gebhart/patrepeval huggingface dataset:
Cancer stem cell-related gene expression as a potential biomarker of response for first-in-class imipridone ONC201 in solid tumors (2017)

Cancer stem cells (CSCs) correlate with recurrence, metastasis and poor survival in clinical studies. Encouraging results from clinical trials of CSC inhibitors have further validated CSCs as therapeutic targets. ONC201 is a first-in-class small molecule imipridone in Phase I/II clinical trials for advanced cancer. We have previously shown that ONC201 targets self-renewing, chemotherapy-resistant colorectal CSCs via Akt/ERK inhibition and DR5/TRAIL induction. In this study, we demonstrate that the anti-CSC effects of ONC201 involve early changes in stem cell-related gene expression prior to tumor cell death induction. A targeted network analysis of gene expression profiles in colorectal cancer cells revealed that ONC201 downregulates stem cell pathways such as Wnt signaling and modulates genes (ID1, ID2, ID3 and ALDH7A1) known to regulate self-renewal in colorectal, prostate cancer and glioblastoma. ONC201-mediated changes in CSC-related gene expression were validated at the RNA and protein level for each tumor type. Accordingly, we observed inhibition of self-renewal and CSC markers in prostate cancer cell lines and patient-derived glioblastoma cells upon ONC201 treatment. Interestingly, ONC201-mediated CSC depletion does not occur in colorectal cancer cells with acquired resistance to ONC201. Finally, we observed that basal expression of CSC-related genes (ID1, CD44, HES7 and TCF3) significantly correlate with ONC201 efficacy in >1000 cancer cell lines and combining the expression of multiple genes leads to a stronger overall prediction. These proof-of-concept studies provide a rationale for testing CSC expression at the RNA and protein level as a predictive and pharmacodynamic biomarker of ONC201 response in ongoing clinical studies.
Novel Serum Biomarker Candidates for Liver Fibrosis in Hepatitis C Patients (2007)

Assessment of hepatic scarring may be performed with a combination of these novel fibrosis biomarkers, thus eliminating the need for liver biopsy. Further evaluation of these candidate markers needs to be performed in larger patient populations. Diagnosis of fibrosis during early stages will allow early treatment, thereby preventing fibrosis progression.
Synthesis and applications of chiral cyclopentadienylmetal complexes (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and applications of chiral cyclopentadienylmetal complexesRonald L. HaltermanCite this: Chem. Rev. 1992, 92, 5, 965–994Publication Date (Print):July 1, 1992Publication History Published online1 May 2002Published inissue 1 July 1992https://pubs.acs.org/doi/10.1021/cr00013a011https://doi.org/10.1021/cr00013a011research-articleACS PublicationsRequest reuse permissionsArticle Views2989Altmetric-Citations513LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Adhesion molecule blockade displaces PbA-specific CD8<sup>+</sup> T cell from cerebral blood vessels and promotes survival. (2016)

&lt;p&gt;(A) Representative maximal projections of 3D time lapses captured through the thinned skull window of a mouse seeded i.v. with 10&lt;sup&gt;4&lt;/sup&gt; naïve mCerulean&lt;sup&gt;+&lt;/sup&gt; OT-I cells (green) and then infected with PbA-OVA-mCherry. Images were captured at d6 p.i. The left panel shows the distribution of OT-I cells along cerebral blood vessels (red) before antibody blockade and the right panel depicts the same vessel after treatment. See corresponding &lt;a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006022#ppat.1006022.s015" target="_blank"&gt;S9 Movie&lt;/a&gt;. (B and C) The bar graphs show quantification of luminal PbA-specific CD8&lt;sup&gt;+&lt;/sup&gt; T cells as a percentage of maximum number in brain vasculature at the denoted time points before and after i.v. treatment with anti-LFA-1 / VLA-4 (B) or isotype control antibodies (C). Data are representative of 4–5 independent experiments. (D) Quantification of PbA-specific CD8&lt;sup&gt;+&lt;/sup&gt; T cells in the brain parenchyma as a percentage of the maximum number after i.v. treatment with anti-LFA-1/VLA-4 antibodies. Data are representative of 5 independent experiments. (E) Representative confocal images of the brainstem from mice at d6 p.i. following propidium iodide (red) injection and immunohistochemical staining for NeuN&lt;sup&gt;+&lt;/sup&gt; neurons (green). Mice were treated with either isotype control antibody (top) or anti-LFA-1/VLA-4 blocking antibodies (Ad block) at d5.5 p.i. Cell nuclei are shown in blue. (F) The bar graph shows quantification of data shown in (E). Each bar represents the total number of brainstem cells that are PI&lt;sup&gt;+&lt;/sup&gt; (gray), and within the bar, the red coloration shows the proportion that are also NeuN&lt;sup&gt;+&lt;/sup&gt; (mean ± SD; n = 4 mice per group; 1 brain section per mouse; 4 images per brain section). Asterisks denote a statistically significant difference from all other groups (***P &lt; 0.05).&lt;/p&gt;
PION ELASTIC SCATTERING FROM POLARIZED13C IN THE ENERGY REGION OF THE [3, 3] RESONANCE (1990)

Analyzing powers, Ay, were measured at the Clinton P. Anderson Meson Physics Facility for π+ and π- elastic scattering from polarized 13C in the energy region of the [3,3] resonance. The Ay were found to be small in general and, at small momentum transfers, q < 1 fm-1, were reproduced best by a first order optical potential description and standard nuclear wave functions. At large momentum transfer, q ≈1.8 fm-1, present nuclear structure and π-nucleus reaction models do not reproduce the data.
Atrial Chamber-specific Expression of Sarcolipin Is Regulated during Development and Hypertrophic Remodeling (2003)

Intracellular Ca2+ regulation is critical in the normal cardiac function and development of pathologic hearts. Phospholamban, an endogenous inhibitor of sarcoplasmic reticulum Ca2+ ATPase in the sarcoplasmic reticulum, plays an important role in Ca2+ cycling in heart. Recently, sarcolipin has been identified as having a similar function as phospholamban in skeletal muscle. Because phospholamban is differentially expressed in atrial and ventricular myocardia and its expression is often altered in diseased hearts, we investigated the cardiac chamber specificity of sarcolipin expression and its regulation during development and hypertrophic remodeling. Northern blot analysis revealed that the expression of mouse sarcolipin mRNA was most abundant in the atria and was undetectable in the ventricles, indicating an atrial chamber-specific expression pattern. Atrial chamber-specific expression of sarcolipin mRNA was increased during development. These findings were confirmed by in situ hybridization studies. In addition, sarcolipin expression was down-regulated in the atria of hypertrophic heart when induced by ventricular specific overexpression of the activated H-ras gene. In humans, sarcolipin mRNA was also expressed in the atria but not detected in the ventricles, although sarcolipin expression was most abundant in skeletal muscle. Taken together, sarcolipin is likely to be an atrial chamber-specific regulator of Ca2+ cycling in heart.
Seeking long‐term relationship: axon and target communicate to organize synaptic differentiation (2006)

Synapses form after growing axons recognize their appropriate targets. The subsequent assembly of aligned pre and postsynaptic specializations is critical for synaptic function. This highly precise apposition of presynaptic elements (i.e. active zones) to postsynaptic specializations (i.e. neurotransmitter receptor clusters) strongly suggests that communication between the axon and target is required for synaptic differentiation. What trans-synaptic factors drive such differentiation at vertebrate synapses? First insights into the answers to this question came from studies at the neuromuscular junction (NMJ), where axon-derived agrin and muscle-derived laminin beta2 induce post and presynaptic differentiation, respectively. Recent work has suggested that axon- and target-derived factors similarly drive synaptic differentiation at central synapses. Specifically, WNT-7a, neuroligin, synaptic cell adhesion molecule (SynCAM) and fibroblast growth factor-22 (FGF-22) have all been identified as target-derived presynaptic organizers, whereas axon-derived neuronal activity regulated pentraxin (Narp), ephrinB and neurexin reciprocally co-ordinate postsynaptic differentiation. In addition to these axon- and target-derived inducers of synaptic differentiation, factors released from glial cells have also been implicated in regulating synapse assembly. Together, these recent findings have profoundly advanced our understanding of how precise appositions are established during vertebrate nervous system development.
[Treatment of osteomyelitis with oral bactericidal antibiotics-- description of 9 cases]. (1996)

The efficacy of oral bactericidal antibiotics in the treatment of osteomyelitis is analyzed retrospectively by a review of 9 cases histories. The first patient was treated in 1982. Clinical and laboratory controls were reviewed up to 1.1.1995. In 6 patients S. aureus was isolated, while in 3 patients the organism could not be cultured but gram + cocci were almost likely. 5 cases of osteomyelitis were acute, 4 were chronic and in one case there was an infection of an artificial knee prothesis. The isolated S. aureus were sensitive to the antibiotics prescribed. 8 patients received a combination of flucloxacillin (2-4 g/day) and rifampicin (600 mg/day); one patient was treated with the combination amoxicillin/clavulanic acid (1500/425 mg/day) followed by ofloxacin (400 mg/day) and finally co-trimoxazole (320/1600 mg/day). 3 patients received all antibiotics orally; in 6 patients oral administration followed a short intravenous course of the antibiotic combination. The duration of treatment varied between 6 and 23 weeks. Follow-up extended over 9 months (n = 1), 14 months (n = 3), 4-7 years (n = 3), and 10-12 years (n = 2). In 8 cases the osteomyelitis was cured (89%). In our view, a combination of bactericidal oral antibiotics with good penetration into bone tissue can be prescribed in selected cases of osteomyelitis to shorten or even avoid the standard intravenous therapy of acute or chronic diseases.
Optical biosensor array based on natural ion channels (2003)

Ion channels are promising biomolecules for sensor applications. They combine high sensitivity with excellent selectivity. Presently the main problem consists in the integration of such ion channels into synthetic matrices but keeping them operative. In this study we report on the development of a microstructured polymer layer as matrix for an ion channel sensor array and an optical method for parallel detection. A thin PMMA layer was prepared by spin coating a gold surface. Small pores with diameter in the range of few micrometers were made by e-beam lithography. FTIR imaging spectroscopy and SPR imaging were used to characterize the quality of microstructured arrays.
Tissue structure, nuclear organization, and gene expression in normal and malignant breast. (1999)

Because every cell within the body has the same genetic information, a significant problem in biology is to understand how cells within a tissue express genes selectively. A sophisticated network of physical and biochemical signals converge in a highly orchestrated manner to bring about the exquisite regulation that governs gene expression in diverse tissues. Thus, the ultimate decision of a cell to proliferate, express tissue-specific genes, or apoptose must be a coordinated response to its adhesive, growth factor, and hormonal milieu. The unifying hypothesis examined in this overview is that the unit of function in higher organisms is neither the genome nor the cell alone but the complex, three-dimensional tissue. This is because there are bidirectional connections between the components of the cellular microenvironment (growth factors, hormones, and extracellular matrix) and the nucleus. These connections are made via membrane-bound receptors and transmitted to the nucleus, where the signals result in modifications to the nuclear matrix and chromatin structure and lead to selective gene expression. Thus, cells need to be studied "in context", i.e., within a proper tissue structure, if one is to understand the bidirectional pathways that connect the cellular microenvironment and the genome. In the last decades, we have used well-characterized human and mouse mammary cell lines in "designer microenvironments" to create an appropriate context to study tissue-specific gene expression. The use of a three-dimensional culture assay, developed with reconstituted basement membrane, has allowed us to distinguish normal and malignant human breast cells easily and rapidly. Whereas normal cells become growth arrested and form organized "acini," tumor cells continue to grow, pile up, and in general fail to respond to extracellular matrix and microenvironmental cues. By correcting the extracellular matrix-receptor (integrin) signaling and balance, we have been able to revert the malignant phenotype when a human breast tumor cell is cultured in, or on, a basement membrane. Most recently, we have shown that whereas beta1 integrin and epidermal growth factor receptor signal transduction pathways are integrated reciprocally in three-dimensional cultures, on tissue culture plastic (two-dimensional monolayers), these are not coordinated. Finally, we have demonstrated that, rather than passively reflecting changes in gene expression, nuclear organization itself can modulate cellular and tissue phenotype. We conclude that the structure of the tissue is dominant over the genome, and that we may need a new paradigm for how epithelial-specific genes are regulated in vivo. We also argue that unless the structure of the tissue is critically altered, malignancy will not progress, even in the presence of multiple chromosomal mutations.
From Bipedal Walking to Quadrupedal Locomotion: Full-Body Dynamics Decomposition for Rapid Gait Generation (2020)

This paper systematically decomposes quadrupeds into bipeds to rapidly generate walking gaits, and then recomposes these gaits to obtain quadrupedal locomotion.We begin by decomposing the full-order, nonlinear and hybrid dynamics of a three-dimensional quadrupedal robot, including its continuous and discrete dynamics, into two bipedal systems that are subject to external forces.Using the hybrid zero dynamics (HZD) framework, gaits for these bipedal robots can be rapidly generated (on the order of seconds) along with corresponding controllers.The decomposition is performed in such a way that the bipedal walking gaits and controllers can be composed to yield dynamic walking gaits for the original quadrupedal robot -the result, therefore, is the rapid generation of dynamic quadruped gaits utilizing the full-order dynamics.This methodology is demonstrated through the rapid generation (3.96 seconds on average) of four stepping-in-place gaits and one ambling gait at 0.35 m/s on a quadrupedal robot -the Vision 60, with 36 state variables and 12 control inputs -both in simulation and through outdoor experiments.This suggested a new approach for fast quadrupedal trajectory planning using full-body dynamics, without the need for empirical model simplification, wherein methods from dynamic bipedal walking can be directly applied to quadrupeds.
Optical and photophysical properties of anisole- and cyanobenzene-substituted perylene diimides (2016)

One- and two-photon absorption cross-sections and spectra and the photophysical properties of eight perylenetetracarboxy-3,4:9,10-diimide (PDI) derivatives are reported and analyzed. The investigated compounds are characterized by direct binding of the phenyl rings of the substituents to the bay positions of the perylene core. They have been designed to test the effects of differences in the electronic nature - electron donating (anisole) or accepting (cyanobenzene) - and binding topology (cis or trans, meta or para disubstitution or tetrasubstitution) of the bay substituents on the above optical and photophysical observables. (TD)DFT and Hückel MO calculations have provided theoretical information on the ground-state geometries, the MOs and the electronic spectra of several model compounds. For tetrasubstituted and cis disubstituted derivatives, strong steric interactions in the bay area determined the preferred conformations, with perylene cores distorted near the substituted bay(s) and a 42-44° twisting of the substituent rings relative to the core, quite irrespective of the electronic nature of the substituents. On the other hand, in trans-disubstituted PDI steric hindrance in the bay areas was much weaker and similar in the cyanobenzene and the anisole derivatives. So, the large differences found in the conformational preferences were completely attributable to electronic effects. With electron-accepting cyanobenzene, the substituent rings were found normal to the central planar perylene core, thus enabling the assignment of the moderate spectroscopic effects to inductive interactions. The DFT analysis of the PDI trans-disubstituted with electron-donating anisoles gave quite strongly distorted perylene-core geometries and less twisted (59°) substituent rings. The corresponding increased substituent/core conjugative interactions resulted in new CT allowed electronic transitions and an extremely pronounced solvent-polarity dependence of the emission spectra and intensities. All anisole substituted PDI feature a very fast radiationless decay path in polar solvents, likely related to a relaxation to a charge-separated configuration in the lowest excited-state.
<title>Development of a high-performance spectral radiometer for EO calibration applications</title> (2004)

Santa Barbara Infrared, Inc (SBIR) has developed a dual-band infrared spectroradiometer for highly accurate radiometric calibration of electro-optical (EO) test stations, light sources, and optical surfaces. The "RAD-9000" design covers the 3-5 mm and 8-12 mm spectral bands, provides thermal sensitivity of better than 40 mK, supports object temperatures from 278-373 K, and delivers better than 2% spectral resolution (Dl/l). The RAD-9000 features computer-controlled operation, an intuitive graphical user interface (GUI), motorized focus adjustment, VIS-CCD sighting/alignment capability, less than 2 mrad detector IFOV, and an internal ambient reference for background subtraction and enhanced stability. In addition to high-performance relative radiometry, the RAD-9000 offers a high degree of absolute radiometric accuracy by utilizing a dedicated radiometric reference module. The reference module incorporates two 8-inch, variable temperature, high-emissivity extended sources to provide a stable, accurate absolute radiometric reference external to the main optics.
<title>Characterization of x-ray polycapillary optics with a high-resolution x-ray optical bench</title> (1996)

We have constructed an x-ray optical test bench which has been used to characterize transmission and manufacturing artifacts associated with monolithic polycapillary optics of the Kumakhov type. The test bench incorporates a conventional 8 keV x-ray source and a sample holder which is capable of high precision translation and rotation. Both non-imaging and imaging detectors are used, including a magnifying x-ray camera capable of resolving the transmission of individual capillary channels in a polycapillary bundle. We demonstrate the use of the bench to determine imperfections in the fabrication of early prototype capillary optics. The images illustrate the anomalies associated with the forming of the capillary bundles, the effects of extended exposure to synchrotron radiation, and the x-ray transmission lateral uniformity. We also show the intense focused beams obtained with complete optics.
Combining slant information from disparity and texture: When is it optimal? (2010)

The brain often combines sensory measurements in a fashion approaching statistical optimality. If sensory measurements are represented as likelihood distributions, the optimal combined percept lies in between two single-cue percepts. When these measurement distributions differ greatly from one another (cue conflict), it may be more sensible to simply use the more reliable (less variable) measurement rather than a combination affected by the less reliable measurement, even if it is not statistically optimal. We investigated how disparity and texture are combined in estimating slant, and in particular how large conflicts affect slant percepts. Previous depth cue combination work has been restricted to small conflicts. We also investigated the effect of cue reliability. We measured two-cue slant percepts using a 2-interval matching procedure. One interval had a cue conflict and the other did not. We presented a large range of conflict sizes. As conflict size increased, observers' slant settings remained nearly optimal: up to surprisingly large conflicts, they followed the weighted average predicted from single-cue measurements and Bayes' Law. With even larger conflicts, the optimal weighted averaging no longer occurred; matches were instead dictated by the more reliable cue. When we increased the reliability of both cues, keeping the relative weights fixed, optimal weighted averaging broke down at smaller conflicts, compared to the less reliable stimuli. Thus, we found that optimal weighted averaging occurs when these distributions overlap substantially: either with smaller conflicts or less reliable cues. Slant percepts are dictated by the more reliable cue when the distributions only overlap minimally.
Electric fields in high-frequency parallel-plate helium discharges (1994)

Spatially and temporally resolved electric fields in the sheath region of a 13.56-MHz, parallel-plate helium discharge have been measured as a function of voltage, pressure, phase, bias, and electrode drive configuration. The electric field was determined from laser-induced fluorescence measurements of the Stark structure of the n=11 singlet Rydberg manifold. Two-dimensional maps of the electric field indicate that the field is uniform across a large fraction of the electrode diameter. Measured values of the sheath electric field are compared with the results of a hybrid Boltzmann-equation–average-equation simulation.