gebhart/patrepeval huggingface dataset:
Transition of Tau Protein from Disordered to Misordered in Alzheimer’s Disease (2010)

The neuronal protein tau, a member of the class of intrinsically disordered proteins, is characterized by the absence of any firm 3-D structure and high solubility when free in solution. The tau protein forms insoluble fibrils in the brain of people suffering from Alzheimer’s disease (AD) and other tauopathies and plays a key role in the neurodegenerative process. Posttranslational events leading to the transition of tau from a disordered highly soluble protein to the insoluble aggregate seem to be associated with hyperphosphorylation, truncation or a combination of both. These modifications are assumed to change the native disorder of tau into a preaggregation state, which then directly initiates the fibrillization process. Conformation-specific anti-tau antibody DC11 detects pathological truncated tau forms present in AD brains but not in the normal human brain. A truncated tau protein selected from this pool of DC11-positive molecules was sufficient to initiate and drive the complete tau cascade of neurofibrillary pathology in a rat model of tauopathy. Thus, DC11 antibody recognizes the AD-specific conformation of tau not found in the normal human brain. We propose the term ‘misdisordered’ for this distinct conformational state of tau, which is the first step in the transition of tau from a soluble disordered protein to its insoluble, misordered aggregated form.
Trehalose rescues Alzheimer's disease phenotypes in APP/PS1 transgenic mice (2013)

These results suggested that trehalose could be a potential therapeutic drug for the treatment of AD.
A genome-wide approach to link genotype to clinical outcome by utilizing next generation sequencing and gene chip data of 6,697 breast cancer patients (2015)

We established a pipeline enabling rapid clinical validation of a discovered mutation in a large breast cancer cohort. An online interface is available for evaluating any human gene mutation or combinations of maximum three such genes ( http://www.g-2-o.com ).
Synthesis Conditions and Oxygen Stoichiometry Effects on Li Insertion into the Spinel LiMn2 O 4 (1994)

Using a new electrolyte composition, which is stable against oxidation up to 5 V, the full electrochemical deintercalation of lithium from the spinel is studied. The origin of two new reversible oxidation‐reduction peaks near 4.5 and 4.9 V are examined. The capacity associated with these peaks depends on both the nominal composition in and the synthesis conditions (annealing temperatures and cooling rates), and thereby can be used as an indicator for electrochemically optimized powders. We present evidence that these peaks are related to local structural defects. Thermogravimetric measurements (TGA) on powders show a reversible loss of oxygen that can reach 5% at 1000°C. We find that some of this weight loss is associated with the conversion of cubic to a new tetragonal spinel phase and then to the decomposition of this phase into the orthorhombic phase plus other products. This new tetragonal spinel is prepared as a single phase, and its electrochemical properties are reported.
Hepatocyte growth factor (HGF) inhibits skeletal muscle cell differentiation: A role for the bHLH protein twist and the cdk inhibitor p27 (2000)

Hepatocyte growth factor (HGF) plays a crucial role in regulating the differentiation of both fetal and adult skeletal myoblasts. This study aimed at defining the intracellular factors that mediate the effect of HGF on adult myoblast differentiation. HGF increased Twist expression while decreasing p27(kip1) protein levels and not affecting the induction of p21(Cip1/Waf1) in satellite cells. Like HGF, overexpression of Twist did not affect p21 expression while inhibiting muscle-specific proteins. Both ectopic Twist-antisense (Twist-AS) and p27 partially rescued the effects of HGF on bromodeoxyuridine (BrdU) incorporation and myosin heavy chain (MHC) expression in muscle satellite cells; the two plasmids together effected full rescue, suggesting that HGF independently regulates these two factors to mediate its effects. Ectopic p27 promoted differentiation in the presence of HGF by blocking the induction of Twist. Using Twist-AS to lower Twist levels restored the HGF-dependent reduction of p27 and MHC. In the presence of ectopic HGF, satellite cells formed thin mononuclear myotubes. Neither ectopic p27, Twist-AS, or their combination reversed this change in cell morphology, suggesting that HGF acts through additional mediators to inhibit downstream events during myogenesis. Taken together, the results suggest that the effects of HGF on muscle cell proliferation and differentiation are mediated through changes in the expression levels of the myogenic-inhibitory basic helix-loop-helix (bHLH) protein Twist and the cell-cycle inhibitor p27.
Resonant detection and frequency multiplication of terahertz radiation utilizing plasma waves in resonant-tunneling transistors (2000)

We propose the use of a resonant-tunneling transistor with high mobility of electrons in its quantum-well channel as a detector and a frequency multiplier of terahertz radiation and analyze its characteristics. The combination of strong nonlinearity of the resonant-tunneling current, negative differential conductivity, and excitation of plasma waves in the channel can provide higher performance of detectors and frequency multipliers based on the resonant-tunneling transistor compared to those considered previously.
Design and Synthesis of Aryl Diphenolic Azoles as Potent and Selective Estrogen Receptor-β Ligands (2004)

New diphenolic azoles as highly selective estrogen receptor-beta agonists are reported. The more potent and selective analogues of these series have comparable binding affinities for ERbeta as the natural ligand 17beta-estradiol but are >100-fold selective over ERalpha. Our design strategy not only followed a traditional SAR approach but also was supported by X-ray structures of ERbeta cocrystallized with various ligands as well as molecular modeling studies. These strategies enabled us to take advantage of a single conservative residue substitution in the ligand-binding pocket, ERalpha Met(421) --> ERbeta Ile(373), to optimize ERbeta selectivity. The 7-position-substituted benzoxazoles (Table 5) were the most selective ligands of both azole series, with ERB-041 (117) being >200-fold selective for ERbeta. The majority of ERbeta selective agonists tested that were at least approximately 50-fold selective displayed a consistent in vivo profile: they were inactive in several models of classic estrogen action (uterotrophic, osteopenia, and vasomotor instability models) and yet were active in the HLA-B27 transgenic rat model of inflammatory bowel disease. These data suggest that ERbeta-selective agonists are devoid of classic estrogenic effects and may offer a novel therapy to treat certain inflammatory conditions.
X-rays and after (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTX-rays and afterRonald A. Brown Cite this: J. Chem. Educ. 1979, 56, 3, 191Publication Date (Print):March 1, 1979Publication History Received3 August 2009Published online1 March 1979Published inissue 1 March 1979https://doi.org/10.1021/ed056p191RIGHTS & PERMISSIONSArticle Views88Altmetric-Citations2LEARN 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 InReddit PDF (2 MB) Get e-Alerts Get e-Alerts
Endocannabinoids in Neuroimmunology and Stress (2005)

Two topics are presented in this review. In the first section, we review data regarding the effects of the endocannabinoids (eCBs) and cannabinoid receptors on neuroimmune function. The function of eCBs in the interaction between the immune system and the central nervous system (CNS) is of particular interest, since the CNS itself is a rich source of eCBs while being exquisitely sensitive to inflammation. There are several sites at which cannabinoids can influence neuroinflammation. Microglial cells express both CB receptors and make eCBs. Activation of CB receptors on these cells seems to promote migration and proliferation but to reduce activation to macrophages. In several neurodegenerative diseases, up-regulation of microglial CB2 receptors have been observed. It is our hypothesis that microglial CB receptor activity is anti-inflammatory and could be exploited to manipulate neuroinflammatory processes with a minimum of unwanted effects. The second topic discussed suggests that the eCB/CB1 receptor pair is involved in the responses of animals to acute, repeated and variable stress. The roles of this pair are complex and dependent upon previous stress, among other things. Dysfunctional responding to stress is a component of several human neuropsychiatric disorders, including anxiety and panic disorders, post-traumatic stress disorders, premenstrual dysphoria and quite possibly, drug abuse. While it is too early to say with certainty, it is very possible that either inhibition or potentiation of endocannabinoid signaling will be an efficacious novel therapeutic approach to more than one human psychiatric disease.
Handbook of Capillary Electrophoresis (1998)

ModesIntroduction to Capillary Electrophoresis, R.P. Oda and J.P. LandersMicellar Electrokinetic Chromatography, J.R. MazzeoCapillary Electrophoresis Separation of Enantiomers by Cyclodextrin Array Chiral Analysis, A. GuttmanCapillary Isoelectric Focusing, R. Rodr guez-D az, T. Wehr, M. Zhu, and V. LeviTheory and Practice of Capillary Electrochromatography, M.M. Dittmann and G.P. RozingAnalyteCapillary Ion Electrophoresis, W.R. JonesAnalysis of Small Organic Molecules by Capillary Electrophoresis, K.D. AltriaCapillary Electrophoresis of Peptides, T. van de Goor, A. Apffel, J. Chakel, and W. HancockCapillary Electrophoresis of Proteins, T. Pritchett and F.A. RobeyCarbohydrate Analysis by Capillary Electrophoresis, J.D. Olechno and J.A. NolanSeparation of DNA by Capillary Electrophoresis, K.J. Ulfelder and B.R. McCordEssential Aspects of Capillary ElectrophoresisOptical Detection Techniques for Capillary Electrophoresis, S.L. Pentoney, Jr. and J.V. SweedlerElectrochemical Detection in Capillary Electrophoresis, C. HaberData Analysis in Capillary Electrophoresis, B.J. WandersEffects of Sample Matrix on Capillary Electrophoretic Analysis, Z.K. ShihabiOn-Line Sample Preconcentration for Capillary Electrophoresis, D.S. Burgi and R.-L. ChienApplicationsCapillary Electrophoresis for the Analysis of Single Cells: Electrochemical, Mass Spectrometric, and Radiochemical Detection, F.D. Swanek, S.S. Ferris, and A.G. EwingCapillary Electrophoresis for the Analysis of Single Cells: Laser-Induced Fluorescence Detection, S.J. Lillard and E.S. YeungCapillary Gel Electrophoresis for Large Scale DNA Sequencing: Separation and Detection, N.J. DovichiCapillary Electrophoresis for the Analysis of Drugs in Biological Fluids, R.P. Oda, M.E. Roche, J.P. Landers, and Z.K. ShihabiUse of Capillary Electrophoresis for Binding Studies, F.A. RobeyImmunoassays and Enzyme Assays Using Capillary Electrophoresis, N.M. Schultz, L. Tao, D.J. Rose, Jr., and R.T. KennedyClinical Applications of Capillary Electrophoresis, R.P. Oda, V.J. Bush, and J.P. LandersSpecialized Aspects of Capillary ElectrophoresisCapillary Surface Modification in Capillary Electrophoresis, A.M. Dougherty, N. Cooke, and P. ShiehImproved Capillary Electrophoretic Separations Associated with Controlling Electroosmotic Flow, C.S. LeeContinuous Separations by Electrophoresis in Rectangular Channels, P.F. Gavin and A.G. EwingTwo-Dimensional Liquid Chromatography-Capillary Electrophoresis, D.J. Jeffery, T.F. Hooker, and J.W. JorgensonCapillary Electrophoresis-Mass Spectrometry, J.C. Severs and R.D. SmithMicrofabricated Devices for Performing Capillary Electrophoresis, S.C. Jacobson and J.M. RamseyFraction Collection with Micro-Preparative Capillary Electrophoresis, M.A. Strausbauch and P.J. WettsteinAppendix 1: Calculations for Practical UseAppendix 2: TroubleshootingAppendix 3: Seperation Conditions for Classes of AnalytesIndex
Application-driven cross-layer optimization for video streaming over wireless networks (2006)

Mobile multimedia applications require networks that optimally allocate resources and adapt to dynamically changing environments. Cross-layer design (CLD) is a new paradigm that addresses this challenge by optimizing communication network architectures across traditional layer boundaries. In this article we discuss the relevant technical challenges of CLD and focus on application-driven CLD for video streaming over wireless networks. We propose a cross-layer optimization strategy that jointly optimizes the application layer, data link layer, and physical layer of the protocol stack using an application-oriented objective function in order to maximize user satisfaction. In our experiments we demonstrate the performance gain achievable with this approach. We also explore the trade-off between performance gain and additional computation and communication cost introduced by cross-layer optimization. Finally, we outline future research challenges in CLD.
Optical and Photophysical Properties of the Oxazole Yellow DNA Probes YO and YOYO (1994)

The photophysical properties of the optical DNA probe YOYO (homodimeric derivative of oxazole yellow) have been characterized in terms of the monomeric part, the YO chromophore. In aqueous solutions YO is virtually nonfluorescent but upon binding to DNA its fluorescence quantum yield is strongly increased. A similar enhancement of the fluorescence is observed for YO in the viscous solvent glycerol. The high fluorescence quantum yield of YO, when bound to DNA or in a viscous solution, is proposed to be a result of decreased rotational mobility around the internuclear bridge between the two aromatic ring systems. This hypothesis is based on similar values of the activation energies for the temperature-dependent nonradiative decay processes (E(A) = 53 kJ/mol) and viscous flow (E(A) = 63 kJ/mol), suggesting related rate-limiting mechanisms. A single electronic transition is found to be responsible for the intense visible absorption band. This conclusion is based on the observation of an essentially wavelength-independent reduced linear dichroism and similarly wavelength independent fluorescence anisotropy, and the fact that the emission spectrum is very nearly a mirror image of the absorption spectrum. The conclusion is further supported by quantum mechanical calculations (CNDO/S). By combination of measurements of fluorescence anisotropy of YO in glycerol and linear dichroism of YO in a stretched poly(vinyl alcohol) film, the transition moment of the strong visible absorption band was found to be nearly long axis polarized, in agreement with the CNDO/S calculations. The low-energy electronic transition and its polarization direction in the YO chromophore remain essentially unperturbed in the YOYO dye, suggesting that the results obtained for the excited state of the YO chromophore are applicable also to YOYO. One difference, though, is that in aqueous solutions the two YO chromophores of YOYO interact with each other, forming an internal dimer, resulting in a distorted absorption spectrum.
cDNA cloning and expression of a hamster α‐thrombin receptor coupled to Ca2+ mobilization (1991)

The serine protease alpha-thrombin (thrombin) potently stimulates G-protein-coupled signaling pathways and DNA synthesis in CCL39 hamster lung fibroblasts. To clone a thrombin receptor cDNA, selective amplification of mRNA sequences displaying homology to the transmembrane domains of G-protein-coupled receptor genes was performed by polymerase chain reaction. Using reverse transcribed poly(A)+ RNA from CCL39 cells and degenerate primers corresponding to conserved regions of several phospholipase C-coupled receptors, three novel putative receptor sequences were identified. One corresponds to an mRNA transcript of 3.4 kb in CCL39 cells and a relatively abundant cDNA. Microinjection of RNA transcribed in vitro from this cDNA in Xenopus oocytes leads to the expression of a functional thrombin receptor. The hamster thrombin receptor consists of 427 amino acid residues with 8 hydrophobic domains, including one at the extreme N-terminus that is likely to represent a signal peptide. A thrombin consensus cleavage site is present in the N-terminal extracellular region of the receptor sequence followed by a negatively charged cluster of residues present in a number of proteins that interact with the anion-binding exosite of thrombin.
Exposure to multiple cholinergic pesticides impairs olfactory learning and memory in honeybees (2013)

Pesticides are important agricultural tools often used in combination to avoid resistance in target pest species, but there is growing concern that their widespread use contributes to the decline of pollinator populations. Pollinators perform sophisticated behaviours while foraging that require them to learn and remember floral traits associated with food, but we know relatively little about the way that combined exposure to multiple pesticides affects neural function and behaviour. The experiments reported here show that prolonged exposure to field-realistic concentrations of the neonicotinoid imidacloprid and the organophosphate acetylcholinesterase inhibitor coumaphos and their combination impairs olfactory learning and memory formation in the honeybee. Using a method for classical conditioning of proboscis extension, honeybees were trained in either a massed or spaced conditioning protocol to examine how these pesticides affected performance during learning and short- and long-term memory tasks. We found that bees exposed to imidacloprid, coumaphos, or a combination of these compounds, were less likely to express conditioned proboscis extension towards an odor associated with reward. Bees exposed to imidacloprid were less likely to form a long-term memory, whereas bees exposed to coumaphos were only less likely to respond during the short-term memory test after massed conditioning. Imidacloprid, coumaphos and a combination of the two compounds impaired the bees' ability to differentiate the conditioned odour from a novel odour during the memory test. Our results demonstrate that exposure to sublethal doses of combined cholinergic pesticides significantly impairs important behaviours involved in foraging, implying that pollinator population decline could be the result of a failure of neural function of bees exposed to pesticides in agricultural landscapes.
Dynamic effects in BTG/SOI MOSFETs and circuits due to distributed body resistance (2002)

Summary form only given. The SOI MOSFET with body tied to gate (BTG) has been proposed for low-voltage CMOS applications. Clearly for DC or quasi-static conditions, the BTG device will have reduced threshold voltage (V/sub T/) when on due to the body bias, and hence increased drive current. Thus BTG/SOI CMOS can conceivably be designed with nominal V/sub T/ high enough to avoid excessive static power while giving good speed performance. Thin-film SOI is the preferred technology for BTG MOSFETs because of minimal source/drain junction area and hence less recombination current in the gate. However, the effects of inherent body resistance in the BTG tie, which have not been addressed in depth, are an issue. In this paper, we present insightful results of circuit simulations that reveal dynamic effects of the finite and distributed body resistance and that give insight concerning optimal design of BTG/SOI CMOS devices and circuits.
Self-Assembly of the Recombinant Capsid Protein of a Bovine Norovirus (BoNV) into Virus-Like Particles and Evaluation of Cross-Reactivity of BoNV with Human Noroviruses (2005)

None of the enteric caliciviruses except Po/Sapo/GIII/Cowden/80/US replicates in cell culture, which complicates efforts to develop control strategies or to study viral replication. To develop serological assays for bovine noroviruses (BoNVs) and to determine the cross-reactivity of BoNV with human noroviruses, we generated two recombinant baculoviruses, rCV186-OH and rJNCV, to express the capsid genes of Bo/CV186-OH/00/US (Norovirus genogroup III [GIII], genotype 2 [GIII/2]). rCV186-OH expressed the expected 57-kDa capsid protein, but rJNCV expressed a truncated capsid protein of 35 kDa. Sequence analysis of rJNCV identified a single nucleotide deletion in the P domain of the capsid gene, which introduced a stop codon at amino acid 323. The recombinant capsid protein produced by rCV186-OH but not that produced by rJNCV self-assembled into virus-like particles (VLPs) similar to native BoNV. An antibody-capture enzyme-linked immunosorbent assay (ELISA) and antigen-capture ELISA (Ag-ELISA) detected serum antibody and antigen, respectively, from calves infected with Bo/CV186-OH/00/US but not antibodies or antigens to other enteric viruses. In other tests of the GIII/2 BoNV Ag-ELISA, no cross-reactivity was observed with VLPs from one GI and four GII human noroviruses and porcine sapovirus Cowden strain. Because, like human noroviruses, BoNVs do not grow in cell culture, the BoNV VLPs will be useful in the serological assays described for the detection of BoNV antibody and antigen. Consistent with the phylogenetic analysis of the capsid genes of bovine and human noroviruses (M. G. Han, J. R. Smiley, C. Thomas, and L. J. Saif, J. Clin. Microbiol. 42:5214-5224, 2004), the results suggest that GIII/2 BoNV does not share significant antigenic relationships with the five characterized human noroviruses tested.
Identification of retinoic acid as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha (2007)

Isothiocyanates and phenolic antioxidants can prevent cancer through activation of Nrf2 (NF-E2 p45-related factor 2), a transcription factor that controls expression of cytoprotective genes through the antioxidant response element (ARE) enhancer. Using a human mammary MCF7-derived AREc32 reporter cell line, we now report that all-trans retinoic acid (ATRA), and other retinoic acid receptor alpha (RARalpha) agonists, markedly reduces the ability of Nrf2 to mediate induction of ARE-driven genes by cancer chemopreventive agents including the metabolite of butylated hydroxyanisole, tert-butylhydroquinone (tBHQ). The basal and tBHQ-inducible expression of aldo-keto reductase (AKR) AKR1C1 and AKR1C2 genes, which are regulated by Nrf2, was also repressed by ATRA in AREc32 cells. Antagonists of RARalpha augmented induction of ARE-driven gene expression by tBHQ, as did knockdown of RARalpha by using RNAi. The expression of the ARE-gene battery was increased in the small intestine of mice fed on a vitamin A-deficient diet, and this increase was repressed by administration of ATRA. By contrast, in the small intestine of Nrf2 null mice, the expression of ARE-driven genes was not affected by vitamin A status. In MCF7 cells, ATRA did not block the nuclear accumulation of Nrf2 but reduced the binding of Nrf2 to the ARE enhancer as a consequence of forming a complex with RARalpha. These data suggest that cross-talk between Nrf2 and RARalpha could markedly influence the sensitivity of cells to electrophiles and oxidative stressors and, as a consequence, to carcinogenesis.