gebhart/patrepeval huggingface dataset:
CXCR3 blockade inhibits T‐cell migration into the CNS during EAE and prevents development of adoptively transferred, but not actively induced, disease (2010)

Autoreactive T-cell infiltration into the CNS is critical in MS and EAE. The chemokine receptor CXCR3 and its ligands are implicated in MS and mouse EAE, but the contribution of CXCR3 to T-cell migration into the inflamed CNS remains controversial. During active disease in a rat EAE model, blood T-cell, spleen T-cell and T lymphoblast migration into the CNS was inhibited by a CXCR3 blocking mAb by, 30-70%, ∼75% and 50-80%, respectively. However, CXCR3 blockade after active immunization did not inhibit EAE, did not alter total T-cell accumulation in the CNS and did not affect Treg accumulation or the presence of cells producing IFN-γ or IL-17. Conversely, CXCR3 blockade during EAE induced by adoptive transfer of myelin basic protein-activated T cells delayed disease onset, shortened its duration and reduced disease severity. Moreover, CXCR3 blockade inhibited leukocyte infiltration of the CNS>95%, virtually abolishing infiltration of transferred T cells. Thus, CXCR3 plays a major role in T-cell migration to the CNS and can be critical for encephalitogenic T-cell migration into the CNS to induce disease, but CXCR3-independent recruitment can also produce EAE.
Liraglutide: once-daily GLP-1 agonist for the treatment of type 2 diabetes (2010)

Liraglutide has been well studied in dual and triple combination therapies with sulfonylureas, metformin and rosiglitazone and appears safe and effective. For patients who cannot tolerate first-line agents, metformin, insulin and sulfonylureas, liraglutide is a reasonable treatment option.
X-ray lithography using a KrF laser-produced plasma (1988)

Experiments to demonstrate the feasibility of a small laser for x-ray lithography are discribed. Resist exposure experiment was performed by x-rays from a plasma produced by a KrF laser, 0.6 J/ 20 ns. With 50 shots exposure, a very fine pattern of 0.5 μm line & space was printed onto a resist EBR-9 at 3 cm from an iron plate target. The conditions for a laser-plasma to be a practical source for x-ray lithography are discussed.
The biophysics of neuronal growth (2010)

For a long time, neuroscience has focused on biochemical, molecular biological and electrophysiological aspects of neuronal physiology and pathology. However, there is a growing body of evidence indicating the importance of physical stimuli for neuronal growth and development. In this review we briefly summarize the historical background of neurobiophysics and give an overview over the current understanding of neuronal growth from a physics perspective. We show how biophysics has so far contributed to a better understanding of neuronal growth and discuss current inconsistencies. Finally, we speculate how biophysics may contribute to the successful treatment of lesions to the central nervous system, which have been considered incurable until very recently.
Vibrational properties of novel diacetylenic monomers (1998)

The frequency and intensity of the infrared and Raman CC modes have been investigated for a large number of molecules. A series of symmetrical and asymmetrical substituted diacetylenic monomers having the carbazole group attached directly or indirectly to the diacetylenic backbone have been studied in their microcrystalline or liquid state. A qualitative assignment has been proposed and particular attention has been given to those systems for which a peculiar behaviour of the infrared and Raman intensities has been observed. This behaviour is found when the diacetylenic skeleton is directly attached to either the 9H-carbazolyl or triethylsilyl group.
Acylation of Amines with 5‐Phenyltetrazol‐2‐ylacetyl Chloride. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Site‐directed mutagenesis of selected residues at the active site of aryl‐alcohol oxidase, an H<sub>2</sub>O<sub>2</sub>‐producing ligninolytic enzyme (2006)

Aryl-alcohol oxidase provides H(2)O(2) for lignin biodegradation, a key process for carbon recycling in land ecosystems that is also of great biotechnological interest. However, little is known of the structural determinants of the catalytic activity of this fungal flavoenzyme, which oxidizes a variety of polyunsaturated alcohols. Different alcohol substrates were docked on the aryl-alcohol oxidase molecular structure, and six amino acid residues surrounding the putative substrate-binding site were chosen for site-directed mutagenesis modification. Several Pleurotus eryngii aryl-alcohol oxidase variants were purified to homogeneity after heterologous expression in Emericella nidulans, and characterized in terms of their steady-state kinetic properties. Two histidine residues (His502 and His546) are strictly required for aryl-alcohol oxidase catalysis, as shown by the lack of activity of different variants. This fact, together with their location near the isoalloxazine ring of FAD, suggested a contribution to catalysis by alcohol activation, enabling its oxidation by flavin-adenine dinucleotide (FAD). The presence of two aromatic residues (at positions 92 and 501) is also required, as shown by the conserved activity of the Y92F and F501Y enzyme variants and the strongly impaired activity of Y92A and F501A. By contrast, a third aromatic residue (Tyr78) does not seem to be involved in catalysis. The kinetic and spectral properties of the Phe501 variants suggested that this residue could affect the FAD environment, modulating the catalytic rate of the enzyme. Finally, L315 affects the enzyme k(cat), although it is not located in the near vicinity of the cofactor. The present study provides the first evidence for the role of aryl-alcohol oxidase active site residues.
Effect of cationization on anti‐hapten antibody responses in sheep and mice (1993)

The effect on anti-hapten immune responses of altering the isoelectric point of hapten-carrier conjugates by cationization was examined in sheep and mice. No adjuvants were employed in these studies. In sheep the cationization of ovalbumin-dinitrophenyl (OVA-DNP) resulted in an enhanced primary anti-dinitrophenyl (DNP) response. The secondary anti-DNP responses were not consistently greater for animals primed with cationized (CAT) OVA-DNP than in animals primed with OVA-DNP. Similar results were obtained with mice immunized with bovine serum albumin (BSA)-DNP or CAT BSA-DNP. Mice and sheep primed with OVA-DNP failed to mount an anamnestic response following secondary immunization with CAT OVA-DNP. Failure of a cationized hapten-carrier to stimulate a secondary anti-DNP response following priming with uncationized hapten-carrier was also observed in mice using BSA-DNP as the model antigen.
High resolution spatial mapping of brominated pyrrole-2-aminoimidazole alkaloids distributions in the marine sponge <i>Stylissa flabellata via</i> MALDI-mass spectrometry imaging (2012)

A number of pharmacologically active brominated pyrrole-2-aminoimidazole (B-P-2-AI) alkaloids have been isolated from several families of marine sponges, including those belonging to the genus Stylissa. In the present study, MALDI mass spectrometry imaging (MALDI-imaging) was applied to determine the spatial distribution of B-P-2-AIs within 20 μm cross sections of S. flabellata. A number of previously characterised B-P-2-AIs were readily identified by MALDI-imaging and confirmed by MS-MS and NMR profiling. Unknown B-P-2-AIs were also observed. Discrete microchemical environments were revealed for several B-P-2-AIs including dibromophakellin which was localised within the external pinacoderm and internal network of choanoderm chambers. Additionally, dibromopalau'amine and konbu'acidin B were also found to be confined to the choanoderm, while sceptrin was found to be highly abundant within the mesohyl. Further brominated compounds of unknown structure were also observed to have distinct localisation in both choanoderm chambers and the pinacoderm. These findings provide insights into the chemical ecology of S. flabellata, as most B-P-2-AIs were found on highly exposed surfaces, where they may act to prevent pathogens, predation and/or biofouling. Moreover this study demonstrates the power of MALDI-imaging to visualise the location of a range of metabolites in situ and to characterise compounds by MS-MS directly from intact specimens without the need for extraction. These methodologies facilitate selective targeting of micro-regions of sponge to screen for symbiotic microbial candidates or genes that may be involved in the production of the correlated compounds, and may represent a change in paradigm for natural product drug development.
Hypothesis: a Y-chromosomal gene causes gonadoblastoma in dysgenetic gonads (1987)

The role of the human Y chromosome in the etiology of gonadoblastoma, a gonadal neoplasm, is considered and a two-part model is presented. According to this hypothesis: (1) There is a gene on the Y chromosome that strongly predisposes dysgenetic gonads to develop gonadoblastomas (Page, 1986) and (2) this postulated GBY gene (GonadoBlastoma locus on Y chromosome) has some physiological function in normal males. GBY may, for example, function in or prior to spermatogenesis in normal testes. Y-DNA hybridization analysis of individuals with gonadoblastoma and partial deletions of the Y chromosome should be of use in testing this proposal. To date, such studies suggest that GBY maps to the region that includes deletion intervals 4B to 7, i.e. it is located near the centromere or on the long arm of the Y chromosome.
<title>Complete simulation of x-ray angiography</title> (1998)

This paper presents a complete simulation of x-ray angiography, which we have used as tool to assist our research work in 3D reconstruction of vasculature from x-ray angiograms. X-ray angiography is an image acquisition technique routinely used in clinical practice to obtain images of blood vessel networks, which operates as follows: x-ray opaque dye is injected into the blood flow and is driven through the vessel network by time varying pressure gradients. An x-ray device captures a sequence of images as the dye flows, yielding an animation in which each image shows part of the vasculature. Once an animation from a given point of view has been acquired, the x-ray device is moved to a new position and the whole process is repeated. The final result is a set of animations. The simulation is able to reproduce all the salient points of x-ray angiography. Given our motivation (reconstructing vascular skeletons) we generalized the simulation so that it can produce static images of complete vasculature, and pre- segmented images that represented key stages in our reconstruction algorithm.
Profiles of Pulp Infiltrating Lymphocytes at Various Times Throughout Feather Regeneration in Smyth Line Chickens with Vitiligo (1997)

Smyth line (SL) chickens develop a spontaneous, autoimmune, posthatch loss of pigment cells (vitiligo) in regenerating feather tissue. Smyth line vitiligo (SLV) is associated with lymphocyte infiltrations prior to and throughout the development of the disorder. It was the purpose of this study to determine the type, relative amounts, and proportions of pulp-infiltrating lymphocytes at various times throughout the growth of regenerating feathers. Feathers were plucked from 8-week-old chickens with and without SLV. Feather pulp cell suspensions were prepared when the regenerating feathers were 2, 3, 4, and 6 weeks of age. Cells were fluorescently labeled using a panel of mouse monoclonal antibodies specific for chicken lymphocytes. Both T and B cells infiltrated the feather pulp of chickens with SLV. T cell levels remained elevated throughout the 6 weeks of feather growth, while B cell levels steadily declined to control levels over the same time. The pulp-infiltrating cells were primarily T cells with an alphabeta T cell receptor expressing the Vbeta1 gene (TCR2+). The ratio between CD4+ and CD8+ cells was 1.42 and 0.75 in 2- and 6-week-old regenerating feathers from chickens with autoimmune SLV, respectively. In non-vitiliginous chickens this ratio was always near 1. These data suggest that TCR2+ T cells play an important role in SLV. CD4+ cells may play a recruiting/activating role, whereas CD8+ cells may have cytotoxic activity specifically directed against melanocytes. Additionally, this is the first report demonstrating the infiltration of B cells into the feather pulp of vitiliginous chickens. These B cells may directly/indirectly contribute to melanocyte destruction in SLV.
K-Ras<sup>G12D</sup> Has a Potential Allosteric Small Molecule Binding Site (2019)

KRAS is the most commonly mutated oncogene in human cancer, with particularly high mutation frequencies in pancreatic cancers, colorectal cancers, and lung cancers [Ostrem, J. M., and Shokat, K. M. (2016) Nat. Rev. Drug Discovery 15, 771-785]. The high prevalence of KRAS mutations and its essential role in many cancers make it a potentially attractive drug target; however, it has been difficult to create small molecule inhibitors of mutant K-Ras proteins. Here, we identified a putative small molecule binding site on K-Ras<sup>G12D</sup> using computational analyses of the protein structure and then used a combination of computational and biochemical approaches to discover small molecules that may bind to this pocket, which we have termed the P110 site, due to its adjacency to proline 110. We confirmed that one compound, named K-Ras allosteric ligand KAL-21404358, bound to K-Ras<sup>G12D</sup>, as measured by microscale thermophoresis, a thermal shift assay, and nuclear magnetic resonance spectroscopy. KAL-21404358 did not bind to four mutants in the P110 site, supporting our hypothesis that KAL-21404358 binds to the P110 site of K-Ras<sup>G12D</sup>. This compound impaired the interaction of K-Ras<sup>G12D</sup> with B-Raf and disrupted the RAF-MEK-ERK and PI3K-AKT signaling pathways. We synthesized additional compounds, based on the KAL-21404358 scaffold with more potent binding and greater aqueous solubility. In summary, these findings suggest that the P110 site is a potential site for binding of small molecule allosteric inhibitors of K-Ras<sup>G12D</sup>.
Polymorphism in 4′-Hydroxyacetophenone: Structure and Energetics (2008)

A new polymorph of 4′-hydroxyacetophenone (form I, monoclinic, P21/c, Z′ = 1) was isolated and characterized. The structural differences between this phase and the previously known one (form II, orthorhombic, P212121, Z′ = 2) were investigated by X-ray diffraction. The two polymorphs exhibit distinct packing features and, at the molecular level, they seem to differ by the relative conformations of the OH and C(O)CH3 groups. The stability domains of the two phases from 298.15 K to the fusion temperature were also studied by a variety of thermodynamic methods and by density functional theory calculations. On the basis of the obtained results, p−T and ΔfGmo−T phase diagrams for 4′-hydroxyacetophenone were defined. Differential scanning calorimetry experiments indicated that the system is enantiotropic, with form II first transforming into form I at 351.2 ± 2.7 K, followed by fusion of form I at 381.9 ± 0.1 K. Solution calorimetry demonstrated that form II is more stable than form I at 298.15 K, with ΔtrsHmo(II→I) = 0.49 ± 0.13 kJ mol−1. Despite this small enthalpy difference compared to the thermal energy at 298.15 K (RT = 2.5 kJ mol−1), a sample of form I could be stored at ambient temperature, for at least 1 year, without change. Results of B3LYP/6–31G(d,p) calculations indicated that the most stable conformation of the isolated molecule is also that corresponding to the most stable polymorph of 4′-hydroxyacetophenone at ambient temperature (form II). The computations further suggest that the occurrence of the II → I transition through a simple rotation of the OH group is unlikely. Finally, the fact that the more stable form II has a greater Z′ than the less stable form I contrasts with the recent proposal that high Z′ polymorphs are metastable precursors of lower Z′ forms along the crystallization pathway.
Природа и бытие человека: материя и тело, идея и плоть (2016)

The article analyzes phenomenon of physicality in the context of the concept of «flesh» and in frame the dichotomy of matter and ideas. There is considers materialistic, postmodern and Christian aspects. The materialistic aspect equalizes «body» and «flesh» concepts. The postmodern aspect transforms the «body» in the «soma». And the Christian aspect of the materiality of the body and postulates the possibility of spiritualization of flesh.
(Self-)Portrait of Prof. R.C.: A Retrospective (2010)

This essay offers a retrospective on the four special issues of this journal (1957, 1980, 1990, 2001) dedicated to the “state of the art” of rhetorical criticism. Drawing on Oscar Wilde's The Portrait of Mr. W. H. as allegory, the essay also functions to queer this retrospective in an ongoing effort to queer rhetorical studies. The essay closes with a prospective call for “critical self-portraiture” and genealogy of rhetorical criticism.
NMR Probeheads for Biophysical and Biomedical Experiments: Theoretical Principles and Practical Guidelines (2006)

Relating the NMR Receiving/Transmitting Coil(s) to the Spectrometer Matching the Probe Resonator to 50 Balancing the Probe Head Quadrature Driving Multiple Frequencies Tuning Magnetic Field Amplitude Estimation Homogeneous Resonators Heterogeneous Resonators. Combination of Coils Adjusting, Evaluating, Testing and Debugging the Probe Useful Information Appendices: Solving the Impedance Matching Calculation of the Current Distribution Calculation of the Magnetic Field Distribution A Simple Linear Network Analysis Program.
Magnetic microsphere-based mixers for microdroplets (2009)

While droplet-based microfluidic systems have several advantages over traditional flow-through devices, achieving adequate mixing between reagents inside droplet-based reactors remains challenging. We describe an active mixing approach based on the magnetic stirring of self-assembled chains of magnetic microspheres within the droplet as these stirrers experience a rotating magnetic field. We measure the mixing of a water-soluble dye in the droplet in terms of a dimensional mixing parameter as the field-rpm, fluid viscosity, and microsphere loading are parametrically varied. These show that the mixing rate has a maximum value at a critical Mason number that depends upon the operating conditions.
Predictive Health Monitoring for Aircraft Systems using Decision Trees (2014)

Unscheduled aircraft maintenance causes a lot problems and costs for aircraft operators. This is due to the fact that aircraft cause significant costs if flights have to be delayed or canceled and because spares are not always available at any place and sometimes have to be shipped across the world. Reducing the number of unscheduled maintenance is thus a great costs factor for aircraft operators. This thesis describes three methods for aircraft health monitoring and prediction; one method for system monitoring, one method for forecasting of time series and one method that combines the two other methods for one complete monitoring and prediction process. Together the three methods allow the forecasting of possible failures. The two base methods use decision trees for decision making in the processes and genetic optimization to improve the performance of the decision trees and to reduce the need for human interaction. Decision trees have the advantage that the generated code can be fast and easily processed, they can be altered by human experts without much work and they are readable by humans. The human readability and modification of the results is especially important to include special knowledge and to remove errors, which the automated code generation produced.
Extracting Bitumen from Inner Mongolia Oil Sands Using Several Common Surfactants (2012)

In this work, four oil displacement surfactants (EL110, SG20, Span60 and Tween80) were used to study the extraction of bitumen from oil sands. The effect of concentration of surfactant, extraction temperature, extraction time, the addition of NaOH and extraction solvents was investigated. The results showed that the best concentration of EL110、SG20 and Tween80 were 3%（wt）, 0.1% and 10%，respectively, corresponding to the yield of bitumen were 26.4%，33.4% and 30.7%. The addition of NaOH to EL110 and SG20 solution improved the yield of bitumen, which were 45.9% and 48.0%. With the temperature increasing, the yield of bitumen increased speedily. The extraction time is 2 hours. For Tween80, at 60°C, using ethanol as solvent gave a higher yield of bitumen than that of using water. At 70°C, using pure ethanol as extraction solvent gave the yield of bitumen 93.3%. At 60°C the yield of bitumen using pure ethanol was 68.9%, addition of 0.5% Span60 improved the yield to 96.9%, but the addition of Tween80 had no effect on the yield.
Architectural Innovation: The Reconfiguration of Existing Product Technologies and the Failure of Established Firms (1990)

Rebecca M. Henderson, Kim B. Clark, Architectural Innovation: The Reconfiguration of Existing Product Technologies and the Failure of Established Firms, Administrative Science Quarterly, Vol. 35, No. 1, Special Issue: Technology, Organizations, and Innovation (Mar., 1990), pp. 9-30
SWAMP: Smith-Waterman using associative massive parallelism (2008)

One of the most commonly used tools by computational biologists is some form of sequence alignment. Heuristic alignment algorithms developed for speed and their multiple results such as BLAST [1] and FASTA [2] are not a total replacement for the more rigorous but slower algorithms like Smith- Waterman [3]. The different techniques complement one another. A heuristic can filter dissimilar sequences from a large database such as GenBank [4] and the Smith-Waterman algorithm performs more detailed, in-depth alignment in a way not adequately handled by heuristic methods. An associative parallel Smith-Waterman algorithm has been improved and further parallelized. Analysis between different algorithms, different types of file input, and different input sizes have been performed and are reported here. The newly developed associative algorithm reduces the running time for rigorous pairwise local sequence alignment.
Comprehensive processing, display and analysis for <i>in vivo</i> MR spectroscopic imaging (2006)

Image reconstruction for magnetic resonance spectroscopic imaging (MRSI) requires specialized spatial and spectral data processing methods and benefits from the use of several sources of prior information that are not commonly available, including MRI-derived tissue segmentation, morphological analysis and spectral characteristics of the observed metabolites. In addition, incorporating information obtained from MRI data can enhance the display of low-resolution metabolite images and multiparametric and regional statistical analysis methods can improve detection of altered metabolite distributions. As a result, full MRSI processing and analysis can involve multiple processing steps and several different data types. In this paper, a processing environment is described that integrates and automates these data processing and analysis functions for imaging of proton metabolite distributions in the normal human brain. The capabilities include normalization of metabolite signal intensities and transformation into a common spatial reference frame, thereby allowing the formation of a database of MR-measured human metabolite values as a function of acquisition, spatial and subject parameters. This development is carried out under the MIDAS project (Metabolite Imaging and Data Analysis System), which provides an integrated set of MRI and MRSI processing functions. It is anticipated that further development and distribution of these capabilities will facilitate more widespread use of MRSI for diagnostic imaging, encourage the development of standardized MRSI acquisition, processing and analysis methods and enable improved mapping of metabolite distributions in the human brain.