gebhart/patrepeval huggingface dataset:
Lymphocyte activation by the Fc region of immunoglobulin. I. Role of prostaglandins in the down regulation of Fc fragment-induced polyclonal antibody production. (1985)

Fc fragment-, subfragment-, and p23-induced polyclonal antibody production are regulated by endogenous and exogenous PGE. Addition of the PG synthetase inhibitor indomethacin (IM) to murine spleen cell cultures resulted in a significant increase in the amount of Ig secreted. Moreover, addition of exogenous PGE to culture resulted in a marked suppression of IgM and IgG secretion. Splenic adherent macrophages and P388D1 cells release PGE upon stimulation with Fc fragments, subfragments, and p23. The inclusion of IM or aspirin in culture was found to abrogate the ability of Fc fragments to induce PGE release from adherent cells. These results suggest a role for PG in immune complex mediated regulation of immune responses.
Monitoring Surface Water Chemistry Near Magnesium Chloride Dust Suppressant Treated Roads in Colorado (2009)

Magnesium chloride (MgCl2)-based dust suppression products are commonly used throughout western United States on nonpaved roads for dust suppression and road stabilization by federal, state, and county transportation agencies. The environmental implications of annually applying these products throughout spring and summer months on adjacent stream chemistry are not known. Sixteen streams were monitored biweekly for 1 to 2 yr in two Colorado counties for a suite of water quality variables up and downstream of nonpaved roads treated with MgCl2-based dust suppression products. Eight of 16 streams had significantly higher downstream than upstream concentrations of chloride or magnesium over the entire monitoring period (p<or=0.05). Mean downstream chloride concentrations ranged from 0.17 to 36.2 mg/L and magnesium concentrations ranged from 1.06 to 12.8 mg/L. Several other ions and compounds, including those commonly found in dust suppression products such as sodium, calcium, and sulfate, were also significantly higher downstream at some sites. Downstream electrical conductivity (EC), chloride and magnesium concentrations were positively correlated with road surface area draining water toward the stream and yearly amount of MgCl2 applied (R2=0.75, 0.51 and 0.49, respectively), indicating that road managers can limit the amount of product entering roadside streams by assessing drainage characteristics and application rates in best management practices. Although MgCl2-based dust suppressants did move into some roadside streams, the concentrations detected were below those reported to adversely affect fresh water aquatic organisms, but the ultimate fate of these ions in Colorado waterbodies are not known.
Fluid motion for microgravity simulations in a random positioning machine (2011)

To understand the role of gravity in biological systems one may decrease inertial acceleration by going into free-fall conditions such as available on various platforms. These experiments are cumbersome and expensive. Thus, alternative techniques like Random Positioning Machines (RPM) are now widely used to simulate the micro-gravity environment (Yuge et al., 2003; Borst and van Loon, 2009; Pardo et al., 2005). These instruments generate random movements so that cumulative gravitational effects cancel out over time. However, comparative studies performed with the RPM and culture cells were unable to reproduce the spaceflight results (Hoson et al., 1997). These differences may be explained by stresses acting on the culture cells in an RPM whereas these stresses are not present in microgravity conditions. They may be caused by internal fluid motion, originating from instationary rotation. The aim of this study is to quantify fluid flow behavior and wall shear stresses (as they are relevant to cells cultured at the flask wall), and internal shear stresses as they are relevant to suspended (free-floating) cells in an RPM container. We do this both experimentally using Particle Image Velocimetry (PIV) and numerically using 3D Direct Numerical Simulation (DNS) of the flow.
A three-nucleotide deletion in the UL97 open reading frame is responsible for the ganciclovir resistance of a human cytomegalovirus clinical isolate (1995)

Multiple human cytomegalovirus (HCMV) strains frequently coexist in patients with AIDS, and chronic ganciclovir treatment may favor the emergence of ganciclovir-resistant viral mutants. We report the molecular and biochemical characterization of a HCMV ganciclovir-resistant strain (VR3480) previously recovered from a patient with AIDS who was undergoing multiple courses of ganciclovir treatment (G. Gerna, F. Baldanti, M. Zavattoni, A. Sarasini, E. Percivalle, and M. G. Revello, Antiviral Res. 19:333-345, 1992). Ganciclovir resistance of strain VR3480 was related to impaired ability to monophosphorylate the drug, as indicated by the finding that ganciclovir phosphorylation values for VR3480 were 30% of those shown by the HCMV reference strain AD169 in an in vitro activity assay. Sequencing of the UL97 gene of VR3480, which encodes the viral kinase responsible for ganciclovir phosphorylation, showed an in-frame deletion of three nucleotides resulting in the loss of a leucine at position 595 in the polypeptide. Mutant VR3480 UL97 DNA was able to transfer resistance to the AD169 strain in marker rescue experiments. Analysis of virus isolates and blood polymorphonuclear leukocyte samples spanning the 2-year follow-up period of the patient showed that ganciclovir-resistant strain VR3480 arose ex novo during prolonged antiviral treatment and accounted for the majority of virus load circulating in blood during the period of clinical resistance to ganciclovir treatment.
Graph-based simulated annealing and support vector machine in malware detection (2011)

As ongoing war between the malware developer and defense mechanism planners there is a great challenge in providing an effective defense mechanism against evasion technique used by malware authors. The present paper provides a framework for malware detection based on the analysis of graphs introduced from instructions of the executable objects. The graph is constructed through the graph extractor, and then we used the simulated annealing algorithm to approximate the graph similarity measure. The threshold value plays a great role to relate the support vector machine to confirm the real class of the file, benign or malicious.
Nanobody-triggered lockdown of VSRs reveals ligand reloading in the Golgi (2018)

Protein degradation in lytic compartments is crucial for eukaryotic cells. At the heart of this process, vacuolar sorting receptors (VSRs) bind soluble hydrolases in the secretory pathway and release them into the vacuolar route. Sorting efficiency is suggested to result from receptor recycling. However, how and to where plant VSRs recycle remains controversial. Here we present a nanobody-epitope interaction-based protein labeling and tracking approach to dissect their anterograde and retrograde transport routes in vivo. We simultaneously employ two different nanobody-epitope pairs: one for the location-specific post-translational fluorescence labeling of receptors and the other pair to trigger their compartment-specific lockdown via an endocytosed dual-epitope linker protein. We demonstrate VSR recycling from the TGN/EE, thereby identifying the cis-Golgi as the recycling target and show that recycled VSRs reload ligands. This is evidence that bidirectional VSR-mediated sorting of vacuolar proteins exists and occurs between the Golgi and the TGN/EE.
Machine learning for comprehensive forecasting of Alzheimer’s Disease progression (2019)

Most approaches to machine learning from electronic health data can only predict a single endpoint. The ability to simultaneously simulate dozens of patient characteristics is a crucial step towards personalized medicine for Alzheimer's Disease. Here, we use an unsupervised machine learning model called a Conditional Restricted Boltzmann Machine (CRBM) to simulate detailed patient trajectories. We use data comprising 18-month trajectories of 44 clinical variables from 1909 patients with Mild Cognitive Impairment or Alzheimer's Disease to train a model for personalized forecasting of disease progression. We simulate synthetic patient data including the evolution of each sub-component of cognitive exams, laboratory tests, and their associations with baseline clinical characteristics. Synthetic patient data generated by the CRBM accurately reflect the means, standard deviations, and correlations of each variable over time to the extent that synthetic data cannot be distinguished from actual data by a logistic regression. Moreover, our unsupervised model predicts changes in total ADAS-Cog scores with the same accuracy as specifically trained supervised models, additionally capturing the correlation structure in the components of ADAS-Cog, and identifies sub-components associated with word recall as predictive of progression.
SUMO-1 conjugation selectively modulates STAT1-mediated gene responses (2005)

Signal transducers and activators of transcription 1 (STAT1) is a critical mediator of interferon (IFN)-induced gene responses. Recently, STAT1 was found to become modified by small ubiquitin-like modifier 1 (SUMO-1) conjugation at Lys703 through the SUMO E3 ligase function of protein inhibitors of activated STAT (PIAS) proteins. However, the physiologic function of sumoylation in STAT1 is still unclear. Here, we show that mutations in the SUMO attachment site in STAT1 result in increased transcriptional activity in a fashion that is selective among IFN-gamma target genes. The sumoylation-defective STAT1 mutant displayed increased induction of guanylate-binding protein 1 (GBP1) and transporters associated with antigen presentation 1 (TAP1) transcription but not interferon regulatory factor 1 (IRF1) transcription. Moreover, the sumoylation-defective mutant STAT1-KR showed a prolonged DNA-binding activity and nuclear localization in response to IFN-gamma stimulation. These results suggest that sumoylation has a defined negative regulatory effect on selective STAT1-mediated transcription responses.
Repression of human activation induced cytidine deaminase by miR-93 and miR-155 (2011)

Together, our findings demonstrate that miR-93 and miR-155 constitutively suppress AID translation in MCF-7 cells, suggesting widespread roles for these miRs in preventing genome cytidine deaminations, mutagenesis, and oncogenic transformation. In addition, our characterization of an obscured miR-93 target site located within the AID 3'UTR supports the recent suggestion that many miR regulations have been overlooked due to the prevalence of truncated 3'UTR annotations.
Increased serum interleukin‐5 and vascular endothelial growth factor in children with acute mycoplasma pneumonia and wheeze (2009)

Acute mycoplasma pneumonia may be accompanied by wheeze in some children considered not to have asthma. The aim of the present study was to evaluate cytokine secretion in children with acute mycoplasma pneumonia and wheeze. We studied 58 patients with mycoplasma pneumonia (12 with wheeze, Group 1; 46 without wheeze, Group 2) and 36 patients of non-mycoplasma pneumonia (Group 3). Serum levels of interleukin (IL)-4, IL-5, interferon (IFN)-gamma, and vascular endothelial growth factor (VEGF) were measured using an enzyme-linked immunosorbent assay kits. The mean +/- SD IL-5 level of Group 1 was 97.1 +/- 73.0 pg/ml, which was significantly higher than that of Group 2 (28.2 +/- 32.2 pg/ml) and that of Group 3 (35.7 +/- 42.0 pg/ml). The mean +/- SD VEGF level of Group 1 was 687.5 +/- 385.8 pg/ml, which was significantly higher than that of Group 2 (310.0 +/- 251.9 pg/ml) and that of Group 3 (402.3 +/- 279.5 pg/ml). No significant differences in serum levels of IL-4, IFN-gamma, and IgE were observed between the groups. Our results show that children with mycoplasma pneumonia and wheeze have significantly higher serum levels of IL-5 and VEGF. These increased immune responses may be associated with the pathophysiological mechanisms by which the Mycoplasma pneumoniae contribute to the development of wheeze during acute mycoplasma pneumonia.
Klaus Seybold : Der aaronitische Segen. Studien zu Numeri 6.22-27, Neukirchener Verlag, 1977 (1979)

Jacob Edmond. Klaus Seybold : Der aaronitische Segen. Studien zu Numeri 6.22-27, Neukirchener Verlag, 1977. In: Revue d'histoire et de philosophie religieuses, 59e année n°1,1979. pp. 86-87.
Decreased kinase activity of insulin receptors from adipocytes of non-insulin-dependent diabetic subjects. (1987)

The tyrosine kinase activity of the insulin receptor was examined with partially-purified insulin receptors from adipocytes obtained from 13 lean nondiabetics, 14 obese nondiabetics, and 13 obese subjects with non-insulin-dependent diabetes (NIDDM). Incubation of receptors at 4 degrees C with [gamma-32P]ATP and insulin resulted in a maximal 10-12-fold increase in autophosphorylation of the 92-kDa beta-subunit of the receptor with a half maximal effect at 1-3 ng/ml free insulin. Insulin receptor kinase activity in the three experimental groups was measured by means of both autophosphorylation and phosphorylation of the exogenous substrate Glu4:Tyr1. In the absence of insulin, autophosphorylation and Glu4:Tyr1 phosphorylation activities, measured with equal numbers of insulin receptors, were comparable among the three groups. In contrast, insulin-stimulated kinase activity was comparable in the control and obese subjects, but was reduced by approximately 50% in the NIDDM group. These findings indicate that the decrease in kinase activity in NIDDM resulted from a reduction in coupling efficiency between insulin binding and activation of the receptor kinase. The insulin receptor kinase defects observed in NIDDM could be etiologically related to insulin resistance in NIDDM and the pathogenesis of the diabetic state.
Long-Term Differential Changes in Mouse Intestinal Metabolomics after γ and Heavy Ion Radiation Exposure (2014)

Tissue consequences of radiation exposure are dependent on radiation quality and high linear energy transfer (high-LET) radiation, such as heavy ions in space is known to deposit higher energy in tissues and cause greater damage than low-LET γ radiation. While radiation exposure has been linked to intestinal pathologies, there are very few studies on long-term effects of radiation, fewer involved a therapeutically relevant γ radiation dose, and none explored persistent tissue metabolomic alterations after heavy ion space radiation exposure. Using a metabolomics approach, we report long-term metabolomic markers of radiation injury and perturbation of signaling pathways linked to metabolic alterations in mice after heavy ion or γ radiation exposure. Intestinal tissues (C57BL/6J, female, 6 to 8 wks) were analyzed using ultra performance liquid chromatography coupled with electrospray quadrupole time-of-flight mass spectrometry (UPLC-QToF-MS) two months after 2 Gy γ radiation and results were compared to an equitoxic ⁵⁶Fe (1.6 Gy) radiation dose. The biological relevance of the metabolites was determined using Ingenuity Pathway Analysis, immunoblots, and immunohistochemistry. Metabolic profile analysis showed radiation-type-dependent spatial separation of the groups. Decreased adenine and guanosine and increased inosine and uridine suggested perturbed nucleotide metabolism. While both the radiation types affected amino acid metabolism, the ⁵⁶Fe radiation preferentially altered dipeptide metabolism. Furthermore, ⁵⁶Fe radiation caused upregulation of 'prostanoid biosynthesis' and 'eicosanoid signaling', which are interlinked events related to cellular inflammation and have implications for nutrient absorption and inflammatory bowel disease during space missions and after radiotherapy. In conclusion, our data showed for the first time that metabolomics can not only be used to distinguish between heavy ion and γ radiation exposures, but also as a radiation-risk assessment tool for intestinal pathologies through identification of biomarkers persisting long after exposure.
Effects of magnetic field gradients on strong relativistic electron rings (1974)

Experimental investigations on the RECE-Berta device at Cornell show that weak gradients in the applied magnetic field do not influence the stability of strong relativistic electron rings for field differences across the rings of up to 0.8%. The main effect of such gradients is a radial displacement of the equilibrium position of the rings toward the low-field region of the tank. The magnitude of this displacement depends on the field gradient, and the strength and geometry of the electron ring. A theory for the displaced electron ring equilibria is presented which assumes a balance of the forces due to the external field and the image fields arising from currents in the conducting tank wall. The theory shows good quantitative agreement with the observed ring movement. From these results it appears that the final “dump” of the rings can be explained by the existence of a gradient in the basic mirror field.
p-Toluenesulfonylation of 1,2-O-Cyclohexylidene-myo-inositol (1971)

Abstract p-Toluenesulfonylation of 1,2-O-cyclohexylidene-myo-inositol (la) afforded one mono (1), three di (1,4, 1,5, and 1,6), three tri (1,4,5, 1,4,6, and 1,5,6), and one tetra (1,4,5,6)-O-p-toluenesulfonyl derivatives of myo-inositol, and all the structures have been established by way of their proton magnetic resonance (PMR) spectra and the reaction sequences.
Asymmetric bismuth-rhodamines as an activatable fluorogenic photosensitizer (2021)

Bismuth-rhodamine compounds stand out for their unique excitable photosensitizing properties and concomitant fluorescence; however, further knowledge of the structure-property relationship is required to expand the scope of their practical application. With this aim, this study describes the first examples of asymmetric bismuth-incorporated rhodamines, BiRNH and BiRAc, including their synthesis, photophysical properties, and photosensitizing abilities. Upon red light excitation, BiRNH exhibits detectable emission and photosensitizing properties, while the N-acetylated derivative BiRAc shows a hypsochromic shift in the absorption wavelength and attenuation of emission and photosensitizing ability. These significantly different photophysical properties enabled us to design an activatable fluorogenic photosensitizer, BiRGlu, which bears a γ-glutamyl group instead of the acetyl group in BiRAc. The γ-glutamyl group can be cleaved by γ-glutamyl transpeptidase (GGT) to produce BiRNH, which acts as a red-light-excitable fluorophore and photosensitizer. A cell study revealed that the phototoxicity and fluorescence of BiRGlu could be simultaneously and selectively activated in the cells with high GGT activity. Thus, we established that BiRNH could be envisaged as a versatile scaffold for activatable fluorogenic photosensitizers.
Borna disease virus infection of a horse in Great Britain (2011)

The cartilage-to-bone transition is an essential process in healthy bone development and repair. Our previous work has shown that when the cells found within the human periosteum (the membrane surrounding the bone) are cultured in human serum (HS) as opposed to the standard animal serum (FBS), these cells have greater bone-forming capacity as assessed in an ectopic assay in nude mice. What is not understood is the molecular interactions that permitted this enhanced biological potency. Herein, virtual networks are created to identify the key proteins driving increased bone formation from these cells. Key signalling factors were identified through a network analysis, where FGFR3 was pinpointed as a major differential regulator between cells grown in HS and cells grown in FBS. This analysis was validated through an analysis of human-derived periosteal progenitor cells (PDCs) containing a constitutively active (ca) FGFR3. Following removal and analysis, we found that the FGFR3-ca cells that were implanted on bone void filler scaffolds in mice had an abundance of bone and cartilage that were present compared to the scaffold containing normal/healthy cells. This suggests that these cells were undergoing enhanced cartilage-to-bone transitions and that this protein may be a potentially novel therapeutic target for diseases where the cartilage-to-bone transition is affected such as during poor fracture healing.
Novel Processes for Treatment of Syncrude Fine Transition and Marine Ore Tailings (2007)

Syncrude Canada Ltd. has compiled a substantial amount of work on tailings research and development to determine the most effective treatment and deposition processes to increase reclamation options, water reuse and thermal energy recovery. This research has shown that the conventional processes using a single flocculant, a single coagulant or a coagulant-flocculant combination are ineffective for transition and marine ore tailings. For example, using a single flocculant to treat transition or marine ore tailings resulted in a thickener overflow of 1∼4% solids content compared with the target solids content of <0.5% obtained with estuarine ore. On the other hand, new processes including Coagulation-Flocculation-Coagulation (CFC), Flocculation-Coagulation (FC) and Flocculation-Coagulation-Flocculation (FCF) have been found to be acceptable options. However, the FCF process outperformed the CFC and FC processes because the FCF process produced huge flocs resulting in fast initial settling rates. The key components of these technologies consist of the recipe of chemicals and their sequences of addition. With these technologies, almost all submicron clay minerals are aggregated together and settle as a whole resulting in a clear supernatant of less than 0.13% solids.
Trends in governance and management of higher education (1998)

This report identifies trends affecting governance and management of higher education based on the experience of some developed countries, featuring issues relevant to the present situation in Brazil. It further examines the impact external changes have on the governance of higher education and how these changes affect labor markets for graduates; how social changes affect student demand in education quality and quantity; why technological changes are perceived to have potential implications for education provision; and, how the growth of issue based research impacts higher education governance. Trends in government fluctuate from control to supervision, through public funds allocation and accountability. Furthermore, the report analyzes governance and management at the institutional level, discussing related changes within higher education institutions themselves. It is suggested these trends lean more towards decision making by consent rather than consensus, eventually enabling universities to move forward with confidence.
Protéolyse protéasomale indépendante de l'ubiquitylation des susbtrats (2010)

International audience
Formation of a transient periodic stripe domain pattern in nematic AB block copolymer solution during photo-induced director reorientation (1998)

A transient periodic stripe domain pattern is observed during photo-induced director reorientation of a sample containing rod-like block copolymer vesicles in a low molecular weight nematic liquid crystal.