965 resultados para simplified CDD
Resumo:
Customs are generally perceived as a time-consuming impediment to international trade. However, few studies have empirically examined the determinants and the impact of this type of government-imposed transaction costs. This paper analyses the role of firm size as a determinant of customs-related transaction costs, as well as the effect of firm size on the relationship between these costs and the international trade intensity of firms. The results of this study indicate that customs-related transaction costs repress international trade activities of firms, even at low levels of these costs. The paper identifies transaction-related economies of scale, simplified customs procedures and advanced information and communication technology as main determinants of customs-related transaction costs. It is shown that when these factors are taken into account, firm size has no effect on customs-related transaction costs. Policy implications are considered for firm strategy and public policy.
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Histone deacetylases ( HDACs) 1 and 2 share a high degree of homology and coexist within the same protein complexes. Despite their close association, each possesses unique functions. We show that the upregulation of HDAC2 in colorectal cancer occurred early at the polyp stage, was more robust and occurred more frequently than HDAC1. Similarly, while the expression of HDACs1 and 2 were increased in cervical dysplasia and invasive carcinoma, HDAC2 expression showed a clear demarcation of high-intensity staining at the transition region of dysplasia compared to HDAC1. Upon HDAC2 knockdown, cells displayed an increased number of cellular extensions reminiscent of cell differentiation. There was also an increase in apoptosis, associated with increased p21(Cip1/WAF1) expression that was independent of p53. These results suggest that HDACs, especially HDAC2, are important enzymes involved in the early events of carcinogenesis, making them candidate markers for tumor progression and targets for cancer therapy.
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We found that procaspase 8 was overexpressed in non-small-cell lung cancers (NSCLCs) compared with matched normal tissues. The caspase 8 inhibitor FLICE-inhibitory protein (FLIP) was also overexpressed in the majority of NSCLCs. Silencing FLIP induced caspase 8 activation and apoptosis in NSCLC cell lines, but not in normal lung cell lines. Apoptosis induced by FLIP silencing was mediated by the TRAIL death receptors DR4 and DR5, but was not dependent on ligation of the receptors by TRAIL. Furthermore, the apoptosis induced by FLIP silencing was dependent on the overexpression of procaspase 8 in NSCLC cells. Moreover, in NSCLC cells, but not in normal cells, FLIP silencing induced co-localization of DR5 and ceramide, and disruption of this co-localization abrogated apoptosis. FLIP silencing supra-additively increased TRAIL-induced apoptosis of NSCLC cells; however, normal lung cells were resistant to TRAIL, even when FLIP was silenced. Importantly, FLIP silencing sensitized NSCLC cells but not normal cells to chemotherapy in vitro, and silencing FLIP in vivo retarded NSCLC xenograft growth and enhanced the anti-tumour effects of cisplatin. Collectively, our results suggest that due to frequent procaspase 8 overexpression, NSCLCs may be particularly sensitive to FLIP-targeted therapies.
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This paper studies the Demmel condition number of Wishart matrices, a quantity which has numerous applications to wireless communications, such as adaptive switching between beamforming and diversity coding, link adaptation, and spectrum sensing. For complex Wishart matrices, we give an exact analytical expression for the probability density function (p.d.f.) of the Demmel condition number, and also derive simplified expressions for the high tail regime. These results indicate that the condition of complex Wishart matrices is dominantly decided by the difference between the matrix dimension and degree of freedom (DoF), i.e., the probability of drawing a highly ill conditioned matrix decreases considerably when the difference between the matrix dimension and DoF increases. We further investigate real Wishart matrices, and derive new expressions for the p.d.f. of the smallest eigenvalue, when the difference between the matrix dimension and DoF is odd. Based on these results, we succeed to obtain an exact p.d.f. expression for the Demmel condition number, and simplified expressions for the high tail regime.
Resumo:
One way to restore physiological blood flow to occluded arteries involves the deformation of plaque using an intravascular balloon and preventing elastic recoil using a stent. Angioplasty and stent implantation cause unphysiological loading of the arterial tissue, which may lead to tissue in-growth and reblockage; termed “restenosis.” In this paper, a computational methodology for predicting the time-course of restenosis is presented. Stress-induced damage, computed using a remaining life approach, stimulates inflammation (production of matrix degrading factors and growth stimuli). This, in turn, induces a change in smooth muscle cell phenotype from contractile (as exists in the quiescent tissue) to synthetic (as exists in the growing tissue). In this paper, smooth muscle cell activity (migration, proliferation, and differentiation) is simulated in a lattice using a stochastic approach to model individual cell activity. The inflammation equations are examined under simplified loading cases. The mechanobiological parameters of the model were estimated by calibrating the model response to the results of a balloon angioplasty study in humans. The simulation method was then used to simulate restenosis in a two dimensional model of a stented artery. Cell activity predictions were similar to those observed during neointimal hyperplasia, culminating in the growth of restenosis. Similar to experiment, the amount of neointima produced increased with the degree of expansion of the stent, and this relationship was found to be highly dependant on the prescribed inflammatory response. It was found that the duration of inflammation affected the amount of restenosis produced, and that this effect was most pronounced with large stent expansions. In conclusion, the paper shows that the arterial tissue response to mechanical stimulation can be predicted using a stochastic cell modeling approach, and that the simulation captures features of restenosis development observed with real stents. The modeling approach is proposed for application in three dimensional models of cardiovascular stenting procedures.
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This paper tries to achieve a balanced view of the ethical issues raised by emotion-oriented technology as it is, rather than as it might be imagined. A high proportion of applications seem ethically neutral. Uses in entertainment and allied areas do no great harm or good. Empowering professions may do either, but regulatory systems already exist. Ethically positive aspirations involve mitigating problems that already exist by supporting humans in emotion-related judgments, by replacing technology that treats people in dehumanized and/or demeaning ways, and by improving access for groups who struggle with existing interfaces. Emotion-oriented computing may also contribute to revaluing human faculties other than pure intellect. Many potential negatives apply to technology as a whole. Concerns specifically related to emotion involve creating a lie, by simulate emotions that the systems do not have, or promoting mechanistic conceptions of emotion. Intermediate issues arise where more general problems could be exacerbated-helping systems to sway human choices or encouraging humans to choose virtual worlds rather than reality. "SIIF" systems (semi-intelligent information filters) are particularly problematic. These use simplified rules to make judgments about people that are complex, and have potentially serious consequences. The picture is one of balances to recognize and negotiate, not uniform good or evil. © 2010-2012 IEEE.
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We evaluated a structured pharmaceutical care program for elderly patients (> 65 yrs) with congestive heart failure (CHF) based on objective measures of disease control, quality of life, and use of health care facilities in a randomized, controlled, longitudinal, prospective clinical trial. The 42 patients in group A received education from a pharmacist on the disease and its treatment, and lifestyle changes that could help control symptoms. Patients also were encouraged to monitor their symptoms and comply with prescribed drug therapy. If necessary, dosage regimens were simplified in liaison with hospital physicians. The 41 control patients (group B) received standard care. The following outcome measures were assessed in all patients at baseline (before the start of the trial) and at 3, 6, 9, and 12 months: 2-minute walk test, blood pressure, body weight, pulse, forced vital capacity, quality of life [disease-specific (Minnesota Living with Heart Failure questionnaire) and generic (SF-36)], knowledge of symptoms and drugs, compliance with therapy, and use of health care facilities (hospital admissions, visits to emergency room, emergency calls). Patients in group A showed improved compliance with drug therapy, which in turn improved their exercise capacity compared with those in group B; education on management of symptoms, lifestyle changes, and dietary recommendations were also of benefit. Group A patients significantly improved knowledge of their drug therapy over the 12-month study and had fewer hospital admissions compared with group B patients. They also had improved outcomes compared with group B, despite the small samples. An extension of this trial to other sites with pooling of results would provide additional evidence of the value of this structured program in elderly patients with CHF.
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Bystander effects, whereby cells that are not directly exposed to ionizing radiation exhibit adverse biological effects, have been observed in a number of experimental systems. A novel stochastic model of the radiation-induced bystander effect is developed that takes account of spatial location, cell killing and repopulation. The ionizing radiation dose- and time-responses of this model are explored, and it is shown to exhibit pronounced downward curvature in the high dose-rate region, similar to that observed in many experimental systems, reviewed in the paper. It is also shown to predict the augmentation of effect after fractionated delivery of dose that has been observed in certain experimental systems. It is shown that the generally intractable solution of the full stochastic system can be considerably simplified by assumption of pairwise conditional dependence that varies exponentially over time. (C) 2004 Elsevier Ltd. All rights reserved.
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FLIP is a potential anti-cancer therapeutic target that inhibits apoptosis by blocking caspase 8 activation by death receptors. We report a novel interaction between FLIP and the DNA repair protein Ku70 that regulates FLIP protein stability by inhibiting its polyubiquitination. Furthermore, we found that the histone deacetylase (HDAC) inhibitor Vorinostat (SAHA) enhances the acetylation of Ku70, thereby disrupting the FLIP/Ku70 complex and triggering FLIP polyubiquitination and degradation by the proteasome. Using in vitro and in vivo colorectal cancer models, we further demonstrated that SAHA-induced apoptosis is dependant on FLIP downregulation and caspase 8 activation. In addition, an HDAC6-speci?c inhibitor Tubacin recapitulated the effects of SAHA, suggesting that HDAC6 is a key regulator of Ku70 acetylation and FLIP protein stability. Thus, HDAC inhibitors with anti-HDAC6 activity act as ef?cient post-transcriptional suppressors of FLIP expression and may, therefore, effectively act as ‘FLIP inhibitors’ © 2012 Macmillan Publishers Limited.
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Analysis of non-traditional Variable Stiffness (VS) laminates, obtained by steering the fiber orientation as a spatial function of location, have shown to improve buckling load carrying capacity of flat rectangular panels under axial compressive loads. In some cases the buckling load of simply supported panels doubled compared to the best conventional laminate with straight fibers. Two distinct cases of stiffness variation, one due to fiber orientation variation in the direction of the loading, and the other one perpendicular to the loading direction, were identified as possible contributors to the buckling load improvements. In the first case, the increase was attributed to the favorable distribution of the transverse in-plane stresses over the panel platform. In the second case, a higher degree of improvement was obtained due to the re-distribution of the applied in-plane loads. Experimental results, however, showed substantially higher levels of buckling load improvements compared with theoretical predictions. The additional improvement was determined to be due to residual stresses introduced during curing of the laminates. The present paper provides a simplified thermomechanical analysis of residual stress state of variable stiffness laminates. Systematic parametric analyses of both cases of fiber orientation variations show that, indeed much higher buckling loads could result from the residual stresses present in such laminates.
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In the present study an experimental investigation of the time-averaged velocity and turbulence intensity distributions from a ship’s propeller, in “bollard pull” condition (zero speed of advance), is reported. Previous studies have focused mainly on the velocity profile of not a rotating ship propeller but a plain jet. The velocity profile of a propeller is investigated experimentally in this study.
The velocity measurements were performed in laboratory by using a Laser Doppler Anemometry (LDA). The measurements demonstrated two-peaked ridges velocity profile with a low velocity core at the centre within the near wake. The two-peaked ridges combined to be one-peaked ridge at 3.68 diameters downstream indicating the end of the zone of flow establishment. The study
provides useful information from a rotating ship’s propeller rather than a simplified plain jet to researchers investigating flow velocity generated from a propeller and probably resulting local scouring.
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To develop real-time simulations of wind instruments, digital waveguides filters can be used as an efficient representation of the air column. Many aerophones are shaped as horns which can be approximated using conical sections. Therefore the derivation of conical waveguide filters is of special interest. When these filters are used in combination with a generalized reed excitation, several classes of wind instruments can be simulated. In this paper we present the methods for transforming a continuous description of conical tube segments to a discrete filter representation. The coupling of the reed model with the conical waveguide and a simplified model of the termination at the open end are described in the same way. It turns out that the complete lossless conical waveguide requires only one type of filter.Furthermore, we developed a digital reed excitation model, which is purely based on numerical integration methods, i.e., without the use of a look-up table.
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Mammary epithelial cells in primary cell culture require both growth factors and specific extracellular matrix (ECM)-attachment for survival. Here we demonstrate for the first time that inhibition of the ECM-induced Erk 1/Erk 2 (p42/44 MAPK) pathway, by PD 98059, leads to apoptosis in these cells. Associated with this cell death is a possible compensatory signalling through the p38 MAP kinase pathway the inhibition of which, by SB 203580, leads to a more rapid onset of apoptosis. This provides evidence for a hitherto undescribed Erk 1/Erk 2 to p38 MAP kinase pathway 'cross-talk' that is essential for the survival of these cells. The cell death associated with inhibition of these two MAP kinase pathways however, occurred in the presence of insulin that activates the classical PI-3 kinase-dependent Akt/PKB survival signals and Akt phosphorylation. Cell death induced by inhibition of the MAP kinase pathways did not affect Akt phosphorylation and may, thus, be independent of PI-3 kinase signalling.
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There is considerable interest in creating embedded, speech recognition hardware using the weighted finite state transducer (WFST) technique but there are performance and memory usage challenges. Two system optimization techniques are presented to address this; one approach improves token propagation by removing the WFST epsilon input arcs; another one-pass, adaptive pruning algorithm gives a dramatic reduction in active nodes to be computed. Results for memory and bandwidth are given for a 5,000 word vocabulary giving a better practical performance than conventional WFST; this is then exploited in an adaptive pruning algorithm that reduces the active nodes from 30,000 down to 4,000 with only a 2 percent sacrifice in speech recognition accuracy; these optimizations lead to a more simplified design with deterministic performance.