gebhart/patrepeval huggingface dataset:
A Mainstreaming: Analysis of a Policy Instrument (2008)

In the world of public policy, waves of innovations and new policy developments are usually followed by movements of rationalisation. Most policy domains, in the EU as elsewhere, progressively become institutionalised, a sedimentation of institutions and policy instruments progressively creating a mille feuilles within which contradictions take place, hence the drive in due course either to add another layer, to change the institution or to create new instruments to rationalise existing ones (...).
Causal inference in epidemiological studies with strong confounding (2012)

One of the identifiability assumptions of causal effects defined by marginal structural model (MSM) parameters is the experimental treatment assignment (ETA) assumption. Practical violations of this assumption frequently occur in data analysis when certain exposures are rarely observed within some strata of the population. The inverse probability of treatment weighted (IPTW) estimator is particularly sensitive to violations of this assumption; however, we demonstrate that this is a problem for all estimators of causal effects. This is due to the fact that the ETA assumption is about information (or lack thereof) in the data. A new class of causal models, causal models for realistic individualized exposure rules (CMRIER), is based on dynamic interventions. CMRIER generalize MSM, and their parameters remain fully identifiable from the observed data, even when the ETA assumption is violated, if the dynamic interventions are set to be realistic. Examples of such realistic interventions are provided. We argue that causal effects defined by CMRIER may be more appropriate in many situations, particularly those with policy considerations. Through simulation studies, we examine the performance of the IPTW estimator of the CMRIER parameters in contrast to that of the MSM parameters. We also apply the methodology to a real data analysis in air pollution epidemiology to illustrate the interpretation of the causal effects defined by CMRIER.
X-ray determination of strains, stress, and relaxation in interconnect metallizations (1994)

Accurate modeling of stresses and strains and prediction of stresses leading to stress‐assisted diffusive voiding in interconnection metallizations requires measurement of the stress/strain state of the lines during thermal cycling. X‐rays are a proven method for measuring strains and calculating stresses in lines and yield precise results when properly interpreted. We highlight two x‐ray geometries we have used to successfully determine the strain and stress state of unpassivated and passivated aluminum alloy lines. There is good agreement between the two techniques. Additionally, we have measured strain relaxation in the lines. We correlate the relaxation in passivated Al alloy lines with direct observation of stress‐induced voiding performed using a scanning transmission electron microscope.
Total Synthesis of Mycalolides A and B through Olefin Metathesis (2015)

An asymmetric total synthesis of the trisoxazole marine macrolides mycalolides A and B is described. This synthesis involves the convergent assembly of highly functionalized C1-C19 trisoxazole and C20-C35 side-chain segments through the use of olefin metathesis and esterification as well as Julia-Kocienski olefination and enamide formation as key steps.
Insights into the neurodegenerative process of Alzheimer's disease: a role for mononuclear phagocyte-associated inflammation and neurotoxicity (1999)

Since the first description of Alzheimer's disease (AD) in 1907, significant progress was made into understanding disease pathophysiology. The enormous effort in AD research has translated into the discovery of genetic linkages for disease, into elucidating the structure and function of the etiologic beta-amyloid protein, and into unraveling the seemingly complex neuroimmunological cascade that affects neuronal dysfunction. Although effective therapies do not currently exist, many are being developed. We propose that the neuropathogenesis of AD, in measure, revolves around the immunological activation of glial cells, which in turn leads to alterations in inflammatory neurotoxin production, and ultimately to neuronal injury and death. Elucidating the mechanisms involved in such glial cell immune activation should provide valuable insights into understanding the disease process and in providing effective therapeutics to prevent and/or retard the devastating neurodegeneration that afflicts so many of our elderly.
Modulation of autophagy by probiotic bacteria: selecting and engineering strains able to stimulate autophagy in intestinal epithelial cells (2018)

National audience
Compact Metamaterial Antenna for Angular Localization of Radio-frequency Sources (2023)

Localization of radio-frequency sources is commonly carried out by adjusting the radiation patterns of phased arrays to scan a specific region. This task could be difficult and expensive to implement in some frequency regimes of the last generation of communication systems. We present an alternative to the classical Radio-frequency angular localization based on a single port compact metamaterial antenna. We use a finite periodic array of sub-wavelength (λ/6) resonators for the design of this antenna. We show that the proposed antenna is able to achieve several complex radiation patterns over a specific narrow frequency band. We implement numerical methods to estimate the direction of a target antenna by taking benefits of the complex frequency signatures over this band. We demonstrate experimentally in the microwave regime that a single port antenna made of a finite array of metamaterial resonators can be used to retrieve the incident direction.
The PAR2 inhibitor I-287 selectively targets Gαq and Gα12/13 signaling and has anti-inflammatory effects (2020)

Protease-activated receptor-2 (PAR2) is involved in inflammatory responses and pain, therefore representing a promising therapeutic target for the treatment of immune-mediated inflammatory diseases. However, as for other GPCRs, PAR2 can activate multiple signaling pathways and those involved in inflammatory responses remain poorly defined. Here, we describe a new selective and potent PAR2 inhibitor (I-287) that shows functional selectivity by acting as a negative allosteric regulator on Gα<sub>q</sub> and Gα<sub>12/13</sub> activity and their downstream effectors, while having no effect on G<sub>i/o</sub> signaling and βarrestin2 engagement. Such selective inhibition of only a subset of the pathways engaged by PAR2 was found to be sufficient to block inflammation in vivo. In addition to unraveling the PAR2 signaling pathways involved in the pro-inflammatory response, our study opens the path toward the development of new functionally selective drugs with reduced liabilities that could arise from blocking all the signaling activities controlled by the receptor.
Activation of human mast cells by retrocyclin and protegrin highlight their immunomodulatory and antimicrobial properties (2015)

Preclinical evaluation of Retrocyclins (RC-100, RC-101) and Protegrin-1 (PG-1) antimicrobial peptides (AMPs) is important because of their therapeutic potential against bacterial, fungal and viral infections. Human mast cells (HMCs) play important roles in host defense and wound healing but the abilities of retrocyclins and protegrin-1 to harness these functions have not been investigated. Here, we report that chemically synthesized RC-100 and PG-1 caused calcium mobilization and degranulation in HMCs but these responses were not blocked by an inhibitor of formyl peptide receptor-like 1 (FPRL1), a known receptor for AMPs. However, RC-100 and PG-1 induced degranulation in rat basophilic leukemia (RBL-2H3) cells stably expressing Mas related G protein coupled receptor X2 (MrgX2). Chemical synthesis of these AMPs is prohibitively expensive and post-synthesis modifications (cyclization, disulfide bonds, folding) are inadequate for optimal antimicrobial activity. Indeed, we found that synthetic RC-100, which caused mast cell degranulation via MrgX2, did not display any antimicrobial activity. Green-fluorescent protein (GFP)-tagged RC-101 (analog of RC-100) and GFP-tagged PG-1 purified from transgenic plant chloroplasts killed bacteria and induced mast cell degranulation. Furthermore, GFP-PG1 bound specifically to RBL-2H3 cells expressing MrgX2. These findings suggest that retrocyclins and protegrins activate HMCs independently of FPRL1 but via MrgX2. Harnessing this novel feature of AMPs to activate mast cell's host defense/wound healing properties in addition to their antimicrobial activities expands their clinical potential. Low cost production of AMPs in plants should facilitate their advancement to the clinic overcoming major hurdles in current production systems.
A Trust-Evaluation-Enhanced Blockchain-Secured Industrial IoT System (2020)

The Industrial Internet of Things (IIoT), allowing direct wireless communications between industrial machines and people, is the key component of Industry 4.0. By grouping several IIoT devices (IIoT-Ds) into IIoT groups (IIoT-Gs), the IIoT-Ds within one group can share information and deter malicious users from accessing the network by modifying the access control list (ACL) in IIoT-Ds. In an IIoT-G, several IIoT-Ds jointly manage the access control of IIoT sensors. The security of ACL is protected by blockchains deployed in IIoT-Ds. Even secured by blockchains, a blockchain-based IIoT-G (B-IIoT-G) still cannot secure correct access control in a system with more than half of the blockchain-based IIoT-Ds (B-IIoT-Ds) from spreading wrong authorization information. In this article, we propose a B-IIoT-G with trust evaluation for each B-IIoT-D to evaluate the weight in voting for final decisions of authorization. By designing a new voting mechanism with trust evaluation for the access control in B-IIoT-G, the system has a higher probability of making correct authorization even with malicious B-IIoT-Ds. Simulation results have demonstrated that the mechanism with trust evaluation can still make, with a high probability, correct authorization even with more than half of the B-IIoT-Ds in B-IIoT-G being malicious.
Optimal coded sampling for temporal super-resolution (2010)

Conventional low frame rate cameras result in blur and/or aliasing in images while capturing fast dynamic events. Multiple low speed cameras have been used previously with staggered sampling to increase the temporal resolution. However, previous approaches are inefficient: they either use small integration time for each camera which does not provide light benefit, or use large integration time in a way that requires solving a big ill-posed linear system. We propose coded sampling that address these issues: using N cameras it allows N times temporal superresolution while allowing ~N/2 times more light compared to an equivalent high speed camera. In addition, it results in a well-posed linear system which can be solved independently for each frame, avoiding reconstruction artifacts and significantly reducing the computational time and memory. Our proposed sampling uses optimal multiplexing code considering additive Gaussian noise to achieve the maximum possible SNR in the recovered video. We show how to implement coded sampling on off-the-shelf machine vision cameras. We also propose a new class of invertible codes that allow continuous blur in captured frames, leading to an easier hardware implementation.
FIBTEM PLUS Provides an Improved Thromboelastometry Test for Measurement of Fibrin-Based Clot Quality in Cardiac Surgery Patients (2013)

The FIBTEM PLUS assay produces precise results. At baseline, it provides greater inhibition of platelets than FIBTEM, but there is no meaningful difference between FIBTEM PLUS and FIBTEM in patients with low platelet counts.
Applications of Lithium‐Containing Hydrides for Energy Storage and Conversion (2014)

Abstract Lithium‐containing hydrides and some derivatives are mainly used in synthetic chemistry for the selective reduction of functional groups. Hydrogen storage applications of complex Li hydrides and reactive mixtures with other metal hydrides or amides have been investigated thoroughly, but practical applications are hampered due to limited reversibility and unfavorable conditions for the sorption and desorption of hydrogen. In the field of electrochemical energy storage, complex Li‐containing hydrides are investigated as Li‐ion‐conducting materials and as active materials for anodes of non‐aqueous batteries.
Evaporative Concentration on a Paper-Based Device to Concentrate Analytes in a Biological Fluid (2014)

We report the first demonstration of using heat on a paper device to rapidly concentrate a clinically relevant analyte of interest from a biological fluid. Our technology relies on the application of localized heat to a paper strip to evaporate off hundreds of microliters of liquid to concentrate the target analyte. This method can be used to enrich for a target analyte that is present at low concentrations within a biological fluid to enhance the sensitivity of downstream detection methods. We demonstrate our method by concentrating the tuberculosis-specific glycolipid, lipoarabinomannan (LAM), a promising urinary biomarker for the detection and diagnosis of tuberculosis. We show that the heat does not compromise the subsequent immunodetectability of LAM, and in 20 min, the tuberculosis biomarker was concentrated by nearly 20-fold in simulated urine. Our method requires only 500 mW of power, and sample flow is self-driven via capillary action. As such, our technology can be readily integrated into portable, battery-powered, instrument-free diagnostic devices intended for use in low-resource settings.
The Congenital Heart Disease Genetic Network Study: Cohort description (2018)

The Pediatric Cardiac Genomics Consortium (PCGC) designed the Congenital Heart Disease Genetic Network Study to provide phenotype and genotype data for a large congenital heart defects (CHDs) cohort. This article describes the PCGC cohort, overall and by major types of CHDs (e.g., conotruncal defects) and subtypes of conotrucal heart defects (e.g., tetralogy of Fallot) and left ventricular outflow tract obstructions (e.g., hypoplastic left heart syndrome). Cases with CHDs were recruited through ten sites, 2010-2014. Information on cases (N = 9,727) and their parents was collected through interviews and medical record abstraction. Four case characteristics, eleven parental characteristics, and thirteen parent-reported neurodevelopment outcomes were summarized using counts and frequencies and compared across CHD types and subtypes. Eleven percent of cases had a genetic diagnosis. Among cases without a genetic diagnosis, the majority had conotruncal heart defects (40%) or left ventricular outflow tract obstruction (21%). Across CHD types, there were significant differences (p<0.05) in the distribution of all four case characteristics (e.g., sex), four parental characteristics (e.g., maternal pregestational diabetes), and five neurodevelopmental outcomes (e.g., learning disabilities). Several characteristics (e.g., sex) were also significantly different across CHD subtypes. The PCGC cohort is one of the largest CHD cohorts available for the study of genetic determinants of risk and outcomes. The majority of cases do not have a genetic diagnosis. This description of the PCGC cohort, including differences across CHD types and subtypes, provides a reference work for investigators who are interested in collaborating with or using publically available resources from the PCGC.
Determining Acceptability of Blood Glucose Meters: Statistical Methods for Determining Error (1996)

In this article we examine the statistics that summarize random error (imprecision) and systematic error (inaccuracy) in the evaluation of blood glucose—monitoring devices. Random error is estimated from replicate testing of patient samples or manufacturers’ controls; systematic error is estimated from the comparison of methods study. Total error combines the measurements of random error and systematic error into a single value and allows comparison of glucose meters’ performance to established standards. Recommendations from the American Diabetes Association Consensus Conference in 1986 specify a 15% maximum performance error. These recommendations are standards currently accepted for evaluations of blood glucose meters.
Phase I trial of 5-azacitidine (5AC) and SNDX-275 in advanced lung cancer (NSCLC) (2008)

19036 Background: Epigenetic gene silencing is a key contributor to lung carcinogenesis. Pre-clinical studies suggest that combining inhibitors of DNA methyltransferase (DNMT) with inhibitors of histone deacetylase (HDAC) synergistically induce re-expression of epigenetically-silenced tumor suppressor genes. Combination of the DNMT inhibitor, 5AC, with the HDAC inhibitor, SNDX-275, in hematologic malignancies has shown remarkable activity. This study proposed to find a safe and tolerable dose of 5AC and SNDX-275 in NSCLC. Methods: Eligible patients were adults with advanced NSCLC and progressive disease after at least one previous chemotherapy regimen. 5AC was given SQ days 1–6 and 8–10 with SNDX-275 at a fixed dose of 7 mg/day on days 3 and 10 of a 28 day cycle. 5AC dose was varied between cohorts using a standard 3+3 phase I dose assessment schema. Diagnostic tumor blocks and serial sputum and serum samples were obtained for pharmacodynamic (PD) analysis of promoter methylation status of candidate genes of interest at baseline and with therapy. Serial blood draws were performed for pharmacokinetic (PK) analysis of both 5AC and SNDX-275. Results: Ten subjects were enrolled in this phase I study. Demographics include: mean age (range) - 63 (51–80); M:F - 5:5; 100% former smokers; Adenocarcinoma:squamous - 8:2; mean number of previous therapies - 3. No dose limiting toxicities (DLT) were seen in the 30 mg/m2 dose cohort. At 40 mg/m2, one subject was replaced due to rapidly progressive disease during week 1. One subject experienced a hematologic DLT (grade 3 neutropenia and thrombocytopenia). No long term adverse outcomes from the DLT were seen. Common low grade toxicities included injection site reactions, nausea/vomiting, constipation, fatigue, and cytopenias. A major and durable partial response has been observed in one patient, which is ongoing at >8 months. Two patients had disease stabilization through ≥2 cycles of therapy; the remaining patients had progressive disease. PK and PD correlative analyses are in progress. Conclusions: 5AC and SNDX-275 are safe and tolerable, and associated with clinical activity in advanced NSCLC patients. We have determined a recommended phase II dose and have initiated phase II enrollment of the same patient population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Oncomethylome Sciences, Pharmion Oncomethylome Sciences, Pharmion Oncomethylome Sciences, Pharmion
Development of a simple new flow cytometric antibody-dependent cellular cytotoxicity (ADCC) assay with excellent sensitivity (2018)

Antibody-based therapeutic strategies have become recognized as useful clinical options in several types of cancer, often with the expectation that such therapies will trigger target cell elimination via antibody-dependent cellar cytotoxicity (ADCC) by natural killer cells. The successful development of therapeutic monoclonal antibodies (mAbs) requires an assay system that permits a critical evaluation of their physicochemical and biological characteristics. At present a number of ADCC assay systems have been reported, however, there is still room for improvement in terms of usability, operability and sensitivity. Here we report a novel flow cytometric ADCC assay that uses a human natural killer cell line stably transfected with mouse FcγRIII, and Fc receptor common-γ chain (FcRγ) and a reporter gene as effector cells. This assay relies on discriminating effector and target cells by their differential immunofluorescence, which allows for clear-cut gating and accurate calculation of the number of surviving cells in a target population. This assay is easy and quick to perform and provides reliable data even for low frequency target cells in assay samples and with low concentrations of mAbs. Furthermore, our approach allows us to identify synergistic ADCC activity of mAbs with different epitope specificities on the same target antigen.
Time-reversal symmetrization of spontaneous emission for quantum state transfer (2014)

We demonstrate the ability to control spontaneous emission from a superconducting qubit coupled to a cavity. The time domain profile of the emitted photon is shaped into a symmetric truncated exponential. The experiment is enabled by a qubit coupled to a cavity, with a coupling strength that can be tuned in tens of nanoseconds while maintaining a constant dressed state emission frequency. Symmetrization of the photonic wave packet will enable use of photons as flying qubits for transferring the quantum state between atoms in distant cavities.
Thermophilic Proteins as Versatile Scaffolds for Protein Engineering (2018)

Literature from the past two decades has outlined the existence of a trade-off between protein stability and function. This trade-off creates a unique challenge for protein engineers who seek to introduce new functionality to proteins. These engineers must carefully balance the mutation-mediated creation and/or optimization of function with the destabilizing effect of those mutations. Subsequent research has shown that protein stability is positively correlated with "evolvability" or the ability to support mutations which bestow new functionality on the protein. Since the ultimate goal of protein engineering is to create and/or optimize a protein's function, highly stable proteins are preferred as potential scaffolds for protein engineering. This review focuses on the application potential for thermophilic proteins as scaffolds for protein engineering. The relatively high inherent thermostability of these proteins grants them a great deal of mutational robustness, making them promising scaffolds for various protein engineering applications. Comparative studies on the evolvability of thermophilic and mesophilic proteins have strongly supported the argument that thermophilic proteins are more evolvable than mesophilic proteins. These findings indicate that thermophilic proteins may represent the scaffold of choice for protein engineering in the future.