transformations carried out by the palladium-catalyzed Wacker and Heck reactions are radically different, but they are both alkenyl C-H bond functionalization reactions that have found extensive use in organic synthesis. The synthetic community depends heavily on these important reactions, but selectivity issues arising from control by the substrate, rather than control by the catalyst, have prevented the realization of their full potential. Because of important similarities in the respective selectivity-determining nucleopalladation and β-hydride elimination steps of these processes, we posit that the mechanistic insight garnered through the development of one of these catalytic reactions may be applied to the other. In this Account, we detail our efforts to develop catalyst-controlled variants of both the Wacker oxidation and the Heck reaction to address synthetic limitations and provide mechanistic insight into the underlying organometallic processes of these reactions. In contrast to previous reports, we discovered that electrophilic palladium catalysts with noncoordinating counterions allowed for the use of a Lewis basic ligand to efficiently promote tert-butylhydroperoxide (TBHP)-mediated Wacker oxidation reactions of styrenes. This discovery led to the mechanistically guided development of a Wacker reaction catalyzed by a palladium complex with a bidentate ligand. This ligation may prohibit coordination of allylic heteroatoms, thereby allowing for the application of the Wacker oxidation to substrates that were poorly behaved under classical conditions. Likewise, we unexpectedly discovered that electrophilic Pd-σ-alkyl intermediates are capable of distinguishing between electronically inequivalent C-H bonds during β-hydride elimination. As a result, we have developed E-styrenyl selective oxidative Heck reactions of previously unsuccessful electronically nonbiased alkene substrates using arylboronic acid derivatives. The mechanistic insight gained from the development of this chemistry allowed for the rational design of a similarly E-styrenyl selective classical Heck reaction using aryldiazonium salts and a broad range of alkene substrates. The key mechanistic findings from the development of these reactions provide new insight into how to predictably impart catalyst control in organometallic processes that would otherwise afford complex product mixtures. Given our new understanding, we are optimistic that reactions that introduce increased complexity relative to simple classical processes may now be developed based on our ability to predict the selectivity-determining nucleopalladation and β-hydride elimination steps through catalyst design.
An Empirical Study of HTTP-based Financial Botnets (2014)

Cyber criminals are covertly attacking critical infrastructures, and botnets are a common component of those attacks. In recent years, botnets have been shifting their focus from broad-based attacks to more targeted ones such as attacking financial institutions, especially banks. The primary reason for this shift towards financial institutions is that, where the money is. We present an empirical study of the components, features and operations of some of the most widely deployed HTTP-based financial botnets (such as Zeus, SpyEye, ICE 1X, Citadel, Carberp, Tinba, Bugat and Shylock). Our study provides critical insights into the design of these botnets and should help the security community to generate intelligence and develop more robust security solutions to defend against cyber attacks by these botnets. In addition, our comparative analysis of insidious techniques pertaining to Command and Control (C&C) communication, system exploitation and data exfiltration also provides an effective and a holistic view of the capabilities of HTTP-based financial botnets. This study also highlights the evolution of various HTTP-based financial botnets over a period of time. Finally, we discuss security solutions that can help mitigate some of the techniques used by HTTP-based financial botnets.
A Time-Frequency Based Approach for Acoustic Emission Assessment of Sliding Wear (2020)

The acoustic emission method is one of few contemporary non-destructive testing techniques enabling continuous on-line health monitoring and control of tribological systems. However, the existence of multiple “pseudo”-acoustic emission (AE) and noise sources during friction, and their random occurrence poses serious challenges for researchers and practitioners when extracting “useful” information from the upcoming AE signal. These challenges and numerous uncertainties in signal classification prevent the unequivocal interpretation of results and hinder wider uptake of the AE technique despite its apparent advantages. Currently, the signal recording and processing technologies are booming, and new applications are born on this support. Specific tribology applications, therefore, call for developing new and tuning existing approaches to the online AE monitoring and analysis. In the present work, we critically analyze, compare and summarize the results of the application of several filtering techniques and AE signal classifiers in model tribological sliding friction systems allowing for the simulation of predominant wear mechanisms. Several effective schemes of AE data processing were identified through extensive comparative studies. Guidelines were provided for practical application, including the online monitoring and control of the systems with friction, characterizing the severity and timing of damage, on-line evaluation of wear as sliding contact tests and instrumented acceleration of tribological testing and cost reduction.
A Reassessment of the FNR Regulon and Transcriptomic Analysis of the Effects of Nitrate, Nitrite, NarXL, and NarQP as Escherichia coli K12 Adapts from Aerobic to Anaerobic Growth (2005)

The transcription factor FNR, the regulator of fumarate and nitrate reduction, regulates major changes as Escherichia coli adapts from aerobic to anaerobic growth. In an anaerobic glycerol/trimethylamine N-oxide/fumarate medium, the fnr mutant grew as well as the parental strain, E. coli K12 MG1655, enabling us to reveal the response to oxygen, nitrate, and nitrite in the absence of glucose repression or artifacts because of variations in growth rate. Hence, many of the discrepancies between previous microarray studies of the E. coli FNR regulon were resolved. The current microarray data confirmed 31 of the previously characterized FNR-regulated operons. Forty four operons not previously known to be included in the FNR regulon were activated by FNR, and a further 28 operons appeared to be repressed. For each of these operons, a match to the consensus FNR-binding site sequence was identified. The FNR regulon therefore minimally includes at least 103, and possibly as many as 115, operons. Comparison of transcripts in the parental strain and a narXL deletion mutant revealed that transcription of 51 operons is activated, directly or indirectly, by NarL, and a further 41 operons are repressed. The narP gene was also deleted from the narXL mutant to reveal the extent of regulation by phosphorylated NarP. Fourteen promoters were more active in the narP+ strain than in the mutant, and a further 37 were strongly repressed. This is the first report that NarP might function as a global repressor as well as a transcription activator. The data also revealed possible new defense mechanisms against reactive nitrogen species.
Influence of Fat and Emulsifiers on the Efficacy of Nisin in Inhibiting Listeria monocytogenes in Fluid Milk (1992)

The recent FDA affirmation of nisin, an antimicrobial peptide, as a GRAS (generally recognized as safe) additive in pasteurized cheese spreads has renewed interest in its potential application in US dairy products. Fluid milks were prepared with varying concentrations of milk fat (0 to 12.9%) and of nisin (0 to 50 U/ml). Biological activity assays using a sensitive indicator microorganism in a well diffusion system indicated that initial nisin activity (50 U/ml) decreased by about 33% when it was added to skim milk and by more than 88% when added to milk containing 12.9% fat. Nisin activity decreased by ca. 50% in milk containing 1.29% fat. Milks containing 0, 10, or 50 U/ml of nisin and varying fat percentages were challenged with approximately log10 7 to 7.5 cfu/ml of log phase Listeria monocytogenes Scott A or Jalisco. At 2 h after inoculation, the viable count of L. monocytogenes Scott A decreased to log10 .30 cfu/ml in skim milk with 50 U/ml of nisin, decreased to log10 2.90 cfu/ml in skim milk with 10 U/ml of nisin, and increased slightly (log10 7.8 cfu/ml) in skim milk without nisin. In half-and-half (12.9% milk fat), nisin was far less effective in inhibiting Listeria with populations decreasing to log10 6.57 cfu/ml for 10 U/ml of nisin and log10 5.87 cfu/ml for 50 U/ml. Similar results were obtained with L. monocytogenes Jalisco. The nonionic emulsifier, Tween 80, partially counteracted decreases of nisin activity in milks, whereas the anionic emulsifier, lecithin, had no effect. Addition of Tween 80 significantly increased the activity of nisin against L. monocytogenes in milk regardless of fat content.
The Alzheimer disease-associated amyloid beta protein precursor gene and familial Alzheimer disease. (1990)

The application of recombinant DNA techniques to AD and DS pathogenesis have provided the molecular biological reagents necessary to delineate the crucial events in the neurodegenerative process in these disorders. Critical issues which remain to be solved include: which form of APP gives rise to beta amyloid deposits and from what cells is it derived? How is APP normally processed and degraded, and does its metabolism differ in various brain regions and cell types in AD and DS patients? Is amyloid toxic to neurons and able to induce NFT formation characteristic of dying neurons or is amyloid simply a secondary by-product of degenerating neurons and nerve terminals in affected regions of AD and DS brain? What is the physical relationship between intracellular amyloid and NFT and how are NFT involved with neuronal cell death? Answers to these questions should elucidate the final events in the degenerative process and provide valuable insights into the basic etiology underlying AD and DS. Meanwhile, isolation and identification of the FAD gene defect on chromosome 21 would provide direct information about the primary cause of FAD. Intensive molecular investigations aimed at deciphering the neuropathogenetic process in AD and DS will hopefully provide valuable biological clues about the primary defect in AD as well as ways to ameliorate the symptoms of both AD and DS.