gebhart/patrepeval huggingface dataset:
mAbs toBacillus anthraciscapsular antigen for immunoprotection in anthrax and detection of antigenemia (2004)

Bacillus anthracis is surrounded by an antiphagocytic polypeptide capsule composed of poly gamma-D-glutamic acid (gammaDPGA). gammaDPGA has been identified recently as a potential target for vaccine development. Studies of the role of gammaDPGA in disease have been hampered by the poor Ab response to this antigen and the lack of immunochemical reagents. As a consequence, neither the extent of gammaDPGA production during anthrax nor the protective activity of gammaDPGA Abs in inhalation anthrax are known. Here we report production of IgG Abs to gammaDPGA in mice following an immunization regimen using gammaDPGA in combination with agonist mAbs to CD40. mAbs were produced that are specific for gammaDPGA. Passive immunization with gammaDPGA mAbs protected >90% of mice in a pulmonary model of anthrax that was lethal in control mice (P < 0.0001). Use of gammaDPGA mAb in an antigen detection immunoassay found that the appearance of gammaDPGA in serum coincided with the emergence of bacteremia. These studies identify CD40 stimulation as a means for production of Ab and generation of mAbs against a weakly immunogenic antigen and demonstrate that the capsule is an effective target for immunoprotection and for antigen detection in the diagnosis of anthrax.
Epidermal growth factor receptor transcriptionally up-regulates vascular endothelial growth factor expression in human glioblastoma cells via a pathway involving phosphatidylinositol 3'-kinase and distinct from that induced by hypoxia. (2000)

Glioblastomas are highly vascular malignant brain tumors that often overexpress vascular endothelial growth factor (VEGF). They also frequently overexpress epidermal growth factor receptor (EGFR) and contain regions of hypoxia, both conditions that can induce VEGF. We examined VEGF regulation in U87 MG human glioblastoma cells and in U87/T691 cells, a clonal derivative that contains a truncated erbB2/Neu receptor that interferes with EGFR signaling through the formation of nonfunctional heterodimeric receptor complexes. U87/T691 cells contained approximately one-half as much VEGF mRNA as did U87 MG cells under normoxic conditions (21% oxygen). Pharmacological inhibition of EGFR, Ras, or PI(3) kinase, but not MAP kinase, led to a significant decrease in VEGF mRNA levels in U87 MG cells. VEGF promoter activity in transient transfections was decreased by either pharmacological or genetic inhibition of EGFR, Ras, or phosphatidylinositol 3'-kinase [PI(3) kinase]. However, inhibition of PI(3) kinase or EGFR did not completely abolish induction of VEGF mRNA by hypoxia (0.2% oxygen). Likewise, VEGF mRNA expression was induced 3-fold by hypoxia in EGFR-inhibited U87/T691 cells, comparable with the fold induction seen in parental U87 MG cells, although the absolute level of message under hypoxia was higher in U87 MG cells. In transient transfections, a luciferase reporter construct containing a 1.2-kb fragment of the VEGF promoter, lacking the known hypoxic-responsive element (HRE), showed up-regulation after EGF stimulation to the same degree as the full-length, 1.5-kb VEGF promoter construct retaining the HRE. Furthermore, activity of the HRE-deleted, 1.2-kb promoter luciferase reporter was down-regulated by PI(3) kinase inhibition. Therefore, in glioblastoma cells, transcriptional regulation of the VEGF promoter by EGFR appears to involve Ras/PI(3) kinase and to be distinct from signals induced by hypoxia.
Well-Differentiated Human Airway Epithelial Cell Cultures (2004)

The airway epithelium occupies a critical environmental interface, protecting the host from a wide variety of inhaled insults, including chemical and particulate pollutants and pathogens. The coordinated regulation of ion and water transport, mucous secretion, and cilia beating underlies mucociliary clearance. Physical trapping and removal of harmful substances, in combination with baseline or inducible secretion of antimicrobial factors, antioxidants, and protease inhibitors and recruitment of nonspecific inflammatory cells (neutrophils, monocytes), constitutes airway innate host defense.
TeV cosmic-ray proton and helium spectra in the myriad model II (2015)

International audience
Dual-Mode Ultrasound Phased Arrays for Image-Guided Surgery (2006)

A 64-element, 1 MHz prototype dual-mode array (DMUA) with therapeutic and imaging capabilities is described. Simulation and experimental results for the characterization of the therapeutic operating field (ThxOF) and imaging field-of-view (IxFOV) for a DMUA are given. In addition, some of the special considerations for imaging with DMUAs are given and illustrated experimentally using wire-target arrays and commercial, quality-assurance phantoms. These results demonstrate what is potentially the most powerful advantage of the use of DMUAs in image-guided surgery; namely, inherent registration between the imaging and therapeutic coordinate systems. We also present imaging results before and after discrete and volumetric HIFU-induced lesions in freshly-excised tissues. DMUA images consistently show changes in echogenicity after lesion formation with shape and extent reflecting the actual shape of the lesion. While changes in echogenicity cannot be used as an indicator of irreversible HIFU-induced tissue damage, they provide important feedback on the location and extent of the expected lesion. Thus, together with the self-registration property of DMUAs, lesion images can be expected to provide immediate and spatially-accurate feedback on the tissue response to the therapeutic HIFU beams. Based on the results provided here, the imaging capabilities of DMUAs can add unique features to other forms of image guidance, e.g. MRI, CT and diagnostic ultrasound.
Palladium‐Mediated [2+1] Cycloaddition of Norbornene Derivatives with Ynamides (2013)

Abstract An efficient palladium‐catalyzed [2+1] cycloaddition between ynamides and norbornenes or norbornadienes is reported. Both phosphapalladacycles and palladium/secondary phosphine oxide catalytic systems were found to be competent for the transformation allowing the preparation of aminomethylenecyclopropanes. The reaction showed general applicability to various functionalized bicyclo[2.2.1]hept‐2‐enes and ynamides. A chiral phosphapalladacycle was tested to carry out this transformation in an enantioselective fashion.
Investigation of substrate rotation at glancing incidence on thin-film morphology (2003)

Films deposited by evaporation at glancing angles form structures dependent on the speed of substrate rotation. If the substrate is held stationary, oblique columns are grown. For slow substrate rotation, helices are formed while faster rotation yields pillars. Silicon and silicon dioxide films grown under similar conditions were found to follow the typical morphological trend. In contrast, aluminum films formed by glancing angle deposition (GLAD) were found to be facetted structures which were peaked and isolated at high rotation speeds (dφ/dt&amp;gt;42 rpm), and flat for dφ/dt∼1.5 rpm. The results suggest that the primary limiting factor controlling GLAD microstructure growth may be a combination of both material temperature and crystal structure of the resulting film.
IKKγ Mediates the Interaction of Cellular IκB Kinases with the Tax Transforming Protein of Human T Cell Leukemia Virus Type 1 (1999)

The Tax oncoprotein of human T cell leukemia virus type 1 constitutively activates transcription factor NF-kappaB by a mechanism involving Tax-induced phosphorylation of IkappaBalpha, a labile cytoplasmic inhibitor of NF-kappaB. To trigger this signaling cascade, Tax associates stably with and persistently activates a cellular IkappaB kinase (IKK) containing both catalytic (IKKalpha and IKKbeta) and noncatalytic (IKKgamma) subunits. We now demonstrate that IKKgamma enables Tax to dock with the IKKbeta catalytic subunit, resulting in chronic IkappaB kinase activation. Mutations in either IKKgamma or Tax that prevent formation of these higher order Tax.IKK complexes also interfere with the ability of Tax to induce IKKbeta catalytic function in vivo. Deletion mapping studies indicate that amino acids 1-100 of IKKgamma are required for this Tax targeting function. Together, these findings identify IKKgamma as an adaptor protein that directs the stable formation of pathologic Tax.IKK complexes in virally infected T cells.
Patterns of cell death. (1988)

Cell death takes two distinct forms, necrosis and apoptosis. Necrosis is a degenerative phenomenon that follows irreversible injury. Apoptosis, in contrast, appears to be an active process requiring protein synthesis for its execution; it is implicated in physiological regulation of tissue size, and, where it occurs pathologically, a homeostatic role for the death is often evident. Morphologically, apoptosis involves condensation of the nuclear chromatin and cytoplasm, fragmentation of the nucleus, and budding of the whole cell to produce membrane-bounded bodies in which organelles are initially intact. These bodies are disposed of by adjacent cells without inflammation. Biochemically, there is distinctive internucleosome cleavage of DNA in apoptosis, which is quite different from the random DNA degradation observed in necrosis.
Soluble CD276 (B7‐H3) is released from monocytes, dendritic cells and activated T cells and is detectable in normal human serum (2008)

Expression of membrane CD276 (mB7-H3) has been reported on dendritic cells (DCs), monocytes, activated T cells, and various carcinoma cells. However, reports concerning its in vivo function have been inconsistent. Moreover, whether there is a soluble form of this protein is not known. In this study, using a sensitive dual monoclonal antibody sandwich enzyme-linked immunosorbent assay (ELISA) to detect the soluble form of B7-H3 (sB7-H3), we demonstrated the release of sB7-H3 by monocytes, DCs, activated T cells, and various mB7-H3+ but not mB7-H3- carcinoma cells. Release from cells was blocked by addition of a matrix metalloproteinase inhibitor (MMPI), which concomitantly caused the accumulation of B7-H3 on the cell surface. To determine the level of circulating sB7-H3, more than 200 serum samples were included in the study. The results indicated that sB7-H3 was present at high levels in all serum samples. Western blotting of sB7-H3 from cell culture supernatants or sera of healthy donors indicated that the molecular size was approximately 16 kDa. Soluble B7-H3 was able to bind to the B7-H3 receptor (B7-H3R) on activated T cells, which showed that sB7-H3 is a functionally active form. These results indicate that release of sB7-H3 from the cell surface is mediated by a matrix metalloproteinase and probably regulates B7-H3R/B7-H3 interactions in vivo. Cleavage of sB7-H3 to an active soluble form would alter both proximal and distal cellular responses.
DNA-Linked Metal Nanosphere Materials:  Structural Basis for the Optical Properties (1999)

The structural basis for the aggregation-induced optical properties of colloidal gold nanosphere aggregates is examined by means of electrodynamics calculations. Recently developed methods for calculating the electrodynamic response of aggregates composed of large numbers of small metal nanospheres in a dielectric medium are used to determine the optical changes associated with the formation of spherical aggregates. The calculations use accurate nanoparticle polarizabilities determined from Mie theory, an iterative conjugate-gradient solution algorithm, and fast-Fourier transform methods for efficient solution of the electrodynamic interacting nanoparticle equations. The UV extinction lowering and the shifting and broadening of the visible plasmon peak observed experimentally in solutions of DNA-linked gold nanospheres are explained as the collective electromagnetic response of thousands of nanoparticles.
Discovery and Optimization of Quinolinone Derivatives as Potent, Selective, and Orally Bioavailable Mutant Isocitrate Dehydrogenase 1 (mIDH1) Inhibitors (2019)

Mutations at the arginine residue (R132) in isocitrate dehydrogenase 1 (IDH1) are frequently identified in various human cancers. Inhibition of mutant IDH1 (mIDH1) with small molecules has been clinically validated as a promising therapeutic treatment for acute myeloid leukemia and multiple solid tumors. Herein, we report the discovery and optimization of a series of quinolinones to provide potent and orally bioavailable mIDH1 inhibitors with selectivity over wild-type IDH1. The X-ray structure of an early lead <b>24</b> in complex with mIDH1-R132H shows that the inhibitor unexpectedly binds to an allosteric site. Efforts to improve the in vitro and in vivo absorption, distribution, metabolism, and excretion (ADME) properties of <b>24</b> yielded a preclinical candidate <b>63</b>. The detailed preclinical ADME and pharmacology studies of <b>63</b> support further development of quinolinone-based mIDH1 inhibitors as therapeutic agents in human trials.
Cytokines in immunogenic cell death: Applications for cancer immunotherapy (2017)

Despite advances in treatments like chemotherapy and radiotherapy, metastatic cancer remains a leading cause of death for cancer patients. While many chemotherapeutic agents can efficiently eliminate cancer cells, long-term protection against cancer is not achieved and many patients experience cancer recurrence. Mobilizing and stimulating the immune system against tumor cells is one of the most effective ways to protect against cancers that recur and/or metastasize. Activated tumor specific cytotoxic T lymphocytes (CTLs) can seek out and destroy metastatic tumor cells and reduce tumor lesions. Natural Killer (NK) cells are a front-line defense against drug-resistant tumors and can provide tumoricidal activity to enhance tumor immune surveillance. Cytokines like IFN-γ or TNF play a crucial role in creating an immunogenic microenvironment and therefore are key players in the fight against metastatic cancer. To this end, a group of anthracyclines or treatments like photodynamic therapy (PDT) exert their effects on cancer cells in a manner that activates the immune system. This process, known as immunogenic cell death (ICD), is characterized by the release of membrane-bound and soluble factors that boost the function of immune cells. This review will explore different types of ICD inducers, some in clinical trials, to demonstrate that optimizing the cytokine response brought about by treatments with ICD-inducing agents is central to promoting anti-cancer immunity that provides long-lasting protection against disease recurrence and metastasis.
Rapid synthesis of block and cyclic copolymers via click chemistry in the presence of copper nanoparticles (2010)

A new method for the rapid and efficient coupling of homopolymers to yield di- and triblock copolymers as well as cyclic polymers using the 3 + 2 π Huisgen copper catalyzed cyclo-addition reaction has been developed. This facile method utilizes commercially available Cu nanoparticles that are tolerant to O(2), easily removable and recyclable.
A Fluid Membrane‐Based Soluble Ligand‐Display System for Live‐Cell Assays (2006)

Getting the right exposure. Membrane-tethered epidermal growth factor (EGF) is found to modulate substrate attachment and spreading of human breast epithelial cells by EGF–EGFR signaling interactions. In a newly implemented system, the fluidity of the supported membrane enables localized enrichment of ligand density in a configuration that reflects cognate-receptor distribution on the cell surface. This technique provides a means to control soluble ligand exposure within a parallel-surface array format.
Bandwidth Reduction For The Transmission Of Sign Language Over Telephone Lines (1988)

This paper describes a system for the transmission of American Sign Language (ASL) over standard telephone lines. Video quality digital images require a transmission bandwidth at least 4000 times wider than that allowable by the standard voice telephone network. This study presents compression, segmentation and coding techniques that reduce the information content of visual images while preserving the meaning of the transmitted message. The resulting processed information can be transmitted at digital rates within the range of the commercially available 9600 baud modems. The simulated real-time animations of the decoded cartoon images used for the experimental data represent ASL and finger spelling with an intelligibility approximating 85%. This result is within the range of the intelligibility provided by speech communication over telephone lines.
Use of different sensing materials and deposition techniques for thin-film sensors to increase sensitivity and selectivity (2003)

The performances of metal oxide semiconducting materials used as gas-sensing detectors depend strongly on their structural and morphological properties. The average grain size has been proved to play a prominent role and better sensor performances were found in polycrystalline films where the grain size is few tens of nm or smaller. On the other hand, thermal treatments during thin-film deposition and/or sample postprocessing could lead to a grain coalescence, thus decreasing the conductivity of the sensing film. Avoiding such a phenomenon, still keeping optimized processing conditions, will increase the sensor performances, maintaining the resistivity at acceptable values. In this work, new gas-sensing materials and new thin-film deposition procedures have been investigated. Aiming to preserve the sensitivity, to enhance selectivity and to reduce the drift, thin films of WO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> and CrTiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> deposited by pulsed-laser ablation (PLA) and of SnO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> deposited by rheotaxial growth and thermal oxidation techniques were comparatively characterized. Three issues were mainly addressed: the variation of the conductivity as a function of RH, the sensitivity toward benzene, CO, acetone, and NO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> , and the selectivity.
The NRIF3 Family of Transcriptional Coregulators Induces Rapid and Profound Apoptosis in Breast Cancer Cells (2004)

Many anticancer drugs kill cancer cells by inducing apoptosis. Despite the progress in understanding apoptosis, how to harness the cellular death machinery to selectively deliver tumor-specific cytotoxicity (while minimizing damage to other cells) remains an important challenge. We report here that expression of the NRIF3 family of transcriptional coregulators in a variety of breast cancer cell lines induces rapid and profound apoptosis (nearly 100% cell death within 24 h). A novel death domain (DD1) was mapped to a short 30-amino-acid region common to all members of the NRIF3 family. Mechanistic studies showed that DD1-induced apoptosis occurs through a novel caspase 2-mediated pathway that involves mitochondrial membrane permeabilization but does not require other caspases. Interestingly, the cytotoxicity of NRIF3 and DD1 appears to be cell type specific, as they selectively kill breast cancer or related cells but not other examined cells of different origins. Our study demonstrates the feasibility of selectively inducing cytotoxicity in a specific cancer and suggests that breast cancer cells contain a novel "death switch" that can be specifically triggered by NRIF3 or DD1. Strategies utilizing NRIF3 and/or DD1 and/or targeting this death switch may lead to the development of novel and more selective therapeutics against breast cancer.
Polarisation-independent Bragg gratings in ion-exchangedglass channel waveguides (2000)

The polarisation dependence of Bragg gratings photowritten in ion-exchanged glass waveguides is characterised for waveguides with different mask-opening widths and burial depths. It is found that polarisation-independent gratings can be written in waveguides with a wide variation in fabrication parameters.
Conformational Changes in the A1 Domain of von Willebrand Factor Modulating the Interaction with Platelet Glycoprotein Ib (1996)

The interaction between von Willebrand factor (vWF) A1 domain and platelet glycoprotein Ib alpha occurs in the presence of high shear stress or when vWF becomes immobilized onto a surface but not appreciably in the normal circulation. To investigate the structural properties regulating A1 domain function, we have used recombinant fragments prepared either in cyclic form with oxidized Cys509-Cys695 disulfide bond or reduced and alkylated. Interaction with glycoprotein Ibalpha was assessed by testing inhibition of monoclonal antibody LJ-Ib1 binding to platelets and inhibition of shear-induced platelet aggregation mediated by native vWF. Fragments exposed to pH between 2.5 and 3.5 adopted the molten globule conformation with loosened tertiary structure intermediate between native and completely unordered state. Maximal receptor binding activity was observed when fragments kept at acidic pH, particularly after reduction of the Cys509-Cys695 disulfide bond, were subjected to quick refolding by rapid pH increase. In contrast, slow refolding by incremental pH change over several hours resulted in at least 20-fold lower activity. A specific single point mutation (I546V) resulted in enhanced receptor binding, whereas another mutation (S561G) caused markedly reduced binding. These results provide experimental evidence that conformational transitions can modulate function of the vWF A1 domain in solution.
LNAzymes:  Incorporation of LNA-Type Monomers into DNAzymes Markedly Increases RNA Cleavage (2002)

Incorporation of two alpha-L-LNA/LNA nucleotides into each of the two binding arms of a "10-23" DNAzyme has been accomplished and the RNA cleavage with these novel LNAzymes studied. In comparison with the unmodified DNAzyme, the LNAzymes show significantly improved cleavage of the phosphodiester backbone at the target nucleotide in a small RNA substrate (58n RNA) under single-turnover conditions. The LNAzymes show efficient multiple turnover. With the LNAzymes, efficient cleavage was accomplished also of a naturally occurring ribosomal RNA at a target site within a highly structured region. The reference DNAzyme was ineffective at cleaving the ribosomal RNA target.
Aortic Pulse Wave Velocity as a Marker of Cardiovascular Risk in Hypertensive Patients (1999)

Large artery damage is a major contributory factor to cardiovascular morbidity and mortality of patients with hypertension. Pulse wave velocity (PWV), a classic evaluation of arterial distensibility, has never been ascertained as a cardiovascular risk marker. To determine the factors influencing aortic PWV and the potential predictor role of this measurement, we studied a cohort of 710 patients with essential hypertension. Atherosclerosis alterations (AA) were defined on the basis of clinical events. Calculation of cardiovascular risks, by use of Framingham equations, was performed in subjects without AA. PWV was higher in the presence of AA (14.9+/-4.0 versus 12.4+/-2.6 m/s, P<0.0001), even after adjustments on confounding factors and was the first determinant (P<0.0001) of the extent of atherosclerosis assessed as the sum of the atherosclerotic sites. In patients without AA, all cardiovascular risks increased constantly with PWV. Furthermore, at a given age, aortic PWV was the best predictor of cardiovascular mortality. The odds ratio of being in a high cardiovascular mortality risk group (>5% for 10 years) for patients in the upper quartile of PWV was 7.1 (95% confidence intervals 4.5 to 11.3). The presence of a PWV >13 m/s, taken alone, appeared as a strong predictor of cardiovascular mortality with high performance values. This study shows that aortic PWV is strongly associated with the presence and extent of atherosclerosis and constitutes a forceful marker and predictor of cardiovascular risk in hypertensive patients.