gebhart/patrepeval huggingface dataset:
Development of 1-((1,4-<i>trans</i>)-4-Aryloxycyclohexyl)-3-arylurea Activators of Heme-Regulated Inhibitor as Selective Activators of the Eukaryotic Initiation Factor 2 Alpha (eIF2α) Phosphorylation Arm of the Integrated Endoplasmic Reticulum Stress Response (2017)

Heme-regulated inhibitor (HRI), an eukaryotic translation initiation factor 2 alpha (eIF2α) kinase, plays critical roles in cell proliferation, differentiation, adaptation to stress, and hemoglobin disorders. HRI phosphorylates eIF2α, which couples cellular signals, including endoplasmic reticulum (ER) stress, to translation. We previously identified 1,3-diarylureas and 1-((1,4-trans)-4-aryloxycyclohexyl)-3-arylureas (cHAUs) as specific activators of HRI that trigger the eIF2α phosphorylation arm of ER stress response as molecular probes for studying HRI biology and its potential as a druggable target. To develop drug-like cHAUs needed for in vivo studies, we undertook bioassay-guided structure-activity relationship studies and tested them in the surrogate eIF2α phosphorylation and cell proliferation assays. We further evaluated some of these cHAUs in endogenous eIF2α phosphorylation and in the expression of the transcription factor C/EBP homologous protein (CHOP) and its mRNA, demonstrating significantly improved solubility and/or potencies. These cHAUs are excellent candidates for lead optimization for development of investigational new drugs that potently and specifically activate HRI.
Interaction of low molecular weight hyaluronan with CD44 and toll‐like receptors promotes the actin filament‐associated protein 110‐actin binding and MyD88‐NFκB signaling leading to proinflammatory cytokine/chemokine production and breast tumor invasion (2011)

Both high and low molecular weight hyaluronan (HMW-HA vs. LMW-HA) exist in various tissues and cells. In this study, we investigated LMW-HA-mediated CD44 interaction with Toll-like receptors (TLRs), the actin filament-associated protein (AFAP-110), and a myeloid differentiation factor (MyD88) in breast tumor cells (MDA-MB-231 cells). Our data indicate that LMW-HA (but not HMW-HA) preferentially stimulates a physical association between CD44 and TLRs followed by a concomitant recruitment of AFAP-110 and MyD88 into receptor-containing complexes in breast tumor cells. LMW-HA-activated AFAP-110 then binds to filamentous actin (F-actin) resulting in MyD88/nuclear factor-κB (NF-κB) nuclear translocation, NF-κB-specific transcription, and target gene [interleukine 1β and interleukine-8 (IL-1β and IL-8)] expression. These signaling events lead to proinflammatory cytokine/chemokine production in the breast tumor cells. AFAP-110-F-actin (activated by LMW-HA) also promotes tumor cell invasion. Downregulation of AFAP-110 or MyD88 by transfecting breast tumor cells with AFAP-110 siRNA or MyD88 siRNA, respectively not only blocks the ability of LMW-HA to stimulate AFAP-110-actin function, but also impairs MyD88-NF-κB nuclear translocation and NF-κB transcriptional activation. Consequently, both IL-1β/IL-8 production and tumor cell invasion are impaired. Taken together, these findings suggest that LMW-HA plays an important role in CD44-TLR-associated AFAP-110-actin interaction and MyD88-NF-κB signaling required for tumor cell behaviors, which may contribute to the progression of breast cancer.
LETHAL PHOTOSENSITIZATION OF MICROORGANISMS WITH LIGHT FROM A CONTINUOUS‐WAVE GAS LASER (1966)

Abstract— Eleven strains of microorganisms were examined for their susceptibility to death by irradiation with 21–30 mW of light at 6328 Å from a continuous‐wave gas laser. Washed cells of seven species were rapidly killed when irradiated aerobically in aqueous solutions of toluidine blue: Sarcina lutea (two strains), Escherichia coli, Chromobacterium violaceum, Arthrobacter atrocyanus, Pseudomonas aeruginosa, Saccharomyces cerevisiae , and Rhodotorula glutinis. Cells remained viable when irradiated anaerobically in toluidine blue. This is not proof that oxygen is required for death since toluidine blue is subject to reduction to the leuco form under anaerobic conditions. None of the microbes tested, including cells of Bacillus cereus, Rhodospirillum rubrum , and Euglena gracilis , were killed in aerated suspensions without toluidine blue. Thus, it is unlikely that any strain has an endogenous photosensitizer capable of acting at 6328 Å. However, more than 95 per cent of the cells of R. rubrum lost their motility. A colorless mutant of S. lutea began dying 10 min faster than the wild strain, which is known to be protected from photosensitized death by carotenoids for at least 2 hr when irradiated in toluidine blue with 1000 ft candles of tungsten light. Since toluidine blue is bleached in irradiated cell suspensions, logarithmic death ceases within an hour with 2·5 × 10 =6 M toluidine blue. Yeasts are less susceptible than bacteria, exhibiting longer lags before death begins. The size of colonies produced by irradiated yeast cells decreases with irradiation time. This suggests that multiple hits are required for death.
<i>In vivo</i> activation of the cystic fibrosis transmembrane conductance regulator mutant ΔF508 in murine nasal epithelium (1997)

The gene causing cystic fibrosis (CF) encodes the CF transmembrane conductance regulator (CFTR), a cAMP-regulated chloride channel. Mutations in this gene result in reduced transepithelial chloride permeability across tissues affected in CF. Consequently, restoring chloride permeability to these tissues may prove therapeutic. Here we report that a combination of forskolin, an adenylate cyclase activator, and milrinone, an inhibitor of class III phosphodiesterases, increases the magnitude of the potential difference across nasal epithelium of mice homozygous for the most common CF mutation, delta F508, while neither drug alone has a significant effect on potential difference. Transgenic mice lacking CFTR do not respond to the milrinone/forskolin combination, indicating that the effect in delta F508 mice requires CFTR. These results suggest that, by pharmacological means, at least partial CFTR-mediated electrolyte transport can be restored in vivo to CF tissues expressing delta F508.
Electronic Portfolios: Engaged Students Create Multimedia-Rich Artifacts (2009)

This paper briefly summarizes the implementation of a university-wide electronic portfolio requirement. We begin with a systemic view of the ePortfolio Program and narrow our focus to a view of ePortfolio integration into two different classes. The rationale behind the Clemson University ePortfolio Program is to build a mechanism through which core competencies are demonstrated and evaluated. The target classes are a general education English class focusing on 20th and 21st century literature and a professional development seminar in computer science. Both classes allow students to select their topics and present their work to the class using a variety of media types, and both include a form of peer evaluation. These classes confirm that when students’ choice is built into the assignments we are pleasantly surprised by the outcomes. In addition, an extensive variety of artifacts are generated from each course that can be used to demonstrate the general education competencies, provide authentic evidence of learning, and generate a career portfolio. In our examples, we will describe the planning, implementation, and dissemination processes necessary to integrate the ePortfolio Program into university courses.
New Methodologies for Differential-Linear Cryptanalysis and Its Extensions. (2010)

Abstract. In 1994 Langford and Hellman introduced differential-linear cryptanalysis, which involves building a differential-linear distinguisher by concatenating a linear approximation with such a (truncated) differential that with probability 1 does not affect the bit(s) concerned by the input mask of the linear approximation. In 2002 Biham, Dunkelman and Keller presented an enhanced approach to include the case when the differential has a probability smaller than 1; and in 2005 they proposed several extensions of differential-linear cryptanalysis, including the high-order differential-linear analysis, the differential-bilinear analysis and the differential-bilinearboomerang analysis. In this paper, we show that Biham et al.’s methodologies for computing the probabilities of a differential-linear distinguisher, a high-order differential-linear distinguisher, a differential-bilinear distinguisher and a differential-bilinear-boomerang distinguisher do not have the generality to describe the analytic techniques. Thus the previous cryptanalytic results obtained by using these techniques of Biham et al. are questionable. Finally, from a mathematical point we give general methodologies for computing the probabilities. The new methodologies lead to some better cryptanalytic results, for example, differential-linear attacks on 13-round DES and 10-round CTC2 with a 255-bit block size and key.
A breakthrough in photonic integration (2009)

Photonic Integrated Circuits, also called optical chips or PICs, are considered as the way\nto make photonic systems or subsystems cheap and ubiquitous. PICs still are several orders of magnitude more expensive than their microelectronic counterparts, however, which has restricted their application to a few niche markets. Recently, a novel approach in photonic integration is emerging which will reduce the R&amp;D costs of PICs by more than a factor of ten. It will bring the application of PICs that integrate complex and advanced photonic functionality on a single chip within reach for a large number of small and larger companies. Europe is leading in this novel approach and the Netherlands is playing a key role.
Insight into the Reactions of Trifluorovinylsilanes with Aromatic Aldehydes (2008)

Abstract The conditions for the selective addition of trialkyl(trifluorovinyl)silanes to the C=O bond of aromatic aldehydes in the presence of cesium fluoride to give the corresponding“silylated” alcohols in high yields was performed. The reactivity of the “silylated” alcohols in the presence of nucleophilic reagents and Brönsted acids was studied. On the basis of isolated compounds and of intermediates detected by NMR spectroscopic methods, several reaction pathways are proposed. Significant differences between the reaction behaviour of triethyl(trifluorovinyl)silane and trimethyl(trifluoromethyl)silane under comparable conditions are pointed out; the differences can be attributed to the highly reactive trifluorovinyl group. The reactions of the “silylated” alcohols proceed with high stereoselectivity to give propenes, acid fluorides and acids of the ( E ) isomers in better than 98 % purity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Neuronal localization of the TNFα converting enzyme (TACE) in brain tissue and its correlation to amyloid plaques (2001)

The tumor necrosis factor (TNF)-alpha converting enzyme (TACE) can cleave the cell-surface ectodomain of the amyloid-beta precursor protein (APP), thus decreasing the generation of amyloid-beta (Abeta) by cultured non-neuronal cells. While the amyloidogenic processing of APP in neurons is linked to the pathogenesis of Alzheimer's disease (AD), the expression of TACE in neurons has not yet been examined. Thus, we assessed TACE expression in a series of neuronal and non-neuronal cell types by Western blots. We found that TACE was present in neurons and was only faintly detectable in lysates of astrocytes, oligodendrocytes, and microglial cells. Immunohistochemical analysis was used to determine the cellular localization of TACE in the human brain, and its expression was detected in distinct neuronal populations, including pyramidal neurons of the cerebral cortex and granular cell layer neurons in the hippocampus. Very low levels of TACE were seen in the cerebellum, with Purkinje cells at the granular-molecular boundary staining faintly. Because TACE was localized predominantly in areas of the brain that are affected by amyloid plaques in AD, we examined its expression in a series of AD brains. We found that AD and control brains showed similar levels of TACE staining, as well as similar patterns of TACE expression. By double labeling for Abeta plaques and TACE, we found that TACE-positive neurons often colocalized with amyloid plaques in AD brains. These observations support a neuronal role for TACE and suggest a mechanism for its involvement in AD pathogenesis as an antagonist of Abeta formation.
Extension of life span of Drosophila melanogaster by the inhibitors of tryptophan-kynurenine metabolism (2011)

Upregulation of kynurenine (KYN) formation from tryptophan (TRY) was associated with aging in animal and human studies. TRY - KYN metabolism is affected by the activities of TRY 2,3-dioxygenase 2 (TDO) and ATP-binding cassette (ABC) transporter regulating TRY access to intracellular TDO. We studied the effects of TDO inhibitor, alpha-methyl tryptophan (aMT), and ABC transported inhibitor, 5-methyl tryptophan (5MT), on the life span of wild strain female Drosophila flies (Oregon-R). aMT and 5MT prolonged mean and maximum life span (by 27% and 43%, and 21% and 23%, resp.). The present results are the first observation of the extension of life span of Drosophila melanogaster by inhibitors of TRY - KYN metabolism, and in line with literature and previous studies on prolonged life span of TDO- and ABC-deficient female Drosophila mutants. Inhibition of TDO and ABC transporter activity might offer the new target for anti-aging and anti-AAMPD interventions.
The use of Transcranial MagneTic sTiMula Tion and TherMography in The exaMina Tion of pa TienTs wiTh Mul Tiple sclerosis (2011)

summary The majority of patients with Multiple sclerosis have motor dysfunction from the early onset of the disease. Both acute presentations and subsequent relapses of the disease contribute to the worsening of the motor deficits that can develop into quadriplegia. Quantification of the deficits is performed using edss scale (1, 7) which can quantify the gait deficits among other parameters. Aim. The present study looked at the variability of both cortical and peripheral latencies on a group of rrMs patients at rest and after exercise on an ergonomic bicycle. Material and methods. furthermore the thermography investigation was performed by looking at the tissue located in posterior lodge of the calf back before and after exercise. Results. The results found were that the shortening of the cortical latency after completion of physical activities was associated with a low temperature of the tissue. Conclusions. physical therapy improves at least transiently the motor cortex excitability as well as the velocities of the nervous impulse. heat loss can be related to partial involvement of the motor units in the muscle contraction but also to the exaggerated losses by altering the sympathetic tone (10, 12).
An Engineering Approach for Quantitative Analysis of the Lengthwise Strokes in Massage Therapies (2008)

Massage therapies are widely used for improving and restoring the function of human tissues. It is generally accepted that such therapies promote human health and well-being by several possible mechanisms, including increase in blood flow and parasympathetic activity, release of relaxation hormones, and inhibition of muscle tension, neuromuscular excitability, and stress hormones. Nonetheless, most of the purported beneficial/adverse effects of massage are based on anecdotal experiences, providing little insight on its effectiveness or the mechanisms underlying its usefulness. Furthermore, most studies to date have not quantitatively demonstrated the efficacy of massage on human health. This might be due to the lack of appropriate tools necessary for the application of quantitatively controlled loading and for the evaluation of the subsequent responses. To address this issue, we developed a device that applies compression in lengthwise strokes to the soft tissues of the New Zealand white rabbit, thereby mimicking the rubbing and effleurage techniques of massage. This device permits control of the magnitude and frequency of mechanical load applied to the rabbit’s hind limb for various durations. The measurement of tissue compliance and the viscoelastic properties as a function of loading parameters was also demonstrated. Findings of this study suggest that this device offers a quantitative analysis of the applied loads on the tissue to determine an optimal range of loading conditions required for the safe and effective use of massage therapies.
Synthesis of l-(+)-Tartaric Acid from l-Ascorbic Acid via 5-Keto-d-Gluconic Acid in Grapes (1984)

5-Keto-l-idionic acid ( identical with5-keto-d-gluconic acid, d-xylo-5-hexulosonic acid) was found as a metabolic product of l-ascorbic acid in slices of immature grapes, Vitis labrusca L. cv ;Delaware'. Specifically labeled compounds, recognized as metabolic products of l-ascorbic acid in grapes, were fed to young grape tissues to investigate the metabolic pathway from l-ascorbic acid to l-(+)-tartaric acid.Label from dehydro-l-[1-(14)C]ascorbic acid, 2-keto-l-[1-(14)C]idonic acid (l-xylo-2-hexulosonic acid), l-[1-(14)C]idonic acid, or 5-keto-l-[1-(14)C] idonic acid was incorporated into l-(+)-tartaric acid in high yields as it was in the l-[1-(14)C]ascorbic acid experiment. In a double label experiment involving a mixture of l-[1-(14)C]idonic acid and l-[2-(3)H]idonic acid, the (3)H/(14)C ratios of 5-keto-l-idonic acid and l-(+)-tartaric acid synthesized in young grape leaves were almost the same as the value of the l-idonic acid fed. Label from 5-keto-l-[6-(14)C]idonic acid was incorporated into sugars and insoluble residue in the same way as l-[6-(14)C]ascorbic acid was metabolized in grapes.These results provide strong evidence that in grapes l-(+)-tartaric acid is synthesized from the C(4) fragment that corresponds to the C1 to C4 group of the 5-keto-l-idonic acid derived from l-ascorbic acid via 2-keto-l-idonic acid and l-idonic acid.
ZnO thin-film transistors with polycrystalline (Ba,Sr)TiO3 gate insulators (2006)

The electrical characteristics of ZnO thin-film transistors with high-k (Ba,Sr)TiO3 gate dielectrics are presented. The ZnO and (Ba,Sr)TiO3 thin films were deposited on Pt, exhibiting polycrystalline characteristics. The thin-film devices demonstrated transistor behavior over the range of 0–10V with a stable threshold voltage of approximately 1.2V. The field effect mobility, subthreshold slope, and on/off ratio were measured to be 2.3cm2V−1s−1, 0.25V∕decade, and 1.5×108, respectively. The measured transistor performance characteristics suggest that ZnO∕(Ba,Sr)TiO3 structures are well suited for both polycrystalline thin-film transistors for display applications and future higher performance transistors based on single crystal ZnO.
Light diffraction from a bilayer lattice of microspheres enhanced by specular resonance (2004)

Anomalously strong diffraction from a bilayer lattice of dielectric microspheres, previously reported by the authors, has been attributed to the enhancement of diffraction by specular resonance in constituent bispheres. On the basis of rigorous calculations and experiments, specular resonance from bispheres is found to be dominant even in the scattering from a cluster of several microspheres. As a consequence, a diffraction model, in which a bilayer lattice of microspheres is viewed as a two-dimensional array of bispheres, is constructed. By incorporating the specular resonance into a diffraction theory of two-dimensional lattices as a structure factor, observed diffraction behavior is explained. In the diffraction from a bilayer lattice of microspheres, the specular resonance functions as a blazing mechanism. Possible configurations and suitable parameters for efficient gratings are discussed, and a self-assembled bilayer lattice of dielectric microspheres with a diameter 1.6–3.2 times as large as the wavelength is found to be promising as a low-cost and highly efficient transmission grating. The spheres can be replaced with cylinders or lenses. Tunable diffraction devices with efficiency exceeding that of conventional gratings would be realized by microelectromechanical systems comprised of two optimally designed microlens arrays.
Antibody-labeled liposomes for CT imaging of atherosclerotic plaques: in vitro investigation of an anti-ICAM antibody-labeled liposome containing iohexol for molecular imaging of atherosclerotic plaques via computed tomography. (2009)

We evaluated the specific binding of anti-intercellular adhesion molecule 1 (ICAM-1) conjugated liposomes (immunoliposomes, or ILs) to activated human coronary artery endothelial cells (HCAEC) with the purpose of designing a computed tomographic imaging agent for early detection of atherosclerotic plaques. Covalent attachment of anti-ICAM-1 monoclonal antibodies to pre-formed liposomes stabilized with polyethylene glycol yielded ILs, with a coupling efficiency of the ICAM-1 to the liposomes of 10% to 24%. The anti-ICAM-1-labeled ILs had an average diameter of 136 nm as determined by dynamic light-scattering and cryogenic electron microscopy. The ILs' encapsulation of 5-[N-acetyl-(2,3-dihydroxypropyl)-amino)-N, N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-benzene-1,3-dicarboxamide (iohexol) was determined to be 18% to 19% by a dialysis technique coupled with ultraviolet detection of free iohexol. This encapsulation corresponded to 30 to 38 mg iodine per mL IL solution, and the ILs exhibited 91% to 98.5% iohexol retention at room temperature and under physiologic conditions. The specific binding of the ILs to cultured, activated HCAEC was measured using flow cytometry, enzyme-linked immunosorbent assays, and fluorescence microscopy. The immunosorbent assays demonstrated the specificity of binding of anti-ICAM-1 to ICAM-1 compared with control studies using nonspecific immunoglobulin G-labeled ILs. Flow cytometry and fluorescence microscopy experiments demonstrated the expression of ICAM-1 on the surface of activated HCAEC. Therefore, our iohexol-filled ILs demonstrated potential for implementation in computed tomographic angiography to noninvasively detect atherosclerotic plaques that are prone to rupture.
Brain-Derived Neurotrophic Factor Gene Val66Met Polymorphism Modulates Reversible Cerebral Vasoconstriction Syndromes (2011)

Background: Reversible cerebral vasoconstriction syndrome (RCVS) could be complicated by cerebral ischemic events. Hypothetical mechanisms of RCVS involve endothelial dysfunction and sympathetic overactivity, both of which were reported to be related to brain-derived neurotrophic factor (BDNF). The study investigated the association between functional BDNF Val66Met polymorphism and RCVS.
Modifying user-defined logic for test access to embedded cores (2002)

Testing embedded cores is a challenge because access to core I/Os is limited. The user-defined logic (UDL) surrounding the core may restrict the set of test vectors that can be applied to the core. Consequently, some of the core test vectors specified by the core supplier may not be contained in the output space of the UDL that drives the core and hence cannot be justified at the core inputs. Conventional solutions to this problem involve placing multiplexers or boundary scan elements at the inputs of the core to provide test access. This can be very costly in terms of area and performance. This paper presents a new approach for providing test access to an embedded core. A procedure is described for inserting control points in the UDL to modify its output space so that it contains the specified core test vectors. The flexibility in selecting the location of the control points is used to avoid performance degradation by keeping test logic off the critical timing paths. Experimental results are shown comparing the control point insertion procedure with other approaches.