gebhart/patrepeval huggingface dataset:
Cytosolic HSC20 integrates de novo iron–sulfur cluster biogenesis with the CIAO1-mediated transfer to recipients (2018)

Iron-sulfur (Fe-S) clusters are cofactors in hundreds of proteins involved in multiple cellular processes, including mitochondrial respiration, the maintenance of genome stability, ribosome biogenesis and translation. Fe-S cluster biogenesis is performed by multiple enzymes that are highly conserved throughout evolution, and mutations in numerous biogenesis factors are now recognized to cause a wide range of previously uncategorized rare human diseases. Recently, a complex formed of components of the cytoplasmic Fe-S cluster assembly (CIA) machinery, consisting of CIAO1, FAM96B and MMS19, was found to deliver Fe-S clusters to a subset of proteins involved in DNA metabolism, but it was unclear how this complex acquired its fully synthesized Fe-S clusters, because Fe-S clusters have been alleged to be assembled de novo solely in the mitochondrial matrix. Here, we investigated the potential role of the human cochaperone HSC20 in cytosolic Fe-S assembly and found that HSC20 assists Fe-S cluster delivery to cytosolic and nuclear Fe-S proteins. Cytosolic HSC20 (C-HSC20) mediated complex formation between components of the cytosolic Fe-S biogenesis pathway (ISC), including the primary scaffold, ISCU1, and the cysteine desulfurase, NFS1, and the CIA targeting complex, consisting of CIAO1, FAM96B and MMS19, to facilitate Fe-S cluster insertion into cytoplasmic and nuclear Fe-S recipients. Thus, C-HSC20 integrates initial Fe-S biosynthesis with the transfer activities of the CIA targeting system. Our studies demonstrate that a novel cytosolic pathway functions in parallel to the mitochondrial ISC to perform de novo Fe-S biogenesis, and to escort Fe-S clusters to cytoplasmic and nuclear proteins.
Cytotoxic Activity of Peripheral Blood Mononuclear Leukocytes, Activated by Interleukin-2/<i>β</i>-Cyclodextrin Nanocomposition against Androgen Receptor-Negative Prostate Cancers (2011)

Nanocomposition comprised of interleukin-2 in suboptimal noneffective concentration and β-cyclodextrin was studied in vitro. This preparation as well as interleukin-2 in optimal concentration was shown to increase natural killer activity to K-562 cells and cytotoxicity of activated peripheral blood mononuclear cells (PBMCs) against PC-3 and DU 145 cells. At the same time β-cyclodextrin or interleukin-2 in equimolar concentrations did not influence the spontaneous killer activity of PBMC. This combination of cyclodextrin + interleukin-2 led to the decrease of interleukin-2 effective concentration by an order. This phenomenon could be explained by cyclodextrins ability to promote the formation of nanoparticles with drugs, which results in enhancing their water solubility and bioavailability. Besides, interleukine-2/β-cyclodextrin nanocomposition as opposed to interleukin-2 alone led to increasing the number of not only lymphocytes, but also macrophages contained in activated PBMC population. Application of low concentration of interleukin-2 allowing for good clinical efficiency may significantly mitigate the side effects of the drug and enable to develop adoption of immunotherapy for patients with androgen-resistant prostate cancer.
<i>TET2</i> and <i>DNMT3A</i> Mutations Exert Divergent Effects on DNA Repair and Sensitivity of Leukemia Cells to PARP Inhibitors (2021)

Somatic variants in <i>TET2</i> and <i>DNMT3A</i> are founding mutations in hematological malignancies that affect the epigenetic regulation of DNA methylation. Mutations in both genes often co-occur with activating mutations in genes encoding oncogenic tyrosine kinases such as <i>FLT3<sup>ITD</sup>, BCR-ABL1, JAK2<sup>V617F</sup></i> , and <i>MPL<sup>W515L</sup></i> , or with mutations affecting related signaling pathways such as <i>NRAS<sup>G12D</sup></i> and <i>CALR<sup>del52</sup></i> . Here, we show that <i>TET2</i> and <i>DNMT3A</i> mutations exert divergent roles in regulating DNA repair activities in leukemia cells expressing these oncogenes. Malignant TET2-deficient cells displayed downregulation of BRCA1 and LIG4, resulting in reduced activity of BRCA1/2-mediated homologous recombination (HR) and DNA-PK-mediated non-homologous end-joining (D-NHEJ), respectively. TET2-deficient cells relied on PARP1-mediated alternative NHEJ (Alt-NHEJ) for protection from the toxic effects of spontaneous and drug-induced DNA double-strand breaks. Conversely, DNMT3A-deficient cells favored HR/D-NHEJ owing to downregulation of PARP1 and reduction of Alt-NHEJ. Consequently, malignant TET2-deficient cells were sensitive to PARP inhibitor (PARPi) treatment <i>in vitro</i> and <i>in vivo</i>, whereas DNMT3A-deficient cells were resistant. Disruption of TET2 dioxygenase activity or TET2-Wilms' tumor 1 (WT1)-binding ability was responsible for DNA repair defects and sensitivity to PARPi associated with TET2 deficiency. Moreover, mutation or deletion of <i>WT1</i> mimicked the effect of <i>TET2</i> mutation on DSB repair activity and sensitivity to PARPi. Collectively, these findings reveal that <i>TET2</i> and <i>WT1</i> mutations may serve as biomarkers of synthetic lethality triggered by PARPi, which should be explored therapeutically. SIGNIFICANCE: <i>TET2</i> and <i>DNMT3A</i> mutations affect distinct DNA repair mechanisms and govern the differential sensitivities of oncogenic tyrosine kinase-positive malignant hematopoietic cells to PARP inhibitors.
Altération du métabolisme du fer dans la maladie de Parkinson : participation du Transporteur 1 de Métaux Divalents (DMT1) et des Protéines Régulatrices du Fer (IRPs) dans la mort des neurones dopaminergiques de la Substantia Nigra Pars Compacta (2008)

La maladie de Parkinson (MP) est caracterisee par la mort preferentielle et acceleree des neurones dopaminergiques de la substance noire (SN) dont la cause est inconnue. De nombreuses etudes ont montre une augmentation des taux de fer dans les neurones dopaminergiques melanises et dans les cellules gliales de cette structure. En raison de son role pro-oxidant, le fer pourrait etre un des facteurs expliquant la mort massive des neurones dopaminergiques dans la MP. Des etudes post-mortem, realisees au sein de notre laboratoire (INSERM UMR679), ont montre que les sites de liaison de la transferrine, impliques dans une voie classique d’entree du fer, sont diminues en numero dans les neurones dopaminergiques de sujets parkinsoniens. Avec l’objectif d’identifier le mecanisme d’augmentation du fer dans la MP, nous avons etudie la participation d’un autre transporteur : le transporteur 1 des metaux divalents (DMT1). Nos experiences ont montre que DMT1 est exprime preferentiellement par les neurones dopaminergiques dans la SN des humains et des rongeurs. D’autre part, le niveau d’expression d’une des isoformes de DMT1 (DMT1+IRE) est augmente dans des modeles animaux de la MP et dans la SN de cerveaux parkinsoniens. Et enfin, des rongeurs portant une mutation dans le gene DMT1 (les souris microcytiques et les rats Belgrade) sont proteges contre les neurotoxines MPTP et 6-OHDA, utilisees comme modeles animaux de la MP. Ces observations soutiennent l’hypothese d’un role de DMT1 dans l’accumulation de fer et la mort neuronale dans la MP. Par la suite, nous nous sommes focalises a etudier la potentielle participation des proteines regulatrices du fer (IRPs) dans la neurodegeneration associee a la MP. Les IRPs controlent la traduction de messagers des proteines du metabolisme du fer, comme DMT1. Normalement impliquees dans homeostasie cellulaire du fer, elles peuvent etre modulees par le stress oxydant et favoriser l’augmentation du fer. En coherence avec cette hypothese nous avons montre que la souris deficiente pour le gene IRP1 est protegee contre la toxicite du MPTP. Cette etude confirme le role du fer dans la neurodegenerescence associee a la MP et suggere la participation de DMT1 et IRP1 dans la neurotoxicite mediee par le fer.
Characterization of smelter slags (2000)

Abstract The chemical and phase compositions of four different slags were studied with emphases on the form of Nickel, Cobalt and Copper. These were INCO slow cooled (IS), INCO fast cooled (IF), Falconbridge‐Sudbury fast cooled (FFS) and Falconbridge‐Timmins fast cooled (FFT) slags. The amount of each of Ni, Co and Cu in all the slags was less than 1%. IS contained the highest amount of Ni and Co of 0.57% and 0.21% respectively. The highest Cu content was found in FFS (0.87 %). The form of Co in all the slags was primarily oxide (> 98%). However, significant portions of Ni and Cu (20%) in IF and IS slag were in the sulphide form. Finer fractions (<270 mesh) of these slags were richer in sulphide forms of Ni and Cu (40%). X‐ray analysis revealed FFS and FFT as predominantly amorphous. Both slags were homogenous, consisting of mainly iron silicate glass. However, IF and IS slags were mostly crystalline, with two predominant phases, fayalite and spinel. In addition, a smaller amount of feldspar (albite) was observed in IS. Reflected light microscopy observation showed more crystalline phases in IS than IF. SEM‐EDS analysis, EMPA elemental mapping and reflected light microscopy studies all indicated the presence of entrained sulphide particles in the slag samples.
NF00659A1, A2, A3, B1 and B2, Novel Antitumor Antibiotics Produced by Aspergillus sp. NF 00659. II. Structural Elucidation. (1997)

NF00659A1, A2, A3, B1 and B2, having insecticidal and antitumor activities, were isolated from a culture mycelium of Aspergillus sp. NF 00659. The novel structure of NF00659s were determined mainly by spectroscopic studies including various NMR measurements. NF00659s have a common structure which consists of acyl, alpha-pyrone and 4,5-seco-tricyclic diterpene moieties.
Identification of equal affinity MDMX/MDM2-p53 interaction small molecule inhibitors (2007)

A208 MDMX is related to MDM2 and is an important regulator of the p53 pathway. It is believe that MDMX can interact with p53 at the promoters of p53-target genes and suppress transcriptional activation. A variety of human tumors with wild type p53 have genetic amplifications of the MDMX gene and increased MDMX protein expression. Some of the tumor types that have been characterized to date with MDMX amplifications include retinoblastoma, breast, colon, prostate and lung cancers as well as leukemia and soft tissue sarcomas. The goal of our research is to identify small molecule inhibitors of the MDMX-p53 interaction in order to induce p53-mediated cell death in tumors with wild type p53. Ideally, we would like to identify a single drug candidate that can inhibit both MDM2 and MDMX to more efficiently induce programmed cell death in tumor cells. We have developed two biochemical assays, fluorescence polarization and alphascreen, to perform high-throughput screening of large chemical libraries to identify lead compounds that can inhibit MDMX-p53 and MDM2-p53 interactions. In a series of pilot experiments using 6,000 bioactive compounds we optimized each assay and identified several small molecules that can inhibit both MDMX-p53 and MDM2-p53 at low micromolar concentrations. This is the first report of an MDMX/MDM2 inhibitor with equal affinity for both proteins.
Specific Orientation and Two-dimensional Crystallization of the Proteasome at Metal-chelating Lipid Interfaces (2002)

The potential of a protein-engineered His tag to immobilize macromolecules in a predictable orientation at metal-chelating lipid interfaces was investigated using recombinant 20 S proteasomes His-tagged in various positions. Electron micrographs demonstrated that the orientation of proteasomes bound to chelating lipid films could be controlled via the location of their His tags: proteasomes His-tagged at their sides displayed exclusively side-on views, while proteasomes His-tagged at their ends displayed exclusively end-on views. The activity of proteasomes immobilized at chelating lipid interfaces was well preserved. In solution, His-tagged proteasomes hydrolyzed casein at rates comparable with wild-type proteasomes, unless the His tags were located in the vicinity of the N termini of alpha-subunits. The N termini of alpha-subunits might partly occlude the entrance channel in alpha-rings through which substrates enter the proteasome for subsequent degradation. A combination of electron micrographs and atomic force microscope topographs revealed a propensity of vertically oriented proteasomes to crystallize in two dimensions on fluid lipid films. The oriented immobilization of His-tagged proteins at biocompatible lipid interfaces will assist structural studies as well as the investigation of biomolecular interaction via a wide variety of surface-sensitive techniques including single-molecule analysis.
The Mg2+ ion as a template for the synthesis of planar nitrogen-donor macrocyclic ligands: pentagonal bipyramidal Mg II complexes (1975)

Pentagonal bipyramidal complexes, [Mg(macro-cycle)(H2O)2]2+, containing planar pentadentate nitrogen-donor macrocyclic ligands, are formed in good yield in hydroxylic solvents by the template condensation of 2,6-diacetylpyridine with a linear tetramine in the presence of Mg2+
Isolation of fresh endothelial cells from porcine heart for cardiovascular studies: a new fast protocol suitable for genomic, transcriptomic and cell biology studies (2019)

We developed a new, fast, and cost-effective isolation method for pig heart ECs. Successful isolation of pure ECs is a prerequisite for several cardiovascular and vascular biology studies.
The role of muscular co-contraction of the hip during movement. (1995)

The joint biomechanics of the hip was studied analyzing the kinematic, kinetic, electromyographic and in vivo pressure parameters during walking, going up stairs, and getting up from a chair. The most significant clinical and biomechanical data emerged when the temporal correlation between intra-articular pressure variations and electric activity of the bi-articular muscles was studied. The presence of co-contraction of the bi-articular muscles during the support and oscillation phases was evident. The maximum joint pressure values were measured while getting up from a chair when the hip was flexed more than 100 degrees. The posterior region of the acetabulum was that most submitted to loading. This data is useful in gaining an understanding of joint physiology, in correctly setting up physio-kinesitherapeutic protocols, and in setting up pre-clinical prosthetic mechanical tests.
Crystallographic Orientation Relationships between the Primary and Secondary Recrystallized Grains in Multi-Layer Molybdenum Crystals. (1998)

A large-scale and multi-layer crystal was prepared from hot-rolled multi-laminated molybdenum sheet doped and stacked alternately with different amounts of dopant by means of secondary recrystallization. It was found that the potential nucleus of the secondary grain from layers with different amounts of dopant occurred first at layer with a small amount of dopant and then grew into the layer with a large amount of dopant during a higher temperature annealing. The orientation of secondary grain developed from each layer was also closely related to the texture gradients in the thickness direction for primary recrystallized sheet. Most of the orientation of multi-layer crystal sheet corresponded to very weak components in the primary recrystallization textures and were related by a rotation of approximately 15°C-30°C about <100> and <110> axes relative to the strong primary {001}<110> and {111}<112> components. Consequently, the main orientations of the secondary grains developed from quintuple-layer molybdenum crystal are composed of a near {100}<001> for the surface layer, a near {112}<111> for the central layer and a near {113}<332>+{112}<111> for the layer between surface and central ones.
Simulation‐Based Material Characterization of Isotropic and Direction‐Dependent Polymers for Use in Active Structure Assemblies (2018)

Piezoceramic sensor and actuator assemblies are of increasing interest for various fields of application and attractive as part of lightweight design. As for the latter, polymers and fiber‐reinforced composites are appropriate as functional materials. Numerical simulations can be performed to predict mechanical and electrical performance of such active structure assemblies. Precise material parameters, however, are indispensable to obtain reliable simulation results. Manufacturer data is often not sufficient since it leads to major deviations between numerical simulation results and measurements. To enable reliable numerical simulations, the authors present a simulation‐based characterization approach for isotropic, transverse isotropic, and orthotropic polymer materials by means of adapting material parameters through an optimization algorithm. Frequency response function measurements of beam‐shaped test samples serve as input values. Thus, it is possible to identify values for linear viscoelastic material models and to provide direction‐dependent material parameters.
Study of the natural antihistamine-like substance in bile of mammals (1976)

A natural antihistamine substance (NAS) present in bile has been investigated. It was found that the antihistamine activity was not due to proteins, lipids, pigments, or amino acids. On ion exchange chromatography and thin-layer chromatography, this activity was associated with bile acids. Many bile acids could, in varying degrees, inhibit this histamine induced guinea pig ileum contraction, desoxycholic acid being the most potent. However NAS activity could be separated from bile acids and their conjugates using a different solvent system. Furthermore, NAS showed a higher antihistamine activity than bile acids. This substance seems to be responsible for 15-20% of the activity of whole bile. The substance has not yet been identified.
Numerical modeling and determination of limiting powers for volume Bragg gratings used in lasers for spectral control (2013)

In this paper we present a model to investigate the thermal limitations of volume Bragg gratings (VBGs) used in lasers for spectral control. Also presented are the limiting optical powers, to which intracavity VBGs of different length could be subjected, before the laser operation rapidly deteriorates. The results revealed that the power limit of a VBG-locked laser is highly dependent on the length of the employed VBG. Furthermore, the power limit expressed in incident power related linearly to the radius of the laser beam irradiating the VBG.
Increased Cerebral Blood Flow Velocity in Infants of Mothers Who Abuse Cocaine (1990)

The pharmacologic effects of cocaine are considered to be secondary to an enhancement of the effects of circulating catecholamines. The effect of intrauterine cocaine exposure on the cerebral blood flow velocity was studied in 20 full-term newborn infants whose urine screens were positive for cocaine and in 18 nonexposed healthy full-term newborn infants whose urine screens were negative for cocaine metabolites. On the first day of life, peak systolic, end diastolic, and mean flow velocities in the pericallosal, internal carotid, and basilar arteries and mean arterial blood pressures were significantly greater in infants who had been exposed to cocaine. On day 2, cerebral blood flow velocities and mean arterial blood pressures were similar in exposed and nonexposed infants. The increase in mean arterial blood pressure and in cerebral blood flow velocity on the first day of life indicates a hemodynamic effect of cocaine that may put the infant exposed to cocaine at a greater risk of intracranial hemorrhage.
Cyber security challenges for cloud based services. (2015)

Areas covered - IoT security - Data loss detection and prevention - Cryptography in the Cloud
Scanning and transmission electron microscopy, and electron probe analysis of the interface between implants and host bone. Osseo-coalescence versus osseo-integration. (1990)

Bioinert materials (e.g., alumina implants) and bioactive ceramics (e.g., calcium phosphate ceramics, glass-ceramics) are now extensively used in dentistry. However, the physico-chemical interactions at the interfaces between the implant and the host bone are poorly understood. The purpose of this study was to define the interactions at these interfaces using a combination of analytical techniques: light microscopy, scanning and transmission electron microscopy, electron probe microanalysis, X-ray microradiography, X-ray diffraction, and infrared spectroscopy. Bioinert (pure titanium) and bioactive materials (hydroxyapatite, beta-tricalcium phosphate and biphasic calcium phosphate) were implanted in dogs, and the implants, recovered after various periods of implantation, were analyzed. The results demonstrated the following: the bioactive materials interact with the biological fluid and the living tissues in a specific manner. This process includes biodissolution/biodegradation, apatite crystal precipitation, and bone formation on the implant surface at the expense of the material. The results are discussed according to the limitations of the analytical techniques used. The medical and chemical word coalescence is suggested to describe the specific interactions of bioactive materials and interaction for the phenomenon of physical contact of the bioinert materials with the host bone.
Inherent size constraints on prokaryote gene networks due to "accelerating" growth (2003)

Networks exhibiting "accelerating" growth have total link numbers growing faster than linearly with network size and can exhibit transitions from stationary to nonstationary statistics and from random to scale-free to regular statistics at particular critical network sizes. However, if for any reason the network cannot tolerate such gross structural changes then accelerating networks are constrained to have sizes below some critical value. This is of interest as the regulatory gene networks of single celled prokaryotes are characterized by an accelerating quadratic growth and are size constrained to be less than about 10,000 genes encoded in DNA sequence of less than about 10 megabases. This paper presents a probabilistic accelerating network model for prokaryotic gene regulation which closely matches observed statistics by employing two classes of network nodes (regulatory and non-regulatory) and directed links whose inbound heads are exponentially distributed over all nodes and whose outbound tails are preferentially attached to regulatory nodes and described by a scale free distribution. This model explains the observed quadratic growth in regulator number with gene number and predicts an upper prokaryote size limit closely approximating the observed value.
Effects of direct Cedrol inhalation into the lower airway on autonomic nervous activity in totally laryngectomized subjects (2007)

The present experiment using totally laryngectomized patients replicated the similar results in healthy subjects who inhaled Cedrol through the nose, suppression of sympathetic outflow and increase in parasympathetic outflow. These results demonstrated that Cedrol acts on the lower airway and pulmonary system, and suggest a new target for drug therapy of hypertension.