gebhart/patrepeval huggingface dataset:
Comparison of OncoBEAM and NGS methods to detect plasma EGFR T790M mutations at progression of NSCLC (2018)

Background: Various methods have been employed to detect plasma EGFR mutations in patients with non-small cell lung cancer patients (NSCLC). Therefore, we evaluated the performance of digital PCR and next generation sequencing (NGS) to detect the p.T790M EGFR mutation in prospectively collected patient samples. Paired plasma samples from patients (CIRCAN cohort) that progressed on first-line EGFR TKI therapy were compared using two platforms: OncoBEAMTM-EGFR (Sysmex Inostics) and NGS (Illumina), utilizing the 56G oncology panel (Swift Biosciences). Methods: 196 stage 4 NSCLC patients with EGFR alteration under TKI were included from various center. Blood was collected in a routine setting, when physician noted changes in CT scans that were suspicious of progression. CfDNA analysis is recommended in front line in this setting in France. Replicate plasma samples were analysed using OncoBEAM and NGS. The thresholds for calling EGFR plasma mutations were 0.5% and 0.02% for NGS and OncoBEAM, respectively and were validated using cfDNA reference standards (Horizon Discovery). Results: OncoBEAM detected the p.T790M mutation in 36/196 patients (18.3%), whereas NGS detected T790M in 20/196 patients (10.2%). The agreement of NGS vs OncoBEAM for T790M detection was 55.6%. The p.T790M-positive samples detected by OncoBEAM but missed by NGS were all found to have low mutant allelic fractions (under 0.35%). With regard to sensitizing EGFR mutations, 28/36 OncoBEAM T790M+ patients had accompanying EGFR mutations, whereas all 20/20 NGS T790M+ samples showed presence of sensitizing mutations. In contrast to OncoBEAM, NGS testing revealed other somatic alterations including ERBB2 amplification, and mutations in TP53. Conclusions: In conclusion, these findings highlight the value of OncoBEAMTM-EGFR and NGS for detecting T790M at early progression. While less sensitive, NGS provided broader genomic coverage which may reveal diverse mechanisms of resistance. In contrast, OncoBEAM delivers superior sensitivity for focused detection of known resistance alterations such as EGFR T790M. Thus, OncoBEAM may provide the sensitivity required to monitor the kinetics of circulating tumor DNA and correlations with therapeutic response. Legal entity responsible for the study: Hospices Civils of Lyon. Funding: Sysmex Innostics / AstraZeneca. Disclosure: C. Tissot, P-J. Souquet: Membership on pharma advisory board. F.S. Jones, D. Edelstein: Sysmex Innostics. S. Couraud: AstraZeneca, Roche, MSD, Novartis, BMS, Boehringher Ingelheim, Chugai, Pfizer, Lilly, Merck. L.F. Payen: Membership on BMS; Advisory board: AstraZeneca. Z. Xu: Sophia Genetics. All other authors have declared no conflicts of interest.
ChemInform Abstract: Asymmetric Synthesis of Anticancer β‐Lactams via Staudinger Reaction: Utilization of Chiral Ketene from Carbohydrate. (2010)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
DICAM promotes T H 17 lymphocyte trafficking across the blood-brain barrier during autoimmune neuroinflammation (2022)

The migration of circulating leukocytes into the central nervous system (CNS) is a key driver of multiple sclerosis (MS) pathogenesis. The monoclonal antibody natalizumab proved that pharmaceutically obstructing this process is an effective therapeutic approach for treating relapsing-remitting MS (RRMS). Unfortunately, the clinical efficacy of natalizumab is somewhat offset by its incapacity to control the progressive forms of MS (PMS) and by life-threatening side effects in RRMS rising from the expression of its molecular target, very late antigen 4 (VLA4), on most immune cells and consequent impairment of CNS immunosurveillance. Here, we identified dual immunoglobulin domain containing cell adhesion molecule (DICAM) as a cell trafficking molecule preferentially expressed by T helper 17 (T<sub>H</sub>17)–polarized CD4<sup>+</sup> T lymphocytes. We found that DICAM expression on circulating CD4<sup>+</sup> T cells was increased in patients with active RRMS and PMS disease courses, and expression of DICAM ligands was increased on the blood-brain barrier endothelium upon inflammation and in MS lesions. Last, we demonstrated that pharmaceutically neutralizing DICAM reduced murine and human T<sub>H</sub>17 cell trafficking across the blood-brain barrier in vitro and in vivo, and alleviated disease symptoms in four distinct murine autoimmune encephalomyelitis models, including relapsing-remitting and progressive disease models. Collectively, our data highlight DICAM as a candidate therapeutic target to impede the migration of disease-inducing leukocytes into the CNS in both RRMS and PMS and suggest that blocking DICAM with a monoclonal antibody may be a promising therapeutic approach.
A License to Think (2008)

No matter what job or profession we end up in, we have the training, and the responsibility, to be the source of contemplation, the ability to evaluate facts and data and come up with explanations and objective suggestions for action; in short, to be the voice of reason in an emotional, stress-filled situation. However, just having earned a Ph.D. does not in itself make us more intelligent, or even better thinkers than others. Like any other skill, it has to be practiced and kept active to be at its peak. Athletes have to “work out” in order to be at the top of their skill. They also have to have the right conditions to produce their peak performance.
Pretreatment of Garlic Oil Extracts Hampers Epithelial Damage in Cell Culture Model of Peptic Ulcer Disease (2022)

<i>Background and Objectives:</i> Peptic ulcer disease is a chronic disease affecting up to 10% of the world's population. Proton pump inhibitors, such as lansoprazole are the gold standard in the treatment of ulcer disease. However, various studies have shown the effectiveness of garlic oil extracts in the treatment of ulcer disease. A cellular model can be established in the human gastric cell line by sodium taurocholate. The aim of this study was to explore the effects of garlic oil extracts pretreatment and LPZ addition in the cell culture model of peptic ulcer disease by examining oxidative stress and F-actin distribution. <i>Materials and Methods:</i> Evaluation was performed by determination of glutathione and prostaglandin E2 concentrations by ELISA; human gastric cell line proliferation by cell counting; expression of ATP-binding cassette, sub-family G, member 2; nuclear factor kappa B subunit 2 by RT PCR; and F-actin cytoskeleton visualization by semi-quantification of Rhodamine Phalloidin stain. <i>Results:</i> Our results showed significant reduction of cell damage after sodium taurocholate incubation when the gastric cells were pretreated with lansoprazole (<i>p</i> < 0.001) and increasing concentrations of garlic oil extracts (<i>p</i> < 0.001). Pretreatment with lansoprazole and different concentrations of garlic oil extracts increased prostaglandin E2 and glutathione concentrations in the cell culture model of peptic ulcer disease (<i>p</i> < 0.001). Positive correlation of nuclear factor kappa B subunit 2 (<i>p</i> < 0.01) with lansoprazole and garlic oil extracts pretreatment was seen, while ATP-binding cassette, sub-family G, member 2 expression was not changed. Treatment with sodium taurocholate as oxidative stress on F actin structure was less pronounced, although the highest concentration of garlic oil extracts led to a statistically significant increase of total amount of F-actin (<i>p</i> < 0.001). <i>Conclusions:</i> Hence, pretreatment with garlic oil extracts had gastroprotective effect in the cell model of peptic ulcer disease. However, further experiments are needed to fully elucidate the mechanism of this protective role.
Parallel Linear Search with no Coordination for a Randomly Placed Treasure (2016)

In STOC'16, Fraigniaud et al. consider the problem of finding a treasure hidden in one of many boxes that are ordered by importance. That is, if a treasure is in a more important box, then one would like to find it faster. Assuming there are many searchers, the authors suggest that using an algorithm that requires no coordination between searchers can be highly beneficial. Indeed, besides saving the need for a communication and coordination mechanism, such algorithms enjoy inherent robustness. The authors proceed to solve this linear search problem in the case of countably many boxes and an adversary placed treasure, and prove that the best speed-up possible by $k$ non-coordinating searchers is precisely $\frac{k}{4}(1+1/k)^2$. In particular, this means that asymptotically, the speed-up is four times worse compared to the case of full coordination. We suggest an important variant of the problem, where the treasure is placed uniformly at random in one of a finite, large, number of boxes. We devise non-coordinating algorithms that achieve a speed-up of $6/5$ for two searchers, a speed-up of $3/2$ for three searchers, and in general, a speed-up of $k(k+1)/(3k-1)$ for any $k \geq 1$ searchers. Thus, as $k$ grows to infinity, the speed-up approaches three times worse compared to the case of full coordination. Moreover, these bounds are tight in a strong sense as no non-coordinating search algorithm for $k$ searchers can achieve better speed-ups. We also devise non-coordinating algorithms that use only logarithmic memory in the size of the search domain, and yet, asymptotically, achieve the optimal speed-up. Finally, we note that all our algorithms are extremely simple and hence applicable.
ON SELECTING THE BEST FEATURES IN A NOISY ENVIRONMENT (1998)

summary:This paper introduces a novel method for selecting a feature subset yielding an optimal trade-off between class separability and feature space dimensionality. We assume the following feature properties: (a) the features are ordered into a sequence, (b) robustness of the features decreases with an increasing order and (c) higher-order features supply more detailed information about the objects. We present a general algorithm how to find under those assumptions the optimal feature subset. Its performance is demonstrated experimentally in the space of moment-based descriptors of 1-D signals, which are invariant to linear filtering.
Seasonal variation in methane fluxes from sedimentary basins to the atmosphere: Results from chamber measurements and modeling of transport from deep sources (2000)

Results from modeling of microseepage are presented that suggest that under proper conditions some thermogenic CH 4 is transported to the atmosphere without complete consumption by methanotrophic bacteria in soils. These computer simulations are supported by direct measurement of CH 4 fluxes in seasonally dry and/or cold climate sedimentary basins where losses to the atmosphere were postulated to occur. Measurements in four semiarid sedimentary basins where a thermogenic CH 4 source is expected found small positive fluxes during cooler/drier seasons and negative fluxes during warmer/wetter seasons. Small positive fluxes up to 43 mg CH 4 m −2 d −1 were found. A similar result was found for two geothermal areas in a semiarid climate where CH 4 derived from the Fischer‐Tropsch reaction operating in the reservoir provides a deep source of CH 4 . The results of the computer simulations, and direct field measurement of CH 4 fluxes in dry and/or cold terrestrial environments suggest that a portion of the global atmospheric budget of CH 4 may be from microseepage.
Dosimetry protocol for the preclinical trials in white‐beam minibeam radiation therapy (2011)

A new promising radiotherapy approach is being explored at the ESRF: Minibeam Radiation Therapy. To assess the therapeutic index of this new modality, in vivo experiments are being planned, for which an accurate knowledge of the dosimetry is essential. For that purpose, a complete set of measurements and Monte Carlo simulations was performed. The first dosimetry protocol for preclinical trials in minibeam radiation therapy was established. This protocol allows to have reproducibility in terms of dose for the different biological studies.
Comparison of the haemodynamic effects of bucindolol, propranolol and pindolol in healthy volunteers. (1985)

The effects of single oral doses of bucindolol (50, 100, 200 and 400 mg), pindolol (10 mg), propranolol (160 mg) and placebo on arterial pressure and heart rate in the supine and standing positions and exercise heart rate were compared in 12 healthy male volunteers. Supine heart rate was significantly greater after all four doses of bucindolol and pindolol in comparison to propranolol. Bucindolol had no significant effect on standing heart rate which was significantly reduced by pindolol and propranolol. Bucindolol, pindolol and propranolol significantly reduced an exercise tachycardia for at least 24 h after drug administration. Supine systolic pressure was not affected by any treatment but supine diastolic pressure was significantly reduced by bucindolol (200 and 400 mg) and by pindolol. All doses of bucindolol, propranolol and pindolol significantly reduced standing systolic blood pressure. There was a significant linear trend for reductions in standing systolic blood pressure and increasing doses of bucindolol. Standing diastolic blood pressure was significantly reduced by bucindolol 200 and 400 mg. Faintness and light headedness occurred in 6 of 12 subjects after 200 mg bucindolol and in 8 of 10 subjects after 400 bucindolol. After bucindolol, analysis of plasma samples demonstrated the presence of bucindolol, 5-hydroxy and 6-hydroxy bucindolol and indolyl-t-butylamine. These observations indicate that in man, bucindolol is a beta-adrenoceptor blocking drug with hypotensive activity and probably partial agonist activity. It is unlikely that the hypotensive effects result from blockade of beta-adrenoceptors or from the drug's partial agonist activity.
Marginal B-6 intake affects protein synthesis in rat tissues (1986)

The role of vitamin B-6 in amino acid metabolism suggests that inadequate B-6 intake may impair protein synthesis. To test this hypothesis, 30 male rats (initially 227 g) were fed AIN76A diets that contained control, marginal or devoid levels of B-6 (5.8, 1.2 or 0.1 mg B-6/kg diet, by analysis) ad libitum for 9 weeks. Protein synthesis rates (PSRs) were measured in liver, kidney and calf muscle using a flooding dose of /sup 3/H-phenylalanine. Marginal and control groups ate and gained weight at similar rates. The marginal diet did not elevate xanthurenic acid (XA) excretion following a tryptophan load. However, marginal B-6 intake did depress liver PSR by 29% (2182 vs 1549 mg/day, P<.05), liver wet weight by 15% (19.0 vs 16.1 g, P<.05) and muscle PSR by 23% (3.0 vs 2.3%/day, P<.10). Unexpectedly, marginal B-6 intake increased PSR in kidney 47% (90 vs 132 mg/day, P<.05). The devoid diet, which increased XA excretion following a tryptophan load by more than 3-fold, depressed PSRs 56% in liver and 31% in muscle. However, the devoid diet decreased food intake by 40% (25.0 vs 15.0 g/day); therefore effects of devoid B-6 intake on PSRs may have been confounded by deficits in protein-energymore » intake in devoid vs control groups. These data demonstrate that marginal B-6 intake alters protein synthesis in tissues of the rat.« less
Cooperative Output Regulation of Heterogeneous Multi-Agent Systems: An $H_{\infty}$ Criterion (2013)

In this note, the cooperative output regulation problem of heterogeneous linear multi-agent systems is investigated. Our approach is based on internal model and dynamic error feedback among the agents. Under some standard assumptions, the problem is solved by an internal model and a stabilizing H <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">∞</sub> controller. We showed that the exo-signal-free system is stabilized if each controlled agent is robust (in the sense of H <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">∞</sub> norm) to resist the disturbance measured by the second largest eigenvalue of the graph adjacency matrix. Then the synthesis problem is solved using algebraic Riccati equation. Furthermore, we showed that this condition is a generalization of existing results.
An experimental and theoretical study of the mixing characteristics of a periodically reoriented irrotational flow (2010)

The minimum-energy method to generate chaotic advection should be to use an irrotational flow. However, irrotational flows have no saddle connections to perturb in order to generate chaotic orbits. To the early work of Jones & Aref (Jones & Aref 1988 Phys. Fluids 31, 469-485 (doi:10.1063/1.866828)) on potential flow chaos, we add periodic reorientation to generate chaotic advection with irrotational experimental flows. Our experimental irrotational flow is a dipole potential flow in a disc-shaped Hele-Shaw cell called the rotated potential mixing flow; it leads to chaotic advection and transport in the disc. We derive an analytical map for the flow. This is a partially open flow, in which parts of the flow remain in the cell forever, and parts of it pass through with residence-time and exit-time distributions that have self-similar features in the control parameter space of the stirring. The theory compares well with the experiment.
Study of the Reaction of Epoxides withCarboxylic Acids by IR and Raman Spectrometry (1996)

IR and Raman spectra were used to follow the reaction of epoxides with carboxylic acids. A number of bands in the IR and Raman spectra were used for quantitative and qualitative analysis of the reaction, including kinetic measurements. The results obtained were used for the analysis of epoxide reactions on a rubber surface, in a rubber–resin mixture and in prepared plastic constructions.
An Association Between Stress‐Induced Disruption of the Hypothalamic‐Pituitary‐Adrenal Axis and Disordered Glucose Metabolism in an Animal Model of Post‐Traumatic Stress Disorder (2009)

Retrospective clinical reports suggesting that traumatic stress populations display an increased propensity for glucose metabolism disorders were examined in a controlled prospective animal model. Stress-induced behavioural and hypothalamic-pituitary-adrenal (HPA) axis response patterns were correlated to central and peripheral parameters of glucose metabolism and signalling, and to body measurements in Sprague-Dawley rats exposed to predator scent stress. Forty days post-exposure, fasting blood glucose and insulin levels, oral glucose tolerance test, body weight and white adipose tissue mass, systemic corticosterone levels and brain expression of insulin receptor (IR) and insulin-sensitive glucose transporter 4 (GLUT4) protein levels were evaluated. In a second experiment inbred strains with hyper- (Fischer) and hypo- (Lewis) reactive HPA axes were employed to assess the association of metabolic data with behavioural phenomenology versus HPA axis response profile. For data analysis, animals were classified according to their individual behavioural response patterns (assessed at day 7) into extreme, partial and minimal response groups. The exposed Sprague-Dawley rats fulfilling criteria for extreme behavioural response (EBR) (20.55%) also exhibited significant increases in body weight, abdominal circumference and abdominal white adipose tissue mass; a hyperglycaemic oral glucose tolerance test; and fasting hyperglycaemia, hyperinsulinaemia and hypercorticosteronemia, whereas minimal responders (MBR) and control animals displayed no such disturbances. Hippocampal and hypothalamic expression of IR and GLUT4 protein were significantly lower in EBR than in MBR and control rats. The inbred strains showed no metabolic differences at baseline. Exposed Fischer rats displayed hyperglycaemia and hyperinsulinaemia, whereas Lewis rats did not. A significant protracted disorder of glucose metabolism was induced by exposure to a stress paradigm. This metabolic response was associated with the characteristic pattern of HPA axis (corticosterone) response, which underlies the behavioural response to stress.
The antifungal activity of human parotid secretion is species-specific (2010)

Candida albicans is the major fungal colonizer of the oral cavity and causes oral candidiasis in immunocompromised patient populations. While antifungal proteins in saliva have been identified and the virulence factors of C. albicans have been well studied, little is known about the role saliva plays in the preferential colonization of the oral cavity by C. albicans. We report that the fungistatic activity of human parotid secretion toward six C. albicans strains is considerably lower than towards nine non-C. albicans fungal species (average IC₅₀ values >1000 mg/l and <70 mg/l, respectively). The species-specific activity of parotid secretion suggests that saliva may play a determining role in oral fungal colonization patterns.
Deeply-scaled CMOS-integrated nanophotonic devices for next generation supercomputers (2011)

High-performance computing (HPC) systems capable of delivering Exaflops performance are envisioned to become a reality by the end of this decade. In order to provide the enormous communication bandwidth that is necessary, hundreds of millions of optical interconnects will have to be deployed to connect together racks, modules and chips. To achieve such massive level of parallelism for HPC systems, monolithic integration of deeply scaled silicon optical circuits into the front-end of standard CMOS process have been demonstrated as a promising technology.
Autonomous image-based ultrasound probe positioning via deep learning (2018)

Although ultrasound (US) is a widely used, non-invasive, and radiation-free imaging modality, manual adjustment of the US probe can be cumbersome and time consuming. An autonomous US scanning device could not only reduce dependence on sonographer’s skills and experience but also improve workflow efficiency especially during interventional procedures. Robot-assisted ultrasound imaging has the potential to improve patient care in rural and underserved areas. There are many previous efforts in this direction but none is fully automatic or accurate enough. In this work, as an initial small step towards independent US imaging workflow solution, we developed and evaluated a robot-assisted fully autonomous ultrasound (RAFAUS) probe positioning system. Desired motion of the probe toward the target view is directly derived from anatomical features implicitly extracted via deep neural network; thus, making this technique (a) invariant to anatomical differences (patient size or organ displacement), (b) decoupled from the robotic system, (c) registration-free, and (d) independent from any external tracking technologies.