gebhart/patrepeval huggingface dataset:
Regulation of IL-6 expression by oncostatin M (1991)

Endothelial cells produce immunomodulatory cytokines in response to soluble mediators of inflammatory/immune reactions. We have previously demonstrated that the leukocyte-derived cytokine, oncostatin M (Onco M) can alter endothelial cell morphology, regeneration, and fibrinolytic activity in vitro. Here we demonstrate that Onco M stimulates the production of the pleiotropic cytokine, IL-6, in cultured human endothelial cells (HEC) in a time- and dose-dependent manner. Specific antibodies to IL-6 neutralize the growth-inhibitory activity for human breast carcinoma cells that is secreted by HEC in response to Onco M treatment. Specific immunoassays indicate greater than 10-fold increases in the IL-6 content of culture supernatants as early as 6 h post-treatment with Onco M (ED50 = 17 pM). This stimulation of IL-6 production by Onco M is associated with a sevenfold increase in intracellular levels of IL-6 mRNA. IL-1 alpha and TNF-alpha are also potent inducers of IL-6 production in these cells, the order of potency being IL-1 alpha greater than Onco M greater than TNF-alpha. TNF-alpha, but not IL-1 alpha, synergizes with Onco M to augment IL-6 production in HEC. HEC are 10 to 20 times more responsive to Onco M than are other nonendothelial cell types. In addition, HEC express 10 to 20 times greater numbers of high affinity cell-surface receptors for Onco M than do other nonendothelial cell types. Based on these findings, we propose that Onco M may represent a new immunomodulator regulating cytokine-induced gene products in endothelial cells.
Quantifying Impact of Chromosome Copy Number on Recombination in Escherichia coli (2015)

The ability to precisely and efficiently recombineer synthetic DNA into organisms of interest in a quantitative manner is a key requirement in genome engineering. Even though considerable effort has gone into the characterization of recombination in Escherichia coli, there is still substantial variability in reported recombination efficiencies. We hypothesized that this observed variability could, in part, be explained by the variability in chromosome copy number as well as the location of the replication forks relative to the recombination site. During rapid growth, E. coli cells may contain several pairs of open replication forks. While recombineered forks are resolving and segregating within the population, changes in apparent recombineering efficiency should be observed. In the case of dominant phenotypes, we predicted and then experimentally confirmed that the apparent recombination efficiency declined during recovery until complete segregation of recombineered and wild-type genomes had occurred. We observed the reverse trend for recessive phenotypes. The observed changes in apparent recombination efficiency were found to be in agreement with mathematical calculations based on our proposed mechanism. We also provide a model that can be used to estimate the total segregated recombination efficiency based on an initial efficiency and growth rate. These results emphasize the importance of employing quantitative strategies in the design of genome-scale engineering efforts.
Rearing Microplitis croceipes in the Laboratory with Heliothis zea as Hosts1234 (1970)

Journal Article Rearing Microplitis croceipes in the Laboratory with Heliothis zea as Hosts Get access W. J. Lewis, W. J. Lewis Entomology Research Division, Agr. Res. Serv., USDA, Tifton, Georgia 31794 Search for other works by this author on: Oxford Academic PubMed Google Scholar R. L. Burton R. L. Burton Entomology Research Division, Agr. Res. Serv., USDA, Tifton, Georgia 31794 Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Economic Entomology, Volume 63, Issue 2, 1 April 1970, Pages 656–658, https://doi.org/10.1093/jee/63.2.656 Published: 01 April 1970 Article history Received: 18 July 1969 Published: 01 April 1970
Oxidation and Nitrosation of Thiols at Low Micromolar Exposure to Nitric Oxide (2003)

Although the nitric oxide (.NO)-mediated nitrosation of thiol-containing molecules is increasingly recognized as an important post-translational modification in cell signaling and pathology, little is known about the factors that govern this process in vivo. In the present study, we examined the chemical pathways of nitrosothiol (RSNO) production at low micromolar concentrations of .NO. Our results indicate that, in addition to nitrosation by the .NO derivative dinitrogen trioxide (N2O3), RSNOs may be formed via intermediate one-electron oxidation of thiols, possibly mediated by nitrogen dioxide (.NO2), and the subsequent reaction of thiyl radicals with .NO. In vitro, the formation of S-nitrosoglutathione (GSNO) from .NO and excess glutathione (GSH) was accompanied by the formation of glutathione disulfide, which could not be ascribed to the secondary reaction of GSH with GSNO. Superoxide dismutase significantly increased GSNO yields and the thiyl radical trap, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), inhibited by 45 and 98% the formation of GSNO and GSSG, respectively. Maximum nitrosation yields were obtained at an oxygen concentration of 3%, whereas higher oxygen tensions decreased GSNO and increased GSSG formation. When murine fibroblasts were exposed to exogenous .NO, RSNO formation was sensitive to DMPO and oxygen tension in a manner similar to that observed with GSH alone. Our data indicate that RSNO formation is favored at oxygen concentrations that typically occur in tissues. Nitrosothiol formation in vivo depends not only on the availability of .NO and O2 but also on the degree of oxidative stress by affecting the steady-state concentration of thiyl radicals.
Humanized Affinity-matured Monoclonal Antibody 8H9 Has Potent Antitumor Activity and Binds to FG Loop of Tumor Antigen B7-H3 (2015)

B7-H3 (CD276) is both an inhibitory ligand for natural killer cells and T cells and a tumor antigen that is widely expressed among human solid tumors. Anti-B7-H3 mouse monoclonal antibody 8H9 has been successfully used for radioimmunotherapy for patients with B7-H3(+) tumors. We present the humanization, affinity maturation, and epitope mapping of 8H9 based on structure determination, modeling, and yeast display methods. The crystal structure of ch8H9 Fab fragment was solved to 2.5-Å resolution and used as a template for humanization. By displaying the humanized 8H9 single chain Fv (scFv) on the surface of yeast, the affinity was matured by sequential random mutagenesis and fluorescence-activated cell sorting. Six mutations (three in the complementarity-determining region and three in the framework regions) were identified and incorporated into an affinity-matured humanized 8H9 construct (hu8H9-6m) and an affinity-matured chimeric 8H9 construct (ch8H9-6m). The hu8H9-6m scFv had a 160-fold improvement in affinity (0.9 nm KD) compared with parental hu8H9 scFv (144 nm KD). The IgG formats of ch8H9-6m and hu8H9-6m (nanomolar to subnanomolar KD) had 2-9-fold enhancements in affinity compared with their parental forms, potent in vitro antibody-dependent cell-mediated cytotoxicity (0.1-0.3 μg/ml EC50), and high tumor uptake in mouse xenografts. Based on in silico docking studies and experimental validation, the molecular epitope of 8H9 was determined to be dependent on the FG loop of B7-H3, a region critical to its function in immunologic blockade and unique among anti-B7-H3 antibodies published to date.
ELAC2/HPC2 Polymorphisms, Prostate-Specific Antigen Levels, and Prostate Cancer (2003)

There is no evidence that either ELAC2 polymorphism is associated with prostate cancer or PSA level.
Melatonin protects against gentamicin‐induced nephrotoxicity in rats (2002)

Acute renal failure is a major complication of gentamicin (GEN), which is widely used in the treatment of gram-negative infections. A large body of in vitro and in vivo evidence indicates that reactive oxygen metabolites (or free radicals) are important mediators of gentamicin nephrotoxicity. In this study we investigated the role of free radicals in gentamicin-induced nephrotoxicity and whether melatonin, a potent antioxidant could prevent it. For this purpose female Sprague-Dawley rats were given intraperitoneally either gentamicin sulphate (40 mg/kg), melatonin (10 mg/kg), gentamicin plus melatonin or vehicle (control) twice daily for 14 days. The rats were decapitated on the 15th day and kidneys were removed. Blood urea nitrogen (BUN) and creatinine levels were measured in the blood and malondialdehyde (MDA) and glutathione (GSH) levels, protein oxidation (PO) and myeloperoxidase (MPO) activity were determined in the renal tissue. Gentamicin was observed to cause a severe nephrotoxicity which was evidenced by an elevation of BUN and creatinine levels. The significant decrease in GSH and increases in MDA levels, PO and MPO activity indicated that GEN-induced tissue injury was mediated through oxidative reactions. On the other hand simultaneous melatonin administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by GEN treatment.
Malignant Cells Can Be Sensitized to Undergo Growth Inhibition and Apoptosis by Arsenic Trioxide Through Modulation of the Glutathione Redox System (1999)

Arsenic trioxide (As2O3) induces clinical remission in acute promyelocytic leukemia (APL) with minimal toxicity and apoptosis in APL-derived NB4 cells at low (1 to 2 micromol/L) concentration. We examined the basis for NB4 cell sensitivity to As2O3 to identify experimental conditions that would render other malignant cells responsive to low concentrations of As2O3. The intracellular glutathione (GSH) content had a decisive effect on As2O3-induced apoptosis. Highly sensitive NB4 cells had the lowest GSH and the sensitivity of other cell lines was inversely proportional to their GSH content. The t(14;18) B-cell lymphoma cell line had low GSH levels and sensitivity to As2O3 at levels slightly higher than in APL cells. Experimental upmodulation of GSH content decreased the sensitivity to As2O3. Ascorbic acid and buthionine sulfoxide (BSO) decreased GSH to a greater extent, and rendered malignant cells more sensitive to As2O3. As2O3-induced apoptosis was not enhanced by ascorbic acid in normal cells, suggesting that the combination of ascorbic acid and As2O3 may be selectively toxic to some malignant cells. Ascorbic acid enhanced the antilymphoma effect of As2O3 in vivo without additional toxicity. Thus, As2O3 alone or administered with ascorbic acid may provide a novel therapy for lymphoma.
Digital Current Control of a Voltage Source Converter With Active Damping of LCL Resonance (2006)

Inductance-capacitor-inductance (LCL)-filters installed at converter outputs offer higher harmonic attenuation than L-filters, but careful design is required to damp LCL resonance, which can cause poorly damped oscillations and even instability. A new topology is presented for a discrete-time current controller which damps this resonance, combining deadbeat current control with optimal state-feedback pole assignment. By separating the state feedback gains into deadbeat and damping feedback loops, transient overcurrent protection is realizable while preserving the desired pole locations. Moreover, the controller is shown to be robust to parameter uncertainty in the grid inductance. Experimental tests verify that fast well-damped transient response and overcurrent protection is possible at low switching frequencies relative to the resonant frequency
Deep Convolutional Neural Networks for Computer-Aided Detection: CNN Architectures, Dataset Characteristics and Transfer Learning (2016)

Remarkable progress has been made in image recognition, primarily due to the availability of large-scale annotated datasets and deep convolutional neural networks (CNNs). CNNs enable learning data-driven, highly representative, hierarchical image features from sufficient training data. However, obtaining datasets as comprehensively annotated as ImageNet in the medical imaging domain remains a challenge. There are currently three major techniques that successfully employ CNNs to medical image classification: training the CNN from scratch, using off-the-shelf pre-trained CNN features, and conducting unsupervised CNN pre-training with supervised fine-tuning. Another effective method is transfer learning, i.e., fine-tuning CNN models pre-trained from natural image dataset to medical image tasks. In this paper, we exploit three important, but previously understudied factors of employing deep convolutional neural networks to computer-aided detection problems. We first explore and evaluate different CNN architectures. The studied models contain 5 thousand to 160 million parameters, and vary in numbers of layers. We then evaluate the influence of dataset scale and spatial image context on performance. Finally, we examine when and why transfer learning from pre-trained ImageNet (via fine-tuning) can be useful. We study two specific computer-aided detection (CADe) problems, namely thoraco-abdominal lymph node (LN) detection and interstitial lung disease (ILD) classification. We achieve the state-of-the-art performance on the mediastinal LN detection, and report the first five-fold cross-validation classification results on predicting axial CT slices with ILD categories. Our extensive empirical evaluation, CNN model analysis and valuable insights can be extended to the design of high performance CAD systems for other medical imaging tasks.
Malnutrition in liver cirrhosis:the influence of protein and sodium. (2013)

Protein calorie malnutrition (PCM) is associated with an increased risk of morbidity and mortality in patients with cirrhosis and occurs in 50%-90% of these patients. Although the pathogenesis of PCM is multifactorial, alterations in protein metabolism play an important role. This article is based on a selective literature review of protein and sodium recommendations. Daily protein and sodium requirements of patients with cirrhosis have been the subject of many research studies since inadequate amounts of both can contribute to the development of malnutrition. Previous recommendations that limited protein intake should no longer be practiced as protein requirements of patients with cirrhosis are higher than those of healthy individuals. Higher intakes of branched-chain amino acids as well as vegetable proteins have shown benefits in patients with cirrhosis, but more research is needed on both topics. Sodium restrictions are necessary to prevent ascites development, but very strict limitations, which may lead to PCM should be avoided.
Response to botulinum toxin F in seronegative botulinum toxin A—resistant patients (1996)

Botulinum toxin type A (btx A) injections are the most effective treatment for most patients with focal dystonia. Some patients who improve after btx A injections and later lose response have serologic evidence of antibodies to btx A with the mouse neutralization assay (seropositive patients). Another group of patients who lose response to btx A do not have detectable antibodies (seronegative patients). Seropositive patients may improve after injections of botulinum toxin type F (btx F), an alternative serotype of botulinum toxin. We treated nine seronegative resistant patients with btx F. None of these patients had muscle atrophy after injection with btx A. Five of the nine had improvement after btx F injection that was sustained for at least three consecutive btx F injections. This observation is consistent with the hypothesis that btx resistance in seronegative patients is caused by undetected antibodies to btx A. If this be the case, then there may be techniques for preventing or reversing btx resistance, as in the case of resistance of factor VIII in the treatment of hemophilia A.
Swab Sample Transfer for Point-Of-Care Diagnostics: Characterization of Swab Types and Manual Agitation Methods (2014)

Excess-volume samples gave the expected recovery for most swabs (based on tip fluid capacity); a polyurethane swab showed enhanced recovery, suggesting an ability to accumulate organisms during sampling. Dry samples led to recovery of ∼20-30% for all swabs tested, suggesting that swab structure and volume is less important when organisms are applied to the outer swab surface. Low-volume samples led to the widest range of transfer efficiencies between swab types. Rayon swabs (63 µL capacity) performed well for excess-volume samples, but showed poor recovery for low-volume samples. Nylon (100 µL) and polyester swabs (27 µL) showed intermediate recovery for low-volume and excess-volume samples. Polyurethane swabs (16 µL) showed excellent recovery for all sample types. This work demonstrates that swab transfer efficiency can be affected by swab material, structure, and fluid capacity and details of the sample. Results and quantitative analysis methods from this study will assist POC assay developers in selecting appropriate swab types and transfer methods.
Ultrasound-mediated DNA transfer for bacteria (2007)

In environmental microbiology, the most commonly used methods of bacterial DNA transfer are conjugation and electroporation. However, conjugation requires physical contact and cell-pilus-cell interactions; electroporation requires low-ionic strength medium and high voltage. These limitations have hampered broad applications of bacterial DNA delivery. We have employed a standard low frequency 40 kHz ultrasound bath to successfully transfer plasmid pBBR1MCS2 into Pseudomonas putida UWC1, Escherichia coli DH5alpha and Pseudomonas fluorescens SBW25 with high efficiency. Under optimal conditions: ultrasound exposure time of 10 s, 50 mM CaCl(2), temperature of 22 degrees C, plasmid concentration of 0.8 ng/microl, P. putida UWC1 cell concentration of 2.5 x 10(9) CFU (colony forming unit)/ml and reaction volume of 500 microl, the efficiency of ultrasound DNA delivery (UDD) was 9.8 +/- 2.3 x 10(-6) transformants per cell, which was nine times more efficient than conjugation, and even four times greater than electroporation. We have also transferred pBBR1MCS2 into E. coli DH5alpha and P. fluorescens SBW25 with efficiencies of 1.16 +/- 0.13 x 10(-6) and 4.33 +/- 0.78 x 10(-6) transformants per cell, respectively. Low frequency UDD can be readily scaled up, allowing for the application of UDD not only in laboratory conditions but also on an industrial scale.
Regenerating lizard tails: A new model for investigating lymphangiogenesis (2003)

Impaired lymphatic drainage in human limbs causes the debilitating swelling termed lymphoedema. In mammals, known growth factors involved in the control of lymphangiogenesis (growth of new lymph vessels) are vascular endothelial growth factors-C and -D (VEGF-C/D). Here we characterize a model of lymphangiogenesis in which the tail of lizards is regenerated without becoming oedematous. Three weeks after the tail is shed (autotomy), there are a small number of large diameter lymphatic vessels in the regenerated tail. Thereafter, the number increases and the diameter decreases. A functional lymphatic network, as determined by lymphoscintigraphy, is established 6 wk after autotomy. The new network differs morphologically and functionally from that in original tails. This lymphatic regeneration is associated with an up-regulation of a reptilian homologue of the VEGF-C/D protein family (rVEGF-C/D), as determined by Western blot analysis using a human reactive VEGF-C polyclonal antibody. Regenerating lizard tails are potentially useful models for studying the molecular basis of lymphangiogenesis with a view to developing possible treatments for human lymphoedema.
Clinical implications of the genetics of sporadic colorectal cancer (2019)

Colorectal cancer (CRC) is common and at least 80% of cases are sporadic, without any significant family history. Prognostication and treatment have been relatively empirical for what has become increasingly identified as a genetically heterogeneous disease. There are three main genetic pathways in sporadic CRC: the chromosomal instability pathway, the microsatellite instability pathway and the CpG island methylator phenotype pathway. There is significant overlap between these complex molecular pathways and this limits the clinical application of CRC genetics. Recent Australian and New Zealand guidelines recommend routine testing of mismatch repair (MMR) status for new cases of CRC and selective KRAS and BRAF testing on the basis of diagnostic, prognostic and therapeutic implications. It is important that all clinicians treating CRC have an understanding of the importance of and basis for identifying key genetic features of CRC. It is likely that in the future better molecular characterization such as that allowed by the consensus molecular subtype classification will allow improved prognostication and targeted therapy in order to deliver more personalized treatment for CRC.
Wood Microbiology: Decay and Its Prevention (1992)

Introductory text on the principles of decay and discoloration processes in wood, with emphasis on the major fungal damages which may develop during the growth, storage, and use of wood. The characteristics, detection, effects, and control of microbial attacks are stressed. Provides a synthesis of the current literature on wood microbiology, a rapidly expanding field of study. (Abstractor's note: This is an important resource for conservation researchers studying the decay of wood in art and architecture.) The following is a list of chapter headings: 1) Introduction to wood microbiology; 2) Wood deterioration agents; 3) Characteristics and classification of fungi and bacteria; 4) Factors affecting the growth and survival of fungi in wood (fungal ecology); 5) Fungal metabolism in relation to wood decay; 6) The decay setting: some structural, chemical, and moisture features of wood in relation to decay development; 7) General features, recognition, and anatomical aspects of wood decay; 8) Chemical changes in wood caused by decay fungi; 9) Ultrastructural features of wood decay; 10) Changes caused by decay fungi in the strength and physical properties of wood; 11) Colonization and microbial interactions in wood decay; 12) Decays originating in the stems of living trees; 13) Biodeterioration of stored wood and its control; 14) Wood stains and discolorations; 15) Decay problems associated with some major uses of wood products; 16) Detection of internal decay; 17) Paint mildew and related degradative problems; 18) Natural decay resistance (wood durability); 19) Chemical protection of wood (wood preservation); and 20) Some trends in wood microbiology research and a new emphasis (biotechnology). -- AATA
Attenuated Human Parainfluenza Virus Type 1 (HPIV1) Expressing the Fusion Glycoprotein of Human Respiratory Syncytial Virus (RSV) as a Bivalent HPIV1/RSV Vaccine (2015)

There are no vaccines for the pediatric respiratory pathogens RSV and HPIV. We are developing live attenuated RSV and HPIV vaccines for use in virus-naive infants. Live attenuated RSV strains in particular are difficult to develop due to their poor growth and physical instability, but these obstacles could be avoided by the use of a vaccine vector. We describe the development and preclinical evaluation of live attenuated rHPIV1 vectors expressing the RSV F protein. Two different attenuated rHPIV1 backbones were each engineered to express RSV F from three different gene positions. The rHPIV1-C(Δ170)-F1 vector, bearing an attenuating deletion mutation (C(Δ170)) in the P/C gene and expressing RSV F from the pre-N position, was attenuated, stable, and immunogenic against the RSV F protein and HPIV1 in the hamster model and provided substantial protection against RSV challenge. This study provides a candidate rHPIV1-RSV-F vaccine virus suitable for continued development as a bivalent vaccine against two major childhood pathogens.