gebhart/patrepeval huggingface dataset:
Solution Structural Study of a DNA Duplex Containing the Guanine-N7 Adduct Formed by a Cytotoxic Platinum−Acridine Hybrid Agent, (2005)

[PtCl(en)(ACRAMTU-S)](NO(3))(2) (PT-ACRAMTU; en = ethane-1,2-diamine, ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea) is a dual metalating/intercalating DNA binding drug conjugate that shows cytotoxicity at micromolar to nanomolar concentrations in a wide range of solid tumor cell lines. In approximately 80% of its adducts, PT-ACRAMTU binds to guanine-N7 in the major groove, selectively at 5'-CG sites [Budiman, M. E. et al. (2004) Biochemistry 43, 8560-8567]. Here, we report the synthesis, physical characterization, and NMR solution structure of a site-specifically modified octamer containing this adduct, 5'-CCTCGTCC-3'/3'-GGAGCAGG-5', where the asterisk indicates the [Pt(en)ACRAMTU)](3+) fragment. The structure was determined by a combination of high-resolution 2-D NMR spectroscopy and restrained molecular dynamics/molecular mechanics (rMD/MM) calculations using 179 NOE distance restraints and refined to an r(6) weighted residual (R(x)) of 9.2 x 10(-)(2) using the complete relaxation matrix approach. An average structure was calculated from the final ensemble of 19 rMD geometries showing pairwise root-mean-square deviations of <1.05 A. The dual binding increases the thermal stability of the octamer compared to the unmodified duplex (DeltaT(m) = 13.2 degrees ). The modified sequence shows structural features reminiscent of both B- and A-type DNA. Watson-Crick hydrogen bonding is intact at and beyond the adduct site. Platinum is bound to the N7 position of G5 in the major groove, and ACRAMTU intercalates into the central 5'-C4G5/C12G13 base-pair step on the 5'-face of the platinated nucleobase. The chromophore's long axis is aligned with the long axes of the adjacent base pairs, maximizing intermolecular pi-pi stacking interactions. PT-ACRAMTU lengthens (rise, 6.62 A) and unwinds (twist, 15.4 degrees ) the duplex at the central base-pair step but does not cause helical bending. No C3'-endo deoxyribose pucker and no significant roll are observed at the site of intercalation/platination, which clearly distinguishes the PT-ACRAMTU-induced damage from the 1,2-intrastrand cross-link formed by cisplatin. Overall, the DNA perturbations produced by PT-ACRAMTU do not appear to mimic those caused by the major cisplatin lesion. Instead, intriguing structural similarities are observed for PT-ACRAMTU's monoadduct and the N7 adducts of dual major-groove alkylating/intercalating antitumor agents, such as the pluramycins.
Directing cell therapy to anatomic target sites in vivo with magnetic resonance targeting (2015)

Cell-based therapy exploits modified human cells to treat diseases but its targeted application in specific tissues, particularly those lying deep in the body where direct injection is not possible, has been problematic. Here we use a magnetic resonance imaging (MRI) system to direct macrophages carrying an oncolytic virus, Seprehvir, into primary and metastatic tumour sites in mice. To achieve this, we magnetically label macrophages with super-paramagnetic iron oxide nanoparticles and apply pulsed magnetic field gradients in the direction of the tumour sites. Magnetic resonance targeting guides macrophages from the bloodstream into tumours, resulting in increased tumour macrophage infiltration and reduction in tumour burden and metastasis. Our study indicates that clinical MRI scanners can not only track the location of magnetically labelled cells but also have the potential to steer them into one or more target tissues.
Strategies for measuring evolutionary conservation of RNA secondary structures (2008)

Structural conservation can be measured accurately with relatively simple and intuitive metrics. They have the potential to form the basis of future RNA gene finders, that face new challenges like finding lineage specific structures or detecting mis-aligned sequences.
The polyphyletic nature ofPaecilomyces sensu latobased on 18S-generated rDNA phylogeny (2004)

Nuclear-encoded small-subunit ribosomal DNA was used to examine phylogenetic relationships in Paecilomyces sensu lato. Phylogenetic analysis of the 18S nr DNA demonstrates that Paecilomyces is polyphyletic across two subclasses, Sordariomycetidae and Eurotiomycetidae. The type species, Paecilomyces variotii, and thermophilic relatives belong in the order Eurotiales (Trichocomaceae), while mesophilic species related to Paecilomyces farinosus are in the order Hypocreales (Clavicipitaceae and Hypocreaceae). One species, Paecilomyces inflatus, had affinities for the order Sordariales. Within the Eurotiales, Paecilomyces is monophyletic. Within the Hypocreales, species of Paecilomyces are polyphyletic, although the data failed to fully resolve these relationships.
Role of glandular kallikreins as growth factor processing enzymes: Structural and evolutionary considerations (1987)

Hormones and growth factors are generally released from larger precursors by limited proteolysis. The causative agents remain poorly defined with respect to location and properties. One subset of proteases, the glandular kallikreins, have been implicated in a few cases, in part because of their specific association with mature forms of some hormones. However, limited distribution and low copy number in some species cast doubt on this hypothesis, and they may well play other physiological functions that remain to be elucidated.
Effect of the Nature of Metallocene Complexes of Group IV Metals on Their Performance in Catalytic Ethylene and Propylene Polymerization (2000)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEffect of the Nature of Metallocene Complexes of Group IV Metals on Their Performance in Catalytic Ethylene and Propylene PolymerizationHelmut G. Alt and Alexander KöpplView Author Information Laboratorium für Anorganische Chemie, Universität Bayreuth, D-95440 Bayreuth, Germany Cite this: Chem. Rev. 2000, 100, 4, 1205–1222Publication Date (Web):March 14, 2000Publication History Received23 July 1999Published online14 March 2000Published inissue 1 April 2000https://pubs.acs.org/doi/10.1021/cr9804700https://doi.org/10.1021/cr9804700research-articleACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views7890Altmetric-Citations963LEARN 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:Catalysts,Hydrocarbons,Ligands,Sandwich compounds,Substituents Get e-Alerts
Models and Inference for Prefix-Constrained Machine Translation (2016)

We apply phrase-based and neural models to a core task in interactive machine translation: suggesting how to complete a partial translation. For the phrase-based system, we demonstrate improvements in suggestion quality using novel objective functions, learning techniques, and inference algorithms tailored to this task. Our contributions include new tunable metrics, an improved beam search strategy, an n-best extraction method that increases suggestion diversity, and a tuning procedure for a hierarchical joint model of alignment and translation. The combination of these techniques improves next-word suggestion accuracy dramatically from 28.5% to 41.2% in a large-scale English-German experiment. Our recurrent neural translation system increases accuracy yet further to 53.0%, but inference is two orders of magnitude slower. Manual error analysis shows the strengths and weaknesses of both approaches.
A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans (1999)

An insulin receptor-like signaling pathway regulates Caenorhabditis elegans metabolism, development, and longevity. Inactivation of the insulin receptor homolog DAF-2, the AGE-1 PI3K, or the AKT-1 and AKT-2 kinases causes a developmental arrest at the dauer stage. A null mutation in the daf-16 Fork head transcription factor alleviates the requirement for signaling through this pathway. We show here that a loss-of-function mutation in pdk-1, the C. elegans homolog of the mammalian Akt/PKB kinase PDK1, results in constitutive arrest at the dauer stage and increased life span; these phenotypes are suppressed by a loss of function mutation in daf-16. An activating mutation in pdk-1 or overexpression of wild-type pdk-1 relieves the requirement for AGE-1 PI3K signaling. Therefore, pdk-1 activity is both necessary and sufficient to propagate AGE-1 PI3K signals in the DAF-2 insulin receptor-like signaling pathway. The activating mutation in pdk-1 requires akt-1 and akt-2 gene activity in order to suppress the dauer arrest phenotype of age-1. This indicates that the major function of C. elegans PDK1 is to transduce signals from AGE-1 to AKT-1 and AKT-2. The activating pdk-1 mutation is located in a conserved region of the kinase domain; the equivalent amino acid substitution in human PDK1 activates its kinase activity toward mammalian Akt/PKB.
Two Novel Nonlinear Companding Schemes With Iterative Receiver to Reduce PAPR in Multi-Carrier Modulation Systems (2006)

Companding transform is an efficient and simple method to reduce the Peak-to-Average Power Ratio (PAPR) for Multi-Carrier Modulation (MCM) systems. But if the MCM signal is only simply operated by inverse companding transform at the receiver, the resultant spectrum may exhibit severe in-band and out-of-band radiation of the distortion components, and considerable peak regrowth by excessive channel noises etc. In order to prevent these problems from occurring, in this paper, two novel nonlinear companding schemes with a iterative receiver are proposed to reduce the PAPR. By transforming the amplitude or power of the original MCM signals into uniform distributed signals, the novel schemes can effectively reduce PAPR for different modulation formats and sub-carrier sizes. Despite moderate complexity increasing at the receiver, but it is especially suitable to be combined with iterative channel estimation. Computer simulation results show that the proposed schemes can offer good system performances without any bandwidth expansion.
Diels‐alder cycloadditions of N‐substituted‐1,2‐dihydropyridines with 1,2,4‐triazoline‐3,5‐diones and maleimides (1976)

Abstract The reaction of N ‐substituted‐1,2‐dihydropyridines 1 with 1,2,4‐triazoline‐3.5‐diones 2 and maleimides 9 proceeds stereospecifically to afford endo cycloaddition products. N ‐Acetyl‐1,2‐dihydropyridines react with 2 to afford a stereo isomeric mixture of 3 and 4 whereas those possessing a N ‐ethoxycarbonyl, methoxycarbonyl, methanesulfonyl or benzenesulfonyl substituent yield 3 exclusively: similar results are also obtained in reactions employing maleimides. Stereochemistry was assigned on the basis of nmr data and use was made of the anisotropic effects of the 7,8 unsaturation on the R 1 and R 2 substituents.
Massive Arrays of Idle Disks For Storage Archives (2002)

The declining costs of commodity disk drives is rapidly changing the economics of deploying large amounts of online or near-line storage. Conventional mass storage systems use either high performance RAID clusters, automated tape libraries or a combination of tape and disk. In this paper, we analyze an alternative design using massive arrays of idle disks, or MAID. We argue that this storage organization provides storage densities matching or exceeding those of tape libraries with performance similar to disk arrays. Moreover, we show that with effective power management of individual drives, this performance can be achieved using a very small power budget. In particular, we show that our power management strategy can result in the performance comparable to an always-on RAID system while using 1/15th the power of such a RAID system.
Palladium-Catalyzed Cross-Coupling Reactions of 4-Tosyl-2(5H)-furanone with Boronic Acids:  A Facile and Efficient Route to Generate 4-Substituted 2(5H)-Furanones (2002)

An efficient and facile synthesis of 4-substituted 2(5H)-furanones using palladium catalyzed cross-coupling reactions between 4-tosyl-2(5H)-furanone and boronic acids is reported herein.
Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies (2015)

Pancreatic cancer is the fourth leading cause of cancer death in the US and is expected to become the second leading cause of cancer-related deaths in the next decade. Despite 5-fluorouracil/leucovorin with irinotecan and oxaliplatin (FOLFIRINOX) and gemcitabine/nab-paclitaxel significantly improving outcomes for metastatic cancer, refractory disease still poses significant challenges. Difficulties with early detection and the inherent chemo- and radio-resistant nature of this malignancy led to attempts to define the sequential biology of pancreatic cancer in order to improve survival outcomes. Pancreatic adenocarcinoma is characterized by several germline or acquired genetic mutations, the most common being KRAS (90%), CDK2NA (90%), TP53 (75%-90%), DPC4/SMAD4 (50%). In addition, the tumor microenvironment, chemoresistant cancer stem cells, and the desmoplastic stroma have been the target of some promising clinical investigations. Among the core pathways reproducibly shown to lead the development and progression of this disease, DNA repair, apoptosis, G1/S cell cycle transition, KRAS, Wnt, Notch, Hedgehog, TGF-beta, and other cell invasion pathways, have been the target of "precision therapeutics". No single molecularly targeted therapeutic though has been uniformly successful, probably due to the tumor heterogeneity, but biomarker research is evolving and it hopes to select more patients likely to benefit. Recent reports note activity with immunotherapies such as CD40 agonists, CCR2 inhibitors, cancer vaccines, and novel combinations against the immunosuppressive tumor milieu are ongoing. While many obstacles still exist, clearly we are making progress in deciphering the heterogeneity within pancreatic cancers. Integrating conventional and immunological targeting will be the key to effective treatment of this deadly disease.
Design of novel FN3 domains with high stability by a consensus sequence approach (2012)

The use of consensus design to produce stable proteins has been applied to numerous structures and classes of proteins. Here, we describe the engineering of novel FN3 domains from two different proteins, namely human fibronectin and human tenascin-C, as potential alternative scaffold biotherapeutics. The resulting FN3 domains were found to be robustly expressed in Escherichia coli, soluble and highly stable, with melting temperatures of 89 and 78°C, respectively. X-ray crystallography was used to confirm that the consensus approach led to a structure consistent with the FN3 design despite having only low-sequence identity to natural FN3 domains. The ability of the Tenascin consensus domain to withstand mutations in the loop regions connecting the β-strands was investigated using alanine scanning mutagenesis demonstrating the potential for randomization in these regions. Finally, rational design was used to produce point mutations that significantly increase the stability of one of the consensus domains. Together our data suggest that consensus FN3 domains have potential utility as alternative scaffold therapeutics.
Electrodeposition of Silicon in Organic Solvent Containing Silicon Chloride (2009)

In this paper it was investigated that silicon be electrodeposited in the room temperature from propylene carbonate solvent. Cyclic voltammograms indicated that it was possible to electrochemical reduction of silicon chloride at -2.3984V versuHg/Hg2Cl2/ KCl (saturation) quasi-reference electrode. Potentiostatic electrolysis yielded deposits, accompanied by the change in electrolyte color from transparent to brown. Scanning electron microscopy (SEM) and energy dispersion spectroscopy (EDS) were used to characterize the physical properties of the silicon. The EDS analysis performed simultaneously with SEM observation demonstrates that the deposit consists of Si, O and Cl.
Fragment-Based Substrate Activity Screening Method for the Identification of Potent Inhibitors of the Mycobacterium tuberculosis Phosphatase PtpB (2007)

A new substrate-based fragment approach for the identification of novel PTP inhibitors is presented. This method was applied to Mycobacterium tuberculosis PtpB, a promising new target for the treatment of tuberculosis. This resulted in the development of the most potent PtpB inhibitor reported to date (0.22 μM) with low molecular weight and good selectivity against a panel of other protein tyrosine phosphatases.
Molecular Characterization of a Purified 5-HT4 Receptor (2005)

Serotonin 5-HT(4(a)) receptor, a G-protein-coupled receptor (GPCR), was produced as a functional isolated protein using Escherichia coli as an expression system. The isolated receptor was characterized at the molecular level by circular dichroism (CD) and steady-state fluorescence. A specific change in the near-UV CD band associated with the GPCR disulfide bond connecting the third transmembrane domain to the second extracellular loop (e2) was observed upon agonist binding to the purified receptor. This is a direct experimental evidence for a change in the conformation of the e2 loop upon receptor activation. Different variations were obtained depending whether the ligand was an agonist (partial or full) or an inverse agonist. In contrast, antagonist binding did not induce any variation. These observations provide a first direct evidence for the fact that free (or antagonist-occupied), active (partial- or full agonist-occupied) and silent (inverse agonist-occupied) states of the receptor involve different arrangements of the e2 loop. Finally, ligand-induced changes in the fluorescence emission profile of the purified receptor confirmed that the partial agonist stabilized a single, well-defined, conformational state and not a mixture of different states. This result is of particular interest in a pharmacological perspective since it directly demonstrates that the efficacy of a drug is likely due to the stabilization of a ligand-specific state rather than selection of a mixture of different conformational states of the receptor.
Combinatorial approach for the synthesis of terpolymers and their novel application as very-high-contrast resists for x-ray nanolithography (2000)

Novel resist systems for x-ray lithography, specifically optimized in terms of contrast enhancement are described. Based on terpolymers of methyl methacrylate (MMA)-tert-butylacrylate-polyhedral oligosilsesquioxanes (POSS) synthesized by solution polymerization, these systems were optimized by a combinatorial approach. It is shown that the mass ratio of MMA/POSS=85.7/14.3 leads to maximum contrast (23.5) without sacrificing the sensitivity (1350 mJ/cm2) which remains comparable to that of standard PMMA. Such major contrast enhancement shows that the above organic/inorganic nanocomposites are promising candidates for sub-100 nm lithography.
Cu(In,Ga)Se2 Thin Film Preparation from a Cu(In,Ga) Metallic Alloy and Se Nanoparticles by an Intense Pulsed Light Technique (2010)

The main contribution of this paper is the development of a novel process for the formation of copper indium gallium diselenide (CIGS) films. CIGS films with a thickness of 4 μm and grain size from 0.3 μm to 1 μm were prepared from a Cu(In0.7Ga0.3) (CIG) metallic alloy and Se nanoparticles by the intense pulsed light (IPL) technique. The melting of the CIG and Se nanoparticles and nucleation of CIGS occurred in a very short reaction time of 2 ms. It is believed that the Se diffuses into the CIG lattice to form the CIGS chalcopyrite crystal structure. The tetragonal chalcopyrite crystal structure was confirmed by x-ray powder diffraction (XRD), while the microstructure and composition were determined by field-emission scanning electron microscopy (FESEM), energy-dispersive x-ray spectroscopy (EDAX), and x-ray fluorescence (XRF) spectroscopy.
Emergency Nurses' Utilization of Ultrasound Guidance for Placement of Peripheral Intravenous Lines in Difficult‐access Patients (2004)

ENs had a high success rate and few complications with use of US guidance for vascular access in a variety of difficult-access patients.
Nanomaterials for Wound Healing and Infection Control (2019)

Wound healing has been intensely studied in order to develop an "ideal" technique that achieves expeditious recovery and reduces scarring to the minimum, thus ensuring function preservation. The classic approach to wound management is represented by topical treatments, such as antibacterial or colloidal agents, in order to prevent infection and promote a proper wound-healing process. Nanotechnology studies submicroscopic particles (maximum diameter of 100 nm), as well as correlated phenomena. Metal nanoparticles (e.g., silver, gold, zinc) are increasingly being used in dermatology, due to their beneficial effect on accelerating wound healing, as well as treating and preventing bacterial infections. Other benefits include: ease of use, less frequent dressing changes and a constantly moist wound environment. This review highlights recent findings regarding nanoparticle application in wound management.
An Open-Label, Phase I Study of the Polo-like Kinase-1 Inhibitor, BI 2536, in Patients with Advanced Solid Tumors (2010)

BI 2536 administered in either treatment schedule has adequate safety in patients with advanced solid tumors, warranting further clinical investigation of polo-like kinase-1 inhibitors.
Interleukin 1 plays a major role in the development of Th2‐mediated immunity (2004)

Expulsion of the gastrointestinal nematode Trichuris muris is mediated by a T helper (Th)2-type response, involving interleukin (IL)-4, IL-9 and IL-13. Here, we show that Th2 response-associated resistance is dependent on the presence of IL-1alpha and IL-1beta. When lymph node cells from naive IL-1alpha- or IL-1beta-deficient mice were subjected to Th2 polarization in vitro, they failed to polarize in the presence of IL-4 alone, but required the addition of exogenous IL-1alpha or IL-1beta. Furthermore, we demonstrate that both IL-1alpha- and IL-1beta-deficient mice are susceptible to chronic T. muris infection and that the inability to expel the worms is associated with a defect in the development of a Th2 response in the mesenteric lymph nodes. These results provide the first demonstration of the critical role of IL-1 in regulating Th2 responses during gastrointestinal nematode infection.
MPEG-compliant joint source/channel coding using discrete cosine transform and substream scheduling for visual communication over packet networks (2001)

The <i>Journal of Electronic Imaging</i> (JEI), copublished bimonthly with the Society for Imaging Science and Technology, publishes peer-reviewed papers that cover research and applications in all areas of electronic imaging science and technology.
The trouble with replication (2006)

Ever wondered whether half the stuff in Nature is worth doing again? Or could be done again if it was worth it? The question of replication of scientific results is an important one, and we take the 4 July 2002 issue of Nature as a test case. The answers are fascinating and relevant to some of the latest innovations in science publishing.