gebhart/patrepeval huggingface dataset:
High-Throughput Raman Flow Cytometry and Beyond (2021)

Flow cytometry is a powerful tool with applications in diverse fields such as microbiology, immunology, virology, cancer biology, stem cell biology, and metabolic engineering. It rapidly counts and characterizes large heterogeneous populations of cells in suspension (e.g., blood cells, stem cells, cancer cells, and microorganisms) and dissociated solid tissues (e.g., lymph nodes, spleen, and solid tumors) with typical throughputs of 1,000-100,000 events per second (eps). By measuring cell size, cell granularity, and the expression of cell surface and intracellular molecules, it provides systematic insights into biological processes. Flow cytometers may also include cell sorting capabilities to enable subsequent additional analysis of the sorted sample (e.g., electron microscopy and DNA/RNA sequencing), cloning, and directed evolution. Unfortunately, traditional flow cytometry has several critical limitations as it mainly relies on fluorescent labeling for cellular phenotyping, which is an indirect measure of intracellular molecules and surface antigens. Furthermore, it often requires time-consuming preparation protocols and is incompatible with cell therapy. To overcome these difficulties, a different type of flow cytometry based on direct measurements of intracellular molecules by Raman spectroscopy, or "Raman flow cytometry" for short, has emerged. Raman flow cytometry obtains a chemical fingerprint of the cell in a nondestructive manner, allowing for single-cell metabolic phenotyping. However, its slow signal acquisition due to the weak light-molecule interaction of spontaneous Raman scattering prevents the throughput necessary to interrogate large cell populations in reasonable time frames, resulting in throughputs of about 1 eps. The remedy to this throughput limit lies in coherent Raman scattering methods such as stimulated Raman scattering (SRS) and coherent anti-Stokes Raman scattering (CARS), which offer a significantly enhanced light-sample interaction and hence enable high-throughput Raman flow cytometry, Raman imaging flow cytometry, and even Raman image-activated cell sorting (RIACS). In this Account, we outline recent advances, technical challenges, and emerging opportunities of coherent Raman flow cytometry. First, we review the principles of various types of SRS and CARS and introduce several techniques of coherent Raman flow cytometry such as CARS, multiplex CARS, Fourier-transform CARS, SRS, SRS imaging flow cytometry, and RIACS. Next, we discuss a unique set of applications enabled by coherent Raman flow cytometry, from microbiology and lipid biology to cancer detection and cell therapy. Finally, we describe future opportunities and challenges of coherent Raman flow cytometry including increasing sensitivity and throughput, integration with droplet microfluidics, utilizing machine learning techniques, or achieving in vivo flow cytometry. This Account summarizes the growing field of high-throughput Raman flow cytometry and the bright future it can bring.
Impact des pressions toxiques multiples sur les écosystèmes aquatiques du Bassin Versant du Rhône (2018)

L’impact écologique potentiel des pressions toxiques multiples exercées sur l’écosystème aquatique a été caractérisé via un indice unique évalué le long du corridor rhodanien. Certaines substances inventoriées n’ont cependant pas pu être incluses du fait d’un manque de connaissances sur leur écotoxicité (cas des polychlorobiphényles - PCB). L’impact écologique résulterait principalement de la présence de certains métaux traces (cuivre, nickel, vanadium et zinc) qui proviennent à la fois de l’érosion des roches et de l’activité humaine. La contribution de chacune de ces sources reste à estimer. La prise en compte des substances très faiblement quantifiées montre que les dichlorodiphényl-trichloroéthanes (DDT) et les hydrocarbures aromatiques polycycliques (HAP) peuvent contribuer de manière non négligeable. Finalement, la variation spatio-temporelle de l’indice est faible et surtout liée à l’hétérogénéité des jeux de données.
Abstract Specifications for Weakly Consistent Data. (2016)

Specifications for Weakly Consistent Data Sebastian Burckhardt Microsoft Research Redmond, WA, USA Jonathan Protzenko Microsoft Research Redmond, WA, USA
Cascade Approach toward the Core Structure of Neosarpagine (2007)

[reaction: see text] A palladium-catalyzed domino sequence was developed to rapidly construct the core structure of neosarpagine and other quinuclidine-related alkaloids. The cyclization of ketone 11 to ethylidene 4 with Pd(dba)2, DPEphos, LiHMDS, and ZnCl2 in THF represents a new domino process wherein a nonstabilized enolate served as a nucleophile.
Insulin Enhancement of Luteinizing Hormone and Follicle-Stimulating Hormone Release by Cultured Pituitary Cells* (1981)

The role of insulin in the regulation of basal and gonadotropin-releasing hormone (GnRH)-stimulated release of LH and FSH was investigated in vitro using primary cultures of rat anterior pituitary cells from adult ovariectomized rats. Anterior pituitary cells were incubated for 2 days in the presence or absence of insulin in a serum-free medium. At the end of the insulin treatment, the cells were washed and reincubated in the presence or absence of GnRH, and the LH and FSH released into the medium were measured by RIA. Treatment with insulin (1.0 microgram/ml) for 2 days resulted in significant increases in both the basal and the maximal release of LH and FSH, as well as a 3.2- and 6.3-fold decrease in the ED50 values for GnRH in terms of LH and FSH release, respectively. Treatment with increasing concentrations (0.1-10,000 ng/ml) of insulin, led to a dose-dependent increase in the GnRH (3 X 10(-10) M)-stimulated release of both LH and FSH. This effect of insulin was significant (P less than 0.05) at a physiological concentration of 1 ng/ml (24 microU/ml) with an ED50 value of 40 ng/ml. Increasing duration of exposure to insulin resulted in time-dependent increases in the GnRH (3 X 10(-10) M)-stimulated release of LH, becoming significant at 24 h with maximal enhancement observed by 48 h. The effect of insulin was specific; epidermal or fibroblast growth factor did not enhance LH release. The augmenting effect of insulin was not associated with cellular proliferation or an overall change in protein or LH synthesis. Furthermore, the effect of insulin was independent of the ambient glucose concentration. Insulin was, however, without effect on gonadotrophs cultured in a serum-supplemented medium. Our findings suggest that the gonadotroph constitutes a target cell of insulin and that insulin may act directly on the anterior pituitary in the regulation of gonadotropin release.
Time-Resolved Optical Monitoring to detect and identify deep flaps (Conference Presentation) (2019)

Monitoring tissue oxygenation is important in clinical applications such as breast surgery, Surgical reconstruction with free flaps is complex: a flap is taken from a healthy area of the body to be transposed into the damaged area. This operation requires microsurgical reconstruction of the vascular network. Tissue alterations may occur if the blood supply of the flap is not normal. This must be rapidly detected in order to avoid irreversible and extremely serious damages. We developed a Time-Resolved approach to get information in depth and separate the contribution of the upper layer from the lower layer of interest (flap). The TR system is detailed in [1-2]. We designed a specific optical stethoscope probe built from materials compliant with the clinical constraints. Distances between sources and detectors (SD) are 6, 8 and 13mm. We focused on the 750-800 and 850nm wavelengths. Abdominal flap were collected and buried on the left lateral abdominal muscle of the pig (~1cm deep of skin, fat and highly absorbing muscle) [3]. Either arterial or venous occlusions were performed (20 minutes of rest / 20 minutes of occlusion / 10-20 minutes release). US control of the upper layer and flap thicknesses has been systematically done. The two layers (surface layer and flap) were systematically controlled and monitored by two invasive LICOX (Integra laboratory) that measure the tissue pressure in Oxygen. We measured and analyzed 16 pigs (32 flaps) with arterial and venous occlusions; clinical control and LICOX were systematically performed. For each acquired data, we compared the results obtained in NIRS (integral of the TR signal) and in Resolved Time. Our results show that while the detection of occlusion depends on its depth in NIRS, we were able to detect occlusions whatever the sample (from the surface down to 1.23 mm) using the Resolved Time signals. In addition, the Oxy and Deoxy concentrations information provided by TR made it possible to identify the type of occlusion, which LICOX does not always allow. References: [1] Planat-Chrétien A., et al. Diffuse Optical Imaging V, H. Dehghani and P. Taroni, eds., Vol. 9538 of SPIE Proceedings (Optical Society of America, 2015), paper 953806 (2015). [2] Planat-Chrétien A., et al., Biomedical Optics Congress 2018, Clinical and Translational, OSA Technical Digest (Optical Society of America, 2018), paper JW3A.27 (2018). [3] Lartizien R, et al.,J Stomatol Oral Maxillofac Surg. 2017 Financial support ANR-15-CE19_0010 (Agence Nationale de Recherche, France).
Catalytic Enantioselective Protoboration of Disubstituted Allenes. Access to Alkenylboron Compounds in High Enantiomeric Purity (2014)

Proto-boryl additions to 1,1-disubstituted allenes in the presence of 1.0-5.0 mol % of chiral NHC-Cu complexes, B2(pin)2, and t-BuOH proceed to afford alkenyl-B(pin) products in up to 98% yield, >98:2 site selectivity, and 98:2 er. The enantiomerically enriched alkenylboron products can be converted to otherwise difficult-to-access alkenyl bromides, methyl ketones or carboxylic acids. What's more, the corresponding boronic acids may be used in highly stereoselective NHC-Cu-catalyzed allylic substitution reactions.
An F-band mixer module with a built-in broadband IF amplifier for spectrum analysis with low intermodulation distortion (2014)

In this study, we developed a mixer module for precise spectrum analysis in the extremely high frequency band above 110 GHz. The mixer MMIC was designed and fabricated using InP HEMT as a single resistive mixer with an IF amplifier. An integrated IF amplifier boosts the conversion gain of the mixer, and it can also widen the bandwidth. After packaging, this mixer module achieved a conversion gain higher than -10 dB with an IF bandwidth wider than 30 GHz. By introducing the IF amplifier, the implementation loss in the higher frequency bands was offset. An evaluation of the linearity of the mixer module showed that the IIP3 degradation caused by the IF amplifier was as low as 2.5 dB. Measurement of LO input power dependence of distortion characteristics showed that the optimum LO power was as low as 0 dBm. These features of a low LO power requirement and good linearity characteristics make the module attractive for the construction of millimeter-wave systems.
The Root Extract of Scutellaria baicalensis Induces Apoptosis in EGFR TKI-Resistant Human Lung Cancer Cells by Inactivation of STAT3 (2021)

Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) is a major obstacle in managing lung cancer. The root of <i>Scutellaria baicalensis</i> (SB) traditionally used for fever clearance and detoxification possesses various bioactivities including anticancer effects. The purpose of this study was to investigate whether SB exhibited anticancer activity in EGFR TKI-resistant lung cancer cells and to explore the underlying mechanism. We used four types of human lung cancer cell lines, including H1299 (<i>EGFR</i> wildtype; EGFR TKI-resistant), H1975 (acquired TKI-resistant), PC9/ER (acquired erlotinib-resistant), and PC9/GR (acquired gefitinib-resistant) cells. The ethanol extract of SB (ESB) decreased cell viability and suppressed colony formation in the four cell lines. ESB stimulated nuclear fragmentation and the cleavage of poly(ADP-ribose) polymerase (PARP) and caspase-3. Consistently, the proportion of sub-G1 phase cells and annexin V+ cells were significantly elevated by ESB, indicating that ESB induced apoptotic cell death in EGFR TKI-resistant cells. ESB dephosphorylated signal transducer and activator of transcription 3 (STAT3) and downregulated the target gene expression. The overexpression of constitutively active STAT3 reversed ESB-induced apoptosis, suggesting that ESB triggered apoptosis in EGFR TKI-resistant cells by inactivating STAT3. Taken together, we propose the potential use of SB as a novel therapeutic for lung cancer patients with EGFR TKI resistance.
Small-Molecule Positive Allosteric Modulators of the β2-Adrenoceptor Isolated from DNA-Encoded Libraries (2018)

Conventional drug discovery efforts at the <i>β</i><sub>2</sub>-adrenoceptor (<i>β</i><sub>2</sub>AR) have led to the development of ligands that bind almost exclusively to the receptor's hormone-binding orthosteric site. However, targeting the largely unexplored and evolutionarily unique allosteric sites has potential for developing more specific drugs with fewer side effects than orthosteric ligands. Using our recently developed approach for screening G protein-coupled receptors (GPCRs) with DNA-encoded small-molecule libraries, we have discovered and characterized the first <i>β</i><sub>2</sub>AR small-molecule positive allosteric modulators (PAMs)-compound (Cmpd)-6 [(<i>R</i>)-<i>N</i>-(4-amino-1-(4-(<i>tert</i>-butyl)phenyl)-4-oxobutan-2-yl)-5-(<i>N</i>-isopropyl-<i>N</i>-methylsulfamoyl)-2-((4-methoxyphenyl)thio)benzamide] and its analogs. We used purified human <i>β</i><sub>2</sub>ARs, occupied by a high-affinity agonist, for the affinity-based screening of over 500 million distinct library compounds, which yielded Cmpd-6. It exhibits a low micro-molar affinity for the agonist-occupied <i>β</i><sub>2</sub>AR and displays positive cooperativity with orthosteric agonists, thereby enhancing their binding to the receptor and ability to stabilize its active state. Cmpd-6 is cooperative with G protein and <i>β</i>-arrestin1 (a.k.a. arrestin2) to stabilize high-affinity, agonist-bound active states of the <i>β</i><sub>2</sub>AR and potentiates downstream cAMP production and receptor recruitment of <i>β</i>-arrestin2 (a.k.a. arrestin3). Cmpd-6 is specific for the <i>β</i><sub>2</sub>AR compared with the closely related <i>β</i><sub>1</sub>AR. Structure-activity studies of select Cmpd-6 analogs defined the chemical groups that are critical for its biologic activity. We thus introduce the first small-molecule PAMs for the <i>β</i><sub>2</sub>AR, which may serve as a lead molecule for the development of novel therapeutics. The approach described in this work establishes a broadly applicable proof-of-concept strategy for affinity-based discovery of small-molecule allosteric compounds targeting unique conformational states of GPCRs.
Multi-Agent Distributed Lifelong Learning for Collective Knowledge\n Acquisition (2017)

Lifelong machine learning methods acquire knowledge over a series of\nconsecutive tasks, continually building upon their experience. Current lifelong\nlearning algorithms rely upon a single learning agent that has centralized\naccess to all data. In this paper, we extend the idea of lifelong learning from\na single agent to a network of multiple agents that collectively learn a series\nof tasks. Each agent faces some (potentially unique) set of tasks; the key idea\nis that knowledge learned from these tasks may benefit other agents trying to\nlearn different (but related) tasks. Our Collective Lifelong Learning Algorithm\n(CoLLA) provides an efficient way for a network of agents to share their\nlearned knowledge in a distributed and decentralized manner, while preserving\nthe privacy of the locally observed data. Note that a decentralized scheme is a\nsubclass of distributed algorithms where a central server does not exist and in\naddition to data, computations are also distributed among the agents. We\nprovide theoretical guarantees for robust performance of the algorithm and\nempirically demonstrate that CoLLA outperforms existing approaches for\ndistributed multi-task learning on a variety of data sets.\n
Occulsion amblyopia. (1976)

There have been a number of reports on the effects of early occlusion on the visual system of cats, monkeys, and humans. In the present paper, a patient with amblyopia resulting from prolonged early occlusion in the treatment of strabismus is described, and implications for management of early strabismus are discussed.
Selective deposition of a-Si:H: a proof-of-concept study (2018)

We present a novel approach to simplify the rear-side a-Si:H patterning of silicon heterojunction interdigitated back-contact solar cells. In our current process, laser ablation and lift-off are used. Since lift-off is not industrially-viable, we propose to replace it with a selective deposition process which ensures a-Si:H is realised only on c-Si surface and not on the SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> mask, at the end of the process, based on cycles of a-Si:H deposition and etching. While neither the deposition nor the etching is truly selective, this method relies on the difference of a-Si:H etch rates on c-Si and SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> surfaces to achieve selectivity as the net end-result. The main challenge is addressing the trade-off between selectivity and c-Si surface passivation.
Effects of Analgesics and Related Compounds on Renal Metabolism in Rats (1977)

1. The metabolic effects of p-aminophenol have been compared with those of paracetamol and other analgesics in studies of rat liver and kidney in vitro. 2. p-Aminophenol injected into rats inhibited gluconeogenesis from lactate in renal cortical tubules, but not in isolated hepatocytes, and reduced kidney ATP content without affecting the ATP content of liver. Perfused kidneys from rats previously injected with p-aminophenol showed a 50% reduction of ATP content, severe inhibition of Na+ reabsorption and reduction of inulin clearance without significant inhibition of gluconeogenesis from lactate. 3. Paracetamol, p-phenetidine, phenazone and aspirin, when given intravenously to rats, had no effect on renal tubular glucose synthesis from lactate or pyruvate. Paracetamol and aspirin both slightly inhibited renal glucose synthesis from several different substrates when added directly to tubules. 4. Paracetamol (4 mmol/l) inhibited glucose synthesis from lactate and other substrates by 50% or more in isolated hepatocytes. Glucose synthesis from lactate was inhibited 30% by concentrations of paracetamol as low as 0.5 mmol/l. 5. These results indicate that p-aminophenol is a potent inhibitor of proximal tubular function, with its main site of action the inhibition of ATP synthesis and energy production, and they confirm the primary hepatotoxic effect of paracetamol.
Absolute Free Energy of Binding Calculations for Macrophage Migration Inhibitory Factor in Complex with a Druglike Inhibitor (2019)

Calculation of the absolute free energy of binding (ΔGbind) for a complex in solution is challenging owing to the need for adequate configurational sampling and an accurate energetic description, typically with a force field (FF). In this study, Monte Carlo (MC) simulations with improved side-chain and backbone sampling are used to assess ΔGbind for the complex of a druglike inhibitor (MIF180) with the protein macrophage migration inhibitory factor (MIF) using free energy perturbation (FEP) calculations. For comparison, molecular dynamics (MD) simulations were employed as an alternative sampling method for the same system. With the OPLS-AA/M FF and CM5 atomic charges for the inhibitor, the ΔGbind results from the MC/FEP and MD/FEP simulations, -8.80 ± 0.74 and -8.46 ± 0.85 kcal/mol, agree well with each other and with the experimental value of -8.98 ± 0.28 kcal/mol. The convergence of the results and analysis of the trajectories indicate that sufficient sampling was achieved for both approaches. Repeating the MD/FEP calculations using current versions of the CHARMM and AMBER FFs led to a 6 kcal/mol range of computed ΔGbind. These results show that calculation of accurate ΔGbind for large ligands is both feasible and numerically equivalent, within error limits, using either methodology.
Randomized Phase III Trial of Irinotecan Plus Cisplatin Compared With Paclitaxel Plus Carboplatin As First-Line Chemotherapy for Ovarian Clear Cell Carcinoma: JGOG3017/GCIG Trial (2016)

No significant survival benefit was found for CPT-P. Both regimens were well tolerated, but the toxicity profiles differed significantly. Treatment with existing anticancer agents has limitations to improving the prognosis of CCC.
Regulated Expression of a Cytokinin Biosynthesis Gene IPT Delays Leaf Senescence and Improves Yield under Rainfed and Irrigated Conditions in Canola (Brassica napus L.) (2015)

Delay of leaf senescence through genetic modification can potentially improve crop yield, through maintenance of photosynthetically active leaves for a longer period. Plant growth hormones such as cytokinin regulate and delay leaf senescence. Here, the structural gene (IPT) encoding the cytokinin biosynthetic enzyme isopentenyltransferase was fused to a functionally active fragment of the AtMYB32 promoter and was transformed into canola plants. Expression of the AtMYB32xs::IPT gene cassette delayed the leaf senescence in transgenic plants grown under controlled environment conditions and field experiments conducted for a single season at two geographic locations. The transgenic canola plants retained higher chlorophyll levels for an extended period and produced significantly higher seed yield with similar growth and phenology compared to wild type and null control plants under rainfed and irrigated treatments. The yield increase in transgenic plants was in the range of 16% to 23% and 7% to 16% under rainfed and irrigated conditions, respectively, compared to control plants. Most of the seed quality parameters in transgenic plants were similar, and with elevated oleic acid content in all transgenic lines and higher oil content and lower glucosinolate content in one specific transgenic line as compared to control plants. The results suggest that by delaying leaf senescence using the AtMYB32xs::IPT technology, productivity in crop plants can be improved under water stress and well-watered conditions.
Magnetooptical Signal Calculation with Simplified Substrate Birefringence Model (1996)

Uniform birefringence is introduced into a simple scalar magnetooptical signal simulation model for polycarbonate substrates. Several effects of vertical and lateral birefringence such as astigmatism, elliptical polarization distribution, reduction of the signal amplitude and DC offset, are discussed.
SiC versus Si—Evaluation of Potentials for Performance Improvement of Inverter and DC–DC Converter Systems by SiC Power Semiconductors (2010)

Switching devices based on wide bandgap materials such as silicon carbide (SiC) offer a significant performance improvement on the switch level (specific on resistance, etc.) compared with Si devices. Well-known examples are SiC diodes employed, for example, in inverter drives with high switching frequencies. In this paper, the impact on the system-level performance, i.e., efficiency, power density, etc., of industrial inverter drives and of dc-dc converter resulting from the new SiC devices is evaluated based on analytical optimization procedures and prototype systems. There, normally on JFETs by SiCED and normally off JFETs by SemiSouth are considered.