gebhart/patrepeval huggingface dataset:
Neurotoxicity of microglial cathepsin D revealed by secretome analysis (2007)

Microglia-driven inflammatory responses have both neuroprotective and neurotoxic effects in the CNS. The excessive and chronic activation of microglia, however, may shift the balance towards neurotoxic effects. In this regard, proteins secreted from activated microglia likely play a key role in the neurotoxic effects. To characterize secreted proteins of activated microglia, conditioned media obtained from BV-2 mouse microglia cells were analyzed by two-dimensional gel electrophoresis or liquid chromatography coupled with tandem mass spectrometry. Among many proteins identified in the secretome of activated microglia, an aspartic endoprotease cathepsin D has been found to mediate microglial neurotoxicity based on the following results: (i) the expression of cathepsin D protein was markedly increased in lipopolysaccharide/interferon-γ-stimulated microglia compared with resting microglia as determined by western blot analysis of conditioned media; (ii) knockdown of cathepsin D expression in microglia using short hairpin RNA diminished the neurotoxicity in the coculture of microglia and neuroblastoma cells and (iii) recombinant procathepsin D protein exerted cytotoxic effects toward cultured neurons. In conclusion, cathepsin D appears to play a central role in the microglial neurotoxicity, and could be a potential biomarker or drug target for the diagnosis and treatment of neurodegenerative diseases that are associated with excessive microglial activation and subsequent neurotoxic inflammation.
Molecular Complexity as a Driver for Chemical Process Innovation in the Pharmaceutical Industry (2019)

A Perspective of our work in the development of innovative synthetic methods within the discipline of Process Research and Development is presented. Through an overview of some of the programs that we have worked on during the past decade, we have selected cases studies to illustrate the challenges faced in development of robust chemical processes for molecules on a multi-kilogram scale. The examples have been selected to demonstrate the innovative chemistry being developed within our laboratories with a focus on fragment design, asymmetric synthesis, new synthetic reagents, and the methods that have allowed us to deliver cost-effective syntheses under reduced timelines in an increasingly competitive environment. The technical challenges are presented in the context of molecule complexity that while increasing in the portfolio of small molecules being developed inspires us to deliver new solutions. Overall, our goal is to highlight the exciting work that can be done within our field to support the discovery and delivery of medicines to patients.
Estimation of melatonin level and core body temperature: heart rate and heart rate variability as circadian rhythm markers (2022)

Because the circadian rhythm is different for each individual depending on what light environment they are exposed to on that day, the circadian rhythm needs to be constantly managed in everyday life. However, the typical circadian markers, changes in melatonin (MLT), and core body temperature (CBT) are difficult to measure 24-hour cycle of daily life. In this study, to propose relatively easy-to-monitor cardiac rhythmicity-related indicators as circadian markers, the biomarkers, including MLT, CBT, heart rate (HR), and heart rate variability (HRV), were collected from 22 Korean men. The MLT and CBT showed the largest positive correlation with R wave-to-R wave (RR) interval (Pearson’s r = .620, p < .001) and HR (Pearson’s r = .476, p < .001), respectively. In addition, the difference between the peak times of the seventh-order fitted MLT (adjusted R2 = .960, peak time 04:56) and RR interval (adjusted R2 = .960, peak time 04:35) was approximately 21 min; especially, the nadir times of the fitted CBT (adjusted R2 = .961, nadir time 04:55) and HR (adjusted R2 = .934, nadir time 04:52) were almost the same. Therefore, we can confidently say that HR and RR intervals are good indicators for estimating an individual’s circadian rhythm.
Genetically Defined Subsets of Human Pancreatic Cancer Show Unique In Vitro Chemosensitivity (2012)

Chemosensitivity of pancreatic cancer cells correlated with some specific genetic profiles. These results support the hypothesis that genetic subsets of pancreatic cancer exist, and these genetic backgrounds may permit one to personalize the chemotherapy of pancreatic cancer in the future. Further work will need to confirm these responses and determine their magnitude in vivo.
Coding Efficiency for Different Switched-Mode (2009)

Conventional RF transmitters with power amplifiers in e.g. Class-AB operation provide only moderate electrical ef- ficiencies for complex modulated signals. To increase the overall efficiency considerably, we can employ switched-mode power ampli- fiers (SMPA) with an appropriate baseband signal processing. Such efficient SMPAs generate a lot of spectral out-of-band components, which has to be attenuated by a bandpass filter before the signal is fed to the transmit antenna. Unfortunately, this impacts the electrical efficiency because these unwanted signal components are usually dissipated within the transmitter. A measure for the electrical efficiency degradation for complex modulated signals in a switched-mode operation is the coding efficiency. In this paper we develop different switched-mode transmitter architectures based on baseband PWM coding and analyze the coding efficiencies for different signal statistics.
Biocidal properties of TiO2 powder modified with Ag nanoparticles (2013)

Silver nanoparticles (NPs) were synthesized sonochemically by the reduction of silver ions with ethylene glycol and simultaneously deposited on different forms of TiO<sub>2</sub> powders (commercial Degussa P-25, synthetic anatase and mesoporous titania). The Ag-TiO<sub>2</sub> nanocomposites were characterized by X-ray electron diffraction (XRD), transmission electron microscopy (TEM), energy-dispersed X-ray analysis (EDX), UV absorption spectroscopy (UV), Z-potential measurements and electron paramagnetic resonance (EPR). The results demonstrated homogeneous distribution of silver nanoparticles ∼3 nm in size, strongly attached to the surface of titania. The antimicrobial properties of Ag-TiO<sub>2</sub> were tested against a number of Gram-positive and Gram-negative bacteria. A high bactericidal effect was found in the absence of UV light. The reduction in bacterial viability was between 3 and 4.2 logs. Based on the experimental data it was concluded that enhanced antimicrobial activity of the Ag-TiO<sub>2</sub> originated from both the oxidative stress generated by silver nanoparticles and the presence of silver ions on the surface of the silver-titania composite.
Innovations Into Minimizing Interfacial Contamination Between Crude Batches due to Dead-Legs in Pump Station Piping Layouts (2016)

Invariably, oil pump station piping layouts may contain multiple dead-legs brought about by closed valves at one end of side branches, while flows continue through the main runs. During the transportation of heavy crude through the pump station, these dead-legs will be filled with this crude. When a light crude batch is introduced next into the pipeline, following the heavy crude ahead, two phenomena will occur. First, contamination between batches at the interface of the two crudes will occur due to axial turbulent diffusion along the length of the pipeline itself. Second, as the light crude flows through the pump station, and passes by each dead-leg containing residual heavy crude from the preceding batch, the heavy crude trapped in these dead-legs will start to drain out into the passing light crude in the main run. This causes further contamination and spreading of the mixing zone between the two batches. The second source of contamination, which is addressed in this paper, could cause appreciable contamination particularly for large dead-leg sizes and numbers. A computational fluid dynamics (CFD) model has been developed to quantify the drainage rate of the contaminating crude into the main stream and its impact on widening the mixed zone (contamination spread) between the two batches. Two drainage mechanisms of the heavy crude in the dead-legs into the main stream of the light crude have been identified and quantified. Finally, potential innovations to mitigate contamination due to dead legs are presented and quantified for their respective effectiveness in minimizing the contamination spreads between batches of different crudes.
The effect of multiple energy-scales on mesospin ordering (2021)

The interplay between topology and energy-hierarchy plays a vital role in the collective magnetic order in artificial ferroic systems. Here we investigate, experimentally, the effect of having one or two activation energies of interacting Ising-like magnetic islands -- mesospins -- in a thermalized, topologically frustrated artificial spin ice. The thermally arrested magnetic states of the elements were determined using synchrotron-based magnetic microscopy after cooling the samples from temperatures above the Curie temperature of the material. Statistical analysis of the correlations between mesospins, across several length-scales, reveals enhanced magnetic order arising from the differences in the activation energy. This enhancement reflects on the amount of ground state plaquettes realized for a topologically frustrated lattice, depending on the presence, or not, of different activation energies.
Deep Self-Taught Learning for Handwritten Character Recognition (2010)

Recent theoretical and empirical work in statistical machine learning has demonstrated the importance of learning algorithms for deep architectures, i.e., function classes obtained by composing multiple non-linear transformations. Self-taught learning (exploiting unlabeled examples or examples from other distributions) has already been applied to deep learners, but mostly to show the advantage of unlabeled examples. Here we explore the advantage brought by {\em out-of-distribution examples}. For this purpose we developed a powerful generator of stochastic variations and noise processes for character images, including not only affine transformations but also slant, local elastic deformations, changes in thickness, background images, grey level changes, contrast, occlusion, and various types of noise. The out-of-distribution examples are obtained from these highly distorted images or by including examples of object classes different from those in the target test set. We show that {\em deep learners benefit more from out-of-distribution examples than a corresponding shallow learner}, at least in the area of handwritten character recognition. In fact, we show that they beat previously published results and reach human-level performance on both handwritten digit classification and 62-class handwritten character recognition.
Novel Hepatitis B Virus Capsid Assembly Modulator Induces Potent Antiviral Responses In Vitro and in Humanized Mice (2019)

Hepatitis B virus (HBV) affects an estimated 250 million chronic carriers worldwide. Though several vaccines exist, they are ineffective for those already infected. HBV persists due to the formation of covalently closed circular DNA (cccDNA)-the viral minichromosome-in the nucleus of hepatocytes. Current nucleoside analogs and interferon therapies rarely clear cccDNA, requiring lifelong treatment. Our group identified GLP-26, a novel glyoxamide derivative that alters HBV nucleocapsid assembly and prevents viral DNA replication. GLP-26 exhibited single-digit nanomolar anti-HBV activity, inhibition of HBV e antigen (HBeAg) secretion, and reduced cccDNA amplification, in addition to showing a promising preclinical profile. Strikingly, long term combination treatment with entecavir in a humanized mouse model induced a decrease in viral loads and viral antigens that was sustained for up to 12 weeks after treatment cessation.
Spexin as a Satiety Factor in Mouse via Regulatory Actions Within the Hypothalamus (2021)

Abstract Spexin (SPX) is a pleiotropic peptide with highly conserved protein sequence from fish to mammals and its biological actions are mediated by GalR2/GalR3 receptors expressed in target tissues. Recently, SPX was found to be a novel satiety factor in fish models but whether the peptide has a similar function in mammals is still unknown. Using the mouse as a model for mammalian species, the functional role of SPX in feeding control and the mechanisms involved were investigated. After food intake, serum SPX could be up-regulated in mice with parallel elevations of transcript expression and tissue content of SPX in the glandular stomach but not in other tissues examined. As revealed by immunostaining, food intake also intensified SPX signals in different cell types within the gastric mucosa of glandular stomach. Furthermore, IP injection of SPX was effective in reducing food consumption with parallel drops in transcript expression of NPY, AgRP, NPY type 5 receptor (NPY5R) and ghrelin receptor (GHSR) in the hypothalamus, and these inhibitory effects could be blocked by GalR3 but not GalR2 antagonism. In agreement with the central actions of SPX, similar inhibition on food intake and hypothalamic expression of NPY, AgRP, NPY5R and GHSR could be observed with ICV injection of SPX. In the same study, parallel rises of transcript expression of leptin receptor (LepR) and melanocortin 4 receptor (MC4R) were also observed in the hypothalamus. These findings, taken together, suggest that the role of SPX as a satiety factor is well-conserved in the mouse. Probably, food consumption can induce SPX production in glandular stomach and contribute to the postprandial rise of SPX in circulation. Through GalR3 activation, this SPX signal can act within the hypothalamus to trigger feedback inhibition on food intake by differential modulation of the feeding regulators (NPY &amp; AgRP) and their receptors (NPY5R, GHSR, LepR &amp; MC4R) involved in the feeding circuitry of the brain.
Flavin–Protein Complexes: Aromatic Stacking Assisted by a Hydrogen Bond (2015)

Enzyme-catalyzed reactions often rely on a noncovalently bound cofactor whose reactivity is tuned by its immediate environment. Flavin cofactors, the most versatile catalyst encountered in biology, are often maintained within the protein throughout numbers of complex ionic and aromatic interactions. Here, we have investigated the role of π-π stacking and hydrogen bond interactions between a tyrosine and the isoalloxazine moiety of the flavin adenine dinucleotide (FAD) in an FAD-dependent RNA methyltransferase. Combining several static and time-resolved spectroscopies as well as biochemical approaches, we showed that aromatic stacking is assisted by a hydrogen bond between the phenol group and the amide of an adjacent active site loop. A mechanism of recognition and binding of the redox cofactor is proposed.
Band Alignments of Ternary Wurtzite and Zincblende III-Nitrides Investigated by Hybrid Density Functional Theory (2020)

Band gaps and electron affinities of binary and ternary, wurtzite (wz-) and zincblende (zb-) III-nitrides are investigated using a unified hybrid density functional theory, and band offsets between wz- and zb- alloys are calculated using Anderson's electron affinity model. A conduction (and valence) band offset of 1.85 (0.89) eV has been calculated for zb-GaN/InN heterojunctions, which is 0.25 eV larger (and 0.26 eV smaller) than that of the wz- counterpart. Such polarization-free zb-GaN/InGaN/GaN quantum well structures with large conduction band offsets have the potential to suppress electron leakage current and quantum-confined Stark effects (QCSEs). Contrarily, the conduction (and valence) band offset of zb-AlN/GaN heterojunctions is calculated to be 1.32 (0.43) eV, which is 1.15 eV smaller (and 0.13 eV larger) than that of the wz- case. The significant reduction in zb-AlN/GaN band offsets is ascribed to the smaller and indirect band gap of zb-AlN-the direct-to-indirect crossover point in zb-Al <i><sub>X</sub></i> Ga<sub>1-<i>X</i></sub> N is when <i>X</i> ∼ 65%. The small band gap of the zb-AlN barrier and the small conduction band offsets imply that electrons can be injected into zb-AlN/GaN/AlN quantum well heterostructures with small bias and less energy loss when captured by the quantum wells, respectively, i.e., loss as heat is reduced. The band gap of ternary III-nitrides does not linearly depend on alloy compositions, implying a nonlinear dependence of band offsets on compositions. As a result, the large bowing of the conduction band offset is identified and ascribed to the cation-like behavior of the conduction band minimum, while the linear dependence of the valence band offset on compositions is attributed to the anion-like character of the valence band maximum.
Urinary cell-free nucleic acid IQGAP3: a new non-invasive diagnostic marker for bladder cancer (2018)

Levels of IQGAP3 urinary cell-free NA in BC patients were significantly higher than those in normal controls or patients with hematuria. High levels of IQGAP3 urinary cell-free NA also reflected high expression in BC tissues. Therefore, IQGAP3 urinary cell-free NA may be a complementary diagnostic biomarker for BC.
The Role of Nanoparticle Layer Separation in the Finite Deformation Response of Layered Polyurethane−Clay Nanocomposites (2010)

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionORIGINAL ARTICLEThis notice is a correctionThe Role of Nanoparticle Layer Separation in the Finite Deformation Response of Layered Polyurethane−Clay NanocompositesAmit K. Kaushik, Paul Podsiadlo, Ming Qin, Charles M. Shaw, Anthony M. Waas, Nicholas A. Kotov, and Ellen M. Arruda*Cite this: Macromolecules 2010, 43, 14, 6241–6244Publication Date (Web):June 29, 2010Publication History Received29 March 2010Published online29 June 2010Published inissue 27 July 2010https://pubs.acs.org/doi/10.1021/ma100678bhttps://doi.org/10.1021/ma100678bcorrectionACS PublicationsCopyright © 2010 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views917Altmetric-Citations1LEARN 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 PDF (3 MB) Get e-AlertscloseSUBJECTS:Nanocomposites,Nanoparticles,Organic polymers,Stiffness,Thickness Get e-Alerts
Presentation of Global Behaviour of Nonlinear AC Power Systems Using Bifurcation Diagrams (1997)

Operational voltage levels can force a.c. power systems into non-linear behaviour. The system global characteristics are presented in bifurcation diagrams, generated using an electromagnetic–transients program. They reveal the onset of ferroresonance, period-doubling and chaos when series capacitance is present between the supply and saturating transformers.
Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain (2014)

Metastases represent the most common brain tumors in adults. Surgical resection alone results in 45% recurrence and is usually accompanied by radiation and chemotherapy. Adequate chemotherapy delivery to the CNS is hindered by the blood-brain barrier. Efforts at delivering chemotherapy locally to gliomas have shown modest increases in survival, likely limited by the infiltrative nature of the tumor. Temozolomide (TMZ) is first-line treatment for gliomas and recurrent brain metastases. Doxorubicin (DOX) is used in treating many types of breast cancer, although its use is limited by severe cardiac toxicity. Intracranially implanted DOX and TMZ microcapsules are compared with systemic administration of the same treatments in a rodent model of breast adenocarcinoma brain metastases. Outcomes were animal survival, quantified drug exposure, and distribution of cleaved caspase 3. Intracranial delivery of TMZ and systemic DOX administration prolong survival more than intracranial DOX or systemic TMZ. Intracranial TMZ generates the more robust induction of apoptotic pathways. We postulate that these differences may be explained by distribution profiles of each drug when administered intracranially: TMZ displays a broader distribution profile than DOX. These microcapsule devices provide a safe, reliable vehicle for intracranial chemotherapy delivery and have the capacity to be efficacious and superior to systemic delivery of chemotherapy. Future work should include strategies to improve the distribution profile. These findings also have broader implications in localized drug delivery to all tissue, because the efficacy of a drug will always be limited by its ability to diffuse into surrounding tissue past its delivery source.
Genetic modifiers of Cep290 -mediated retinal degeneration (2022)

ABSTRACT Mutations in CEP290 cause up to 30% of cases of Leber congenital amaurosis (LCA), a severe childhood blindness resulting from abnormalities in the photoreceptor connecting cilia that lead to rapid retinal degeneration. Like many genetic diseases, CEP290-LCA has considerable variable expressivity, indicating the presence of other factors that influence phenotypic outcome. Here, we have undertaken a phenotype-driven approach in mice to identify genetic modifiers of CEP290-mediated retinal degeneration through backcrosses and intercrosses between BXD24- Cep290 rd16 mice and the genetically distinct inbred CAST strain to introduce genetic variation. Optical coherence tomography was used to quantitatively measure retinal thickness as a surrogate indication of photoreceptor degeneration in the resulting rd16 -mutant mice. It was readily apparent that CEP290-mediated retinal degeneration in the resulting mice is sensitive to genetic background, with some mice exhibiting relatively thick laminated retinas and others having thin retinas with advanced disease. Quantitative trait locus (QTL) analysis identified multiple genomic loci capable of influencing the retinal degeneration phenotype in Cep290 -mutant mice that together account for 71.7% of the phenotypic variation in retinal thickness observed in our population. Following the QTL analysis, two suppressor loci were studied in detail through a combination of physical and molecular approaches to narrow the critical region for each QTL and identify the probable causative genetic variations.