770 research outputs found

    Magnetohydrodynamics (MHD) Engineering Test Facility (ETF) 200 MWe power plant. Design Requirements Document (DRD)

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    A description and the design requirements for the 200 MWe (nominal) net output MHD Engineering Test Facility (ETF) Conceptual Design, are presented. Performance requirements for the plant are identified and process conditions are indicated at interface stations between the major systems comprising the plant. Also included are the description, functions, interfaces and requirements for each of these major systems. The lastest information (1980-1981) from the MHD technology program are integrated with elements of a conventional steam electric power generating plant

    Emergence of pointer states in a non-perturbative environment

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    We show that the pointer basis distinguished by collisional decoherence consists of exponentially localized, solitonic wave packets. Based on the orthogonal unraveling of the quantum master equation, we characterize their formation and dynamics, and we demonstrate that the statistical weights arising from an initial superposition state are given by the required projection. Since the spatial width of the pointer states can be obtained by accounting for the gas environment in a microscopically realistic fashion, one may thus calculate the coherence length of a strongly interacting gas.Comment: 8 pages, 1 figure; corresponds to published versio

    Regulation of the ESC transcriptome by nuclear long non-coding RNAs

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    Long noncoding (lnc)RNAs have recently emerged as key regulators of gene expression. Here, we performed high-depth poly(A)+ RNA sequencing across multiple clonal populations of mouse embryonic stem cells (ESCs) and neural progenitor cells (NPCs) to comprehensively identify differentially regulated lncRNAs. We establish a biologically robust profile of lncRNA expression in these two cell types and further confirm that the majority of these lncRNAs are enriched in the nucleus. Applying weighted gene co-expression network analysis, we define a group of lncRNAs that are tightly associated with the pluripotent state of ESCs. Among these, we show that acute depletion of PAT-14 using antisense oligonucleotides impacts the differentiation- and development-associated gene expression program of ESCs. Furthermore, we demonstrate that Firre, a lncRNA highly enriched in the nucleoplasm and previously reported to mediate chromosomal contacts in ESCs, controls a network of genes related to RNA processing. Together, we provide a comprehensive, up-to-date and high resolution compilation of lncRNA expression in ESCs and NPCs and show that nuclear lncRNAs are tightly integrated into the regulation of ESC gene expression

    Structural insights into how Prp5 proofreads the pre-mRNA branch site

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    During the splicing of introns from precursor messenger RNAs (pre-mRNAs), the U2 small nuclear ribonucleoprotein (snRNP) must undergo stable integration into the spliceosomal A complex-a poorly understood, multistep process that is facilitated by the DEAD-box helicase Prp5 (refs. 1-4). During this process, the U2 small nuclear RNA (snRNA) forms an RNA duplex with the pre-mRNA branch site (the U2-BS helix), which is proofread by Prp5 at this stage through an unclear mechanism5. Here, by deleting the branch-site adenosine (BS-A) or mutating the branch-site sequence of an actin pre-mRNA, we stall the assembly of spliceosomes in extracts from the yeast Saccharomyces cerevisiae directly before the A complex is formed. We then determine the three-dimensional structure of this newly identified assembly intermediate by cryo-electron microscopy. Our structure indicates that the U2-BS helix has formed in this pre-A complex, but is not yet clamped by the HEAT domain of the Hsh155 protein (Hsh155HEAT), which exhibits an open conformation. The structure further reveals a large-scale remodelling/repositioning of the U1 and U2 snRNPs during the formation of the A complex that is required to allow subsequent binding of the U4/U6.U5 tri-snRNP, but that this repositioning is blocked in the pre-A complex by the presence of Prp5. Our data suggest that binding of Hsh155HEAT to the bulged BS-A of the U2-BS helix triggers closure of Hsh155HEAT, which in turn destabilizes Prp5 binding. Thus, Prp5 proofreads the branch site indirectly, hindering spliceosome assembly if branch-site mutations prevent the remodelling of Hsh155HEAT. Our data provide structural insights into how a spliceosomal helicase enhances the fidelity of pre-mRNA splicing

    Conceptual design of the MHD Engineering Test Facility

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    The reference conceptual design of the MHD engineering test facility, a prototype 200 MWe coal-fired electric generating plant designed to demonstrate the commerical feasibility of open cycle MHD is summarized. Main elements of the design are identified and explained, and the rationale behind them is reviewed. Major systems and plant facilities are listed and discussed. Construction cost and schedule estimates are included and the engineering issues that should be reexamined are identified

    ERDA/Lewis research center photovoltaic systems test facility

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    A national photovoltaic power systems test facility (of initial 10-kW peak power rating) is described. It consists of a solar array to generate electrical power, test-hardware for several alternate methods of power conversion, electrical energy storage systems, and an instrumentation and data acquisition system

    Coronary flow reserve in stress-echo lab. From pathophysiologic toy to diagnostic tool

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    The assessment of coronary flow reserve by transthoracic echocardiography has recently been introduced into clinical practice with gratifying results for the diagnosis of left anterior descending artery disease simultaneously reported by several independent laboratories. This technological novelty is changing the practice of stress echo for 3 main reasons. First, adding coronary flow reserve to regional wall motion allows us to have – in the same sitting – high specificity (regional wall motion) and a high sensitivity (coronary flow reserve) diagnostic marker, with an obvious improvement in overall diagnostic accuracy. Second, the technicalities of coronary flow reserve shift the balance of stress choice in favour of vasodilators, which are a more robust hyperemic stress and are substantially easier to perform with dual imaging than dobutamine or exercise. Third, the coronary flow reserve adds a quantitative support to the exquisitely qualitative assessment of wall motion analysis, thereby facilitating the communication of stress echo results to the cardiological world outside the echo lab. The next challenges involve the need to expand the exploration of coronary flow reserve to the right and circumflex coronary artery and to prove the additional prognostic value – if any – of coronary flow reserve over regional wall motion analysis, which remains the cornerstone of clinically-driven diagnosis in the stress echo lab

    State determination in continuous measurement

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    The possibility of determining the state of a quantum system after a continuous measurement of position is discussed in the framework of quantum trajectory theory. Initial lack of knowledge of the system and external noises are accounted for by considering the evolution of conditioned density matrices under a stochastic master equation. It is shown that after a finite time the state of the system is a pure state and can be inferred from the measurement record alone. The relation to emerging possibilities for the continuous experimental observation of single quanta, as for example in cavity quantum electrodynamics, is discussed.Comment: 12 pages, 4 figures, Revte

    RNA-binding protein CPEB1 remodels host and viral RNA landscapes.

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    Host and virus interactions occurring at the post-transcriptional level are critical for infection but remain poorly understood. Here, we performed comprehensive transcriptome-wide analyses revealing that human cytomegalovirus (HCMV) infection results in widespread alternative splicing (AS), shortening of 3' untranslated regions (3' UTRs) and lengthening of poly(A)-tails in host gene transcripts. We found that the host RNA-binding protein CPEB1 was highly induced after infection, and ectopic expression of CPEB1 in noninfected cells recapitulated infection-related post-transcriptional changes. CPEB1 was also required for poly(A)-tail lengthening of viral RNAs important for productive infection. Strikingly, depletion of CPEB1 reversed infection-related cytopathology and post-transcriptional changes, and decreased productive HCMV titers. Host RNA processing was also altered in herpes simplex virus-2 (HSV-2)-infected cells, thereby indicating that this phenomenon might be a common occurrence during herpesvirus infections. We anticipate that our work may serve as a starting point for therapeutic targeting of host RNA-binding proteins in herpesvirus infections

    No Changes in Human Immunodeficiency Virus (HIV) Suppression and Inflammatory Markers in Cerebrospinal Fluid in Patients Randomly Switched to Dolutegravir Plus Lamivudine (Spanish HIV/AIDS Research Network, PreEC/RIS 62)

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    A major concern of HIV dual therapy is a potential lower efficacy in viral reservoirs, especially in the central nervous system (CNS). We evaluated HIV RNA, neuronal injury and inflammatory biomarkers and dolutegravir (DTG) exposure in cerebrospinal fluid (CSF) in patients switching to DTG+lamivudine (3TC). All participants maintained viral suppression in plasma and CSF at week 48. We observed no increase in CSF markers of inflammation or neuronal injury. Median (IQR) total and unbound DTG in CSF were 7.3(5.9-8.4) ng/mL and 1.7(1.2-1.9) ng/mL, respectively. DTG+3TC may maintain viral control without changes in inflammatory/injury markers within the CNS reservoir
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