gebhart/patrepeval huggingface dataset:
Abstract 1738: JNJ-42756493 is an inhibitor of FGFR-1, 2, 3 and 4 with nanomolar affinity for targeted therapy (2014)

Abstract The fibroblast growth factor (FGF) signaling axis is increasingly implicated in tumorigenesis and chemoresistance. Alterations in FGFR family members including focal amplification of FGF receptor 1 (FGFR1), mutations in FGFR 2, 3 and 4, translocations involving FGFR 2 and FGFR3, as well as amplification or transcriptional upregulation of various ligand family members have been associated with tumor growth and survival, suggesting that FGFR inhibitors may be a viable therapeutic option in subsets of various disease settings. A number of agents targeting the FGF signaling axis including small-molecule FGFR targeted agents, with diverse kinase inhibitory and pharmacological profiles, are currently in clinical development. JNJ-42756493 (first disclosure of the structure) has a pharmacological profile that is differentiated from other agents in this class currently under investigation. JNJ-42756493 displays single digit nanomolar FGFR (1, 2, 3 4) tyrosine kinase inhibitory activity. JNJ-42756493 inhibited recombinant FGFR kinase activity in vitro and suppressed FGFR signaling and growth in engineered cell lines and tumor cell lines dependent upon deregulated FGFR expression. JNJ-42756493 demonstrated highly specific tumor inhibitory effects in FGFR1-4 dependent cell lines, in vitro cell lines based xenografts and direct patient derived xenografts, with no discernible activity in models that were not dependent on FGFR signaling. JNJ-42756493 showed favorable drug like properties and displayed a high distribution to lung, liver and kidney tissue. JNJ-42756493 was well tolerated at efficacious doses and resulted in potent dose-dependent antitumor activity accompanied by pharmacodynamic modulation of tumor FGFR and downstream pathway components. Data presented here highlights JNJ-42756493 as a novel, highly potent and selective small-molecule inhibitor of all four known active FGFR kinase family members with potent antitumor activity against FGFR-dependent tumor models. These data, together with emerging observations from our ongoing Phase 1 clinical trial, position JNJ-42756493 as a differentiated FGFR 1, 2, 3 and 4 kinase inhibitor and support its continued clinical development in lung cancer and other malignancies associated with aberrant FGFR signaling. Citation Format: Timothy Perera, Eleanora Jovcheva, Jorge Vialard, Tinne Verhulst, Norbert Esser, Berthold Wroblowski, Ron Gilissen, Eddy Freyne, Peter King, Suso Platero, Olivier Querolle, Laurence Mevellec, Christopher Murray, Lynsey Fazal, Gordon Saxty, George Ward, Matthew Squires, Neil Thompson, David Newell, Patrick Angibaud. JNJ-42756493 is an inhibitor of FGFR-1, 2, 3 and 4 with nanomolar affinity for targeted therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1738. doi:10.1158/1538-7445.AM2014-1738
Ambient intelligence - key technologies in the information age (2004)

In this paper, applications are discussed that describe achievements along the road towards 'Ambient Intelligence'. Appliances and devices disappear into the environment of the individual; instead services come into focus. Key to this development are system solutions that lead to a significant improvement of the human-machine interface. Along this line, we present important technologies and key system components ranging from low-cost electronic technologies and systems, to ubiquitous sensor networks and electronics in smart textiles. In conclusion, this presentation relates the semiconductor technology roadmap to a future world in which electronics meets human needs in a pervasive, intuitive and beneficial way.
Iron-Catalyzed C(sp2)–H Alkylation of Indolines and Benzo[h]quinoline with Unactivated Alkyl Chlorides through Chelation Assistance (2020)

Regioselective C–H bond alkylation of indolines and benzo[h]quinoline with a wide range of unactivated and highly demanded primary and secondary alkyl chlorides is accomplished using a low-cost iron catalyst. This reaction tolerates diverse functionalities, such as C(sp2)–Cl, fluoro, alkenyl, silyl, ether, thioether, pyrrolyl, and carbazolyl groups including cyclic and acyclic alkyls as well as alkyl-bearing fatty-alcohol and polycyclic-steroid moieties. The demonstrated iron-catalyzed protocol proceeded via either a five-membered or a six-membered metallacycle. Intriguingly, the C-7-alkylated indolines can be readily functionalized into free-NH indolines/indoles and tryptamine derivatives. A detailed mechanistic investigation highlights the participation of an active Fe(I) catalyst and the involvement of a halogen-atom transfer process via a single-electron-based mechanism. Deuterium labeling and kinetics analysis indicate that the C–H metalation of indoline is the probable turnover-limiting step. Overall, the experimental and theoretical studies supported an Fe(I)/Fe(III) pathway for the alkylation reaction comprising the two-step, one-electron oxidative addition of alkyl chloride.
Scanning-beam digital x-ray (SBDX) technology for interventional and diagnostic cardiac angiography (2006)

The scanning-beam digital x-ray (SBDX) system is designed for x-ray dose reduction in cardiac angiographic applications. Scatter reduction, efficient detection of primary x-rays, and an inverse beam geometry are the main components of the entrance dose reduction strategy. This paper reports the construction of an SBDX prototype, image reconstruction techniques, and measurements of spatial resolution and x-ray output. The x-ray source has a focal spot that is electronically scanned across a large-area transmission target. A multihole collimator beyond the target defines a series of x-ray beams directed at a distant small-area detector array. The prototype has a 23 cm X 23 cm target, 100 X 100 focal spot positions, and a 5 cm X 5 cm CdTe detector positioned 150 cm from the target. With this nonmechanical method of beam scanning, patient images with low detected scatter are generated at up to 30 frame/s. SBDX data acquisition is tomosynthetic. The prototype simultaneously reconstructs 16 planes spaced throughout the cardiac volume using shift-and-add backprojection. Image frames analogous to conventional projection images are generated with a multiplane compositing algorithm. Single-plane versus multiplane reconstruction of contrast-filled coronary arteries is demonstrated with images of the porcine heart. Phantom and porcine imaging studies show multiplane reconstruction is practicable under clinically realistic levels of patient attenuation and cardiac motion. The modulation transfer function for an in-plane slit at mechanical isocenter measured 0.41-0.56 at 1 cycle/mm, depending on the detector element to image pixel interpolation technique. Modeling indicates that desired gains in spatial resolution are achievable by halving the detector element width. The x-ray exposure rate 15 cm below isocenter, without table or patient in the beam, measured 11.5 R/min at 120 kVp, 24.3 kWp and 3.42 R/min at 70 kVp, 14.2 kWp.
Cyclic Adenosine Monophosphate in Bacteria (1970)

Both cyclic AMP and a specific inducer acting in concert are required for the synthesis of many inducible enzymes in E. coli. Little enzyme is made in the absence of either. In contrast to the specific inducers which stimulate the synthesis only of the proteins required for their metabolism, cyclic AMP controls the synthesis of many proteins. Glucose and certain other carbohydrates decrease the differential rate of synthesis of inducible enzymes by lowering cyclic AMP concentrations. In the lac operon, cyclic AMP acts at the promoter site to facilitate initiation of transcription. This action requires another protein, the cyclic AMP receptor protein. The nucleotide stimulates tryptophanase synthesis at a translational level. The action of cyclic AMP in E. coli may serve as a model to understand its action on transcriptional and translational processes in eukaryotes.
Sim VQA: Exploring Simulated Environments for Visual Question Answering (2022)

Existing work on VQA explores data augmentation to achieve better generalization by perturbing images in the dataset or modifying existing questions and answers. While these methods exhibit good performance, the diversity of the questions and answers are constrained by the available images. In this work we explore using synthetic computer-generated data to fully control the visual and language space, allowing us to provide more diverse scenarios. We quantify the effectiveness of leveraging synthetic data for real-world VQA. By exploiting 3D and physics simulation platforms, we provide a pipeline to generate synthetic data to expand and replace type-specific questions and answers without risking exposure of sensitive or personal data that might be present in real images. We offer a comprehensive analysis while expanding existing hyper-realistic datasets to be usedfor VQA. We also propose Feature Swapping (F-SWAP) - where we randomly switch object-level features during training to make a VQA model more domain invariant. We show that F-SWAP is effective for improving VQA models on real images without compromising on their accuracy to answer existing questions in the dataset.
Supplementary Table S4 from Supraphysiologic Testosterone Induces Ferroptosis and Activates Immune Pathways through Nucleophagy in Prostate Cancer (2023)

&lt;p&gt;Bioplex assay for measurement of chemokines&lt;/p&gt;
A closer look at recognition-based graphical passwords on mobile devices (2010)

Graphical password systems based on the recognition of photographs are candidates to alleviate current over-reliance on alphanumeric passwords and PINs. However, despite being based on a simple concept -- and user evaluations consistently reporting impressive memory retention -- only one commercial example exists and overall take-up is low. Barriers to uptake include a perceived vulnerability to observation attacks; issues regarding deployability; and the impact of innocuous design decisions on security not being formalized. Our contribution is to dissect each of these issues in the context of mobile devices -- a particularly suitable application domain due to their increasing significance, and high potential to attract unauthorized access. This produces: 1) A novel yet simple solution to the intersection attack that permits greater variability in login challenges; 2) Detailed analysis of the shoulder surfing threat that considers both simulated and human testing; 3) A first look at image processing techniques to contribute towards automated photograph filtering. We operationalize our observations and gather data in a field context where decentralized mechanisms of varying entropy were installed on the personal devices of participants. Across two working weeks success rates collected from users of a high entropy version were similar to those of a low entropy version at 77%, and login durations decreased significantly across the study.
Rapidly Correcting Frameshift Mutations in the Mycobacterium tuberculosis orn Gene Produce Reversible Ethambutol Resistance and Small-Colony-Variant Morphology (2020)

We have identified a previously unknown mechanism of reversible high-level ethambutol (EMB) resistance in <i>Mycobacterium tuberculosis</i> that is caused by a reversible frameshift mutation in the <i>M. tuberculosis</i><i>orn</i> gene. A frameshift mutation in <i>orn</i> produces the small-colony-variant (SCV) phenotype, but this mutation does not change the MICs of any drug for wild-type <i>M. tuberculosis</i> However, the same <i>orn</i> mutation in a low-level EMB-resistant double <i>embB-aftA</i> mutant (MIC = 8 μg/ml) produces an SCV with an EMB MIC of 32 μg/ml. Reversible resistance is indistinguishable from a drug-persistent phenotype, because further culture of these <i>orn-embB-aftA</i> SCV mutants results in rapid reversion of the <i>orn</i> frameshifts, reestablishing the correct <i>orn</i> open reading frame, returning the culture to normal colony size, and reversing the EMB MIC back to that (8 μg/ml) of the parental strain. Transcriptomic analysis of <i>orn-embB-aftA</i> mutants compared to wild-type <i>M. tuberculosis</i> identified a 27-fold relative increase in the expression of <i>embC</i>, which is a cellular target for EMB. Expression of <i>embC</i> in <i>orn-embB-aftA</i> mutants was also increased 5-fold compared to that in the parental <i>embB-aftA</i> mutant, whereas large-colony <i>orn</i> frameshift revertants of the <i>orn-embB-aftA</i> mutant had levels of <i>embC</i> expression similar to that of the parental <i>embB-aftA</i> strain. Reversible frameshift mutants may contribute to a reversible form of microbiological drug resistance in human tuberculosis.
A concise summary of spatial anomalies and its application in efficient real-time driving behaviour monitoring (2016)

This work is motivated by a smart car application which analyses streams of data generated from cars to enhance transportation safety. We treated the problem as real-time abnormal driving behaviour detection using spatio-temporal data collected from mobile devices including GPS location, speed and steering angle. A concise summary was proposed to summarise spatial patterns from GPS trajectory data for efficient real-time anomaly detection. An approach solving this problem by nearest neighbour search has O(n) space and O(log(n) + k) query time complexity, where k is the neighbourhood size and n is the data size. On the other hand, the concise summary approach requires only O(ε * n) memory space and has O(log(ε * n)) query time complexity, where k is several orders of magnitude smaller than one. Experiments with two large datasets from Porto and Beijing showed that our method used only a few megabytes to summarise datasets with n = 80 million data points and was able to process 30K queries per second which was several orders of magnitude faster than the baseline approach. Besides, in the work, interesting spatio-temporal patterns regarding abnormal driving behaviours from the real-world datasets are also discussed to demonstrate potential application of the work in many industries including insurance, transportation safety enhancement and city transport management.
Design and demonstration of a far-field imaging system with a one-dimensional form factor (2016)

We present a far-field imaging system with a one-dimensional form factor based on coupling light into the side of an optical fiber. The point spread function of this threadlike camera is determined analytically and confirmed experimentally. Because the system is one-dimensional, high resolution is available in one spatial dimension. An imaging device is demonstrated with an angular resolution of 100 micro-radians. Diffraction-limited imaging is achieved for aperture lengths as large as 1 cm. An image is formed from a light field produced by a Dammann grating illuminated by a laser.
Data from Activation of <i>Notch</i> and <i>Myc</i> Signaling via B-cell–Restricted Depletion of <i>Dnmt3a</i> Generates a Consistent Murine Model of Chronic Lymphocytic Leukemia (2023)

&lt;div&gt;Abstract&lt;p&gt;Chronic lymphocytic leukemia (CLL) is characterized by disordered DNA methylation, suggesting these epigenetic changes might play a critical role in disease onset and progression. The methyltransferase &lt;i&gt;DNMT3A&lt;/i&gt; is a key regulator of DNA methylation. Although &lt;i&gt;DNMT3A&lt;/i&gt; somatic mutations in CLL are rare, we found that low &lt;i&gt;DNMT3A&lt;/i&gt; expression is associated with more aggressive disease. A conditional knockout mouse model showed that homozygous depletion of &lt;i&gt;Dnmt3a&lt;/i&gt; from B cells results in the development of CLL with 100% penetrance at a median age of onset of 5.3 months, and heterozygous &lt;i&gt;Dnmt3a&lt;/i&gt; depletion yields a disease penetrance of 89% with a median onset at 18.5 months, confirming its role as a haploinsufficient tumor suppressor. B1a cells were confirmed as the cell of origin of disease in this model, and &lt;i&gt;Dnmt3a&lt;/i&gt; depletion resulted in focal hypomethylation and activation of &lt;i&gt;Notch&lt;/i&gt; and &lt;i&gt;Myc&lt;/i&gt; signaling. Amplification of chromosome 15 containing the &lt;i&gt;Myc&lt;/i&gt; gene was detected in all CLL mice tested, and infiltration of high-&lt;i&gt;Myc&lt;/i&gt;–expressing CLL cells in the spleen was observed. Notably, hyperactivation of &lt;i&gt;Notch&lt;/i&gt; and &lt;i&gt;Myc&lt;/i&gt; signaling was exclusively observed in the &lt;i&gt;Dnmt3a&lt;/i&gt; CLL mice, but not in three other CLL mouse models tested (&lt;i&gt;Sf3b1-Atm&lt;/i&gt;, &lt;i&gt;Ikzf3&lt;/i&gt;, and &lt;i&gt;MDR&lt;/i&gt;), and &lt;i&gt;Dnmt3a&lt;/i&gt;-depleted CLL were sensitive to pharmacologic inhibition of &lt;i&gt;Notch&lt;/i&gt; signaling &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt;. Consistent with these findings, human CLL samples with lower &lt;i&gt;DNMT3A&lt;/i&gt; expression were more sensitive to &lt;i&gt;Notch&lt;/i&gt; inhibition than those with higher &lt;i&gt;DNMT3A&lt;/i&gt; expression. Altogether, these results suggest that &lt;i&gt;Dnmt3a&lt;/i&gt; depletion induces CLL that is highly dependent on activation of &lt;i&gt;Notch&lt;/i&gt; and &lt;i&gt;Myc&lt;/i&gt; signaling.&lt;/p&gt;Significance:&lt;p&gt;Loss of &lt;i&gt;DNMT3A&lt;/i&gt; expression is a driving event in CLL and is associated with aggressive disease, activation of &lt;i&gt;Notch&lt;/i&gt; and &lt;i&gt;Myc&lt;/i&gt; signaling, and enhanced sensitivity to &lt;i&gt;Notch&lt;/i&gt; inhibition.&lt;/p&gt;&lt;/div&gt;
Real-time testbed implementation of a distributed cooperative MAC and PHY (2010)

We present the implementation and experimental evaluation of a new, fully distributed protocol for random access systems that exploits symbol-level physical layer cooperation. By allowing single-antenna nodes to cooperate with their neighbors, MIMO-like performance is achieved. Our Distributed On-demand Cooperation (DOC) protocol is unique in its ability to realize a cooperative mode only under circumstances where cooperation can assist. Thus, under high SNR scenarios where cooperation is rarely necessary, DOC gracefully reverts to a standard CSMA/CA protocol. Our implementation of the custom DOC MAC and PHY is built on the Rice University Wireless Open-Access Research Platform (WARP). It operates in real-time without any offline processing, allowing for standalone operation and packet exchanges at timescales comparable to commercial IEEE 802.11 devices. This implementation of the DOC MAC/PHY system addresses real-world degradations like imperfections in synchronization and link-level coordination. Extensive experimental results demonstrate that our implementation delivers substantial improvement in end-to-end throughput over that of a non-cooperative link.
ChemInform Abstract: TRANSITION METAL‐METHYLENE COMPLEXES. XXX. STEPWISE FORMATION OF METHYLENE BRIDGES BY CARBENE ADDITION TO METAL‐METAL DOUBLE BONDS (1982)

Abstract Aus dem Halbsandwich‐Komplex (I) wird thermisch der zweikernige Komplex (II) mit Cobalt‐ Cobalt‐Doppelbindungen erhalten, aus dem durch Carben‐Übertragung mit den Diazoalkanen (III) bzw. (VI) die u‐Alkyliden‐Komplexe (IV) und (VII) zugänglich sind.
On The Dissolution Kinetics Of Positive Photoresists: The Secondary Structure Model (1987)

Dissolution kinetics of several model resins with well defined molecular structures were studied extensively. These include a pure m-cresol formaldehyde novolac resin and an alternating m,R-cresol novolac. Other phenolic materials, such as poly(4-hydroxy-styrene), were also examined. Secondary structures of these materials were predicted by molecular mechanics energy minimization techniques and corroborated by comparison with existing experimentally determined X-ray crystallographic data, where available. The excellent agreement between theory and experiment for simple systems lends credence to structural predictions for our model systems. The salient conformational features of these molecules are manifested in the variety of inter- and intramolecular hydrogen bonding interactions which influence strongly the dissolution properties of a given resin. Dissolution kinetics were studied as a function of cation type, developer ionic strength, normality and temperature. The results are explained in terms of the inter- and intramolecular interactions predicted for these resins. Finally we show results which indicate the utility of our model to the design of resist/developer systems.
A Weighted Viewport Quality Metric for Omnidirectional Images (2019)

Thanks to the ability to bring immersive experiences to users, Virtual Reality (VR) technologies have been gaining popularity in recent years. A key component in VR systems is omnidirectional content, which can provide 360-degree views of scenes. However, at a given time, only a portion of the full omnidirectional content, called viewport, is displayed corresponding to the user's current viewing direction. In this work, we first develop Weighted-Viewport PSNR (W-VPSNR), an objective quality metric for quality assessment of omnidirectional content. The proposed metric takes into account the foveation feature of the human visual system. Then, we build a subjective database consisting of 72 stimuli with spatial varying viewport quality. By using this database, an evaluation of the proposed metric and four conventional metrics is conducted. Experiment results show that the W-VPSNR metric well correlates with the mean opinion scores (MOS) and outperforms the conventional metrics. Also, it is found that the conventional metrics do not perform well for omnidirectional content.
Principled multilingual grammars for large corpora (1994)

In-depth text understanding for large-scale applica-tions requires a broad-coverage, robust grammar. We describe a multilingual implementation of such a grammar, and its advantages over both principle-based parsing and ad-hoc grammar design. We show how X-bar theory and language-independent semantic constraints facilitate grammar development. Our im-plementation includes innovative handling of (1) syn-tactic gaps, (2) logical structure alternations, and (3) conjunctions. Each of these innovations enhances per-formance in both large-scale and multilingual natural language processing applications. Phrase structure grammars are hardly new. The nov-elty in this paper comes from the use of practical