gebhart/patrepeval huggingface dataset:
Use of Telaprevir to Treat Hepatitis C Recurrence after Liver Transplantation in an HIV Co-infected Patient (2013)

Purpose: A 62-year-old Caucasian male with HIV and chronic HCV genotype 1b, complicated by cirrhosis and hepatocellular carcinoma, underwent OLT. He developed recurrent hepatitis C, 9 months post-transplantation. HAART regimen included emtricitabine-tenofovir 200-300 mg daily, etravirine 200 mg BID, and darunavir-ritonavir 600 mg-100 mg BID, due to previously failed therapy and HIV resistance. CD4 count was 461 cells/μL, and he was negative for HIV-1 RNA by PCR. His immunosuppression regimen consisted of tacrolimus 0.5 mg every 15 days (while on HIV protease inhibitors), and mycophenolate mofetil 500 mg bid. His transaminases were in the 150-300 U/L range. Baseline HCV RNA was at 4,920,000 IU/mL, and interleukin 28B genotype was CT. Prior to starting TVR-based triple therapy, we stopped darunavir-ritonavir and started raltegravir 400 mg BID to avoid having the patient on both HCV and HIV protease inhibitors. His tacrolimus level was increased to 0.5 mg BID during the transition. On day one of TVR-based therapy, the patient was started on TVR 750 mg TID, ribavirin 400 mg BID, and pegylated interferon α2a 180 mcg weekly. In addition, he took 0.5 mg of tacrolimus, and the tacrolimus level was checked at 12 and 24 hours, and every other day thereafter for 2 weeks. Tacrolimus goal level was 4-6 ng/mL. The mean area under the concentration time curve (AUC) for tacrolimus while on TVR was 348 ng.hr/mL, compared to an expected AUC of 67 ng.hr/mL without TVR. The highest tacrolimus level encountered was 10 ng/mL (12 hours after the initial dose). Maintenance dose of tacrolimus while on TVR was 0.5 mg every 5 days. HCV RNA was not quantifiable (<43 IU/mL) at week four of HCV therapy, and was undetectable at week eight. He completed 12 weeks of telaprevir, continued on ribavirin/pegylated interferon α2a, and switched back to his HAART regimen. HCV RNA remained negative at week 24. This case demonstrates that telaprevir-based triple therapy can be used to treat HCV recurrence in HIV co-infected patients with frequent adjustments to tacrolimus dosage. Disclosure: Dr. Alkhouri - Consultant/speaker: Vertex Pharmaceuticals Incorporated.Table: Table. Laboratory tests and virological responsesFigure: Different treatment time points and changes to tacrolimus dose.
GLISp-r: A preference-based optimization algorithm with convergence guarantees (2022)

Preference-based optimization algorithms are iterative procedures that seek the optimal calibration of a decision vector based only on comparisons between couples of different tunings. At each iteration, a human decision-maker expresses a preference between two calibrations (samples), highlighting which one, if any, is better than the other. The optimization procedure must use the observed preferences to find the tuning of the decision vector that is most preferred by the decision-maker, while also minimizing the number of comparisons. In this work, we formulate the preference-based optimization problem from a utility theory perspective. Then, we propose GLISp-r, an extension of a recent preference-based optimization procedure called GLISp. The latter uses a Radial Basis Function surrogate to describe the tastes of the decision-maker. Iteratively, GLISp proposes new samples to compare with the best calibration available by trading off exploitation of the surrogate model and exploration of the decision space. In GLISp-r, we propose a different criterion to use when looking for new candidate samples that is inspired by MSRS, a popular procedure in the black-box optimization framework. Compared to GLISp, GLISp-r is less likely to get stuck on local optima of the preference-based optimization problem. We motivate this claim theoretically, with a proof of global convergence, and empirically, by comparing the performances of GLISp and GLISp-r on several benchmark optimization problems.
State Estimation and Fault Detection for Nonlinear Dynamic Systems (2018)

In practical problems, the dynamic systems are usually nonlinear. In this case, the traditional Kalman filter cannot be used for state estimation or fault detection. The two typical extension based on Kalman filtering framework is the Extended Kalman Filter (EKF) and the Unscented Kalman Filter (UKF). Theoretically speaking, UKF is better than EKF when estimation accuracy is concerned, especially for high degree nonlinear cases. This paper is concerned with the state estimation and fault detection problem for a class of nonlinear dynamic systems. A novel fault detection and analyse method is presented based on the period residual of EKF and UKF. For different kind of faults, mainly, the system parameter error, the sensor/data error, EKF and UKF are used and the estimation and fault detection effects are compared and analyzed.
E-posters are Better than Traditional Posters: The Debate (2020)

With the advent of this century, information technology has become an integral part of medical education and research. Posters have always been a strong medium of information dissemination amongst researchers and students alike. E-Posters are the talk of the hour, with most of the major events having provisions for the same. Some researchers consider it a must in today's world, whereas others still consider traditional posters as being more personal and having a stronger impact. This debate has been put forth in the following article, with each author putting forth their points in favor of their respective preferences and finally coming up with a conclusion about the topic.
A comparative study on the in vitro metabolism of cisapride using subcellular liver fractions of dog, rabbit, and male and female rats (1986)

Abstract Cisapride‐ 3 H, labeled at the fluorophenyl moiety or at the piperidine ring, was incubated with the supernatant and microsomal fractions of various animal livers and an NADPH‐generating system. The major metabolites were identified by co‐chromatography with high performance liquid chromatography (HPLC) and by mass spectrometry. A mass balance of the major metabolites in incubates was made up by radio‐HPLC. The rate of metabolism of the drug decreased in the following order: rabbit ≥ male rat ≥ dog ≥ female rat. The major in vitro metabolic pathways in the animal species were rather similar. Main biotransformation routes were oxidative N ‐dealkylation at the piperidine nitrogen and aromatic hydroxylation occurring either at the fluorophenyl or at the benzamide moiety. Hydroxylation was relatively more abundant in female compared to male rats, whereas oxidative O ‐dealkylation was important in incubates with rabbit subcellular fractions only. Furthermore, the formation of at least four sulfate conjugates could be demonstrated. Metabolism experiments with phenobarbital‐induced or 3‐methylcholanthrene‐induced microsomes indicated that phenobarbital inducible cytochrome P‐450 isoenzyme(s) are involved in the in vitro metabolism of cisapride.
Aerosol formation pathways from aviation emissions (2022)

Abstract Aviation emissions are responsible for an estimated 24,000 premature mortalities annually and 3.5% of anthropogenic radiative forcing (RF). Emissions of nitrogen and sulfur oxides (NO x and SO x ) contribute to these impacts. However, the relative contributions and mechanisms linking these emissions to formation and impacts of secondary aerosols (as opposed to direct aerosol emissions) have not been quantified, including how short-lived aerosol precursors at altitude can increase surface-level aerosol concentrations. We apply global chemistry transport modeling to identify and quantify the different chemical pathways to aerosol formation from aviation emissions, including the resulting impact on radiative forcing. We estimate a net aerosol radiative forcing of –8.3 mWm −2 , of which –0.67 and –7.8 mWm −2 result from nitrate and sulfate aerosols respectively. We find that aviation NO x causes –1.7 mWm −2 through nitrate aerosol forcing but also –1.6 mWm −2 of sulfate aerosol forcing by promoting oxidation of SO 2 to sulfate aerosol. This accounts for 21% of the total sulfate forcing, and oxidation of SO 2 due to aviation NO x is responsible for 47% of the net aviation NO x attributable RF. Aviation NO x emissions in turn account for 41% of net aviation-aerosol-attributable RF (non-contrail). This is due to ozone-mediated oxidation of background sulfur and the ‘nitrate bounce-back’ effect, which reduces the net impact of sulfur emissions. The ozone-mediated mechanism also explains the ability of cruise aviation emissions to significantly affect surface aerosol concentrations. We find that aviation NO x emissions cause 72% of aviation-attributable, near-surface aerosol loading by mass, compared to 27% from aviation SO x emissions and less than 0.1% from direct emission of black carbon. We conclude that aviation NO x and SO x emissions are the dominant cause of aviation-attributable secondary inorganic aerosol radiative forcing, and that conversion of background aerosol precursors at all altitudes is amplified by enhanced production of aviation attributable oxidants at cruise altitudes.
Insertion des légumineuses dans les systèmes de culture : source d’azote symbiotique et de diversification des assolements (2017)

National audience
Role of deep-sea equipment in promoting the forefront of studies on life in extreme environments (2021)

The deep-sea environment creates the largest ecosystem in the world with the largest biological community and extensive undiscovered biodiversity. Nevertheless, these ecosystems are far from well known. Deep-sea equipment is an indispensable approach to research life in extreme environments in the deep-sea environment because of the difficulty in obtaining access to these unique habitats. This work reviewed the historical development and the state-of-the-art of deep-sea equipment suitable for researching extreme ecosystems, to clarify the role of this equipment as a promoter for the progress of life in extreme environmental studies. Linkages of the developed deep-sea equipment and the discovered species are analyzed in this study. In addition, Equipment associated with researching the deep-sea ecosystems of hydrothermal vents, cold seeps, whale falls, seamounts, and oceanic trenches are introduced and analyzed in detail. To clarify the thrust and key points of the future promotion of life in extreme environmental studies, prospects and challenges related to observing equipment, samplers, laboratory simulation systems, and submersibles are proposed. Furthermore, a blueprint for the integration of <i>in situ</i> observations, sampling, controllable culture, manned experiments in underwater environments, and laboratory simulations is depicted for future studies.
Event-driven Security-Constrained Unit Commitment (2016)

Power system operators commonly rely on a security-constrained unit commitment (SCUC) to schedule available generation resources for satisfying the forecasted load and ensuring system security in response to limited components unavailability. Although widely used and proved viable, the SCUC problem cannot guarantee a useful solution in response to extreme events with potentially multiple outages. This paper proposes and formulates an Event-driven SCUC (E-SCUC) model which ensures a resilient supply of loads in case of multiple component outages. The new N-1-m reliability criterion, in which m is the number of components on outage due to the extreme event, is proposed and integrated with the model. A probabilistic estimation model of possible component outages is further investigated. The E-SCUC problem is formulated using mixed-integer linear programming (MILP). Merits and effectiveness of the proposed models are demonstrated using the standard IEEE 30-bus system. Comparing the results of the E-SCUC with the SCUC demonstrates the resiliency benefits of the proposed model as it ensures a considerably lower load curtailment at the expense of nominal cost increase.
New quantitative approach reveals heterogeneity in mitochondrial structure–function relations in tumor-initiating cells (2019)

Steady-state mitochondrial structure or morphology is primarily maintained by a balance of opposing fission and fusion events between individual mitochondria, which is collectively referred to as mitochondrial dynamics. The details of the bidirectional relationship between the status of mitochondrial dynamics (structure) and energetics (function) require methods to integrate these mitochondrial aspects. To study the quantitative relationship between the status of mitochondrial dynamics (fission, fusion, matrix continuity and diameter) and energetics (ATP and redox), we have developed an analytical approach called mito-SinCe<sup>2</sup> After validating and providing proof of principle, we applied mito-SinCe<sup>2</sup> on ovarian tumor-initiating cells (ovTICs). Mito-SinCe<sup>2</sup> analyses led to the hypothesis that mitochondria-dependent ovTICs interconvert between three states, that have distinct relationships between mitochondrial energetics and dynamics. Interestingly, fusion and ATP increase linearly with each other only once a certain level of fusion is attained. Moreover, mitochondrial dynamics status changes linearly with ATP or with redox, but not simultaneously with both. Furthermore, mito-SinCe<sup>2</sup> analyses can potentially predict new quantitative features of the opposing fission versus fusion relationship and classify cells into functional classes based on their mito-SinCe<sup>2</sup> states.This article has an associated First Person interview with the first author of the paper.
A biventricular multimodal (MRI/ultrasound) cardiac phantom (2012)

A cardiac phantom can be of crucial importance in the development and validation of ultrasound and cardiac magnetic resonance (MR) imaging and image analysis methods. A biventricular multimodal cardiac phantom has been manufactured in-house that can simulate normal and pathologic hearts with different degrees of infarction. The two-chamber structure can simulate the asymmetric left ventricular motion. Poly Vinyl Alcohol (PVA) is utilized as the basic material since it can simulate the shape, elasticity, and MR and ultrasound properties of the heart. The cardiac shape is simulated using a two-chamber acrylic mold. An additional pathologic heart phantom has been built to simulate aneurysm and infarction. Segmental dyskinesis is modeled based on three inclusions of different shapes and different degrees of elasticity. The cardiac elasticity is adjusted based on freeze-thaw cycles of the PVA cryogel for normal and scarred regions.
Bicoherence-based structural health monitoring of fixed offshore structures (2010)

Structural integrity management is key to the safe and economic operation of offshore structures. Presently, regular manual inspections are conducted. This is expensive, time consuming, and prone to human error. This paper investigates the possibility of using the bicoherence function of the measured structural acceleration to provide automatic early detection of damage in an offshore structure. The method is shown to be insensitive to typical operating parameter variations and to variations in wave excitation force, and demonstrates that very small changes in stiffness of individual structural members are detectable from measurements of global structural motion.
Parametric down conversion with a depleted pump as a heuristic model for black hole particle production (2014)

In this paper we extend the investigation of Adami and Ver Steeg [Class. Quantum Grav. \textbf{31}, 075015 (2014)] to treat the process of black hole particle emission effectively as the analogous quantum optical process of parametric down conversion (PDC) with a dynamical (depleted vs. non-depleted) `pump' source mode which models the evaporating black hole (BH) energy degree of freedom. We investigate both the short time (non-depleted pump) and long time (depleted pump) regimes of the quantum state and its impact on the Holevo channel capacity for communicating information from the far past to the far future in the presence of Hawking radiation. The new feature introduced in this work is the coupling of the emitted Hawking radiation modes through the common black hole `source pump' mode which phenomenologically represents a quantized energy degree of freedom of the gravitational field. This (zero-dimensional) model serves as a simplified arena to explore BH particle production/evaporation and back-action effects under an explicitly unitary evolution which enforces quantized energy/particle conservation. Within our analogous quantum optical model we examine the entanglement between two emitted particle/anti-particle and anti-particle/particle pairs coupled via the black hole (BH) evaporating `pump' source. We also analytically and dynamically verify the `Page information time' for our model which refers to the conventionally held belief that the information in the BH radiation becomes significant after the black hole has evaporated half its initial energy into the outgoing radiation. Lastly, we investigate the effect of BH particle production/evaporation on two modes in the exterior region of the BH event horizon that are initially maximally entangled, when one mode falls inward and interacts with the black hole, and the other remains forever outside and non-interacting.
Novel Pyrogen Tests Based on the Human Fever Reaction (2001)

3Biochemical Pharmacology, University of Konstanz, P.O. Box M 655, 78457 Konstanz, Germany; 4National Institute of Public Health (NIPH), Department of Vaccinology, P.O. Box 4404 Torshov, Geitmyrsveien 75, 0403 Oslo, Norway; 5Milenia-Biotec, Hohe Strasse 4–8, 61231 Bad Nauheim, Germany; 6Medical Products Agency, P.O. Box 26, Husargatan 8, 751 03 Uppsala, Sweden; 7European Directorate for the Quality of Medicines, Council of Europe, P.O. Box 907, 67029 Strasbourg Cedex 1, France; 8ECVAM, JRC Institute for Health and Consumer Protection, European Commission, 21020 Ispra (VA), Italy; 9Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51–59, 63225 Langen, Germany; 10National Institute for Public Health and the Environment (RIVM), LGM, P.O. Box 1, 3720 BA Bilthoven, The Netherlands; 11Analysis and Control Department, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark; 12Pharma Hameln GmbH, Langes Feld 13, 31789 Hameln, Germany; 13Division of Endocrinology, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK; 14Office of Testing and Research, Center for Drug Evaluation and Research, Food and Drug Administration, FD-900, Parklawn Building, Room 13B-06, 5600 Fishers Lane, Rockville, MD 20857, USA; 15Institut fur Medizinische Chemie und Biochemie, Universitat Innsbruck, Fritz-Pregl-Strasse 3, 6020 Innsbruck, Austria ATLA 29, 99–123, 2001 99
Avoiding the pull-in instability of a dielectric elastomer film and the potential for increased actuation and energy harvesting (2017)

Pull-in instability often occurs when a film of a dielectric elastomer is subjected to an electric field. In this work, we concoct a set of simple, experimentally implementable, conditions that render the dielectric elastomer film impervious to pull-in instability for all practical loading conditions. We show that a uniaxially pre-stretched film has a significantly large actuation stretch in the direction perpendicular to the pre-stretch and find that the maximal specific energy of a dielectric elastomer generator can be increased from 6.3 J g<sup>-1</sup> to 8.3 J g<sup>-1</sup> by avoiding the pull-in instability.
Some Digital Editions and Some Remaining Challenges (2012)

While the digital edition has made enormous progress since the advent of the web, there is also much that we still don't know how to achieve. I examine a number of editions and some things they have taught us. Then I discuss a few open questions regarding digital editions: how to involve volunteers in the creation and upkeep of the edition, how to lower the cost of creating editions and how to deal with threats to their longevity.
More flexible and simpler logic circuits implemented with resonant tunneling transistors (1995)

MOBILE is a logic gate exploiting the monostable-bistable transition of a circuit consisting of two resonant tunneling transistors. This paper describes the application of MOBILEs to fabricate more flexible, simpler logic circuits, such as variable-function logic gates and simple one-dimensional cellular automata for a random sequence generator.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Hydrogel plug for independent sample and buffer handling in continuous microchip capillary electrophoresis (2013)

In microchip capillary electrophoresis most frequently electrokinetic sample injection is utilized, which does not allow pressure driven sample handling and is sensitive for pressure drops due to different reservoir levels. For efficient field tests a multitude of samples have to be processed with the least amount of external equipment. We present the use of a hydrogel plug to separate the sample from clean buffer to enable independent sample change and buffer refreshment. In-situ polymerization of the gel does away with complex membrane fabrication techniques. The sample is electrokinetically injected through the gel and subsequently separated by a voltage between the second gel inlet and the buffer outlet. By blocking of disturbing flows by the gel barrier a well-defined ion plug is obtained. After each experiment, the sample and the separation channel can be flushed independently, allowing for a continuous operation mode in order to process multiple samples.
Use of a water-soluble busulfan formulation--pharmacokinetic studies in a canine model (1995)

In a canine model we investigated the toxicity and pharmacokinetics of a water soluble busulfan preparation. Busulfan was dissolved in dimethylsulfoxide (DMSO) and administered either orally or intravenously in a single dose of 1 mg/kg. The application in either preparation was well tolerated. In seven dogs, peak levels in the range of 730 ng/mL to 1,000 ng/mL were measured after intravenous injection with an area under curve (AUC) of 75 ng.h/kg.mL to 146 ng.h/kg.mL. It was of note that even the oral administration of the same busulfan preparation resulted in AUC values in the same range as observed after parenteral application. The absorption rate of busulfan tablets in our model was as unpredictable as documented in clinical trials. On the basis of the present study, clinical trials using busulfan dissolved in DMSO given either intravenously or orally appear warranted. This approach should lead to predictable blood levels, reduced toxicity, and increased efficacy of busulfan-containing regimens.
Ytterbium triflate (and trimethylsilyl triflate) catalyzed isomerization of glycidic esters to α-hydroxy-β,γ-unsaturated esters and their conversion into cyclopentanoids using Johnson-Claisen rearrangement (2002)

A variety of glycidic esters undergo smooth isomerization to the corresponding -hydroxy-, unsaturated esters upon reaction with Yb(OTf) 3 or TMSOTf. These -hydroxy-, -unsaturated esters undergo Johnson-Claisen rearrangement to appropriately substituted diesters, some of which are converted into cyclopentanoids.