gebhart/patrepeval huggingface dataset:
Prophylactic and therapeutic implications of toll‐like receptor ligands (2010)

The evolutionary conserved Toll-like receptors (TLRs) are the first identified and best characterized pattern recognition receptors (PRRs) which discriminate self from nonself, providing an early and effective immune response against invading pathogens. The ever expanding knowledge of TLR signaling network make it one of the most promising therapeutic strategies to modulate the immune response in various human diseases. Immune modulating strategies based on TLR-specific agonists elicit a potent immune response to adjuvant vaccine immunotherapy, cancers, allergic diseases, and chronic viral infections while minimizing the risk of uncontrolled provocation of systemic inflammatory response. Moreover, the contribution of TLR signaling in the pathogenesis of chronic noninfectious inflammatory and autoimmune diseases provides the rationale for the development and clinical implementation of TLR-specific antagonists. At present, a few TLR-specific agonists have been approved for both prophylactic and therapeutic applications, while the ongoing preclinical and clinical studies show promising results on various novel therapeutic molecules as an adjunctive to conventional pharmacotherapy or stand-alone therapeutic strategy.
The Burning Rate of Energetic Films of Nanostructured Porous Silicon (2011)

A systematic study of nanoenergetic films consisting of nanostructured porous silicon impregnated with sodium perchlorate is carried out. The explosive properties of these films are investigated as a function of thickness, porosity, and confinement. The films' burning rates are investigated using fiber-optic velocity probes, demonstrating that flame-front velocities vary between approximately 1 and 500 m s(-1) and are very sensitive to the films' structural characteristics. Analysis of the flame profile by high-speed video is also presented, suggesting that the reaction type is a deflagration rather than a detonation. A strong plume of flame is emitted from the surface, indicating the potential for this material to perform useful work either as an initiator or as a propellant. The shape of the flame front transitioned from an inverted V at thin-film thicknesses to a neat square-shaped front once the material became self-confining at 50 μm.
The performance of interventional loopless MRI antennae at higher magnetic field strengths (2008)

Interventional, "loopless antenna" MRI detectors are currently limited to 1.5 T. This study investigates whether loopless antennae offer signal-to-noise ratio (SNR) and field-of-view (FOV) advantages at higher fields, and whether device heating can be controlled within safe limits. The absolute SNR performance of loopless antennae from 0.5 to 5 T is investigated both analytically, using electromagnetic (EM) dipole antenna theory, and numerically with the EM method of moments, and found to vary almost quadratically with field strength depending on the medium's electrical properties, the noise being dominated by direct sample conduction losses. The prediction is confirmed by measurements of the absolute SNR of low-loss loopless antennae fabricated for 1.5, 3, and 4.7 T, immersed in physiologically comparable saline. Gains of 3.8 +/- 0.2- and 9.7 +/- 0.3-fold in SNR, and approximately 10- and 50-fold gains in the useful FOV area are observed at 3 and 4.7 T, respectively, compared to 1.5 T. Heat testing of a 3 T biocompatible nitinol-antenna fabricated with a redesigned decoupling circuit shows maximum heating of approximately 1 degrees C for MRI operating at high MRI exposure levels. Experiments in the rabbit aorta confirm the SNR and FOV advantages of the 3 T antenna versus an equivalent commercial 1.5 T device in vivo. This work is the first to study the performance of experimental internal MRI detectors above 1.5 T. The large SNR and FOV gains realized present a major opportunity for high-resolution imaging of vascular pathology and MRI-guided intervention.
?-? INTERACTIONS IN SELF-ASSEMBLY (1997)

The recent surge of interest in the control of molecular organization in both the solution state (i.e. self-assembly) and the solid state (i.e. crystal engineering) has led researchers to recognize increasingly the importance of weak non-covalent interactions. The design and synthesis of an efficient molecular construction set are dependent upon a very close interplay between x-ray crystallography and synthetic chemistry. π–π Stacking interactions between π-donors, such as hydroquinone, resorcinol or dioxynaphthalene residues, and π-accepting ring systems, such as bipyridinium or π-extended viologen units, can govern the self-assembly of a variety of complexes and interlocked molecular compounds in both the solid and solution states. Non-covalent bonding interactions (i.e. π–π interactions) can be considered as information vectors: they define and rule the self-assembly processes that lead to the formation of the desired molecular and supramolecular architectures, and thereafter they still govern the dynamic processes occurring within the self-assembled structures and superstructures. The manner in which such molecules and supermolecules can contribute to an understanding of non-covalent interactions at both structural and superstructural levels is described, with reference to numerous examples of self-assembly processes in synthesis, of dynamic processes in the solution state, and of the packing of molecules and molecular complexes in the solid state. © 1997 John Wiley & Sons, Ltd.
A Phase I Study with Neratinib (HKI-272), an Irreversible Pan ErbB Receptor Tyrosine Kinase Inhibitor, in Patients with Solid Tumors (2009)

The maximum tolerated dose of once-daily oral neratinib is 320 mg. The most common neratinib-related toxicity was diarrhea. Antitumor activity was observed in patients with breast cancer who had previous treatment with trastuzumab, anthracyclines, and taxanes, and tumors with a baseline ErbB-2 immunohistochemical staining intensity of 2+ or 3+. The antitumor activity, tolerable toxicity profile, and pharmacokinetic properties of neratinib warrant its further evaluation.
Super-Resolution Using Hidden Markov Model and Bayesian Detection Estimation Framework (2006)

This paper presents a new method for super-resolution (SR) reconstruction of a high-resolution (HR) image from several low-resolution (LR) images. The HR image is assumed to be composed of homogeneous regions. Thus, the a priori distribution of the pixels is modeled by a finite mixture model (FMM) and a Potts Markov model (PMM) for the labels. The whole a priori model is then a hierarchical Markov model. The LR images are assumed to be obtained from the HR image by lowpass filtering, arbitrarily translation, decimation, and finally corruption by a random noise. The problem is then put in a Bayesian detection and estimation framework, and appropriate algorithms are developed based on Markov chain Monte Carlo (MCMC) Gibbs sampling. At the end, we have not only an estimate of the HR image but also an estimate of the classification labels which leads to a segmentation result.
Living-Free-Radical Emulsion Photopolymerization of Methyl Methacrylate by a Surface Active Iniferter (Suriniferter) (2003)

A novel surface-active RAFT agent as a suriniferter, composed of the dithiobenzoyl main structure and a benzoic hydrophobic carboxylate hydrophilic moiety, was synthesized and applied to the living-radical emulsion polymerization of methyl methacrylate (MMA) initiated by UV irradiation in the absence of added surfactant and additional initiator at various temperatures. A stable spherical bead of PMMA was successfully obtained using the suriniferter, maintaining the living-radical polymerization characteristics. Monomer conversion, molecular weight evolution and distribution, and final particle sizes were characterized. The higher the iniferter concentration, the higher the conversion and the lower the molecular weight, final particle size, and molecular weight distribution (PDI) obtained. A linear increase in molecular weight with respect to conversion is observed, implying that this technique using the suriniferter follows living-radical polymerization. The PDI varies from 1.21 to 1.43, and the final particle sizes vary from 407 to 304 nm with an increase in the polymerization temperature from 60 to 80 °C. The ratios of the triad tacticity for syndiotactic, atactic, and isotactic configurations of the synthesized PMMA are 54.3, 38.6, and 7.1, respectively, and the glass-transition temperature (Tg) is 126.6 °C, which is much higher than that of commercial PMMA (Tg = 105 °C). Thus, it is believed that the suriniferter used in living-free-radical emulsion polymerization modifies the stereoregularity of the PMMA.
Down-regulated melanoma differentiation associated gene (mda-7) expression in human melanomas (2001)

The melanoma differentiation associated gene-7 (mda-7) has a potential inhibitory role in melanoma progression, although the mechanisms underlying this effect are still unknown. mda-7 mRNA has been found to be present at higher levels in cultured normal melanocytes compared with metastatic melanoma cell lines. Furthermore, levels of mda-7 message have shown an inverse correlation with melanoma progression in human tumor samples, suggesting that mda-7 may be a novel tumor suppressor gene. We have designed this study to investigate MDA-7 protein expression in different stages of melanoma progression and to examine its antiproliferative effects in vitro. Our data demonstrate that MDA-7 protein can be found in normal melanocytes and early stage melanomas. It is also observed in smooth muscle cells in the skin. However, in keeping with a possible role as a tumor suppressor, MDA-7 expression is decreased in more advanced melanomas, with nearly undetectable levels in metastatic disease. We also investigated antitumor effects of overexpressed MDA-7 on human melanoma cells in vitro. Our results demonstrate that Ad-mda-7 induces apoptosis and G2/M cell cycle arrest in melanoma cells, but not in normal human melanocytes.
Structural Dynamics of Green Fluorescent Protein Alone and Fused with a Single Chain Fv Protein (2000)

Structural information on intracellular fusions of the green fluorescent protein (GFP) of the jellyfish Aequorea victoria with endogenous proteins is required as they are increasingly used in cell biology and biochemistry. We have investigated the dynamic properties of GFP alone and fused to a single chain antibody raised against lipopolysaccharide of the outer cell wall of gram-negative bacteria (abbreviated as scFv-GFP). The scFv moiety was functional as was proven in binding assays, which involved the use of both fluorescence correlation spectroscopy observing the binding of scFv-GFP to gram-negative bacteria and a surface plasmon resonance cell containing adsorbed lipopolysaccharide antigen. The rotational motion of scFv-GFP has been investigated with time-resolved fluorescence anisotropy. However, the rotational correlation time of scFv-GFP is too short to account for globular rotation of the whole protein. This result can only be explained by assuming a fast hinge motion between the two fused proteins. A modeled structure of scFv-GFP supports this observation.
Tumor immunology : immunotherapy and cancer vaccines (1996)

Contributors Series Editor's Preface Abbreviations 1. Introduction and historical perspectives Michael Browning and A. G. Dalgleish 2. The immunosurveillance of cancer: specific and non-specific mechanisms Richard G. Vile, Heung Chong and Sina Dorudi 3. Antigen processing and presentation Nicholas C. Testifo and Michael Wang 4. The role of the MHC class I in tumor immunity Michael Browning 5. Human tumor antigens recognized by Cytolytic T Lymphocytes Pierre G Coulie 6. Peptide-specific CTL directed against viral oncogene products Mariet C.W. Feltkamp, Cornelis J. M. Melief and W. Martin Kast 7. Cellular oncogenes for tumor immunity: immunotherapy Hans J. Strauss and A. Maria Dahl 8. Co-stimulatory molecules and their role in tumour immunity A. G. Dalgleish 9. The role of cytokines in tumour rejection Guido Forni and Robin Foa 10. Inhibition of nonhemopoietic cancer cell growth by Interleukin-4 and related cytokines Dave S. B. Hoon, Takashi Morisaki and Richard Essner 11. Current concepts concerning melanoma vaccines Donald L. Morton and Mepur H. Ravindranath 12. Immune responses to mucins Rosalind A. Graham and Joyce Taylor-Papadimitriou 13. Heat shock protein-peptide complexes: pan-valent vaccines against cancers and infectious diseases Ryuichiro Suto and Pramod K. Srivastave 14. The potential of gene transfer to alter the immune response to tumors Bernard A. Fox and Gary J. Nabel 15. Applications of antibody gene technology Robert E. Hawkins and Kerry A. Chester Index.
The Role of the Microtubules in Tumor Necrosis Factor-α–Induced Endothelial Cell Permeability (2003)

Tumor necrosis factor (TNF)-alpha, a major proinflammatory cytokine, triggers endothelial cell activation and barrier dysfunction which are implicated in the pathogenesis of pulmonary edema associated with acute lung injury syndromes. The mechanisms of TNF-alpha-induced vascular permeability are not completely understood. Our initial experiments demonstrated that TNF-alpha-induced decreases in transendothelial electrical resistance across human pulmonary artery endothelial cells are independent of myosin light chain phosphorylation catalyzed by either myosin light chain kinase or Rho kinase. We next assessed the involvement of another cytoskeletal component, the tubulin-based microtubule network, and found TNF-alpha to induce a decrease in stable tubulin content and partial dissolution of peripheral microtubule network as evidenced by anti-acetylated tubulin and anti-beta-tubulin immunofluorescent staining, respectively. Microtubule-stabilizing agents, paclitaxel and epothilone B, significantly attenuated TNF-alpha-induced decreases in transendothelial electrical resistance, inhibited the cytokine-induced increases in actin stress fibers, formation of intercellular gap, and restored the TNF-alpha-compromised vascular endothelial (VE)-cadherin-based cell-cell junctions. Importantly, neither TNF-alpha nor paclitaxel treatment was associated with endothelial cell apoptosis. Inhibition of p38 mitogen-activated protein kinase by SB203580 significantly attenuated TNF-alpha-induced microtubule destabilization, actin rearrangement, and endothelial barrier dysfunction. These results strongly suggest the involvement of microtubule rearrangement in TNF-alpha-induced endothelial cell permeability via p38 mitogen-activated protein kinase activation.
Mpi recombinase globally modulates the surface architecture of a human commensal bacterium (2003)

The mammalian gut represents a complex and diverse ecosystem, consisting of unique interactions between the host and microbial residents. Bacterial surfaces serve as an interface that promotes and responds to this dynamic exchange, a process essential to the biology of both symbionts. The human intestinal microorganism, Bacteroides fragilis, is able to extensively modulate its surface. Analysis of the B. fragilis genomic sequence, together with genetic conservation analyses, cross-species cloning experiments, and mutational studies, revealed that this organism utilizes an endogenous DNA inversion factor to globally modulate the expression of its surface structures. This DNA invertase is necessary for the inversion of at least 13 regions located throughout the genome, including the promoter regions for seven of the capsular polysaccharide biosynthesis loci, an accessory polysaccharide biosynthesis locus, and five other regions containing consensus promoter sequences. Bacterial DNA invertases of the serine site-specific recombinase family are typically encoded by imported elements such as phage and plasmids, and act locally on a single region of the imported element. In contrast, the conservation and unique global regulatory nature of the process in B. fragilis suggest an evolutionarily ancient mechanism for surface adaptation to the changing intestinal milieu during commensalism.
Qualitative Microwave Imaging With Scattering Parameters Measurements (2015)

Microwave imaging (MWI) systems extensively employ vector network analyzers for microwave measurements due to their high availability and accuracy. This is in contrast to theoretical models, which are naturally formulated in terms of scattered electric field vectors. Accordingly, experimental verification of MWI methods requires an intermediate step where measured scattering parameters are converted to scattered electric fields. In parallel to recent research, which formulates the Born iterative method in terms of scattering parameters, we develop formulations of two closely related qualitative inverse scattering methods-the linear sampling method and the factorization method-directly in terms of scattering parameters to avoid the intermediate conversion step. To this aim, we introduce vector S-parameters and we extend the vector Green's function for S-parameters to the dyadic case. There are certain advantages of these formulations over their electric field counterparts. First of all, the resulting formulations inherently incorporate the antenna radiation characteristics. Moreover, they reduce the measurement time since they do not require any pre- or post-measurement process. We experimentally verified the presented novel formulations against multi-frequency measurements performed inside an anechoic chamber. Obtained results show that the proposed methodologies can accurately reconstruct the shape of the targets by directly exploiting multifrequency measurements in the imaging process.
Inhibition of Henipavirus fusion and infection by heptad-derived peptides of the Nipah virus fusion glycoprotein (2005)

Nipah virus and Hendra virus infection in vitro can be potently blocked by specific HR-2 peptides. The improved synthesis and solubility characteristics of the second generation HR-2 peptides will facilitate peptide synthesis for pre-clinical trial application in an animal model of Henipavirus infection. The applied chemical modifications are also predicted to increase the serum half-life in vivo and should increase the chance of success in the development of an effective antiviral therapy.
Structure and Mechanism of ORF36, an Amino Sugar Oxidizing Enzyme in Everninomicin Biosynthesis, (2010)

Everninomicin is a highly modified octasaccharide that belongs to the orthosomycin family of antibiotics and possesses potent Gram-positive antibiotic activity, including broad-spectrum efficacy against multidrug resistant enterococci and Staphylococcus aureus. Among its distinctive structural features is a nitro sugar, l-evernitrose, analogues of which decorate a variety of natural products. Recently, we identified a nitrososynthase enzyme encoded by orf36 from Micromonospora carbonacea var. africana that mediates the flavin-dependent double oxidation of synthetically generated thymidine diphosphate (TDP)-l-epi-vancosamine to the corresponding nitroso sugar. Herein, we utilize a five-enzyme in vitro pathway both to verify that ORF36 catalyzes oxidation of biogenic TDP-l-epi-vancosamine and to determine whether ORF36 exhibits catalytic competence for any of its biosynthetic progenitors, which are candidate substrates for nitrososynthases in vivo. Progenitors solely undergo single-oxidation reactions and terminate in the hydroxylamine oxidation state. Performing the in vitro reactions in the presence of 18O2 establishes that molecular oxygen, rather than oxygen from water, is incorporated into ORF36-generated intermediates and products and identifies an off-pathway product that correlates with the oxidation product of a progenitor substrate. The 3.15 Å resolution X-ray crystal structure of ORF36 reveals a tetrameric enzyme that shares a fold with acyl-CoA dehydrogenases and class D flavin-containing monooxygenases, including the nitrososynthase KijD3. However, ORF36 and KijD3 have unusually open active sites in comparison to these related enzymes. Taken together, these studies map substrate determinants and allow the proposal of a minimal monooxygenase mechanism for amino sugar oxidation by ORF36.
MECHANISMS IN THE QUANTUM YIELD OF CYPRIDINA BIOLUMINESCENCE* (1970)

Abstract— –The influence of temperature, pH, salts, and reactant concentrations on the biolumin‐escent oxidation of Cypridina luciferin catalyzed by Cypridina luciferase indicates a highest quantum yield φ (einsteins per mole of luciferin oxidized) of 0.31 in H 2 O, or 0.33 in 99% D 2 O. With the aid of data on fluorescence of the light‐emitting oxyluciferin‐luciferase complex, and of oxyluciferin in diglyme, partial explanations are suggested for the observed variations in φ, including the relatively low φ, of 0.03 for chemiluminescence of luciferin in organic solvents, wherein a different pathway of luciferin degradation, as indicated by chromatographic evidence, results in much less population of the excited state.
Gene therapy for genetic diseases (1998)

Gene therapy provides the potential to permanently cure selected genetic diseases. However, a major obstacle is the effective delivery of the normal gene to specific target sites of pathology and continuous expression at therapeutic levels. A variety of viral and non-viral vectors have been developed to deliver genes to various cells, tissues and organs by ex vivo and in vivo strategies. Among the viral-based vectors, retroviruses, adenovirus, adeno-associated virus and herpes virus have been the most extensively studied. Among non-viral-based vectors, liposomes have been used to introduce plasmid DNA directly into animals, and DNA protein conjugates are being developed to exploit receptor-mediated uptake pathways. Each of these gene delivery systems is reviewed here and their advantages and disadvantages compared. In addition, the current status and future prospects for human gene therapy trials for genetic diseases are discussed.
The Inhibitory Effect of Curcumin on Virus-Induced Cytokine Storm and Its Potential Use in the Associated Severe Pneumonia (2020)

Coronavirus infection, including SARS-CoV, MERS-CoV, and SARS-CoV2, causes daunting diseases that can be fatal because of lung failure and systemic cytokine storm. The development of coronavirus-evoked pneumonia is associated with excessive inflammatory responses in the lung, known as "cytokine storms," which results in pulmonary edema, atelectasis, and acute lung injury (ALI) or fatal acute respiratory distress syndrome (ARDS). No drugs are available to suppress overly immune response-mediated lung injury effectively. In light of the low toxicity and its antioxidant, anti-inflammatory, and antiviral activity, it is plausible to speculate that curcumin could be used as a therapeutic drug for viral pneumonia and ALI/ARDS. Therefore, in this review, we summarize the mounting evidence obtained from preclinical studies using animal models of lethal pneumonia where curcumin exerts protective effects by regulating the expression of both pro- and anti-inflammatory factors such as IL-6, IL-8, IL-10, and COX-2, promoting the apoptosis of PMN cells, and scavenging the reactive oxygen species (ROS), which exacerbates the inflammatory response. These studies provide a rationale that curcumin can be used as a therapeutic agent against pneumonia and ALI/ARDS in humans resulting from coronaviral infection.