gebhart/patrepeval huggingface dataset:
Faculty Opinions recommendation of Frequency-dependent kinetics and prevalence of kiss-and-run and reuse at hippocampal synapses studied with novel quenching methods. (2006)

The kinetics of exo-endocytotic recycling could restrict information transfer at central synapses if neurotransmission were entirely reliant on classical full-collapse fusion. Nonclassical fusion retrieval by kiss-and-run would be kinetically advantageous but remains controversial. We used a hydrophilic quencher, bromophenol blue (BPB), to help detect nonclassical events. Upon stimulation, extracellular BPB entered synaptic vesicles and quenched FM1-43 fluorescence, indicating retention of FM dye beyond first fusion. BPB also quenched fluorescence of VAMP (synaptobrevin-2)-EGFP, thus indicating the timing of first fusion of vesicles in the total recycling pool. Comparison with FM dye destaining revealed that kiss-and-run strongly prevailed over full-collapse fusion at low frequency, giving way to a near-even balance at high frequency. Quickening of kiss-and-run vesicle reuse was also observed at higher frequency in the average single vesicle fluorescence response. Kiss-and-run and reuse could enable hippocampal nerve terminals to conserve scarce vesicular resources when responding to widely varying input patterns. PMID: 16423698 Funding information This work was supported by: NIMH NIH HHS, United States Grant ID: MH64070
Discovery of a Novel Class of Potent HCV NS4B Inhibitors: SAR Studies on Piperazinone Derivatives (2014)

HTS screening identified compound 2a (piperazinone derivative) as a low micromolar HCV genotype 1 (GT-1) inhibitor. Resistance mapping studies suggested that this piperazinone chemotype targets the HCV nonstructural protein NS4B. Extensive SAR studies were performed around 2a and the amide function and the C-3/C-6 cis stereochemistry of the piperazinone core were essential for HCV activity. A 10-fold increase in GT-1 potency was observed when the chiral phenylcyclopropyl amide side chain of 2a was replaced with p-fluorophenylisoxazole-carbonyl moiety (67). Replacing the C-6 nonpolar hydrophobic moiety of 67 with a phenyl moiety (95) did not diminish the GT-1 potency. A heterocyclic thiophene moiety (103) and an isoxazole moiety (108) were incorporated as isosteric replacements for the C-6 phenyl moiety (95), resulting in significant improvement in GT-1b and 1a potency. However, the piperazonone class of compounds lacks GT-2 activity and, consequently, were not pursued further into development.
Rejection of Primary Lymphoma Cells Derived from c-myc-Transgenic Mice after Haploidentical Transplantation: Treatment of the Tumor May Confer to Resistance Against GvL-Effect. (2005)

Abstract The long term prognosis of the High Grade B-cell-lymphoma in adults is still very poor, especially in the case of resistance to chemotherapy. To date allogeneic stem cell transplantation as a last treatment option results in poor outcomes due to high transplant related mortality or disease progression. This dilemma raises the question of whether transplant related mortality could be reduced by earlier transplantation, and whether such tumors can be recognized by an allogeneic graft providing a graft versus lymphoma effect. The immunology behind allogeneic rejection of high grade lymphomas is poorly understood due to a dearth of good animal models. Using a transgenic mouse model in which the human c-myc oncogene is driven by the human immunoglobuline lambda locus mimicking a t(8;22) translocation of Burkitt’s lymphoma, we established primary lymphoma cell lines. C57BL/6c-myc tg mice were crossbred with DBA mice and lymph nodes from tumor bearing F1-mice were explanted and seeded on irradiated human MRC5 fibroblast feeder cells. Approximately 70% of all explanted lymphomas established long term cultures which could be maintained free of feeder cells after 4 to 6 weeks. FACS analysis of lymphoma cells displayed strong CD19 expression, reduced expression of MHC Class I and II and, in several cases, low expression of costimulatory molecules such as CD80, CD86 and CD54. The phenotype was maintained over time with a follow up of up to 4 months. As few as 100 lymphoma cells gave rise to orthotopic tumors or systemic disease within 40 days after s.c. or i.v. injection, respectively. On the contrary, when 50 Mio. F1-lymphoma cells were injected into haploidentical C57BL6 parental animals, no tumor growth could be observed after at least 100 days of follow up. Despite fast growth and low expression of MHC Class I and costimulatory molecules, lymphoma cells were easily rejected in a haploidentical setting. Ex vivo chemotherapy treatment of lymphoma cells resulted in resistance after 2 courses of 100nM Adriamycine. Increased doses up to 500nM Adriamycine further accelerated resistance and growth speed of the cells. Flow cytometric analysis indicated a reduced fraction of apoptotic cells in culture suggesting selection for cells bearing alteration in the apoptotic pathways. In further experiments altered cells will be tested in haploidentical settings to confirm clinical experience in our model.
Evaluation of painful knee arthroplasty (2001)

Evaluation of the painful knee arthroplasty requires a careful history and examination with judicious use of laboratory tests, aspiration of joint fluid for synovial fluid analysis and culture testing, and occasional use of radionuclide imaging tests. The investigative process requires differentiation of the potential extrinsic and intrinsic causes of knee pain. Classification of intrinsic sources of knee pain into aseptic loosening, infection, instability, impingement, wear debris, and miscellaneous categories facilitates the evaluation process. Use of an algorithm to proceed through the process of selecting appropriate testing modalities is helpful. Newer technologies hold promise for differentiating certain entities such as infection or polyethylene wear.
Activation of Cytokine Production by Secreted Phospholipase A2 in Human Lung Macrophages Expressing the M-Type Receptor (2005)

Secreted phospholipases A(2) (sPLA(2)) are enzymes released in plasma and extracellular fluids during inflammatory diseases. Because human group IB and X sPLA(2)s are expressed in the lung, we examined their effects on primary human lung macrophages (HLM). Both sPLA(2)s induced TNF-alpha and IL-6 release in a concentration-dependent manner by increasing their mRNA expression. This effect was independent of their enzymatic activity because 1) the capacity of sPLA(2)s to mobilize arachidonic acid from HLM was unrelated to their ability to induce cytokine production; and 2) two catalytically inactive isoforms of group IB sPLA(2) (bromophenacyl bromide-inactivated human sPLA(2) and the H48Q mutant of the porcine sPLA(2)) were as effective as the catalytically active sPLA(2)s in inducing cytokine production. HLM expressed the M-type receptor for sPLA(2)s at both mRNA and protein levels, as determined by RT-PCR, immunoblotting, immunoprecipitation, and flow cytometry. Me-indoxam, which decreases sPLA(2) activity as well as binding to the M-type receptor, suppressed sPLA(2)-induced cytokine production. Incubation of HLM with the sPLA(2)s was associated with phosphorylation of ERK1/2, and a specific inhibitor of this pathway, PD98059, significantly reduced the production of IL-6 elicited by sPLA(2)s. In conclusion, two distinct sPLA(2)s produced in the human lung stimulate cytokine production by HLM via a mechanism that is independent of their enzymatic activity and involves activation of the ERK1/2 pathway. HLM express the M-type receptor, but its involvement in eliciting cytokine production deserves further investigation.
UWB RF receiver front-end with band-notch characteristic of 5 GHz WLAN (2006)

This paper proposes a method of realizing band-notch characteristic in the UWB antenna and the low noise amplifier (LNA) such that the UWB RF receiver can fully suppress high-power interference signal in 5 GHz WLAN band. Two procedures of band-notching in RF signal reception are combined, and in fact, such a UWB RF receiver front-end has not been reported yet.
P‐194: Modification of the staggered start and randomized withdrawal clinical trial designs: Toward a practical demonstration of disease modification in Alzheimer's disease (AD) (2007)

Demonstration of Disease Modification in AD is a complicated topic that has been approached in many ways. Among the strategies proposed are two approaches based on measuring clinical outcomes in a cross-over type study: 1. the staggered start design and 2. the randomized withdrawal design. These two study designs are complicated by the long duration of the studies, leading to high dropout rates which introduce bias. A suggested alternative is a parallel groups design comparing slopes and severity of disease at baseline. The objective is to demonstrate that a more practical, parallel group design is equivalent to either a randomized withdrawal or staggered start clinical trial design in demonstrating disease modification based on identifying relevant patterns of clinical disease progression. A randomized withdrawal design can be used to distinguish between a disease modifying and a symptomatic drug. A disease modifying drug will maintain a clinical benefit even when the drug is withdrawn. The staggered start design can be mathematically proven to be equivalent to the randomized withdrawal design. The connections between the clinical outcomes used in these designs and the underlying disease progression are investigated and described. A proposed “natural history staggered start” design based on parallel groups is compared to the staggered start and randomized withdrawal designs to see whether it is also capable of distinguishing between a disease modifying and a symptomatic drug. A “natural history staggered start” design is described in which an analysis of slope divergence is combined with an analysis assessing difference in treatment effect depending on severity of disease at baseline. This design is shown to be mathematically equivalent to a staggered start or randomized withdrawal design. The staggered start and randomized withdrawal designs are impractical because of the long duration of treatment required, the bias introduced by the associated high dropout rates, and ethical concerns. A novel and practical parallel groups design allows measurement of the same underlying patterns of drug effect and differentiation of symptomatic and disease modification drug effects without the complications of these cross-over approaches.
Editorial: Inflammation and Fibrosis in the Gastrointestinal Tract and Liver: Mechanisms and Targets (2021)

EDITORIAL article Front. Pharmacol., 24 September 2021 | https://doi.org/10.3389/fphar.2021.773228
How search and its subtasks scale in N robots (2009)

The present study investigates the effect of the number of controlled robots on performance of an urban search and rescue (USAR) task using a realistic simulation. Participants controlled either 4, 8, or 12 robots. In the fulltask control condition participants both dictated the robots' paths and controlled their cameras to search for victims. In the exploration condition, participants directed the team of robots in order to explore as wide an area as possible. In the perceptual search condition, participants searched for victims by controlling cameras mounted on robots following predetermined paths selected to match characteristics of paths generated under the other two conditions. By decomposing the search and rescue task into exploration and perceptual search subtasks the experiment allows the determination of their scaling characteristics in order to provide a basis for tentative task allocations among humans and automation for controlling larger robot teams. In the fulltask control condition task performance increased in going from four to eight controlled robots but deteriorated in moving from eight to twelve. Workload increased monotonically with number of robots. Performance per robot decreased with increases in team size. Results are consistent with earlier studies suggesting a limit of between 8-12 robots for direct human control.
Bioanalytical Applications of Capillary Electrophoresis (2006)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTBioanalytical Applications of Capillary ElectrophoresisJames Kraly, Md. Abul Fazal, Regine M. Schoenherr, Ryan Bonn, Melissa M. Harwood, Emily Turner, Megan Jones, and Norman J. DovichiView Author Information Department of Chemistry, University of Washington, Seattle, Washington 98195-1700 Cite this: Anal. Chem. 2006, 78, 12, 4097–4110Publication Date (Web):May 5, 2006Publication History Published online5 May 2006Published inissue 1 June 2006https://pubs.acs.org/doi/10.1021/ac060704chttps://doi.org/10.1021/ac060704creview-articleACS PublicationsCopyright © 2006 American Chemical SocietyRequest reuse permissionsArticle Views2402Altmetric-Citations108LEARN 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:Capillary electrophoresis,Coating materials,Genetics,Monomers,Peptides and proteins Get e-Alerts
Plasma studies on a hollow cathode, magnetic multipole ion source for neutral beam injection (1982)

A series of Langmuir probe studies has been undertaken on the hydrogen plasma of an 8×8-cm extraction area hollow cathode, magnetic multipole ion source intended for use in neutral beam injection systems. Five movable probes were utilized to measure plasma density, electron temperature, plasma potential, and primary electron density as a function of position in the plasma generator and performance of the ion source. The measurements indicate that at discharge current below 150 A, a fairly uniform plasma over the source volume, with a potential positive with respect to the anode, is generated. The performance of the plasma generator at low currents resembles the filament discharge, magnetic multipole confinement ion source. The ion source in this case has good efficiency and plasma uniformity, but atomic species fractions of less than 70%. As the discharge current is increased, the plasma separates into a high-density, high-ionization, positive potential region near the cathode, and a lower-density, negative potential plasma near the extraction grids. This plasma near the acceleration electrodes is characterized by a relatively low primary electron to plasma electron density ratio of about 2%. The performance of the source significantly increases over the uniform volume plasma case with atomic species output of typically 85% and gas utilization efficiencies of 40%–65%. The high-current, hollow cathode discharge produces a plasma configuration and output performance similar to that of the duoPIGatron ion source, but with lower noise levels.
Dynamics of Photoinduced Phase Transitions in a Prussian Blue Analog Studied by CN Vibrational Spectroscopy (2015)

Background: Recent progress in the study of photoinduced phase transition phenomena in cyano-bridged metal complexes called Prussian blue analog by means of CN vibrational spectroscopy is reviewed. The material discussed in this article is one of the most attractive and well-studied material, RbxMn[Fe(CN)6]y·nH2O, which shows a thermal phase transition accompanying a charge transfer and a change in magnetization around room temperature. Owing to a unique opportunity in this material to investigate the domains as well as the initial and final phases, by using the CN stretching vibration modes, domain growth dynamics and the nuclear formation processes are investigated in detail. Raman Spectroscopy: Raman spectroscopy is used to distinguish ion pairs corresponding to the low and high temperature phases and the boundary. The resonant Raman spectroscopy reveals the coupling of the CN ions with the local electronic states, and gives some information about the local lattice structure. Domain Growth: Time dependence of the phase fractions and the amount of boundary under irradiation of light is investigated. Continuous frequency shift suggests relaxation of the local strain during the growth of the domain. The domain growth process is found to be dependent on the excitation power density and the behavior is described by a kinetic model based on mean field approximation. Ultrafast Dynamics: A picosecond infrared spectroscopy is utilized to observe the ultrafast phenomena following the femtosecond pulse excitation. In addition to the decrease of the initial phases, creation of a large number of boundary component is found for photoinduced phase transition in both directions. Keywords: CN vibration, domain growth, infrared absorption, nucleus, photoinduced phase transition, Prussian blue analogue, picosecond, Raman scattering.
Interstitial fluid pressure due to externally applied force in breast tissue (2007)

Manipulation of Interstitial Fluid Pressure (IFP) has clinical potential when used in conjunction with near infrared spectroscopy for detection and characterization of breast cancer. IFP is a function of blood chemistry, vessel microanatomy, mechanical properties of the tissue, tissue geometry, and external force. IFP has been demonstrated higher in tumors than normal tissue, and it has been suggested that increased IFP can lead to changes in near infrared absorbing and scattering coefficients. While it is known that external forces can increase IFP, the relationship of force to IFP in a viscoelastic, hyperelastic solid such as tissue is complex. Fluid pressure measurements were taken in gelatin phantoms of equivalent elastic modulus to adipose and glandular tissues of the breast using a WaveMap pressure transducer. 3D pressure maps were obtained for the volumes of the phantoms with an externally applied force of 10mmHg, demonstrating the contribution of shear stress, non-linear mechanical properties, and tissue geometry. Linear elastic computational models were formulated for breast tissue with and without an inclusion of tumor-like mechanical properties. Comparison of experimental and computational model data indicates that light external pressure can lead to heterogeneous IFP distribution within tissues and increased IFP gradients around tumor-like inclusions.
Distribution of a Limited Sir2 Protein Pool Regulates the Strength of Yeast rDNA Silencing and Is Modulated by Sir4p (1998)

Transcriptional silencing in Saccharomyces cerevisiae occurs at the silent mating-type loci HML and HMR, at telomeres, and at the ribosomal DNA (rDNA) locus RDN1. Silencing in the rDNA occurs by a novel mechanism that depends on a single Silent Information Regulator (SIR) gene, SIR2. SIR4, essential for other silenced loci, paradoxically inhibits rDNA silencing. In this study, we elucidate a regulatory mechanism for rDNA silencing based on the finding that rDNA silencing strength directly correlates with cellular Sir2 protein levels. The endogenous level of Sir2p was shown to be limiting for rDNA silencing. Furthermore, small changes in Sir2p levels altered rDNA silencing strength. In rDNA silencing phenotypes, sir2 mutations were shown to be epistatic to sir4 mutations, indicating that SIR4 inhibition of rDNA silencing is mediated through SIR2. Furthermore, rDNA silencing is insensitive to SIR3 overexpression, but is severely reduced by overexpression of full-length Sir4p or a fragment of Sir4p that interacts with Sir2p. This negative effect of SIR4 overexpression was overridden by co-overexpression of SIR2, suggesting that SIR4 directly inhibits the rDNA silencing function of SIR2. Finally, genetic manipulations of SIR4 previously shown to promote extended life span also resulted in enhanced rDNA silencing. We propose a simple model in which telomeres act as regulators of rDNA silencing by competing for limiting amounts of Sir2 protein.
Ontology-based State Space Model Generation for Automatic Design of Sequence Control Program (2002)

An ontology-based, automated generation method for state space models is presented. The models are used to derive sequence control program specifications writen in SFC (Sequencial Function Chart). The state space models feature (i) dividing the plant state space into the machine state space and the equipment state space, (ii) allowing the generation of the machine-level state space models before searches, and (iii) reducing both the search space for planning, and the number of planning steps. It is currently difficult to make practical state space models, however, because of the large size of such models and the difficulty of expressing the details of operations. To overcome this problem, we propose a method of automatically generating the machine-level state space models from plant ontology in short time without errors. The plant ontology includes actions, side effects, constraints, and hierarchical states that are used to represent other parts of the ontology. To investigate the effectiveness of the method, we have applyed it to a planning-based VIsual Programming System for Sequence control program SpeciFiCation Design (VIPS/S-SFCD).
Approaching the microjoule frontier with femtosecond laser oscillators (2005)

Broadening the ultrashort laser pulse in a Kerr-lens mode-locked laser by net positive round-trip group-delay dispersion has proven to be a powerful concept for scaling the pulse energy directly achievable with a femtosecond laser oscillator without external amplification. Drawing on this concept, we demonstrate here Ti: Sa chirped-pulse oscillators delivering sub-40fs pulses of 0.5 μJ and 50 nJ energy at average power levels of 1 and 2.5 W (repetition rate: 2 and 50 MHz), respectively, which to the best of our knowledge constitute the highest pulse energy and average power achieved with a femtosecond (<100 fs) laser oscillator to date. The 0.5 μJ pulses have a peak power in excess of 10 MW and reach a peak intensity > 10 <sup>15</sup> W cm <sup>-2</sup> (when focused down to ∼1 μm <sup>2</sup>), both of which represent record values from a laser oscillator. These pulse parameters appear to be limited merely by the pump power available, affording promise of scaling chirped-pulse femtosecond Ti: Sa oscillators to microjoule pulse energies and - by simultaneous spectral broadening - towards peak power levels of several hundred megawatts. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft.