gebhart/patrepeval huggingface dataset:
P2‐288: Abeta‐mediated glutamate release from astrocytes (2010)

Excitotoxicity is defined as excessive exposure to the neurotransmitter glutamate or overstimulation of its membrane receptors, leading to neuronal injury or death. Several lines of evidence indicate that synaptic damage and neuronal loss can result from excessive NMDA-type glutamate receptor (NMDAR)-dependent Ca2+ entry. Dysregulation of intracellular Ca2+ homeostasis and glutamate-dependent excitotoxic injury has been suggested to underlie amyloid β-peptide (Aβ) toxicity in Alzheimer's disease (AD), but the exact mechanism remains unknown. We used the glutamate sensing fluorescent reporter (SuperGluSnFR) developed by Roger Tsien's laboratory to perform quantitative optical measurements of glutamate release in response to oligomerized Aβ peptide in cultures of rodent astrocytes. Astrocytes are known to modulate neuronal excitability and synaptic transmission. We extend these findings here by showing that astrocytes can release toxic levels of glutamate in response to oligomerized Aβ. The main objective of this project was to directly measure and quantify glutamate release in from purified rat cortical astrocytes in response to Aβ oligomers. We performed Foerster resonance energy transfer (FRET) microscopy to image glutamate release using the glutamate “sniffer” SuperGluSnFR. This probe provides a sensitive fluorescent readout of glutamate concentration by FRET-dependent changes in the CFP/YFP emission ratio. We co-transfected HEK 293T cells with SuperGluSnFr and Neuroligin, and then co-cultured them with purified rat cortical astrocytes. We used the protein Neuroligin, which is known to induce functional synaptic contacts between cells, to allow the ‘probe’ HEK cells to come into close contact with astrocytes that were suspected of releasing glutamate. Aβ oligomers, as well as Aβ in its non-oligomerized form as a control, were applied during FRET measurements. Aβ oligomers induced glutamate release from astrocytes at a level similar to that known to cause synaptic loss and excitotoxic damage in neurons. Taken together with prior studies, this work suggests that the ill effects of Aβ oligomers on neurons may be mediated by local release of injurious amounts of glutamate from astrocytes.
Prostaglandin D2-Mediated Microglia/Astrocyte Interaction Enhances Astrogliosis and Demyelination intwitcher (2006)

Prostaglandin (PG) D2 is well known as a mediator of inflammation. Hematopoietic PGD synthase (HPGDS) is responsible for the production of PGD2 involved in inflammatory responses. Microglial activation and astrogliosis are commonly observed during neuroinflammation, including that which occurs during demyelination. Using the genetic demyelination mouse twitcher, a model of human Krabbe's disease, we discovered that activated microglia expressed HPGDS and activated astrocytes expressed the DP1 receptor for PGD2 in the brain of these mice. Cultured microglia actively produced PGD2 by the action of HPGDS. Cultured astrocytes expressed two types of PGD2 receptor, DP1 and DP2, and showed enhanced GFAP production after stimulation of either receptor with its respective agonist. These results suggest that PGD2 plays an important role in microglia/astrocyte interaction. We demonstrated that the blockade of the HPGDS/PGD2/DP signaling pathway using HPGDS- or DP1-null twitcher mice, and twitcher mice treated with an HPGDS inhibitor, HQL-79 (4-benzhydryloxy-1-[3-(1H-tetrazol-5-yl)-propyl]piperidine), resulted in remarkable suppression of astrogliosis and demyelination, as well as a reduction in twitching and spasticity. Furthermore, we found that the degree of oligodendroglial apoptosis was also reduced in HPGDS-null and HQL-79-treated twitcher mice. These results suggest that PGD2 is the key neuroinflammatory molecule that heightens the pathological response to demyelination in twitcher mice.
A WDM-Compatible 4 × 32-Gb/s CMOS-Driven Electro-Absorption Modulator Array (2015)

A four-channel electro-absorption-modulator array, driven by 32-nm CMOS drivers providing 2-V peak-to-peak output swing, operates with BER &lt; 10-12 at a data rate of 4 × 32 Gb/s and dissipates 170 mW of power.
Carriage of intestinal spirochaetes by humans: epidemiological data from Western Australia (2001)

The purpose of this study was to investigate carriage of intestinal spirochaetes by selected population groups in Western Australia. Stool specimens from 293 rural patients with gastrointestinal disorders, and from 227 healthy migrants from developing countries were cultured. Spirochaete isolates were identified using PCR, and typed by pulsed field gel electrophoresis (PFGE). Brachyspira aalborgi was not isolated. Brachyspira pilosicoli was recovered from 15 rural patients, all Aboriginal. Prevalence was 9.9% in 151 Aboriginals and 0% in 142 non-Aboriginals. Carriage of B. pilosicoli amongst migrants was 10.6% (24/227). Carriage was significantly increased in Aboriginal children aged 2-5 years (P = 0.0027) and in migrant individuals from the Middle East and Africa (P = 0.0034). Carriage was significantly associated with detection of faecal protozoa in both Aboriginals (P = 0.0021) and migrants (P = 0.012). PFGE results indicated that the B. pilosicoli strains were genetically diverse.
Observations on Pratylenchus penetrans Cobb, 1917 parasitizing the coastal dune grass Ammophila arenaria (L') Link in the Netherlands (2001)

The mechanism of action of clebopride on the motility of guinea pig stomach was examined by the receptor binding assay for bovine brain membrane and by measuring gastric contractility and the release of acetylcholine from the stomach. The receptor binding assay revealed that clebopride bound to the D2 dopamine receptor with a high affinity and to the alpha-2 adrenoceptor and 5-HT2 serotonin receptor with relatively lower affinity, and not to D1 dopamine, alpha-1 adrenergic, muscarinic acetylcholine, H1 histamine, or opioid receptor. In strips of the stomach, clebopride at 10(-8) M to 10(-5) M enhanced the electrical transmural stimulation-evoked contraction and the release of acetylcholine. This enhancement was attributed to the blockade of the D2 dopamine receptor and alpha-2 adrenoceptor because: 1) Maximum responses obtained with specific D2 dopamine receptor antagonist, domperidone, and with specific alpha-2 adrenoceptor antagonist, yohimbine, were smaller than that with clebopride, and the sum of the effects of these two specific receptor antagonists is approximately equal to the effect of clebopride. 2) The facilitatory effect of clebopride was partially eliminated by pretreatment of the sample with domperidone or yohimbine, and the facilitatory effect of clebopride was not observed in preparations treated with the combination of domperidone and yohimbine. Clebopride also antagonized the inhibitory effects of dopamine and clonidine on the electrical transmural stimulation-evoked responses. These results indicate that clebopride acts on post ganglionic cholinergic neurons at D2 and alpha-2 receptors in this preparation to enhance enteric nervous system stimulated motility.
Targeted Drug Delivery in Plants: Enzyme‐Responsive Lignin Nanocarriers for the Curative Treatment of the Worldwide Grapevine Trunk Disease Esca (2019)

Nanocarrier (NC)-mediated drug delivery is widely researched in medicine but to date has not been used in agriculture. The first curative NC-based treatment of the worldwide occurring grapevine trunk disease Esca, with more than 2 billion infected plants causing a loss yearly of $1.5 billion, is presented. To date, only repetitive spraying of fungicides is used to reduce chances of infection. This long-term treatment against Esca uses minimal amounts of fungicide encapsulated in biobased and biodegradable lignin NCs. A single trunk injection of <10 mg fungicide results in curing of an infected plant. Only upon Esca infection, ligninolytic enzymes, secreted by the Esca-associated fungi, degrade the lignin NC to release the fungicide. The specific antifungal activity is confirmed in vitro and in planta (in <i>Vitis vinifera</i> L. cv. 'Portugieser'). All treated plants prove to exhibit significantly fewer symptoms several weeks after treatment, and their condition is monitored for 5 years (2014-2018), proving a long-term curative effect of this NC treatment. This study proves the efficacy of this NC-mediated drug delivery for agriculture, using a minimum amount of fungicides. It is believed that this concept can be extended to other plant diseases worldwide to reduce extensive spraying of agrochemicals.
Evaluation of articulatory codebooks (1987)

The design of a codebook of articulatory shapes was recently reported [M. M. Sondhi, J. Schroeter, and J. N. Larar, J. Acoust. Soc. Am. Suppl. 1 81, S78 (1987)]. The codebook is used in an automatic articulatory analysis/synthesis scheme relying on good initial estimates of vocal tract cross-sectional areas to start up an optimization procedure [J. Schroeter, J. N. Larar, and M. M. Sondhi, Proc. IEEE ICASSP, 308–311 (1987)]. An application-oriented way to evaluate the codebook would be to determine how much the final optimized shape deviates from the shape initially selected. A more general evaluation is to compute the average distortion incurred in quantizing some input record of speech. Using this procedure with an appropriate distance measure, various aspects of codebook formation are evaluated. In particular, the focus is on the strategies utilized for generating training data. Also considered is the effect of different approaches to code-word formation once the training data have been obtained. Evaluation results for this work done to refine the codebook will be presented along with the performance as a function of codebook size.
Shifting Hierarchies of Interleukin-10-Producing T Cell Populations in the Central Nervous System during Acute and Persistent Viral Encephalomyelitis (2011)

Interleukin-10 (IL-10) mRNA is rapidly upregulated in the central nervous system (CNS) following infection with neurotropic coronavirus and remains elevated during persistent infection. Infection of transgenic IL-10/green fluorescent protein (GFP) reporter mice revealed that CNS-infiltrating T cells were the major source of IL-10, with minimal IL-10 production by macrophages and resident microglia. The proportions of IL-10-producing cells were initially similar in CD8(+) and CD4(+) T cells but diminished rapidly in CD8(+) T cells as the virus was controlled. Overall, the majority of IL-10-producing CD8(+) T cells were specific for the immunodominant major histocompatibility complex (MHC) class I epitope. Unlike CD8(+) T cells, a large proportion of CD4(+) T cells within the CNS retained IL-10 production throughout persistence. Furthermore, elevated frequencies of IL-10-producing CD4(+) T cells in the spinal cord supported preferential maintenance of IL-10 production at the site of viral persistence and tissue damage. IL-10 was produced primarily by the CD25(+) CD4(+) T cell subset during acute infection but prevailed in CD25(-) CD4(+) T cells during the transition to persistent infection and thereafter. Overall, these data demonstrate significant fluidity in the T-cell-mediated IL-10 response during viral encephalitis and persistence. While IL-10 production by CD8(+) T cells was limited primarily to the time of acute effector function, CD4(+) T cells continued to produce IL-10 throughout infection. Moreover, a shift from predominant IL-10 production by CD25(+) CD4(+) T cells to CD25(-) CD4(+) T cells suggests that a transition to nonclassical regulatory T cells precedes and is retained during CNS viral persistence.
Organization of Immunoglobulin Genes: Reiteration Frequency of the Mouse κ Chain Constant Region Gene (1974)

Hybridization kinetic analyses with synthetic DNA indicate that there are only two to three copies of the kappa constant region gene per haploid genome. This result lends weight to the argument that the immunoglobulin light chain is encoded by more than one continuous gene sequence.
Visualization of concurrent computations (1993)

Declarative visualization is a paradigm which treats program visualization as a mapping from a program to an image. This paradigm is particularly suitable for the visualization of concurrent computations. A rule-based model for constructing declarative visualizations has been developed. The computational abilities of the model have been assessed, and by showing that these abilities are Turing-equivalent it is demonstrated that the model is capable of performing any computable mapping. The mappings are shown to be evaluable by fast parallel match algorithms similar to those used in production systems.
The analytic methodology of visualization uses program correctness properties to guide the development of visualizations. Application of the methodology to a number of case studies is demonstrated. The results indicate the effectiveness of the methodology and its applicability to concurrent computations.
To demonstrate the feasibility of the declarative model and provide a testbed for investigating both the model and the analytic methodology, a prototype declarative visualization system called Pavane was developed. Images from several Pavane program visualizations are shown. Although originally designed for program visualization, Pavane is also suitable for some limited types of scientific visualization, and images from several such applications are also shown.
Cytokinins control secondary cell wall formation in the inflorescence stem of Arabidopsis (2023)

Abstract Spatiotemporal control over developmental programs is vital to all organisms. Here we show that cytokinin (signaling) deficiency leads to early secondary cell wall (SCW) formation in Arabidopsis inflorescence stem that associates with precocious upregulation of a SCW transcriptional cascade controlled by NAC TFs (NSTs). We demonstrate that cytokinin signaling through the AHK2/3 and the ARR1/10/12 suppresses the expression of several NSTs and SCW formation in the apical portions of stems. Exogenous cytokinin application reconstituted both proper development and apical-basal gradient of NST1 and NST3 in a cytokinin biosynthesis-deficient mutant. We show that AHK2 and AHK3 required functional NST1 or NST3 to control SCW initiation in the interfascicular fibers, further evidencing that cytokinins act upstream of NST s transcription factors. The premature onset of a rigid SCW biosynthesis and altered expression of NST1/3 and VND6/7 due to cytokinin deficiency led to the formation of smaller tracheary elements (TEs) and impaired hydraulic conductivity. We conclude that cytokinins downregulate NSTs to inhibit premature SCW formation in the apical part of the inflorescence stem, facilitating thus the development of fully functional TEs and interfascicular fibers. Summary statement Cytokinins attenuate premature secondary cell wall (SCW) formation via downregulating the expression of NAC TFs, the master switches of SCW transcriptional cascade, thus affecting the tracheary elements size and conductivity.
Atomic Force Microscopy Cantilevers for Sensitive Lateral Force Detection (1999)

In order to enhance the lateral force sensitivity of atomic force microscopy (AFM) to detect atomic or molecular scale interaction, two types of force sensors were fabricated by additional processing of commercial sensors with the help of focused ion beam (FIB) technology. In one type of cantilever, a hinge was fabricated in the middle of the commercial cantilever by FIB milling, resulting in the reduction of the lateral force constant from 1204 N/m to 118 N/m. For further enhancement of the lateral sensitivity without causing snap-in behavior, a novel force sensor was designed and fabricated through a combination of FIB milling and FIB deposition techniques. The lateral force constant was reduced, for example, from 3600 N/m to 20 N/m, and the measured lateral force resolution attained the order of 1 nN.
Systematic Molecular Engineering of a Series of Aniline-Based Squaraine Dyes and Their Structure-Related Properties (2018)

With the objective of developing new near-infrared fluorescent probes and understanding the effect molecular structure exerts on physical properties, a series of aniline-based squaraine dyes with different number and position of methoxy substituents adjacent to the squaraine core were synthesized and investigated. Using both computational and experimental methods, we found that the subtle changes of the number or position of the methoxy substituents influenced the twisting angle of the structure and led to significant variations in optical properties. Moreover, the methoxy substituent also affected aggregation behavior due to steric effects. The X-ray crystal structure of one of the key members of the series, SD-2a, clearly demonstrates the distortion between the four-membered squaraine core and the adjacent aniline ring due to methoxy substitution. Structure-related fast relaxation processes were investigated by femtosecond pump–probe experiments and transient absorption spectra. Quantum chemical calculations and essential state models were exploited to analyze the primary experimental results. The comprehensive investigation of structure-related properties of dihydroxylaniline-based squaraine dyes, with systematic substitution of OH by OCH3 functional groups, serves as a guide for the design of novel squaraine dyes for photonics applications.
Multiple regions of chromosome 4 demonstrating allelic losses in breast carcinomas. (1999)

Allelotyping studies suggest that allelic losses at one or both arms of chromosome 4 are frequent in several tumor types, but information about breast cancer is scant. A recent comparative genomic hybridization analysis revealed frequent losses of chromosome 4 in breast carcinomas. In an effort to more precisely locate the putative tumor suppressor gene(s) on chromosome 4 involved in the pathogenesis of breast carcinomas, we performed loss of heterozygosity studies using 19 polymorphic microsatellite markers. After precise microdissection of archival surgical cases, we analyzed DNA obtained from 44 breast carcinomas for loss of heterozygosity. In addition, DNA from tumor cell lines derived from 14 of these 44 breast carcinomas were also analyzed. We observed deletions of chromosome 4 at multiple sites in both tumor cell lines and breast carcinomas. The deletions in cell lines and their corresponding tumors were extensive in nature, whereas they were more localized in noncultured breast carcinomas. The localized deletions in the noncultured breast carcinomas clearly defined four nonoverlapping regions of frequent deletions: 4q33-34 (76%); 4q25-26 (63%); 4p15.1-15.3 (57%); and 4p16.3 (50%). Our results suggest that there may be multiple putative tumor suppressor genes, located on both arms of chromosome 4, whose inactivation is important in the pathogenesis of breast cancer.
Optically pumped photoconductivity and its use for assessing traps in Si:Pt (1983)

The use of double-beam photoconductivity for assessing the properties of traps between the dark Fermi level and the nearer band in semi-insulating material is described. Provided unipolar conduction (either electrons or holes but not both) can be ensured, the effect of a relatively intense pump beam is to sweep the majority-carrier quasi-Fermi level from its equilibrium position towards the band edge. By adjusting the sample temperature and the pump intensity the quasi-Fermi level can be swept in a controlled way through all the traps in the material, up to and including shallow levels. The traps can thus be detected in small-signal chopped photoconductivity due to a probe beam and their photoionisation spectra determined. The technique is applied to deep traps in Si:Pt. Shallow-level spectra show oscillatory photoconductivity. Four 'deep' levels are found in p-Si:Pt and two in n-Si:Pt.
CoSearch: Leveraging Multiple Devices to Enhance Collaboration in Resource-Constrained Environments (2016)

It is common for large groups of people to simultaneously share a single computer in resource-constrained communities in the developing world. However, sharing computing resources can be frustrating and can limit users’ experience with and exposure to technology. In this paper, we present the motivation behind the CoSearch system, a tool to facilitate co-located group Web search in resourceconstrained environments. CoSearch leverages additional devices that are cheap and pervasive even in developing countries in order to enhance the experience of all group members collaborating around a single computer. We also discuss possible avenues for further research on CoSearchlike applications within the context of the developing world.
The dimerisation of 2-methoxycarbonylbuta-1,3-diene: the importance of paralocalisation energy in assessing diene reactivity (1998)

The dimerisation and competitive cycloaddition of 2-methoxycarbonylbuta-1,3-diene with electron-rich dienes has been investigated. Experimental results provide evidence that the enthalpy of the π-system significantly influences the energy of the transition state of cycloadditions of this type. This has been corroborated by ab initio calculations. We propose an early reorganisation of the π-electrons in such cycloadditions to explain the influence stated above.
NMR Studies of the E140Q Mutant of the Carboxy-Terminal Domain of Calmodulin Reveal Global Conformational Exchange in the Ca2+-Saturated State (1997)

In the present investigation, the Ca2+ activation of the C-terminal domain of bovine calmodulin and the effects of replacing the bidentate Ca2+-coordinating glutamic acid residue in the 12th and last position of loop IV with a glutamine are studied by NMR spectroscopy. The mutation E140Q results in sequential Ca2+ binding in this domain and has far-reaching effects on the structure of (Ca2+)2 TR2C, thereby providing further evidence for the critical role of this glutamic acid residue for the Ca2+-induced conformational change of regulatory EF-hand proteins. Analyses of the NOESY spectra of the mutant under Ca2+-saturated conditions, such that 97% of the protein is in the (Ca2+)2 form, revealed two sets of mutually exclusive NOEs. One set of NOEs is found to be consistent with the closed structure observed in the apo state of the C-terminal domain of the wild-type protein, while the other set supports the open structure observed in the Ca2+-saturated state. In addition, several residues in the hydrophobic core exhibit broadened resonances. We conclude that the (Ca2+)2 form of the mutant experiences a global conformational exchange between states similar to the closed and open conformations of the C-terminal domain of wild-type calmodulin. A population of 65 +/- 15% of the open conformation and an exchange rate of (1-7) x 10(4) s(-1) were estimated from the NMR data and the chemical shifts of the wild-type protein. From a Ca2+ titration of the 15N-labeled mutant, the macroscopic binding constants [log(K1) = 4.9 +/- 0.3 and log(K2) = 3.15 +/- 0.10] and the inherent chemical shifts of the intermediate (Ca2+)1 form of the mutant were determined using NMR. Valuable information was also provided on the mechanism of the Ca2+ activation and the roles of the structural elements in the two Ca2+-binding events. Comparison with the wild-type protein indicates that the (Ca2+)1 conformation of the mutant is essentially closed but that some rearrangement of the empty loop IV toward the Ca2+-bound form has occurred.
Design of a Superheterodyne Receiver Using M-Phase Filters (2013)

In the previous chapters, conventional M-phase filters that can provide a high-Q bandpass filter with a center controlled by clock frequency were introduced. The evolution of the conventional M-phase filter to other useful forms such as high-Q image-rejection filters and high-Q filters with their centers controlled by sum or difference of two clocks was also introduced. In this chapter, we will show how various structures of the previously described M-phase filters have been used in a fully integrated superheterodyne receiver.