gebhart/patrepeval huggingface dataset:
Chemical Biology Strategy Reveals Pathway-Selective Inhibitor of NF-κB Activation Induced by Protein Kinase C (2010)

Dysregulation of NF-kappaB activity contributes to many autoimmune and inflammatory diseases. At least nine pathways for NF-kappaB activation have been identified, most of which converge on the IkappaB kinases (IKKs). Although IKKs represent logical targets for potential drug discovery, chemical inhibitors of IKKs suppress all known NF-kappaB activation pathways and thus lack the selectivity required for safe use. A unique NF-kappaB activation pathway is initiated by protein kinase C (PKC) that is stimulated by antigen receptors and many growth factor receptors. Using a cell-based high-throughput screening (HTS) assay and chemical biology strategy, we identified a 2-aminobenzimidazole compound, CID-2858522, which selectively inhibits the NF-kappaB pathway induced by PKC, operating downstream of PKC but upstream of IKKbeta, without inhibiting other NF-kappaB activation pathways. In human B cells stimulated through surface immunoglobulin, CID-2858522 inhibited NF-kappaB DNA-binding activity and expression of endogenous NF-kappaB-dependent target gene, TRAF1. Altogether, as a selective chemical inhibitor of the NF-kappaB pathway induced by PKC, CID-2858522 serves as a powerful research tool and may reveal new paths toward therapeutically useful NF-kappaB inhibitors.
The genome of woodland strawberry (Fragaria vesca) (2010)

The woodland strawberry, Fragaria vesca (2n = 2x = 14), is a versatile experimental plant system. This diminutive herbaceous perennial has a small genome (240 Mb), is amenable to genetic transformation and shares substantial sequence identity with the cultivated strawberry (Fragaria × ananassa) and other economically important rosaceous plants. Here we report the draft F. vesca genome, which was sequenced to ×39 coverage using second-generation technology, assembled de novo and then anchored to the genetic linkage map into seven pseudochromosomes. This diploid strawberry sequence lacks the large genome duplications seen in other rosids. Gene prediction modeling identified 34,809 genes, with most being supported by transcriptome mapping. Genes critical to valuable horticultural traits including flavor, nutritional value and flowering time were identified. Macrosyntenic relationships between Fragaria and Prunus predict a hypothetical ancestral Rosaceae genome that had nine chromosomes. New phylogenetic analysis of 154 protein-coding genes suggests that assignment of Populus to Malvidae, rather than Fabidae, is warranted.
2D Electron Gas: Reversible Formation of 2D Electron Gas at the LaFeO3/SrTiO3 Interface via Control of Oxygen Vacancies (Adv. Mater. 10/2017) (2017)

In article number 1604447, Stuart Parkin and co-workers demonstrate that the oxygen vacancy is a major contributor to the two-dimensional electron gas formed at the interface between epitaxial LaFeO3 layers >3 unit cells thick and the surface of SrTiO3 single crystals. The ionic liquid gating geometry used to tune the interface conductivity by creation/removal of oxygen vacancies is shown here (Artwork: K. Roche).
Laid and flush-buried mine detection using an 8- to 12-μm polarimetric imager (1998)

In this paper we present results we obtained in mine detection, in the course of a multi-national European research program. Trials were performed in the Joint Research Center in ISPRA, using polarimetric infrared imagers. Usually the 3 - 5 micrometer spectral band is used for this application, however we explain that the 8 - 12 micrometer band is physically a better choice. We thus obtained information on the polarization of the self emitted radiations of the objects so that our method should be more versatile regarding the environment. Images of the global intensity, the radiation global ellipticity and orientation are presented on several types of mines. The obvious increase of contrast between the observed mines and the clutter demonstrates the usefulness of this technique in mine and UXO detection.
Cycle-by-Cycle Air-to-Fuel Ratio Calculation During Transient Engine Operation Using Fast Response CO and CO2 Sensors (2012)

Stringent engine emission regulations highlight the importance of proper engine control during transient operation. In recent years, fast emissions analyzers that measure CO and CO2 simultaneously have allowed for fast air-to-fuel ratio (AFR) calculation under steady-state engine operation. However, using a steady-state methodology to calculate AFR under transient conditions can lead to significant data interpretation errors. This research introduces an experimental cycle-by-cycle AFR calculation routine developed for transient operation using cycle-resolved CO2 and CO analyzers. Need for the new technique arises when the composition of recycled exhaust gases vary significantly from expected post-combustion products corresponding to the true in-cylinder AFR. This condition commonly occurs when AFR is changed from one cycle to the next. The peak difference between the new method and traditional methods is demonstrated to be in the range of 0.1 relative air-to-fuel ratio points, or approximately 10%. These results are for low dilution conditions where the new method should show minimal difference as compared to traditional methods. If residual gas fraction levels were increased the difference in corrected to uncorrected results would become even greater, motivating the use of the new method in high-dilution engines.
Microstructure effects on the phase transition behavior of a prototypical quantum material (2022)

Materials with insulator-metal transitions promise advanced functionalities for future information technology. Patterning on the microscale is key for miniaturized functional devices, but material properties may vary spatially across microstructures. Characterization of these miniaturized devices requires electronic structure probes with sufficient spatial resolution to understand the influence of structure size and shape on functional properties. The present study demonstrates the use of imaging soft X-ray absorption spectroscopy with a spatial resolution better than 2 [Formula: see text]m to study the insulator-metal transition in vanadium dioxide thin-film microstructures. This novel technique reveals that the transition temperature for the conversion from insulating to metallic vanadium dioxide is lowered by 1.2 K ± 0.4 K close to the structure edges compared to the center. Facilitated strain release during the phase transition is discussed as origin of the observed behavior. The experimental approach enables a detailed understanding of how the electronic properties of quantum materials depend on their patterning at the micrometer scale.
Road condition monitoring and alert application: Using in-vehicle Smartphone as Internet-connected sensor (2012)

The proposal describes a road condition monitoring and alert application using the in-vehicle Smartphone as connected sensors, which are connected to an Internet-of-Things platform over the Internet. In addition to providing a generic Internet-of-Things based platform, the proposed solution brings in novel energy-efficient phone-orientation-agnostic accelerometer analytics in phone, reduces the data volume that needs be communicated between phone and the back-end over Internet, brings in multi-user fusion concepts to create authentic road condition maps and addresses privacy concerns for the phone user for sharing the required data.
Repopulation of primary renal cells for whole organ engineering: functional evaluations (2015)

Abolbashari, Mehran MD; Lee, Mi Kyung MD; Agcaoili, Sigrid MD; Aboushwareb, Tamer MD, PhD; Jackson, John D. PhD; Ko, In Kap PhD; Yoo, James MD, PhD; Atala, Anthony MD, FACS Author Information
Selective blockade of the hydrolysis of the endocannabinoid 2-arachidonoylglycerol impairs learning and memory performance while producing antinociceptive activity in rodents (2015)

Monoacylglycerol lipase (MAGL) represents a primary degradation enzyme of the endogenous cannabinoid (eCB), 2-arachidonoyglycerol (2-AG). This study reports a potent covalent MAGL inhibitor, SAR127303. The compound behaves as a selective and competitive inhibitor of mouse and human MAGL, which potently elevates hippocampal levels of 2-AG in mice. In vivo, SAR127303 produces antinociceptive effects in assays of inflammatory and visceral pain. In addition, the drug alters learning performance in several assays related to episodic, working and spatial memory. Moreover, long term potentiation (LTP) of CA1 synaptic transmission and acetylcholine release in the hippocampus, two hallmarks of memory function, are both decreased by SAR127303. Although inactive in acute seizure tests, repeated administration of SAR127303 delays the acquisition and decreases kindled seizures in mice, indicating that the drug slows down epileptogenesis, a finding deserving further investigation to evaluate the potential of MAGL inhibitors as antiepileptics. However, the observation that 2-AG hydrolysis blockade alters learning and memory performance, suggests that such drugs may have limited value as therapeutic agents.
The novel calcineurin inhibitor ISA247: a more potent immunosuppressant than cyclosporine in vitro (2004)

Abstract ISA247 is a novel cyclosporine analog. In this study we compare, in vitro, the effects of ISA247 on immune function with those of cyclosporine. Whole blood from cynomolgus monkeys (n= 5) was incubated with different concentrations of ISA247 or cyclosporine and stimulated with different mitogens in culture medium. Lymphocyte proliferation was assessed by [3H]-TdR incorporation assay and by flow cytometry. Flow cytometry was also used to assess production of intracellular cytokines by T cells and expression of T cell activation surface antigens. The concentration of drug necessary to attain 50% of the maximum effect (EC50) was subsequently calculated. EC50 values for ISA247 were lower than for cyclosporine, and the differences were statistically significant for lymphocyte proliferation, T cell cytokine production, and expression of all T cell activation surface antigens but one. We conclude that ISA247 suppresses diverse immune functions more potently than cyclosporine in vitro.
Dynamic personalized recommendation of comment-eliciting stories (2012)

Media Websites often solicit users' comments on content items such as videos, news stories, blog posts, etc. Commenting activity increases user engagement with the sites, by both comment writers and readers, and so sites are looking for ways to increase the volume of comments. This work develops a recommender system aiming to present users with items -- news stories, in our case -- on which they are likely to comment. We combine items' content with a collaborative-filtering approach (utilizing users' co-commenting patterns) in a latent factor modeling framework. Building upon previous work, we focus on a continuous, real-time approach to address the problem above. After an initial training period during which commenting activity of users is observed, the system is tested at each subsequent comment submission event by predicting which story is being commented on by a given user at a given time. Our results show that we are able to overcome the site's inherent presentation bias and outperform a strong baseline as users' commenting history grows.
INDEL detection, the ‘Achilles heel’ of precise genome editing: a survey of methods for accurate profiling of gene editing induced indels (2020)

Advances in genome editing technologies have enabled manipulation of genomes at the single base level. These technologies are based on programmable nucleases (PNs) that include meganucleases, zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated 9 (Cas9) nucleases and have given researchers the ability to delete, insert or replace genomic DNA in cells, tissues and whole organisms. The great flexibility in re-designing the genomic target specificity of PNs has vastly expanded the scope of gene editing applications in life science, and shows great promise for development of the next generation gene therapies. PN technologies share the principle of inducing a DNA double-strand break (DSB) at a user-specified site in the genome, followed by cellular repair of the induced DSB. PN-elicited DSBs are mainly repaired by the non-homologous end joining (NHEJ) and the microhomology-mediated end joining (MMEJ) pathways, which can elicit a variety of small insertion or deletion (indel) mutations. If indels are elicited in a protein coding sequence and shift the reading frame, targeted gene knock out (KO) can readily be achieved using either of the available PNs. Despite the ease by which gene inactivation in principle can be achieved, in practice, successful KO is not only determined by the efficiency of NHEJ and MMEJ repair; it also depends on the design and properties of the PN utilized, delivery format chosen, the preferred indel repair outcomes at the targeted site, the chromatin state of the target site and the relative activities of the repair pathways in the edited cells. These variables preclude accurate prediction of the nature and frequency of PN induced indels. A key step of any gene KO experiment therefore becomes the detection, characterization and quantification of the indel(s) induced at the targeted genomic site in cells, tissues or whole organisms. In this survey, we briefly review naturally occurring indels and their detection. Next, we review the methods that have been developed for detection of PN-induced indels. We briefly outline the experimental steps and describe the pros and cons of the various methods to help users decide a suitable method for their editing application. We highlight recent advances that enable accurate and sensitive quantification of indel events in cells regardless of their genome complexity, turning a complex pool of different indel events into informative indel profiles. Finally, we review what has been learned about PN-elicited indel formation through the use of the new methods and how this insight is helping to further advance the genome editing field.
Structure and Bonding at Ni–ZrO2 (Cubic) Interfaces Formed by the Reduction of a NiO–ZrO2 (Cubic) Composite (1997)

Structure and Bonding at NiFATAL ERROR -- Missing abstract.ndash;ZrO 2 (Cubic) Interfaces Formed by the Reduction of a NiOFATAL ERROR -- Missing abstract.ndash;ZrO 2 (Cubic) Composite
P152 EVALUATING THE EFFICACY OF GLUTAMATE CARBOXYPEPTIDASE II (GCPII) INHIBITORS IN “WILD-TYPE” MICE: LESSONS LEARNED FROM THE DEDICATOR OF CYTOKINESIS 2 MUTANT MOUSE (2020)

Abstract Background Glutamate carboxypeptidase II (GCPII) is highly upregulated in human IBD and is a therapeutic target under active investigation by our laboratory. We recently published that a spontaneously occurring loss-of-function mutation in dedicator of cytokinesis 2 (Dock2Hsd) that was present in commercially-purchased “wild-type” C57Bl6/NHsd mice increased their sensitivity to DSS-colitis and caused them to closely resemble human IBD with respect to GCPII. The DSS-exposed Dock2Hsd mice had significantly elevated colon GCPII activities and were sensitive to treatment with the GCPII inhibitor, 2-PMPA. We hypothesized that if colitis of the same severity were to be induced in Dock2WT mice, that they would also exhibit heightened colon GCPII activity and would be equally sensitive to 2-PMPA treatment. Methods DSS-colitis was induced in weight-, age- and gender-matched C57Bl/6NHsd mice (Dock2Hsd and Dock2WT). Increasing concentrations of DSS were utilized (2.5%-4.0%) and disease activity index was monitored daily. Mice received once daily treatment with vehicle or GCPII inhibitor 2-PMPA (IP). Results With increased DSS concentrations (4%), a severe colitis could be established in the Dock2WT mice which closely resembled the disease seen in Dock2Hsd mice induced with 2.5% DSS. Interestingly, despite similarity in DAI scores and disease progression, the GCPII activity in colons of Dock2WT mice (4% DSS) remained significantly lower than that of Dock2Hsd mice (2.5% DSS) (p&amp;lt;0.001, t-test). Further, while 2-PMPA was effective in both groups, higher systemic doses were required in the IBD-resistant Dock2WT mice. Conclusions Following identification that the spontaneously occurring mutation Dock2Hsd influences murine DSS-colitis sensitivity and alters the activity of our therapeutic target protein, GCPII, in the colon, we sought to re-establish our DSS model using Dock2WT mice. While we were successfully able to recapitulate disease severity in the Dock2WT mice by increasing the DSS concentration from 2.5% to 4%, the underlying disease biology was not conserved. Despite having comparable DAI scores at study termination, Dock2WT mice had decreased GCPII activity in their colons relative to Dock2Hsd mice and were less sensitive to inhibition with the GCPII inhibitor, 2-PMPA. These data caution that target protein expression must be verified even with subtle changes to experimental method when utilizing the DSS-colitis model.
ChemInform Abstract: Synthesis and Antitumor Activity of New Derivatives of Flavone‐8‐ acetic Acid (FAA). Part 2. Ring‐Substituted Derivatives (1997)

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.
Measurement of the Difference of Time-Integrated CP Asymmetries in D[superscript 0] → K[superscript −]K[superscript +] and D[superscript 0] → π[superscript −]π[superscript +] Decays (2016)

A search for CP violation in D[superscript 0] → K[superscript -]K[superscript +] and D[superscript 0] → π[superscript -]π[superscript +] decays is performed using pp collision data, corresponding to an integrated luminosity of 3 fb[superscript -1], collected using the LHCb detector at center-of-mass energies of 7 and 8 TeV. The flavor of the charm meson is inferred from the charge of the pion in D[superscript *+] → D[superscript 0]π[superscript +] and D[superscript *-] → [bar over D][superscript 0]π[superscript -] decays. The difference between the CP asymmetries in D[superscript 0] → K[superscript -]K[superscript +] and D[superscript 0] → π[superscript -]π[superscript +] decays, ΔA[subscript CP] ≡ A[subscript CP](K[superscript -]K[superscript +]) - A[subscript CP](π[superscript -]π[superscript +]), is measured to be [-0.10 ± 0.08(stat) ± 0.03(syst)]%. This is the most precise measurement of a time-integrated CP asymmetry in the charm sector from a single experiment.
Engineering Biological-Based Vascular Grafts Using a Pulsatile Bioreactor (2011)

Much effort has been devoted to develop and advance the methodology to regenerate functional small-diameter arterial bypasses. In the physiological environment, both mechanical and chemical stimulation are required to maintain the proper development and functionality of arterial vessels. Bioreactor culture systems developed by our group are designed to support vessel regeneration within a precisely controlled chemo-mechanical environment mimicking that of native vessels. Our bioreactor assembly and maintenance procedures are fairly simple and highly repeatable. Smooth muscle cells (SMCs) are seeded onto a tubular polyglycolic acid (PGA) mesh that is threaded over compliant silicone tubing and cultured in the bioreactor with or without pulsatile stimulation for up to 12 weeks. There are four main attributes that distinguish our bioreactor from some predecessors. 1) Unlike other culture systems that simulate only the biochemical surrounding of native blood vessels, our bioreactor also creates a physiological pulsatile environment by applying cyclic radial strain to the vessels in culture. 2) Multiple engineered vessels can be cultured simultaneously under different mechanical conditions within a controlled chemical environment. 3) The bioreactor allows a mono layer of endothelial cells (EC) to be easily coated onto the luminal side of engineered vessels for animal implantation models. 4) Our bioreactor can also culture engineered vessels with different diameter size ranged from 1 mm to 3 mm, saving the effort to tailor each individual bioreactor to fit a specific diameter size. The engineered vessels cultured in our bioreactor resemble native blood vessels histologically to some degree. Cells in the vessel walls express mature SMC contractile markers such as smooth muscle myosin heavy chain (SMMHC). A substantial amount of collagen is deposited within the extracellular matrix, which is responsible for ultimate mechanical strength of the engineered vessels. Biochemical analysis also indicates that collagen content of engineered vessels is comparable to that of native arteries. Importantly, the pulsatile bioreactor has consistently regenerated vessels that exhibit mechanical properties that permit successful implantation experiments in animal models. Additionally, this bioreactor can be further modified to allow real-time assessment and tracking of collagen remodeling over time, non-invasively, using a non-linear optical microscopy (NLOM). To conclude, this bioreactor should serve as an excellent platform to study the fundamental mechanisms that regulate the regeneration of functional small-diameter vascular grafts.
Texture, Twinning, and Metastable “Tetragonal” Phase in Ultrathin Films of HfO[sub 2] on a Si Substrate (2009)

Thin HfO&lt;sub&gt;2&lt;/sub&gt; films grown on the lightly oxidised surface of (100) Si wafers have been examined using dark-field transmission electron microscopy and selected area electron diffraction in plan view. The polycrystalline film has a grain size of the order of 100 nm and many of the grains show evidence of twinning on (110) and (001) planes. Diffraction studies showed that the film had a strong [110] out-of-plane texture, and that a tiny volume fraction of a metastable (possibly tetragonal) phase was retained. The reasons for the texture, twinning and the retention of the metastable phase are discussed.
Assessing the unmet needs of patients with advanced cancer treated by biological and precision therapies: protocol for TARGET, a mixed methods study (2023)

This study was approved by National Health Service (NHS) Heath Research Authority Northeast Tyne and Wear South Research Ethics Committee (REC ref: 21/NE/0028). Dissemination of the research findings will take several formats to reach different audiences, including patients, healthcare professionals and researchers.
Visual Analytics: Foundations and Experiences in Malware Analysis (2017)

Visual Analytics (VA) is a data analysis approach that focuses on effectively intertwining human and computerized analysis processes through interactive visual interfaces. These interfaces provide visual representations of data at different levels of detail and allow direct interaction techniques to navigate the data and adjust parameters for computer-based analysis techniques. This chapter starts by providing some background in behavior-based malware analysis. Subsequently, it introduces VA and its main components based on the knowledge generation model for VA. Visual Analytics (VA) is a young research field that emerged from the combination of interactive data visualization with concepts from data mining, machine learning, statistics, human-computer interaction, and cognitive science. A major tenet of VA is that analytical reasoning is not a routine activity that can be automated completely. Instead it depends heavily on analysts initiative and domain experience which they can exercise through interactive visual interfaces.