gebhart/patrepeval huggingface dataset:
SCIDOT-42. FT-2102 – A POTENT AND SELECTIVE BRAIN PENETRANT INHIBITOR OF MUTANT ISOCITRATE DEHYDROGENASE (2019)

Abstract BACKGROUND Iocitrate dehydrogenase mutations (mIDH1) are present in >70% of patients with Grade II/III gliomas resulting in production and accumulation of (R)-2-hydroxyglutarate (2-HG) causing DNA hypermethylation and promoting tumorigenesis. This abstract summarizes the structure-based design of FT-2102, a potent and selective inhibitor of mutated IDH1-R132 with brain distribution (Kpuu) that is in context of minimal effective concentrations required in brain to modulate 2-HG. METHODS The crystal structure of mutated IDH1 in complex with FT-2102 and NADPH cofactor (2.1A resolution) was determined via sitting-drop vapour-diffusion set-ups. HCT116/IDH1 R132H were implanted in Balb/c nude mice and FT-2102 was administered orally twice daily. FT-2102 and 2-HG levels in plasma and xenografts were determined by LC/MS. In silico and in vitro models were used to determine the extent of brain distribution and ex-vivo rat data was generated to validate the projected distribution into brain tissue (Kpuu). RESULTS In tumor Xenograft (HCT116/IDH1-R132H), FT-2102 inhibits tumor 2-HG production with an IC50 of 24nM which is consistent with its in vitro IC50 of 18nM. FT-2102 unbound plasma concentrations of 256nM in xenografted mice were found to achieve 90% reduction of 2-HG in tumor. Rat data showed that FT-2102 partitions into brain with a Kpuu of 0.45. Based on these data, the concentration of FT-2102 in brain to significantly reduce 2HG is predicted to be 115nM. Recent publications (Natsume, et al, ASCO19) propose 90% reduction of 2-HG (90%) is associated with tumor reduction in the brain. CONCLUSION The structure-based design of FT-2102 has facilitated CNS penetration in animal models and is undergoing evaluation in ongoing clinical trials including patients with CNS based IDH1m tumors (NCT: 03684811).
Fast screening of polycyclic aromatic hydrocarbons using trapped ion mobility spectrometry – mass spectrometry (2014)

In the present paper, we showed the advantages of trapped ion mobility spectrometry coupled too mass spectrometry (TIMS-MS) combined with theoretical calculations for fast identification (millisecond timescale) of polycyclic aromatic hydrocarbons (PAH) compounds from complex mixtures. Accurate PAH collision cross sections (CCS, in nitrogen as a bath gas) are reported for the most commonly encountered PAH compounds and the ability to separate PAH geometric isomers is shown for three isobaric pairs with mobility resolution exceeding 150 (3-5 times higher than conventional IMS devices). Theoretical candidate structures (optimized at the DFT/B3LYP level) are proposed for the most commonly encountered PAH compounds showing good agreement with the experimental CCS values (<5%). The potential of TIMS-MS for the separation and identification of PAH compounds from complex mixtures without the need of lengthy pre-separation steps is illustrated for the case of a complex soil mixture.
Endothelial polyamine uptake: selective stimulation by L-arginine deprivation or polyamine depletion (1994)

Uptake of putrescine and spermidine by cultured porcine aortic endothelial cells was time dependent and linear for 60 min. Transport, against a 5- to 10-fold concentration gradient, demonstrated both saturable and non-saturable components. Apparent concentration giving one-half maximal transport (Kt) values for putrescine and spermidine were 9 and 0.6 microM, respectively. Transport was reduced at 0 degrees C, suggesting that the process is energy requiring; inhibition by N-ethylmaleimide or p-chloromercuribenzoate suggested a requirement for sulfydryl groups. Transport of putrescine, but not spermidine, was partially activated by Na+. Spermidine and spermine did not inhibit putrescine uptake, and putrescine and spermine did not inhibit spermidine uptake, suggesting the presence of a separate transporter for each polyamine. Pretreatment with DL-2-difluoromethy-lornithine increased the uptake of putrescine but not spermidine. The endothelial cell putrescine transporter is thus sensitive to polyamine depletion, suggesting that transport from the extracellular space may be an important source of polyamines. L-Ornithine or L-arginine were not inhibitory, indicating that polyamine and cationic amino acid transport is mediated by independent systems. The sensitivity of putrescine transport to L-arginine but not to L-ornithine deprivation suggests that intracellular levels of arginine rather than ornithine regulate polyamine metabolism and transport in these cells. Thus factors that affect arginine utilization may also influence polyamine metabolism.
A novel test method for quantifying surface tack of polypropylene compound surfaces (2011)

While adhesiveness is required for polymer surfaces in special applications, tacky surfaces are generally undesirable in many applications like automotive interior parts. The tackiness of polymer surface results from a combination of composition and additivation, and it can change significantly in natural or accelerated ageing. Since there is no established, uniform method to characterize surface tack, the major focus of the present work was on the development of an objective quantification method. A setup having a soft die tip attached to a standard tensile tester was developed aiming for correlation to the human sense of touch. Three different model thermoplastic polyolefin (TPO) compound formulations based on a high-impact isotactic polypropylene (iPP) composition with varying amounts and types of anti-scratch additives were used for these investigations. As the surface tack phenomenon is related to ageing and weathering, the material's examination was also performed after various intervals of weathering. The developed method allows a fast assessment of the effect of polymer composition variations and different additive formulations on surface tack and gives identical rankings as the standardized haptic panel.
Electrical conduction through adsorbed monolayers (1978)

Electrical conduction was studied in Al/adsorbed monolayer/Al junctions. The adsorbed monolayers were long chain saturated fatty acids (23 to 14 carbon atom chain), short chain perfluorinated fatty acids (10 to 7 carbon atom chain), and n-octadecyl-trichlorosilane. The current observed decreased rapidly with decreasing temperature from 295 K to approximately 77 K at which point the decrease in current with decreasing temperature became very small. At room temperature (295 K) there was no definite relation between the dc conductivity and the length of the fatty acids. At 77 K and lower temperatures, however, the dc conductivity was exponentially dependent on the fatty acid chain length. These results suggest that at 77 K and lower temperatures the conduction mechanism is tunneling through the monolayer. The tunneling barrier height was found to be of the order of 2.8 and 5.2 eV for fatty acids and perfluorinated fatty acids, respectively. By artificially producing molecular holes in monolayers it was shown that in the presence of such holes the current increases by at least one order of magnitude while the effective barrier height is lowered by 10%. Differences between the present results and those previously obtained with monolayers deposited from an air–water interface (Langmuir–Blodgett monolayers) are discussed.
Confirmation of intersubunit connectivity and topology of designed protein complexes by native MS (2018)

Computational protein design provides the tools to expand the diversity of protein complexes beyond those found in nature. Understanding the rules that drive proteins to interact with each other enables the design of protein-protein interactions to generate specific protein assemblies. In this work, we designed protein-protein interfaces between dimers and trimers to generate dodecameric protein assemblies with dihedral point group symmetry. We subsequently analyzed the designed protein complexes by native MS. We show that the use of ion mobility MS in combination with surface-induced dissociation (SID) allows for the rapid determination of the stoichiometry and topology of designed complexes. The information collected along with the speed of data acquisition and processing make SID ion mobility MS well-suited to determine key structural features of designed protein complexes, thereby circumventing the requirement for more time- and sample-consuming structural biology approaches.
Recent Advances and Future Perspectives on Microfluidic Liquid Handling (2017)

The interdisciplinary research field of microfluidics has the potential to revolutionize current technologies that require the handling of a small amount of fluid, a fast response, low costs and automation. Microfluidic platforms that handle small amounts of liquid have been categorised as continuous-flow microfluidics and digital microfluidics. The first part of this paper discusses the recent advances of the two main and opposing applications of liquid handling in continuous-flow microfluidics: mixing and separation. Mixing and separation are essential steps in most lab-on-a-chip platforms, as sample preparation and detection are required for a variety of biological and chemical assays. The second part discusses the various digital microfluidic strategies, based on droplets and liquid marbles, for the manipulation of discrete microdroplets. More advanced digital microfluidic devices combining electrowetting with other techniques are also introduced. The applications of the emerging field of liquid-marble-based digital microfluidics are also highlighted. Finally, future perspectives on microfluidic liquid handling are discussed.
Development of a fabrication process for a MEMS component from ultra fine grained alloys (2010)

This thesis presents a study on the feasibility of fabricating a MEMS component by embossing using ultra-fine grained (UFG) aluminium alloys.The main elements of the work involved designing the equipment, production of UFG aluminium alloys through equal channel angular pressing (ECAP), embossing of the UFG alloys and the construction of models that improve the understanding of the main elements of the processing.ECAP was performed on Al-1050, AlZr and AlZrSiFe alloys to produce UFG Al alloys.Microstructure and texture evolution were analyzed by electron backscattered diffraction (EBSD) and transmission electron microscopy (TEM).A new predictive model of grain refinement allows the understanding of the grain refinement process.Microhardness inhomogeneity of UFG Al-1050 processed by one pass of ECAP was studied through measuring the distribution of Vickers hardness and microstructure on the cross section before and after annealing at different temperature.Microhardness of UFG Al alloys processed by various passes of ECAP was measured after annealing at various temperatures.The relation between microhardness and microstructure was studied with the aid of a dislocation model.The model suggests that most of the strengthening in the severely plastically deformed alloys is due to enhanced dislocation density.Nanoindentation hardness of UFG Al-1050 was also measured.A modified model of indentation size effect was derived.The model was justified through comparison with our own data and data in literature.The UFG Al alloys were embossed using a micro silicon die with a pattern of microchannels at both room temperature and high temperature.The topography of embossed sample was observed by scanning electron microscopy (SEM), optical microscopy (OM) and confocal laser system.Nanoindentation hardness was measured on cross section of the embossed sample to detect the hardness distribution.Focus ion beam (FIB) and EBSD were used to characterize the microstructure on the cross section.A model employing concept of geometrically necessary dislocations (GND) was present to predict embossing force and hardness distribution on the cross section.This study shows a good potential for fabrication of microdevices by embossing UFG alloys processed by ECAP.An optimized process was obtained through analysis of microstructure and properties of the UFG alloys before and after embossing.The understanding of the processing was enhanced through construction of models.
Volume-encoded UV-maps (2016)

UV-maps are required in order to apply a 2D texture over a 3D model. Conventional UV-maps are defined by an assignment of uv positions to mesh vertices. We present an alternative representation, volume-encoded UV-maps, in which each point on the surface is mapped to a uv position which is solely a function of its 3D position. This function is tailored for a target surface: its restriction to the surface is a parametrization exhibiting high quality, e.g. in terms of angle and area preservation; and, near the surface, it is almost constant for small orthogonal displacements. The representation is applicable to a wide range of shapes and UV-maps, and unlocks several key advantages: it removes the need to duplicate vertices in the mesh to encode cuts in the map; it makes the UV-map representation independent from the meshing of the surface; the same texture, and even the same UV-map, can be shared by multiple geometrically similar models (e.g. all levels of a LoD pyramid); UV-maps can be applied to representations other than polygonal meshes, like point clouds or set of registered range-maps. Our schema is cheap on GPU computational and memory resources, requiring only a single, cache-coherent indirection to a small volumetric texture per fragment. We also provide an algorithm to construct a volume-encoded UV-map given a target surface.
The Consequences of Decentralized Security in a Cooperative Storage System (2006)

Traditional storage systems have considered security as a problem to be solved at the perimeter: once a user is authenticated, each device internal to the system trusts the decision made elsewhere. However, as storage systems become ever more distributed, shared, and dynamic, it becomes necessary to enforce security at the boundaries of each storage device, rather than around the system as a whole. This form of decentralized security presents several new challenges in the design and implementation of distributed storage systems. We explore challenges in distributed file systems, third party transfer, active storage, and group management in the context of a 200-node cooperative storage system deployed at the University of Notre Dame. These explorations result in three recommendations for future system designs.
The human gene for gammaS-crystallin: alternative transcripts and expressed sequences from the first intron. (2000)

The human CRYGS gene can give rise to at least two transcripts through alternative polyadenylation. A minor transcript results from alternative splicing into sequences in intron 1. These sequences form part of a transcription unit (Mys) expressed in several non-lens tissues. The identity and function Mys of is not yet known, however, the cryptic splicing of CRYGS could produce a defective protein product, with potentially deleterious results for the adult human lens.
Commissioning of the Main Magnet of Kolkata K-500 Superconducting Cyclotron (2006)

Commission of the Kolkata K-500 superconducting cyclotron magnet has been underway at the Variable Energy Cyclotron Centre. The cooldown and energisation experience is described in this paper.
A new approach to the load compensation of a single-phase nonsinusoidal system (1984)

A microprocessor-based instrument to compute the value of capacitance and/or inductance which minimises the RMS value of line current when connected in parallel with the load, is described. The instrument can be used with systems having arbitrary voltage/current waveforms. The method is based on obtaining the least-squares solution of a set of equations which are formed by taking samples of derivatives of line voltage, integrals of line voltage and line current.
Temperature sensitivity of neurons in slices of the rat PO/AH area: effect of bombesin and substance P (1993)

The effects of bombesin (Bom) and substance P (SP) were investigated in 156 temperature-sensitive and -insensitive neurons in slices of the preoptic and anterior hypothalamic area (PO/AH) of rats. Application of Bom increased the firing rate (FR) in 68% (n = 38) of the warm-sensitive and in 62% (n = 39) of the temperature-insensitive neurons. One cold-sensitive neuron was excited; a second was not affected by the peptide. No neuron decreased its activity after Bom application. SP excited 80% (n = 15) of the warm-sensitive neurons and 48% (n = 29) of the temperature-insensitive neurons. Two cold-sensitive neurons were inhibited by SP, a third one was not affected. The opposite effect on thermoregulation in vivo caused by the two peptides cannot be explained simply by their relatively similar excitatory effects on the FR of PO/AH neurons. After Bom application the temperature coefficient (TC) was significantly elevated in 7 out of 11 warm-sensitive neurons and in 19 out of 21 temperature-insensitive neurons. After SP application the TC was significantly reduced in 6 out of 7 warm-sensitive and 1 out of 12 temperature-insensitive neurons. Bom caused grouped discharges (bursts) in 7 out of 42 PO/AH neurons; SP never produced bursts in the discharge pattern. The increase of the TC of warm-sensitive and the transformation of temperature-insensitive into warm-sensitive neurons by Bom might be regarded as the neurophysiological basis for the decreased body temperature after Bom application. It is concluded that the temperature sensitivity of PO/AH neurons is not an unchangeable inherent property of certain cells but may be altered or even evoked by physiological processes like the release of neuromodulators.
INTEGRATED FRACTURED RESERVOIR CHARACTERIZATION USING NEURAL NETWORKS AND FUZZY LOGIC: THREE CASE STUDIES (2001)

Two categories of natural fractures are generally recognized: regional orthogonal fractures and structure‐related or tectonic fractures. Over the past eight years or so, we have developed a methodology using neural networks and fuzzy logic to assist with the characterization of naturally fractured reservoir rocks. Conventional methods use only one or two geological parameters to characterize a naturally fractured reservoir. However, an integrated approach that utilizes all the information available (including lithology, thickness, state of stress and fault patterns) is required. Our approach makes use of fuzzy logic to quantify and rank the importance of each geological parameter on fracturing; a neural network is used to find the complex, non‐linear relationship between these geological parameters and the fracture index. Three case studies are described in this paper to illustrate the use of this methodology. They report respectively on a faulted limestone oil reservoir in North Africa which is deformed by fault‐related fractures; a carbonate oil reservoir in New Mexico which is characterized by fold‐related fractures; and a sandstone gas reservoir in NW New Mexico which has regional orthogonal fractures. These three case studies illustrate fracture identification and prediction using static information (i.e. image logs) and/or dynamic information (i.e. well performance) as a fracture index. The results of these studies are described as they relate to infill drilling, understanding the fractured reservoir and improved reservoir simulation.
Tracking Immune Cell Proliferation and Cytotoxic Potential Using Flow Cytometry (2010)

In the second edition of this series, we described the use of cell tracking dyes in combination with tetramer reagents and traditional phenotyping protocols to monitor levels of proliferation and cytokine production in antigen-specific CD8+ T cells. In particular, we illustrated how tracking dye fluorescence profiles could be used to ascertain the precursor frequencies of different subsets in the T-cell pool that are able to bind tetramer, synthesize cytokines, undergo antigen-driven proliferation, and/or carry out various combinations of these functional responses.
Forkhead Box F1 Is Essential for Migration of Mesenchymal Cells and Directly Induces Integrin-Beta3 Expression (2007)

The Forkhead box f1 (Foxf1) transcription factor is expressed in mesenchymal cells of the lung, liver, and gallbladder. Although Foxf1 deficiency causes severe abnormalities in the development of these organs, the molecular mechanisms underlying Foxf1 function remain uncharacterized. In this study we inactivated Foxf1 function in lung mesenchymal cells and mouse embryonic fibroblasts (MEFs) by use of either short interfering RNA duplexes or a membrane-transducing Foxf1 dominant negative (DN) mutant protein (Foxf1 DN), the latter of which is fused to the human immunodeficiency virus TAT protein transduction domain. Although Foxf1 did not influence DNA replication or cell survival, Foxf1 depletion severely diminished mesenchyme migration. Foxf1 deficiency in mesenchymal cells was associated with reduced expression of the integrin-beta3 (Itgbeta3) subunit. Furthermore, we generated transgenic mice containing a tetracycline-inducible Foxf1 DN transgene. Adenovirus-mediated activation of Foxf1 DN in transgenic MEFs caused diminished cell migration and reduced Itgbeta3 expression. A chromatin immunoprecipitation assay demonstrated that Foxf1 protein binds to the bp -871 to -815 region of the mouse Itgbeta3 promoter. Deletion of the -871 to -815 Itgbeta3 promoter region completely abolished the ability of Foxf1 to activate transcription of the Itgbeta3 promoter in cotransfection experiments, indicating that the mouse Itgbeta3 is a direct transcriptional target of Foxf1 protein. Foxf1 plays an essential role in mesenchyme migration by transcriptionally regulating Itgbeta3.
Adaptive resource management for flow-based IP/ATM hybrid switching systems (2002)

This paper proposes a novel approach for adaptive flow classification for flow-based hybrid switching systems to match the time varying traffic/resource characteristics. It minimizes the maximum of the system resource utilizations associated with packet processing power, signalling capacity and routing table size. After formulating the proposed flow adaptation as a min-max stochastic control problem, a heuristic algorithm is developed. The simulation study based on real traces shows the viability of the proposed flow adaptation for dynamic resource management in hybrid switching system design. The algorithm is simple to implement and only requires the adaptation of two global variables at time intervals of every few seconds based on the present usage of resources.
Infection as a Risk Factor for Infarction and Atherosclerosis (1991)

A growing amount of clinical and experimental evidence suggests a link between infection and atherosclerotic diseases including both myocardial and cerebral infarction. A prime example is a greatly increased risk of stroke in septicaemic patients with and without endocarditis. Controlled clinical studies have recently shown, however, that certain other milder bacterial infections are also a risk factor for infarction. A preceding febrile respiratory infection was a major risk factor for stroke in young and middle aged patients. In patients with acute myocardial infarction Chlamydia pneumoniae and dental infections seem to be risk factors according to one controlled clinical study. Several possible mechanisms could explain the observed association of infection and infarction. For instance, infection causes a hypercoagulable state which increases the risk of thrombosis. In addition, infection has profound and harmful effects on prostaglandin and lipid metabolism. Infection may also have some role in the atherosclerotic process itself by inducing damage and inflammation in vascular endothelium in the presence of hypercholesterolemia. So far, however, little clinical evidence is available to suggest that by controlling infection the risk of infarction or development of atherosclerotic lesions might be reduced except in patients with endocarditis, where the risk of thromboembolic complications rapidly diminished when the infection is controlled with antimicrobial therapy.