gebhart/patrepeval huggingface dataset:
Data from Caveolae-Mediated Endocytosis as a Novel Mechanism of Resistance to Trastuzumab Emtansine (T-DM1) (2023)

&lt;div&gt;Abstract&lt;p&gt;Trastuzumab emtansine (T-DM1) is an antibody–drug conjugate (ADC) that has demonstrated clinical benefit for patients with HER2&lt;sup&gt;+&lt;/sup&gt; metastatic breast cancer; however, its clinical activity is limited by inherent or acquired drug resistance. The molecular mechanisms that drive clinical resistance to T-DM1, especially in HER2&lt;sup&gt;+&lt;/sup&gt; tumors, are not well understood. We used HER2&lt;sup&gt;+&lt;/sup&gt; cell lines to develop models of T-DM1 resistance using a cyclical dosing schema in which cells received T-DM1 in an “on-off” routine until a T-DM1–resistant population was generated. T-DM1–resistant N87 cells (N87-TM) were cross-resistant to a panel of trastuzumab-ADCs (T-ADCs) with non–cleavable-linked auristatins. N87-TM cells do not have a decrease in HER2 protein levels or an increase in drug transporter protein (e.g., MDR1) expression compared with parental N87 cells. Intriguingly, T-ADCs using auristatin payloads attached via an enzymatically cleavable linker overcome T-DM1 resistance in N87-TM cells. Importantly, N87-TM cells implanted into athymic mice formed T-DM1 refractory tumors that remain sensitive to T-ADCs with cleavable-linked auristatin payloads. Comparative proteomic profiling suggested enrichment in proteins that mediate caveolae formation and endocytosis in the N87-TM cells. Indeed, N87-TM cells internalize T-ADCs into intracellular caveolin-1 (CAV1)–positive puncta and alter their trafficking to the lysosome compared with N87 cells. T-DM1 colocalization into intracellular CAV1-positive puncta correlated with reduced response to T-DM1 in a panel of HER2&lt;sup&gt;+&lt;/sup&gt; cell lines. Together, these data suggest that caveolae-mediated endocytosis of T-DM1 may serve as a novel predictive biomarker for patient response to T-DM1. &lt;i&gt;Mol Cancer Ther; 17(1); 243–53. ©2017 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Determining the Required Probe Vehicle Size for Real-Time Travel Time Estimation on Signalized Arterial (2018)

Determining the required probe vehicle size for real-time travel time estimation is an important issue in probe-data-based applications, such as traffic monitoring on a roadway network. This paper provides an innovative approach for the determination of proper sample sizes with the aid of a simulation model. The model, which was built for El Camino Real, a major arterial in the California San Francisco Bay Area, helps to provide the necessary detailed data to verify the proposed methodology. Our proposed approach is based on the findings that the distribution of travel time estimate error can be constructed with the generalized Pareto distribution function. Considering that travel times vary within a signal cycle and among different movements (through, left-turning and right-turning) at intersections, our study uses data in 15-s intervals to examine the travel time variations associated with different intersection movements. Our findings show that when the penetration rate of probe vehicles is 40%, the probability that the relative error will be less than 0.10 within the time period is 90%, whereas a penetration rate greater than 60% is needed to attain a 0.95 confidence level at the same error rate. For left-turning vehicles, a 10% penetration of probe vehicles is sufficient for estimating their travel times with relative errors less than 0.10 at a 90% confidence level, whereas through vehicles and right-turning vehicles require substantially higher penetration rates of approximately 50% and 30%, respectively, to attain the same confidence level.
Altered intracellular localization of fibroblast growth factor receptor 3 in human breast cancer (2001)

Immunohistochemical staining of human breast tissues, using an antibody against fibroblast growth factor receptor 3 [FGFR-3], showed differences in cellular distribution. Both malignant and non-malignant epithelial cells contained FGFR-3 immunoreactivity, but myoepithelial cells and stroma were negative. The staining pattern in malignant epithelial cells was predominantly nuclear, whereas epithelial cells in normal breast tissue showed both cytoplasmic and nuclear elements. Reverse transcription-polymerase chain reaction (RT-PCR) revealed two isoforms of FGFR-3 corresponding to the FGFR-3-IIIb variant and a previously described exon-deleted nuclear form of FGFR-3, which were present in both malignant and non-malignant epithelial cells. The higher level of nuclear staining and loss of cytoplasmic staining seen in malignant epithelial cells did not correspond to an increase in expression of the exon-deleted form of FGFR-3, nor to any detectable activating point mutations. Since receptor activation can result in its movement to a perinuclear localization, an alternative explanation for the redistribution of FGFR-3-IIIb could be different degrees of activation by a ligand (FGF1 or FGF9). No FGF9 was detected by immunohistochemistry in breast tissues. FGF1, however, is present in the majority of breast cancers and a different tissue distribution of FGF1 was found in breast tissues, showing predominantly nuclear, or a mix of nuclear and cytoplasmic FGFR-3. The difference in FGFR-3 staining patterns may implicate this ligand-receptor pair in breast cancer. Copyright © 2001 John Wiley & Sons, Ltd.
Calibration and Estimation of Attitude Errors for a Rotating Fan-Beam Scatterometer Using Calibration Ground Stations (2014)

The rotating fan-beam scatterometer (RFSCAT) onboard Chinese-French Oceanic SATellite (CFOSAT) due to launch in 2018 is a new type of radar scatterometer system for ocean surface wind vector measurement. It can give observations with more azimuth and incidence angles for a single wind vector cell (WVC) than other available scatterometers. This has been proved effective in bettering the retrieved wind quality by the simulation approach. However, its innovative observing geometry is challenging for the coming in-orbit external calibration. In this paper, CFOSAT attitude errors are estimated, and its antenna gain pattern is monitored and verified based on the external calibration strategy of a Ku-band scatterometer employing calibration ground stations (CGSs). The effects of satellite attitude errors on the measurements are also analyzed, together with simulation results for the external calibration. It is shown that a gain pattern with accuracy of 0.08 dB and attitude errors within 0.025° are achieved.
Albactam, a novel β- lactam derivative from the flowers of Albizia lebbeck with platelets anti-aggregatory activity in vitro (2010)

Genus Albizia is used in folk medicine to treat several inflammatory pathologies such as asthma, arthritis and burns. It is also reported that A. lebbeck flowers are commonly used to treat anxiety, depression and insomnia in traditional Chinese medicine. Genus Albizia is characterized by different classes of secondary metabolites such as triterpenoidal saponins, flavonoids and alkaloids. Phytochemical investigation of the alcoholic extract of the inflorescences afforded a novel β-lactam derivative, albactam. It showed an anti-aggregatory activity against adenosine diphosphate and arachidonic acid-induced Guniea Pigs' platelets aggregation in vitro at a dose 208µg/ml and 172µg/ml respectively. Moreover, monoterpene derivative (epoxy linalol), two tritepenes (β- amyrin and 11α, 12α-oxidotaraxerol), two ceramides and rutin have been isolated. Structural elucidation was achieved utilizing different spectroscopic techniques, including 1D and 2D NMR.
Anisotropic muonium with random hyperfine distortions: A new static relaxation theory (1986)

The spin dynamics associated with random hyperfine distortions of an ensemble of muons, which have thermalized in a solid as static muonium atoms, is approximated with the motion generated by averaging the spin evolution of a single isolated anisotropic muonium atom over a product of continuous hyperfine frequency distributions. That is, since each muonium atom in the ensemble is assumed to have a given set of nonunique anisotropic hyperfine frequencies, then the frequency distributions represent the ensemble average of many such muonium atoms. The hyperfine tensor includes an isotropic Fermi contact term and a symmetric traceless dipole-dipole term. There is no antisymmetric contribution. In this work the hyperfine tensor is expanded in terms of second-rank spherical tensors while the expansion coefficients are used to parametrize the distortion. Thus there are six frequencies associated with an anisotropic muonium atom, one associated with the isotropic part of the hyperfine tensor and five corresponding to the anisotropic components. Relaxation functions are calculated for muonium in both the zero- and high-field limits. The different anisotropic components of the hyperfine tensor lead to different (anisotropic) observable motion functions. For an amorphous or powder sample, only the isotropic motion function is observable, and the different anisotropic frequencies lead to motion functions with differing shapes. These functions have been applied to the case of fused quartz where the spin relaxation is well known to be entirely due to random hyperfine distortions.
Tutorial on Fourier space coverage for scattering experiments, with application to SAR (2010)

The Fourier Diffraction Theorem relates the data measured during electromagnetic, optical, or acoustic scattering experiments to the spatial Fourier transform of the object under test. The theorem is well-known, but since it is based on integral equations and complicated mathematical expansions, the typical derivation may be difficult for the non-specialist. In this paper, the theorem is derived and presented using simple geometry, plus undergraduatelevel physics and mathematics. For practitioners of synthetic aperture radar (SAR) imaging, the theorem is important to understand because it leads to a simple geometric and graphical understanding of image resolution and sampling requirements, and how they are affected by radar system parameters and experimental geometry. Also, the theorem can be used as a starting point for imaging algorithms and motion compensation methods. Several examples are given in this paper for realistic scenarios.
A comparison of optimum detector spatial resolution in nuclear imaging based on statistical theory and on observer performance (1978)

An expression for the expected image of a spherical tumour in a uniform background was derived in terms of background thickness and concentration of radioactivity, the tumour size, depth and uptake ratio, the gamma -ray energy and the detector response function. Three models of human observer performance for tumour detection were developed from different signal-to-noise ratio measures based on the statistical theory of detection. The optimum detector spatial resolution predicted by each model was then compared to that obtained from an observer performance study in which the subjects viewed computer-simulated scintigrams.
Plasma-Lyte 148: A clinical review (2016)

Plasma-Lyte 148 is an isotonic, buffered intravenous crystalloid solution with a physiochemical composition that closely reflects human plasma. Emerging data supports the use of buffered crystalloid solutions in preference to saline in improving physicochemical outcomes. Further large randomized controlled trials assessing the comparative effectiveness of Plasma-Lyte 148 and other crystalloid solutions in measuring clinically important outcomes such as morbidity and mortality are needed.
What Is Intellect? Part One (1952)

Well, as we may expect, opinions differ, and among psychologists as well as philosophers. But the psychologist, being a professed empirical scientist, focuses on the succession of events going on in the mind, whereas the philosopher's concern is with intellect as man's instrument for grasping reality. The latter puts the problem here taken up: What are the office and status of intellect in respect of man's grasp of reality? But, of course, the answer is not independent of the psychological facts; it reveals their significance for knowledge of the real world about us.
Influence of polarity on dose-response relationships of intrathecal opioids in rats (1990)

Dose-response curves were constructed for intrathecal morphine (M), oxymorphone (OM), hydromorphone (HM), diamorphine (DM), 14-hydroxydihydromorphine (OHM), oxycodone (OC), hydrocodone (HC) and fentanyl (F). Intrathecal catheters were placed in 69 rats under halothane/N2O anaesthesia. After recovery, baseline hot plate and tail flick latencies were measured, and a dose of opioid was given. Hot plate and tail flick latencies were assessed at 5, 15, 30, 60, 90, 120 min and then hourly until they returned to within 25% of baseline. Response latencies were converted to per cent of maximum possible effect (% MPE) and the area under the % MPE X time curve was taken as the response. This measure includes information about both potency and duration of action. Each rat received 3 opioids and saline at intervals of 2-3 days. On a fifth occasion, the animal's first treatment was repeated. Each opioid was studied over an 8-fold dose range. Results of both hot plate and tail flick were best described by a model including log(dose), a component due to development of tolerance over the 5 experimental days, and an among-rat variation term. In the hot plate test, doses equieffective in producing a response (AUC) over the dose range studied were in the order OHM less than OM less than HM less than M less than F less than DM less than HC less than OC. Slopes of the log(dose)-response curves were similar for all drugs except OHM, which had a steeper slope. A model is proposed in which hot plate and tail flick latencies are prolonged while CSF concentrations of a drug are above its minimum effective concentration, and drug is cleared from the CSF by a first-order process, possibly uptake into the spinal cord and removal via the blood. This model predicts that log(dose)-response curves will be linear, as was observed, with slopes inversely proportional to the rate constant for clearance from CSF. According to this model the steeper slope of the OHM log(dose)-response may be interpreted as indicating slower clearance from CSF. OHM has the lowest octanol/pH 7.4 buffer distribution coefficient (0.34) of all opioids studied, possibly leading to a lower rate of uptake into the spinal cord.
In memory of Peter Verhofstadt (2001)

Peter Verhofstadt, a close friend and colleague of many of us in the solid-state circuits community, passed away on May 10, 2001, after a long battle with cancer. Peter contributed enormously to solidstate circuits community. In the 1970s he was an early pioneer in areas such as semiconductor memory, digital signal processing and computer-aided design. In 1991 he joined the SRC and subsequently played a very significant role in shaping the structure of research support for microelectronics. For example, the SRC Focus Center Research Program is largely his creation.
Circulating DNA analysis and concordance with tumor section analysis in the detection of KRAS and BRAF point mutations from metastatic colorectal cancer. (2012)

10505 Background: We developed a specific method for circulating cell-free DNA (ctDNA) enabling the detection of point mutations. CtDNA exists at high level in patients with different types of cancer, and presents great potential in regards, in particular, to its low invasiveness, rapid data turnaround and cost effectiveness. We described here the first blinded prospective study on the comparison of KRAS and BRAF mutational status data obtained from the analysis of ctDNA and tumor section. Methods: Intplex is a refined Q-PCR-based method specifically designed to analyze ctDNA. IntPlex allows not only the detection of point mutations, but also the determination of tumor-ctDNA concentration and fragmentation index simultaneously. Intplex sensitivity is 0.01% (mutant to WT ratio) and is unprecedented among Q-PCR-based methods. The study was conducted from a multicenter cohort of 79 metastatic CRC patients not having received chemo- or radio-therapy within the month prior to blood sample collection. Results: Mutational status could not be determined in 9 samples with one of the two methods. CtDNA analysis showed 100% specificity and 87% sensitivity for KRAS detection (only three samples are misclassified) as compared to tumor section analysis with 23/70 (33%) positive samples, the concordance value being 96%. For BRAF mutation, the method exhibited a specificity and a sensibility of 100% with 5/70 (7%) positive samples (concordance of 100%). When combining KRAS and BRAF mutations, 100% specificity, 89% sensibility and 98% concordance were determined. The three discordant samples may be explained by the malignant genotype of primary tumor versus metastasis, or by the sensitivity of our detection method. The mutation load (median, 12.4%) expressed as the proportion of mutant allele in ctDNA is highly variable (0.037% to 69%) among mutated samples showing a very high inter-individual heterogeneity. Conclusions: Our blinded prospective multicenter study clearly showed for the first time that tumor section analysis might be advantageously replaced by ctDNA analysis, enlarging personalized medicine power for cancer patients.
Full-waveform Inversion in an Anisotropic Elastic Earth - Can We Isolate the Role of Density and Shear Wave Velocity? (2016)

Summary Five parameters are needed to describe VTI anisotropy in 2-D elastic media. With conventional streamer data, an optimal parameterization for full-waveform inversion (FWI) consists in using the horizontal velocity vh, the anellipicity parameter η, and the parameter that relates the horizontal-to-vertical velocity, ε. This parameterization, derived with a pseudo- acoustic formulation of the wave equation, minimizes crosstalks. We extend this analysis to the elastic case and wonder what are the effects of density and shear-wave velocity on the inversion results if ignored. Using radiation patterns derived in the elastic case and a modified version of the Marmousi II model, we see that PP-waves are mostly helping to recover vh and ε, while PS-waves are mostly helping to recover η. For all scattering angles and wave modes, ε and ρ are strongly coupled. Keeping ρ and vs unchanged during the inversion is a valid strategy if their background models are good enough. For small vs and ρ errors, the vs perturbation will map into η while ρ will map into ε. For large errors, vs adversely affects the recovery of η and might leak into vh while ρ will preferentially leak into ε, then η and, in smaller proportions, into vh.
Frequency-selective reflection and transmission by a periodic dielectric layer (1989)

The feasibility of using a periodic dielectric layer, composed of alternating bars having dielectric constants epsilon /sub 1/ and epsilon /sub 2/, as a dichroic surface at millimeter-wave frequencies is examined. For oblique incidence, it is found that total transmission and total reflection can be obtained at different frequencies for proper choices of epsilon /sub 1/ and epsilon /sub 2/ and the geometric parameters. The frequencies of total reflection and transmission can be estimated from wave phenomena occurring in a layer of uniform dielectric constant equal to the average value in the periodic layers. For some of the frequencies of total transmission, the bandwidth for 90% transmission is found to be 40%. The bandwidth for 90% reflection is always found to be much narrower, the greatest value obtained being 2.5%.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
High resolution emission and transmission imaging using the same detector (2010)

We demonstrate the capability of one detector, the Micro-Angiographic Fluoroscope (MAF) detector, to image for two types of applications: nuclear medicine imaging and radiography. The MAF has 1024 × 1024 pixels with an effective pixel size of 35 microns and is capable of real-time imaging at 30 fps. It has a CCD camera coupled by a fiber-optic taper to a light image intensifier (LII) viewing a 300-micron thick CsI phosphor. The large variable gain of the LII provides quantum-limited operation with little additive instrumentation noise and enables operation in both energy-integrating (EI) and sensitive low-exposure single photon counting (SPC) modes. We used the EI mode to take a radiograph, and the SPC mode to image a custom phantom filled with 1 mCi of I-125. The phantom is made of hot rods with diameters ranging from 0.9 mm to 2.3 mm. A 1 mm diameter parallel hole, medium energy gamma camera collimator was placed between the phantom and the MAF and was moved multiple times at equal intervals in random directions to eliminate the grid pattern corresponding to the collimator septa. Data was acquired at 20 fps. Two algorithms to localize the events were used: 1) simple threshold and 2) a weighted centroid method. Although all the hot rods could be clearly identified, the image generated with the simple threshold method shows more blurring than that with the weighted centroid method. With the diffuse cluster of pixels from each single detection event localized to a single pixel, the weighted centroid method shows improved spatial resolution. A radiograph of the phantom was taken with the same MAF in EI mode without the collimator. It shows clear structural details of the rods. Compared to the radiograph, the sharpness of the emission image is limited by the collimator resolution and could be improved by optimized collimator design. This study demonstrated that the same MAF detector can be used in both radioisotope and x-ray imaging, combining the benefits of each.
Time-domain addressing of remote fiber-optic interferometric sensor arrays (1987)

This paper describes and analyzes a particular application of high duty-cycle time-division multiplexing to the separation and identification of signals from an interferometric sensor array. Using the method discussed here, the coherence length of the laser is no longer a severe design constraint. Also, the source phase-induced intensity noise which limits some other multiplexing methods may be overcome, leading to a higher sensitivity. The arrays of all-passive remote sensors exhibit minimal crosstalk between sensors, and have downlead insensitivity. A synthetic heterodyne demodulation technique prevents environmentally induced signal fading. Analysis includes coupling ratios for all directional couplers in the system, signal and noise spectra, minimum detectable phase shift, and the effect of ac coupling on noise and crosstalk. An experimental all-fiber implementation of a two sensor array has yielded a measured sensitivity of approximately 10 μrad/ <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\sqrt{Hz}</tex> over a range of signal frequencies, and a crosstalk level of better than 55 dB.
Front Cover: Addressing the Reproducibility of Photocatalytic Carbon Dioxide Reduction (ChemCatChem 6/2020) (2020)

The Front Cover shows mountain scenery on top of which the conversion of CO2 and water into CO, HCO2H and H2 mediated by light is depicted. Variable heights of the highlighted spots on the yellow mountain ridge (TON ridge) symbolize the fluctuant turnover numbers of a poorly reproducible catalytic reaction. In their Full Paper, M. Marx et al. outline problems with the reproducibility of photocatalytic transformations, specifically carbon dioxide reduction. Utilizing Fe hydrogenase mimics in combination with a Cu photosensitizer they highlight that complex equilibria and general problems associated with photocatalysis reaction set-up can result in low reproducibility. Based on their results, suggestions are made on how to achieve higher reproducibility in such catalyst development. This main objective is also highlighted on the central signpost in the cover picture. More information can be found in the Full Paper by M. Marx et al. on page 1603 in Issue 6, 2020 (DOI: 10.1002/cctc.201901686).