gebhart/patrepeval huggingface dataset:
Induction of a heat shock factor 1-dependent stress response alters the cytotoxic activity of hsp90-binding agents. (2000)

In addition to its classic role in the cellular stress response, heat shock protein 90 (Hsp90) plays a critical but less well appreciated role in regulating signal transduction pathways that control cell growth and survival under basal, nonstress conditions. Over the past 5 years, the antitumor antibiotics geldanamycin and radicicol have become recognized as selective Hsp90-binding agents (HBA) with a novel ability to alter the activity of many of the receptors, kinases, and transcription factors involved in these cancer-associated pathways. As a consequence of their interaction with Hsp90, however, these agents also induce a marked cellular heat shock response. To study the mechanism of this response and assess its relevance to the anticancer action of the HBA, we verified that the compounds could activate a reporter construct containing consensus binding sites for heat shock factor 1 (HSF1), the major transcriptional regulator of the vertebrate heat shock response. We then used transformed fibroblasts derived from HSF1 knock-out mice to show that unlike conventional chemotherapeutics, HBA increased the synthesis and cellular levels of heat shock proteins in an HSF1-dependent manner. Compared with transformed fibroblasts derived from wild-type mice, HSF1 knock-out cells were significantly more sensitive to the cytotoxic effects of HBA but not to doxorubicin or cisplatin. Consistent with these in vitro data, we found that systemic administration of an HBA led to marked increases in the level of Hsp72 in both normal mouse tissues and human tumor xenografts. We conclude that HBA are useful probes for studying molecular mechanisms regulating the heat shock response both in cells and in whole animals. Moreover, induction of the heat shock response by HBA will be an important consideration in the clinical application of these drugs, both in terms of modulating their cytotoxic activity as well as monitoring their biological activity in individual patients.
A General Method for Suzuki–Miyaura Coupling Reactions Using Lithium Triisopropyl Borates (2012)

Conditions for the Suzuki-Miyaura coupling of lithium triisopropyl borates are reported, as well as a procedure for a one-pot lithiation, borylation, and subsequent Suzuki-Miyaura coupling of various heterocycles with aryl halides. These borate species are much more stable toward protodeboronation than the corresponding boronic acids and can conveniently be stored on benchtop at room temperature.
Data from Prevalent and Diverse Intratumoral Oncoprotein-Specific CD8<sup>+</sup> T Cells within Polyomavirus-Driven Merkel Cell Carcinomas (2023)

&lt;div&gt;Abstract&lt;p&gt;Merkel cell carcinoma (MCC) is often caused by persistent expression of Merkel cell polyomavirus (MCPyV) T-antigen (T-Ag). These non-self proteins comprise about 400 amino acids (AA). Clinical responses to immune checkpoint inhibitors, seen in about half of patients, may relate to T-Ag–specific T cells. Strategies to increase CD8&lt;sup&gt;+&lt;/sup&gt; T-cell number, breadth, or function could augment checkpoint inhibition, but vaccines to augment immunity must avoid delivery of oncogenic T-antigen domains. We probed MCC tumor-infiltrating lymphocytes (TIL) with an artificial antigen-presenting cell (aAPC) system and confirmed T-Ag recognition with synthetic peptides, HLA-peptide tetramers, and dendritic cells (DC). TILs from 9 of 12 (75%) subjects contained CD8&lt;sup&gt;+&lt;/sup&gt; T cells recognizing 1–8 MCPyV epitopes per person. Analysis of 16 MCPyV CD8&lt;sup&gt;+&lt;/sup&gt; TIL epitopes and prior TIL data indicated that 97% of patients with MCPyV&lt;sup&gt;+&lt;/sup&gt; MCC had HLA alleles with the genetic potential that restrict CD8&lt;sup&gt;+&lt;/sup&gt; T-cell responses to MCPyV T-Ag. The LT AA 70–110 region was epitope rich, whereas the oncogenic domains of T-Ag were not commonly recognized. Specific recognition of T-Ag–expressing DCs was documented. Recovery of MCPyV oncoprotein–specific CD8&lt;sup&gt;+&lt;/sup&gt; TILs from most tumors indicated that antigen indifference was unlikely to be a major cause of checkpoint inhibition failure. The myriad of epitopes restricted by diverse HLA alleles indicates that vaccination can be a rational component of immunotherapy if tumor immune suppression can be overcome, and the oncogenic regions of T-Ag can be modified without impacting immunogenicity.&lt;/p&gt;&lt;/div&gt;
Nonlinear harmonic analysis of structures containing joints with impacts and friction (2014)

An algorithm is proposed which can be applied to finite element models in order to efficiently perform nonlinear harmonic analyses without neglecting nonlinear effects due to joint friction and impacts. In order to decrease the size of the nonlinear differential equation to be solved, the proposed algorithm reduces the structural matrices of the system to be investigated using the Craig-Bampton method after importing them from commercially available FE codes. Depending on the geometrical setup and materials of the system joints, different discretization assumptions can be applied. The implemented contact model is based on Coulomb friction and Newton impact constraints which are being determined by a linear complementarity problem (LCP) formulation. The computation itself is performed in time domain using a modified Newmark time stepping approach for numerical stability even if the time step size chosen is fairly large. Both the mathematical approach itself as well as numerical results are presented for the simple system of a cylindrical beam in contact with a rigid wall in order to give an in-depth description of the proposed algorithm.
Bioequivalence Study of Three Ciclosporin Capsule Formulations in Healthy Volunteers (2011)

The study was conducted in order to assess the bioequivalence of three capsule formulations containing 100 mg of ciclosporin (CAS 59865-13-3). 24 Healthy volunteers, 20 to 37 years of age (mean 26, SD 5.3 years), weighing 51 to 76 kg (mean 65, SD 7.0 kg) and a body height of 1.5 to 1.83 m (mean 1.68, SD 0.07 m) were enrolled in the study. Each volunteer received a single oral dose of 300 mg (3 100 mg ciclosporin capsules) on three separate occasions according to a randomized, single-dose, three-way crossover design with three formulations of ciclosporin: Treatment I (reference formulation, capsules), Treatment II (test formulation 1, soft gel capsules), Treatment III (test formulation 2, hard gel capsules). Blood samples for the determination of ciclosporin were drawn at scheduled intervals up to 56 h after dosing. Ciclosporin concentrations in whole blood were determined by a specific HPLC method with ultraviolet detection. Quantitation of ciclosporin was validated for concentrations range from 25 to 1600 ng/ml. Since the 90% confidence intervals for the “test/reference” mean ratio of the Log-transformed pharmacokinetic variables C<sub>max</sub>, AUC<sub>0–t</sub> and AUC<sub>0–∞</sub> were clearly within the bioequivalence range of 80% to 125%, the treatments were considered bioequivalent in terms of both the rate and extent of absorption.
Acquisition of a Combined Mechano-Electro-Chemical Characterization Equipment for Advanced Nanocomposites Research and Education (2009)

Abstract : We have acquired a custom-designed Nanonics Multiview 400 Combined microRaman, Scanning Probe Microscope (SPM), and Nanoindenter system. Such combined system integration permits correlation of SPM topography of a sample surface with microRaman spectra. The Nanonics SPM/NSOM component generates surface morphology images while Raman components can measure electrical properties and chemical signatures. The presence of the Nanoindenter allows simultaneous detection of Raman peaks under stress. The broad goal is to permit characterization of local mechanical, chemical and electrical properties in-situ and simultaneously in active polymers and nanocomposites. The proposed equipment will greatly impact an ongoing AFOSR project on active nanocomposites, as well as ongoing and proposed DoD and NSF projects lead by the Pis. The capabilities of the custom-designed Nanonics expand to nanoscale mechanical, electrical, and chemical properties of metallic and ceramic thin films and coatings, and MEMS and NEMS devices, extending its impact to a variety of ongoing and future collaborations and research projects. The combination of micron-scale and nano-scale techniques in the proposed equipment makes it uniquely capable of bridging the gap between interfacial interactions and macroscale properties in advanced materials in general and nanostructured materials in particular. The surface morphological information, internal stress, and electrical properties of such materials have been studied separately and the structure-property is yet to be related intrinsically. Having such a system will enable us to investigate the interfacial forces between components and understand the effects of molecular structure and inclusion distribution on nanocomposites. The simultaneous capabilities of the custom-designed equipment are unique and will complement and expand our research and current materials characterization infrastructure, specifically in the area of multifunctional materials.
Inhibition of bleomycin-induced DNA breakage by superoxide dismutase. (1981)

Inhibition of bleomycin (BLM)-induced DNA breakage by superoxide dismutase (SOD) has been reported and presumed to be due to its removal of the superoxide free radicals generated by BLM in the presence of iron(II). We have studied the possibility that the inhibitory effect might result from DNA-binding of SOD. The effect of copper-zinc SOD on BLM-induced DNA degradation was investigated using the PM-2 DNA fluorescence technique. PM-2 DNA was incubated with BLM in the presence or absence of native and heat-inactivated copper-zinc SOD as determined by the epinephrine autoxidation method. The concentrations of SOD required to inhibit 50% PM-2 DNA degradation for the native and the inactivated SOD were 100 and 120 microgram/ml, respectively. Analysis of the reaction mixture by agarose gel electrophoresis confirmed the absence of DNA degradation by BLM in the presence of either form of SOD. PM-2 DNA was shown to bind native or inactivated SOD by Sephadex G-100 column chromatography, fluorescence-quenching studies, and agarose gel electrophoresis. Thus, these results indicate that SOD is able to bind to PM-2 DNA and inhibit BLM-induced degradation independently of its free radical-scavenging activity. The inhibitor was more effective against BLM than other compounds which degrade PM-2 DNA. This suggests that SOD may bind to BLM-binding and/or BLM degradation sites in PM-2 DNA, and the observed inhibition is unrelated to its effects on free radicals.
What is the minimal vestibular function required for compensation? (1996)

Living with an uncompensated, abnormal vestibular system requires oppressive modification of life style and often prevents return to work and activities of daily living. Patients with vestibular abnormalities were studied to determine the minimal residual vestibular function required to achieve compensation. Three groups of patients with (a) complete unilateral loss of vestibular function with normal horizontal canal-vestibulo-ocular (HCVOR) function in the opposite ear, (b) complete unilateral loss with abnormal HCVOR function in the opposite ear, and (c) bilateral reduction of vestibular function from aminoglycoside toxicity underwent vestibuloocular (VOR), optokinetic (OKN), visual-VOR (VVOR), and computerized dynamic posturography (CDP) tests before and after therapeutic procedures. Results suggest that a minimal VOR response amplitude must be present for compensation of VVOR function to occur. The roles of VOR and OKN phase shifts in vestibular compensation are more complicated and require further study. Compensation of vestibulospinal function does not necessarily accompany VOR or VVOR compensation. Ascending and descending vestibular compensatory mechanisms may involve different spatial sensory inputs. Results of these studies have important implications for the diagnosis and treatment of patients with vestibular disorders, including selection and monitoring of patients for therapeutic regimens such as vestibular nerve section and streptomycin therapy.
Low-temperature GaAs films grown on Ge and Ge/SiGe/Si substrates (2003)

The growth and structural properties of low-temperature GaAs (LT-GaAs) films grown on Ge/SiGe/Si substrates using solid-source molecular-beam epitaxy were investigated. Identical structures were also grown on both Ge and GaAs substrates in order to ascertain the effects of heterovalent interfaces, lattice mismatch, and surface morphology on the structural properties and excess As incorporation of LT-GaAs. Triple-axis x-ray diffraction measurements revealed nearly identical lattice expansion due to excess As incorporation for LT-GaAs layers on all substrates, with the excess As concentration estimated to be 0.34%. Subsequent in situ annealing resulted in complete layer relaxation coupled with the formation of randomly distributed As precipitates of similar sizes throughout the LT-GaAs layers on each substrate as determined by transmission electron microscopy. Secondary ion mass spectroscopy measurements confirmed the incorporation of excess As to be identical for growth on each substrate type, indicating that LT-GaAs with ideal structural properties can be grown on compositionally graded SiGe/Si substrates with no apparent impact from crosshatched surface morphology or heterovalent interfaces.
Full InGaN red (625 nm) micro-LED (10 μm) demonstration on a relaxed pseudo-substrate (2021)

International audience
Steady-State Characteristics of Resonant Switched Capacitor Converter (2004)

Conventional switched capacitor converters have an inherent drawback that their efficiency is much decreased as the output current is increased. This inherent drawback is due to a periodical forced charging and discharging operation in the internal switched capacitors accompanied by a large capacitor current, so that their efficiency can not be increased by decreasing its internal resistance. As a result, conventional switched capacitor converters have been limited to be used with a very small output current. To solve this problem we presented a novel switched capacitor converter topology that uses a resonant operation instead of the forced charging and discharging operation. Its advantage over a conventional switched capacitor converter is a high efficiency even in a high output current region. In this paper, the operation analysis and steady-state characteristics are described in detail for a half buck type switched capacitor converter, and they are confirmed by experiments.
Gastrointestinal involvement attenuates COVID-19 severity and mortality (2020)

Intestinal infection with SARS-CoV-2 is associated with a mild inflammatory response and improved clinical outcomes.
A new antenna concept for RF excitation at 9.4T (2013)

Purpose/Introduction: By introducing of the higher static magnetic field, B1 + field distribution becomes inhomogeneous due to the shorter wavelength in tissue. Different experimental hardware and methods are used in order to reduce B1 + field inhomogeneity [1-3]. In this work we present a new antenna concept used for the first time as RF transmit coil at 9.4T. Antenna is used in two configurations which produce complementary B1 + field patterns that cover whole head region. Subjects and Methods: Experiments were performed on a 9.4T MR scanner (Siemens Medical Solutions, Erlangen, Germany). The original antenna is described in [4] and is modified for operation inside of 9.4T scanner. Proposed antenna does not contain any lumped elements or matching circuits and all antenna parts are made of copper. Antenna's geometry is shown in Fig. 1. Antenna consists of an ‘empty' rectangular box that has five sides and is placed 2mm above ground plane. Ground plane size is 300x300mm and box size is 210x200x55mm. Two short copper straps connect box sides and ground plane. Antenna 1 and antenna 2 are used for RF excitation. The difference between them is in position of ground plane connections. Antenna 1 has ground plane connections starting from the midpoint of the box sides while short straps of the antenna 2 are 7mm shifted from the midpoint (Fig. 1b). In measurement setup, antenna was placed at 15cm distance from the phantom's head. Figure 2. Measured B1 + field patterns in central sagittal slice (uT/V) with antenna 1 (a) and antenna 2 (b). Figs. 2a and 2b are initial measurement results with presented antennas. Different current distributions on antennas result in complementary B1 + field measured on a phantom. Replacement of short grounding straps with RF MEMS switches is intended which would allow obtaining presented results with one antenna. Discussion/Conclusion: A new antenna has been used for the first time as RF transmitting coil at 9.4T. Antenna is of very simple geometry without any lumped elements. Initial measurements performed with two antennas show B1 + produced over large complementary parts of head. Producing a homogeneous B1 + field with one antenna is intended.
Fibronectin binding to thrombin-stimulated platelets: evidence for fibrin(ogen) independent and dependent pathways (1985)

Plasma fibronectin binds in a specific and saturable manner to thrombin-stimulated platelets. gamma-Thrombin stimulated 80% as much fibronectin binding to platelets as alpha-thrombin with conversion of less than or equal to 1% of platelet fibrinogen to fibrin. Afibrinogenemic and normal platelets bound similar quantities of fibronectin in the presence of calcium or magnesium-ethylene glycol tetra-acetic acid (EGTA). These observations indicate that fibronectin can interact with platelets without involvement of fibrin or fibrinogen. Nevertheless, two different effects of fibrin(ogen) on fibronectin binding were observed. First, exogenous fibrinogen inhibited fibronectin binding to thrombin-stimulated platelets. This inhibition was unidirectional, as fibronectin did not inhibit fibrinogen binding to ADP or thrombin-stimulated cells. Second, formaldehyde-fixed cells with surface-associated fibrin bound significant quantities of fibronectin. This interaction required calcium and did not occur on fixed cells with or without surface-bound fibrinogen. A portion of the ligand bound to fixed cells with surface-associated fibrin was modified to form a derivative with a molecular weight identical to that of the fibronectin subunit cross-linked to the alpha-chain of fibrin. This high mol wt derivative was also observed to a variable extent with living cells in the presence of magnesium or calcium but not in the presence of magnesium-EGTA. Thus, fibronectin binds to platelets by at least two mechanisms: (1) a fibrin(ogen)-independent pathway that requires divalent ions and is inhibited by exogenous fibrinogen; and (2) a fibrin-dependent pathway with an absolute calcium requirement. With nonaggregated, thrombin-stimulated platelets, the former pathway appears to predominate.
Polar effects in free radical reactions. Induced decompositions of peroxo compounds in the substitution of heteroaromatic bases by nucleophilic radicals (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPolar effects in free radical reactions. Induced decompositions of peroxo compounds in the substitution of heteroaromatic bases by nucleophilic radicalsFrancesco Minisci, Claudio Giordano, Elena Vismara, Silvio Levi, and Vito TortelliCite this: J. Am. Chem. Soc. 1984, 106, 23, 7146–7150Publication Date (Print):November 1, 1984Publication History Published online1 May 2002Published inissue 1 November 1984https://pubs.acs.org/doi/10.1021/ja00335a048https://doi.org/10.1021/ja00335a048research-articleACS PublicationsRequest reuse permissionsArticle Views681Altmetric-Citations48LEARN 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
A dual-band low-profile bidirectional antenna with a metal cover and a triangular monopole antenna (2023)

This paper describes a dual-band low-profile bidirectional antenna fed by a triangular monopole antenna (TMA) with a U-shaped metal cover. In addition to the higher band resonance of the TMA, another lower band resonance is generated by the coupling between the TMA and the metal cover so that the proposed antenna has dual operation bands. The proposed antenna has bidirectional radiation patterns for both bands, and the peak actual gain are 2.2dBi and 4.7dBi at the lower band and the higher band, respectively. The measured and analyzed results of the proposed antenna were in good agreement.
CD4+ T lymphocytes mediate in vivo clearance of plasmid DNA vaccine antigen expression and potentiate CD8+ T-cell immune responses (2008)

There is evidence that the limited immunogenicity of plasmid DNA vaccines is the result, at least in part, of the rapid clearance of vaccine antigen expression by antigen-specific immune responses. However, the cell types responsible for the clearance of plasmid DNA vaccine antigens are not known. Here we demonstrate that macrophages, NK cells, and CD8(+) T cells did not significantly contribute to the DNA antigen clearance but CD4(+) T cells played the crucial role in attenuating plasmid DNA vaccine antigen expression. Adoptive transfer experiments demonstrate that CD4(+) T cells facilitated DNA vaccine antigen clearance in a Fas/FasL-dependent manner. Furthermore, we show that depletion of CD4(+) T cells prevented the clearance of vaccine antigen and the appearance of a CD8(+) T-cell immune response. Inoculation of major histocompatibility complex class II KO mice with the plasmid DNA led to persistent antigen expression and abolition of a CD8(+) T-cell immune response. Importantly, the prolongation of antigen expression by disrupting the CD4(+) T-cell Fas/FasL myocytes signaling led to a 3- to 5-fold increase of antigen-specific CD8(+) T-cell responses. These data demonstrate a dominant role of CD4(+) T cell-mediated cytotoxicity in plasmid DNA vaccine antigen clearance.