417 research outputs found

    Energy radiation from intermediate to large magnitude earthquakes: implications for dynamic fault weakening

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    The amount of energy radiated from an earthquake can be measured using recent methods based on earthquake coda signals and spectral ratios. Such methods are not altered by either site or directivity effects, with the advantage of a greatly improved accuracy. Several studies of earthquake sequences based on the above measurements showed evidence of a breakdown in self-similarity in the moment to energy relation. Radiated energy can be also used as a gauge to estimate the average dynamic stress drop on the fault. Here we compute the dynamic stress drop, infer the co-seismic friction and estimate the co-seismic heating resulting from the frictional work during events from different main shock-aftershock earthquake sequences. We relate the dynamic friction to the maximum temperature rise estimated on the faults for each earthquake. Our results are strongly indicative that a thermally triggered dynamic frictional weakening is present, responsible for the breakdown in self-similarity. These observations from seismic data are compatible with recent laboratory evidence of thermal weakening in rock friction under seismic slip-rates, associated to various physical processes such as melting, decarbonation or dehydration

    Generations of Trees without Duplications

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    Coordinated Science Laboratory was formerly known as Control Systems LaboratoryDepartment of the Army / DA-28-043-AMC-00073(E)Department of the Air Force (Office of Scientific Research) / AF 49(638) - 138

    RNA splicing at human immunodeficiency virus type 1 3 ' splice site A2 is regulated by binding of hnRNP A/B proteins to an exonic splicing silencer element

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    The synthesis of human immunodeficiency virus type 1 (HIV-1) mRNAs is a complex process by which more than 30 different mRNA species are produced by alternative splicing of a single primary RNA transcript. HIV-1 splice sites are used with significantly different efficiencies, resulting in different levels of mRNA species in infected cells. Splicing of Tat mRNA, which is present at relatively low levels in infected cells, is repressed by the presence of exonic splicing silencers (ESS) within the two tat coding exons (ESS2 and ESS3). These ESS elements contain the consensus sequence PyUAG. Here we show that the efficiency of splicing at 3 ' splice site A2, which is used to generate Vpr mRNA, is also regulated by the presence of an ESS (ESSV), which has sequence homology to ESS2 and ESS3. Mutagenesis of the three PyUAG motifs within ESSV increases splicing at splice site A2, resulting in increased Vpr mRNA levels and reduced skipping of the noncoding exon flanked by A2 and D3. The increase in Vpr mRNA levels and the reduced skipping also occur when splice site D3 is mutated toward the consensus sequence. By in vitro splicing assays, we show that ESSV represses splicing when placed downstream of a heterologous splice site. A1, A1(B), A2, and B1 hnRNPs preferentially bind to ESSV RNA compared to ESSV mutant RNA. Each of these proteins, when added back to HeLa cell nuclear extracts depleted of ESSV-binding factors, is able to restore splicing repression. The results suggest that coordinate repression of HIV-1 RNA splicing is mediated by members of the hnRNP A/B protein family

    Evidence for the function of an exonic splicing enhancer after the first catalytic step of pre-mRNA splicing

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    Exonic splicing enhancers (ESEs) activate pre-mRNA splicing by promoting the use of the flanking splice sites, They are recognized by members of the serine/arginine-rich (SR) family of proteins, such as splicing factor 2/alternative splicing factor (SF2/ASF), which recruit basal splicing factors to form the initial complexes during spliceosome assembly. The in vitro splicing kinetics of an ESE-dependent IgM pre-mRNA suggested that an SF2/ASF-specific ESE has additional functions later in the splicing reaction, after the completion of the first catalytic step. A bimolecular exon ligation assay, which physically uncouples the first and second catalytic steps of splicing in a trans-splicing reaction, was adapted to test the function of the ESE after the first step. A 3' exon containing the SF2/ASF-specific ESE underwent bimolecular exon ligation, whereas 3' exons without the ESE or with control sequences did not. The ESE-dependent trans-splicing reaction occurred after inactivation of U1 or U2 small nuclear ribonucleoprotein particles, compatible with a functional assay for events after the first step of splicing. The ESE-dependent step appears to take place before the ATP-independent part of the second catalytic step. Bimolecular exon ligation also occurred in an S100 cytosolic extract, requiring both the SF2/ASF-dependent ESE and complementation with SF2/ASF, These data suggest that some ESEs can act late in the splicing reaction, together with appropriate SR proteins, to enhance the second catalytic step of splicing

    Regional Analysis of Lg Attenuation: Comparison of 1D Methods in Northern California and Application to the Yellow Sea / Korean Peninsula

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    The measurement of regional attenuation Q{sup -1} can produce method dependent results. The discrepancies among methods are due to differing parameterizations (e.g., geometrical spreading rates), employed datasets (e.g., choice of path lengths and sources), and methodologies themselves (e.g., measurement in the frequency or time domain). We apply the coda normalization (CN), two-station (TS), reverse two-station (RTS), source-pair/receiver-pair (SPRP), and the new coda-source normalization (CS) methods to measure Q of the regional phase, Lg (Q{sub Lg}), and its power-law dependence on frequency of the form Q{sub 0}f{sup {eta}} with controlled parameterization in the well-studied region of northern California using a high-quality dataset from the Berkeley Digital Seismic Network. We test the sensitivity of each method to changes in geometrical spreading, Lg frequency bandwidth, the distance range of data, and the Lg measurement window. For a given method, there are significant differences in the power-law parameters, Q{sub 0} and {eta}, due to perturbations in the parameterization when evaluated using a conservative pairwise comparison. The CN method is affected most by changes in the distance range, which is most probably due to its fixed coda measurement window. Since, the CS method is best used to calculate the total path attenuation, it is very sensitive to the geometrical spreading assumption. The TS method is most sensitive to the frequency bandwidth, which may be due to its incomplete extraction of the site term. The RTS method is insensitive to parameterization choice, whereas the SPRP method as implemented here in the time-domain for a single path has great error in the power-law model parameters and {eta} is greatly affected by changes in the method parameterization. When presenting results for a given method it is best to calculate Q{sub 0}f{sup {eta}} for multiple parameterizations using some a priori distribution. We also investigate the difference in power-law Q calculated among the methods by considering only an approximately homogeneous subset of our data. All methods return similar power-law parameters, though the 95% confidence region is large. We adapt the CS method to calculate Q{sub Lg} tomography in northern California. Preliminary results show that by correcting for the source, tomography with the CS method may produce better resolved attenuation structure

    Deletion of the N-terminus of SF2/ASF Permits RS-Domain-Independent Pre-mRNA Splicing

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    Serine/arginine-rich (SR) proteins are essential splicing factors with one or two RNA-recognition motifs (RRMs) and a C-terminal arginine- and serine-rich (RS) domain. SR proteins bind to exonic splicing enhancers via their RRM(s), and from this position are thought to promote splicing by antagonizing splicing silencers, recruiting other components of the splicing machinery through RS-RS domain interactions, and/or promoting RNA base-pairing through their RS domains. An RS domain tethered at an exonic splicing enhancer can function as a splicing activator, and RS domains play prominent roles in current models of SR protein functions. However, we previously reported that the RS domain of the SR protein SF2/ASF is dispensable for in vitro splicing of some pre-mRNAs. We have now extended these findings via the identification of a short inhibitory domain at the SF2/ASF N-terminus; deletion of this segment permits splicing in the absence of this SR protein's RS domain of an IgM pre-mRNA substrate previously classified as RS-domain-dependent. Deletion of the N-terminal inhibitory domain increases the splicing activity of SF2/ASF lacking its RS domain, and enhances its ability to bind pre-mRNA. Splicing of the IgM pre-mRNA in S100 complementation with SF2/ASF lacking its RS domain still requires an exonic splicing enhancer, suggesting that an SR protein RS domain is not always required for ESE-dependent splicing activation. Our data provide additional evidence that the SF2/ASF RS domain is not strictly required for constitutive splicing in vitro, contrary to prevailing models for how the domains of SR proteins function to promote splicing

    Structural basis for terminal loop recognition and stimulation of pri-miRNA-18a processing by hnRNP A1

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    International audiencePost-transcriptional mechanisms play a predominant role in the control of microRNA (miRNA) production. Recognition of the terminal loop of precursor miRNAs by RNA-binding proteins (RBPs) influences their processing; however, the mechanistic basis for how levels of individual or subsets of miRNAs are regulated is mostly unexplored. We previously showed that hnRNP A1, an RBP implicated in many aspects of RNA processing, acts as an auxiliary factor that promotes the Microprocessor-mediated processing of pri-mir-18a. Here, by using an integrative structural biology approach, we show that hnRNP A1 forms a 1:1 complex with pri-mir-18a where both RNA recognition motifs (RRMs) bind to cognate RNA sequence motifs in the terminal loop of pri-mir-18a. Terminal loop binding induces an allosteric destabilization of base-pairing in the pri-mir-18a stem that promotes its downstream processing. Our results highlight terminal loop RNA recognition by RBPs as a potential general principle of miRNA biogenesis and regulation

    Need for enforcement of ethicolegal education – an analysis of the survey of postgraduate clinical trainees

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    BACKGROUND: The number of medical lawsuits in Japan was between 14 and 21 each year before 1998, but increased to 24 to 35 per year after 1999. There were 210 lawsuits during this 10-year period. There is a need for skills and knowledge related to ethics, which is as fundamental to the practice of medicine as basic sciences or clinical skills. in Japan education in ethics is relatively rare and its importance is not yet recognized. Establishing ethics education using legal precedents, which has already been achieved in Western countries, will be a very important issue in Japan. In the present study, a questionnaire survey was conducted among graduate intern doctors, in order to investigate whether ethics education using precedents might have a positive effect in Japan. METHODS: In 2002, a questionnaire survey entitled Physicians' Clinical Ethics was carried out in a compulsory orientation lecture given to trainees before they started clinical practice in our hospital. The attendees at this lecture were trainees who came from colleges in various districts of Japan. During the lecture, 102 questionnaires were distributed, completed by attendees and collected. The recovery rate was 100%. The questionnaire consisted of 22 questions (in three categories), of which 20 were answered by multiple choices, and the other two were answered by description. The time required to complete the questionnaire was about 10 minutes. RESULTS: The recovered questionnaires were analyzed using statistical analysis software (SPSS for Windows, Release 10.07J-1/June/2000), in addition to simple statistical analysis. answers using multiple choices for the 20 questions in the questionnaire were input into SPSS. The principal component analysis was performed for each question. As a result, the item that came to the fore was "legal precedent". Since many intern doctors were interested in understanding laws and precedents, learning about ethical considerations through education using precedents might better meet with their needs and interests. CONCLUSION: We applied a new method in which the results of principal component analysis and frequencies of answers to other questions were combined. From this we deduced that the precedent education used in Western countries was useful to help doctors acquire ethical sensitivity and was not against their will. A relationship was found between reading precedents and the influence of lawsuits, and it was thought that student participation-type precedent education would be useful for doctors in order to acquire ethical sensitivity
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