32 resultados para BMPR-IA


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The bake-hardening (BH) behavior of TRansformation Induced Plasticity (TRIP) and Dual-Phase (DP) steels after intercritical annealing (IA) has been studied using transmission electron microscopy, X-ray diffraction and three dimensional atom probe tomography. It was found for the DP steel that carbon can segregate to dislocations in the ferrite plastic deformation zones where there is a high dislocation density around the "asquenched" martensite. The carbon pinning of these dislocations, in turn, increases the yield strength after aging. It was shown that bake-hardening also leads to rearrangement of carbon in the martensite leading to the formation of rod-like low temperature carbides in the DP steel. Segregation of carbon to microtwins in retained austenite of the TRIP steel was also evident. These factors, in combination with the dislocation rearrangement in ferrite through the formation of cells and microbands in the TRIP steel after pre-straining, lead to the different bake-hardening responses of the two steels.

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Previously it was shown that spinal excitability during hopping and drop jumping is high in the initial phase of ground contact when the muscle is stretched but decreases toward takeoff. To further understand motor control of stretch-shortening cycle, this study aimed to compare modulation of spinal and corticospinal excitability at distinct phases following ground contact in drop jump. Motor-evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) and H-reflexes were elicited at the time of the short (SLR)-, medium (MLR)-, and long (LLR, LLR2)-latency responses of the soleus muscle (SOL) after jumps from 31 cm height. MEPs and H-reflexes were expressed relative to the background electromyographic (EMG) activity. H-reflexes were highly facilitated at SLR (172%) and then progressively decreased (MLR = 133%; LLR = 123%; LLR2 = 110%). TMS showed no effect at SLR, MLR, and LLR, whereas MEPs were significantly facilitated at the LLR2 (122%; P = 0.003). Background EMG was highest at LLR and lowest at LLR2. Strong H-reflex facilitation at the beginning of the stance phase indicated significant contribution of Ia-afferent input to the α-motoneurons during this phase that then progressively declined toward takeoff. Conversely, corticospinal excitability was exclusively increased at the phase of push off (LLR2, ∼120 ms). It is argued that corticomotoneurons increased their excitability at LLR2. At LLR (∼90 ms), Ia-afferent transmission as well as corticospinal excitability was low, whereas background EMG was high. Therefore it is speculated that other sources, presumably subcortical in origin, contributed to the EMG activity at LLR in drop jumps.

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Pcf11p, an essential subunit of the yeast cleavage factor IA, is required for pre-mRNA 3' end processing, binds to the C-terminal domain (CTD) of the largest subunit of RNA polymerase II (RNAP II) and is involved in transcription termination. We show that the conserved CTD interaction domain (CID) of Pcf11p is essential for cell viability. Interestingly, the CTD binding and 3' end processing activities of Pcf11p can be functionally uncoupled from each other and provided by distinct Pcf11p fragments in trans. Impaired CTD binding did not affect the 3' end processing activity of Pcf11p and a deficiency of Pcf11p in 3' end processing did not prevent CTD binding. Transcriptional run-on analysis with the CYC1 gene revealed that loss of cleavage activity did not correlate with a defect in transcription termination, whereas loss of CTD binding did. We conclude that Pcf11p is a bifunctional protein and that transcript cleavage is not an obligatory step prior to RNAP II termination.

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Many nuclear and nucleolar small RNAs are accumulated as nonpolyadenylated species and require 3′-end processing for maturation. Here, we show that several genes coding for box C/D and H/ACA snoRNAs and for the U5 and U2 snRNAs contain sequences in their 3′ portions which direct cleavage of primary transcripts without being polyadenylated. Genetic analysis of yeasts with mutations in different components of the pre-mRNA cleavage and polyadenylation machinery suggests that this mechanism of 3"-end formation requires cleavage factor IA (CF IA) but not cleavage and polyadenylation factor activity. However, in vitro results indicate that other factors participate in the reaction besides CF IA. Sequence analysis of snoRNA genes indicated that they contain conserved motifs in their 3" noncoding regions, and mutational studies demonstrated their essential role in 3"-end formation. We propose a model in which CF IA functions in cleavage and polyadenylation of pre-mRNAs and, in combination with a different set of factors, in 3"-end formation of nonpolyadenylated polymerase II transcripts.

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Cleavage and polyadenylation factor (CPF) is a multi‐protein complex that functions in pre‐mRNA 3′‐end formation and in the RNA polymerase II (RNAP II) transcription cycle. Ydh1p/Cft2p is an essential component of CPF but its precise role in 3′‐end processing remained unclear. We found that mutations in YDH1 inhibited both the cleavage and the polyadenylation steps of the 3′‐end formation reaction in vitro. Recently, we demonstrated that an important function of CPF lies in the recognition of poly(A) site sequences and RNA binding analyses suggesting that Ydh1p/Cft2p interacts with the poly(A) site region. Here we show that mutant ydh1 strains are deficient in the recognition of the ACT1 cleavage site in vivo. The C‐terminal domain (CTD) of RNAP II plays a major role in coupling 3′‐end processing and transcription. We provide evidence that Ydh1p/Cft2p interacts with the CTD of RNAP II, several other subunits of CPF and with Pcf11p, a component of CF IA. We propose that Ydh1p/Cft2p contributes to the formation of important interaction surfaces that mediate the dynamic association of CPF with RNAP II, the recognition of poly(A) site sequences and the assembly of the polyadenylation machinery on the RNA substrate.

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Recognition of poly(A) sites in yeast pre-mRNAs is poorly understood. Employing an in vitro cleavage system with cleavage and polyadenylation factor (CPF) and cleavage factor IA we show that the efficiency and positioning elements are dispensable for poly(A)-site recognition within a short CYC1 substrate in vitro. Instead, U-rich elements immediately upstream and downstream of the poly(A) site mediate cleavage-site recognition within CYC1 and ADH1 pre-mRNAs. These elements act in concert with the poly(A) site to produce multiple recognition sites for the processing machinery, since combinations of mutations within these elements were most effective in cleavage inhibition. Intriguingly, introduction of a U-rich element downstream of the GAL7 poly(A) site strongly enhanced cleavage, underscoring the importance of downstream sequences in general. RNA- binding analyses demonstrate that cleavage depends on the recognition of the poly(A)-site region by CPF. Consistent with in vitro results, mutation of sequences upstream and downstream of the poly(A) site affected 3'-end formation in vivo. A model for yeast pre-mRNA cleavage-site recognition outlines an unanticipated high conservation of yeast and mammalian 3'-end processing mechanisms.

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Background : The Beck Depression Inventory (BDI) is one of the most commonly used instruments to assess depression in persons with obesity. While it has been validated in normal and psychiatric populations, in obese populations, its validity remains uncertain. This study aimed to investigate the validity and reliability of the BDI-IA and BDI-II in severely obese bariatric surgery candidates.

Methods : Consecutive new candidates at a bariatric surgery clinic were invited to participate in the study by their consulting surgeon. All candidates were assessed using the Structured Clinical Interview for DSM-IV Disorders (SCID-I); 118 completed the BDI-IA and 83 completed the BDI-II. Two hundred one patients (response rate, 88 %) participated in the study. The current sample (82 % female) had an average body mass index of 42.83 ± 6.34 and an average age of 45 ± 12 years.

Results : Based on the SCID-I, 54 candidates (26.9 %) met the criteria for a mood disorder, with 37 meeting the criteria for current major depressive disorder. Individuals diagnosed with a clinical mood disorder had significantly higher scores on the BDI (BDI-IA, 23.59 ± 9.69 vs. 12.76 ± 8.29; BDI-II, 22.93 ± 5.22 vs. 11.25 ± 8.44). Our results indicated that, as a screening tool for a clinical mood disorder, the BDI-II had an optimal cutoff of 13, with a sensitivity of 100 and specificity of 67.75.

Conclusions : Results indicated that the BDI-IA should not be used as a tool to measure depressive symptomatology in obese bariatric surgery candidates. No cutoff was identified with adequate sensitivity and specificity, and over 20 % of patients were misclassified. As a screening tool for a clinical mood disorder, the BDI-II was adequate; however, prevalence rates were significantly overestimated.

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 RNA polymerase II (RNAP II) transcription and pre-mRNA 3' end formation are linked through physical and functional interactions. We describe here a highly efficient yeast in vitro system that reproduces both transcription and 3' end formation in a single reaction. The system is based on simple whole-cell extracts that were supplemented with a hybrid Gal4-VP16 transcriptional activator and supercoiled plasmid DNA templates encoding G-less cassette reporters. We found that the coupling of transcription and processing in vitro enhanced pre-mRNA 3' end formation and reproduced requirements for poly(A) signals and polyadenylation factors. Unexpectedly, however, we show that in vitro transcripts lacked m⁷G-caps. Reconstitution experiments with CF IA factor assembled entirely from heterologous components suggested that the CTD interaction domain of the Pcf11 subunit was required for proper RNAP II termination but not 3' end formation. Moreover, we observed reduced termination activity associated with extracts prepared from cells carrying a mutation in the 5'-3' exonuclease Rat1 or following chemical inhibition of exonuclease activity. Thus, in vitro transcription coupled to pre-mRNA processing recapitulates hallmarks of poly(A)-dependent RNAP II termination. The in vitro transcription/processing system presented here should provide a useful tool to further define the role of factors involved in coupling.

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This study explores internal audit (IA) practices in selected Ethiopian organizations to identify factors associated with attributes of IA departments. Analytical questionnaire survey responses of 188 IA directors and staff from Ethiopian government ministries, state-owned enterprises and private companies were used. Canonical analysis results show that IA proficiency, scope of IA work and quality of IA planning and execution are higher in organizations where organizational policy authorizing IA is clearly defined, organizational risk exposure is high and internal audit's linkage with external audit is strong. The findings suggest that in organizations that are exposed to high risk, management tends to appreciate IA's assistance in managing risk and thus strengthens IA. Results also suggest the importance of internal and external audit linkages and IA charter (or similar organizational policy) to strengthen IA. The study provides further evidence of differences in IA attributes between public and private sector entities.

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There is evidence emerging from Diffusion Tensor Imaging (DTI) research that autism spectrum disorders (ASD) are associated with greater impairment in the left hemisphere. Although this has been quantified with volumetric region of interest analyses, it has yet to be tested with white matter integrity analysis. In the present study, tract based spatial statistics was used to contrast white matter integrity of 12 participants with high-functioning autism or Aspergers syndrome (HFA/AS) with 12 typically developing individuals. Fractional Anisotropy (FA) was examined, in addition to axial, radial and mean diffusivity (AD, RD and MD). In the left hemisphere, participants with HFA/AS demonstrated significantly reduced FA in predominantly thalamic and fronto-parietal pathways and increased RD. Symmetry analyses confirmed that in the HFA/AS group, WM disturbance was significantly greater in the left compared to right hemisphere. These findings contribute to a growing body of literature suggestive of reduced FA in ASD, and provide preliminary evidence for RD impairments in the left hemisphere.

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This paper introduces a method to classify EEG signals using features extracted by an integration of wavelet transform and the nonparametric Wilcoxon test. Orthogonal Haar wavelet coefficients are ranked based on the Wilcoxon test’s statistics. The most prominent discriminant wavelets are assembled to form a feature set that serves as inputs to the naïve Bayes classifier. Two benchmark datasets, named Ia and Ib, downloaded from the brain–computer interface (BCI) competition II are employed for the experiments. Classification performance is evaluated using accuracy, mutual information, Gini coefficient and F-measure. Widely used classifiers, including feedforward neural network, support vector machine, k-nearest neighbours, ensemble learning Adaboost and adaptive neuro-fuzzy inference system, are also implemented for comparisons. The proposed combination of Haar wavelet features and naïve Bayes classifier considerably dominates the competitive classification approaches and outperforms the best performance on the Ia and Ib datasets reported in the BCI competition II. Application of naïve Bayes also provides a low computational cost approach that promotes the implementation of a potential real-time BCI system.

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BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets. FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action. FUNDING: Bill & Melinda Gates Foundation.

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Purpose - The aim of this exploratory study is to examine the perceptions of stakeholders regarding the scope of internal audit (IA) work in Libyan state-owned enterprises. Design/methodology/approach - Data were gathered through semi-structured interviews with chief executive officers, IA directors, administrative affairs managers, financial affairs managers and external auditors, which were supplemented with a review of relevant documentary evidence. Findings - The results of the study show that the scope of IA in Libyan organizations may not be sufficiently wide ranging to be considered as a value-adding service. The scope of the IA function may need to be expanded to cover a broader range of organizational functions if internal auditors are to offer value-adding services to their stakeholders. Practical implications - The IA profession has received scant attention in the literature, especially in the context of developing countries such as Libya. Therefore, such settings offer the potential to enhance the understanding of IA practices. As a study on a developing economy, it enhances understanding of the IA profession’s global configuration beyond the predominantly market-driven, industrialized Western economies. Originality/value - In contrast to most previous studies, this study covers a broad range of IA stakeholders’ views on the role of internal auditors. This coverage enabled an in-depth investigation of the factors affecting IA scope and understanding of stakeholder perceptions on the IA function.

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The nonlinear, noisy and outlier characteristics of electroencephalography (EEG) signals inspire the employment of fuzzy logic due to its power to handle uncertainty. This paper introduces an approach to classify motor imagery EEG signals using an interval type-2 fuzzy logic system (IT2FLS) in a combination with wavelet transformation. Wavelet coefficients are ranked based on the statistics of the receiver operating characteristic curve criterion. The most informative coefficients serve as inputs to the IT2FLS for the classification task. Two benchmark datasets, named Ia and Ib, downloaded from the brain-computer interface (BCI) competition II, are employed for the experiments. Classification performance is evaluated using accuracy, sensitivity, specificity and F-measure. Widely-used classifiers, including feedforward neural network, support vector machine, k-nearest neighbours, AdaBoost and adaptive neuro-fuzzy inference system, are also implemented for comparisons. The wavelet-IT2FLS method considerably dominates the comparable classifiers on both datasets, and outperforms the best performance on the Ia and Ib datasets reported in the BCI competition II by 1.40% and 2.27% respectively. The proposed approach yields great accuracy and requires low computational cost, which can be applied to a real-time BCI system for motor imagery data analysis.

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This paper introduces an approach to classify EEG signals using wavelet transform and a fuzzy standard additive model (FSAM) with tabu search learning mechanism. Wavelet coefficients are ranked based on statistics of the Wilcoxon test. The most informative coefficients are assembled to form a feature set that serves as inputs to the tabu-FSAM. Two benchmark datasets, named Ia and Ib, downloaded from the brain-computer interface (BCI) competition II are employed for the experiments. Classification performance is evaluated using accuracy, mutual information, Gini coefficient and F-measure. Widely-used classifiers, including feedforward neural network, support vector machine, k-nearest neighbours, ensemble learning Adaboost and adaptive neuro-fuzzy inference system, are also implemented for comparisons. The proposed tabu-FSAM method considerably dominates the competitive classifiers, and outperforms the best performance on the Ia and Ib datasets reported in the BCI competition II.