973 resultados para microrna target systems


Relevância:

30.00% 30.00%

Publicador:

Resumo:

With careful calculation of signal forwarding weights, relay nodes can be used to work collaboratively to enhance downlink transmission performance by forming a virtual multiple-input multiple-output beamforming system. Although collaborative relay beamforming schemes for single user have been widely investigated for cellular systems in previous literatures, there are few studies on the relay beamforming for multiusers. In this paper, we study the collaborative downlink signal transmission with multiple amplify-and-forward relay nodes for multiusers in cellular systems. We propose two new algorithms to determine the beamforming weights with the same objective of minimizing power consumption of the relay nodes. In the first algorithm, we aim to guarantee the received signal-to-noise ratio at multiusers for the relay beamforming with orthogonal channels. We prove that the solution obtained by a semidefinite relaxation technology is optimal. In the second algorithm, we propose an iterative algorithm that jointly selects the base station antennas and optimizes the relay beamforming weights to reach the target signal-to-interference-and-noise ratio at multiusers with nonorthogonal channels. Numerical results validate our theoretical analysis and demonstrate that the proposed optimal schemes can effectively reduce the relay power consumption compared with several other beamforming approaches. © 2012 John Wiley & Sons, Ltd.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Whilst target costing and strategic management accounting (SMA) continue to be of considerable interest to academic accountants, both suffer from a relative dearth of empirically based research. Simultaneously, the subject of economic value added (EVA) has also been the subject of little research at the level of the individual firm.The aim of this paper is to contribute to both the management accounting and value based management literatures by analysing how one major European based MNC introduced EVA into its target costing system. The case raises important questions about both the feasibility of cascading EVA down to product level and the compatibility of customer facing versus shareholder focused systems of performance management. We provide preliminary evidence that target costing can be used to align both of these perspectives, and when combined with other SMA techniques it can serve as " the bridge connecting strategy formulation with strategy execution and profit generation" ( Ansari et al., 2007, p. 512). © 2012 Elsevier Ltd.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

The hypoxia-inducible factor (HIF) is a key regulator of the transcriptional response to hypoxia. While the mechanism underpinning HIF activation is well understood, little is known about its resolution. Both the protein and the mRNA levels of HIF-1a (but not HIF-2a) were decreased in intestinal epithelial cells exposed to prolonged hypoxia. Coincident with this, microRNA (miRNA) array analysis revealed multiple hypoxiainducible miRNAs. Among these was miRNA-155 (miR-155), which is predicted to target HIF-1a mRNA. We confirmed the hypoxic upregulation of miR-155 in cultured cells and intestinal tissue from mice exposed to hypoxia. Furthermore, a role for HIF-1a in the induction of miR-155 in hypoxia was suggested by the identification of hypoxia response elements in the miR-155 promoter and confirmed experimentally. Application of miR-155 decreased the HIF-1a mRNA, protein, and transcriptional activity in hypoxia, and neutralization of endogenous miR-155 reversed the resolution of HIF-1a stabilization and activity. Based on these data and a mathematical model of HIF-1a suppression by miR-155, we propose that miR-155 induction contributes to an isoform-specific negative-feedback loop for the resolution of HIF-1a activity in cells exposed to prolonged hypoxia, leading to oscillatory behavior of HIF-1a-dependent transcription. © 2011, American Society for Microbiology.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

There is growing peer and donor pressure on African countries to utilize available resources more efficiently in a bid to support the ongoing efforts to expand coverage of health interventions with a view to achieving the health-related Millennium Development Goals. The purpose of this study was to estimate the technical and scale efficiency of national health systems in African continent. Methods The study applied the Data Envelopment Analysis approach to estimate the technical efficiency and scale efficiency among the 53 countries of the African Continent. Results Out of the 38 low-income African countries, 12 countries national health systems manifested a constant returns to scale technical efficiency (CRSTE) score of 100%; 15 countries had a VRSTE score of 100%; and 12 countries had a SE score of one. The average variable returns to scale technical efficiency (VRSTE) score was 95% and the mean scale efficiency (SE) score was 59%; meaning that while on average the degree of inefficiency was only 5%, the magnitude of scale inefficiency was 41%. Of the 15 middle-income countries, 5 countries, 9 countries and 5 countries had CRSTE, VRSTE and SE scores of 100%. Ten countries, six countries and 10 countries had CRSTE, VRSTE and SE scores of less than 100%; and thus, they were deemed inefficient. The average VRSTE (i.e. pure efficiency) score was 97.6%. The average SE score was 49.9%. Conclusion There are large unmet need for health and health-related services among countries of the African Continent. Thus, it would not be advisable for health policy-makers address NHS inefficiencies through reduction in excess human resources for health. Instead, it would be more prudent for them to leverage health promotion approaches and universal access prepaid (tax-based, insurance-based or mixtures) health financing systems to create demand for under utilised health services/interventions with a view to increasing ultimate health outputs to efficient target levels.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

The present report reviews behavioural, electroencephalographic, and especially magnetoencephalographic findings on the cortical mechanisms underlying attentional processes that separate targets from distractors and that ensure durable target representations for goal-directed action. A common way of investigation is to observe the system’s overt and covert behaviour when capacity limitations are reached. Here we focus on the aspect of temporally enhanced processing load, namely on performance deficits occurring under rapid-serial-visual-presentation (RSVP) conditions. The most prominent of these deficits is the so-called “attentional blink” (AB) effect. We first report MEG findings with respect to the time course of activation that shows modulations around 300 ms after target onset which reflect demands and success of target consolidation. Then, findings regarding long-range inter-area phase synchronization are reported that are hypothesized to mediate communication within the attentional network. Changes in synchronization reflect changes in the attentional demands of the task and are directly related to behavioural performance. Furthermore, enhanced vigilance of the system elicits systematically increased synchronization indices. A hypothetical framework is sketched out that aims at explaining limitations in multiple target consolidation under RSVP conditions.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

The oxidoreductase Trx-1 (thioredoxin 1) is highly conserved and found intra- and extra-cellularly in mammalian systems. There is increasing interest in its capacity to regulate immune function based on observations of altered distribution and expression during ageing and disease. We have investigated previously whether extracellular T-cell or peripheral blood mononuclear cell Trx-1 levels serve as a robust marker of ageing. In a preliminary study of healthy older adults compared with younger adults, we showed that therewas a significant, butweak, relationshipwith age. Interestingly, patientswith rheumatoid arthritis and cancer have been described by others to secrete or express greater surface Trx-1 than predicted. It is interesting to speculate whether a decline in Trx-1 during ageing protects against such conditions, but correspondingly increases risk of disease associated with Trx-1 depletion such as cardiovascular disease. These hypotheses are being explored in the MARK-AGE study, and preliminary findings confirm an inverse correlation of surface Trx-1 with age. We review recent concepts around the role of Trx-1 and its partners in T-cell function on the cell surface and as an extracellular regulator of redox state in a secreted form. Further studies on the redox state and binding partners of surface and secreted Trx-1 in larger patient datasets are needed to improve our understanding of why Trx-1 is important for lifespan and immune function. © The Authors Journal compilation © 2014 Biochemical Society.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

The link between off-target anticholinergic effects of medications and acute cognitive impairment in older adults requires urgent investigation. We aimed to determine whether a relevant in vitro model may aid the identification of anticholinergic responses to drugs and the prediction of anticholinergic risk during polypharmacy. In this preliminary study we employed a co-culture of human-derived neurons and astrocytes (NT2.N/A) derived from the NT2 cell line. NT2.N/A cells possess much of the functionality of mature neurons and astrocytes, key cholinergic phenotypic markers and muscarinic acetylcholine receptors (mAChRs). The cholinergic response of NT2 astrocytes to the mAChR agonist oxotremorine was examined using the fluorescent dye fluo-4 to quantitate increases in intracellular calcium [Ca2+]i. Inhibition of this response by drugs classified as severe (dicycloverine, amitriptyline), moderate (cyclobenzaprine) and possible (cimetidine) on the Anticholinergic Cognitive Burden (ACB) scale, was examined after exposure to individual and pairs of compounds. Individually, dicycloverine had the most significant effect regarding inhibition of the astrocytic cholinergic response to oxotremorine, followed by amitriptyline then cyclobenzaprine and cimetidine, in agreement with the ACB scale. In combination, dicycloverine with cyclobenzaprine had the most significant effect, followed by dicycloverine with amitriptyline. The order of potency of the drugs in combination frequently disagreed with predicted ACB scores derived from summation of the individual drug scores, suggesting current scales may underestimate the effect of polypharmacy. Overall, this NT2.N/A model may be appropriate for further investigation of adverse anticholinergic effects of multiple medications, in order to inform clinical choices of suitable drug use in the elderly.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

The relatively high phase noise of coherent optical systems poses unique challenges for forward error correction (FEC). In this letter, we propose a novel semianalytical method for selecting combinations of interleaver lengths and binary Bose-Chaudhuri-Hocquenghem (BCH) codes that meet a target post-FEC bit error rate (BER). Our method requires only short pre-FEC simulations, based on which we design interleavers and codes analytically. It is applicable to pre-FEC BER ∼10-3, and any post-FEC BER. In addition, we show that there is a tradeoff between code overhead and interleaver delay. Finally, for a target of 10-5, numerical simulations show that interleaver-code combinations selected using our method have post-FEC BER around 2× target. The target BER is achieved with 0.1 dB extra signal-to-noise ratio.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Forward error correction (FEC) plays a vital role in coherent optical systems employing multi-level modulation. However, much of coding theory assumes that additive white Gaussian noise (AWGN) is dominant, whereas coherent optical systems have significant phase noise (PN) in addition to AWGN. This changes the error statistics and impacts FEC performance. In this paper, we propose a novel semianalytical method for dimensioning binary Bose-Chaudhuri-Hocquenghem (BCH) codes for systems with PN. Our method involves extracting statistics from pre-FEC bit error rate (BER) simulations. We use these statistics to parameterize a bivariate binomial model that describes the distribution of bit errors. In this way, we relate pre-FEC statistics to post-FEC BER and BCH codes. Our method is applicable to pre-FEC BER around 10-3 and any post-FEC BER. Using numerical simulations, we evaluate the accuracy of our approach for a target post-FEC BER of 10-5. Codes dimensioned with our bivariate binomial model meet the target within 0.2-dB signal-to-noise ratio.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

The immune system is perhaps the largest yet most diffuse and distributed somatic system in vertebrates. It plays vital roles in fighting infection and in the homeostatic control of chronic disease. As such, the immune system in both pathological and healthy states is a prime target for therapeutic interventions by drugs-both small-molecule and biologic. Comprising both the innate and adaptive immune systems, human immunity is awash with potential unexploited molecular targets. Key examples include the pattern recognition receptors of the innate immune system and the major histocompatibility complex of the adaptive immune system. Moreover, the immune system is also the source of many current and, hopefully, future drugs, of which the prime example is the monoclonal antibody, the most exciting and profitable type of present-day drug moiety. This brief review explores the identity and synergies of the hierarchy of drug targets represented by the human immune system, with particular emphasis on the emerging paradigm of systems pharmacology. © the authors, publisher and licensee Libertas Academica Limited.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

AMS subject classification: 49N35,49N55,65Lxx.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Police often use facial composites during their investigations, yet research suggests that facial composites are generally not effective. The present research included two experiments on facial composites. The first experiment was designed to test the usefulness of the encoding specificity principle for determining when facial composites will be effective. Instructions were used to encourage holistic or featural cues at encoding. The method used to construct facial composites was manipulated to encourage holistic or featural cues at retrieval. The encoding specificity principle suggests that an interaction effect should occur. If the same cues are used at encoding and retrieval, better composites should be constructed than when the cues are not the same. However, neither the expected interaction nor the main effects for encoding and retrieval were significant. The second study was conducted to assess the effectiveness of composites generated by two different facial composite construction systems, E-Fit and Mac-A-Mug Pro. These systems differ in that the E-Fit system uses more sophisticated methods of composite construction and may construct better quality facial composites. A comparison of E-Fit and Mac-A-Mug Pro composites demonstrated that E-Fit composites were of better quality than Mac-A-Mug Pro composites. However, neither E-Fit nor Mac-A-Mug Pro composites were useful for identifying the target person from a photograph lineup. Further, lineup performance was at floor level such that both E-Fit and Mac-A-Mug Pro composites were no more useful than a verbal description. Possible limitations of the studies are discussed, as well as suggestions for future research. ^

Relevância:

30.00% 30.00%

Publicador:

Resumo:

The purpose of this study was to develop, explicate, and validate a comprehensive model in order to more effectively assess community injury prevention needs, plan and target efforts, identify potential interventions, and provide a framework for an outcome-based evaluation of the effectiveness of interventions. A systems model approach was developed to conceptualize the major components of inputs, efforts, outcomes and feedback within a community setting. Profiling of multiple data sources demonstrated a community feedback mechanism that increased awareness of priority issues and elicited support from traditional as well as non-traditional injury prevention partners. Injury countermeasures including education, enforcement, engineering, and economic incentives were presented for their potential synergistic effect impacting on knowledge, attitudes, or behaviors of a targeted population. Levels of outcome data were classified into ultimate, intermediate and immediate indicators to assist with determining the effectiveness of intervention efforts. A collaboration between business and health care was successful in achieving data access and use of an emergency department level of injury data for monitoring of the impact of community interventions. Evaluation of injury events and preventive efforts within the context of a dynamic community systems environment was applied to a study community with examples detailing actual profiling and trending of injuries. The resulting model of community injury prevention was validated using a community focus group, community injury prevention coordinators, and injury prevention national experts. ^

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Existing instrumental techniques must be adaptable to the analysis of novel explosives if science is to keep up with the practices of terrorists and criminals. The focus of this work has been the development of analytical techniques for the analysis of two types of novel explosives: ascorbic acid-based propellants, and improvised mixtures of concentrated hydrogen peroxide/fuel. In recent years, the use of these explosives in improvised explosive devices (IEDs) has increased. It is therefore important to develop methods which permit the identification of the nature of the original explosive from post-blast residues. Ascorbic acid-based propellants are low explosives which employ an ascorbic acid fuel source with a nitrate/perchlorate oxidizer. A method which utilized ion chromatography with indirect photometric detection was optimized for the analysis of intact propellants. Post-burn and post-blast residues if these propellants were analyzed. It was determined that the ascorbic acid fuel and nitrate oxidizer could be detected in intact propellants, as well as in the post-burn and post-blast residues. Degradation products of the nitrate and perchlorate oxidizers were also detected. With a quadrupole time-of-flight mass spectrometer (QToFMS), exact mass measurements are possible. When an HPLC instrument is coupled to a QToFMS, the combination of retention time with accurate mass measurements, mass spectral fragmentation information, and isotopic abundance patterns allows for the unequivocal identification of a target analyte. An optimized HPLC-ESI-QToFMS method was applied to the analysis of ascorbic acid-based propellants. Exact mass measurements were collected for the fuel and oxidizer anions, and their degradation products. Ascorbic acid was detected in the intact samples and half of the propellants subjected to open burning; the intact fuel molecule was not detected in any of the post-blast residue. Two methods were optimized for the analysis of trace levels of hydrogen peroxide: HPLC with fluorescence detection (HPLC-FD), and HPLC with electrochemical detection (HPLC-ED). Both techniques were extremely selective for hydrogen peroxide. Both methods were applied to the analysis of post-blast debris from improvised mixtures of concentrated hydrogen peroxide/fuel; hydrogen peroxide was detected on variety of substrates. Hydrogen peroxide was detected in the post-blast residues of the improvised explosives TATP and HMTD.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

This dissertation presents and evaluates a methodology for scheduling medical application workloads in virtualized computing environments. Such environments are being widely adopted by providers of "cloud computing" services. In the context of provisioning resources for medical applications, such environments allow users to deploy applications on distributed computing resources while keeping their data secure. Furthermore, higher level services that further abstract the infrastructure-related issues can be built on top of such infrastructures. For example, a medical imaging service can allow medical professionals to process their data in the cloud, easing them from the burden of having to deploy and manage these resources themselves. In this work, we focus on issues related to scheduling scientific workloads on virtualized environments. We build upon the knowledge base of traditional parallel job scheduling to address the specific case of medical applications while harnessing the benefits afforded by virtualization technology. To this end, we provide the following contributions: (1) An in-depth analysis of the execution characteristics of the target applications when run in virtualized environments. (2) A performance prediction methodology applicable to the target environment. (3) A scheduling algorithm that harnesses application knowledge and virtualization-related benefits to provide strong scheduling performance and quality of service guarantees. In the process of addressing these pertinent issues for our target user base (i.e. medical professionals and researchers), we provide insight that benefits a large community of scientific application users in industry and academia. Our execution time prediction and scheduling methodologies are implemented and evaluated on a real system running popular scientific applications. We find that we are able to predict the execution time of a number of these applications with an average error of 15%. Our scheduling methodology, which is tested with medical image processing workloads, is compared to that of two baseline scheduling solutions and we find that it outperforms them in terms of both the number of jobs processed and resource utilization by 20–30%, without violating any deadlines. We conclude that our solution is a viable approach to supporting the computational needs of medical users, even if the cloud computing paradigm is not widely adopted in its current form.