gebhart/patrepeval huggingface dataset:
mRNA-LNP expressing PfCSP and Pfs25, two leading vaccine candidates targeting infection and transmission of Plasmodium falciparum (2022)

Abstract Malaria is a deadly disease responsible for between 550,000 and 627,000 deaths annually. There is a pressing need to develop vaccines focused on malaria elimination. The complex lifecycle of Plasmodium falciparum provides opportunities not only to target the infectious sporozoite stage, introduced by anopheline mosquitoes, but also the sexual stages, which are ingested by mosquitoes during blood feeding, leading to parasite transmission. It is widely recognized that a vaccine targeting multiple stages would induce efficacious transmission reducing immunity. Technological advancements offer new vaccine platforms, such as mRNA-LNPs, which can be used to develop highly effective malarial vaccines. We evaluated the immunogenicity of two leading P. falciparum vaccine candidates, Pfs25 and PfCSP, delivered as mRNA-LNP vaccines. Both vaccines induced extremely potent immune responses when administered alone or in combination. Purified IgGs from Pfs25 mRNA-LNPs immunized mice were highly potent in reducing malaria transmission to mosquitoes. Additionally, mice after three and four immunizations with PfCSP mRNA-LNP provided evidence for varying degrees of protection against sporozoite challenge. The comparison of immune responses and stage-specific functional activity induced by each mRNA-LNP vaccine, administered alone or in combination, also supports the development of an effective combination vaccine without any risk of immune interference for targeting malaria parasites at various life cycle stages. A combination of vaccines targeting both the infection stage and sexual/midgut stages is expected to interrupt malaria transmission, which is critical for achieving elimination goals.
Impact of asymmetries on fuel performance in inertial confinement fusion (2018)

Low-mode asymmetries prevent effective compression, confinement, and heating of the fuel in inertial confinement fusion (ICF) implosions, and their control is essential to achieving ignition. Ion temperatures (${T}_{\mathrm{ion}}$) in ICF experiments are inferred from the broadening of primary neutron spectra. Directional motion (flow) of the fuel at burn also impacts broadening and will lead to artificially inflated ``${T}_{\mathrm{ion}}$'' values. Flow due to low-mode asymmetries is expected to give rise to line-of-sight variations in measured ${T}_{\mathrm{ion}}$. We report on intentionally asymmetrically driven experiments at the OMEGA laser facility designed to test the ability to accurately predict and measure line-of-sight differences in apparent ${T}_{\mathrm{ion}}$ due to low-mode asymmetry-seeded flows. Contrasted to chimera and xrage simulations, the measurements demonstrate how all asymmetry seeds have to be considered to fully capture the flow field in an implosion. In particular, flow induced by the stalk that holds the target is found to interfere with the seeded asymmetry. A substantial stalk-seeded asymmetry in the areal density of the implosion is also observed.
Staining with Fluorescein Diacetate Correlates with Hepatocyte Function (1993)

To establish the importance of fluorescein diacetate (FDA) as a viability stain for cultured hepatocytes, we hypothesized that FDA staining would correlate positively with hepatocyte viability and function. Mixtures of live and dead cells were stained with FDA and scanned by flow cytometry. A close correlation was observed between the live cell fraction and percent viability as determined by FDA staining (R2 = 0.962). Hepatocytes were also sorted into low fluorescence and high fluorescence groups. Both albumin production and lidocaine metabolism (P-450 activity) were significantly increased in the high fluorescence group compared to the low fluorescence group. An automated, fluorescence-activated assay was useful for rapid assessment of hepatocyte viability. In addition, the intensity of green fluorescence following staining with FDA correlated well with two specific measures of hepatocyte function.
Intrinsic Resistance to JAK2 Inhibition in Myelofibrosis (2011)

Abstract Abstract 2825 Myeloproliferative neoplasms (MPN) are a group of clonal hematopoietic stem cell disorders with a variable clinical course: essential thrombocytosis (ET) and polycythemia vera (PV) are associated with excess clotting and bleeding but an overall normal or near-normal life expectancy, while myelofibrosis has a variable but generally poor prognosis. The disorders are unified by the constitutive activation of the JAK2 pathway, most commonly by a point mutation in the pseudokinase domain of JAK2 (JAK2 V617F). Small molecule tyrosine kinase inhibitors have been shown to be active in both preclinical and late-phase clinical testing, and yet notably pharmacodynamic validation of target (JAK2) inhibition has never been rigorously demonstrated in clinical studies. Clinical investigation of JAK2 inhibitors has focused on myelofibrosis, with some unexpected results: while reduction in spleen size and amelioration of constitutional symptoms are frequent, only modest changes in mutant clonal burden have been observed and complete responses by any criteria are exceedingly rare. In order to develop a feasible and informative pharmacodynamic assay for measuring JAK2 signaling, we used phospho-specific flow cytometry on whole peripheral blood to measure phosphorylation of STAT3 and STAT5, the canonical targets of JAK2 in hematopoietic cells. Treating whole blood with tyrosine kinase inhibitors currently in clinical development, we observed a dose-dependent decrease in phospho-STAT5 and STAT3 in granulocytes treated ex vivo in cells from normal donors, patients with ET, PV and to a lesser extent from patients with myelofibrosis. We found that phosphorylation of STAT3 and STAT5 in cells from patients with myelofibrosis were significantly less inhibited than in PV and ET as well as normal donors. Using quantitative RT-PCR, we found that sensitivity to inhibition did not correlate with JAK2 V617F clonal burden. To determine whether extracellular determinants conferred resistance, mixing studies showed that plasma from patients with myelofibrosis did not transfer resistance. Plasma cytokines that signal through JAK2 and/or are known to be altered in myelofibrosis were measured and no single cytokine appeared to account for the observed pattern of resistance. Taken together these observations suggest that there are cell intrinsic mechanisms that define a priori resistance to JAK2 inhibition in myelofibrosis, and the lesion is localized upstream of STAT3 and STAT5. Disclosures: Carroll: Sanofi Aventis Corporation: Research Funding; TetraLogic Pharmaceuticals: Research Funding; Agios Pharmaceuticals: Research Funding; Glaxo Smith Kline, Inc.: Research Funding.
Use of MagniSep chromium dioxide particles in an immunoassay system. (1990)

The use of chromium dioxide particles as a solid support for very sensitive and rapid immunoassays, is the result of the combination of large surface area (40 m2) and high protein uptake capacity (40 mg/g) allowing rapid capture kinetics and high binding capacity. Magnetic and physical properties of these particles give a rapid separation, a complete resuspension and a rapid high-efficiency washing, highly desirable characteristics for efficient automation of immunoassays. Good precision and accuracy, exemplified by excellent recovery, parallelism and correlation were demonstrated. Test results prove that the technology is highly flexible and applicable to a variety of assay formats.
Copolymerization of Carbon–carbon Double-bond Monomer (Styrene) with Cyclic Monomer (Tetrahydrofuran) (2012)

We reported in this work that the cationic copolymerization in one step takes place between carbon–carbon double-bond monomer styrene with cyclic monomer tetrahydrofuran. The comonomers studied belong to different families: vinylic and cyclic ether. The reaction is initiated with maghnite-H+ an acid exchanged montmorillonite as acid solid ecocatalyst. Maghnite-H+ is already used as catalyst for polymerization of many vinylic and heterocyclic monomers. The oxonium ion of tetrahydrofuran and carbonium ion of styrene propagated the reaction of copolymerization. The acetic anhydride is essential for the maintenance of the ring opening of tetrahydrofuran and the entry in copolymerization. The temperature was kept constant at 40°C in oil bath heating for 6 hours. A typical reaction product was analyzed by 1H-NMR, 13C-NMR and IR and the formation of the copolymer was confirmed. The reaction was proved by matched with analysis. The maghnite-H+ allowed us to obtain extremely pure copolymer in good yield by following a simples operational conditions. © 2012 by Authors, Published by BCREC Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0)
Vinylpolymerisation. 216. Mitt. polmerisation von methylencycloalkanen (1968)

Abstract Die Polymerisation sowie due Copolymerisation von Methylencyclobutan, ‐cyclopentan und ‐cyclohexan wurden untev verschiedenen Bedingungen untersucht. Es ergab sich, daß Methylencycloalkane nicht homopolymerisieren, aber radikalisch mit einigen Vinylmonomeren ziemlich leicht copolymerisiert werden können. Die Aktivierungsenergien sowieentropien bei der Copymermerisation von Methylencycloalkanen wurden ermittelt.
Novel antiphospholipid antibodies in autoimmune bullous diseases (2015)

aPL auto antibodies are more prevalent in ABD. Any clinical association should be further determined.
TWO MILLIPEDS OF THE GENUS <i>RHYSODESMUS</i> FROM MEXICO (1942)

The type specimens of the two species of Rhysodesmus described below were collected by Mr. Phil Rau, through whose courtesy the author received them for study. The specimens are at present in the author's collection.
Three New Acetylenes from the Palauan Sponge <i>Haliclona</i> sp. (1996)

Three acetylenic metabolites 1−3 were isolated from the marine sponge Haliclona sp. from Palau, Western Caroline Islands. The structures were elucidated by interpretation of spectral data, and the absolute configuration of (3R,4E,23Z)-3-hydroxy-11-methylhexacosa-4,23-diene-1,25-diyne (1) was determined using the Mosher method.
<i>EMF</i> , an <i>Arabidopsis</i> Gene Required for Vegetative Shoot Development (1992)

In higher plants, the transition from the vegetative to the; reproductive state in the shoot meristem initiates flowering. To study this floral transition, Constitutively flowering mutant of Arabidopsis thaliana ecotype columbia, embryonic flower (emf), was characterized. No vegetative shoots were produced from emf embryos or calli; the shoot apical meristems (SAMs) in the emf embryos were altered compared to wild-type SAMs. The mutant SAMs enlarged precociously and produced inflorescence meritems upon germination. These results suggest that the dominant, wild-type allele EMF is required for the vegetative state of the SAM. In the absence of EMF function, the mutant embryo assumes the reproductive state.
ChemInform Abstract: 3‐ALKOXYALLENYLLITHIUM REAGENTS AS β‐ACYL VINYL ANION EQUIVALENTS. A NEW SYNTHESIS OF PYRENOPHORIN (1985)

Abstract Das Allen (I) liefert ein Li‐Derivat (II), das mit Elektrophilen zu den Z‐ und E‐isomeren Substitutionsprodukten (III) und (IV) führt.
Evidence for central summation of C and Aδ nociceptive activity in man (1994)

Using two different stimulators, we have induced activity in A delta and C afferents in order to investigate a possible summation of nociceptive activity from these two fiber types. We used nociceptive electrical stimulation to evoke activity in A delta fibers. High-intensity light from a xenon lamp, focused into a liquid light guide which was positioned on a spot painted black under the sole of the foot, resulted in a characteristic delayed burning sensation, indicating selective C-fiber activation. By varying the delay between radiant heat and electrical stimuli (0-3000 msec), sensations evoked by these stimuli were brought to coincide. When we elicited the electrical stimulation during on-going burning pain, corresponding to a delay of approximately 1 sec between the stimulations, we found a significantly higher nociceptive withdrawal reflex in tibialis anterior (P < 0.01) and a higher overall pain rating (P < 0.05). The existence of a summation mechanism at the spinal cord is the most likely explanation for our findings. Furthermore, the results demonstrate that the nociceptive reflex may be modulated by on-going C-fiber activity.
Airway basal cells of healthy smokers express an embryonic stem cell signature relevant to lung cancer (2013)

Activation of the human embryonic stem cell (hESC) signature genes has been observed in various epithelial cancers. In this study, we found that the hESC signature is selectively induced in the airway basal stem/progenitor cell population of healthy smokers (BC-S), with a pattern similar to that activated in all major types of human lung cancer. We further identified a subset of 6 BC-S hESC genes, whose coherent overexpression in lung adenocarcinoma (AdCa) was associated with reduced lung function, poorer differentiation grade, more advanced tumor stage, remarkably shorter survival, and higher frequency of TP53 mutations. BC-S shared with hESC and a considerable subset of lung carcinomas a common TP53 inactivation molecular pattern which strongly correlated with the BC-S hESC gene expression. These data provide transcriptome-based evidence that smoking-induced reprogramming of airway BC toward the hESC-like phenotype might represent a common early molecular event in the development of aggressive lung carcinomas in humans.
Continuous2HHO determination in H2O solution by a computer-controlled mass spectrometer (1982)

Direct interfacing of a membrane based mass spectometer separator to an aqueous solution of water-saturted gas stream allows continuous monitoring of a vareity of dissolved volatile compunds. Even if the solution is saturated with atmoshpheric gases, we demonstrate that deuterated water concentration in aqueous solution can be measured over concentration ranges of interest to physiological studies, with an estimated, extrapolated detection limit less than the natural abundance.
Quantification of Dual Reporter Cell Cultures via Image Analysis (2015)

The successful performance of experiments is tightly related to the efficiency and reliability of the analytical methods used for the data analysis. This is particularly true when data is collected as images and the quantification of the biological effect behind the picture is often an issue. Consistent evaluation represents a challenge even for experienced biologists. Even though other techniques allow the quantification of fluorescent cell populations, (FACS, among others) image analysis is widely used. For this reason there is an increasing need of methods for reliable and reproducible\nquantification of images. To this aim a new algorithm for image analysis has been developed that allows rapid quantification of fluorescent Dual Reporter cells populations. These cells can express RFP (αSMA) or EGFP (collagen), and, via epi-fluorescence, come up as red or green, or yellow when RFP and GFP co-localize within the same cell. The algorithm can quantify and classify these sub-sets, by using a fuzzy, two-pass class partitioning, in addition to Difference of Gaussians and watershed segmentation techniques for blob detection and extraction. Results show average errors in the 2-6% range and an analysis time of 6-9 seconds per acquired image. The algorithm was validated against manual quantification techniques and compared to other state-of-the-art software. It allows rapid detection and extraction of Dual Reporter cells distributions in acquired epi-fluorescence optical fields. Finally, thanks to the implementation of semi-automated calibration procedures, the algorithm constitutes a totally objective instrument for quantification and classification measurements, especially when class boundaries are not sharply defined.
Historical Aspects of the Development of Live Virus Vaccines in Poliomyelitis (1960)

Today when scientific genius has extended man's intellectual control far beyond the horizons of this planet, it somehow does not seem quite apropos to discuss an infection which, so far as we know, affects the population of only one of the planets and causes illness in only a very small fraction of this population. However, the Committee of the College of Physicians of Philadelphia, who have greatly honored me as a recipient of the Alvarenga Prize, suggested that I should consider vaccination against poliomyelitis as a likely topic and, acquiescing to their demands, I have decided to trace tonight the history of the development of live polio vaccine. "History" is one word in the lexicon of all languages which is subject to constant misinterpretation. Hegel was probably right when he said that we learn from history that men never learn anything from history. And there is Fabre's aphorism: "History records
Cardioprotective effects of trimetazidine: a review (2003)

The efficacy of trimetazidine, an anti-ischaemic agent, has been largely assessed and presented in the international literature through its metabolic effects, selective and specific fatty acid oxidation inhibition and lack of haemodynamic effects in stable angina pectoris. As such, trimetazidine has opened up a new class of metabolic agents that reduce fatty acid oxidation: the 3-KAT (3-ketoacyl-CoA thiolase) inhibitors. The aim of this review article is to demonstrate the cardioprotective benefits of trimetazidine, and how this can be translated into positive effects in the treatment of cardiac disorders. Trimetazidine has been assessed in several double-blind randomised studies as a treatment of ischaemic heart disease or as an agent given prior to or during percutaneous transluminal coronary angioplasty, coronary artery bypass grafting and thrombolysis to prevent or limit ischaemia/reperfusion damage in the heart. All these studies demonstrate that trimetazidine protects the heart from the deleterious consequences of ischaemia by switching cardiac metabolism from fatty acid oxidation to glucose oxidation. Study results cast no doubts on the value of the cardioprotective effects of trimetazidine and support the fact that trimetazidine has a direct anti-ischaemic effect on human myocardial cells. Trimetazidine has proven antianginal efficacy, and can be also used in other cardiac diseases with ischaemic signs.
Effect of Ascorbic Acid and Growth Factors on Collagen Metabolism of Flexor Retinaculum Cells From Individuals With and Without Carpal Tunnel Syndrome (2000)

The effects of ascorbic acid and various growth factors on the proliferation rate and collagen metabolism were studied in cells from the flexor retinaculum of individuals with carpal tunnel syndrome (FR-CTS) and without carpal tunnel syndrome (FR control) and in human dermal fibroblasts. Ascorbic acid and four growth factors, including basic fibroblast growth factor, transforming growth factor, platelet-derived growth factor, and epidermal growth factors, were used. Ascorbic acid stimulates type I collagen production more in FR control than in FR-CTS. Growth factor treatment resulted in the following responses by the cells: (1) a higher mitogenic response than in the control cells; (2) a higher stimulation of type III collagen production and a lower stimulation of type I collagen production in CTS cells as compared with control cells; and (3) more alpha 2 (I) than alpha 1 (I) collagen production in CTS cells, unlike in control cells. We concluded that cells of the FR from individuals with CTS are physiologically altered.
Ultrasonic interferometric characterization of highly attenuative materials (1989)

Experimental techniques for the ultrasonic characterization of materials usually aim at the determination of either their ultrasonic velocity or their attenuation. In this article, a technique is presented that allows a simultaneous measurement of both. It provides, also, a method for a quantitative nondestructive evaluation of material irregularities. This technique is based on the propagation of ultrasonsic continuous waves through a slab of material, designed in the shape of a wedge, and on a correlation analysis between reference (incident) and received signals. Experiments performed on several specimens of various polymers confirm the efficiency and reliability of the method.
Generation and Focusing of High Brightness Pulsed X-rays: Toward the X-ray Driven Micro-Ship (2003)

A method for energetic micro‐X‐ray‐beam formation is proposed using a pulse‐powered radiation source and a grazing incidence mirror. The expected radiation sources for the micro‐beam formation are X‐pinch plasmas, bremsstrahlung point sources and capillary X‐ray lasers. Radiations from the pulse power driven source are focused using a Wolter mirror. The Wolter mirror is made of pyrex‐glass and has a capability to focus photons from a point radiation source with energy up‐to a few keV. Based on the experimental results, potentiality of the pulse power point X‐ray source as a driver of micro‐ships is discussed.
Conception intégrée par optimisation multicritère d’un système d’actionnement électrique pour l’aéronautique (2013)

International audience
Heparin inhibits EcoRI endonuclease cleavage of DNA at certain EcoRI sites (1990)

Studies presented here demonstrate that heparin inhibits EcoRI endonuclease cleavage of DNA whereas related proteoglycans show no effect. The inhibition occurs at particular EcoRI sites that are near or overlap with palindromic sequences in the murine lambda 5 and Lyt-2 genes. Endogenous heparin from peritoneal mast cells co-isolates with DNA and inhibits digestion of peritoneal cell DNA at the inhibitable sites. Digestion of spleen DNA is inhibited at the same sites when commercial heparin is added prior to digestion. In both cases, the inhibition is abolished by pre-treating the DNA with heparinase. Thus, potential artifacts in restriction fragment length analyses could occur with DNA isolated either from cells that are naturally rich in heparin or from cells to which heparin has been added, e.g., as an anticoagulant.
High‐molecular‐weight symmetrical multiblock copolymers: Synthesis by RAFT polymerization and characterization (2013)

ABSTRACT High‐molecular‐weight (MW) symmetrical multiblock copolymers, based on the hydrophobic monomers styrene (Sty) and methyl methacrylate (MMA), and the more polar monomer, 2‐vinyl pyridine (2VPy), were prepared using stepwise reversible addition‐fragmentation chain transfer polymerization. All copolymers shared a common poly(ethylene glycol) (PEG) midblock, introduced as a bifunctional macromolecular chain transfer agent. In total, five ABA triblock copolymers, five ABCBA pentablock terpolymers, and two ABCDCBA heptablock quaterpolymers (comprising four different monomer types) were synthesized. The MWs of the multiblock polymers were determined using gel permeation chromatography (GPC) and proton nuclear magnetic resonance ( 1 H NMR) spectroscopy, with the latter values being closer to the theoretically expected, whereas GPC MW distributions were relatively narrow, broadening with the number of blocks. The compositions of the synthesized polymers, as determined by 1 H NMR spectroscopy, were also close to the expected values. Finally, films cast from chloroform solutions of the pentablock terpolymers P2VPy‐ b ‐PSty‐ b ‐PEG‐ b ‐PSty‐ b ‐P2VPy, PSty‐ b ‐PMMA‐ b ‐PEG‐ b ‐PMMA‐ b ‐PSty, and P2VPy‐ b ‐PMMA‐ b ‐PEG‐ b ‐PMMA‐ b ‐P2VPy examined using transmission electron microscopy exhibited PSty and PMMA cylinders (first two) and lamellae (third terpolymer). © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51 , 4957–4965