gebhart/patrepeval huggingface dataset:
A cysteine residue in the third membrane-spanning segment of the human D2 dopamine receptor is exposed in the binding-site crevice. (1994)

The binding site in G-protein-linked neurotransmitter receptors is formed among their membrane-spanning segments. Because the binding site is in the plane of the bilayer and is accessible to charged, water-soluble agonists, it must lie in a crevice open to the extracellular, aqueous medium. Information about the structure of these receptors can be obtained by identifying the residues in the membrane-spanning segments which face this water-filled crevice. Human D2 dopamine receptor was expressed in human embryonic kidney 293 cells. Small, charged, sulfhydryl-specific methanethiosulfonate (MTS) derivatives irreversibly inhibited the binding of the D2-specific antagonist [3H]YM-09151-2 to these cells. The highly polar MTS derivatives should react with cysteine sulfhydryl groups only at the water-accessible surface of the receptor, which includes the surface of the binding-site crevice. In contrast, these reagents will have little access to sulfhydryls facing the lipid bilayer or buried in the protein interior. Positively charged MTS reagents irreversibly inhibited binding several hundredfold faster than a negatively charged MTS reagent, consistent with the affinity of the binding site for positively charged dopamine agonists and antagonists. Furthermore, both agonists and antagonists of the D2 receptor protected against irreversible inhibition by the MTS reagents. To identify the susceptible cysteine, we mutated, one at a time, five transmembrane and two extracellular cysteine residues to serine. Only the mutation of Cys118 to serine decreased the susceptibility of antagonist binding to irreversible inhibition by the MTS reagents. Thus, Cys118, a residue in the middle of the third membrane-spanning segment, is exposed in the D2 receptor binding-site crevice.
Structural Analysis of Oligosaccharides from Lipopolysaccharide (LPS) of Escherichia coli K12 Strain W3100 Reveals a Link between Inner and Outer Core LPS Biosynthesis (2003)

Lipopolysaccharide (LPS) from Escherichia coli K12 W3100 is known to contain several glycoforms, and the basic structure has been investigated previously by methylation analyses (Holst, O. (1999) in Endotoxin in Health and Disease (Brade, H., Opal, S. M., Vogel, S. N., and Morrison, D., eds) pp. 115-154; Marcel Dekker, Inc., New York). In order to reveal dependences of gene activity and LPS structure, we have now determined the composition of de-O-acylated LPS by electrospray ionization-Fourier transform ion cyclotron-mass spectrometry (ESI-FT-MS) and identified 11 different LPS molecules. We have isolated the major glycoforms after de-O- and de-N-acylation and obtained four oligosaccharides that differed in their carbohydrate structure and phosphate substitution. The main oligosaccharide accounted for approximately 70% of the total and had a molecular mass of 2516 Da according to ESI-FT-MS. The dodecasaccharide structure (glycoform I) as determined by NMR was consistent with MS and compositional analysis. One minor oligosaccharide (5%) of the same carbohydrate structure did not contain the 4'-phosphate of the lipid A. Two oligosaccharides contained the same phosphate substitution but differed in their carbohydrate structure, one (5%) which contained an additional beta-D-GlcN in 1-->7 linkage on a terminal heptose residue (glycoform II) which was N-acetylated in LPS. A minor amount of a molecule lacking the terminal L-alpha-D-Hep in the outer core but otherwise identical to the major oligosaccharide (glycoform III) could only be identified by ESI-FT-MS of the de-O-acylated LPS. The other oligosaccharide (20%) contained an alpha-Kdo-(2-->4)-[alpha-l-Rha-(1-->5)]-alpha-Kdo-(2-->4)-alpha-Kdo branched tetrasaccharide connected to the lipid A (glycoform IV). This novel inner core structure was accompanied by a truncation of the outer core in which the terminal disaccharide L-alpha-D-Hep-(1-->6)-alpha-D-Glc was missing. The latter structure was identified for the first time in LPS and revealed that changes in the inner core structure may be accompanied by structural changes in the outer core.
Design, Synthesis, and Evaluation of A-, C-, and D-Ring Analogs of the Fungal Metabolite K-76 as Potential Complement Inhibitors (1995)

The terpenoid 6,7-diformyl-3',4',4a',5',6',7',8',8a'-octahydro-4,6',7'-trihydrox y-2',5',5', 8a'-tetramethylspiro[1'(2'H)-naphthalene-2(3H)-benzofuran] (1a; K-76), a natural product of fungal origin, and its monocarboxylate sodium salt 1c (R = COONa; K-76COONa) inhibit the classical and alternative pathways of complement, and 1c was shown to inhibit the classical pathway at the C5 activation step. In an attempt to elucidate the essential pharmacophore of 1a,c, the natural product was used as a "topographical model" for the design of partial analogs retaining the desired complement inhibiting potency. Therefore, A/C/D-ring analogs have been synthesized, as shown in Scheme 1 using 3-methoxyphenol (3) and limonene chloride (5) as starting materials, which contain functional groups similar to those found on the natural product. The use of (4R)-(+)- and (4S)(-)-limonene chloride (5a,b, respectively) provided two series of compounds differing in the stereochemistry of the C-4 chiral center (limonene moiety numbering). The in vitro assay results of the inhibition of anaphylatoxin production and classical complement-mediated hemolysis revealed that 7-carboxy-2-(R,S)-methyl-2-(1'-methylcyclohexen-(4'R)-yl)-4-met hoxybenzofuran (13a) and 7-carboxy-2-(R,S)-methyl-2-(1'-methylcyclohexen-(4'S)-yl)-4-met hoxybenzofuran (13b) were active in the same range of concentrations as the natural product.
[Evaluation of selected parameters of connective tissue metabolism in patients with primary open angle glaucoma]. (1997)

The concentration of P III NP in the blood serum was markedly increased (3.99 +/- 1.5 micrograms/l) compared with control group (2.84 +/- 0.77 micrograms/l), p < 0.05. There was not significant difference in concentration of P I CP in both groups.
The c-KIT mutation causing human mastocytosis is resistant to STI571 and other KIT kinase inhibitors; kinases with enzymatic site mutations show different inhibitor sensitivity profiles than wild-type kinases and those with regulatory-type mutations (2002)

Mutations of c-KIT causing spontaneous activation of the KIT receptor kinase are associated with sporadic adult human mastocytosis (SAHM) and with human gastrointestinal stromal tumors. We have classified KIT-activating mutations as either "enzymatic site" type (EST) mutations, affecting the structure of the catalytic portion of the kinase, or as "regulatory" type (RT) mutations, affecting regulation of an otherwise normal catalytic site. Using COS cells expressing wild-type or mutant KIT, 2 compounds, STI571 and SU9529, inhibited wild-type and RT mutant KIT at 0.1 to 1 microM but did not significantly inhibit the Asp816Val EST mutant associated with SAHM, even at 10 microM. Using 2 subclones of the HMC1 mast cell line, which both express KIT with an identical RT mutation but which differ in that one also expresses the Asp816Val EST mutation, both compounds inhibited the RT mutant KIT, thereby suppressing proliferation and producing apoptosis in the RT mutant-only cell line. Neither compound suppressed activation of Asp816Val EST mutant KIT, and neither produced apoptosis or significantly suppressed proliferation of the cell line expressing the Asp816Val mutation. These studies suggest that currently available KIT inhibitors may be useful in treating neoplastic cells expressing KIT activated by its natural ligand or by RT activating mutations such as gastrointestinal stromal tumors but that neither compound is likely to be effective against SAHM. Furthermore, these results help establish a general paradigm whereby classification of mutations affecting oncogenic enzymes as RT or EST may be useful in predicting tumor sensitivity or resistance to inhibitory drugs.
βCaMKII in Lateral Habenula Mediates Core Symptoms of Depression (2013)

The lateral habenula (LHb) has recently emerged as a key brain region in the pathophysiology of depression. However, the molecular mechanism by which LHb becomes hyperactive in depression remains unknown. Through a quantitative proteomic screen, we found that expression of the β form of calcium/calmodulin-dependent protein kinase type II (βCaMΚΙΙ) was significantly up-regulated in the LHb of animal models of depression and down-regulated by antidepressants. Increasing β-, but not α-, CaMKII in the LHb strongly enhanced the synaptic efficacy and spike output of LHb neurons and was sufficient to produce profound depressive symptoms, including anhedonia and behavioral despair. Down-regulation of βCaMKII levels, blocking its activity or its target molecule the glutamate receptor GluR1 reversed the depressive symptoms. These results identify βCaMKII as a powerful regulator of LHb neuron function and a key molecular determinant of depression.
Cerebral Apoptosis in Severe Traumatic Brain Injury Patients: An In Vitro, In Vivo , and Postmortem Study (2008)

One of the most important recent observations in traumatic brain injury (TBI) relates to the potential role of apoptosis in secondary brain injury. We aimed to analyze the presence of apoptosis and the expression of apoptosis-related proteins in brain samples from patients with TBI. We also tried to find any association between the in situ results and the in vitro observations in a neuronal model of induced-apoptosis. Brain tissue from the pericontusional zone (PCZ) of patients with traumatic contusions and from post-mortem samples was analyzed. Immunohistochemical analyses of apoptosis-related proteins and the terminal deoxynucleotide transferase-mediated nick end labeling (TUNEL) method to determine the presence of apoptotic cells were performed. Apoptotic rates on neuronal cells induced by jugular bulb vein sera was determined by flow cytometry. TUNEL-positive cells were detected in all PCZ of traumatic contusions and in most of PCZ in post-mortem specimens (none in control; p = 0.026). In vivo samples showed higher expression of antiapoptotic proteins Bcl-2 (p = 0.027) and Bcl-XL (p = 0.014) than post-mortem samples. In autopsies, the expression of Fas and Bim (p < 0.05) were higher in PCZ than in the zone distal from the contusion. In vitro studies showed that apoptotic rate was an independent factor associated with mortality at 6 months (p = 0.014). In the receiving operator curve (ROC) curve, a cut-off point of 66.5% showed a sensitivity of 89.5% and specificity of 66.7% in the prediction of patients' death. Cerebral apoptosis is a prominent form of cell death in the PCZ of human traumatic cerebral contusions, and high rates of in vitro apoptosis are associated with a poorer prognosis after TBI.
A Self-Service Supporting Business Intelligence and Big Data Analytics Architecture (2017)

Self-service Business Intelligence (SSBI) is an emerging topic for many companies. Casual users should be enabled to independently build their own analyses and reports. This accelerates and simplifies the decision-making processes. Although recent studies began to discuss parts of a self-service environment, none of these present a comprehensive architecture. Following a design science research approach, this study proposes a new self-service oriented BI architecture in order to address this gap. Starting from an in-depth literature review, an initial model was developed and improved by qualitative data analysis from interviews with 18 BI and IT specialists form companies across different industries. The proposed architecture model demonstrates the interaction between introduced self-service elements with each other and with traditional BI components. For example, we look at the integration of collaboration rooms and a self-learning knowledge database that aims to be a source for a report recommender.
The Influence Curve and its Role in Robust Estimation (1974)

Abstract This paper treats essentially the first derivative of an estimator viewed as functional and the ways in which it can be used to study local robustness properties. A theory of robust estimation “near” strict parametric models is briefly sketched and applied to some classical situations. Relations between von Mises functionals, the jackknife and U-statistics are indicated. A number of classical and new estimators are discussed, including trimmed and Winsorized means, Huber-estimators, and more generally maximum likelihood and M-estimators. Finally, a table with some numerical robustness properties is given.
Evidence of pulmonary tropism of bamifylline and its main active metabolite. (1989)

The extent of the extraplasmatic tropism of bamifylline (Bamifix) was evaluated in the rat and in man by assaying concentrations of bamifylline and of its main active metabolite AC-119 in lung tissue and plasma. After a single oral and intravenous administration of bamifylline in the rat, the ratio between pulmonary and plasma concentrations was between 2.0 and 3.2 for bamifylline, and between 4 and 15 for AC-119 during the observation period considered. On the other hand, the same ratios, calculated after the oral and intravenous administration of theophylline, ranged between 0.20 and 0.39. In studies on man, samples of plasma and lung tissue were obtained during surgery in subjects affected by pulmonary neoplasia and previously subjected to therapy with bamifylline according to the usual dosage scheme. The ratios between tissue and plasma concentrations, at the steady-state and in conditions of equilibrium between the compartments, were 9.4 for bamifylline and 34.7 for its active metabolite. The particular tissue tropism of bamifylline, that appears to be due to its high lipophilic character, could partly explain its high therapeutic index.
[Construction and expression of recombinant adenovirus expression vector of beta-defensin-2]. (2006)

The recombinant adenovirus vector can express cationic peptide beta-defensin-2 in eukaryocytes.
Light Generation, Modulation, And Amplification By N-I-P-I Doping Superlattices (1986)

The n-i-p-i doping superlattices, periodic structures composed of n- and p-doped layers, possibly with undoped (i-) regions of the same semi-conductor material in between, form a new class of semiconductors. Apart from their two-dimensional and highly anisotropic electronic structure, a property they share with their compositional superlattice counterparts, they exhibit widely tunable electrical and optical properties that make them very appealing for various applications. Carrier concentration, lumines-cence spectra, absorption coefficient, and refractive index can be modulated by unusually large amounts by weak light signals, injection currents, or external fields. We briefly review the basic theoretical concept and some of the experiments that have confirmed the theory. Then we describe a number of optoelectronic and purely optical device applications. These include wavelength-tunable incoherent and coherent light-emitting devices with high modulation frequency, fast optical modulators, and nonlinear optical devices, possibly exhibiting optical multistability. Although the concept is applicable to any semiconductor that can be doped appropriately, a combination of periodic doping and composition ("hetero n-i-p-i") exhibits particularly appealing potential for devices in the 0.8 to 1.55 µm wavelength range.
Influence of Si, Ca and Ag addition on corrosion behaviour of new wrought Mg–Zn alloys (2006)

The development of new wrought magnesium alloys for automotive industry has increased in recent years owing to their high potential as structural materials for low density and high strength/weight ratio demands. However, the poor mechanical properties and low corrosion resistance of the magnesium alloys have led to searching a new kind of magnesium alloys for better strength, ductility and high corrosion resistance. The main objective of the present research is to investigate the mechanical properties and the corrosion behaviour of new magnesium alloys, Mg–Zn–Ag (ZQ) and Mg–Zn–Si–Ca (ZS) alloys. The ZQ6X and ZS6X–YCa alloys were prepared by using hot extrusion method. Hardness AC and DC polarisation tests were carried out on the extruded rods, which contain different amounts of silver or silicon and calcium. The potential difference in air between different phases and the matrix was examined using scanning Kelvin probe force microscopy. The microstructure was examined using optical and electron microscopy (TEM and SEM), X-ray analysis and EDS. The results showed that the silver addition improved the mechanical properties but decreased the corrosion resistance. The addition of silicon and calcium also affected both mechanical properties and corrosion behaviour. These results can be explained by the effects of alloying elements on microstructure of Mg–Zn alloys such as grain size and precipitates caused by the change in precipitation and recrystallisation behaviour.
Faster Subband Signal Processing [dsp Tips&Tricks] (2013)

Subband signal processing is an important tool in numerous applications such as acoustic echo cancellation, noise reduction, signal enhancement, adaptive beam forming, and signal separation, among other applications. Subband signal processing uses a filter bank to split each input signal into a set of frequency signals, each covering a fraction of the input signal bandwidth. Subband processing provides an efficient way to divide and conquer tedious problems by a set of parallel and smaller subband algorithms. In many cases, the subband processing is performed together with decimation, which reduces the dimensionality of the data in the subband algorithm. The focus in this article is on temporal subband processing, i.e., time-frequency transformation, although spatial subband processing may also gain from the discussion here.
Different cell surface oligomeric states of B7-1 and B7-2: Implications for signaling (2005)

The costimulatory ligands B7-1 and B7-2 are expressed on the surface of antigen-presenting cells and interact with the costimulatory receptors CD28 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) expressed on T cells. Although B7-1 and B7-2 are homologous ligands having common receptors, they exhibit distinct biochemical features and roles in immune regulation. Several biochemical and structural studies have indicated differences in the oligomeric state of B7-1 and B7-2. However, the organization of B7 ligands on the cell surface has not been examined. By using photobleaching-based FRET (pbFRET), we demonstrate that B7-1 and B7-2 adopt different oligomeric states on the cell surface. Our study shows that B7-2 exists as a monomer on the cell surface whereas B7-1 exists predominantly as dimers on the cell surface. A series of mutations in B7-1 result in the expression of a predominantly monomeric species on the cell surface and validate the dimer interface proposed by prior crystallographic analysis. The difference in the oligomeric states of B7-1 and B7-2 provides insight into the geometric organization of the costimulatory receptor-ligand complexes in the immunological synapse and suggests constraints on signal transduction mechanisms involved in T cell activation.
Breath Ethanol and Acetone as Indicators of Serum Glucose Levels: An Initial Report (2005)

The integrated analysis of multiple exhaled gases may serve as a marker of blood glucose levels. Further studies are needed to assess the usefulness of this method in different populations.
Synthesis and NMD A Antagonistic Properties of the Enantiomers of 4‐(3‐phosphonopropyl)piperazine‐2‐carboxylic acid (CPP) and of the unsaturated analogue (E)‐4‐(3‐phosphonoprop‐2‐enyl)piperazine‐2‐carboxylic acid (CPP‐ene) (1989)

Abstract The ( R )‐ and ( s )‐enantiomers of 4‐(3‐phosphonopropyl)piperazine‐2‐carboxylic acid ( D ‐ and L ‐CPP, resp.; 15 and 16 , resp.), and of its unsaturated analogue ( E )‐4‐(3‐phosphonoprop‐2‐enyl)piperazine‐2‐carboxylic acid ( D ‐ and L ‐CPP‐ene, resp.; 13 and 14 , resp.) were prepared. The absolute configuration of the enantiomers was determined by a chemical correlation of the menthyl ester 7 with D ‐asparagine. The affinity of these derivatives for the NMDA receptor was determined by displacement of [ 3 H]CPP in rat cerebral cortical membranes. In two functional tests (the frog hemisected spinal cord preparation and the sodium efflux test from rat brain slices), D ‐CPP‐ene appears to be the most potent, enantiomerically pure, competitive NMDA antagonist known to date.
Microdroplet Growth Mechanism during Water Condensation on Superhydrophobic Surfaces (2012)

By promoting dropwise condensation of water, nanostructured superhydrophobic coatings have the potential to dramatically increase the heat transfer rate during this phase change process. As a consequence, these coatings may be a facile method of enhancing the efficiency of power generation and water desalination systems. However, the microdroplet growth mechanism on surfaces which evince superhydrophobic characteristics during condensation is not well understood. In this work, the sub-10 μm dynamics of droplet formation on nanostructured superhydrophobic surfaces are studied experimentally and theoretically. A quantitative model for droplet growth in the constant base (CB) area mode is developed. The model is validated using optimized environmental scanning electron microscopy (ESEM) imaging of microdroplet growth on a superhydrophobic surface consisting of immobilized alumina nanoparticles modified with a hydrophobic promoter. The optimized ESEM imaging procedure increases the image acquisition rate by a factor of 10-50 as compared to previous research. With the improved imaging temporal resolution, it is demonstrated that nucleating nanodroplets coalesce to create a wetted flat spot with a diameter of a few micrometers from which the microdroplet emerges in purely CB mode. After the droplet reaches a contact angle of 130-150°, its base diameter increases in a discrete steplike fashion. The droplet height does not change appreciably during this steplike base diameter increase, leading to a small decrease of the contact angle. Subsequently, the drop grows in CB mode until it again reaches the maximum contact angle and increases its base diameter in a steplike fashion. This microscopic stick-and-slip motion can occur up to four times prior to the droplet coalescence with neighboring drops. Lastly, the constant contact angle (CCA) and the CB growth models are used to show that modeling formation of a droplet with a 150° contact angle in the CCA mode rather than in the CB mode severely underpredicts both the drop formation time and the average heat transfer rate through the drop.
Editable dynamic textures (2002)

This technical sketch presents a simple and efficient algorithm for editing realistic sequences of images of dynamic scenes that exhibit some form of temporal regularity. Such scenes include flowing water, steam, smoke, flames, foliage of trees in wind, crowds, dense traffic flow etc. We call this kind of scenes dynamic textures.
Loin pain hematuria syndrome: Pain control with RFA to the splanchanic plexus (2000)

Click to increase image sizeClick to decrease image sizeKeywords: Hematurialoinpainradio-frequency ablation