gebhart/patrepeval huggingface dataset:
Role of α-Synuclein Carboxy-Terminus on Fibril Formation in Vitro (2003)

Alpha-synuclein (alpha-syn) is the major component of intracellular inclusions in several neurodegenerative diseases, and the conversion of soluble alpha-syn into filamentous aggregates may contribute to disease pathogenesis. Since mechanisms leading to the formation of alpha-syn inclusions are unclear, in vitro models of alpha-syn aggregation may yield insights into this process. To that end, we examined the consequences on the progressive deletion of the carboxy-terminus of alpha-syn in regulating fibril formation, and we show here that carboxy-terminal truncated alpha-syn proteins aggregate faster than the full-length molecule. Protease digestion and immunoelectron microscopy indicate that the alpha-syn amino- and carboxy-termini are more solvent exposed than the central core and that filaments formed from carboxy-terminal truncated alpha-syn are narrower in diameter than the full-length molecule. Moreover, seeding experiments under conditions where full-length alpha-syn did not readily aggregate revealed that carboxy-truncated alpha-syn extending from amino acids 1-102 and 1-110 but not 1-120 were efficient in seeding full-length alpha-syn aggregation over a range of concentrations. Using site-directed mutagenesis, the negatively charged residues 104, 105 and 114, 115 in the carboxy-terminus were implicated in this reduced aggregation and the lack of seeding of full-length alpha-syn fibrillogenesis by 1-120. Our data support the view that the middle region of alpha-syn forms the core of alpha-syn filaments and that negative charges in the carboxy-terminus counteract alpha-syn aggregation. Thus, the carboxy-terminus of alpha-syn may regulate aggregation of full-length alpha-syn and determine the diameter of alpha-syn filaments.
DOSE DEPENDENT IN VIVO INHIBITION OF HUMAN COLORECTAL CANCER (LoVo) BY THE GASTRIN RECEPTOR ANTAGONIST, CI‐988 (1996)

1. The dose-response relationship of a new, potent and selective cholecystokinin B receptor antagonist, CI-988, on the growth of LoVo, a human colon cancer cell line, was studied in vivo. 2. We have previously shown the growth of LoVo to be inhibited both in vitro and in vivo by CI-988. 3. LoVo was grown for 10 days in nude mice that were then treated with CI-988 at 1, 5, 10, 25 and 50 mg/kg per day orally for 20 days. 4. CI-988 significantly inhibited the growth of xenografts at all concentrations except the highest concentration of 50 mg/kg per day (P < 0.00001; ANOVA). The largest inhibitory activity was caused by the 10 mg/kg per day dose, causing a 47% inhibition at day 29 (P = 0.00003: Newman-Keul's test). 5. CI-988 may be of use in inhibiting the growth of colorectal cancer.
2‐Chloro‐3H‐indol‐3‐one and its reactions with nucleophiles (1989)

Abstract The title compound reacts with N ‐ and S ‐nucleophiles to form 3‐substituted indol‐2‐ones, but with C ‐nucleo‐philes to afford either these or the corresponding 2‐substituted indol‐3‐ones. This dichotomy of behavior is documented and rationalized.
Distribution and abundance of metabotropic glutamate receptor subtype 2 in rat brain revealed by [3H]LY354740 binding in vitro and quantitative radioautography: Correlation with the sites of synthesis, expression, and agonist stimulation of [35S]GTPγs binding (2005)

Until recently, there was a lack of selective radioligands for the subtypes of metabotropic glutamate (mGlu) receptors. [(3)H]LY354740 ((+)-2-aminobicyclo[3,1,0]hexane-2,6-dicarboxylic acid), a selective agonist for group II receptors (mGlu2 and -3, which are negatively coupled to cAMP production), has now been used to map their brain distribution and abundance by in vitro binding and quantitative radioautography. The selective cation dependence of its binding allowed the discrimination between mGlu2 and mGlu3 receptor labeling. Thus, in the presence of Ca(2+) and Mg(2+) ions, the agonist bound selectively to mGlu2 receptors as evidenced by: 1) the correlative distribution and abundance of binding sites (highest in the lacunosum moleculare of the hippocampus and lowest in white matter) with mGlu2 receptor mRNA and protein revealed by in situ hybridization histochemistry and immunohistochemistry, respectively; 2) its selective pharmacology; and 3) the distribution of LY354740-stimulated [(35)S]GTPgammaS binding (25-97% above basal, according to the brain region), revealing G protein-coupled receptor coupling to G(i) proteins. Nonspecific binding (in the presence of 10 muM DCG-IV, a group II-selective, mGlu2-preferring, receptor agonist) was <10% of total. In adjacent sections, the distribution of binding sites for [(3)H]DCG-IV was very similar. This extensive study paves the way for investigations of the regional expression and regulation of mGlu2 receptors in human CNS diseases, such as Alzheimer's disease, which may reveal their functional roles and identify potential therapeutic drug targets. Indeed, it has recently been demonstrated (Higgins et al. [2004] Neuropharmacology 46:907-917) that pharmacological manipulation of mGlu2 receptors influences cognitive performance in the rodent.
Fleet management information services for the transportation industry (2003)

Summary form only given. The author presents Telesat Mobile's vision of the scope and integration of new applications for the transportation market. The corporation's current development and implementation program and short-term plans are reviewed. It is noted that to achieve a competitive advantage in North American industry an open architecture approach, industry-wide cooperation, and a strong application focus are required. >
Phosphorus removal using bauxite refining residue (red mud) (1993)

The removal of phosphate-phosphorus from drain water using bauxite refining residue was investigated by conducting tests mixing phosphate solution with red mud, and red mud neutralized with phosphogypsum or copperas. Phosphate adsorption isotherms (24 h) followed Freundlich relationship with red mud amended with acidic calcium sulphate and ferrous sulphate having up to 18 times adsorption capacity compared to untreated red mud. Experiments contacting phosphate solution with red muds for 30 seconds followed by 24 h settling to simulate proposed removal of phosphate from drain water flowing to the Peel Harvey estuary in Western Australia indicate that up to 97% phosphate removal is achievable.
PI-103 and sorafenib inhibit hepatocellular carcinoma cell proliferation by blocking Ras/Raf/MAPK and PI3K/AKT/mTOR pathways. (2010)

The combination of sorafenib and PI-103 can significantly inhibit EGF-stimulated Huh7 proliferation by blocking both Ras/Raf/MAPK and PI3K/AKT/mTOR pathways.
Statistical challenges associated with detecting copy number variations with next-generation sequencing (2012)

In this review, we describe and discuss areas of potential biases in CNV detection for each of the four methods. In particular, we focus on issues pertaining to (i) mappability, (ii) GC-content bias, (iii) quality control measures of reads and (iv) difficulty in identifying duplications. To gain insights to some of the issues discussed, we also download real data from the 1000 Genomes Project and analyse its DOC data. We show examples of how reads in repeated regions can affect CNV detection, demonstrate current GC-correction algorithms, investigate sensitivity of DOC algorithm before and after quality control of reads and discuss reasons for which duplications are harder to detect than deletions.
Frequent Occurrence of Pre-existing α2→8-Linked Disialic and Oligosialic Acids with Chain Lengths Up to 7 Sia Residues in Mammalian Brain Glycoproteins (2000)

The pre-existence of alpha2-->8-linked disialic acid (di-Sia) and oligosialic acid (oligo-Sia) structures with up to 7 Sia residues was shown to occur on a large number of brain glycoproteins, including neural cell adhesion molecules (N-CAMs), by two highly sensitive chemical methods (Sato, C., Inoue, S., Matsuda, T., and Kitajima, K. (1998) Anal. Biochem. 261, 191-197; Sato, C., Inoue, S., Matsuda, T., and Kitajima, K. (1999) Anal. Biochem. 266, 102-109). This unexpected finding was also confirmed using a newly developed antibody prepared using a copolymer of alpha2-->8-linked N-acetylneuraminyl p-vinylbenzylamide and acrylamide as an immunogen and known antibodies whose immunospecificities were determined to be di- and oligo-Sia residues with defined chain lengths. The major significance of the new finding that di- and oligo-Sia chains exist on a large number of brain glycoproteins is 2-fold. First, it reveals a surprising diversity in the number and M(r) of proteins distinct from N-CAM that are covalently modified by these short sialyl glycotopes. Second, it suggests that synthesis of di- and/or oligo-Sia units may be catalyzed by alpha2-->8-sialyltransferase(s) that are distinct from the known polysialyltransferases, STX and PST, which are partially responsible for polysialylation of N-CAM.
Dose Proportionality and Pharmacokinetics of Oral Transmucosal Fentanyl Citrate (1998)

Oral transmucosal fentanyl citrate exhibits dose-proportional pharmacokinetics over the dose range of 200-1,600 microg.
The Snaking Wells In Champion West, Offshore Brunei. Best Practices for ERD Well Construction (2008)

Abstract The Champion West field was discovered in 1975 and named Champion West in 1990. The field is located in the North of the Brunei Offshore sector. Phase 3 of this project, is the latest development with 20 wells (oil &amp; gas). These Extended Reach Drilling (ERD) wells, are designed as "snake" wells penetrating the reservoir several times, in order to create multiple drainage points snake well develop oil rim reservoirs. All the wells are of different horizontal lengths, as can be seen in Figure 1 and 2. The objective of this paper, is to present the learning and best practices gained after drilling 5 of these snake oil wells, during Champion West phase 3a. Best practices refers to those developed during the project, that have resulted in: reduction of costs, by reducing trouble time (Non Productive Time)reduction bit off-bottom circulation timesincrease of bit on-bottom timeimproved ability to clean the hole, resulting in trouble-free tripstrouble free casing runsthe deepest SMART completion in the world The 350 days campaign was delivered 49 days earlier than planned and below budget. Total cumulative drilling length was of 34 km. This performance allowed the Well Construction team, to achieve the Shell Global EP, Rig of the Fleet award, twice in 3 years.
Antioxidants inhibit the in vitro production of inflammatory cytokines in Crohn's disease and ulcerative colitis (1998)

Our results suggest that the studied antioxidants, or related compounds, may be of interest in inflammatory bowel disease treatment.
Cultured peripheral nervous system cells support peripheral nerve regeneration through tubes in the absence of distal nerve stump (1985)

Axons of a cut peripheral nerve will grow across a gap (less than or equal to 10 mm in adult rodents) formed when the proximal and distal stumps are placed at opposite ends of an impermeable, inert tube, but will not grow to the end of a blind-ended tube in the absence of the distal stump [Williams et al, 1984]. Work reported here demonstrates that cultured peripheral nervous system (PNS) cells suspended in a collagen matrix will provide an effective milieu that directs and supports axonal regeneration from a severed nerve into a blind-ended tube in the absence of a distal stump. Adult mouse sciatic nerves were cut and the proximal stumps were inserted into close-ended tubes that contained either a collagen matrix containing dissociated cells from embryonic mouse dorsal root ganglia (DRG), a collagen matrix saturated with medium conditioned by cultured DRG cells, or a collagen matrix saturated with fresh medium. In all three cases cellular cables formed that ran the full length of the tubes, but myelinated and unmyelinated axons regenerated the length of the tubes only when cultured cells had been added. The critical factor in influencing axonal regeneration through the length of the tubes was the presence of cultured cells, since collagen alone or collagen saturated with conditioned medium did not support axonal regrowth even though cells had migrated into the chambers from the proximal stumps in all cases. Ordered structure was not a requisite for axonal growth, since the cultures consisted of random arrays of dissociated cells.
Superluminescent Diode (SLD) Wavelength Control In High Performance Fiber Optic Gyroscopes (1987)

High performance fiber optic gyroscopes require a high degree of scale factor stability. Scale factor is directly dependent&apos; on the wavelength of the light source, regardless of whether the fiber optic gyroscope is operated open or closed loop. The light source of choice is a broadband AlGaAs superluminescent diode (SLD). This paper describes a compact, stable, passive SLD wavelength monitoring device which can measure the mean wavelength of an SLD to an accuracy that meets stability requirements.
Dual tropism for macrophages and lymphocytes is a common feature of primary human immunodeficiency virus type 1 and 2 isolates (1994)

We have investigated the ability of human immunodeficiency virus type 1 (HIV-1) and HIV-2 isolates to infect and replicate in primary human macrophages. Monocytes from blood donors were allowed to differentiate into macrophages by culture in the presence of autologous lymphocytes and human serum for 5 days before infection. A panel of 70 HIV-1 and 12 HIV-2 isolates were recovered from seropositive individuals with different severities of HIV infection. A majority of isolates (55 HIV-1 and all HIV-2) were obtained from peripheral blood mononuclear cells, but isolates from cerebrospinal fluid, monocytes, brain tissue, plasma, and purified CD4+ lymphocytes were also included. All isolates were able to infect monocyte-derived macrophages, even though the replicative capacity of the isolates varied. Interestingly, isolates with a rapid/high, syncytium-inducing phenotype did not differ from slow/low, non-syncytium-inducing isolates in their ability to replicate in monocyte-derived macrophages. Others have reported that rapid/high, syncytium-inducing isolates have a reduced ability to infect and replicate in monocytes. However, different methods to isolate and culture the monocytes/macrophages were used in these studies and our study. Thus, the ability of HIV isolates to replicate in monocytes/macrophages appears to be strongly influenced by the isolation and culture procedures. It remains to be determined which culture procedure is more relevant for the in vivo situation.
Selective Brain-Targeted Antagonism of p38 MAPKα Reduces Hippocampal IL-1β Levels and Improves Morris Water Maze Performance in Aged Rats (2015)

Selective inhibition of p38 MAPKα with VX-745 in aged rats reduces hippocampal IL-1β levels and improves performance in the MWM. As the two effects occur at different dose levels, the behavioral effect appears to be via a mechanism that is independent of reducing cytokine production. The predicted human doses should minimize risks of systemic toxicity.
Hybrid scheme for perceptual object window design with joint scene analysis and eye-gaze tracking for media encoding based on perceptual attention (2006)

The possibility of perceptual compression using live eye tracking has been anticipated for some time by many researchers. Among the challenges of real-time eye-gaze-based perceptual video compression are how to handle the fast nature of eye movements with the relative complexity of video transcoding and also take into account the delay associated with transmission in the network. Such a delay requires additional consideration in perceptual encoding because it increases the size of the area that requires high-quality coding. We present a hybrid scheme, one of the first to our knowledge, that combines eye tracking with fast in-line scene analysis to drastically narrow the high acuity area without the loss of eye-gaze containment.
Control and signal processing for photoresist processing in microlithography (2003)

The lithography process is a critical step in the fabrication of nanostructures for integrated circuit manufacturing. In this paper, a summary is presented of several projects applying control and signal processing techniques to lithography. We begin with a presentation of a nonoptical lithography process under development in our lab. The proposed lithography technique is based on chemically altering the surface in a spatially selective manner to achieve a patterned substrate. In addition to the exposure step, photoresist processing is also critical in lithography. Based on current limitations of photoresist thermal processing system, a new integrated system is designed to improve the performance of temperature sensitive chemically amplified photoresists used in deep-UV lithography. Two case studies where control and signal processing techniques have made an impact in photoresist processing are also presented.
Raman Spectroscopic Measurement of Relative Concentrations in Mixtures of Oral Bacteria (2007)

Near-infrared Raman spectroscopy has been used for species identification of pure microbial specimens for more than a decade. More recently, this optical method has been extended to the analysis of specimens containing multiple species. In this report, we demonstrate rapid, reagent-free quantitative analysis of a simplified model of oral plaque containing three oral bacteria species, S. mutans, S. sanguis, and S. gordonii, using near-infrared Raman spectroscopy. Raman spectra were acquired from bacterial mixtures in 200 seconds. A prediction model was calibrated by the partial least squares method and validated by additional samples. On a scale from 0 to 1, relative fractions of each species could be predicted with a root mean square error of 0.07. These results suggest that near-infrared Raman spectroscopy is potentially useful in quantification of microbial mixtures in general and oral plaques in particular.
Glucose Generates Sub-plasma Membrane ATP Microdomains in Single Islet β-Cells (1999)

Increases in the concentration of free ATP within the islet beta-cell may couple elevations in blood glucose to insulin release by closing ATP-sensitive K+ (KATP) channels and activating Ca2+ influx. Here, we use recombinant targeted luciferases and photon counting imaging to monitor changes in free [ATP] in subdomains of single living MIN6 and primary beta-cells. Resting [ATP] in the cytosol ([ATP]c), in the mitochondrial matrix ([ATP]m), and beneath the plasma membrane ([ATP]pm) were similar ( approximately 1 mM). Elevations in extracellular glucose concentration (3-30 mM) increased free [ATP] in each domain with distinct kinetics. Thus, sustained increases in [ATP]m and [ATP]pm were observed, but only a transient increase in [ATP]c. However, detectable increases in [ATP]c and [ATP]pm, but not [ATP]m, required extracellular Ca2+. Enhancement of glucose-induced Ca2+ influx with high [K+] had little effect on the apparent [ATP]c and [ATP]m increases but augmented the [ATP]pm increase. Underlying these changes, glucose increased the mitochondrial proton motive force, an effect mimicked by high [K+]. These data support a model in which glucose increases [ATP]m both through enhanced substrate supply and by progressive Ca2+-dependent activation of mitochondrial enzymes. This may then lead to a privileged elevation of [ATP]pm, which may be essential for the sustained closure of KATP channels. Luciferase imaging would appear to be a useful new tool for dynamic in vivo imaging of free ATP concentration.
c-Src Tyrosine Phosphorylation of Epidermal Growth Factor Receptor, P190 RhoGAP, and Focal Adhesion Kinase Regulates Diverse Cellular Processes (2001)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTc-Src Tyrosine Phosphorylation of Epidermal Growth Factor Receptor, P190 RhoGAP, and Focal Adhesion Kinase Regulates Diverse Cellular ProcessesMichelle D. Haskell, Jill K. Slack, J. Thomas Parsons, and Sarah J. ParsonsView Author Information Department of Microbiology and Cancer Center, P.O. Box 800734, University of Virginia Health System, Charlottesville, Virginia 22908 Cite this: Chem. Rev. 2001, 101, 8, 2425–2440Publication Date (Web):July 13, 2001Publication History Received12 October 2000Published online13 July 2001Published inissue 1 August 2001https://pubs.acs.org/doi/10.1021/cr0002341https://doi.org/10.1021/cr0002341research-articleACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views609Altmetric-Citations51LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Cell and molecular biology,Monomers,Peptides and proteins,Post-translational modification,Receptors Get e-Alerts
Effect of D to E mutation of the RGD motif in rhodostomin on its activity, structure, and dynamics: Importance of the interactions between the D residue and integrin (2009)

Rhodostomin (Rho) is a snake venom protein containing an RGD motif that specifically inhibits the integrin-binding function. Rho produced in Pichia pastoris inhibits platelet aggregation with a K(I) of 78 nM as potent as native Rho. In contrast, its D51E mutant inhibits platelet aggregation with a K(I) of 49 muM. Structural analysis of Rho and its D51E mutant showed that they have the same tertiary fold with three two-stranded antiparallel beta-sheets. There are no structural backbone differences between the RG[D/E] loop which extends outward from the protein core and the RG[D/E] sequence at its apex in a four-residue RG[D/E]M type I turn. Two minor differences between Rho and its D51E mutant were only found from their backbone dynamics and 3D structures. The R(2) value of E51 is 13% higher than that of the D51 residue. A difference in the charge separation of 1.76 A was found between the sidechains of positive (R49) and negative residues (D51 or E51).The docking of Rho into integrin alphavbeta3 showed that the backbone amide and carbonyl groups of the D51 residue of Rho were formed hydrogen bonds with the integrin residues R216 and R214, respectively. In contrast, these hydrogen bonds were absent in the D51E mutant-integrin complex. Our findings suggest that the interactions between both the sidechain and backbone of the D residue of RGD-containing ligands and integrin are important for their binding.