gebhart/patrepeval huggingface dataset:
A Transcription Start Site Map in Human Pancreatic Islets Reveals Functional Regulatory Signatures (2021)

Identifying the tissue-specific molecular signatures of active regulatory elements is critical to understand gene regulatory mechanisms. Here, we identify transcription start sites (TSS) using cap analysis of gene expression (CAGE) across 57 human pancreatic islet samples. We identify 9,954 reproducible CAGE tag clusters (TCs), ~20% of which are islet-specific and occur mostly distal to known gene TSSs. We integrated islet CAGE data with histone modification and chromatin accessibility profiles to identify epigenomic signatures of transcription initiation. Using a massively parallel reporter assay, we validated the transcriptional enhancer activity for 2,279 of 3,378 (~68%) tested islet CAGE elements (5% FDR). TCs within accessible enhancers show higher enrichment to overlap type 2 diabetes genome-wide association study (GWAS) signals than existing islet annotations, which emphasizes the utility of mapping CAGE profiles in disease-relevant tissue. This work provides a high-resolution map of transcriptional initiation in human pancreatic islets with utility for dissecting active enhancers at GWAS loci.
Leukotriene C4 Is a Tight-binding Inhibitor of Microsomal Glutathione Transferase-1 (1999)

Microsomal glutathione transferase-1 (MGST-1) is an abundant protein that catalyzes the conjugation of electrophilic compounds with glutathione, as well as the reduction of lipid hydroperoxides. Here we report that leukotriene C4 is a potent inhibitor of MGST-1. Leukotriene C4 was found to be a tight-binding inhibitor, with a Ki of 5.4 nM for the unactivated enzyme, and 9.2 nM for the N-ethylmaleimide activated enzyme. This is the first tight-binding inhibitor characterized for this enzyme. Leukotriene C4 was competitive with respect to glutathione and non-competitive toward the second substrate, CDNB. Analysis of stoichiometry supports binding of one molecule of inhibitor per homotrimer. Leukotrienes A4, D4, and E4 were much weaker inhibitors of the purified enzyme (by at least 3 orders of magnitude). Leukotriene C4 analogues, which have been developed as antagonists of leukotriene receptors, were found to display varying degrees of inhibition of MGST-1. In particular, the cysteinyl-leukotriene analogues SKF 104,353, ONO-1078, and BAYu9773 were strong inhibitors (IC50 values: 0.13, 3. 7, and 7.6 microM, respectively). In view of the partial structural similarity between MGST-1, leukotriene C4 synthase, and 5-lipoxygenase activating protein (FLAP), it was of interest that leukotriene C4 synthesis inhibitors (which antagonize FLAP) also displayed significant inhibition (e.g. IC50 for BAYx1005 was 58 microM). In contrast, selective 5-lipoxygenase inhibitors such as zileuton only marginally inhibited activity at high concentrations (500 microM). Our discovery that leukotriene C4 and drugs developed based on its structure are potent inhibitors of MGST-1 raises the possibility that MGST-1 influences the cellular processing of leukotrienes. These findings may also have implications for the effects and side-effects of drugs developed to manipulate leukotrienes.
Cytokine, chemokine and secretory IgA levels in human milk in relation to atopic disease and IgA production in infants (2003)

The relationship between breast-feeding, IgA production and development of atopic disease in children is a matter of controversy. Some of this controversy might be due to individual differences in the composition of breast milk. The aim of this study was to relate the levels of cytokines, chemokines and secretory (S)-IgA antibodies in breast milk to the development of atopic manifestation and salivary IgA production in infants. Cytokine, chemokine and SIgA levels, as measured with enzyme-linked immunosorbent assay (ELISA), in colostrum and mature milk were analyzed in relation to the development of positive skin-prick tests (SPT), allergic symptoms and salivary IgA antibody production during the first 2 years of life in 53 infants. There was no association between levels of IL-4, -5, -6, -8, -10, -13, -16, IFN-gamma, TGF-beta1, -beta2, RANTES, eotaxin or SIgA levels in the breast milk with either SPT-positivity, development of allergic symptoms or salivary IgA levels during the first 2 years of life in the infants. Thus, differences in the composition of cytokines, chemokines and SIgA in breast milk did not, to any major degree, affect the development of a positive SPT, atopic symptoms, nor salivary IgA antibody production during the first 2 years of life.
Gain dynamics in THz QCLs and its implication for THz comb sources (2019)

In this contribution we present investigation of the interactions between the individual quantum cascade sections of a heterogeneous terahertz quantum cascade laser and their role in the stable operation of a broadband gain material. We employed THz-pump/THz-probe time domain spectroscopy (TDS) and reveal the spectrally resolved gain recovery time for each quantum cascade section that has multi-exponential decay character. Obtained results are discussed with respect to a frequency comb formation.
A Simple Silver Nanowire Patterning Method Based on Poly(Ethylene Glycol) Photolithography and Its Application for Soft Electronics (2017)

Hydrogel-based flexible microelectrodes have garnered considerable attention recently for soft bioelectronic applications. We constructed silver nanowire (AgNW) micropatterns on various substrates, via a simple, cost-effective, and eco-friendly method without aggressive etching or lift-off processes. Polyethylene glycol (PEG) photolithography was employed to construct AgNW patterns with various shapes and sizes on the glass substrate. Based on a second hydrogel gelation process, AgNW patterns on glass substrate were directly transferred to the synthetic/natural hydrogel substrates. The resultant AgNW micropatterns on the hydrogel exhibited high conductivity (ca. 8.40 × 10<sup>3</sup> S cm<sup>-1</sup>) with low sheet resistance (7.51 ± 1.11 Ω/sq), excellent bending durability (increases in resistance of only ~3 and ~13% after 40 and 160 bending cycles, respectively), and good stability in wet conditions (an increase in resistance of only ~6% after 4 h). Considering both biocompatibility of hydrogel and high conductivity of AgNWs, we anticipate that the AgNW micropatterned hydrogels described here will be particularly valuable as highly efficient and mechanically stable microelectrodes for the development of next-generation bioelectronic devices, especially for implantable biomedical devices.
Learning to Be (In)variant: Combining Prior Knowledge and Experience to Infer Orientation Invariance in Object Recognition (2016)

How does the visual system recognize images of a novel object after a single observation despite possible variations in the viewpoint of that object relative to the observer? One possibility is comparing the image with a prototype for invariance over a relevant transformation set (e.g., translations and dilations). However, invariance over rotations (i.e., orientation invariance) has proven difficult to analyze, because it applies to some objects but not others. We propose that the invariant transformations of an object are learned by incorporating prior expectations with real-world evidence. We test this proposal by developing an ideal learner model for learning invariance that predicts better learning of orientation dependence when prior expectations about orientation are weak. This prediction was supported in two behavioral experiments, where participants learned the orientation dependence of novel images using feedback from solving arithmetic problems.
Nuclear Magnetic Resonance Studies of BF3 Addition Compounds. I. The Exchange of BF3 between (CH3)2O·BF3 and (C2H5)2O·BF3 (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNuclear Magnetic Resonance Studies of BF3 Addition Compounds. I. The Exchange of BF3 between (CH3)2O·BF3 and (C2H5)2O·BF3A. C. Rutenberg, A. A. Palko, and J. S. DruryCite this: J. Am. Chem. Soc. 1963, 85, 18, 2702–2704Publication Date (Print):September 1, 1963Publication History Published online1 May 2002Published inissue 1 September 1963https://pubs.acs.org/doi/10.1021/ja00901a004https://doi.org/10.1021/ja00901a004research-articleACS PublicationsRequest reuse permissionsArticle Views93Altmetric-Citations25LEARN 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
Studies on the SPEEK membrane with low degree of sulfonation as a stable proton exchange membrane for fuel cell applications (2017)

Sulfonated poly (ether ether ketone) (SPEEK) with a low degree of sulfonation (DS = 40%) was prepared for proton exchange membrane fuel cells (PEMFC). Poly (ether ether ketone) (PEEK) was sulfonated in concentrated H2SO4 under N2 atmosphere and characterized by the hydrogen nuclear magnetic resonance (H-NMR) technique. After preparation of the SPEEK polymer, the obtained polymer was dissolved in dimethylacetamide (DMAC) solvent and then the solution casting method was applied for the fabrication of membranes. Water uptake behavior, ion exchange capacity (IEC), and the proton conductivity at different temperatures and different relative humidity were determined and compared with a commercial Nafion 117 membrane. The IEC and the proton conductivity results showed that the sulfonation process successfully created proton conduction channels. In addition, the thermal, mechanical, chemical, and hydrolytic stabilities were thoroughly investigated for the prepared membrane. The low degree of sulfonation SPEEK showed a desirable chemical durability with a higher dimensional, mechanical, and thermal stability than Nafion-117 but lower water uptake and proton conductivity.
N‐Methyl‐d‐aspartate receptors are required for synaptic targeting of Alzheimer’s toxic amyloid‐β peptide oligomers (2010)

Soluble amyloid-β peptide (Aβ) oligomers, known to accumulate in Alzheimer's disease brains, target excitatory post-synaptic terminals. This is thought to trigger synapse deterioration, a mechanism possibly underlying memory loss in early stage Alzheimer's disease. A major unknown is the identity of the receptor(s) targeted by oligomers at synapses. Because oligomers have been shown to interfere with N-methyl-d-aspartate receptor (NMDAR) function and trafficking, we hypothesized that NMDARs might be required for oligomer binding to synapses. An amplicon vector was used to knock-down NMDARs in mature hippocampal neurons in culture, yielding 90% reduction in dendritic NMDAR expression and blocking neuronal oxidative stress induced by Aβ oligomers, a pathological response that has been shown to be mediated by NMDARs. Remarkably, NMDAR knock-down abolished oligomer binding to dendrites, indicating that NMDARs are required for synaptic targeting of oligomers. Nevertheless, oligomers do not appear to bind directly to NMDARs as indicated by the fact that both oligomer-attacked and non-attacked neurons exhibit similar surface levels of NMDARs. Furthermore, pre-treatment of neurons with insulin down-regulates oligomer-binding sites in the absence of a parallel reduction in surface levels of NMDARs. Establishing that NMDARs are key components of the synaptic oligomer binding complex may illuminate the development of novel approaches to prevent synapse failure triggered by Aβ oligomers.
Abstract 820: Somatic mutations to identify tumors for highly selective chemosensitization by Nrf2 depletion (2012)

Abstract Therapeutic resistance remains a critical challenge in cancer treatment. Effective chemosensitizers must target more than a single mechanism of resistance and must also selectively sensitize only tumor and not normal tissue. Nrf2 is a transcription factor that regulates a battery of cytoprotective genes, and is shown in multiple experimental systems to have a significant impact on sensitivity to cytotoxic treatments. Regulation of Nrf2 levels is largely post-translationally, as a result of its physical interaction with adapter protein Keap1, which targets it for proteosomal degradation. An increasing number of human tumors and cancer cell lines are found to have loss of function mutations in Keap1 that results in constitutively elevated Nrf2 and drug resistance. In such circumstances alternative pathways for Nrf2 degradation may predominate, including the PI3kinase pathway protein GSK-3β, which exports Nrf2 from the nucleus to the proteosome. When relatively common somatic mutations in the PI3kinase pathway result in phosphorylation of GSK-3β at Ser9, it is inactivated. However, the addition of a PI3kinase pathway inhibitors increases GSK-3β, depletes Nrf2 and significantly sensitizes these cells. We are further exploring mechanisms, and at the same time screening biobanks of various tumors to determine the incidence of somatic loss of function mutations in Keap1 and mutations in the Pi3K pathway that activate it. This would represent a molecular signature of tumors that would be highly selectively sensitized by this strategy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 820. doi:1538-7445.AM2012-820
Almost Periodic Factorization of 2 × 2 Triangular Matrix Functions: New Cases of Off Diagonal Spectrum (2010)

Many known results on almost periodic factorization of almost periodic 2 × 2 triangular matrix functions of the form $$ \left[ {\begin{array}{*{20}c} {e^{i\lambda x} } & 0 \\ * & {e^{ - i\lambda x} } \\ \end{array} } \right] $$ are reviewed from a unified point of view, with particular attention to the case when the off diagonal entry is at most a quadrinomial almost periodic function. New results are obtained on almost periodic factorization for off diagonal entry having its Bohr-Fourier spectrum in a union of two shifted grids, i.e., arithmetic progressions, with the same difference, and perhaps an additional point. When specializing these results to the case of off diagonal almost periodic trinomials, new cases of factorability are obtained. The main technical tool is the Portuguese transformation, a known algorithm.
Enhanced Discrimination Techniques for Radar-Based On-Metal Identification Tags. (2011)

To mom and dad; the greatest parents in the universe. ii ACKNOWLEDGEMENTS Most importantly, I would like to thank my committee chair, Professor Kamal Sarabandi, for his kindness, motivation and support throughout this process. He nothing short of inspiring and I am grateful for the opportunity to pursue my PhD under the supervision of a person that I so deeply respect and admire. I would also like to thank Dr. Christopher McCarroll of Raytheon Corporation for his invaluable mentorship and guidance throughout this process both at Raytheon and at the University of Michigan. I am deeply grateful for his support along with that of Prof. Mahta Moghaddam, Prof. Anythony Grbic, and Prof. Jerome Lynch for their service on my dissertation committee and Raytheon IDS for their generous financial support of my post-graduate education. I would also like to acknowledge the financial
Co-inoculum of Beauveria brongniartii and B. bassiana shows in vitro different metabolic behaviour in comparison to single inoculums (2017)

The use of entomopathogenic fungi for biocontrol of plant pests is recently receiving an increased interest due to the need of reducing the impact of agricultural practices on the environment. Biocontrol efficacy could be improved by co-inoculation of different microorganisms. However, interactions between the fungal species can trigger or depress the biocontrol activity. Co-inoculation of two entomopathogenic fungi (Beauveria bassiana and B. brongniartii) was performed in vitro to evaluate the effects of their joint behaviour on a range of different carbon sources in comparison to single inoculation. The two species showed a very different metabolic profile by Phenotype MicroArray<sup>TM</sup>. B. bassiana showed a broader metabolism than B. brongniartii on a range of substrates. B. brongniartii showed a greater specificity in substrate utilization. Several carbon sources (L-Asparagine, L-Aspartic Acid, L- Glutamic Acid, m- Erythritol, D-Melezitose, D-Sorbitol) triggered the fungal metabolism in the co-inoculum. SSR markers and Real Time qPCR analysis showed that different substrates promoted either the growth of one or the other species, suggesting a form of interaction between the two fungi, related to their different ecological niches. The methodological approach that combines Phenotype MicroArray<sup>TM</sup> and SSR genotyping appeared useful to assess the performance and potential competition of co-inoculated entomopathogenic fungi.
Synthesis and properties of nucleoside 5'-phosphoazidates derived from guanosine and adenosine nucleotides: effect on elongation factors G and Tu dependent reactions (1977)

A new type of nucleoside poly (5'-phosphate) analogue, nucleoside 5"-phosphoazidate, with an azido group on the terminal phosphate of GTP, ATP, GDP, GMP, AND AMP, has been synthesized by nucleophilic displacement of the corresponding activated nucleosides by azide ion in yields of 25-45%. Guanosine 5-phosphoazidates is readily photolyzed by ultraviolet light; the corresponding adenosine derivative photolyzes more slowly. Guanosine 5'-O-(2-azidodiphosphate) and guanosine 5"-O-(3-azidotrophosphate) are competitive inhibitors of the formation of the ribosome-EF-G-GDP-fusidic acid complex and of the ribosome-EF-G GTPase. The dissociation constants of the former reaction are calculated to be 27 and 7 micrometer, respectively, or 270 and 73 times that of GDP. In the latter reaction, which is conducted in the absence of fusidic acid, the Ki values are 330 and 28 micrometer, respectively, or 12 and 1 times that of GDP. Guanosine 5"-O-(2-azidodiphosphate) and guanosine 5'-O-(3-azidotriphosphate) also complete with GTP in the formation of the binary complex. EF-Tu-GTP, with respective Kd values of 750 and 75 relative to GTP.
Alterations in Human Mitral Valve Mechanical Properties Secondary to Left Ventricular Remodeling: A Biaxial Mechanical Study (2022)

Secondary mitral regurgitation occurs when a left ventricular problem causes leaking of the mitral valve. The altered left ventricular geometry changes the orientation of the subvalvular apparatus, thereby affecting the mechanical stress on the mitral valve. This in turn leads to active remodeling of the mitral valve, in order to compensate for the ventricular remodeling. In this study, a biomechanical analysis was performed on eight human mitral valves with secondary mitral regurgitation and ten healthy human mitral valves to better understand this pathophysiology and its effect on the mechanical properties of these tissues. Samples were obtained from the anterior and posterior leaflet and used for planar biaxial mechanical experiments. Uniaxial experiments were performed on four groups of mitral valve chords: anterior basal, anterior marginal, posterior basal and posterior marginal chords. The mechanical response of the mitral valve leaflets was fitted to the May-Newman and Yin constitutive model, whereas the material parameters of the third order Ogden model were determined for the chord samples. Next, stiffnesses calculated at low and high stress levels were statistically analyzed. Leaflet samples with secondary mitral regurgitation showed a small thickness increase and a change in anisotropy index compared to healthy control valves. Diseased leaflets were more compliant circumferentially and stiffer radially, resulting in anisotropic samples with the radial direction being stiffest. In addition, chord samples were slightly thicker and less stiff at high stress in secondary mitral regurgitation, when grouped per leaflet type and insertion region. These results confirm mechanical alterations due to the pathophysiological valvular changes caused by left ventricular remodeling. It is important that these changes in mechanical behavior are incorporated into computational models of the mitral valve.
A 2.1 mW 2 MHz-BW 73.8 dB-SNDR Buffer-Embedded Noise-Shaping SAR ADC (2021)

This paper presents a buffer-embedded noise-shaping SAR ADC, whose input buffer separates the capacitive DAC (CDAC) and the sampling capacitor (C <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">S</sub> ) at the input and output of the input buffer. This compensates for the non-linearity of the input buffer and reduces the C <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">S</sub> value, resulting in a significant power saving in the input buffer. This buffer-embedded architecture enables the effective implementation of the following passive loop filter and enhances energy efficiency. A bootstrapping switch in the feedback CDAC is coupled to the output of the buffer, thereby avoiding a signal dependency due to the parasitic capacitance of the switch. The buffer-embedded noise-shaping SAR ADC occupies 0.08mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> in a 65 nm CMOS process and features a parasitic input capacitor of 0.2 pF. It achieves 73.8 dB SNDR, 77 dB DR and 87.3 dB SFDR in a 2 MHz bandwidth without any calibration. Including the power consumption of the input buffer, the ADC consumes only 2.1 mW.
Addition of Azomethine Ylides to Aldehydes: Mechanistic Dichotomy of Differentially Substituted α‐Imino Esters (2010)

Abstract The formal 1,3‐dipolar cycloaddition of azomethine ylides and aldehydes is explored, as hydrolysis of the resulting oxazolidine product gives facile access to valuable syn ‐β‐aryl‐β‐hydroxy‐α‐amino esters. The use of using benzaldehyde‐derived imines as the ylide precursor results in 1,3‐dipolar cycloaddition with high conversions but low diastereoselectivity. In contrast, the employment of benzophenone‐derived imines as the ylide precursor results in an aldol reaction, which gives the intermediate oxazolidine in high diastereoselectivity and requires a weak acid catalyst to achieve higher conversions.
IMPLEMENTATION OF QUASI-AUTONOMOUS PEER-ASSESSMENT ACTIVITIES USING A SAKAI-BASED E-LEARNING PLATFORM (2021)

J. García-Rupérez 1, M.J. Muñoz Portero1, M.A. Bes Piá1, M.E. Blasco Tamarit1, L.A. Tortajada Genaro1, M.J. Bañuls Polo1, B. Vidal1, P. Sanchis Kilders1, M.L. Fenollosa Ribera1, R. Sánchez Tovar2 1Universitat Politecnica de Valencia (SPAIN) 2Universitat de Valencia (SPAIN)