gebhart/patrepeval huggingface dataset:
Nitric Oxide Inhibition of Homocysteine-induced Human Endothelial Cell Apoptosis by Down-regulation of p53-dependent Noxa Expression through the Formation of S-Nitrosohomocysteine (2004)

Hyperhomocysteinemia is believed to induce endothelial dysfunction and promote atherosclerosis; however, the pathogenic mechanism has not been clearly elucidated. In this study, we examined the molecular mechanism by which homocysteine (HCy) causes endothelial cell apoptosis and by which nitric oxide (NO) affects HCy-induced apoptosis. Our data demonstrated that HCy caused caspase-dependent apoptosis in cultured human umbilical vein endothelial cells, as determined by cell viability, nuclear condensation, and caspase-3 activation and activity. These apoptotic characteristics were correlated with reactive oxygen species (ROS) production, lipid peroxidation, p53 and Noxa expression, and mitochondrial cytochrome c release following HCy treatment. HCy also induced p53 and Noxa expression and apoptosis in endothelial cells from wild type mice but not in the p53-deficient cells. The NO donor S-nitroso-N-acetylpenicillamine, adenoviral transfer of inducible NO synthase gene, and antioxidants (alpha-tocopherol and superoxide dismutase plus catalase) but not oxidized SNAP, 8-Br-cGMP, nitrite, and nitrate, suppressed ROS production, p53-dependent Noxa expression, and apoptosis induced by HCy. The cytotoxic effect of HCy was decreased by small interfering RNA-mediated suppression of Noxa expression, indicating that Noxa up-regulation plays an important role in HCy-induced endothelial cell apoptosis. Overexpression of inducible NO synthase increased the formation of S-nitroso-HCy, which was inhibited by the NO synthase inhibitor N-monomethyl-l-arginine. Moreover, S-nitroso-HCy did not increase ROS generation, p53-dependent Noxa expression, and apoptosis. These results suggest that up-regulation of p53-dependent Noxa expression may play an important role in the pathogenesis of atherosclerosis induced by HCy and that an increase in vascular NO production may prevent HCy-induced endothelial dysfunction by S-nitrosylation.
Optical switching and modulation in parallel dielectric waveguides (1973)

Coupling of electromagnetic energy between parallel single-mode dielectric waveguides is investigated theoretically. Expressions giving the decrease in coupling length due to an antisymmetric change in refractive index are derived. The minimum parallel-guide path length, l, required for switching or modulation is determined from coupling length calculations. It is shown that, for large waveguide separations, Δnl=3λ/4, where λ is the free-space wavelength and Δn is the magnitude of the antisymmetric index change. Calculations for slab and square-cross-section waveguide geometries indicate that antisymmetric index changes are much more effective than symmetric changes for switching or modulation.
Tissue clearing of human iPSC-derived organ-chips enables high resolution imaging and analysis (2022)

Engineered microfluidic organ-chips enable increased cellular diversity and function of human stem cell-derived tissues grown <i>in vitro</i>. These three dimensional (3D) cultures, however, are met with unique challenges in visualization and quantification of cellular proteins. Due to the dense 3D nature of cultured nervous tissue, classical methods of immunocytochemistry are complicated by sub-optimal light and antibody penetrance as well as image acquisition parameters. In addition, complex polydimethylsiloxane scaffolding surrounding the tissue of interest can prohibit high resolution microscopy and spatial analysis. Hyperhydration tissue clearing methods have been developed to mitigate similar challenges of <i>in vivo</i> tissue imaging. Here, we describe an adaptation of this approach to efficiently clear human pluripotent stem cell-derived neural tissues grown on organ-chips. We also describe critical imaging considerations when designing signal intensity-based approaches to complex 3D architectures inherent in organ-chips. To determine morphological and anatomical features of cells grown in organ-chips, we have developed a reliable protocol for chip sectioning and high-resolution microscopic acquisition and analysis.
Experimental performance of a fully tunable complex-coefficient optical FIR filter using wavelength conversion and chromatic dispersion (2012)

We experimentally characterize the performance of a continuously tunable all-optical complex-coefficient finite-impulse-response (FIR) filter that exploits nonlinear signal processing (multiplexing and multicasting) and conversion-dispersion-based optical delays. Various length (three and four) optical FIR filters with different tap amplitudes (from 0 to -9 dB), tap phases (from 0 to 2π), and tap delays (~37.4 ps and 25 ps) are realized, showing reconfiguration and tuning capabilities of this FIR filter. The measured frequency responses show close agreement with the theoretical filter responses.
Supplementary Figure S7 from Evolution of Castration-Resistant Prostate Cancer in ctDNA during Sequential Androgen Receptor Pathway Inhibition (2023)

&lt;p&gt;Supplementary Figure S7 shows the concordance of gene coverage logratios between 72-gene targeted sequencing and whole exome sequencing&lt;/p&gt;
Derivation of indices of socioeconomic status for health services research in Asia (2015)

These indices may prove useful for policy-makers to identify spatially varying risk factors, and in turn help identify geographically targeted intervention programs, which can be more cost effective to conduct.
Efficient system-level functional verification methodology for multimedia applications (2003)

Multimedia application design exploration should begin at the system level, to meet low-power and minimum-area requirements. Existing validation techniques mainly concentrate on lower abstraction levels. This system-level methodology combines formal verification of loop-oriented transformations with correctness verification of arithmetic constructs and related control flows. A videoconferencing-decoder example illustrates the methodology's efficiency.
The Influence of Biomaterials on Cytokine Production in 3D Cultures (2017)

As a result of improved relevance to in vivo physiology, in vitro studies are increasingly performed in diverse, three-dimensional (3D) biomaterials. However, material-cell type pairing effects on cytokine availability remain unclear. We cultured five cell types in agarose, alginate, collagen, Matrigel, or RGD-functionalized polyethylene glycol (PEG) hydrogels. We measured 21 cytokines in the conditioned media, and we identified differences in measured cytokine levels that were cell-type- or material-dependent. We further evaluated our data using principal component analysis. Interestingly, component one identified two classes of biomaterials with characteristic cytokine expression levels. Component two identified cell-type-dependent differences in cytokines related to the wound response. Although elements of soluble cytokine availability are shared despite parameter differences, material and cellular properties variably influenced cytokine levels, underlining the influence of biomaterial-cell type pairings on in vitro assay outcomes. Relationships between material properties, cellular responses, and cytokine availability in 3D in vitro models warrant further investigation.
Maximizing Science in the Era of LSST, Stars Study Group Report: Rotation and Magnetic Activity in the Galactic Field Population and in Open Star Clusters (2016)

This is the stars chapter of the Kavli workshop report, which resulted from the community-based study of needed US OIR capabilities in the LSST era. The full report, which will include this chapter, is anticipated to be available in Fall 2016. See NOAO website (http://www.noao.edu/meetings/lsst-oir-study/) for more details.
Differential response and withdrawal profile of glucocorticoid-treated human trabecular meshwork cells (2020)

The goal of the study was to examine secreted protein response and withdrawal profiles from cultured human trabecular meshwork (HTM) cells following short- and long-term glucocorticoid treatment. Primary cultures of five human HTM cell strains isolated from 5 different individual donor eyes were tested. Confluent HTM cells were differentiated in culture media containing 1% FBS for at least one week, and then treated with Dexamethasone (Dex, 100 nM) 3 times/week for 1 or 4 weeks. Cell culture supernatant was collected 3 times per week for 8 weeks. Secretion profiles of myocilin (MYOC), matrix metalloproteinase-2 (MMP2) and fibronectin (FN) were determined by Western blot analysis and MMP2 activity by zymography. Dex treatment reduced MMP2 expression and activity, returning to normal levels shortly after Dex withdrawal in 5 HTM cell strains. All five cell strains significantly upregulated MYOC in response to Dex treatment by an average of 17-fold, but recovery to basal levels after Dex withdrawal took vastly different periods of time depending on cell strain and treatment duration. Dex treatment significantly increased FN secretion in all strains but one, which decreased FN secretion in the presence of Dex. Interestingly, secretion of FN and MYOC negatively correlated during a 4 week recovery period following 4 weeks of Dex treatment. Taken together, the time course and magnitude of response and recovery for three different secreted, extracellular matrix-associated proteins varied greatly between HTM cell strains, which may underlie susceptibility to glucocorticoid-induced ocular hypertension.
Simultaneous 3D visualization and quantification of the bone marrow adiposity and vascularity using novel contrast agents for contrast-enhanced computed tomography (2016)

Introduction A detailed visualization of the complex 3D blood vessel and adipose tissue network in bone and bone marrow may help to link alterations in these tissues with impaired bone remodeling, healing and regeneration. For this purpose, we propose contrast-enhanced computed tomography (CE-CT). We have compared phosphotungstic acid (PTA) with two novel contrast agents for their non-invasive character and their potential to visualize in 3D blood vessels and adipose tissue in different mouse models (ageing and Type 2 diabetes). Methods and results Both novel contrast agents are metal-substituted polyoxotungstates, and are further referred to as Hf-POT (Hf-substituted) and Zr-POT (Zr-substituted). To investigate whether the staining provoked tissue shrinkage, we used femurs of 30 week old mice. After harvest and fixation in paraformaldehyde, the samples were scanned, stained and rescanned. Using image registration, tissue shrinkage (with focus on bone) was assessed, showing that PTA does induce shrinkage of bone after 24 hours of staining in a 3.5% PTA/PBS (phosphate buffered saline) solution. Both novel contrast agents however did not induce shrinkage using the same concentration and staining time. To further assess the non-invasiveness of the contrast agents, we investigated the potential to perform immunological staining after CE-CT imaging. Therefore, we first stained tibias of 4 weeks old mice, scanned these using CE-CT, and processed subsequently for CD31 immunostaining for blood vessel visualization. We included control samples that were not stained using the contrast agents, and performed blind scoring. PTA staining did not allow CD31 staining, while both novel contrast agents showed excellent CD31 tracing. Finally, we scanned tibias of old (30 weeks - OLD), young (7 weeks - YNG) and diabetic (30 weeks - diet-induced obese model, DIO) mice. Both novel contrast agents were able to pick up differences between the three groups (Fig. 1). Ageing induced a significant increase in bone marrow adiposity and adipocyte thickness, but did show a significant change in the blood vessel content. Obesity-induced Type 2 diabetes even increased the bone marrow adiposity and adipocyte thickness, and moreover resulted in a significant decrease in the blood vessel content. Conclusion CE-CT is a multi-tissue 3D imaging technique that can reveal the 3D structure of different skeletal tissues (i.e. bone, bone marrow, adipocytes and blood vessels). Since it is promising for providing additional information to standard histomorphometry, with a spatial dimension, CE-CT might bring novel insights in the biological processes during tissue remodeling and regeneration.
An Efficient and Scalable Synthesis of Substituted Phenanthrenequinones by Intramolecular Friedel−Crafts Reaction of Imidazolides (2007)

An efficient synthesis of 9,10-phenanthrenequinones is described. The two carbonyl groups were introduced by an orthoselective intermolecular Friedel-Crafts reaction of 3-methoxyphenol with ethyl chlorooxoacetate. The formation of a biaryl bond by Suzuki-Miyaura coupling reaction, followed by the hydrolysis of the ester, gave a biaryloxoacetic acid. Treatment of this acid with CDI gave the corresponding imidazolide. The ring closure to the desired phenanthrenequinone was accomplished by intramolecular Friedel-Crafts reaction of the imidazolide promoted by TiCl(4).
Characterization of Outer Insulation in Long-Term-Implanted Leads (2016)

Success of pacemakers and implantable cardioverter defibrillators may be limited by premature lead failure. Lead insulation polymers, such as polyurethane (PU) and polydimethylsiloxane (PDMS), are reported to degrade over time in vivo. PU is known to undergo oxidation, whereas PDMS undergoes surface hydrolysis. Previous studies have characterized polymer degradation in vitro, in animals or in short-term human study; however, complex effects of the biochemical and mechanical environment on the lead insulation can only be fully understood by evaluating long-term-implanted leads. Therefore, we established a retrieval program to systematically characterize the chemical and surface changes in 37 of 104 retrieved pacing and defibrillator leads, implanted for ≥5 yr. Fourier transform infrared (FTIR) spectroscopy was used for chemical analysis, and a scanning electron microscope was used for surface degradation evaluation. PDMS leads were investigated for changes in the ratio of Si-O-Si to Si-C peaks, whereas PU degradation was evaluated by changes in ether (C-O-C), carbonyl (C=O), methylene (C-H), and amino (C-N/N-H) peaks. Under SEM, PDMS showed enhanced roughness but no statistical increase in Si-O-Si bonds. PU showed uniform cracking throughout the lead body and statistical changes in each of the oxidation indicative peaks. Overall, both polymers showed surface changes in the physiological environment, but PU was the only material to show chemical changes. This work is a large-scale characterization study on long-term-implanted leads that confirmed PU oxidation but not hydrolysis of PDMS in vivo. It provides important insight for manufacturers when making design improvements and for surgeons when making decisions about lead implantation.
Novel PAK4 inhibitors for pancreatic cancer therapy. (2014)

233 Background: Pancreatic cancer (PC) is a deadly disease in urgent need of novel molecularly targeted drugs. Gene copy number amplification studies in PC patient cohorts has shown amplification of the p21-activated kinase (PAK) family member PAK4. PAK4 acts as a key effector of the Rho family GTPases downstream of Ras signaling. Moreover, PAK4 protein is over-expressed in PC cell lines but not in normal human pancreatic ductal epithelial (HPDE) cells. Most importantly, RNA interference of PAK4 has been shown to suppress PC cell proliferation. These studies clearly make PAK4 an attractive therapeutic target especially because direct targeting of Kras has been a failure. Methods: We have identified a new class of PAK4 allosteric modulators that show anti-proliferative activity against several PC cell lines (IC 50s &lt;250nM) while sparing normal HPDE (IC 50s 5 fold higher). Results: Cell growth inhibition is concurrent with apoptosis induction and suppression of colony formation in the PC cell lines (and not in HPDE cells). Our small molecule PAK4 allosteric modulator, KPT-7189, suppresses PAK4 protein expression and caused reversal of anti-apoptotic signaling. PAK4 RNA interference enhances KPT-7189 activity, and co-immunoprecipitation experiments showed disruption of PAK4 binding partners. KPT-7189 also inhibited spheroid forming ability of highly resistant PC cells carrying markers of cancer stem cells (CSCs;triple positive for CD33 + CD44 + EpCAM +) consistent with epithelial-to-mesenchymal (EMT) phenotype. Molecular analyses of KPT-7189 treated CD33 + CD44 + EpCAM + spheroids showed suppression of EMT and CSC markers with re-expression of epithelial phenotype markers. Another potent PAK allosteric modulator in the same series, KPT-7651 showing good oral bioavailability (%F = 95%) was well tolerated by mice with a maximum tolerated dose of 60 mg/kg following oral administration. Pre-clinical animal efficacy trial in sub-cutaneous, orthotopic and LSL-Kras G12D/+ ;LSL-Trp53 R172H/+ ;Pdx-1-Cre transgenic mice model is currently under investigation. Conclusions: This is the first proof of concept study demonstrating the development of a PAK4-targeted drug for the treatment of PC, and thus further pre-clinical and clinical investigations are warranted.
Core–Shell Gyroid in ABC Bottlebrush Block Terpolymers (2022)

Block polymer self-assembly provides a versatile platform for creating useful materials endowed with three-dimensional periodic network morphologies that support orthogonal physical properties such as high ionic conductivity and a high elastic modulus. However, coil configurations limit conventional linear block polymers to finite ordered network dimensions, which are further restricted by slow self-assembly kinetics at high molecular weights. A bottlebrush architecture can circumvent both shortcomings owing to extended backbone configurations due to side chain crowding and molecular dynamics substantially free of chain entanglements. However, until now, network morphologies have not been reported in AB bottlebrush block copolymers, notwithstanding favorable mean-field predictions. We explored the phase behavior by small-angle X-ray scattering of 133 poly(ethylene-<i>alt</i>-propylene)-<i>b</i>-polystyrene (PEP-PS) diblock and PEP-PS-PEO triblock bottlebrush copolymers prepared by ring-opening metathesis polymerization (ROMP) of norbornene-functionalized poly(ethylene-<i>alt</i>-propylene) (PEP), poly(styrene) (PS), and poly(ethylene oxide) (PEO) macromonomers with total backbone degrees of polymerization <i>N</i><sub>bb</sub> between 20 and 40. The PEP-PS diblocks exhibited only cylindrical and lamellar morphologies over the composition range of ca. 30-70%. However, addition of variable-length bottlebrush PEO blocks to diblocks containing 30-50% PS led to the formation of a substantial core-shell double gyroid (GYR) phase window containing 20 bottlebrush triblock specimens, which is the focus of this report. Encouragingly, the GYR unit cell dimensions increased as <i>d</i> ∼ <i>N</i><sub>bb</sub><sup>0.92</sup>, portending the ability to access larger network dimensions than previously obtained with linear AB or ABC block polymers. This work highlights extraordinary opportunities associated with applying facile ROMP chemistry to multiblock bottlebrush polymers.
DNA substrate structural requirements for the exonuclease and polymerase activities of prokaryotic and phage DNA polymerases (1989)

A DNA duplex covalently cross-linked between specific bases has been prepared. This and similar duplexes are substrates for the polymerase and exonuclease activities of the Klenow fragment of Escherichia coli DNA polymerase I and T4 and T7 DNA polymerases. The action of Klenow fragment on these duplexes indicates that the polymerase site does not require that the DNA duplex undergo strand separation for activity, whereas the exonuclease site requires that at least four base pairs of the primer strand must melt out for the exonucleolytic removal of nucleotides from the primer terminus. The exonucleolytic action of T4 and T7 DNA polymerases requires that only two and three bases respectively melt out for excision of nucleotides from the primer terminus. Klenow fragment and T4 DNA polymerase are able to polymerize onto duplexes incapable of strand separation, whereas T7 DNA polymerase seems to require that the primer terminus be at least three bases from the cross-linked base pair. A DNA duplex with a biotin covalently linked to a specific base has been prepared. In the presence of the biotin binding protein avidin, the exonucleolytic activity of Klenow fragment requires that the primer terminus be at least 15 base pairs downstream from the base with the biotin-avidin complex. On the other hand, the polymerase activity of Klenow fragment required that the primer terminus be at least six base pairs downstream from the base with the biotin-avidin complex. These results suggest that the polymerase and exonuclease sites of Klenow are physically separate in solution and exhibit different substrate structural requirements for activity.
Acknowledgement of Invited Editors (2015)

On behalf of the editors of mBio, I gratefully acknowledge the following individuals, who served as Invited Editors for the journal in 2014. While not members of the Board of Editors, Invited Editors serve an important role in the review process. Invited Editors are experts in their fields of research who add an additional level of quality to the review process. An Editor may assign a paper to an Invited Editor when he/she would like to have an additional expert opinion of the reviews or when the subject area falls outside the Editor's primary area of expertise.
Convection in Nanofluids (2007)

This chapter contains sections titled: Fundamentals of Convective Heat Transfer Convection in Suspensions and Slurries Convection in Nanofluids Analysis of Convection in Nanofluids Numerical Studies of Convection in Nanofluids Convective Simulation for Chip Cooling Application References
Fake data - the future of advanced computer vision systems (2018)

Recent research shows that Data Augmentation techniques and Synthetic Data can improve the accuracy and reduce the susceptibility of Deep Neural Networks to Adversarial Attacks. In this presentation we consider some of the new tools that are available to build advanced virtual models that can be used to render large 2D training datasets suitable for training tomorrow's advanced Computer Vision systems for deployment in consumer and smart-city use cases.