146 research outputs found
Different Policy Objectives of the Road Pricing Problem -a Game Theory Approach
Abstract Using game theory we investigate a new approach to formulate and solve optimal tolls with a focus on different policy objectives of the road authority. The aim is to gain more insight into determining optimal tolls as well as into the behavior of users after tolls have been imposed on the network. The problem of determining optimal tolls is stated and defined using utility maximization theory, including elastic demand on the travelers' side and different objectives for the road authority. Game theory notions are adopted regarding different games and players, rules and outcomes of the games played between travelers on the one hand and the road authority on the other. Different game concepts (Cournot, Stackelberg and social planner game) are mathematically formulated and the relationship between players, their payoff functions, and rules of the games are defined. The games are solved for different scenarios and different objectives for the road authority, using the Nash equilibrium concept. Using the Stackelberg game concept as being most realistic for road pricing, a few experiments are presented illustrating the optimal toll design problem subject to different pricing policies considering different objectives of the road authority. Results show different outcomes both in terms of optimal tolls as well as in payoffs for travelers. There exist multiple optimal solutions and the objective functions may have a non-continuous shape. The main contribution is the two-level separation between the network users and the road authority in terms of their objectives and influences
Determination of Microstructural Changes By Severely Plastically Deformed Copper-Aluminum Alloy: Optical Study
Our work deals with the problem of producing a complex metal-ceramic composite using the processes of internal oxidation (IO) and severe plastic deformation. For this purpose, Cu-Al alloy with 0.4wt.% of Al was used. IO of sample serves in the first step of the processing as a means for attaining a fine dispersion of nanosized oxide particles in the metal matrix. Production technology continues with repeated application of severe plastic deformation (SPD) of the resulting metal-matrix composite to produce the bulk nanoscaled structural material. SPD was carried out with equal channel angular pressing (ECAP), which allowed that the material could be subjected to an intense plastic strain through simple shear. Microstructural characteristics of one phase and multiphase material was studied on internally oxidized Cu with 0.4wt.% of Al sample composed of one phase copper-aluminum solid solution in the core and fine dispersed oxide particles in the same matrix in the mantle region. In this manner AFM, X-ray diffraction and Raman spectroscopy were used. Local structures in plastically deformed samples reflect presence of Cu, CuO, Cu2O, Cu4O3 or Al2O3 structural characteristics, depending on type of sample
Multiple Promoters and Alternative Splicing: Hoxa5 Transcriptional Complexity in the Mouse Embryo
The genomic organization of Hox clusters is fundamental for the precise spatio-temporal regulation and the function of each Hox gene, and hence for correct embryo patterning. Multiple overlapping transcriptional units exist at the Hoxa5 locus reflecting the complexity of Hox clustering: a major form of 1.8 kb corresponding to the two characterized exons of the gene and polyadenylated RNA species of 5.0, 9.5 and 11.0 kb. This transcriptional intricacy raises the question of the involvement of the larger transcripts in Hox function and regulation.We have undertaken the molecular characterization of the Hoxa5 larger transcripts. They initiate from two highly conserved distal promoters, one corresponding to the putative Hoxa6 promoter, and a second located nearby Hoxa7. Alternative splicing is also involved in the generation of the different transcripts. No functional polyadenylation sequence was found at the Hoxa6 locus and all larger transcripts use the polyadenylation site of the Hoxa5 gene. Some larger transcripts are potential Hoxa6/Hoxa5 bicistronic units. However, even though all transcripts could produce the genuine 270 a.a. HOXA5 protein, only the 1.8 kb form is translated into the protein, indicative of its essential role in Hoxa5 gene function. The Hoxa6 mutation disrupts the larger transcripts without major phenotypic impact on axial specification in their expression domain. However, Hoxa5-like skeletal anomalies are observed in Hoxa6 mutants and these defects can be explained by the loss of expression of the 1.8 kb transcript. Our data raise the possibility that the larger transcripts may be involved in Hoxa5 gene regulation.Our observation that the Hoxa5 larger transcripts possess a developmentally-regulated expression combined to the increasing sum of data on the role of long noncoding RNAs in transcriptional regulation suggest that the Hoxa5 larger transcripts may participate in the control of Hox gene expression
Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort
BACKGROUND:
Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice.
METHODS:
A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively.
RESULTS:
SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655.
CONCLUSIONS:
In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin
New Mediterranean biodiversity records (March 2016)
In this Collective Article on “New Mediterranean Biodiversity Records”, we present additional records of species found
in the Mediterranean Sea. These records refer to eight different countries mainly throughout the northern part of the basin, and
include 28 species, belonging to five Phyla. The findings per country include the following species: Spain: Callinectes sapidus
and Chelidonura fulvipunctata; Monaco: Aplysia dactylomela; Italy: Charybdis (Charybdis) feriata, Carcharodon carcharias,
Seriola fasciata, and Siganus rivulatus; Malta: Pomacanthus asfur; Croatia: Lagocephalus sceleratus and Pomadasys incisus;
Montenegro: Lagocephalus sceleratus; Greece: Amathia (Zoobotryon) verticillata, Atys macandrewii, Cerithium scabridum,
Chama pacifica, Dendostrea cf. folium, Ergalatax junionae, Septifer cumingii, Syphonota geographica, Syrnola fasciata, Oxyu-
richthys petersi, Scarus ghobban, Scorpaena maderensis, Solea aegyptiaca and Upeneus pori; Turkey: Lobotes surinamensis,
Ruvettus pretiosus and Ophiocten abyssicolum. In the current article, the presence of Taractes rubescens (Jordan & Evermann,
1887) is recorded for the first time in the Mediterranean from Italy. The great contribution of citizen scientists in monitoring
biodiversity records is reflected herein, as 10% of the authors are citizen scientists, and contributed 37.5% of the new findings.peer-reviewe
Cognitive and Psychological Reactions of the General Population Three Months After the 2011 Tohoku Earthquake and Tsunami
BACKGROUND: The largest earthquake on record in Japan (magnitude 9.0) occurred on March 11, 2011, and the subsequent tsunami devastated the Pacific coast of Northern Japan. These further triggered the Fukushima I nuclear power plant accidents. Such a hugely complex disaster inevitably has negative psychological effects on general populations as well as on the direct victims. While previous disaster studies enrolled descriptive approaches focusing on direct victims, the structure of the psychological adjustment process of people from the general population has remained uncertain. The current study attempted to establish a path model that sufficiently reflects the early psychological adaptation process of the general population to large-scale natural disasters. METHODS AND FINDINGS: Participants from the primary disaster area (n = 1083) and other areas (n = 2372) voluntarily participated in an online questionnaire study. By constructing path models using a structural equation model procedure (SEM), we examined the structural relationship among psychological constructs known related to disasters. As post-traumatic stress symptoms (PTS) were significantly more present in people in the primarily affected area than in those in secondary- or non-affected areas, the path models were constructed for the primary victims. The parsimoniously depicted model with the best fit was achieved for the psychological-adjustment centered model with quality of life (QoL) as a final outcome. CONCLUSION: The paths to QoL via negative routes (from negative cognitive appraisal, PTS, and general stress) were dominant, suggesting the importance of clinical intervention for reducing negative cognitive appraisal, and for caring for general stress and PTS to maintain QoL at an early stage of psychological adaptation to a disaster. The model also depicted the presence of a positive route where positive cognitive appraisal facilitates post-traumatic growth (PTG) to achieve a higher QoL, suggesting the potential importance of positive psychological preventive care for unexpected natural disasters
MEDLEM database, a data collection on large elasmobranchs in the Mediterranean and Black Seas
The Mediterranean Large Elasmobranchs Monitoring (MEDLEM) database contains more than 3,000 records (with more than 4,000 individuals) of large elasmobranch species from 21 different countries around the Mediterranean and Black seas, observed from 1666 to 2017. The principal species included in the archive are the devil ray (1,868 individuals), the basking shark (935 individuals), the blue shark (622 individuals), and the great white shark (342 individuals). In the last decades, other species such as the thresher shark (187 individuals), the shortfin mako (180 individuals), and the spiny butterfly ray (138) were reported with increasing frequency. This was possibly due to increased public awareness on the conservation status of sharks, and the consequent development of new monitoring programs. MEDLEM does not have homogeneous reporting coverage throughout the Mediterranean and Black seas and it should be considered as a database of observed species presence. Scientific monitoring efforts in the south-eastern Mediterranean and Black seas are generally lower than in the northern sectors and the absence of some species in our database does not imply their actual absence in these regions. However, the available data allowed us to analyse the frequency and spatial distribution of records, the size frequencies for a few selected the available data allowed us to analyse the frequency and spatial distribution of records, the size frequencies for a few selected species, the overall area coverage, and which species are involved as bycatch by different fishing gears
Prospective research on musculoskeletal disorders in office workers (PROMO): study protocol
BACKGROUND: This article describes the background and study design of the PROMO study (Prospective Research on Musculoskeletal disorders in Office workers). Few longitudinal studies have been performed to investigate the risk factors responsible for the incidence of hand, arm, shoulder and neck symptoms among office workers, given the observation that a large group of office workers might be at risk worldwide. Therefore, the PROMO study was designed. The main aim is to quantify the contribution of exposure to occupational computer use to the incidence of hand, arm, shoulder and neck symptoms. The results of this study might lead to more effective and/or cost-efficient preventive interventions among office workers. METHODS/DESIGN: A prospective cohort study is conducted, with a follow-up of 24 months. In total, 1821 participants filled out the first questionnaire (response rate of 74%). Data on exposure and outcome is collected using web-based self-reports. Outcome assessment takes place every three months during the follow-up period. Data on computer use are collected at baseline and continuously during follow-up using a software program. DISCUSSION: The advantages of the PROMO study include the long follow-up period, the repeated measurement of both exposure and outcome, and the objective measurement of the duration of computer use. In the PROMO study, hypotheses stemming from lab-based and field-based research will be investigated
Mouse Transgenesis Identifies Conserved Functional Enhancers and cis-Regulatory Motif in the Vertebrate LIM Homeobox Gene Lhx2 Locus
The vertebrate Lhx2 is a member of the LIM homeobox family of
transcription factors. It is essential for the normal development of the
forebrain, eye, olfactory system and liver as well for the differentiation of
lymphoid cells. However, despite the highly restricted spatio-temporal
expression pattern of Lhx2, nothing is known about its
transcriptional regulation. In mammals and chicken, Crb2,
Dennd1a and Lhx2 constitute a conserved
linkage block, while the intervening Dennd1a is lost in the
fugu Lhx2 locus. To identify functional enhancers of
Lhx2, we predicted conserved noncoding elements (CNEs) in
the human, mouse and fugu Crb2-Lhx2 loci and
assayed their function in transgenic mouse at E11.5. Four of the eight CNE
constructs tested functioned as tissue-specific enhancers in specific regions of
the central nervous system and the dorsal root ganglia (DRG), recapitulating
partial and overlapping expression patterns of Lhx2 and
Crb2 genes. There was considerable overlap in the
expression domains of the CNEs, which suggests that the CNEs are either
redundant enhancers or regulating different genes in the locus. Using a large
set of CNEs (810 CNEs) associated with transcription factor-encoding genes that
express predominantly in the central nervous system, we predicted four
over-represented 8-mer motifs that are likely to be associated with expression
in the central nervous system. Mutation of one of them in a CNE that drove
reporter expression in the neural tube and DRG abolished expression in both
domains indicating that this motif is essential for expression in these domains.
The failure of the four functional enhancers to recapitulate the complete
expression pattern of Lhx2 at E11.5 indicates that there must
be other Lhx2 enhancers that are either located outside the
region investigated or divergent in mammals and fishes. Other approaches such as
sequence comparison between multiple mammals are required to identify and
characterize such enhancers
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