gebhart/patrepeval huggingface dataset:
Cholesterol Modulates the Membrane- Disordering Effects of Beta-Amyloid Peptides in the Hippocampus: Specific Changes in Alzheimer’s Disease (2000)

Cholesterol represents an important determinant of the physical state of biological membranes. In Alzheimer's disease (AD) brains, specific changes in the distribution of cholesterol and its membrane-ordering effects take place. In the present study, membrane fluidity was investigated at the level of the hydrocarbon core and of the heads of the phospholipid bilayers using two different fluorescent probes. Hippocampal membranes of AD brains showed a reduced fluidity in the hydrocarbon core region only. Fluidity was correlated with the cholesterol content in AD and control membranes. Aggregated beta-amyloid peptides (Abeta) disrupted brain membrane structure in AD patients and controls in the same fashion. However, this effect was correlated with the cholesterol content in AD membranes only. It is suggested that in AD the brain becomes specifically sensitive for the modulation by membrane-bound cholesterol of the membrane-disturbing and ultimately neurotoxic properties of Abeta.
Molecular Basis of Neural-Specific Gene Expression (1993)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
The Common Variant rs1447295 on Chromosome 8q24 and Prostate Cancer Risk: Results from an Australian Population-Based Case-Control Study (2007)

A recent study from deCode reported an association between common variants in the region 8q24 and prostate cancer risk. The strongest association was found with the single nucleotide polymorphism rs1447295. We genotyped 821 prostate cancer cases and 732 population controls for rs1447295 to test the association between this common variant and prostate cancer risk, and examine whether this association depends on Gleason score. Our case-control study confirmed the association between rs1447295 and prostate cancer risk (P = 0.0005). The odds ratio (OR) for prostate cancer was 1.52 [95% confidence interval (CI), 1.20-1.93] for carriers of any A allele compared with noncarriers. The OR for Gleason score 5 to 6 prostate cancer (1.48; 95% CI, 1.13-1.95) was similar to the OR for Gleason score 7 to 10 prostate cancer (1.58; 95% CI, 1.18-2.11, P for heterogeneity = 0.7). We conclude that the A allele of rs1447295 is associated with a higher risk of prostate cancer regardless of tumor aggressiveness, suggesting that such a variant, or a variant in linkage disequilibrium with it, plays a role early in prostate carcinogenesis.
Numerical Investigation of Engine Effects on a Transport Aircraft with Circulation Control (2015)

The scope of this paper is to illustrate the installation effects of a turboprop engine on a high-lift configuration of a short takeoff and landing aircraft with circulation control. In addition to the influence on the wing performance, the impact on the longitudinal static stability of the aircraft is also investigated. Furthermore, critical failure cases, namely one engine inoperative, as well as an asymmetric circulation control failure, are assessed. Therefore, steady computational-fluid-dynamics calculations based on the Reynolds-averaged Navier–Stokes equations were performed. The propeller is modeled with an actuator-disk approach. The results show strong potential of increasing lift by synergy effects between circulation control and propeller slipstream. However, the longitudinal stability and controllability are adversely affected. Regarding the case of one engine inoperative, the resulting yawing moments are twice as high as the actual yawing moments from the asymmetric thrust and are therefore higher than expected.
A Novel SH2-Containing Phosphatidylinositol 3,4,5-Trisphosphate 5-Phosphatase (SHIP2) Is Constitutively Tyrosine Phosphorylated and Associated With src Homologous and Collagen Gene (SHC) in Chronic Myelogenous Leukemia Progenitor Cells (1999)

Abstract Because of the probable causal relationship between constitutive p210bcr/abl protein tyrosine kinase activity and manifestations of chronic-phase chronic myelogenous leukemia (CML; myeloid expansion), a key goal is to identify relevant p210 substrates in primary chronic-phase CML hematopoietic progenitor cells. We describe here the purification and mass spectrometric identification of a 155-kD tyrosine phosphorylated protein associated with src homologous and collagen gene (SHC) from p210bcr/abl-expressing hematopoietic cells as SHIP2, a recently reported, unique SH2-domain–containing protein closely related to phosphatidylinositol polyphosphate 5-phosphatase SHIP. In addition to an N-terminal SH2 domain and a central catalytic region, SHIP2 (like SHIP1) possesses both potential PTB(NPXY) and SH3 domain (PXXP) binding motifs. Thus, two unique 5-ptases with striking structural homology are coexpressed in hematopoietic progenitor cells. Stimulation of human hematopoietic growth factor responsive cell lines with stem cell factor (SCF), interleukin-3 (IL-3), and granulocyte-macrophage colony-stimulating factor (GM-CSF) demonstrate the rapid tyrosine phosphorylation of SHIP2 and its resulting association with SHC. This finding suggests that SHIP2, like that reported for SHIP1 previously, is linked to downstream signaling events after activation of hematopoietic growth factor receptors. However, using antibodies specific to these two proteins, we demonstrate that, whereas SHIP1 and SHIP2 selectively hydrolyze PtdIns(3,4,5)P3 in vitro, only SHIP1 hydrolyzes soluble Ins(1,3,4,5)P4. Such an enzymatic difference raises the possibility that SHIP1 and SHIP2 may serve different functions. Preliminary binding studies using lysates from p210bcr/abl-expressing cells indicate that both Ptyr SHIP2 and Ptyr SHIP1 bind to the PTB domain of SHC but not to its SH2 domain. Interestingly, SHIP2 was found to selectively bind to the SH3 domain of ABL, whereas SHIP1 selectively binds to the SH3 domain of Src. Furthermore, in contrast to SHIP1, SHIP2 did not bind to either the N-terminal or C-terminal SH3 domains of GRB2. These observations suggest (1) that SHIP1 and SHIP2 may have a different hierarchy of binding SH3 containing proteins and therefore may modulate different signaling pathways and/or localize to different cellular compartments and (2) that they may be substrates for tyrosine phosphorylation by different tyrosine kinases. Because recent evidence has clearly implicated both PI(3,4,5)P3 and PI(3,4)P2 in growth factor-mediated signaling, our finding that both SHIP1 and SHIP2 are constitutively tyrosine phosphorylated in CML primary hematopoietic progenitor cells may thus have important implications in p210bcr/abl-mediated myeloid expansion.
Origin ofp-type doping difficulty in ZnO: The impurity perspective (2002)

We investigate the p-type doping difficulty in ZnO by first-principles total-energy calculations. The dopants being considered are group-I elements Li, Na, and K and group-V elements N, P, and As. We find that substitutional group-I elements are shallow acceptors, while substitutional group-V elements such as P and As are deep acceptors. The AX centers that convert acceptors into deep donors are found to be unstable except for P and As. Without compensation by intrinsic defects, the most likely cause for doping difficulty is the formation of interstitials for group-I elements and antisites for group-V elements. Among all the dopants studied here, N is a relatively better candidate for p-type ZnO.
Organization of the Neurofascin Gene and Analysis of Developmentally Regulated Alternative Splicing (1997)

Neurofascin is an axonal member of the L1 subgroup of the immunoglobulin superfamily implicated in neurite extension in the course of embryonic development. Here we have isolated and characterized the gene encoding chicken neurofascin. Comparison of genomic sequences with cDNA sequences provides the structure and localization of intron/exon boundaries and indicates that neurofascin isoforms are generated by alternative splicing of its pre-mRNA. The neurofascin gene is composed of 33 exons distributed over 72 kilobases. Each of the six immunoglobulin- and five fibronectin-type III-like domains is encoded by two exons. While introns between domains are of phase 1, others are of phase 0, 1, or 2. Alternative splicing of neurofascin is developmentally regulated as shown by polymerase chain reaction analysis. Furthermore, plasmid libraries from long range polymerase chain reaction-amplified cDNA of neurofascin were used to examine and quantify the distribution of alternatively spliced exons in individual neurofascin molecules. We found 50 different neurofascin isoforms at different developmental stages and revealed the existence of one major "early" in comparison with multiple "late" neurofascin isoforms.
Certolizumab pegol plus methotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis: Findings of a fifty‐two–week, phase III, multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group study (2008)

Treatment with certolizumab pegol 200 or 400 mg plus MTX resulted in a rapid and sustained reduction in RA signs and symptoms, inhibited the progression of structural joint damage, and improved physical function as compared with placebo plus MTX treatment in RA patients with an incomplete response to MTX.
Effect of amino‐acid substitutions on Alzheimer's amyloid‐β peptide–glycosaminoglycan interactions (2000)

One of the major clinical features of Alzheimer's disease is the presence of extracellular amyloid plaques that are associated with glycosaminoglycan-containing proteoglycans. It has been proposed that proteoglycans and glycosaminoglycans facilitate amyloid fibril formation and/or stabilize these aggregates. Characterization of proteoglycan-protein interactions has suggested that basic amino acids in a specific conformation are necessary for glycosaminoglycan binding. Amyloid-beta peptide (Abeta) has a cluster of basic amino acids at the N-terminus (residues 13-16, His-His-Gln-Lys), which are considered critical for glycosaminoglycan interactions. To understand the molecular recognition of glycosaminoglycans by Abeta, we have examined a series of synthetic peptides with systematic alanine substitutions. These include: His13-->Ala, His14-->Ala, Lys16-->Ala, His13His14Lys16-->Ala and Arg5His6-->Ala. Alanine substitutions result in differences in both the secondary and fibrous structure of Abeta1-28 as determined by circular dichroism spectroscopy and electron microscopy. The results demonstrate that the His-His-Gln-Lys region of Abeta, and in particular His13, is an important structural domain, as Ala substitution produces a dysfunctional folding mutant. Interaction of the substituted peptides with heparin and chondroitin sulfate glycosaminoglycans demonstrate that although electrostatic interactions contribute to binding, nonionic interactions such as hydrogen bonding and van der Waals packing play a role in glycosaminoglycan-induced Abeta folding and aggregation.
Bacteroides fragilis NCTC9343 Produces at Least Three Distinct Capsular Polysaccharides: Cloning, Characterization, and Reassignment of Polysaccharide B and C Biosynthesis Loci (2000)

Bacteroides fragilis produces a capsular polysaccharide complex (CPC) that is directly involved in its ability to induce abscesses. Two distinct capsular polysaccharides, polysaccharide A (PS A) and PS B, have been shown to be synthesized by the prototype strain for the study of abscesses, NCTC9343. Both of these polysaccharides in purified form induce abscesses in animal models. In this study, we demonstrate that the CPC of NCTC9343 is composed of at least three distinct capsular polysaccharides: PS A, PS B, and PS C. A previously described locus contains genes whose products are involved in the biosynthesis of PS C rather than PS B as was originally suggested. The actual PS B biosynthesis locus was cloned, sequenced, and found to contain 22 genes in an operon-type structure. A mutant with a large chromosomal deletion of the PS B biosynthesis locus was created so that the contribution of PS B to the formation of abscesses could be assessed in a rodent model. Although purified PS B can induce abscesses, removal of this polysaccharide does not attenuate the organism's ability to induce abscesses.
Axon: a high speed communication architecture for distributed applications (2002)

The primary goal of the Axon architecture is to support a high-performance data path delivering VHSI (very high speed internetwork) bandwidth directly to applications. The significant features of Axon are: (1) an integrated design of host and network interface architecture, operating systems, and communication protocols; (2) a network virtual storage facility which includes support for virtual shared memory on loosely coupled systems; (3) a high-performance, lightweight object transport facility which can be used by both message-passing and shared-memory mechanisms; and (4) a pipelined network interface which can provide a path directly between the VHSI and host memory.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Capillary Electrophoresis Guidebook: Principles, Operation, and Applications (1995)

This book is intended to be a working guide to the operation of capillary electrophoresis (CE) instrumentation. Since CE is still a rap­ idly maturing technique, detailed validated protocols are not widely established. Therefore, extensive experimental procedures are not pro­ vided for individual analyses. The intention is to provide general guide­ lines on the principles and practice of CE and to give an overview of the specific technologies and important application areas. Part I provides operating instructions for standard commercially available instruments. Guidelines are included for activities such as changing capillaries, method development, quantitative procedures, optimization of precision and sensitivity, and the validation of meth­ ods, fraction collection, and troubleshooting, as well as a quick guide to running a separation. The application range of CE is possibly the most diverse of all analytical techniques and ranges from large, complex macromolecules, such as proteins and nucleic acids, to small solutes, such as organic drugs and inorganic anions and cations
Sulfur Tolerance and DeSOx Studies on Diesel SCR Catalysts (2008)

&lt;div class="htmlview paragraph"&gt;Base metal/zeolite catalysts, particularly containing copper and iron, are among the leading candidates for treatment of NOx emissions for diesel applications. Even with the use of ultra low sulfur fuel, sulfur poisoning is still a durability issue for base metal/zeolite SCR catalysts. In this study, the impact of sulfur poisoning on SCR activity and the stored sulfur removal effectiveness were investigated on several Cu and Fe/zeolite SCR catalysts after different thermal aging. The impact of sulfur was more significant on the Cu than on Fe/zeolite SCR catalysts for the NOx activity. It was found that the sensitivity of thermal aging status to the sulfur poisoning impact was different. The impact of sulfur on NOx activity changed with thermal aging on some catalysts, while it remained relatively the same for other catalysts. The most thermally durable SCR catalyst was not necessarily the most durable to sulfur poisoning. These results suggested that each base metal/zeolite SCR catalyst has its own characteristic response to sulfur poisoning. Control of sulfur poisoning and strategy for deSOx might be different depending on the formulation as well as thermal aging status. This study provides a better estimate of the durability of SCR catalysts as well as the strategy of deSOx for diesel engine aftertreatment.&lt;/div&gt;
Fluorinated Nucleotide Modifications Modulate Allele Selectivity of SNP-Targeting Antisense Oligonucleotides (2017)

Antisense oligonucleotides (ASOs) have the potential to discriminate between subtle RNA mismatches such as SNPs. Certain mismatches, however, allow ASOs to bind at physiological conditions and result in RNA cleavage mediated by RNase H. We showed that replacing DNA nucleotides in the gap region of an ASO with other chemical modification can improve allele selectivity. Herein, we systematically substitute every position in the gap region of an ASO targeting huntingtin gene (HTT) with fluorinated nucleotides. Potency is determined in cell culture against mutant HTT (mtHTT) and wild-type HTT (wtHTT) mRNA and RNase H cleavage intensities, and patterns are investigated. This study profiled five different fluorinated nucleotides and showed them to have predictable, site-specific effects on RNase H cleavage, and the cleavage patterns were rationalized from a published X-ray structure of human RNase H1. The results herein can be used as a guide for future projects where ASO discrimination of SNPs is important.
Purification and structural characterization of the CD11b/CD18 integrin α subunit I domain reveals a folded conformation in solution (1995)

The alpha subunits of the leukocyte CD11/CD18 integrins contain an approximately 200 amino acid 'inserted' or I domain. The I domain of the cell-surface Mac-1 (CD11b/CD18) integrin has been shown to be the major recognition site for several adhesion ligands, including iC3b, fibrinogen, factor X, and ICAM-1. The I domain from the Mac-1 alpha subunit has been expressed in Escherichia coli as a soluble GST-fusion protein containing a factor Xa sensitive cleavage site. Analytical characterization of the purified I domain reveals that it is obtained in very high quality at high yields. CD and NMR spectra indicate that I domain adopts a predominantly folded structure in solution, independent of the remainder of the alpha subunit. Addition of Ca2+ and Mg2+ did not significantly perturb the structural conformation.
High-performance optical retarders based on all-dielectric immersion nanogratings (2005)

High-performance true zero-order optical retarders were realized based on all-dielectric immersion nanogratings. All-dielectric nanolaminate materials, deposited by atomic layer deposition, were utilized to fill the trenches of the nanogratings to form immersion nanogratings. The refractive index of the nanolaminate material can be dialed and controlled precisely by controlling the ratio of the two compositions forming the nanolaminate material. This significantly improves the design and process windows for realizing precise optical retarders, particularly very-low-phase retarders. Three 100-mm-diameter very-low-phase retarders with highly precise and uniform phase retardance and very high transmittance were realized by use of the all-dielectric immersion grating design and an atomic layer deposition technique.
Design and Implementation of a Practical I/O-efficient Shortest Paths Algorithm (2009)

We report on initial experimental results for a practical I/O-efficient Single-Source Shortest-Paths (SSSP) algorithm on general undirected sparse graphs where the ratio between the largest and the smallest edge weight is reasonably bounded (for example integer weights in {1, …, 232}) and the realistic assumption holds that main memory is big enough to keep one bit per vertex. While our implementation only guarantees average-case efficiency, i.e., assuming randomly chosen edge-weights, it turns out that its performance on real-world instances with non-random edge weights is actually even better than on the respective inputs with random weights. Furthermore, compared to the currently best implementation for external-memory BFS [6], which in a sense constitutes a lower bound for SSSP, the running time of our approach always stayed within a factor of five, for the most difficult graph classes the difference was even less than a factor of two. We are not aware of any previous I/O-efficient implementation for the classic general SSSP in a (semi) external setting: in two recent projects [10, 23], Kumar/Schwabe-like SSSP approaches on graphs of at most 6 million vertices have been tested, forcing the authors to artificially restrict the main memory size, M, to rather unrealistic 4 to 16 MBytes in order not to leave the semi-external setting or produce huge running times for larger graphs: for random graphs of 220 vertices, the best previous approach needed over six hours. In contrast, for a similar ratio of input size vs. M, but on a 128 times larger and even sparser random graph, our approach was less than seven times slower, a relative gain of nearly 20. On a real-world 24 million node street graph, our implementation was over 40 times faster. Even larger gains of over 500 can be estimated for random line graphs based on previous experimental results for Munagala/Ranade-BFS. Finally, we also report on early results of experiments in which we replace the hard disk by a solid state disk (flash memory).
Enhancement of Antimicrobial Activity against Pseudomonas aeruginosa by Coadministration of G10KHc and Tobramycin (2006)

Pseudomonas aeruginosa is a common opportunistic human pathogen that is associated with life-threatening acute infections and chronic airway colonization during cystic fibrosis. Previously, we converted the wide-spectrum antimicrobial peptide novispirin G10 into a selectively-targeted antimicrobial peptide (STAMP), G10KHc. Compared to novispirin G10, the STAMP had an enhanced ability to kill Pseudomonas mendocina. In this study, we explored the activity of G10KHc against P. aeruginosa. G10KHc was found to be highly active (as active as tobramycin) against P. aeruginosa clinical isolates. Most interestingly, we observed a synergistic-like enhancement in killing activity when biofilms and planktonic cultures of P. aeruginosa were cotreated with G10KHc and tobramycin. The data indicate that the mechanism of enhanced activity may involve increased tobramycin uptake due to G10KHc-mediated cell membrane disruption. These results suggest that G10KHc may be useful against P. aeruginosa during acute and chronic infection states, especially when it is coadministered with tobramycin.
Residual pulmonary vasoreactivity to inhaled nitric oxide in patients with severe obstructive pulmonary hypertension and Eisenmenger syndrome (2001)

NO inhalation is safe and is associated with a dose dependent increase in circulating cGMP concentrations. Pulmonary vasodilatation in response to iNO was observed in 29% of patients and was influenced by baseline pulmonary haemodynamics. Responsiveness to acute iNO may identify patients with advanced obstructive pulmonary hypertension and Eisenmenger syndrome who could benefit from sustained vasodilator treatment.
State estimation for highly dynamic flying systems using key frame odometry with varying time delays (2012)

System state estimation is an essential part for robot navigation and control. A combination of Inertial Navigation Systems (INS) and further exteroceptive sensors such as cameras or laser scanners is widely used. On small robotic systems with limitations in payload, power consumption and computational resources the processing of exteroceptive sensor data often introduces time delays which have to be considered in the sensor data fusion process. These time delays are especially critical in the estimation of system velocity. In this paper we present a state estimation framework fusing an INS with time delayed, relative exteroceptive sensor measurements. We evaluate its performance for a highly dynamic flight system trajectory including a flip. The evolution of velocity and position errors for varying measurement frequencies from 15Hz to 1Hz and time delays up to 1s is shown in Monte Carlo simulations. The filter algorithm with key frame based odometry permits an optimal, local drift free navigation while still being computationally tractable on small onboard computers. Finally, we present the results of the algorithm applied to a real quadrotor by flying from inside a house out through the window.