gebhart/patrepeval huggingface dataset:
Biochemical characterization of a <i>Neisseria meningitidis</i> polysialyltransferase reveals novel functional motifs in bacterial sialyltransferases (2007)

The extracellular polysaccharide capsule is an essential virulence factor of Neisseria meningitidis, a leading cause of severe bacterial meningitis and sepsis. Serogroup B strains, the primary disease causing isolates in Europe and America, are encapsulated in alpha-2,8 polysialic acid (polySia). The capsular polymer is synthesized from activated sialic acid by action of a membrane-associated polysialyltransferase (NmB-polyST). Here we present a comprehensive characterization of NmB-polyST. Different from earlier studies, we show that membrane association is not essential for enzyme functionality. Recombinant NmB-polyST was expressed, purified and shown to synthesize long polySia chains in a non-processive manner in vitro. Subsequent structure-function analyses of NmB-polyST based on refined sequence alignments allowed the identification of two functional motifs in bacterial sialyltransferases. Both (D/E-D/E-G and HP motif) are highly conserved among different sialyltransferase families with otherwise little or no sequence identity. Their functional importance for enzyme catalysis and CMP-Neu5Ac binding was demonstrated by mutational analysis of NmB-polyST and is emphasized by structural data available for the Pasteurella multocida sialyltransferase PmST1. Together our data are the first description of conserved functional elements in the highly diverse families of bacterial (poly)sialyltransferases and thus provide an advanced basis for understanding structure-function relations and for phylogenetic sorting of these important enzymes.
Nucleic Acid Interactions. VI. Effects of Steroidal Diamines<sup>*</sup> (1966)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNucleic Acid Interactions. VI. Effects of Steroidal Diamines*H. R. Mahler, Robert Goutarel, Qui Khuong-Huu, and Minh Truong HoCite this: Biochemistry 1966, 5, 7, 2177–2191Publication Date (Print):July 1, 1966Publication History Published online1 May 2002Published inissue 1 July 1966https://pubs.acs.org/doi/10.1021/bi00871a005https://doi.org/10.1021/bi00871a005research-articleACS PublicationsRequest reuse permissionsArticle Views42Altmetric-Citations26LEARN 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
Synthesis and Characterization of Star Poly(ε-caprolactone)-<i>b</i>-Poly(ethylene glycol) and Poly(<scp>l</scp>-lactide)-<i>b</i>-Poly(ethylene glycol) Copolymers: Evaluation as Drug Delivery Carriers (2008)

Two types of 32 arm star polymers incorporating amphiphilic block copolymer arms have been synthesized and characterized. The first type, stPCL-PEG 32, is composed of a polyamidoamine (PAMAM) dendrimer as the core with radiating arms having poly(epsilon-caprolactone) (PCL) as an inner lipophilic block in the arm and poly(ethylene glycol) (PEG) as an outer hydrophilic block. The second type, stPLA-PEG 32, is similar but with poly(L-lactide) (PLA) as the inner lipophilic block. Characterization with SEC, (1)H NMR, FTIR, and DSC confirmed the structure of the polymers. Micelle formation by both star copolymers was studied by fluorescence spectroscopy. The stPCL-PEG 32 polymer exhibited unimolecular micelle behavior. It was capable of solubilizing hydrophobic molecules, such as pyrene, in aqueous solution, while not displaying a critical micelle concentration. In contrast, the association behavior of stPLA-PEG 32 in aqueous solution was characterized by an apparent critical micelle concentration of ca. 0.01 mg/mL. The hydrophobic anticancer drug etoposide can be encapsulated in the micelles formed from both polymers. Overall, the stPCL-PEG 32 polymer exhibited a higher etoposide loading capacity (up to 7.8 w/w % versus 4.3 w/w % for stPLA-PEG 32) as well as facile release kinetics and is more suitable as a potential drug delivery carrier.
Uroplakin Ia is the urothelial receptor for uropathogenic<i>Escherichia coli</i>: evidence from in vitro FimH binding (2001)

The binding of uropathogenic Escherichia coli to the urothelial surface is a crucial initial event for establishing urinary tract infection because it allows the bacteria to gain a foothold on the urothelial surface, thus preventing them from being removed by micturition. In addition, it triggers bacterial invasion as well as host urothelial defense. This binding is mediated by the FimH adhesin located at the tip of the bacterial type 1-fimbrium, a filamentous attachment apparatus, and its urothelial receptor. We have prepared a biotinylated, recombinant FimH-FimC adhesin:chaperone complex and used it to identify its mouse urothelial receptor. The FimH-FimC complex binds specifically to a single 24 kDa major mouse urothelial plaque protein, which we identified as uroplakin Ia by mass spectrometry, cDNA cloning and immunoreactivity. The terminal mannosyl moieties on Asn-169 of uroplakin Ia are responsible for FimH as well as concanavalin A binding. Although FimH binds to uroplakin Ia with only moderate strength (K(d) approximately 100 nM between pH 4 and 9), the binding between multiple fimbriae of a bacterium and the crystalline array of polymerized uroplakin receptors should achieve high avidity and stable bacterial attachment. The FimH-FimC complex binds preferentially to the mouse urothelial umbrella cells in a pattern similar to uroplakin staining. Our results indicate that the structurally related uroplakins Ia and Ib are glycosylated differently, that uroplakin Ia serves as the urothelial receptor for the type 1-fimbriated E. coli, and that the binding of uropathogenic bacteria to uroplakin Ia may play a key role in mediating the urothelial responses to bacterial attachment.
Polymeric materials: patterned polymer carpets (2011)

For the development of polymer carpets as active devices for micro- and nanotechnology, a control of the polymer carpet morphology and especially control of the stimulus responsive polymer brush is needed. Here, we report on the first example for the fabrication of patterned polymer carpets. On a two-dimensional framework of fully crosslinked and chemically patterned nanosheets, polymer brushes of styrene and 4-vinyl pyridine were grafted by self-initiated surface photopolymerization and photografting (SIPGP). It was found that polymer grafting by SIPGP occurred over the entire nanosheets but with a preferred grafting on the amino functionalized nanosheet areas. This results in continuous polymer carpets with an intact nanosheet framework but with amplification of the chemical patterning into a three dimensional topography of the grafted polymer brush. In the case of negative patterned nanosheets, the patterned carpet could be prepared as freestanding ultrathin membranes. Furthermore, swelling experiments with poly(4-vinyl pyridine) carpets showed that the patterns induces a directional buckling of the flexible polymer carpet. This may open the possibility of the development of micro- or nanoactuator devices with anisotropic responds upon environmental changes. Copyright 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Frequency dependent polarization analysis of high‐frequency seismograms (1987)

We present a multitaper algorithm to estimate the polarization of particle motion as a function of frequency from three‐component seismic data. This algorithm is based on a singular value decomposition of a matrix of eigenspectra at a given frequency. The right complex eigenvector corresonding to the largest singular value of the matrix has the same direction as the dominant polarization of seismic motion at that frequency. The elements of the polarization vector specify the relative amplitudes and phases of motion measured along the recorded components within a chosen frequency band. The width of this frequency band is determined by the time‐bandwidth product of the prolate spheroidal tapers used in the analysis. We manipulate the components of to determine the apparent azimuth and angle of incidence of seismic motion as a function of frequency. The orthogonality of the eigentapers allows one to calculate easily uncertainties in the estimated azimuth and angle of incidence. We apply this algorithm to data from the Anza Seismic Telemetered Array in the frequency band 0 ≤ ƒ ≤ 30 Hz. The polarization is not always a smooth function of frequency and can exhibit sharp jumps, suggesting the existence of scattered modes within the crustal waveguide and/or receiver site resonances.
A phase 1b study of ONT-380, an oral HER2-specific inhibitor, combined with capecitabine and trastuzumab, in HER2+ metastatic breast cancer (MBC). (2014)

TPS663 Background: ONT-380 is a selective small molecule inhibitor of HER2 kinase with nanomolar potency. Unlike dual HER2/EGFR agents, it does not inhibit EGFR at clinically relevant concentrations, decreasing the potential for EGFR-related toxicities. In preclinical studies, ONT-380 demonstrated greater than additive activity with trastuzumab, and was active in models of CNS metastases. In a single-agent phase 1 study in 50 patients (pts) with metastatic HER2+ cancer, the MTD was 600 mg BID, with DLT consisting of reversible gr 3 ALT/AST in 2/4 pts at 800 mg. In 22 HER2+ breast cancer pts treated at doses ≥ 600 mg BID, the clinical benefit rate (partial response [n = 3] plus stable disease for at least 6 months [n = 3]) was 27%. Based on data supporting dual blockade of HER2, as well as preclinical activity of ONT-380 in the CNS, ONT-380 is now being evaluated in combination with capecitabine and trastuzumab. Methods: The study objectives are to determine the MTD/Phase 2 dose and preliminary anti-tumor activity of ONT-380 given with capecitabine alone, trastuzumab alone, and both capecitabine and trastuzumab in pts with and without CNS metastases. The study population includes adult pts with HER2+ MBC who have received trastuzumab and ado-trastuzumab emtansine (T-DM1) but not capecitabine for metastatic disease. A 3+3 design will evaluate up to three dose levels of ONT-380 (starting at 300 mg PO BID) given in combination with either capecitabine (1000 mg/mg2 PO BID for 14 days of a 21-day cycle) or trastuzumab (8 mg/kg IV loading dose; 6 mg/kg IV once every 21 days). If both combinations are tolerable, ONT-380 will be evaluated with both capecitabine and trastuzumab. Expanded cohorts of pts with and without CNS metastases may be enrolled for either doublet or triplet combinations. Tumor response will be evaluated using RECIST 1.1. CNS response will be also evaluated by modified RECIST 1.1 and volumetric criteria. Potential biomarkers of response, including p95 HER2 and HER2 mutations, will be assessed in archived tumor biopsies. Treatment will continue until unacceptable toxicity, disease progression, or withdrawal of consent. Clinical trial information: NCT02025192.
The waffle iron store (1963)

THIS PAPER will present a progress report on a 256-word, 400-nsec waffle-iron store.
Gel‐permeation chromatography: Examination of universal calibration procedures for polydimethylsiloxane in a poor solvent (1970)

Abstract Various procedures for universal calibration in gel‐permeation chromatography with polystyrene gels are examined for polystyrene and polydimethylsiloxane fractions. For o ‐dichlorobenzene at 138°C, experimental intrinsic viscosity–molecular weight data show that the Mark‐Houwink exponents are 0.70 and 0.57 for polystyrene and polydimethylsiloxane, respectively. In principle, this difference permits a distinction between the various polymer size parameters proposed for universal calibration. An interpretation of the experimental polydimethylsiloxane calibration for o ‐dichlorobenzene at 138°C requires a consideration of errors in average molecular weights and errors arising from the use of average molecular weight instead of peak molecular weight. When calibration procedures utilizing hydrodynamic volume and unperturbed dimensions are examined, the difference between them is comparable with experimental error. If the Flory‐Fox viscosity expression is employed, the perturbed end‐to‐end distance (or radius of gyration) and the hydrodynamic volume give equivalent universal calibrations. The experimental data are sufficiently accurate to show that the perturbed dimension determined with the Ptitsyn‐Eizner relation does not give an adequate universal calibration.
Narrowband microwave suppression filters (1968)

A theoretical and experimental investigation into narrow-bandwidth microwave rejection filters, which can be constructed from simple, standard microwave components, is described. Suppression factors of at least 50dB at resonance are possible, and the bandwidth can be easily controlled. A simple form of analysis, which indicates clearly the effects of variation in the parameters, gives good agreement with experimental measurements. The possibility of using a 2-cavity system to obtain a slightly broader frequency response and a very low insertion loss, at the expense of a lower suppression factor at the centre frequency, is indicated.
Anthracycline antibiotic-stimulated superoxide, hydrogen peroxide, and hydroxyl radical production by NADH dehydrogenase. (1983)

This study investigated the effect of the anthracycline antibiotics on oxygen radical metabolism by cardiac mitochondrial reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase [NADH:(acceptor) oxidoreductase, EC 1.6.99.3]. Superoxide formation by NADH dehydrogenase after anthracycline treatment appeared to follow saturation kinetics with an apparent Km of 167.3, 73.3, 64.0, or 47.6 microM for doxorubicin, daunorubicin, rubidazone, or aclacinomycin A, respectively. Superoxide formation by NADH dehydrogenase after doxorubicin treatment occurred with a pH optimum of 7.6 and was accompanied by the production of hydrogen peroxide. Furthermore, drug-related hydroxyl radical generation was detected in this enzyme system by the evolution of methane gas from dimethyl sulfoxide. Hydroxyl radical production proceeded only in the presence of superoxide anion, hydrogen peroxide, and trace amounts of iron or a chelate of iron and ethylenediaminetetraacetate and thus was probably the by-product of a transition metal-catalyzed Haber-Weiss reaction. The antitumor agents mitoxantrone and actinomycin D did not significantly enhance reactive oxygen metabolism by NADH dehydrogenase. These results suggest that the specific activation of the anthracycline antibiotics to free radicals by NADH dehydrogenase leads to the formation of a variety of reactive oxygen species that may contribute to the mitochondrial toxicity of these drugs.
Top‐down identification of endogenous peptides up to 9 kDa in cerebrospinal fluid and brain tissue by nanoelectrospray quadrupole time‐of‐flight tandem mass spectrometry (2005)

Recent work on protein and peptide biomarker patterns revealed the difficulties in identifying their molecular components, which is indispensable for validation of the biological context. Cerebrospinal fluid and brain tissue are used as sources to discover new biomarkers, e.g. for neurodegenerative diseases. Many of these biomarker candidates are peptides with a molecular mass of <10 kDa. Their identification is favourably achieved with a 'top-down' approach, because this requires less purification and an enzymatic cleavage will often not yield enough specific fragments for successful database searches. Here, we describe an approach using quadrupole time-of-flight mass spectrometry (TOFMS) as a highly efficient mass spectrometric purification and identification tool after off-line decomplexation of biological samples by liquid chromatography. After initial peptidomic screening with matrix-assisted laser desorption/ionization (MALDI) TOFMS, the elution behaviour in chromatography and the exact molecular mass were used to locate the same signals in nanoelectrospray measurements. Most of the peaks detected in MALDI-TOFMS could be retrieved in nanoelectrospray quadrupole TOFMS. Suitable collision energies for informative fragment spectra were investigated for different parent ions, charge states and molecular masses. After collision-induced dissociation, the resulting fragmentation data of multiply charged ions can become much more complicated than those derived from tryptic peptide digests. However, the mass accuracy and resolution of quadrupole TOF instruments results in high-quality data suitable for determining peptide sequences. The protein precursor, proteolytic processing and post-translational modifications were identified by automated database searches. This is demonstrated by the exemplary identifications of thymosin beta-4 (5.0 kDa) and NPY (4.3 kDa) from rat hypothalamic tissue and ubiquitin (8.6 kDa) from human cerebrospinal fluid. The high data quality should also allow for de novo identification. This methodology is generally applicable for peptides up to a molecular mass of about 10 kDa from body fluids, tissues or other biological sources.
Laser-Induced Graphene (2018)

ConspectusResearch on graphene abounds, from fundamental science to device applications. In pursuit of complementary morphologies, formation of graphene foams is often preferred over the native two-dimensional (2D) forms due to the higher available area. Graphene foams have been successfully prepared by several routes including chemical vapor deposition (CVD) methods and by wet-chemical approaches. For these methods, one often needs either high temperature furnaces and highly pure gases or large amounts of strong acids and oxidants. In 2014, using a commercial laser scribing system as found in most machine shops, a direct lasing of polyimide (PI) plastic films in the air converted the PI into 3D porous graphene, a material termed laser-induced graphene (LIG). This is a one-step method without the need for high-temperature reaction conditions, solvent, or subsequent treatments, and it affords graphene with many five-and seven-membered rings. With such an atomic arrangement, one might call LIG “kinetic graphene” since there is no annealing in the process that causes the rearrangement to the preferred all-six-membered-ring form. In this Account, we will first introduce the approaches that have been developed for making LIG and to control the morphology as either porous sheets or fibrils, and to control porosity, composition, and surface properties. The surfaces can be varied from being either superhydrophilic with a 0° contact angle with water to being superhydrophobic having >150° contact angle with water. While it was initially thought that the LIG process could only be performed on PI, it was later shown that a host of other polymeric substrates, nonpolymers, metal/plastic composites, and biodegradable and naturally occurring materials and foods could be used as platforms for generating LIG. Methods of preparation include roll-to-roll production for fabrication of in-plane electronics and two different 3D printing (additive manufacturing) routes to specific shapes of LIG monoliths using both laminated object manufacturing and powder bed fabrication methods. Use of the LIG in devices is performed very simply. This is showcased with high performance supercapacitors, fuel cell materials for oxygen reduction reactions, water splitting for both hydrogen and oxygen evolution reactions coming from the same plastic sheet, sensor devices, oil/water purification platforms, and finally applications in both passive and active biofilm inhibitors. So the ease of formation of LIG, its simple scale-up, and its utility for a range of applications highlights the easy transition of this substrate-bound graphene foam into commercial device platforms.
&beta;-Catenin is important for cancer stem cell generation and tumorigenic activity in nasopharyngeal carcinoma (2016)

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors with poor prognosis and recurrence in South China. The hard eradication of NPC in clinic is predominantly due to cancer stem cells (CSCs). Increasing evidence revealed that the aberrant activation of Wnt/β-catenin was positively correlated with the produce of CSCs. To further investigate the effect of β-catenin on CSCs and tumorigenesis in NPC, a CNE2 cell line (pLKO.1-sh-β-catenin-CNE2) with stably suppressed expression of β-catenin was used in this study. The expressions of biomarkers in CSCs including c-myc, Nanog, Oct3/4, Sox2, EpCAM as well as adhesion-related proteins like E-cadherin and vimentin were analyzed by western blot analysis and immunofluorescent staining. The proliferation and migration abilities were investigated by MTT assay and Transwell assay, respectively. Cell cycle was analyzed by flow cytometry. Finally, xenograft was performed to determine the effect of β-catenin on oncogenesis in vivo. Results showed that the expressions of c-myc, Nanog, Oct3/4, Sox2, and EpCAM were all decreased in pLKO.1-sh-β-catenin-CNE2 cells. It was also found that vimentin was downregulated, while E-cadherin was upregulated. Results of MTT and Transwell assays suggested that the proliferation and migration abilities were impaired by silencing of β-catenin, and more cells were arrested in G1 phase when compared with the control. In vivo study indicated that the tumor growth was markedly suppressed in experimental group. Based on current findings, β-catenin may function as an essential protein for the maintenance of migration and proliferation abilities of NPC cells, and a complicated network consisting of c-myc, Nanog, Oct3/4, Sox2, EpCAM, E-cadherin, vimentin, and β-catenin may be involved in the inherent regulation mechanisms.
Layered long-term co-culture of hepatocytes and endothelial cells on a transwell membrane: toward engineering the liver sinusoid (2013)

This paper presents a novel liver model that mimics the liver sinusoid where most liver activities occur. A key aspect of our current liver model is a layered co-culture of primary rat hepatocytes (PRHs) and primary rat liver sinusoidal endothelial cells (LSECs) or bovine aortic endothelial cells (BAECs) on a transwell membrane. When a layered co-culture was attempted with a thin Matrigel layer placed between hepatocytes and endothelial cells to mimic the space of Disse, the cells did not form completely separated monolayers. However, when hepatocytes and endothelial cells were cultured on the opposite sides of a transwell membrane, PRHs co-cultured with LSECs or BAECs maintained their viability and normal morphology for 39 and 57 days, respectively. We assessed the presence of hepatocyte-specific differentiation markers to verify that PRHs remained differentiated in the long-term co-culture and analyzed hepatocyte function by monitoring urea synthesis. We also noted that the expression of cytochrome P-450 remained similar in the co-cultured system from day 1 to day 48. Thus, our novel liver model system demonstrated that primary hepatocytes can be cultured for extended times and retain their hepatocyte-specific functions when layered with endothelial cells.