gebhart/patrepeval huggingface dataset:
Synthesis and biological evaluation of Tc-99m-cyclopentadienyltricarbonyltechnetium-labeled A-85380 as a ligand for imaging central nicotinic acetylcholine receptors (2006)

1826 Objectives: Visualization of central nicotinic acetylcholine receptors (nAChRs) in human brain has been of great interest and 5-[123I]iodo-A-85380 has been reported as a suitable ligand for imaging nAChRs using SPECT. In this study, to improve the availability of SPECT imaging agents for routine studies of nAChRs, we synthesized and evaluated 99mTc-labeled A-85380. Methods: We selected cyclopentadiene as a chelating unit to form a small-sized and chemically stable technetium chelate and introduced it to the 5-position of the pyridine ring based on the structure-activity relationship of A-85380 derivatives. (S)-(5-(azetidin-2-ylmethoxy)pyridine-3-yl)methyl cyclopentadienyltricarbonyl rhenium carboxylate (CpTR-A-E), and cyclopentadienyltricarbonyl rhenium 5-[3-(2(S)-azetidinyl- methoxy)pyridinyl] methyl ketone (CpTR -A-K) were synthesized and the affinity to nAChRs was evaluated by competitive binding assays using [3H]cytisine and rat brain homogenates. Furthermore, we synthesized [99mTc]CpTT-A-E and evaluated its selectivity to nAChRs by competitive binding assay, the regional distribution in rat brain by in vitro autoradiography, and the biodistribution in living mice. Results: CpTR-A-E showed higher affinity to nAChRs than CpTR-A-K (Ki = 0.55 and 6.0 nM, respectively). The radiochemical yield of [99mTc]CpTT-A-E was 37% and the radiochemical purity was greater than 97%. The binding of [99mTc]CpTT-A-E to rat brain homogenates was displaced by the nAChR alpha4beta2-subtype ligand, 5IA (IC50 = 140 ± 23 uM), however, it was not displaced by the nAChR alpha7-subtype ligand, MLA (IC50 > 1000 uM), nor by the muscarinic receptor ligand, scopolamine (IC50 > 1000 uM). In vitro autoradiography demonstrated that the distribution of [99mTc]CpTT-A-E was highly correlated with the known distribution of nAChRs (R2 = 0.94). The brain uptake in living mice was 0.35 ± 0.04 %ID/g at 2 min after the intravenous injection. Conclusions: Despite of the introduction of the technetium chelate unit, [99mTc]CpTT-A-E maintained the high affinity and selectivity to nAChRs. Thus, the drug designs in this study which were based on the concept of the bifunctional chelating agents were useful for the development of technetium-labeled ligands for imaging nAChRs.
Flight Testing In-Time Safety Assurance Technologies for UAS Operations (2022)

View Video Presentation: https://doi.org/10.2514/6.2022-3458.vid Ongoing research at NASA is driven by a strategic plan defined by the Aeronautics Research Mission Directorate and a vision for future In-Time Aviation Safety Management Systems (IASMS) as described by the National Academies. In both visions, system safety awareness and provision are expanded through increased access to relevant data; integrated analysis and predictive capabilities; improved real-time detection and alerting of domain-specific hazards; decision support, and in some cases, automated risk mitigation strategies. One primary research focus is to develop means by which more timely (i.e., “in-time”) actions may be taken to mitigate precursors, anomalies, or trends that are observed during operations. In this paper, we describe such means as a collection of Services, Functions, and Capabilities (SFCs) that are supported by an underlying information system. For example, an integrated risk assessment capability is envisioned that continuously monitors safety-related metrics and margins and recommends timely operational changes. Assessment functions and/or services can be based on data analytics and predictive models derived from heterogeneous data sets that span relevant indicator metrics and their time histories. Likewise, on-board functions can identify and reduce susceptibility to precursor conditions that have led (and can lead) to aircraft loss-of-control or out-of-control accidents. This paper summarizes development and testing of such an information system tailored to hazards anticipated for future highly autonomous flight missions near and over densely populated areas. Testing is accomplished via simulation and by using small, unmanned aircraft operating over a test range at NASA’s Langley Research Center. Flight plans and test scenarios are defined to emulate several use-cases, including package delivery; reconnaissance; fire management; and urban air taxi vertiport operations. Two test phases are summarized with Phase 1 occurring in (2019-2020) and Phase 2 ongoing (2021-present). Results focus on SFC performance, technology readiness level assessment, and requirements discovery/validation. Companion papers are cited throughout for additional details on the recent testing.
Identification and Characterization of Negative Regulators of Rgg1518 Quorum Sensing in Streptococcus pneumoniae (2023)

Streptococcus pneumoniae is an agent of otitis media, septicemia, and meningitis and remains the leading cause of community-acquired pneumonia regardless of vaccine use. Of the various strategies that S. pneumoniae takes to enhance its potential to colonize the human host, quorum sensing (QS) is an intercellular communication process that provides coordination of gene expression at a community level. Numerous putative QS systems are identifiable in the S. pneumoniae genome, but their gene-regulatory activities and contributions to fitness have yet to be fully evaluated. To contribute to assessing regulatory activities of <i>rgg</i> paralogs present in the D39 genome, we conducted transcriptomic analysis of mutants of six QS regulators. Our results find evidence that at least four QS regulators impact the expression of a polycistronic operon (encompassing genes <i>spd_1517</i> to <i>spd_1513</i>) that is directly controlled by the Rgg/SHP1518 QS system. As an approach to unravel the convergent regulation placed on the <i>spd_1513-1517</i> operon, we deployed transposon mutagenesis screening in search of upstream regulators of the Rgg/SHP1518 QS system. The screen identified two types of insertion mutants that result in increased activity of Rgg1518-dependent transcription, one type being where the transposon inserted into <i>pepO</i>, an annotated endopeptidase, and the other type being insertions in <i>spxB</i>, a pyruvate oxidase. We demonstrate that pneumococcal PepO degrades SHP1518 to prevent activation of Rgg/SHP1518 QS. Moreover, the glutamic acid residue in the conserved "HExxH" domain is indispensable for the catalytic function of PepO. Finally, we confirmed the metalloendopeptidase property of PepO, which requires zinc ions, but not other ions, to facilitate peptidyl hydrolysis. <b>IMPORTANCE</b> Streptococcus pneumoniae uses quorum sensing to communicate and regulate virulence. In our study, we focused on one Rgg quorum sensing system (Rgg/SHP1518) and found that multiple other Rgg regulators also control it. We further identified two enzymes that inhibit Rgg/SHP1518 signaling and revealed and validated one enzyme's mechanisms for breaking down quorum sensing signaling molecules. Our findings shed light on the complex regulatory network of quorum sensing in Streptococcus pneumoniae.
The selection of layer thicknesses to control acoustic radiation force profiles in layered resonators (2003)

Ultrasonic standing waves can be used to generate radiation forces on particles within a fluid. A number of authors have derived detailed representations of these forces but these are most commonly applied using an approximation to the energy distribution based upon an idealized standing wave within a mode based upon rigid boundaries. An electro-acoustic model of the acoustic energy distribution within a standing wave with arbitrary thickness boundaries has been expanded to model the radiation force on an example particle within the acoustic field. This is used to examine the force profile on a particle at resonances other than those predicted with rigid boundaries, and with pressure nodes at different positions. A simple analytical method for predicting modal conditions for combinations of frequencies and layer thickness characteristics is presented, which predicts that resonances can exist that will produce a pressure node at arbitrary positions in the fluid layer of such a system. This can be used to design resonators that will drive particles to positions other than the center of the fluid layer, including the fluid/solid boundary of the layer, with significant potential applications in sensing systems. Further, the model also predicts conditions for multiple subwavelength resonances within the fluid layer of a single resonator, each resonance having different nodal planes for particle concentration.
Prognostic factors for short-term survival in alcoholic hepatitis in Japan: analysis by logistic regression. (1996)

Prognostic factors for the outcome of patients with alcoholic hepatitis were identified by logistic regression analysis. To predict the outcome immediately after admission, clinical data from 97 patients with alcoholic hepatitis on admission were introduced to multivariate analysis. Independent prognostic factors for favorable outcome were hepaplastin time, peripheral white blood cell count, age (40 to 60 years), and serum creatinine level (below 1.4 mg/dl). Sensitivity, specificity, positive predictive value, negative predictive value, and predictive accuracy were 0.78, 0.89, 0.78, 0.89, and 0.86, respectively. The resultant equation for the death rate was applied to another set of patients with alcoholic hepatitis as a validation study. Predictive accuracy estimated 0.95 in validation. The prognostic index derived was simple, accurate, and useful in the prediction of the outcome in patients with alcoholic hepatitis. Furthermore, it provides the clinician with an indication of the necessity for the intensive care of patients in a critical condition.
Mycobacterial Dose Defines the Th1/Th2 Nature of the Immune Response Independently of Whether Immunization Is Administered by the Intravenous, Subcutaneous, or Intradermal Route (1998)

It is believed that cell-mediated immunity alone can contain Mycobacterium tuberculosis, the pathogen responsible for tuberculosis. The induction of antibody, or of a mixed cell-mediated/humoral response, is associated with tuberculous disease. It is therefore important to determine the conditions of immunization with bacille Calmette Guérin (BCG), the attenuated strain of Mycobacterium bovis used to vaccinate humans against tuberculosis, that optimally induces an exclusive cell-mediated, Th1 response. Such a determination will then allow an assessment of whether the generation of such an exclusive Th1 response results in the generation of a Th1 imprint against mycobacteria. This Th1 imprint would ensure that the Th1 response is predominant following any challenge. We therefore tested the proposition that the dose of mycobacteria used for immunization generally determines the Th1/Th2 nature of the ensuing response. Our results demonstrate that relatively low doses lead to an almost exclusive cell-mediated, Th1 response, while higher doses induce a mixed Th1/Th2 response. Furthermore, the dependence on dose is independent of whether BCG is administered intravenously, subcutaneously, or intradermally. The implications of our findings to understanding how different classes of immunity are induced, to the epidemiology of tuberculosis, and to the design of effective vaccination strategies are discussed.
Intracellular Calcium Response and Adhesiveness of Chick Embryonic Retinal Neurons to Photoelectric Dye‐coupled Polyethylene Films as Prototypes of Retinal Prostheses (2006)

Photoelectric dyes, which absorb light and convert photon energy to electric potentials, were shown to stimulate retinal neurons in culture. One of these dyes coupled with polyethylene film surface, as a prototype of retinal prostheses, could induce intracellular calcium elevation in chick embryonic retinal tissues. In this study, we used retinal cells from chick embryos in which no photoreceptor outer segments yet developed, and assessed cell adhesiveness and response to the original and modified types of our retinal prostheses. Extruded-blown film of high density polyethylene was used as the original polyethylene film. Polyethylene film surface was modified either by coupling with type 1 collagen or by crystallization from the melt of the original polyethylene film. A photoelectric dye, 2-[2-[4-(dibutylamino)phenyl]ethenyl]-3-carboxymethylbenzothiazolium bromide, was coupled to these different types of polyethylene films through amide linkage. Retinal cells from chick embryos at the 12-day embryonic stage were cultured on the surface of dye-coupled films. The response of retinal cells to the dye-coupled films was observed by calcium imaging. Cell types, either neurons or glial cells, were detected by immunocytochemical staining and also observed by scanning electron microscopy (SEM). Intracellular calcium elevation was observed in cells, including both neurons and glial cells, on the surface of the original dye-coupled film, collagen-coated dye-coupled film, and dye-coupled recrystallized film, in contrast with no response of cells cultured on the dye-uncoupled plain film. Retinal neurons grew upon colonies of glial cells settling on the surface of all different types of the films. The number of retinal neurons on the collagen-coated dye-coupled film and dye-coupled recrystallized film was significantly larger than the number of neurons on the dye-uncoupled plain film (P = 0.0004, analysis of variance; P < 0.05, Tukey-Kramer test). With SEM, Muller cell-like large cells covered the original dye-coupled film and collagen-coated dye-coupled film, while neuron-like small cells settled directly on the dye-coupled recrystallized film and also formed large colonies on Muller-like cells. Retinal neurons and glial cells were cultured directly on the different types of dye-coupled polyethylene films. Photoelectric dye-coupled polyethylene films could be used as prototypes of retinal prostheses.
Lipid peroxidation in cord blood at birth: the effect of labour (1998)

The findings indicate that high levels of free oxygen radical activity in the fetus are a function of the labour process, as are changes in acid-base balance.
An Operating Strategy Approach for Serial/Parallel Hybrid Electric Vehicles (2022)

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;In this paper, a serial/parallel hybrid electric vehicle with a 17 kWh battery and 400 V voltage level is simulated. The vehicle is a C-segment vehicle, which has optimized driving resistances. It also has an external recharge possibility, which enables fully electric driving. The vehicle uses an Otto-engine concept as well as two electric motors. One motor is a permanent magnet synchronous motor and can be used as traction motor or generator, the other one is an induction motor used as main traction motor for the vehicle. The vehicle uses a 2-speed gearbox, where the electric motors are mounted in P2-configuration. To reach optimal results for the fuel consumption, an operating strategy based on the Equivalent Consumption Minimization Strategy (ECMS) is introduced and implemented in the vehicle simulation. This operating strategy uses a global optimization algorithm in combination with the local optimized fuel consumption, provided by the ECMS, to calculate the minimum possible fuel consumption for the vehicle. The simulated vehicle also targets EURO-7 emissions standards by using an electrical heated three-way-catalyst as well as a gasoline particle filter. To create proper simulation data, three different drive cycles are used for the simulations, including a low load, a medium load and a high load scenario. The different drive modes of the simulated vehicle are then analyzed and discussed to show the use of the internal combustion engine and the electric drive systems. In addition, the results of the simulations are shown and discussed to highlight the potential of the concept for future powertrain architectures.&lt;/div&gt;&lt;/div&gt;
Impact of donor factors on post-transplant delayed recovery of graft function in deceased donor kidney transplantation (2020)

Background: Deceased donor (DD) factors influence absolutely the post-transplant delayed recovery of graft function (DGF) in deceased donor kidney transplantation (DDKT). Although there are some tools for the status of DD such as expanded criteria donor criteria or kidney donor profile index score, but these tools do not fully reflect impact of DD factors on post-transplant DGF. Therefore, we aimed at investigating the DD factors related with the occurrence of DGF in DDKT. Methods: We retrospectively analyzed the medical records of DDKT performed at Keimyung University Dongsan Medical Center between February 2014 and September 2019. Our study enrolled 186 kidney transplant recipients (KTRs), with median follow-up of 45 months after DDKT. Results: Eighty-seven DDs (46.5%) had a documented history of smoking; 108 (57.8%), proteinuria; 80 (42.8%), transfusion; 95 (50.8%), acute kidney injury (AKI); and continuous renal replacement therapy (CRRT), 18 (9.6%). The incidence of DGF was significantly higher in KTRs from DDs with CRRT compared to those from DDs without CRRT (P=0.002). The incidence of DGF was also higher in KTRs from DDs with smoking history, but there were no significant association with the presence and amount of proteinuria and transfusion. Allograft function was significantly lower in the KTRs with DGF until 1 month after KT compared to those without DGF, but there was no significant difference of allograft function between the two groups at 12 months after KT. In Kaplan-Meier analysis, graft and patient survivals did not show the differences according to the characteristics of DDs with smoking, proteinuria, transfusion, AKI, and CRRT. In multivariate logistic analysis, AKI, CRRT, smoking, and donor hypertension were independent risk factors for DGF. Conclusions: DDs with AKI, CRRT, smoking, and hypertension can increase the risk of occurrence of DGF in KTRs. Therefore, DDKT from DDs with significant risk factors should be performed carefully.
Development of a peptide‐functionalized imaging nanoprobe for the targeting of (FXYD2)γa as a highly specific biomarker of pancreatic beta cells (2015)

Diabetes is characterized by a progressive decline of the pancreatic beta cell mass (BCM), which is responsible for insufficient insulin secretion and hyperglycaemia. There are currently no reliable methods to measure non-invasively the BCM in diabetic patients. Our work describes a phage display-derived peptide (P88) that is highly specific to (FXYD2)γa expressed by human beta cells and is proposed as a molecular vector for the development of functionalized imaging probes. P88 does not bind to the exocrine pancreas and is able to detect down to ~156 human pancreatic islets/mm(3) in vitro after conjugation to ultra-small particles of iron oxide (USPIO), as proven by the R2 measured on MR images. For in vivo evaluation, MRI studies were carried out on nude mice bearing Capan-2 tumours that also express (FXYD2)γa. A strong negative contrast was obtained subsequent to the injection of USPIO-P88, but not in negative controls. On human histological sections, USPIO-P88 seems to be specific to pancreatic beta cells, but not to duodenum, stomach or kidney tissues. USPIO-P88 thus represents a novel and promising tool for monitoring pancreatic BCM in diabetic patients. The quantitative correlation between BCM and R2 remains to be demonstrated in vivo, but the T2 mapping and the black pixel estimation after USPIO-P88 injection could provide important information for the future pancreatic BCM evaluation by MRI.
Specificity of two lipoxygenases from rice: Unusual regiospecificity of a lipoxygenase isoenzyme (1996)

The regio- and stereospecificity of two lipoxygenases from rice were investigated using arachidonic acid as the substrate. Rice seed lipoxygenase-2 (RSL-2) catalyzed oxygenation of arachidonic acid into a mixture of 5(S)-hydroperoxy-6,8,11,14-eicosatetraenoic acid [5(S)-HPETE] and 15(S)-hydroperoxy-5,8,11,13-eicosatetraenoic acid [15(S)-HPETE]. In addition, two double dioxygenase products, 5(S), 15(S)-dihydroperoxy-6,8,11,13 -eicosatetraenoic acid and 8(S),15(S)-dihydroperoxy-5,9,11,13 -eicosatetraenoic acid, were obtained in a lower yield. The regiospecificity of the RSL-2-catalyzed oxygenation was pH-dependent. Thus, incubation at pH 6.7 led to the formation of 5(S)-HPETE and 15(S)-HPETE in a ratio of 52:48, and incubation at pH 9.8 strongly suppressed production of 5(S)-HPETE and led to formation of 5(S)-HPETE and 15(S)-HPETE in a ratio of 3:97. A pH-dependent orientation of arachidonic acid at the active site is proposed to explain these findings. Rice leaf pathogen-inducible lipoxygenase [Peng, Y.-L., Shirano, Y., Ohta, H., Hibino, T., Tanaka, K., and Shibata, D. (1994) J. Biol. Chem. 269, 3755-3761] catalyzed oxygenation of arachidonic acid into a single hydroperoxide isomer of high optical purity, i.e., 15(S)-HPETE (99.5% S).
External system line outage identification using phasor measurement units (2012)

This paper investigates the problem of line outage detection in an area external to the operating area boundaries. The so-called “internal system” is assumed to be fully observable and the base case topology of the external system is assumed to be known. A limited number of phasor measurements are also assumed to be available from the external system. The paper takes advantage of the equivalent representation of a line outage by a pair of injections at the line's terminal buses and formulates the outage detection problem as an integer programming problem. Results are verified by simulating various external line outage scenarios using the IEEE 118-bus test system.
Triptolide‐Induced Expression of MicroRNA‐142‐3p Mediates Apoptosis of Pancreatic Cancer Cells by Inhibition of HSP70 (2011)

Triptolide inhibits cancer cell growth in vitro and blocks growth and metastatic spread in vivo . Our lab has shown that triptolide triggers apoptosis via inhibition of heat shock protein 70 (HSP70). As regulators gene expression, microRNAs (miRNAs) are increasingly recognized as powerful gatekeepers of apoptosis. Objective We would like to understand how triptolide affects miRNA expression and to identify miRNAs that mediate apoptosis. We hypothesize that triptolide inhibits HSP70 expression via a novel mechanism of inducing the expression of miR‐142‐3p. Methods We performed miRNA microarray analysis of human pancreatic cancer cells before and after triptolide treatment. We transfected miR‐142‐3p mimics and measured cell viability, caspase‐3 activation and HSP70 levels. Results MicroRNA‐142‐3p, predicted to target HSP70, was found in our miRNA microarray analysis to increase immediately after treatment. This finding has been validated by qRT‐PCR. Overexpression of miR‐142‐3p decreases cell viability, triggers caspase‐3 activation and decreases HSP70 expression. Conclusions Triptolide triggers the expression of miR‐142‐3p. Whether altered miR‐142‐3p expression may manipulate chemosensitivity to triptolide would be interesting to investigate. This research is funded in part by the PharmacoNeuroImmunology Training Grant: T32 DA07097
Supplementary Figure 7 from Identification of Alternative Splicing Markers for Breast Cancer (2023)

Supplementary Figure 7 from Identification of Alternative Splicing Markers for Breast Cancer
A low V<inf>&#x03C0;</inf>L modulator with GHz bandwidth based on an electro-optic polymer-clad silicon slot waveguide (2010)

We demonstrate a near-infrared modulator with a bandwidth exceeding 1GHz, based on a silicon strip-loaded slot waveguide clad in a nonlinear electro-optic polymer. Our device achieves a V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">π</sub> L figure of merit of 0.8V-cm.