gebhart/patrepeval huggingface dataset:
Abstract LB-96: Sensitivity to combined MEK and mTORC1/2 inhibition in colorectal cancer is dictated by p53 mutational status. . (2013)

Abstract Activating mutations in RAS and PI3K pathways confer resistance to currently used anti-EGFR-based therapies in colorectal cancer (CRC). Although dual inhibition of MEK and PI3K/Akt has proven some efficacy in CRC preclinical models with aberrations in both pathways, little is known about other possible alterations that can limit the efficacy of this combination and preclude patient selection. Here, we explored whether p53 mutations influence the response to combined MEK and PI3K pathway inhibition by analyzing the antiproliferative activity of the investigational dual mTORC1/2 inhibitor MLN0128, and the MEK inhibitor PD0325901, in three p53 wild-type and three p53 mutated CRC cell lines with concomitant KRAS/BRAF and PIK3CA mutations. Expectedly, PD0325901 and MLN0128 inhibited ERK and mTOR signaling, respectively, across all cell-lines. However, the treatment combination selectively enhanced apoptosis only in p53 wild-type cell lines. Overexpression of mutant p53 in p53 wild-type CRC cells prevented the proapoptotic effects of combined PD0325901 and MLN0128, underscoring the causative role of mutant p53 in limiting the sensitivity to this pharmacological approach. Similar results were observed in vivo, where the inhibition of MEK and mTORC1/2 reduced tumor growth in a higher extent than single agents in p53 wild-type xenograft models, but not in p53 mutant ones. p53 can inhibit cell apoptosis and cycle progression partly by increasing the expression of the cyclin-dependent kinase inhibitor p21, which, in turn, is regulated by MEK-ERK-cMyc pathway. Accordingly, we observed a decrease of cMyc and an increase of p21 levels following MEK inhibition, which could exert an anti-apoptotic function in wild-type p53 CRC. As expected, the combined treatment with the mTORC1/2 inhibitor prevented the PD0325901-induced p21 expression and resulted in enhanced apoptosis. Knockdown of p21 in p53 wild-type cells also sensitized CRC cells to MEK inhibitor-induced apoptosis, confirming the antiapoptotic role of p21 upon PD0325901 treatment and supporting the hypothesis that p21-downregulation mediated by MLN0128 is needed to achieve cell death following dual MEK and mTOR inhibition. In summary, our data suggest that the presence of wild-type p53 is a determinant of sensitivity to the combined suppression of MEK and PI3K-pathways in CRC. Citation Format: Celina García-García, Martín A. Rivas, Yasir H. Ibrahim, María Teresa Calvo, Judit Grueso, Pilar Antón, Claudia Aura, Katti Jessen, Héctor Palmer, Josep Tabernero, Maurizio Scaltriti, José Baselga, Violeta Serra. Sensitivity to combined MEK and mTORC1/2 inhibition in colorectal cancer is dictated by p53 mutational status. . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-96. doi:10.1158/1538-7445.AM2013-LB-96
Communication—Supercritically-Dried Membranes and Powders of >90% Porosity Silicon with Pore Volumes Exceeding 4 cm 3 g −1 (2020)

Porous silicon structures can display full biodegradability into orthosilicic acid and are under development for medical uses such as drug delivery. Here we demonstrate optimized electrochemical etching and drying conditions to achieve ultrahigh porosity structures (“silicon aerocrystals”), which should enable ultrahigh nanostructured drug payloads. Supercritical drying (SCD) of detached 41 to 210 micron thick films from etched p + wafers generates structures with pore volumes 3.5 to 5.13 cm 3 g −1 , average pore diameters of 29 nm to 35 nm and surface areas 425 to 549 m 2 g −1 . For anodized p + wafers, the benefits of SCD vs air drying (AD) are primarily elevated pore volumes.
Morphologies and Mechanical Properties of a Series of Block-Double-Graft Copolymers and Terpolymers (2002)

Morphological characteristics and mechanical properties of a series of block-double-graft (BDG) copolymers and terpolymers polystyrene−[1,2-polybutadiene-g-X2] (X = 1,4-polybutadiene, polyisoprene, polystyrene, and polystyrene-b-polyisoprene diblocks) were investigated by transmission electron microscopy (TEM), small-angle X-ray scattering (SAXS), and tensile testing. All BDG materials have linear polystyrene−1,2-polybutadiene (PS-b-1,2-PBD) diblock copolymer backbones. Two identical branches are grafted at every randomly distributed tetrafunctional junction point on the 1,2-PBD part of the backbone. Standard microstructures, such as body-center-cubic spheres, hexagonally packed cylinders, and lamellae, are obtained at different total PS volume fractions. It is found that when the branches are polydienes, the BDG molecules form the same morphologies as their linear diblock counterparts. In such cases, phase separation occurs between the polystyrene domain and a combined diene microdomain formed by the backbone 1,2-PBD part and the polydiene branches. In BDG materials in which the branches are polystyrene−polyisoprene diblock copolymers, lamellae are obtained at a total PS volume fraction close to 0.50. It is found that the domain spacings of these materials are predominately determined by the molecular weights of the diblock branches instead of the backbones. A lamellae-forming BDG terpolymer with an average of three tetrafunctional junction points per molecule exhibited characteristic thermoplastic elastomer properties with a stress at break of 32 MPa and strain at break of 1000%. It is proposed that the high strength of this BDG terpolymer is attributed to the chain conformation in the microphase-separated state. The elastic PBD blocks of the backbone bridge adjacent PS domains through multiple junction points, resulting in the enhanced elastomeric properties. Several parameters are found to influence the mechanical properties of these BDG materials: (1) the existence of backbone PS, (2) the molecular weight of the branches, and (3) the number and functionality of branch points on the 1,2-PBD part of the backbone.
Microstructure simulation of grain growth in Cu Through Silicon Via using phase-field modeling (2014)

In this paper, a time-efficient 3D phase-field model, for simulating grain growth in Through Silicon Via (TSV) is presented. This model is modified to model grain growth in the cylindrical shape of a TSV to capture the effect of temperature in its microstructure. The data generated from this simulation is used to explain large distribution of Cu pumping (i.e. non reversible thermal expansion of TSV). To achieve this, generated results must be used as an input in a Finite Element Model of a TSV structure to study the effect of grain growth and asymmetry in distribution of Cu pumping. Results generated from a sample FEM model with grain structure input confirms this capability.
A Glycan FRET Assay for Detection and Characterization of Catalytic Antibodies to the Cryptococcus neoformans Capsule (2020)

&lt;p&gt;Classical antibody functions include opsonization, complement activation, and enhancement of cellular antimicrobial function. Antibodies can also have catalytic activity, although the contribution of catalysis to their biological functions has been more difficult to establish. With the ubiquity of catalytic antibodies against glycans virtually unknown, we sought to advance this knowledge. The use of a glycan microarray allowed epitope mapping of several monoclonal antibodies (mAbs) against the capsule of &lt;i&gt;Cryptococcus neoformans&lt;/i&gt;. From this, we designed and synthesized two glycan based Förster Resonance Energy Transfer (FRET) probes, which we used to discover antibodies with innate glycosidase activity and analyse their enzyme kinetics, including mAb 2H1, a polysaccharide lyase, and the most efficient glycosidase to date. The validity of the FRET assay was confirmed by demonstrating that the mAbs mediate glycosidase activity on intact cryptococcal capsules, as observed by a reduction in capsule diameter. Further the mAb 18B7, a glycosidase hydrolase, resulted in the appearance of reducing ends in the capsule as labelled by hydroxylamine-armed fluorescent (HAAF) probe. Finally, we demonstrate that exposing &lt;i&gt;C. neoformans &lt;/i&gt;cells to catalytic antibodies results in changes in complement deposition and increased phagocytosis by macrophages — suggesting the anti-phagocytic properties of the capsule have been impaired. Our results raise questions over the ubiquity of antibodies with catalytic activity against glycans and establish the utility of glycan-based FRET and HAAF probes as tools for investigating this activity.&lt;/p&gt;
Offshore Deployment of Marine Substation in the Lysekil Research Site (2015)

The wave power project at the Division of Electricity, Uppsala University, started in 2001. The first full scale wave energy converter (WEC) was developed and deployed outside the Swedish West coast in 2006. Since then, another 13 WECs have been deployed. In order to transfer the absorbed wave energy to the shoreline, offshore marine substations have been proposed as an offshore interconnection point. The substation offers several benefits, such as a compatible gridconnection, reduced number of cables, improved transmission efficiency and individual WEC control. A major expense in wave power technology is the associated offshore operation costs. As the substation may need maintenance within a few years interval, it is important to minimize its deployment costs. In this paper, a very inexpensive deployment strategy is proposed, and described step by step. The procedure has been verified experimentally offshore, with pictures from the operation presented. The cost with this strategy is reduced by almost a factor of ten compared to the previous installation procedure.
Nickel‐Catalyzed Synthesis of Acrylamides from α‐Olefins and Isocyanates. (2007)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis of aminomethylated 4-fluoropiperidines and 3-fluoropyrrolidines (2010)

A short and efficient synthesis of 4-aminomethyl-4-fluoropiperidines and 3-aminomethyl-3-fluoropyrrolidines is described. These fluorinated azaheterocycles are of specific interest as bifunctional building blocks for fluorinated pharmaceutical compounds. The key step of the synthetic pathway involves the regioselective bromofluorination of N-Boc-4-methylenepiperidine and 3-methylenepyrrolidine using Et(3)N.3HF and NBS.
Skin Transfection Patterns and Expression Kinetics of Electroporation-Enhanced Plasmid Delivery Using the CELLECTRA-3P, a Portable Next-Generation Dermal Electroporation Device (2015)

The CELLECTRA-3P dermal electroporation device (Inovio Pharmaceuticals, Plymouth Meeting, PA) has been evaluated in the clinic and shown to enhance the delivery of an influenza DNA vaccine. To understand the mechanism by which this device aids in enhancing the host immune response to DNA vaccines we investigated the expression kinetics and localization of a reporter plasmid (pGFP) delivered via the CELLECTRA-3P. Histological analysis revealed green fluorescent protein (GFP) expression as early as 1 hr posttreatment in the epidermal and dermal layers, and as early as 2 hr posttreatment in the subdermal layers. Immunofluorescence techniques identified keratinocytes, fibrocytes, dendritic-like cells, adipocytes, and myocytes as the principal cell populations transfected. We proceeded to demonstrate elicitation of robust host immune responses after plasmid DNA (pDNA) vaccination. In guinea pigs equivalent humoral (antibody binding titers) immune responses were observed between protocols using either CELLECTRA-3P or intramuscular electroporation to deliver the DNA vaccine. In nonhuman primates, robust interferon-γ enzyme-linked immunospot and protective levels of hemagglutination inhibition titers after pDNA vaccination were observed in groups treated with the CELLECTRA-3P. In conclusion, these findings may assist in the future to design efficient, tolerable DNA vaccination strategies for the clinic.
Assessing metabolic rate and indoor air quality with passive environmental sensors (2018)

The present work introduces the use of environmental sensors to assess indoor air quality (IAQ) in combination with human biometrics. The sensor array included temperature, relative humidity, carbon dioxide, and noise monitors. The array was used in a classroom as well as in a vehicle cabin to assess the carbon dioxide production rate of individuals in a closed ventilation environment. Analysis of carbon dioxide production allowed for the quantification of the average metabolic rate of the group of individuals in the classroom, and for one individual in the vehicle cabin. These results yielded a mere 5% difference from the values assessed using commercial metabolic rate instruments, and averaged values from epidemiological studies. The results presented in this work verify the feasibility of determining an individual's metabolic rate using passive environmental sensors; these same sensors are able to provide a metric of IAQ that helps characterize the safety of the environment in which the individual is present.
Seemingly Anomalous Angular Distributions in H + D 2 Reactive Scattering (2012)

When a hydrogen (H) atom approaches a deuterium (D(2)) molecule, the minimum-energy path is for the three nuclei to line up. Consequently, nearly collinear collisions cause HD reaction products to be backscattered with low rotational excitation, whereas more glancing collisions yield sideways-scattered HD products with higher rotational excitation. Here we report that measured cross sections for the H + D(2) → HD(v' = 4, j') + D reaction at a collision energy of 1.97 electron volts contradict this behavior. The anomalous angular distributions match closely fully quantum mechanical calculations, and for the most part quasiclassical trajectory calculations. As the energy available in product recoil is reduced, a rotational barrier to reaction cuts off contributions from glancing collisions, causing high-j' HD products to become backward scattered.
(18)F-click labeling of a bombesin antagonist with an alkyne-(18)F-ArBF(3) (-): in vivo PET imaging of tumors expressing the GRP-receptor. (2013)

A clickable alkyne-modified arylborimidine is rapidly converted in 15 minutes to a highly polar (18)F-aryltrifluoroborate anion ((18)F-ArBF(3) (-)) at high specific activity. Following labeling, the alkyne-(18)F-ArBF(3) (-) was conjugated to the peptide bombesin (BBN) within 25 minutes in a second step without need for prior work-up making this one-pot-two-step method easy, user-friendly, and generally applicable. Bombesin was chosen to provide functional PET images of prostate cancer xenografts in mice of which there are few. Whereas BBN is labeled to provide some of the first in vivo tumor images based on this technique, click-labeling is recognized for its generality and broad substrate scope. Hence these results are likely to be useful for click labeling most peptides and other biomolecules.
Grid code compliance of grid-side converter in wind turbine systems (2006)

Until recently, there were no specific requirements in the grid codes for connecting the wind turbines/farms to the electrical network. Nowadays the power system operators e.g. in Denmark, Germany and Spain, have started to issue new grid codes addressed to wind turbines/farms. The grid connection requirements are addressed both at distribution and transmission level and can be applied to on-shore units as well as to off-shore ones. The focus in these grid codes is on the power quality, grid stability, control capabilities and on the performances of the wind turbines/farms under fault conditions as well. These requirements can vary considerably from one specific grid code to another and one of the major goals for the wind turbine industry is to meet them without major changes in the control algorithms as well as in the hardware. The grid side converter is a key element in achieving the grid code requirements regarding the compatibility levels for voltages and currents in the Point of Common Coupling (PCC). An analysis of these compatibility levels for voltages and currents in the PCC for different control strategies of the grid side converter in large wind turbine applications is presented in this paper. Different grid conditions as well as different connection method to PCC are considered. The analysis is based on the existing recommendation within the grid codes.
Relative effect of spam and irrelevant documents on user interaction with search engines (2011)

Meaningful evaluation of web search must take account of spam. Here we conduct a user experiment to investigate whether satisfaction with search engine result pages as a whole is harmed more by spam or by irrelevant documents. On some measures, search result pages are differentially harmed by the insertion of spam and irrelevant documents. Additionally we find that when users are given two documents of equal utility, the one with the lower spam score will be preferred; a result page without any spam documents will be preferred to one with spam; and an irrelevant document high in a result list is surprisingly more damaging to user satisfaction than a spam document. We conclude that web ranking and evaluation should consider both utility (relevance) and "spamminess" of documents.
A heuristic method for generating 2D CSG trees from bitmaps (1997)

This paper presents a method for generating compact and effective constructive-solid-geometry (CSG) object representations from 2D bitmap representations. The method consists of two parts: a stochastic search procedure for finding candidate CSG trees and a local optimization procedure that modifies the primitives of a given CSG tree to effect a better match. Results for several sample input bitmaps are presented and an application of this method to automatic geometric morphing between pairs of bitmaps is shown.
Computing using Quantum Dynamics of Nanostructured Arrays (2019)

Quantum field is back at the headlines with several research areas such as: quantum sensing, quantum communication, quantum cryptography and quantum computing. A novel concept of a computer exploiting quantum confinement and nonlinear optics is the basis of an EC H2020 consortium named COPAC [[i],[ii],[iii]]. We joined this consortium which uses the dynamic response of assembled nanostructures in solid arrays short laser pulses and implement a novel paradigm for parallel information processing. Within current paper we will discuss the nanostructures materials and configurations as designed for the project, especially the interaction of the nanostructures with the addressing laser beam unit. This work is supported by the FET open H2020 EC project COPAC, #766563 [[i]] COPAC = Coherent Optical PArallel Computing; consortium: ULg: University of Liège; HUJI: Hebrew University of Jerusalem Israel; UNIPD: University of Padua; CNR: Italian National Research Council; PB: ProbaYes Software; ESL: Elbit Systems. [[ii]] http://www.copac-fet.eu/ [[iii]] This work is supported by the FET open H2020 EC project COPAC, #766563
Synthesis of p-benzylcalix[4]arene and its sulfonated water soluble derivative (2001)

p-Benzylcalix[4]arene is formed in good yield by a direct "one pot" reaction involving p-benzylphenol and formaldehyde, selectively converted to the corresponding chlorosulfonyl and sulfonate analogues.
A capacitively coupled chopper instrumentation amplifier with a &#x00B1;30V common-mode range, 160dB CMRR and 5&#x03BC;V offset (2012)

This paper describes a capacitively coupled chopper instrumentation amplifier (CCIA) for current-sensing applications. A capacitively driven input chopper enables a ±30V input common-mode (CM) range and an input offset less than 5μV. The CCIA does not draw supply current from its input terminals or require a separate high-voltage (HV) supply; and has a common-mode rejection ratio (CMRR) in excess of 160dB, both of which represent significant improvements on the state-of-the-art [1-3]. Implemented in a HV CMOS 0.7μm technology, the CCIA achieves an NEF of 6.1 (6.5× better than [1-3]), while drawing only 26μA from a 3V supply.
Helping Mobile Learners Know Unknown Words through their Reading Behavior (2022)

Vocabulary acquisition is a fundamental part of learning a new language. In order to acquire new vocabulary, words with meanings that are unknown to the learner must be added to the language learning process. When searching for material in the target language, it is useful to know how much of a document is made up of currently unknown words. One simple way to estimate the unknown words in a document is to use the frequency of occurrence, which indicates the difficulty of the word. However, this approach can lead to missed unknown words. In this study, we aim to improve the accuracy of unknown word estimation by using reading activity data obtained from smartphone sensors and taking into account the individual learner’s English reading behavior. We apply a novel user interface which allows us to improve estimation through reading behavior, without the use of eye-trackers.
Friendly barriers (2014)

This paper addresses the problem of efficiently supporting parallelism within a managed runtime. A popular approach for exploiting software parallelism on parallel hardware is task parallelism, where the programmer explicitly identifies potential parallelism and the runtime then schedules the work. Work-stealing is a promising scheduling strategy that a runtime may use to keep otherwise idle hardware busy while relieving overloaded hardware of its burden. However, work-stealing comes with substantial overheads. Recent work identified sequential overheads of work-stealing, those that occur even when no stealing takes place, as a significant source of overhead. That work was able to reduce sequential overheads to just 15%.
Single-cell RNA-seq reveals novel regulators of human embryonic stem cell differentiation to definitive endoderm (2016)

We report the analysis of 1776 cells by scRNA-seq covering distinct human embryonic stem cell-derived progenitor states. By reconstructing a differentiation trajectory at single-cell resolution, novel regulators of the mesendoderm transition to DE are elucidated and validated. Our strategy of combining single-cell analysis and genetic approaches can be applied to uncover novel regulators governing cell fate decisions in a variety of systems.
Plasmonic versus dielectric enhancement in thin-film solar cells (2012)

Several studies have indicated that broadband absorption of thin-film solar cells can be enhanced by use of surface-plasmon induced resonances of metallic parts like strips or particles. The metallic parts may create localized modes or scatter incoming light to increase absorption in thin-film semiconducting material. For a particular case, we show that coupling to the same type of localized slab-waveguide modes can be obtained by a surface modulation consisting of purely dielectric strips. The purely dielectric device turns out to have a significantly higher broadband enhancement factor compared to its metallic counterpart. We show that the enhanced normalized short-circuit current for a cell with silicon strips can be increased 4 times compared to the best performance for strips of silver, gold, or aluminium. For this particular case, the simple dielectric grating may outperform its plasmonic counterpart due to the larger Ohmic losses associated with the latter.