gebhart/patrepeval huggingface dataset:
Lung Cell-specific Expression of the Murine Surfactant Protein A (SP-A) Gene Is Mediated by Interactions between the SP-A Promoter and Thyroid Transcription Factor-1 (1995)

Cis-acting elements determining lung epithelial cell-selective transcription of the murine surfactant protein A (SP-A) gene were identified between nucleotide positions -255 and -57. This region of the murine SP-A gene contained nucleotide sequences consistent with thyroid transcription factor-1 (TTF-1) binding motifs. An SP-A-CAT plasmid containing the TTF-1 binding sites was transcriptionally active in mouse lung epithelial (MLE-15) cells but not in HeLa, 3T3, or H441 cells. However, transcription of the SP-A-CAT construct was activated after cotransfection of HeLa cells with a vector expressing recombinant TTF-1, pCMV-TTF-1. Recombinant TTF-1 homeodomain protein bound to four distinct binding sites located between nucleotides -166 to -117 [corrected]. Proteins in nuclear extracts of MLE-15 cells bound TTF-1 binding sites and were supershifted by TTF-1 antibody. Mutations of three of the TTF-1 binding sites in this region reduced expression of the SP-A-CAT construct in transfected MLE-15 cells and reduced transactivation in HeLa cells. TTF-1 interacts with complex protein/DNA binding sites located in the 5'-flanking region of the murine SP-A gene enhancing lung epithelial cell-specific expression in vitro.
The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging (2013)

International audience
Studies on the Sicca Syndrome in Patients with Rheumatoid Arthritis (1970)

SummarySecretion from the parotid and the lacrimal glands has been studied in two similar groups of 48 subjects, one consisting of RA patients, the other a control group. Sialometry and sialography has been performed as regards the parotid glands; the secretion of the lacrimal glands has been measured with Schirmer's test I and the occurrence of conjunctival and corneal epithelial defects stainable with Rose-Bengal has been studied.It has been shown that lacrimal and parotid secretion was significantly reduced in the RA group as compared with the control group; that epithelial defects typical for KCS occurred significantly more often in the RA group; that parenchymal changes, sialodochiectasias, existed in the RA group but that sialodochiectasias were completely absent in the control group; that there was no significant co-variation in the RA group between lacrimal and salivary secretion or lacrimal secretion and sialodochiectasias; that criteria for Sjögren's syndrome were fulfilled by 15 subjects in the RA group. The results of the study indicate that Sjögren's syndrome is to be regarded as part of the RA complex.
Synergic activities of streptococcal pyrogenic exotoxin A and lipoteichoic acid in cytokine induction. (2000)

The present study was carried out to gain insight into the mechanisms involved in the pathogenesis of streptococcal toxic shock syndrome (TSS) and other acute invasive diseases caused by Streptococcus pyogenes (GAS). Specifically, since both whole bacteria and their soluble products are often present in the blood in these conditions, we sought to detect possible synergic activities of somatic and extracellular products in inducing mediators release. For this purpose, whole blood cultures from healthy donors were incubated with different concentrations of streptococcal pyrogenic exotoxin A (SpeA), which is considered a major molecular effector of TSS, heat-killed GAS and cell-wall components such as lipoteichoic acid (LTA) and soluble peptidoglican (sPGN). Significant levels of TNF-alpha, IL-1 alpha and IFN-gamma were found in supernatants from cultures incubated with each of the four inducers alone. Whole GAS and both cell-wall components were more effective (p < 0.05) than SpeA in inducing cytokine release. Whole GAS, at weight basis, was a more potent inducer than LTA and sPGN and LTA, at weight basis, was a more potent inducer than sPGN. In order to verify possible additive or synergic effects of exotoxic and parietal compounds in inducing cytokine release, whole blood cells were incubated with mixtures of SpeA and LTA at different molecular ratio. TNF-alpha, IL-1 alpha and IFN-gamma levels in supernatants were significantly (p < 0.05) higher in supernatants of cultures stimulated simultaneously with the two components than those of cultures stimulated with a single agent. Moreover, these levels were significantly higher than the sum of cytokine levels induced by single components. This study shows that parietal compounds can act in synergy with exotoxins in inducing the release of cytokines, which appear to be the major mediators of TSS.
Constitutive Expression of phVEGF 165 After Intramuscular Gene Transfer Promotes Collateral Vessel Development in Patients With Critical Limb Ischemia (1998)

These findings may be cautiously interpreted to indicate that intramuscular injection of naked plasmid DNA achieves constitutive overexpression of VEGF sufficient to induce therapeutic angiogenesis in selected patients with critical limb ischemia.
Domain walls inside localised orientifolds (2015)

The equations of motion of toroidal orientifold compactifications with fluxes are in one-to-one correspondence with gauged supergravity if the orientifold (and D-brane) sources are smeared over the compact space. This smeared limit is identical to the approximation that ignores warping. It is therefore relevant to compare quantities obtained from the gauged supergravity with the true 10d solution with localised sources. In this paper we find the correspondence between BPS domain walls in gauged SUGRA and 10D SUGRA with localised sources. Our model is the simplest orientifold with fluxes we are aware of: an O6/D6 compactification on $$ {\mathbb{T}}^3/{\mathbb{Z}}_2 $$ in massive IIA with H 3-flux. The BPS domain walls correspond to a O6/D6/NS5/D8 bound state. Our analysis reveals that the domain wall energy computed in gauged SUGRA is unaffected by the localisation of the O6/D6 sources.
Structural Difference in the Complement Activation Site of Human IgG1 and IgG3 (2009)

The C1q binding epicentre on IgG molecules involves residues Asp(270), Lys(322), Pro(329) and Pro(331) in the C(H)2 domain. IgG1 and IgG3 are usually the most efficient of the four human IgG subclasses in activating complement and they both share all these residues. To reveal possible differences in the structural requirement for complement activation, we created a number of NIP (5-iodo-4-hydroxy-3-nitro-phenacetyl) specific IgG1 and IgG3 antibodies with parallel mutations in or near the putative C1q binding site. The mutants were tested simultaneously for antibody induced, antibody-dependent complement-mediated lysis (ADCML) at high and low antigen concentration on the target cells using sera of human, rabbit and guinea pig as complement source. In addition, we tested the antibodies against target cells decorated with the NP hapten, which has 10-fold lower affinity for the antibodies compared to the NIP hapten. We also used ELISA methods to measure complement activation. We observed a clear difference between IgG1 and IgG3 localized to residues Asp(270), Leu(334), Leu(335). For all these residues, and especially for Asp(270), IgG1 was heavily reduced in complement activation, while IgG3 was only moderated reduced, by alanine substitution. This difference was independent of the long hinge region of IgG3, demonstrated by hinge region truncation of this isotype such that it resembles that of IgG1. This report indicates the presence of structural differences between human IgG1 and IgG3 in the C1q binding site, and points to a specialization of the two isotypes with respect to complement activation.
Three-dimensional modeling of the gas field distribution of a high-pressure gas jet used in laser fusion cutting (2001)

A three-dimensional mathematical model for investigating theoretically the gas flow field distribution of the free exit gas jet from both subsonic and supersonic nozzles under the regime of high-pressure gas-assisted laser fusion cutting is presented in this article. The influence of the flow nonuniformity in the subsonic nozzle exit upon the field distribution in the free gas jet is considered in this model. The calculated results are in good agreement with those observed by shadowgraphy. The relationships between the inlet stagnation pressure and the flow field distribution, incident shock, and normal shock of a gas jet in free space are established. The processing characteristics of the free space gas jet in the high-pressure gas-assisted laser cutting process for both subsonic and supersonic nozzles are analyzed in detail. Compared with that from the subsonic nozzle, such as the commonly used conical or conical–cylindrical nozzle, the gas jet from the supersonic nozzle (Laval nozzle) possesses good features such as uniform distribution, maximum even momentum thrust, and a parallel jet boundary under the condition of the designed “working pressure.”
Age-related changes in the default mode network are more advanced in Alzheimer disease (2011)

The results of this study indicate that the DMN abnormalities observed in patients with AD represent an accelerated aging pattern of connectivity compared with matched controls.
Toward an understanding of flow in video games (2008)

In the domain of computer games, research into the interaction between player and game has centred on 'enjoyment', often drawing in particular on optimal experience research and Csikszentmihalyi's 'Flow theory'. Flow is a well-established construct for examining experience in any setting and its application to game-play is intuitive. Nevertheless, it's not immediately obvious how to translate between the flow construct and an operative description of game-play. Previous research has attempted this translation through analogy. In this article we propose a practical, integrated approach for analysis of the mechanics and aesthetics of game-play, which helps develop deeper insights into the capacity for flow within games. The relationship between player and game, characterized by learning and enjoyment, is central to our analysis. We begin by framing that relationship within Cowley's user-system-experience (USE) model, and expand this into an information systems framework, which enables a practical mapping of flow onto game-play. We believe this approach enhances our understanding of a player's interaction with a game and provides useful insights for games' researchers seeking to devise mechanisms to adapt game-play to individual players.
Alpha-mannosidosis (2008)

Alpha-mannosidosis is an inherited lysosomal storage disorder characterized by immune deficiency, facial and skeletal abnormalities, hearing impairment, and intellectual disability. It occurs in approximately 1 of 500,000 live births. The children are often born apparently normal, and their condition worsens progressively. Some children are born with ankle equinus or develop hydrocephalus in the first year of life. Main features are immune deficiency (manifested by recurrent infections, especially in the first decade of life), skeletal abnormalities (mild-to-moderate dysostosis multiplex, scoliosis and deformation of the sternum), hearing impairment (moderate-to-severe sensorineural hearing loss), gradual impairment of mental functions and speech, and often, periods of psychosis. Associated motor function disturbances include muscular weakness, joint abnormalities and ataxia. The facial trait include large head with prominent forehead, rounded eyebrows, flattened nasal bridge, macroglossia, widely spaced teeth, and prognathism. Slight strabismus is common. The clinical variability is significant, representing a continuum in severity. The disorder is caused by lysosomal alpha-mannosidase deficiency. Alpha-mannosidosis is inherited in an autosomal recessive fashion and is caused by mutations in the MAN2B1 gene located on chromosome 19 (19 p13.2-q12). Diagnosis is made by measuring acid alpha-mannosidase activity in leukocytes or other nucleated cells and can be confirmed by genetic testing. Elevated urinary secretion of mannose-rich oligosaccharides is suggestive, but not diagnostic. Differential diagnoses are mainly the other lysosomal storage diseases like the mucopolysaccharidoses. Genetic counseling should be given to explain the nature of the disease and to detect carriers. Antenatal diagnosis is possible, based on both biochemical and genetic methods. The management should be pro-active, preventing complications and treating manifestations. Infections must be treated frequently. Otolaryngological treatment of fluid in the middle ear is often required and use of hearing aids is invariably required. Early educational intervention for development of social skills is needed and physiotherapy is important to improve bodily function. Orthopedic surgery may be necessary. The long-term prognosis is poor. There is an insidiously slow progression of neuromuscular and skeletal deterioration over several decades, making most patients wheel-chair dependent. No patients manage to be completely socially independent. Many patients are over 50 years of age.
Collaborative or Simply Uncaged? Understanding Human-Cobot Interactions in Automation (2020)

Collaborative robots, or cobots, represent a breakthrough technology designed for high-level (e.g. collaborative) interactions between workers and robots with capabilities for flexible deployment in industries such as manufacturing. Understanding how workers and companies use and integrate cobots is important to inform the future design of cobot systems and educational technologies that facilitate effective worker-cobot interaction. Yet, little is known about typical training for collaboration and the application of cobots in manufacturing. To close this gap, we interviewed nine experts in manufacturing about their experience with cobots. Our thematic analysis revealed that, contrary to the envisioned use, experts described most cobot applications as only low-level (e.g. pressing start/stop buttons) interactions with little flexible deployment, and experts felt traditional robotics skills were needed for collaborative and flexible interaction with cobots. We conclude with design recommendations for improved future robots, including programming and interface designs, and educational technologies to support collaborative use.
Overlapping distribution of KATP channel‐forming Kir6.2 subunit and the sulfonylurea receptor SUR1 in rodent brain (1997)

ATP-sensitive K+ channels comprise a complex of at least two proteins: a member of the inwardly rectifying Kir6 family (e.g. Kir6.2) and a sulphonylurea receptor (e.g. SUR1) which belongs to the ATP-binding cassette (ABC) superfamily. Using specific radiolabeled antisense oligonucleotides, the cellular localization of both mRNAs was investigated in the rodent brain by in situ hybridization. The distribution of both transcripts was widespread throughout the brain and showed a high degree of overlap with peak expression levels in the hippocampus, neocortex, olfactory bulb, cerebellum, and several distinct nuclei of the midbrain and brainstem, indicating their important role in vital brain function.
High doses of tyrosine kinase inhibitor PTK787 enhance the efficacy of ischemic hypoxia for the treatment of hepatocellular carcinoma: dual effects on cancer cell and angiogenesis (2006)

The present study aimed to investigate the therapeutic efficacy of combining vascular endothelial growth factor (VEGF) receptor blockade using tyrosine kinase inhibitor PTK787 with hypoxia for the treatment of hepatocellular carcinoma (HCC). The in vivo effects of the treatments were determined in a rat orthotopic HCC model, in which hypoxia was generated by hepatic artery ligation (HAL). Compared with HAL alone, PTK787 combined with HAL significantly prolonged the animal survival, reduced the tumor size, induced more tumor tissue necrosis and apoptosis, and down-regulated the expression of von Willebrand factor. The mechanism was explored in vitro using murine HCC and endothelial cell lines, respectively. PTK787 combined with hypoxia decreased the expression of VEGF and VEGF receptors in both cell lines and suppressed the cell viability by induction of cell cycle arrest and promotion of apoptosis. Up-regulation of cleaved form caspase-9 and down-regulation of Bcl-2 and cyclin D1 were detected with the combined treatment. Hypoxia sensitized endothelial cells to the inhibitory effect of PTK787 on forming tubular-like structure. The motility of tumor cells was inhibited by hypoxia and the combined approach, with down-regulation of Rac1, Rho, and phosphorylated Akt expression. However, in the endothelial cells, the combined treatment inhibited the hypoxia-enhanced cell motility, with suppressed Rac1, Rho, and phosphorylated Akt expression. In conclusion, PTK787 combined with hypoxia achieved a better therapeutic efficacy than hypoxia alone through enhancing hypoxia-induced antitumor cell effect and preventing the activation of angiogenic process.
Influence of Electrolyte on Lithium Cycling Efficiency with Pressurized Electrode Stack (1994)

The dependence of lithium cycling efficiency on stack pressure was studied for several electrolytes. To evaluate the cycling efficiency , we calculated the figure of merit of lithium as . The effect of solvents on the change with pressure was examined for solute electrolytes containing 2‐methyltetrahydrofuran (2MeTHF), ethylene carbonate (EC)/2MeTHF, propylene carbonate (PC), or EC/PC. The electrolyte showed the largest (80 at 125 kg/cm2). With the electrolytes and , was less dependent on stack pressure than it was with the electrolytes and EC/2MeTHF, probably because a different separator was used for the former electrolytes. Examining the effect of the solute on the change with pressure showed that the for reached maximum values at 50 and 75 kg/cm2, respectively, and that the values for increased with increasing stack pressure up to at least 125 kg/cm2.
Human linker histones: interplay between phosphorylation and O-β-GlcNAc to mediate chromatin structural modifications (2011)

Eukaryotic chromatin is a combination of DNA and histone proteins. It is established fact that epigenetic mechanisms are associated with DNA and histones. Initial studies emphasize on core histones association with DNA, however later studies prove the importance of linker histone H1 epigenetic. There are many types of linker histone H1 found in mammals. These subtypes are cell specific and their amount in different types of cells varies as the cell functions. Many types of post-translational modifications which occur on different residues in each subtype of linker histone H1 induce conformational changes and allow the different subtypes of linker histone H1 to interact with chromatin at different stages during cell cycle which results in the regulation of transcription and gene expression. Proposed O-glycosylation of linker histone H1 promotes condensation of chromatin while phosphorylation of linker histone H1 is known to activate transcription and gene regulation by decondensation of chromatin. Interplay between phosphorylation and O-β-GlcNAc modification on Ser and Thr residues in each subtype of linker histone H1 in Homo sapiens during cell cycle may result in diverse functional regulation of proteins. This in silico study describes the potential phosphorylation, o-glycosylation and their possible interplay sites on conserved Ser/Thr residues in various subtypes of linker histone H1 in Homo sapiens.
Chemical Mutagenesis of Human Interferon-β: Construction, Expression in E. coli , and Biological Activity of Sodium Bisulfite-Induced Mutations (1987)

A series of modified human interferon-beta (IFN-beta) genes was produced by sodium bisulfite treatment of the IFN-beta gene cloned in M13. A library of mutated sequences was generated from which subgenomic fragments containing one or a small number of coding alterations were isolated and substituted into the IFN-beta gene in an E. coli expression vector. A number of modified genes and their expression products were evaluated. In several instances levels of expression and biological activity profiles are altered compared to the parental gene product. A number of key amino acids can be identified, whose substitutions have marked effects on biological activity of IFN-beta.
Structure‐function studies on human macrophage colony‐stimulating factor (M‐CSF) (1997)

M-CSF (CSF-1) can be produced in a variety of structural forms that may affect function in vivo. Truncated, nonglycosylated forms of recombinant M-CSF (rM-CSF) from E. coli have been refolded in vitro in high yield and shown to be functionally equivalent in vitro to glycosylated rM-CSF secreted from mammalian cells. An N-terminal domain of 149 amino acids is produced by all of the known M-CSF mRNA splice variants and is the region responsible for bioactivity observed in vitro. Heterodimeric rM-CSFs from different splice variants containing this domain were produced in pure form by refolding in vitro, and are fully active, but have yet to be observed in vivo. The circulating half-life of truncated M-CSF forms injected intravenously into rats increased with the MW of the M-CSF used. Large increases in half-life in vivo were observed following chemical addition of a single molecule of 10 kD polyethylene glycol to rM-CSF in vitro. The crystal structure of rM-CSF revealed that M-CSF is a member of a family of molecules related by having a distinctive four-helical-bundle structural core. Site-directed mutagenesis showed that residues in or near helix A and helix C are involved in receptor binding, as reflected by decreased bioactivity and receptor binding of certain mutants. A soluble form of the M-CSF receptor, c-fms, was produced in a baculovirus/Sf9 expression system and purified to homogeneity. The MW of rM-CSF saturated with this soluble receptor was determined by molecular sieve chromatography and light scattering. Each dimeric M-CSF molecule appears to bind two soluble receptor molecules in vitro, supporting the observation that M-CSF signaling is linked to receptor dimerization. Mol Reprod Dev 46:31–38, 1997. © 1997 Wiley-Liss, Inc.
A non-classical translocation involving 17q12 (retinoic acid receptor alpha) in acute promyelocytic leukemia (APML) with atypical features. (1994)

Acute promyelocytic leukemia (APML) almost always involves a chromosomal translocation t(15:17) that results in the fusion of the retinoic acid receptor alpha (RAR alpha) gene with a transcription factor gene called PML. Several cases of APML with t(11;17) have recently been described, involving fusion of the RAR alpha gene with a new zinc finger gene named PLZF. We report here a second non-classical translocation, t(5;17), with a rearranged RAR alpha gene in a child with APML. Based on restriction endonuclease analysis, the rearrangement of RAR alpha occurred within the second intron, the common breakpoint site for t(15;17). The leukemic cells in the bone marrow aspirate were a mixture of hypergranular and hypogranular bilobed promyelocytes. Although less than 1% abnormal promyelocytes were identified after induction therapy, cytogenetics revealed persistent t(5;17). Therefore, the child was treated with all-trans-retinoic acid (ATRA). There was no disease progression, and one marrow was interpreted as remission, with confirmation by cytogenetics which failed to reveal the translocation. However, disease reoccurred shortly after completion of ATRA. This poor response to ATRA may be an additional characteristic associated with non-classical translocations in APML. The identification of a second variant translocation involving the RAR alpha gene in APML suggests yet another RAR alpha rearrangement related to neoplastic myelopoiesis.