gebhart/patrepeval huggingface dataset:
Tumor necrosis factor/cachectin plays a key role in bleomycin-induced pneumopathy and fibrosis. (1989)

The role of TNF-alpha/cachectin in the pneumopathy elicited by bleomycin has been investigated. After a single intratracheal bleomycin instillation, an increase of the lung TNF-alpha mRNA level was evident, from days 5 to 15, as shown by Northern gel analysis of whole lung RNA. In contrast, lung IL-1-alpha and GM-CSF mRNA were not detectable. In mice passively immunized with rabbit anti-mouse TNF-alpha IgG, the bleomycin-induced collagen deposition, evaluated by the total lung hydroxyproline assay on day 15, was prevented. Depletion of the CD4 and CD8 T lymphocytes by an in vivo treatment with mAb prevented the bleomycin-induced increase of TNF mRNA level and fibrosis. After an administration of bleomycin in continuous intraperitoneal perfusion, the diffuse alveolar damage observed by light and electron microscopy was almost completely prevented by anti-TNF antibody. These results indicate that in response to bleomycin, the T lymphocytes induce, by an undefined mechanism, an increase of the pulmonary TNF production, which leads to alveolar damage, growth of fibroblast, and collagen deposition.
The T-cell receptor gamma chain-CD3 complex: implication in the cytotoxic activity of a CD3+ CD4- CD8- human natural killer clone. (1987)

A subset of human T cells has recently been described. These cells express the CD3 complex but they do not carry the classical T-cell receptor (TCR)-alpha/-beta heterodimer on their surface (WT31- CD3+). Instead, they express a TCR-gamma chain associated with another type of polypeptide termed TCR-delta. We report here that a T-cell clone with natural killer (NK)-like activity, WM-14, had a disulfide bridged TCR-gamma homodimer associated with CD3 on its surface. The TCR-gamma chains of WM-14 cells were present in three different glycosylation forms of 43, 40, and 38 kDa, but they appeared to contain the same polypeptide backbone. Since cytotoxicity by WM-14 could be inhibited by anti-CD3 antibodies, we concluded that the TCR-gamma-CD3 complex was involved in the NK-like unrestricted killer activity. Although normal CD3-gamma, CD3-delta, and CD3-epsilon chains were present in this clone, the association with the TCR-gamma homodimer may be the cause of a complete processing of the N-linked oligosaccharides attached to the CD3-delta chain.
The transcription factor Fra‐2 regulates the production of extracellular matrix in systemic sclerosis (2009)

We demonstrate that Fra-2 is overexpressed in SSc and acts as a novel downstream mediator of the profibrotic effects of TGFbeta and PDGF. Since transgenic overexpression of Fra-2 causes not only fibrosis but also vascular disease, Fra-2 might be an interesting novel candidate for molecular-targeted therapies for SSc.
Pairwise Interactions of Three Related Pseudomonas Species in Plant Roots and Inert Surfaces (2021)

Bacteria are social organisms that interact extensively within and between species while responding to external stimuli from their environments. Designing synthetic microbial communities can enable efficient and beneficial microbiome implementation in many areas. However, in order to design an efficient community, one must consider the interactions between their members. Using a reductionist approach, we examined pairwise interactions of three related <i>Pseudomonas</i> species in various microenvironments including plant roots and inert surfaces. Our results show that the step between monoculture and co-culture is already very complex. Monoculture root colonization patterns demonstrate that each isolate occupied a particular location on wheat roots, such as root tip, distance from the tip, or scattered along the root. However, pairwise colonization outcomes on the root did not follow the bacterial behavior in monoculture, suggesting various interaction patterns. In addition, we show that interspecies interactions on a microscale on inert surface take part in co-culture colonization and that the interactions are affected by the presence of root extracts and depend on its source. The understanding of interrelationships on the root may contribute to future attempts to manipulate and improve bacterial colonization and to intervene with root microbiomes to construct and design effective synthetic microbial consortia.
Polarization-switching techniques for coherent optical communications (1988)

Several techniques which rely on forcing the polarization state of either the transmitted signal or local oscillator to vary with time in a nonadaptive manner so that polarization-sensitive performance is obtained are discussed. The proposed schemes adopt a novel approach which uses a birefringent medium (for example, high-birefringence single-mode fibers) to implement polarization switching. These techniques require only a single photodetector and give a fixed level of detection performance, with a power penalty of 3 dB relative to heterodyne detection with perfectly matched polarizations.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Bright Light‐Emitting Diodes Based on Organometal Halide Perovskite Nanoplatelets (2015)

Bright light-emitting diodes based on solution-processable organometal halide perovskite nanoplatelets are demonstrated. The nanoplatelets created using a facile one-pot synthesis exhibit narrow-band emissions at 529 nm and quantum yield up to 85%. Using these nanoparticles as emitters, efficient electroluminescence is achieved with a brightness of 10 590 cd m(-2) . These ligand-capped nanoplatelets appear to be quite stable in moisture, allowing out-of-glovebox device fabrication.
Healing of fresh tibial fractures with OP-1. A preliminary report. (2002)

Osteogenic proteins (OP) are elements of a class of natural growth factors called Bone Morphogenetic Proteins (BMP). A specific member of this class is OP-1, a human recombinant protein that has osteogenic properties. The osteoinductive and osteoconductive properties of OP-1, with its specific collagen matrix, promote the generation of new functionally active, biologically and biomechanically mature bone. We carried out a clinical study to verify the potential of this protein in fresh tibial closed fractures, using OP-1 associated with osteosynthesis by means of a monolateral external fixator.
Glidobactins A, B and C, new antitumor antibiotics. II. Structure elucidation. (1988)

The structures of new antitumor antibiotics, glidobactins A (Ia), B (Ib) and C (Ic) were elucidated by a combination of chemical and enzymatic degradations and spectral analyses. They have in common a cyclized tripeptide nucleus composed of L-threonine, 4(S)-amino-2(E)-pentenoic acid and erythro-4-hydroxy-L-lysine, and differ from each other in the unsaturated fatty acid moiety attached to the peptide.
Circulating CD14+CD16+ monocyte levels predict tissue invasive character of cholangiocarcinoma (2010)

Chronic inflammation as a risk factor for cancer development is driven in part by monocyte/macrophages, which in many cancers exhibit pro-tumorigenic activity. In this study we identified elevation in CD14(+) CD16(+) , a minor blood monocyte subpopulation in cholangiocarcinoma (CCA) patients, compared to normal and biliary disease patient specimens. Tumour association was suggested by the observation that this elevated level decreased to normal after tumour resection. Moreover, the elevated level of CD14(+) CD16(+) monocytes in CCA patient blood correlated with degree of MAC387-positive (recent blood-derived macrophage migrant-specific marker) tumour-associated macrophage infiltration as determined by immunohistochemistry. These CD14(+) CD16(+) monocytes were suggested to enhance tumour progression as this subpopulation possesses (i) high expression of adhesion molecules (CD11c, CD49d, and CD54) and scavenger receptor (CD163), which enable them to adhere strongly to endothelial cells, and (ii) that peripheral blood monocytes from CCA patients express high levels of growth and angiogenic factor-related genes (epiregulin, VEGF-A and CXCL3). Elevation of peripheral CD14(+) CD16(+) monocyte levels was associated with features associated with poor prognosis CCA parameters (non-papillary type and high number of tissue macrophages). These data indicate that the CD14(+) CD16(+) monocytes from CCA patients with pro-tumorigenic characteristics may associate with rapid tumour progression and poor patient outcome. If confirmed in subsequent studies, the level of CD14(+) CD16(+) monocytes may serve as a marker for disease activity in CCA patients and serve as a target for pathogenic macrophage specific drug development.
Stochastic optimization based economic dispatch and interruptible load management with distributional forecast of wind farm generation (2014)

We study stochastic optimization of economic dispatch (ED) and interruptible load management using short-term distributional forecast of wind farm generation. Specifically, we develop a Markov-chain-based distributional forecast model for wind farm generation based on spatial and temporal characteristics of the wind turbine power output in a wind farm. Built on the distributional forecast model, the joint optimization of ED and interruptible load management is cast as a stochastic optimization problem. The proposed stochastic ED problem is compared with the deterministic ED problem using the persistence wind generation forecast model, and also with the scenario-based ED formulation which uses all possible wind generation states. Numerical studies, using a modified IEEE RTS 24-bus system and realistic wind measurement data from an actual wind farm, demonstrate the significant benefits obtained by leveraging the Markov-chain-based distributional forecast and the interruptible load management.
Specific Interactions between Biotin and Avidin Studied by Atomic Force Microscopy Using the Poisson Statistical Analysis Method (1999)

The interactions between biotin and avidin or streptavidin, a prototypical example of a specific biological ligand−receptor system, were studied by atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and time-of-flight secondary ion mass spectrometry (TOF-SIMS). Although this and other ligand−receptor systems have been studied by several techniques, including AFM, in this paper, a statistical analysis method which makes use of the properties of the Poisson distribution was applied, and the rupture strength of an individual interaction was obtained from the total adhesion forces measured by the AFM. Tip- and surface-modification chemistries were investigated by XPS and TOF-SIMS. The magnitudes of the interactions between biotin−avidin and biotin-streptavidin pairs, as determined by the Poisson method, were found to be 173 ± 19 and 326 ± 33 pN, respectively, for loading rates between 2 × 105 and 8 × 105 pN·s-1. These values are comparable to the values reported by other groups for the same systems. The statistical method used in this work has several advantages. It requires no assumptions about the surface energies or contact area between the AFM tip and the substrate, it is not limited by the force resolution of the instrument, and the number of measurements required to extract the individual unbinding force is significantly lower than that required by other methods.
Phytochemicals potentiate interleukin-2 generated lymphokine-activated killer cell cytotoxicity against murine renal cell carcinoma. (1992)

The success of adoptive immunotherapy using recombinant interleukin-2 (rIL-2) and lymphokine-activated killer (LAK) cells in several cancers has been hampered by severe toxicity associated with high doses of rIL-2. Methods that reduce the dosage of rIL-2 without loss of clinical efficacy are needed. In this study we determined the in vitro effect of a phytochemical immune modulator, Astragalus membranaceus (AM), and two fractions isolated by high-performance liquid chromatography on the cytotoxicity of rIL-2-generated LAK cells against a murine renal cell carcinoma. Our results indicated a 10-fold potentiation of rIL-2-generated LAK cell cytotoxicity manifested by tumor cell lysis of 88% in the group with 100 U/ml of rIL-2 plus AM versus 86% in the group with 1,000 U/ml of rIL-2 alone. Potentiation was obtained with the purified fractions as well. A significantly reduced number of LAK cells was required to achieve the tumor cytotoxicity after LAK cell generation with rIL-2 plus the phytochemicals as compared with rIL-2 alone. Our data indicate that AM is an effective immune modulator, capable of potentiating in vitro the antitumor activity of rIL-2-generated LAK cells.
Ubiquitin-Specific Proteases as Cancer Drug Targets (2011)

Ubiquitin-specific proteases are deubiquitinating enzymes involved in the removal of ubiquitin from specific protein substrates resulting in protein salvage from proteasome degradation, regulation of protein localization or activation. DNA alteration and overexpression in different cancer types, as well as involvement in many cancer-associated pathways, make ubiquitin-specific proteases attractive for the cancer drug discovery purposes. Their proteolytic function associated to available structural biology data reinforce their potential for pharmacological interference. Here, we review this class of enzymes as cancer drug targets in terms of validation and druggability.
Regulation and guidance of cell behavior for tissue regeneration via the siRNA mechanism (2007)

ABSTRACT RNA intereference and short‐interfering RNA (siRNA) have been proven to be effective at decreasing the expression of target genes and provide a valuable tool for promoting and directing the growth of functional tissues for repair and reconstructive tissue engineering applications. siRNA is a gene‐silencing mechanism that involves double‐stranded RNA‐mediated sequence‐specific mRNA degradation and is a powerful mechanism for controlling cell behavior. The use of siRNA to reduce the expression of a target gene can induce the expression of one or more tissue‐inductive factors, direct the differentiation of stem or progenitor cells, or remove a factor that inhibits regeneration, which can be useful in fundamental studies of tissue formation or in applications to promote in vivo regeneration. The potential of siRNA is illustrated through specific examples within the fields of angiogenesis, bone and nerve regeneration, and wound healing. In addition, challenges to deliver siRNA effectively for tissue engineering applications are addressed. siRNA represents a powerful tool to investigate and/or promote tissue formation, and numerous opportunities exist for identifying targets that promote regeneration of tissue and developing effective delivery systems.
Recombinant respiratory syncytial virus from which the entire SH gene has been deleted grows efficiently in cell culture and exhibits site-specific attenuation in the respiratory tract of the mouse (1997)

The small hydrophobic protein SH of human respiratory syncytial virus (RSV) is a short transmembrane surface protein of unknown function. A full-length cDNA of RSV strain A2 (subgroup A) antigenomic RNA was modified such that the entire SH gene, including the transcription signals and the complete mRNA-encoding sequence, was deleted and replaced by a synthetic intergenic region. This reduced the length of the antigenome by 398 nucleotides and ablated expression of 1 of the 10 RSV mRNAs. Recombinant virus containing this engineered deletion was recovered, and the absence of the SH gene was confirmed by reverse transcription in conjunction with PCR. Northern blot analysis of intracellular RNAs and gel electrophoresis of labeled intracellular proteins confirmed the lack of expression of the SH mRNA and protein. The absence of the SH gene did not noticeably affect RNA replication, but two effects on transcription were noted. First, synthesis of the G, F, and M2 mRNAs was increased, presumably due to their being one position closer to the promoter in the gene order. Second, transcription of genes downstream of the engineered site exhibited a steeper gradient of polarity. On monolayers of HEp-2 cells, the SH-minus virus produced syncytia which were at least equivalent in size to those of the wild type and produced plaques which were 70% larger. Furthermore, the SH-minus virus grew somewhat better (up to 12.6-fold) than wild-type recombinant RSV in certain cell lines. While the function of the SH protein remains to be determined, it seems to be completely dispensable for growth in tissue culture and fusion function. When inoculated intranasally into mice, the SH-minus virus resembled the wild-type recombinant virus in its efficiency of replication in the lungs, whereas it replicated 10-fold less efficiently in the upper respiratory tract. In mice, the SH-minus and wild-type recombinant viruses were similarly immunogenic and effective in inducing resistance to virus challenge.
Molecular Imaging of Angiogenesis in Early-Stage Atherosclerosis With α v β 3 -Integrin–Targeted Nanoparticles (2003)

This molecular imaging approach might provide a method for defining the burden and evolution of atherosclerosis in susceptible individuals as well as responsiveness of individual patients to antiatherosclerotic therapies.
Host adaptations reduce the reproductive success ofVarroa destructorin two distinct European honey bee populations (2012)

Honey bee societies (Apis mellifera), the ectoparasitic mite Varroa destructor, and honey bee viruses that are vectored by the mite, form a complex system of host-parasite interactions. Coevolution by natural selection in this system has been hindered for European honey bee hosts since apicultural practices remove the mite and consequently the selective pressures required for such a process. An increasing mite population means increasing transmission opportunities for viruses that can quickly develop into severe infections, killing a bee colony. Remarkably, a few subpopulations in Europe have survived mite infestation for extended periods of over 10 years without management by beekeepers and offer the possibility to study their natural host-parasite coevolution. Our study shows that two of these "natural" honey bee populations, in Avignon, France and Gotland, Sweden, have in fact evolved resistant traits that reduce the fitness of the mite (measured as the reproductive success), thereby reducing the parasitic load within the colony to evade the development of overt viral infections. Mite reproductive success was reduced by about 30% in both populations. Detailed examinations of mite reproductive parameters suggest these geographically and genetically distinct populations favor different mechanisms of resistance, even though they have experienced similar selection pressures of mite infestation. Compared to unrelated control colonies in the same location, mites in the Avignon population had high levels of infertility while in Gotland there was a higher proportions of mites that delayed initiation of egg-laying. Possible explanations for the observed rapid coevolution are discussed.
Uncoupling between Epidermal Growth Factor Receptor and Downstream Signals Defines Resistance to the Antiproliferative Effect of Gefitinib in Bladder Cancer Cells (2005)

Abstract Activation of the epidermal growth factor receptor (EGFR) and downstream signaling pathways, such as phosphatidylinositol-3 kinase/Akt and Ras/mitogen-activated protein kinase (MAPK), have been implicated in causing resistance to EGFR-targeted therapy in solid tumors, including the urogenital tumors. To investigate the mechanism of resistance to EGFR inhibition in bladder cancer, we compared EGFR tyrosine kinase inhibitor (Gefitinib, Iressa, ZD1839) with respect to its inhibitory effects on three kinases situated downstream of EGFR: MAPK, Akt, and glycogen synthase kinase-3β (GSK-3β). We found that the resistance to the antiproliferative effects of gefitinib, in vitro as well as in vivo in nude mice models, was associated with uncoupling between EGFR and MAPK inhibition, and that GSK-3β activation and degradation of its target cyclin D1 were indicators of a high cell sensitivity to gefitinib. Further analysis of one phenotypic sensitive (253J B-V) and resistant (UM-UC13) cell lines revealed that platelet-derived growth factor receptor-β (PDGFRβ) activation was responsible for short circuiting the EGFR/MAPK pathway for mitogenic stimuli. However, invasion as well as actin dynamics were efficiently reduced by EGFR inhibition in UM-UC13. Chemical disruption of signaling pathways or of PDGFR kinase activity significantly reduced the inactive pool of cellular GSK-3β in UM-UC13 cells. In conclusion, our data show that the uncoupling of EGFR with mitogenic pathways can cause resistance to EGFR inhibition in bladder cancer. Although this uncoupling may arise through different mechanisms, we suggest that the resistance of bladder cancer cells to EGFR blockade can be predicted early in the course of treatment by measuring the activation of GSK-3β and of nuclear cyclin D1.
The laboratory diagnosis of Lyme disease (1991)

• Growing awareness of Lyme disease, caused by the tickborne spirochete<i>Borrelia burgdorferi</i>has led to a marked increase in laboratory procedures to help in its diagnosis. Despite the frequent ordering of serologic tests specific for Lyme disease, there remains confusion in the accurate interpretation of these tests. Because of the important cutaneous manifestations of<i>B burgdorferi</i>infection, dermatologists should understand the role of the laboratory in<i>Borrelia</i>related conditions. This article reviews laboratory techniques available for the diagnosis of Lyme disease. The role of histologic findings and culture, the sensitivity, specificity, and reproducibility of commonly used serologic tests, the effects of disease duration and treatment on serologic results, and the future of laboratory diagnosis are described. (<i>Arch Dermatol.</i>1991;127:866-870)
Ecteinascidin-743: A Marine-Derived Compound in Advanced, Pretreated Sarcoma Patients—Preliminary Evidence of Activity (2001)

ET-743 has activity in advanced, highly pretreated STS and osteosarcoma patients and warrants further trials to establish the extent of its activity in this setting.
Effect of High Dose of Pyridoxine on Mammary Tumorigenesis (2005)

The effect of high-dose pyridoxine (PN) on mammary tumorigenesis was examined in female Sprague-Dawley rats. The first mammary tumors appeared between 84 and 90 days after 7,12-dimethylbenzanthracene treatment. There was no effect of PN level on tumor incidence at 90 days but at 98, 104, and 111 days. Tumor incidence was lower in the high-dose group (35 mg PN/kg diet) compared with the controls (7 mg PN/kg diet). All tumors were identified as adenocarcinoma and most as papillary type. The number of microcarcinomas in mammary glands of the 35-mg PN group tended to be reduce than that of the 7-mg group. The number of proliferating Ki67-positive cells was significantly reduced by supplementation with PN.
Direct and indirect role of Toll-like receptors in T cell mediated immunity. (2004)

Toll-like receptors (TLRs) are pathogen-associated molecular patterns (PAMPs) recognition receptors that play an important role in protective immunity against infection and inflammation. They act as central integrators of a wide variety of signals, responding to diverse agonists of microbial products. Stimulation of Toll-like receptors by microbial products leads to signaling pathways that activate not only innate, but also adaptive immunity by APC dependent or independent mechanisms. Recent evidence revealed that TLR signals played a determining role in the skewing of naive T cells towards either Th1 or Th2 responses. Activation of Toll-like receptors also directly or indirectly influences regulatory T cell functions. Therefore, TLRs are required in both immune activation and immune regulation. Study of TLRs has significantly enhanced our understanding of innate and adaptive immune responses and provides novel therapeutic approaches against infectious and inflammatory diseases.