gebhart/patrepeval huggingface dataset:
Intra- and Interspecies Regulation of Gene Expression byActinobacillus actinomycetemcomitansLuxS (2001)

The cell density-dependent control of gene expression is employed by many bacteria for regulating a variety of physiological functions, including the generation of bioluminescence, sporulation, formation of biofilms, and the expression of virulence factors. Although periodontal organisms do not appear to secrete acyl-homoserine lactone signals, several species, e.g., Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum, have recently been shown to secrete a signal related to the autoinducer II (AI-2) of the signal system 2 pathway in Vibrio harveyi. Here, we report that the periodontal pathogen Actinobacillus actinomycetemcomitans expresses a homolog of V. harveyi luxS and secretes an AI-2-like signal. Cell-free conditioned medium from A. actinomycetemcomitans or from a recombinant Escherichia coli strain (E. coli AIS) expressing A. actinomycetemcomitans luxS induced luminescence in V. harveyi BB170 >200-fold over controls. AI-2 levels peaked in mid-exponential-phase cultures of A. actinomycetemcomitans and were significantly reduced in late-log- and stationary-phase cultures. Incubation of early-log-phase A. actinomycetemcomitans cells with conditioned medium from A. actinomycetemcomitans or from E. coli AIS resulted in a threefold induction of leukotoxic activity and a concomitant increase in leukotoxin polypeptide. In contrast, no increase in leukotoxin expression occurred when cells were exposed to sterile medium or to conditioned broth from E. coli AIS(-), a recombinant strain in which luxS was insertionally inactivated. A. actinomycetemcomitans AI-2 also induced expression of afuA, encoding a periplasmic iron transport protein, approximately eightfold, suggesting that LuxS-dependent signaling may play a role in the regulation of iron acquisition by A. actinomycetemcomitans. Finally, A. actinomycetemcomitans AI-2 added in trans complemented a luxS knockout mutation in P. gingivalis by modulating the expression of the luxS-regulated genes uvrB and hasF in this organism. Together, these results suggest that LuxS-dependent signaling may modulate aspects of virulence and the uptake of iron by A. actinomycetemcomitans and induce responses in other periodontal organisms in mixed-species oral biofilm.
LC-MS/MS Peptide Mapping with Automated Data Processing for Routine Profiling of N-Glycans in Immunoglobulins (2014)

Protein N-Glycan analysis is traditionally performed by high pH anion exchange chromatography (HPAEC), reversed phase liquid chromatography (RPLC), or hydrophilic interaction liquid chromatography (HILIC) on fluorescence-labeled glycans enzymatically released from the glycoprotein. These methods require time-consuming sample preparations and do not provide site-specific glycosylation information. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) peptide mapping is frequently used for protein structural characterization and, as a bonus, can potentially provide glycan profile on each individual glycosylation site. In this work, a recently developed glycopeptide fragmentation model was used for automated identification, based on their MS/MS, of N-glycopeptides from proteolytic digestion of monoclonal antibodies (mAbs). Experimental conditions were optimized to achieve accurate profiling of glycoforms. Glycan profiles obtained from LC-MS/MS peptide mapping were compared with those obtained from HPAEC, RPLC, and HILIC analyses of released glycans for several mAb molecules. Accuracy, reproducibility, and linearity of the LC-MS/MS peptide mapping method for glycan profiling were evaluated. The LC-MS/MS peptide mapping method with fully automated data analysis requires less sample preparation, provides site-specific information, and may serve as an alternative method for routine profiling of N-glycans on immunoglobulins as well as other glycoproteins with simple N-glycans.
Growth in children with 45,Xo Turner's syndrome (1974)

<h3>Abstract</h3> The mode of action for most mosquito repellents is unknown. This is primarily due to the difficulty in monitoring how the mosquito olfactory system responds to repellent odors. Here, we used the Q-system of binary expression to enable activity-dependent Ca<sup>2+</sup> imaging in olfactory neurons of the African malaria mosquito <i>Anopheles coluzzii</i>. This system allows neuronal responses to common insect repellents to be directly visualized in living mosquitoes from all olfactory organs including the antenna. The synthetic repellents DEET and IR3535 did not activate Odorant Receptor Co-Receptor (Orco) expressing olfactory receptor neurons (ORNs) at any concentration, while picaridin weakly activated ORNs only at high concentrations. In contrast, natural repellents (<i>i.e</i>. lemongrass oil and eugenol) strongly activated small numbers of ORNs in the mosquito antennae at low concentrations. We determined that DEET, IR3535, and picaridin decrease the response of Orco expressing ORNs when these repellents are physically mixed with activating human-derived odorants. We present evidence that synthetic repellents may primarily exert their olfactory mode of action by decreasing the amount of activating ligand reaching ORNs. These results suggest that synthetic repellents disruptively change the chemical profile of host scent signatures on the skin surface rendering humans invisible to mosquitoes.
Toward classification of dysphagic patients using biomechanical measurements. (1994)

Identification of a patient at risk of aspiration is a major problem in the rehabilitation of the dysphagic patient. The present methods of diagnosis are based on clinical evaluation or videofluorography or fiberoptic endoscopic examination of swallowing (FEES). Recently, we developed biomechanical techniques for noninvasive quantitative assessment of the dysphagic patient. The purpose of the present investigation was to assess the clinical validity of the technique. In a double-blind study, both biomechanical test results and videofluorography (including bedside evaluation) results were used to independently classify the patients into four categories of risk for aspiration. Of the 36 patients studied, there was complete agreement between the biomechanical and clinical classifications in 21 patients. In 11 patients, the biomechanical technique overestimated the risk by one category, and underestimated the risk by one category in four patients. The biomechanical technique presents a useful tool for continued patient assessment; however, further studies are needed.
Three‐Dimensional Electromagnetic Catheter Technology: (1997)

Three-dimensional electroanatomical mapping of the right atrium allowed detailed reconstruction of the chamber geometry and activation sequence. The sites of origin of ectopic atrial tachycardias could be identified precisely. The system allowed accurate renavigation to the site of earliest activation, thereby guiding successful ablation of the foci.
Fructan synthesis in transgenic tobacco and chicory plants expressing barley sucrose:fructan 6‐fructosyltransferase (1997)

We have recently cloned a cDNA encoding sucrose:fructan 6-fructosyltransferase (6-SFT), a key enzyme of fructan synthesis forming the beta-2,6 linkages typical of the grass fructans, graminans and phleins [Sprenger et al. (1995) Proc. Natl. Acad. Sci. USA 92, 11652-11656]. Here we report functional expression of 6-SFT from barley in transgenic tobacco and chicory. Transformants of tobacco, a plant naturally unable to form fructans, synthesized the trisaccharide kestose and a series of unbranched fructans of the phlein type (beta-2,6 linkages). Transformants of chicory, a plant naturally producing only unbranched fructans of the inulin type (beta-2,1 linkages), synthesized in addition branched fructans of the graminan type, particularly the tetrasaccharide bifurcose which is also a main fructan in barley leaves.
A time- and cost-efficient system for high-level protein production in mammalian cells (2006)

Most proteins for structural biology studies are produced by high-level expression in Escherichia coli. However, prokaryotic based expression systems fail to generate correctly folded functional forms of many proteins and hence a variety of eukaryotic based expression systems have been developed. Of these, yeast and baculovirus-infected insect cells currently represent the expression systems of choice for structural biologists. Here, protocols for a simple, fast and affordable method for transient protein expression in mammalian cells are reported. The results demonstrate that it combines several features necessary for the production of suitable samples for structural biology, in particular protein crystallography, namely high protein yield, straightforward purification, selenomethionine incorporation and control of N-linked glycosylation. The system is suitable for use in conventional laboratories or can be implemented in a medium- or high-throughput pipeline.
Sequential PKC- and Cdc2-mediated phosphorylation events elicit zebrafish nuclear envelope disassembly (1999)

Molecular markers of the zebrafish inner nuclear membrane (NEP55) and nuclear lamina (L68) were identified, partially characterized and used to demonstrate that disassembly of the zebrafish nuclear envelope requires sequential phosphorylation events by first PKC, then Cdc2 kinase. NEP55 and L68 are immunologically and functionally related to human LAP2beta and lamin B, respectively. Exposure of zebrafish nuclei to meiotic cytosol elicits rapid phosphorylation of NEP55 and L68, and disassembly of both proteins. L68 phosphorylation is completely inhibited by simultaneous inhibition of Cdc2 and PKC and only partially blocked by inhibition of either kinase. NEP55 phosphorylation is completely prevented by inhibition or immunodepletion of cytosolic Cdc2. Inhibition of cAMP-dependent kinase, MEK or CaM kinase II does not affect NEP55 or L68 phosphorylation. In vitro, nuclear envelope disassembly requires phosphorylation of NEP55 and L68 by both mammalian PKC and Cdc2. Inhibition of either kinase is sufficient to abolish NE disassembly. Furthermore, novel two-step phosphorylation assays in cytosol and in vitro indicate that PKC-mediated phosphorylation of L68 prior to Cdc2-mediated phosphorylation of L68 and NEP55 is essential to elicit nuclear envelope breakdown. Phosphorylation elicited by Cdc2 prior to PKC prevents nuclear envelope disassembly even though NEP55 is phosphorylated. The results indicate that sequential phosphorylation events elicited by PKC, followed by Cdc2, are required for zebrafish nuclear disassembly. They also argue that phosphorylation of inner nuclear membrane integral proteins is not sufficient to promote nuclear envelope breakdown, and suggest a multiple-level regulation of disassembly of nuclear envelope components during meiosis and at mitosis.
Analysis of Flue-Cured Tobacco Essential Oil by Hyphenated Analytical Techniques (1988)

The major components of an alkaloid-free, flue-cured, tobacco essential oil sample are isolated and identified. This is accomplished by utilizing modern hyphenated analytical methods. The instrumentation developed to accomplish this are an automated multidimensional gas chromatograph/mass spectrometer/flame ionization detector (MDGC/MS/FID) and a multidimensional gas chromatograph/matrix isolation/Fourier transform infrared spectrometer (MDGC/MI/FTIR). A total of 306 compounds is identified in the essential oil, of which 80 are found as tobacco constituents for the first time.
OS06.4 Identification of novel NTRK fusion in glioneuronal tumors and radiographic response following therapy with an NTRK inhibitor (2017)

Glioneuronal tumors constitute a histologically diverse group of primary CNS neoplasms, with no effective systemic therapy after surgery has failed. To further characterize this group of tumors, we collected a cohort of 26 glioneuronal tumors and performed in-depth genomic analysis. We identified mutations in BRAF (34%) and oncogenic fusions (30%). In addition, we discovered novel oncogenic fusions involving members of the NTRK gene family in a subset of our cohort. One patient with BCAN exon 13 fused to NTRK1 exon 11 initially underwent a subtotal resection for a 4th ventricular glioneuronal tumor but ultimately required additional therapy due to progressive, symptomatic disease. Given the patient’s targetable fusion, the patient was enrolled on a clinical trial with entrectinib, a pan-Trk, ROS1 and ALK inhibitor. The patient was treated for 11 months and during this time volumetric analysis of the lesion demonstrated a maximum reduction of 60% in the contrast-enhancing tumor compared to his pre-treatment MRI. The radiologic response was associated with resolution of his clinical symptoms and was maintained for eleven months on treatment. This represents the first report of BCAN-NTRK1 fusion in glioneuronal tumors and highlights its clinical importance as a novel, targetable alteration.
Effects of a calcium-channel antagonist on large and small coronary arteries in conscious dogs. (1982)

The effects of i.v. nifedipine, 20 micrograms/kg, on left ventricular (LV) pressure, dP/dt, aortic pressure, heart rate, LV diameters, cardiac output, coronary blood flow and left circumflex coronary arterial diameter, and calculations of late diastolic coronary and total peripheral resistances and left circumflex coronary cross-sectional area were examined in 11 conscious dogs. In dogs with spontaneous rhythm, nifedipine induced an early, transient response characterized by hypotension and peak increases in coronary blood flow and decreases in total peripheral and late diastolic coronary vascular resistances. The peak effects on large coronary arteries were observed 2--5 minutes later, when mean arterial pressure was only 8.2 +/- 1.6 mm Hg below control and LV end-diastolic pressure and diameter were not significantly different from control. LV dP/dt was elevated by 7.1 +/- 1.1%, heart rate was elevated by 25 +/- 3.3 beats/min, and cardiac output remained elevated by 54 +/- 7.4%. At this time, coronary cross-sectional area was elevated by 26 +/- 3.0%, late diastolic coronary vascular resistance was reduced by 50 +/- 2.7%, and total peripheral resistance was 40 +/- 3.8% below control. The coronary sinus oxygen content was elevated by 3.4 +/- 0.8 vol% and the arteriovenous oxygen difference fell by 3.5 +/- 0.8 vol%. After beta-adrenergic blockade with propranolol and with heart rate constant or varying, the increases in coronary cross-sectional area and decreases in late diastolic coronary vascular resistance induced by nifedipine were still observed, but were significantly smaller (p less than 0.01). Thus, nifedipine dilates both large coronary arteries and coronary resistance vessels, effects that could be attributed in part to beta-adrenergic mechanisms. Nifedipine also exerts potent effects on coronary and peripheral arterial vessels, but has little effect on preload.
Plasmonic Effects in Dynamic Tunable Metal-dielectric Composites (2008)

Sub-wavelength metal-dielectric-metal (MDM) composites support localized elec- tromagnetic modes that are strongly conflned in periodic structures. These modes can be con- trolled by tuning the shape of the composites as we demonstrated in previous works. Moreover, the Localized Surface Plasmon Resonance (LSPR) can be applied in new sensor applications. In this paper, we use the Finite-Difierence Time-Domain (FDTD) method to study double-periodic metal-dielectric-metal composites and put emphasis to interactions with the dielectric cover layer. The numerical results demonstrate that variation of the refractive index (RI) of the cover layer as well as the layer thickness afiect the LSPR response of the proposed MDM composite. The resonance-curve min/max groove period, the resonance-curve width, and the resonance-curve amplitudes from the MDM sensor output indicate that the proposed composite may flnd use as an efiective sub-wavelength dielectric sensing optical component for photonic applications.
iPCA: An Interactive System for PCA‐based Visual Analytics (2009)

Abstract Principle Component Analysis (PCA) is a widely used mathematical technique in many fields for factor and trend analysis, dimension reduction, etc. However, it is often considered to be a “black box” operation whose results are difficult to interpret and sometimes counter‐intuitive to the user. In order to assist the user in better understanding and utilizing PCA, we have developed a system that visualizes the results of principal component analysis using multiple coordinated views and a rich set of user interactions. Our design philosophy is to support analysis of multivariate datasets through extensive interaction with the PCA output. To demonstrate the usefulness of our system, we performed a comparative user study with a known commercial system, SAS/INSIGHT's Interactive Data Exploration. Participants in our study solved a number of high‐level analysis tasks with each interface and rated the systems on ease of learning and usefulness. Based on the participants' accuracy, speed, and qualitative feedback, we observe that our system helps users to better understand relationships between the data and the calculated eigenspace, which allows the participants to more accurately analyze the data. User feedback suggests that the interactivity and transparency of our system are the key strengths of our approach.
Tracer feasibility for monitoring tumor radiotherapy: a quadruple tracer study with fluorine-18-fluorodeoxyglucose or fluorine-18-fluorodeoxyuridine, L-[methyl-14C]methionine, [6-3H]thymidine, and gallium-67. (1991)

In a rat AH109A tumor model, metabolic tracers for glucose, amino acid, and nucleic acid metabolisms (2-deoxy-2-[18F]fluoro-D-glucose (18FDG), L-[methyl-14C]methionine (14C-Met), [6-3H]thymidine (3H-Thd), and 2'-deoxy-5-[18F]fluorouridine (18FdUrd], and the conventional radionuclide 67Ga-citrate were used to assess the feasibility of monitoring tumor radiotherapy using a quadruple tracer technique. Two combinations of four tracers (18FDG or 18FdUrd, 14C-Met, 3H-Thd and 67Ga) were compared in a time-course study after single-dose irradiation (20 Gy) and were also used in a dose-dependency study performed 6 days after 5, 10, 15, or 20 Gy of irradiation. Fluorine-18-FDG showed a large change in uptake and a steady response to radiotherapy. Fluorodeoxyuridine showed a rapid decrease after radiotherapy, but the range of change in uptake was narrow. Gallium-67 could not detect tumor response early after treatment, but showed a marked change in uptake later. [6-3H]Thd and 14C-Met showed a rapid response to irradiation and a high sensitivity for monitoring radiotherapy, suggesting that they may be feasible for PET studies.
Escherichia coli Mutants Lacking All Possible Combinations of Eight Penicillin Binding Proteins: Viability, Characteristics, and Implications for Peptidoglycan Synthesis (1999)

The penicillin binding proteins (PBPs) synthesize and remodel peptidoglycan, the structural component of the bacterial cell wall. Much is known about the biochemistry of these proteins, but little is known about their biological roles. To better understand the contributions these proteins make to the physiology of Escherichia coli, we constructed 192 mutants from which eight PBP genes were deleted in every possible combination. The genes encoding PBPs 1a, 1b, 4, 5, 6, and 7, AmpC, and AmpH were cloned, and from each gene an internal coding sequence was removed and replaced with a kanamycin resistance cassette flanked by two res sites from plasmid RP4. Deletion of individual genes was accomplished by transferring each interrupted gene onto the chromosome of E. coli via lambda phage transduction and selecting for kanamycin-resistant recombinants. Afterwards, the kanamycin resistance cassette was removed from each mutant strain by supplying ParA resolvase in trans, yielding a strain in which a long segment of the original PBP gene was deleted and replaced by an 8-bp res site. These kanamycin-sensitive mutants were used as recipients in further rounds of replacement mutagenesis, resulting in a set of strains lacking from one to seven PBPs. In addition, the dacD gene was deleted from two septuple mutants, creating strains lacking eight genes. The only deletion combinations not produced were those lacking both PBPs 1a and 1b because such a combination is lethal. Surprisingly, all other deletion mutants were viable even though, at the extreme, 8 of the 12 known PBPs had been eliminated. Furthermore, when both PBPs 2 and 3 were inactivated by the beta-lactams mecillinam and aztreonam, respectively, several mutants did not lyse but continued to grow as enlarged spheres, so that one mutant synthesized osmotically resistant peptidoglycan when only 2 of 12 PBPs (PBPs 1b and 1c) remained active. These results have important implications for current models of peptidoglycan biosynthesis, for understanding the evolution of the bacterial sacculus, and for interpreting results derived by mutating unknown open reading frames in genome projects. In addition, members of the set of PBP mutants will provide excellent starting points for answering fundamental questions about other aspects of cell wall metabolism.
Automating Infrastructure Composition for Internet Services (2001)

This paper describes a framework for automatically configuring relationships that tie together the software and hardware infrastructure components for an Internet-based service, which we also call composing the service infrastructure. Management and infrastructure software employ the framework to specify, discover, and react to changes in the infrastructure components participating in the service, automatically configuring cross-component relationships based on this information. This plays a key role in increasing the flexibility of a highly dynamic service infrastructure by reducing manual configuration required to redeploy resources. The framework also facilitates enterprises distributed across multiple autonomous administrative domains by automating chores required to tie resources distributed among the domains together into a cohesive service. We advocate extending existing service discovery protocols to distribute the information needed by the framework and suggest this as an area for future standardization.
Understanding Simple Asynchronous Evolutionary Algorithms (2015)

In many applications of evolutionary algorithms, the time required to evaluate the fitness of individuals is long and variable. When the variance in individual evaluation times is non-negligible, traditional, synchronous master-slave EAs incur idle time in CPU resources. An asynchronous approach to parallelization of EAs promises to eliminate idle time and thereby to reduce the amount of wall-clock time it takes to solve a problem. However, the behavior of asynchronous evolutionary algorithms is not well understood. In particular, it is not clear exactly how much faster the asynchronous algorithm will tend to run, or whether its evolutionary trajectory may follow a sub-optimal search path that cancels out the promised benefits. This paper presents a preliminary analysis of simple asynchronous EA performance in terms of speed and problem-solving ability.
Stereoselective Binding of Indomethacin Ethanolamide Derivatives to Cyclooxygenase-1 (2005)

We have used molecular modeling studies and molecular dynamics simulations to generate three-dimensional models for cyclooxygenase-1 complexes with a series of indomethacin ethanolamide derivatives. These studies provide a plausible explanation for the stereoselective ligand binding preferences observed experimentally for these inhibitors and predict the general binding mode as well as specific structural details for the ligand-enzyme complexes. These studies provide insight into the nature of cyclooxygenase-1 interactions with a series of novel inhibitors and should help increase our understanding of key structural determinants for cyclooxygenase isozyme-selective inhibitor binding.