gebhart/patrepeval huggingface dataset:
Utility of customized PEG linkers for the delivery of oligonucleotides without the use of transfection reagents (2007)

C119 Background: Locked Nucleic Acid (LNA) represents the latest antisense technology with high target binding affinity and tissue stability. Nanomolar to sub-nanomolar concentrations of LNAs can inhibit mRNA expression when tissue culture cells are treated with LNAs in the presence of transfection reagents (e.g. lipofectamine). Therefore, LNA has emerged as a promising new therapeutic for many human diseases including cancer. Systemic delivery of LNA, as well as any oligonucleotide, would benefit from advances involving pharmacological properties such as cell penetration and important pharmacokinetic (PK) profiles. We describe here the utility of Customized PEG linkers that mediate potent down regulation of target mRNA in human tumor cells in vitro in the absence of transfection reagents.  Material and Methods: Positively charged Customized PEG linkers were synthesized by incorporating either peptide fragments, or synthetic positive moieties into the backbone of PEG polymers. These PEG polymers were then converted to releasable linkers before being conjugated with LNA. An anti-survivin LNA oligonucleotide was used as a model compound for proof-of-concept of our technology development. This oligonucleotide was also conjugated with FITC dye at the 3’-end for cellular uptake study by fluorescence and confocal microscopy technology and FACS method. Target gene down modulation of PEG-LNA conjugates was studied using Real-Time QPCR technique in a panel of tumor cell lines in the absence of any transfection agents (i.e. lipofectamine).  Results: The PEG-LNA conjugates are stable under physiological conditions and have shown enhanced stability in plasma. Excellent intracellular delivery of PEG-LNA-FITC conjugate was demonstrated by fluorescence and confocal microscopy method with the transfection efficiency comparable to cells transfected with lipofectamine. PEG-LNA conjugates have shown concentration-dependent and specific target mRNA gene down modulation by Real-Time QPCR study in a panel of tumor cell lines without using lipofectamine. Three lead constructs have been identified with IC50 values below 200 nM in A549 human lung cancer cells.  Conclusions: Delivery of LNA oligonucleotides using Customized PEG linkers has improved the in vitro cellular uptake into cancer cells. PEG-LNA conjugates can knock down target mRNA in a concentration dependent fashion with great sequence specificity. The lead compounds have achieved IC50 values of less than 200 nM in A549 human lung cancer cells. Positively charged Customized PEG linkers may provide a promising approach for more efficient in vivo delivery of oligonucleotides including LNA and siRNA. Preclinical human xenograft models will be used to assess biodistribution, tumor-specific down-modulation of target mRNA, and efficacy of Customized PEG Linker technology.
Enhanced laser crystallization of thin film amorphous molybdenum disulfide (MoS2) by means of pulsed laser ultrasound (2019)

Experimental evidence is presented that pulsed laser generated ultrasound can reduce the power necessary to phase convert a nm-scale amorphous film into the crystalline phase. The amount of energy carried by pulsed ultrasound is scant when compared to the CW laser power used to crystallize but the effect is substantial. The evidence points to the extra-ordinary effects possible when a small energy perturbation is applied at a critical juncture in dynamical systems. The candidate system is MoS<sub>2</sub> (10 nm) sputtered on yttrium-stabilized zirconia single crystal substrate. A focused CW laser elevates the film - initially in a metastable disordered phase - to the order-disorder conversion (crystallization) temperature. Approximately 25 spot sizes removed from the heating source is a second, high repetition rate laser that induces ultrasonic excitation within the film/substrate via thermoelastic action. The processing is done on a moving stage with direct write patterning control. High resolution ex situ Raman spectroscopy, optical profilometry, and TEM are used to characterize the converted material. For this experimental configuration, we measure a 10% reduction in the heating power required to initiate crystalline formation. The measured phenomenon cannot be attributed to excess thermal energy supplied by the ultrasonic laser.
Microdistribution of fluorescently-labeled monoclonal antibody in a peritoneal dissemination model of ovarian cancer (2010)

The microdistribution of therapeutic monoclonal antibodies within a tumor is important for determining clinical response. Nonuniform microdistribution predicts therapy failure. Herein, we developed a semiquantitative method for measuring microdistribution of an antibody within a tumor using in situ fluorescence microscopy and sought to modulate the microdistribution by altering the route and timing of antibody dosing. The microdistribution of a fluorescently-labeled antibody, trastuzumab (50-&mu;g and 150-&mu;g intraperitoneal injection (i.p.), and 100-&mu;g intravenous injection (i.v.)) was evaluated in a peritoneal dissemination mouse model of ovarian cancer. In addition, we evaluated the microdistribution of concurrently-injected (30-&mu;g i.p. and 100-&mu;g i.v.) or serial (two doses of 30-&mu;g i.p.) trastuzumab using in situ multicolor fluorescence microscopy. After the administration of 50-&mu;g i.p. and 100-&mu;g i.v. trastuzumab fluorescence imaging showed no significant difference in the central to peripheral signal ratio (C/P ratio) and demonstrated a peripheral-dominant accumulation, whereas administration of 150-&mu;g i.p. trastuzumab showed relatively uniform, central dominant accumulation. With concurrent-i.p.-i.v. injections trastuzumab showed slightly higher C/P ratio than concurrently-injected i.p. trastuzumab. Moreover, in the serial injection study, the second injection of trastuzumab distributed more centrally than the first injection, while no difference was observed in the control group. Our results suggest that injection routes do not affect the microdistribution pattern of antibody in small peritoneal disseminations. However, increasing the dose results in a more uniform antibody distribution within peritoneal nodules. Furthermore, the serial i.p. injection of antibody can modify the microdistribution within tumor nodules. This work has implications for the optimal delivery of antibody based cancer therapies.
Ebola Virus Modulates Transforming Growth Factor β Signaling and Cellular Markers of Mesenchyme-Like Transition in Hepatocytes (2014)

Ebola virus (EBOV), formerly Zaire ebolavirus, causes a severe hemorrhagic disease in humans and nonhuman primates and is the most lethal Ebola virus species, with case fatality rates of up to 90%. Although EBOV is considered a worldwide concern, many questions remain regarding EBOV molecular pathogenesis. As it is appreciated that many cellular processes are regulated through kinase-mediated phosphorylation events, we employed temporal kinome analysis to investigate the functional responses of human hepatocytes to EBOV infection. Administration of kinase inhibitors targeting signaling pathway intermediates identified in our kinome analysis inhibited viral replication in vitro and reduced EBOV pathogenesis in vivo. Further analysis of our data also demonstrated that EBOV infection modulated TGF-β-mediated signaling responses and promoted "mesenchyme-like" phenotypic changes. Taken together, these results demonstrated that EBOV infection specifically modulates TGF-β-mediated signaling responses in epithelial cells and may have broader implications in EBOV pathogenesis.
Nano-analytical investigation of the forming process in an HfO2-based resistive switching memory (2021)

Metal oxide-based resistive random access memory devices are highly attractive candidates for next-generation nonvolatile memories, but the resistive switching phenomena remain poorly understood. This article focuses on the microscopic understanding of the initial forming step, which is decisive for the switching process. The integrated resistive switching memory effect in Ti/HfO2/TiWN metal insulator metal structures is studied. After forming, transmission electron microscopy investigations pointed out the presence of a funnel-shaped region, in the ON state of the cell, where slightly oxidized Ti (TiOx) was present within HfO2 dielectric. Modeling of the measured ON state conductance of the cell with the semi-classical approximation is consistent with a conductive nanometric TiOx filament (or a sum of sub-nanometric TiOx filaments) present in the funnel-shaped region. The conductive area is likely formed by diffusion after the dielectric breakdown.
Recombinant antigen expression on yeast surface (RAYS) for the detection of serological immune responses in cancer patients. (2003)

The serological analysis of antigens by recombinant expression cloning (SEREX) has identified a multitude of new tumor antigens in many different tumor entities. These antigens can be grouped into different classes according to their specificities, with cancer/testis antigens appearing to be the most attractive candidates for vaccine development. The observation that CD8 and CD4 T-cell responses against cancer/testis antigens such as NY-ESO-1 correlate with the presence of specific antibodies demonstrates the importance of serological monitoring patients participating in vaccine trials. However, all serological assays available (Western blot, phage display and ELISA) are hampered by the fact that the protein cannot be analyzed in its natural conformation. We have thus developed a yeast display system where the antigen is expressed on the yeast surface (RAYS), allowing for a more natural folding of the protein. To validate this approach we displayed the A33 colorectal cancer antigen on the yeast cell surface and demonstrated specific binding by an A33 monoclonal antibody recognizing a conformation-dependent epitope on the A33 antigen. We then compared RAYS with the more commonly used ELISA and Western blot serological monitoring methods by analyzing 50 sera from cancer patients with known NY-ESO-1 antibody status and 10 sera from patients with unknown SSX2 antibody status in a blind fashion. RAYS appears at least equivalent to both ELISA and Western blotting for the monitoring of antibodies against NY-ESO-1 as regards specificity and sensitivity, while antibodies against SSX2 were detected more frequently by RAYS than by ELISA or phage display.
Circulating fluidized bed with moving bed downcomers and gas sealing between reactors (2023)

A system and process for carrying out one or more chemical reactions are provided and include one or more chemical reactors having particulate solids forming a bed therein, and a gas stripping zone forming a non-mechanical seal between said reactors which includes a conduit connecting the reactors. The conduit includes an inlet for a stripping gas which is adapted to prevent process gas from passing between reactors while permitting particulate solids to pass between reactors.
Juicebox Provides a Visualization System for Hi-C Contact Maps with Unlimited Zoom (2016)

Hi-C experiments study how genomes fold in 3D, generating contact maps containing features as small as 20 bp and as large as 200 Mb. Here we introduce Juicebox, a tool for exploring Hi-C and other contact map data. Juicebox allows users to zoom in and out of Hi-C maps interactively, just as a user of Google Earth might zoom in and out of a geographic map. Maps can be compared to one another, or to 1D tracks or 2D feature sets.
R410 – Immunosuppressive Properties of Tonsil‐Derived MSCs (2008)

Problem We have previously shown that stroma of human palatine tonsils contains mesenchymal stem cells (MSCs) that can be isolated and expanded in culture. These tonsil‐derived MSCs (T‐MSCs) show multipotent differentiation properties, i.e. can differentiate along multiple mesenchymal lineages, including osteoblasts, chondrocytes, adipocytes, and myocytes. Recent findings also show that MSCs display immunoregulatory properties. Although the exact immunosuppressive mechanisms are unknown, the capacity of MSCs to suppress T‐cell proliferation stimulated by allogeneic lymphocytes, dendritic cells, and phytohemaglutinin (PHA) is well documented. This study explores immunosuppressive characteristics of T‐MSCs and compares them with characteristics of bone marrow‐derived MSCs (BM‐MSCs), a well‐characterized cell population. Methods The mixed lymphocyte reaction (MLR) using human peripheral blood mononuclear cells (PBMC) from healthy donors and xenogeneic murine splenocytes was used to test the immunosuppressive properties of T‐MSCs and BMMSCs. Indoleamine 2,3‐dioxygenase (IDO) enzyme activity was measured spectrophotometrically based on tryptophan‐to‐kynurenine conversion in the supernatant. Interferon (IFN)‐g in culture supernatants was quantified using a commercially available ELISA kit. Results Addition of BM‐MSCs and T‐MSCs both inhibited the PHA‐induced proliferative response of PBMC and xenogeneic splenocytes. The difference in immunosuppressive activity correlates with the level of cell surface interferon (IFN)‐g receptor as well as the differential ability of IFN‐g to stimulate of IDO activity by T‐MSCs compared to BM‐MSCs. Conclusion T‐MSCs share similar immunosuppressive characteristics as BM‐MSCs in MLR. The immunosuppressive activity is significant and dose‐dependent, although at a lower level than that of BM‐MSCs. Significance Owing to their ease of isolation, rapid proliferation in the culture and self‐renewal capacity, MSCs to date are considered an attractive candidate cell type for the development of novel cell‐based therapies. They could be relevant in a wide range of clinical applications, including tissue and organ repair, drug or gene delivery to diseased tissues, improvement of allogenic hematopoietic cell transplantation, and the management of graft‐versus‐host disease. Support Supported by NIAMS Intramural Research Program (NIH ZO1 AR 41131). Sasa Janjanin is a recipient of the Fulbright Scholarship of the U.S. Department of State.
Immunization with superantigen-derived oligopeptides protect against S. aureus bacteremia (VAC8P.1058) (2015)

Abstract Staphylococcal superantigens are exotoxins that play a major role in disease pathogenesis. Using a T cell epitope prediction tool from the Immune Epitope Database Analysis Resource (IEDB) site, sequences within staphylococcal enterotoxin A and B (SEA, SEB) and Toxic Shock Syndrome Toxin with high affinity towards H2-Iab were identified and oligopeptides SEA_aa116-128, SEB_aa16-28 and TSST-1_aa212-224 were generated. C57BL/6 mice were immunized with a cocktail of oligopeptides or whole toxins in Al(OH)3. Serum samples from peptide-immunized mice tested positive towards individual peptides and whole toxins, however, samples from mice immunized with whole toxins did not bind to any of the peptides. To determine peptide-specific T cell response primed CD4 T cells isolated from spleens and total LNs of immunized mice were co-cultured with peptide-pulsed BMDCs and cytokine response was evaluated. Only cells of peptide-immunized mice resulted in elevated levels of IL-4, IL-5, IL-10, IL-13, GM-CSF, IFNg and TNFa, while cells obtained from whole toxin-immunized mice did not differ from baseline levels. To evaluate protective efficacy of peptides against toxin expressing strains, immunized mice were infected intravenously with MNHOCH (SEB+) or Newman (SEA+) and monitored up to 13 days. Mice that were infected with MNHOCH showed significantly extended survival compared to non-immunized mice (P=0.03). No significant difference in survival was observed when infected with strain Newman.
Testing, Repairing and Packaging Technology for the CMOS-MEMS Integrated Tactile Sensor (2013)

The CMOS-MEMS integrated tactile sensor enables the robot to have dense and large area tactile sensor on the whole body. The ASIC (Application Specific Integrated Circuit) with the CMOS technology provides the communication function for the bus connected tactile sensor. The size of integrated chips is reduced by wafer-level-packaging (WLP) technology down to mm-scale size. Because the yield of the fabrication process of the tactile sensor will be a critical issue for this sensor network system, the testing and repairing procedure should be developed at the experimental phase, as well as designing the wafer-level fabrication process. The testing and repairing process in the middle of the fabrication provides a quick feedback to the yield optimization. In this paper, a novel process flow for testing and repairing in the process of the fabrication was developed. The test environments were prepared at each checkpoint of the fabrication process, and repairing process with Focused Ion Beam (FIB) was also applied to modify and repair the device. Finally, completed tactile sensors are fabricated with about 40% yield, and mounted on the flexible cable by the developed low-temperature flip chip bonding technology.
Numerical calculation and experimental validation of RCS analysis for radome-enclosed scatterer by using PMCHWT-formulation (2011)

This paper investigates the accuracy of RCS analysis for radome-enclosed scatterer by using the PMCHWT-formulation. The analysis method based on a surface integral equation known as the PMCHWT-formulation is outlined shortly. We show that calculated scattering cross section patterns of a dielectric coated conducting sphere agree with exact solutions. Then a RCS pattern of an acrylic hemisphere covered conducting disk is compared with measurement result. Calculated RCS patterns of ellipsoidal radome-enclosed scatterer are also presented. We verify the method of moments using the PMCHWT-formulation is sufficiently accurate for RCS analysis of radome-enclosed scatterer.
A 10 fJ·K2 Wheatstone Bridge Temperature Sensor With a Tail-Resistor-Linearized OTA (2020)

This article describes a highly energy-efficient Wheatstone bridge temperature sensor. To maximize sensitivity, the bridge is made from resistors with positive (silicided diffusion) and negative (poly) temperature coefficients. The bridge is balanced by a resistive (poly) FIR-DAC, which is part of a 2nd-order continuous-time delta-sigma modulator (CTΔΣM). Each stage of the modulator is based on an energy-efficient current-reuse OTA. To efficiently suppress quantization noise foldback, the 1st stage OTA employs a tail-resistor linearization scheme. Sensor accuracy is enhanced by realizing the poly arms of the bridge and the DAC from identical unit elements. Fabricated in a 180-nm CMOS technology, the sensor draws 55 μW from a 1.8-V supply and achieves a resolution of 150 μKrms in an 8-ms conversion time. This translates into a state-of-the-art resolution figure-ofmerit (FoM) of 10 fJ·K2. Furthermore, the sensor achieves an inaccuracy of ±0.4 °C (3σ) from -55 °C to 125 °C after a ratio-based one-point trim and systematic non-linearity removal, which improves to ±0.1 °C (3σ) after a 1st-order fit.
Fast stability analysis of large-scale SRAM arrays and the impact of NBTI degradation (2009)

This paper presents Read Margin analysis for large SRAM arrays with a fast test method that even can be realized in dual-V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DD</sub> product chips. Classical Static Noise Margin (SNM) is mostly suitable for single-cell simulation. Read Margin (RM) measurement allows analysis of large arrays and correlates to SNM, but requires a dedicated test structure and long measurement time. The presented method analyzes the flipping of cells over varying supply voltage. The stability of large arrays can be characterized in read as well as in hold state depending on the state of the access transistors. Applying this method, the impact of Negative Bias Temperature Instability (NBTI) is demonstrated on both Read and Hold Margin in a 65 nm low power technology.
Variability of radiation output dynamic range in modern cardiac catheterization imaging systems (1998)

Automatic exposure control (AEC) is one of the most important characteristics for optimizing cardiac catheterization imaging; this allows the X-ray system to provide sufficient radiation output under a variety of clinical conditions so that a satisfactory image is obtained. AEC was assessed in 97 cardiac catheterization laboratories using a standard set of phantoms. Three different copper attenuators were used to simulate three patient sizes. As magnification increased, many systems had limited dynamic range and were unable to increase radiation output. With increasing atttenuator thickness, the problem worsened. With the thickest attenuator and largest magnification (4.5"-5.0" FOV), 60% of systems could not achieve the typical 70% increase in exposure while 20% were unable to increase radiation output at all.
Human tooth, by near-ambient pressure x-ray photoelectron spectroscopy (2019)

Near-ambient pressure x-ray photoelectron spectroscopy (NAP-XPS) is a less traditional form of XPS that allows samples to be analyzed at relatively high pressures, i.e., greater than 2500 Pa. With NAP-XPS, XPS can be used to analyze moderately volatile liquids, biological samples, porous materials, and/or polymeric materials that outgas significantly. In this submission, the authors present the NAP-XPS survey, C 1s, O 1s, Ca 2p, and P 2p narrow scans from a human adult molar tooth, a biological material that would be challenging to analyze by conventional approaches. No pretreatment or cleaning of this dental specimen was performed prior to analysis. Three different regions (top, middle, and root) of the tooth were analyzed. The survey spectra, which differed considerably from each other, show the presence of carbon, oxygen, nitrogen, calcium, and phosphorous. Tin and sulfur are also present in small amounts on the top part of the tooth. C 1s narrow spectra are well fitted with four synthetic peaks.
Correction to Structure–Activity Relationship of N,N′-Disubstituted Pyrimidinetriones as CaV1.3 Calcium Channel-Selective Antagonists for Parkinson’s Disease (2013)

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionCorrection to Structure–Activity Relationship of N,N′-Disubstituted Pyrimidinetriones as CaV1.3 Calcium Channel-Selective Antagonists for Parkinson's DiseaseSoosung Kang, Garry Cooper, Sara Fernandez Dunne, Chi-Hao Luan, D. James Surmeier, and Richard B. Silverman*Cite this: J. Med. Chem. 2013, 56, 14, 5984Publication Date (Web):July 15, 2013Publication History Published online15 July 2013Published inissue 25 July 2013https://pubs.acs.org/doi/10.1021/jm400891rhttps://doi.org/10.1021/jm400891rcorrectionACS PublicationsCopyright © 2013 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 Views752Altmetric-Citations-LEARN 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 (127 KB) Get e-Alertsclose Get e-Alerts