gebhart/patrepeval huggingface dataset:
Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers (2019)

<i>KRAS</i>, an oncogene mutated in nearly one third of human cancers, remains a pharmacologic challenge for direct inhibition except for recent advances in selective inhibitors targeting the G12C variant. Here, we report that selective inhibition of the protein tyrosine phosphatase, SHP2, can impair the proliferation of KRAS-mutant cancer cells <i>in vitro</i> and <i>in vivo</i> using cell line xenografts and primary human tumors. <i>In vitro</i>, sensitivity of KRAS-mutant cells toward the allosteric SHP2 inhibitor, SHP099, is not apparent when cells are grown on plastic in 2D monolayer, but is revealed when cells are grown as 3D multicellular spheroids. This antitumor activity is also observed <i>in vivo</i> in mouse models. Interrogation of the MAPK pathway in SHP099-treated KRAS-mutant cancer models demonstrated similar modulation of p-ERK and DUSP6 transcripts in 2D, 3D, and <i>in vivo</i>, suggesting a MAPK pathway-dependent mechanism and possible non-MAPK pathway-dependent mechanisms in tumor cells or tumor microenvironment for the <i>in vivo</i> efficacy. For the KRAS<sup>G12C</sup> MIAPaCa-2 model, we demonstrate that the efficacy is cancer cell intrinsic as there is minimal antiangiogenic activity by SHP099, and the effects of SHP099 is recapitulated by genetic depletion of SHP2 in cancer cells. Furthermore, we demonstrate that SHP099 efficacy in KRAS-mutant models can be recapitulated with RTK inhibitors, suggesting RTK activity is responsible for the SHP2 activation. Taken together, these data reveal that many KRAS-mutant cancers depend on upstream signaling from RTK and SHP2, and provide a new therapeutic framework for treating KRAS-mutant cancers with SHP2 inhibitors.
Transforming or Conforming (2011)

John Nelson looks at current educational initiatives to do with the national curriculum, national literacy and numeracy testing and the My School website.
Development of an Ablative 3D Quartz / Cyanate Ester Composite for the Orion Spacecraft Compression Pad (2015)

With the successful flight test of the Orion Multipurpose Crew Vehicle last December, NASA is well on its way to sending humans into deep space with the goal of putting astronauts on Mars in the 2030s. Orion will receive some upgrades for its next launch in 2018 including a newly developed 3D Quartz Cyanate Ester composite material for the compression pad. The compression pads are 10-inches in diameter and 3-inches thick. The pucks are at 4 locations in the heat shield that serve as a part of the mechanism for holding the Crew and Service modules together during most mission phases prior to separation followed by Earth re-entry. Thus the compression pad has structural, aerothermal and thermal protection requirements.This paper describes the approach used for developing the new 3D composite, including continuous 3D weaving on an automated loom followed by resin transfer molding. Mechanical, thermal and arc jet testing of the 3D composite are also described.
Severe acute respiratory syndrome coronavirus papain-like protease: Structure of a viral deubiquitinating enzyme (2006)

Replication of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) requires proteolytic processing of the replicase polyprotein by two viral cysteine proteases, a chymotrypsin-like protease (3CLpro) and a papain-like protease (PLpro). These proteases are important targets for development of antiviral drugs that would inhibit viral replication and reduce mortality associated with outbreaks of SARS-CoV. In this work, we describe the 1.85-A crystal structure of the catalytic core of SARS-CoV PLpro and show that the overall architecture adopts a fold closely resembling that of known deubiquitinating enzymes. Key features, however, distinguish PLpro from characterized deubiquitinating enzymes, including an intact zinc-binding motif, an unobstructed catalytically competent active site, and the presence of an intriguing, ubiquitin-like N-terminal domain. To gain insight into the active-site recognition of the C-terminal tail of ubiquitin and the related LXGG motif, we propose a model of PLpro in complex with ubiquitin-aldehyde that reveals well defined sites within the catalytic cleft that help to account for strict substrate-recognition motifs.
The Organic Chem Lab Survival Manual: A Student's Guide to Techniques (1984)

Safety First, Last, and Always. Keeping a Notebook. Interpreting a Handbook. Jointware. Microscale Jointware. Other Interesting Equipment. Pipet Tips. Syringes, Needles, and Septa. Clean and Dry. Drying Agents. On Products. The Melting Point Experiment. Recrystallization. Recrystallization: Microscale. Extraction and Washing. Extraction and Washing: Microscale. And NowBoiling Stones. Sources of Heat. Clamps and Clamping. Distillation. Microscale Distillation. Reflux and Addition. Reflux: Microscale. Sublimation. Microscale Boiling Point. Chromatography: Some Generalities. Thin-Layer Chromatography: TLC. Wet-Column Chromatography. Refractometry. Instrumentation in the Lab. Gas Chromatography. HP Liquid Chromatography. Infrared Spectroscopy. Nuclear Magnetic Resonance. Theory of Distillation. Theory of Extraction. Index.
SecureBPMN (2012)

Modern enterprise systems have to comply to regulations such as Basel III resulting in complex security requirements. These requirements need to be modeled at design-time and enforced at runtime. Moreover, modern enterprise systems are often business-process driven, i.e., the system behavior is described as high-level business processes that are executed by a business process execution engine.
Surface Effect on Mechanical Properties and Local Mobility of Ultrathin Polystyrene Films from Molecular Dynamics Simulations (2016)

Thin polystyrene (PS) film has shown anomalous properties such as reduced glass transition temperature when the thickness is below 100 nm. However, few attentions have been paid to its mechanical properties, which are important in understanding the stability and reliability of polymer nano-structures. In this work, we aim at elucidating the size dependent mechanical properties of ultrathin polystyrene films using molecular dynamics (MD) simulations. Coarse grained MD samples of free-standing PS films with different thicknesses were generated using the augmented phantom chain growth method. Active deformations were applied by moving two repulsive walls to determine the size dependent mechanical properties of the films. The distribution of local atomic mobility was investigated through dividing the films into equidistant bins along thickness and calculating the mean square displacement (MSD) for each bin. The local mobility of atoms at different positions of the chain as well as the mobility of the entire chain are also investigated. The results indicate the existence of a softened surface layer with reduced modulus and enhanced local atom mobility compared to the bulk state. It shows the deformation has an enhancing effect on the local atom mobility, especially along the thickness direction. This work can provide insights into the size dependent mechanical properties of ultrathin PS films.
Therapeutic potential of larval excretory/secretory proteins of the pig whipworm<i>Trichuris suis</i>in allergic disease (2014)

Taken together, these data demonstrate that the released proteins of larval T. suis have significant immunomodulatory capacities and efficiently dampen allergic airway hyperreactivity. Thus, the therapeutic potential of defined larval E/S proteins should be exploited for the treatment of human allergic disorders.
Second thyroid neoplasms after prophylactic cranial irradiation for acute lymphoblastic leukemia (1998)

An understanding of the pathogenesis of second cancers may help in their prevention. We report on two children who were treated for acute lymphoblastic leukemia (ALL), with an exclusively cranial prophylactic irradiation (18 Gy) and who presented with a thyroid carcinoma (TC) 12 and 13 years later. From a thorough review of the literature of TC after ALL and of radiation-induced TC, a strong case can be made that these tumors are caused by late effects of scattered radiation. The risk is at its highest in small children. After cranial irradiation, patients require clinical monitoring of the thyroid and cervical area for nodules, continued indefinitely. We suggest that, in most cases, an alternative form of neuromeningeal prophylaxis should be offered in small children with ALL. Am. J. Hematol. 59:91–94, 1998. © 1998 Wiley-Liss, Inc.
Picone, Michael D. 1996. <i>Anglicisms, Neologisms and Dynamic French</i>. (<i>Lingvisticae Investigationes: Supplementa</i> Vol. 18.) Amsterdam: John Benjamins. 462 + xii pp. ISSN: 0165 7569 ISBN (USA) 1 55619 258 4 (2001)

Picone, Michael D. 1996. Anglicisms, Neologisms and Dynamic French. (Lingvisticae Investigationes: Supplementa Vol. 18.) Amsterdam: John Benjamins. 462 + xii pp. ISSN: 0165 7569 ISBN (USA) 1 55619 258 4 - Volume 11 Issue 2
Optimization and Application of Direct Infusion Nanoelectrospray HRMS Method for Large-Scale Urinary Metabolic Phenotyping in Molecular Epidemiology (2017)

Large-scale metabolic profiling requires the development of novel economical high-throughput analytical methods to facilitate characterization of systemic metabolic variation in population phenotypes. We report a fit-for-purpose direct infusion nanoelectrospray high-resolution mass spectrometry (DI-nESI-HRMS) method with time-of-flight detection for rapid targeted parallel analysis of over 40 urinary metabolites. The newly developed 2 min infusion method requires <10 μL of urine sample and generates high-resolution MS profiles in both positive and negative polarities, enabling further data mining and relative quantification of hundreds of metabolites. Here we present optimization of the DI-nESI-HRMS method in a detailed step-by-step guide and provide a workflow with rigorous quality assessment for large-scale studies. We demonstrate for the first time the application of the method for urinary metabolic profiling in human epidemiological investigations. Implementation of the presented DI-nESI-HRMS method enabled cost-efficient analysis of >10 000 24 h urine samples from the INTERMAP study in 12 weeks and >2200 spot urine samples from the ARIC study in <3 weeks with the required sensitivity and accuracy. We illustrate the application of the technique by characterizing the differences in metabolic phenotypes of the USA and Japanese population from the INTERMAP study.
Automatic real-time fault detection for industrial assets using metasensors (2015)

Large-scale industrial plants require physical sensors to continuously measure quantities such as temperatures or pressures. A large number of sensors is required to accurately describe the operating state of the plant, which unfortunately makes it very difficult for them to be effectively monitored by human operators. In this work we present a method to construct so-called metasensors, virtual sensors that compress the information from several sensors in an optimal manner. These metasensors are used as inputs to a novel anomaly detection system that automatically alerts operators to abnormal operation behaviour.
Estimation of delay phase offset in multi-carrier differential phase modulation systems (2004)

Propagation delay introduces unwanted delay phase offsets among carriers using different frequencies and deters differential phase demodulation in the hybrid frequency and differential phase modulation systems. Operating on the preamble sequence with two alternately transmitted pulsed carriers, an estimation approach is proposed in this paper to extract the delay phase offsets among carriers using different frequencies. It is shown that delay phase offsets can be reliably estimated when the preamble sequence is sufficiently long.
Cyan laser diode grown by plasma-assisted molecular beam epitaxy (2014)

Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter Facebook Reddit LinkedIn Tools Icon Tools Reprints and Permissions Cite Icon Cite Search Site Citation H. Turski, G. Muziol, P. Wolny, S. Grzanka, G. Cywiński, M. Sawicka, P. Perlin, C. Skierbiszewski; Cyan laser diode grown by plasma-assisted molecular beam epitaxy. Appl. Phys. Lett. 13 January 2014; 104 (2): 023503. https://doi.org/10.1063/1.4861655 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAIP Publishing PortfolioApplied Physics Letters Search Advanced Search |Citation Search
SAQIP (2019)

Proposing an architecture that efficiently compensates for the inefficiencies of physical hardware with extra resources is one of the key issues in quantum computer design. Although the demonstration of quantum systems has been limited to some dozen qubits, scaling the current small-sized lab quantum systems to large-scale quantum systems that are capable of solving meaningful practical problems can be the main goal of much research. Focusing on this issue, in this article a scalable architecture for quantum information processors, called SAQIP, is proposed. Moreover, a flow is presented to map and schedule a quantum circuit on this architecture. Experimental results show that the proposed architecture and design flow decrease the average latency and the average area of quantum circuits by about 81% and 11%, respectively, for the attempted benchmarks.
Ensemble of exemplar-SVMs for object detection and beyond (2011)

This paper proposes a conceptually simple but surprisingly powerful method which combines the effectiveness of a discriminative object detector with the explicit correspondence offered by a nearest-neighbor approach. The method is based on training a separate linear SVM classifier for every exemplar in the training set. Each of these Exemplar-SVMs is thus defined by a single positive instance and millions of negatives. While each detector is quite specific to its exemplar, we empirically observe that an ensemble of such Exemplar-SVMs offers surprisingly good generalization. Our performance on the PASCAL VOC detection task is on par with the much more complex latent part-based model of Felzenszwalb et al., at only a modest computational cost increase. But the central benefit of our approach is that it creates an explicit association between each detection and a single training exemplar. Because most detections show good alignment to their associated exemplar, it is possible to transfer any available exemplar meta-data (segmentation, geometric structure, 3D model, etc.) directly onto the detections, which can then be used as part of overall scene understanding.
Synthesis of mesoporous hollow silica nanospheres using polymeric micelles as template and their application as a drug-delivery carrier (2013)

Mesoporous hollow silica nanospheres with uniform particle sizes of 31-33 nm have been successfully synthesized by cocondensation of tetramethoxysilane (TMOS) and alkyltrimethoxysilanes [RSi(OR)3], where the latter also acts as a porogen. ABC triblock copolymer micelles of poly(styrene-b-2-vinyl pyridine-b-ethylene oxide) (PS-PVP-PEO) with a core-shell-corona architecture have been employed as a soft template at pH 4. The cationic shell block with 2-vinyl pyridine groups facilitates the condensation of silica precursors under the sol-gel reaction conditions. Phenyltrimethoxysilane, octyltriethoxysilane, and octadecyltriethoxysilanes were used as porogens for generating mesopores in the shell matrix of hollow silica and the octadecyl precursor produced the largest mesopore among the different porogens, of dimension ca. 4.1 nm. The mesoporous hollow particles were thoroughly characterized by small-angle X-ray diffraction (SXRD), thermal (TG/DTA) and nitrogen sorption analyses, infra-red (FTIR) and nuclear magnetic resonance ((13)C-CP MAS NMR and (29)Si MAS NMR) spectroscopies, and transmission electron microscopy (TEM). The mesoporous hollow silica nanospheres have been investigated for drug-delivery application by an in vitro method using ibuprofen as a model drug. The hollow silica nanospheres exhibited higher storage capacity than the well-known mesoporous silica MCM-41. Propylamine functionalized hollow particles show a more sustained release pattern than their unfunctionalized counterparts, suggesting a huge potential of hollow silica nanospheres in the controlled delivery of small drug molecules.
Remote Elemental Analysis by Laser-Induced Breakdown Spectroscopy Using a Fiber-Optic Cable (1995)

The elemental composition of solids can be determined rapidly and simply with the use of laser-induced breakdown spectroscopy (LIBS). This method, described in detail elsewhere, uses powerful laser pulses to form a microplasma or spark on a sample. A small amount of material is vaporized, and emitting species in the plasma are identified by spectrally and temporally resolving the spark light. Although LIBS measurements can be performed remotely on solids at distances up to 24 m from the laser and detection system with a long-focal-length lens, this method has some disadvantages including safety (the possibility of ocular damage by the high-energy laser pulses), need for a clear line of sight to the analysis area, scattering of incident pulse energy by dusts or fogs, and problems associated with precise focusing of laser beams at long distances. In particular, the plasma will preferentially form on dust particles in front of the sample because of the long Rayleigh length of the focused beam.
Compact Millimeter-Wave Sensor for Remote Monitoring of Vital Signs (2011)

A compact millimeter-wave (MMW) sensor has been developed for remote monitoring of human vital signs (heart and respiration rate). The low-power homodyne transceiver operating at 94 GHz was assembled by using solid-state active and passive block-type components and can be battery operated. A description of the MMW system front end and the back-end acquisition hardware and software is presented. Representative test case results on the application of various signal processing and data analysis algorithms developed to extract faint physiological signals of interest in presence of strong background interference are provided. Although the laboratory experiments so far have been limited to standoff distances of up to 15 m, the upper limit of the detection range is expected to be higher. In comparison with its microwave counterparts, the MMW system described here provides higher directivity, increased sensitivity, and longer detection range for measuring subtle mechanical displacements associated with heart and respiration functions. The system may be adapted for use in a wide range of standoff sensing applications including for patient health care, structural health monitoring, nondestructive testing, biometric sensing, and remote vibrometry in general.
The Human Fetal Retinal Pigment Epithelium: A Target Tissue for Thyroid Hormones (1999)

Thyroid hormone (T(3)) has previously been shown to regulate visual function in experimental animals and humans. To determine if T(3) exerts direct effects on retinal function, cultured human fetal retinal pigment epithelial (RPE) cells were tested for the presence of thyroid hormone receptors (TRs) and T(3) responses. Using TR-isoform-specific reverse-transcriptase polymerase chain reaction techniques, mRNA was detected for alpha1, alpha2 and beta1 TR isoforms. Immunohistochemistry using a polyclonal antibody that simultaneously recognizes alpha1, alpha2 and beta1 TRs showed nuclear staining of the fetal RPE. Specific binding of (125)I-T(3) to RPE cell nuclear extracts was detected, and Scatchard analysis revealed a K(d) of 110 pM. To determine if RPE cells can respond to T(3), hyaluronic acid (HA) levels in cell culture media were measured after 2, 4 or 6 days of growth in medium containing 10(-7) M T(3). T(3) inhibited accumulation of HA in the cell culture medium of RPE cells. This effect was not evident at 2 days, but at 4 days there was 42.8% less HA in cell culture medium of RPE cells grown in 10(-7) M T(3) (p < 0.01, t test). The effect persisted through 6 days, when there was 46.3% less HA in cell culture medium of RPE cells grown in 10(-7) M T(3) (p < 0.001, t test). The data indicate that human fetal RPE cells are a direct target for thyroid hormones.
Integration of Multivariate Data Streams With Bandpower Signals (2013)

The urge to further our understanding of multimodal neural data has recently become an important topic due to the ever increasing availability of simultaneously recorded data from different neural imaging modalities. In case where EEG is one of the modalities, it is of interest to relate a nonlinear function of the raw EEG time-domain signal, say, EEG band power, to another modality such as the hemodynamic response, as measured with NIRS or fMRI. In this work we tackle exactly this problem defining a novel algorithm that we denote multimodal source power correlation analysis (mSPoC). The validity and high performance of the mSPoC framework is demonstrated for simulated and real-world multimodal data.
Clinical Relevance of Cortical Spreading Depression in Neurological Disorders: Migraine, Malignant Stroke, Subarachnoid and Intracranial Hemorrhage, and Traumatic Brain Injury (2010)

Cortical spreading depression (CSD) and depolarization waves are associated with dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells, increased energy metabolism and changes in cerebral blood flow (CBF). There is strong clinical and experimental evidence to suggest that CSD is involved in the mechanism of migraine, stroke, subarachnoid hemorrhage and traumatic brain injury. The implications of these findings are widespread and suggest that intrinsic brain mechanisms have the potential to worsen the outcome of cerebrovascular episodes or brain trauma. The consequences of these intrinsic mechanisms are intimately linked to the composition of the brain extracellular microenvironment and to the level of brain perfusion and in consequence brain energy supply. This paper summarizes the evidence provided by novel invasive techniques, which implicates CSD as a pathophysiological mechanism for this group of acute neurological disorders. The findings have implications for monitoring and treatment of patients with acute brain disorders in the intensive care unit. Drawing on the large body of experimental findings from animal studies of CSD obtained during decades we suggest treatment strategies, which may be used to prevent or attenuate secondary neuronal damage in acutely injured human brain cortex caused by depolarization waves.