438 research outputs found

    MHD oxidant intermediate temperature ceramic heater study

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    The use of three types of directly fired ceramic heaters for preheating oxygen enriched air to an intermediate temperature of 1144K was investigated. The three types of ceramic heaters are: (1) a fixed bed, periodic flow ceramic brick regenerative heater; (2) a ceramic pebble regenerative heater. The heater design, performance and operating characteristics under conditions in which the particulate matter is not solidified are evaluated. A comparison and overall evaluation of the three types of ceramic heaters and temperature range determination at which the particulate matter in the MHD exhaust gas is estimated to be a dry powder are presented

    Structure-function mapping of a heptameric module in the nuclear pore complex.

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    The nuclear pore complex (NPC) is a multiprotein assembly that serves as the sole mediator of nucleocytoplasmic exchange in eukaryotic cells. In this paper, we use an integrative approach to determine the structure of an essential component of the yeast NPC, the ~600-kD heptameric Nup84 complex, to a precision of ~1.5 nm. The configuration of the subunit structures was determined by satisfaction of spatial restraints derived from a diverse set of negative-stain electron microscopy and protein domain-mapping data. Phenotypic data were mapped onto the complex, allowing us to identify regions that stabilize the NPC's interaction with the nuclear envelope membrane and connect the complex to the rest of the NPC. Our data allow us to suggest how the Nup84 complex is assembled into the NPC and propose a scenario for the evolution of the Nup84 complex through a series of gene duplication and loss events. This work demonstrates that integrative approaches based on low-resolution data of sufficient quality can generate functionally informative structures at intermediate resolution

    Nonprofit governance: Improving performance in troubled economic times

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    Nonprofit management is currently pressured to perform effectively in a weak economy. Yet, nonprofit governance continues to suffer from unclear conceptions of the division of labor between board of directors and executive directors. This online survey of 114 executive directors aims to provide clarification and recommendations for social administration

    The chromatin reader ZMYND8 regulates Igh enhancers to promote immunoglobulin class switch recombination

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    Class switch recombination (CSR) is a DNA recombination reaction that diversifies the effector component of antibody responses. CSR is initiated by activation-induced cytidine deaminase (AID), which targets transcriptionally active immunoglobulin heavy chain (Igh) switch donor and acceptor DNA. The 3' Igh super-enhancer, 3' regulatory region (3'RR), is essential for acceptor region transcription, but how this function is regulated is unknown. Here, we identify the chromatin reader ZMYND8 as an essential regulator of the 3'RR. In B cells, ZMYND8 binds promoters and super-enhancers, including the Igh enhancers. ZMYND8 controls the 3'RR activity by modulating the enhancer transcriptional status. In its absence, there is increased 3'RR polymerase loading and decreased acceptor region transcription and CSR. In addition to CSR, ZMYND8 deficiency impairs somatic hypermutation (SHM) of Igh, which is also dependent on the 3'RR. Thus, ZMYND8 controls Igh diversification in mature B lymphocytes by regulating the activity of the 3' Igh super-enhancer

    Architecture of Pol II(G) and molecular mechanism of transcription regulation by Gdown1.

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    Tight binding of Gdown1 represses RNA polymerase II (Pol II) function in a manner that is reversed by Mediator, but the structural basis of these processes is unclear. Although Gdown1 is intrinsically disordered, its Pol II interacting domains were localized and shown to occlude transcription factor IIF (TFIIF) and transcription factor IIB (TFIIB) binding by perfect positioning on their Pol II interaction sites. Robust binding of Gdown1 to Pol II is established by cooperative interactions of a strong Pol II binding region and two weaker binding modulatory regions, thus providing a mechanism both for tight Pol II binding and transcription inhibition and for its reversal. In support of a physiological function for Gdown1 in transcription repression, Gdown1 co-localizes with Pol II in transcriptionally silent nuclei of early Drosophila embryos but re-localizes to the cytoplasm during zygotic genome activation. Our study reveals a self-inactivation through Gdown1 binding as a unique mode of repression in Pol II function

    Academic freedom in Europe: a preliminary comparative analysis

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    Using comparative data from 23 states within the European Union, this paper is a preliminary assessment of the protection for, and (by extension) the health of, academic freedom in the universities of the nations of the European Union. The paper examines constitutional and legislative protection for academic freedom, along with legal regulations concerning institutional governance, the appointment of the Rector and the existence of academic tenure, in order to create a composite picture of the health of academic freedom in the universities within the European Union nations. Additionally the paper considers how this preliminary analysis could be extended through possible further research to aid refinement of the results, and what policy steps could usefully be adopted at European level to protect and strengthen academic freedom

    Neuromagnetic Evidence for Early Auditory Restoration of Fundamental Pitch

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    Background: Understanding the time course of how listeners reconstruct a missing fundamental component in an auditory stimulus remains elusive. We report MEG evidence that the missing fundamental component of a complex auditory stimulus is recovered in auditory cortex within 100 ms post stimulus onset. Methodology: Two outside tones of four-tone complex stimuli were held constant (1200 Hz and 2400 Hz), while two inside tones were systematically modulated (between 1300 Hz and 2300 Hz), such that the restored fundamental (also knows as ‘‘virtual pitch’’) changed from 100 Hz to 600 Hz. Constructing the auditory stimuli in this manner controls for a number of spectral properties known to modulate the neuromagnetic signal. The tone complex stimuli only diverged on the value of the missing fundamental component. Principal Findings: We compared the M100 latencies of these tone complexes to the M100 latencies elicited by their respective pure tone (spectral pitch) counterparts. The M100 latencies for the tone complexes matched their pure sinusoid counterparts, while also replicating the M100 temporal latency response curve found in previous studies. Conclusions: Our findings suggest that listeners are reconstructing the inferred pitch by roughly 100 ms after stimulus onset and are consistent with previous electrophysiological research suggesting that the inferential pitch is perceived i

    Dietary polyunsaturated fat intake is associated with low-density lipoprotein size, but not with susceptibility to oxidation in subjects with impaired glucose metabolism and type II diabetes: the Hoorn study

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    OBJECTIVE: A high monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) intake is associated with lower plasma low-density lipoprotein (LDL)-cholesterol. However, PUFA may increase the susceptibility of LDL to undergo oxidative modifications. The aim of this study was to analyze the association of habitual dietary fat intake with LDL size and oxidizability. DESIGN: Cross-sectional. SETTING: Cohort study. SUBJECTS: Seven hundred and fifty-eight subjects with normal, impaired glucose metabolism and type II diabetes. INTERVENTIONS: Mean LDL size was measured by high-performance gel-filtration chromatography. In vitro oxidizability of LDL was determined by measuring lag time, reflecting the resistance of LDL to copper-induced oxidation. Information about dietary fat intake was obtained by a validated food frequency questionnaire. RESULTS: PUFA intake (energy percent) was significantly and negatively associated with LDL size in subjects with type II diabetes (standardized beta (95% confidence interval) -0.17 (-0.28;-0.06)) and impaired glucose metabolism - although not statistically significant - (-0.09 (-0.24;0.05)), but not in subjects with normal glucose metabolism (0.01 (-0.10;0.12)) (P-value for interaction=0.02). No significant associations were observed for total, saturated fat and MUFA intake with LDL size. Intake of fat was associated with lag time; however, the small magnitude of the associations suggested that the composition of dietary fat is not a major factor affecting lag time. The same association with lag time was observed in all three glucose metabolism categories. CONCLUSIONS: In individuals with abnormal glucose metabolism, higher PUFA intake is associated with smaller LDL particle size, but does not alter the susceptibility of LDL to in vitro oxidation. SPONSORSHIP: Dutch Diabetes Research Foundation, and the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO)

    First dose behavioral tolerance to phencyclidine on food-rewarded bar pressing behavior in the rat

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    The behavioral effects of single doses of phencyclidine (PCP) were examined in drug-naive adult male Holtzman rats trained to press a bar on a fixed ratio (4) schedule (FR 4 ), i.e., a reward of sugarsweetened milk was earned on every fourth bar press. Groups of rats (four to eight rats per group) received specific doses of PCP which were held constant for each group throughout the study. Dose-response curves for PCP given in doses of 1.0, 1.8, 2.4, and 3.2 mg/kg IP were first determined and then redetermined at weekly intervals. A drug-free interval of 7–8 days was maintained between injections given weekly over a period of 4 weeks. The final dose of PCP was administered after a 4-week drug-free period. Evidence was obtained for first dose behavioral tolerance as shown by the significantly shortened duration of suppression of bar pressing on subsequent injections. Although subsequent weekly effects of equal doses of PCP showed no significant differences, they all differed significantly from the first injection. The reduced response to PCP was shown to be due to learned behavioral tolerance as demonstrated when PCP (3.2 mg/kg IP) was given to drug-naive animals in their home cages and 1 week later given the second dose in the operant behavioral situation. Under these circumstances, the second dose of PCP showed a similarly protracted depression of FR 4 responding as other animals given the drug for the first time in the operant situation. Subsequent weekly injections in the operant situation produced similar behavioral tolerance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46412/1/213_2004_Article_BF00426513.pd

    The 4D nucleome project

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