1,433 research outputs found
CVaR minimization by the SRA algorithm
Using the risk measure CV aR in �nancial analysis has become
more and more popular recently. In this paper we apply CV aR for portfolio optimization. The problem is formulated as a two-stage stochastic programming model, and the SRA algorithm, a recently developed heuristic algorithm, is applied for minimizing CV aR
The GATA1s isoform is normally down-regulated during terminal haematopoietic differentiation and over-expression leads to failure to repress MYB, CCND2 and SKI during erythroid differentiation of K562 cells
Background: Although GATA1 is one of the most extensively studied haematopoietic transcription factors little is currently known about the physiological functions of its naturally occurring isoforms GATA1s and GATA1FL in humans—particularly whether the isoforms have distinct roles in different lineages and whether they have non-redundant roles in haematopoietic differentiation. As well as being of general interest to understanding of haematopoiesis, GATA1 isoform biology is important for children with Down syndrome associated acute megakaryoblastic leukaemia (DS-AMKL) where GATA1FL mutations are an essential driver for disease pathogenesis.
<p/>Methods: Human primary cells and cell lines were analyzed using GATA1 isoform specific PCR. K562 cells expressing GATA1s or GATA1FL transgenes were used to model the effects of the two isoforms on in vitro haematopoietic differentiation.
<p/>Results: We found no evidence for lineage specific use of GATA1 isoforms; however GATA1s transcripts, but not GATA1FL transcripts, are down-regulated during in vitro induction of terminal megakaryocytic and erythroid differentiation in the cell line K562. In addition, transgenic K562-GATA1s and K562-GATA1FL cells have distinct gene expression profiles both in steady state and during terminal erythroid differentiation, with GATA1s expression characterised by lack of repression of MYB, CCND2 and SKI.
<p/>Conclusions: These findings support the theory that the GATA1s isoform plays a role in the maintenance of proliferative multipotent megakaryocyte-erythroid precursor cells and must be down-regulated prior to terminal differentiation. In addition our data suggest that SKI may be a potential therapeutic target for the treatment of children with DS-AMKL
Vitellogenin Underwent Subfunctionalization to Acquire Caste and Behavioral Specific Expression in the Harvester Ant Pogonomyrmex barbatus
PMCID: PMC3744404This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication
The international effort: building the bridge for Translational Medicine: Report of the 1st International Conference of Translational Medicine (ICTM)
Background: Supported by the International Society for Translational Medicine (ISTM), Wenzhou Medical College and the First Affiliated Hospital of Wenzhou Medical College, the International Conference on Translational Medicine (ICTM) was held on October 22–23, 2011 in Wenzhou, China. Nearly 800 registrants attended the meeting, primarily representing institutes and hospitals in Europe, The United States of America, And Asia, and China. The meeting was chaired and organized by Dr. Xiangdong Wang, Xiaoming Chen, Richard Coico, Jeffrey M. Drazen, Richard Horton, Francesco M. Marincola, Laurentiu M. Popescu, Jia Qu and Aamir Shahzad. Findings: The meeting focused on the communication of the need to foster translational medicine (TM) by building and broadening bridges between basic research and clinical studies at the international level. The meeting included distinguished TM experts from academia, the pharmaceutical and diagnostics industries, government agencies, regulators, and clinicians and provided the opportunity to identify shared interests and efforts for collaborative approaches utilizing cutting edge technologies, innovative approaches and novel therapeutic interventions. The meeting defined the concept of TM in its two-way operational scheme and emphasized the need for bed to bench efforts based directly on clinical observation. Conclusions: It was the meeting participants’ realization that the shared main goals of TM include breaking the separation between clinic practice and basic research, establishing positive feedback by understanding the basis of expected and unexpected clinical outcomes and accelerating basic research relevant to human suffering. The primary objectives of the meeting were two-fold: to accelerate the two-way translation by informing the participants representing the different disciplines about the state of art activities around TM approaches; and to identify areas that need to be supported by redirecting limited resources as well as identifying new sources of funding. This report summarizes key concepts presented during the meeting representing the state-of-art translational research and salient aspects of the ensuing discussions
Весовые соотношения тимуса и надпочечников у антенатально погибших плодов
ТИМУСНАДПОЧЕЧНИКИтимомегалиядети первого года жизнидети раннего возрастаМЛАДЕНЕЦ, СМЕРТНОСТЬЭНДОКРИННОЙ СИСТЕМЫ БОЛЕЗНИСМЕРТНОСТЬ ДЕТСКАЯсиндром внезапной детской смерт
Cluster Lenses
Clusters of galaxies are the most recently assembled, massive, bound
structures in the Universe. As predicted by General Relativity, given their
masses, clusters strongly deform space-time in their vicinity. Clusters act as
some of the most powerful gravitational lenses in the Universe. Light rays
traversing through clusters from distant sources are hence deflected, and the
resulting images of these distant objects therefore appear distorted and
magnified. Lensing by clusters occurs in two regimes, each with unique
observational signatures. The strong lensing regime is characterized by effects
readily seen by eye, namely, the production of giant arcs, multiple-images, and
arclets. The weak lensing regime is characterized by small deformations in the
shapes of background galaxies only detectable statistically. Cluster lenses
have been exploited successfully to address several important current questions
in cosmology: (i) the study of the lens(es) - understanding cluster mass
distributions and issues pertaining to cluster formation and evolution, as well
as constraining the nature of dark matter; (ii) the study of the lensed objects
- probing the properties of the background lensed galaxy population - which is
statistically at higher redshifts and of lower intrinsic luminosity thus
enabling the probing of galaxy formation at the earliest times right up to the
Dark Ages; and (iii) the study of the geometry of the Universe - as the
strength of lensing depends on the ratios of angular diameter distances between
the lens, source and observer, lens deflections are sensitive to the value of
cosmological parameters and offer a powerful geometric tool to probe Dark
Energy. In this review, we present the basics of cluster lensing and provide a
current status report of the field.Comment: About 120 pages - Published in Open Access at:
http://www.springerlink.com/content/j183018170485723/ . arXiv admin note:
text overlap with arXiv:astro-ph/0504478 and arXiv:1003.3674 by other author
Interpopulation variation in female remating is attributable to female and male effects in Callosobruchus chinensis
The evolution of female multiple mating is best understood by consideration of male and female reproductive perspectives. Females should usually be selected to remate at their optimum frequencies whereas males should be selected to manipulate female remating to their advantage. Female remating behavior may therefore be changed by variation of male and female traits. In this study, our objective was to separate the effects of female and male strains on female remating for the adzuki bean beetle, Callosobruchus chinensis, for which there is interstrain variation in female remating frequency. We found that interstrain variation in female remating is primarily attributable to female traits, suggesting genetic variation in female receptivity to remating in C. chinensis. Some interstrain variation in female remating propensity was attributable to an interaction between female and male strains, however, with the males of some strains being good at inducing nonreceptivity in females from one high-remating strain whereas others were good at inducing copulation in nonvirgin females from the high-remating strain. There is, therefore, interstrain variation in male ability to deter females from remating and in male ability to mate successfully with nonvirgin females. These results suggest that mating traits have evolved along different trajectories in different strains of C. chinensis.</p
Augmented acquisition of cocaine self-administration and altered brain glucose metabolism in adult female but not male rats exposed to a cannabinoid agonist during adolescence
Marijuana consumption during adolescence has been proposed to be a stepping stone for adult cocaine addiction. However, experimental evidence for this hypothesis is missing. In this work we chronically injected male and female Wistar rats with either the
cannabinoid agonist CP 55,940 (CP; 0.4 mg/kg) or its corresponding vehicle. Adult acquisition (seven 30 min daily sessions) and
maintenance (fourteen 2 h daily sessions) of cocaine self administration (1 mg/kg), food reinforced operant learning under conditions of
normal (ad libitum access to food), and high motivation (food restriction schedule) were measured. Additionally, brain metabolic activity
was analyzed by means of [18F] fluorodeoxyglucose positron emission tomography. During the acquisition phase, female CP treated rats
showed a higher rate of cocaine self administration as compared to vehicle treated females and males; no differences were found
between both male groups. This effect disappeared in the maintenance phase. Moreover, no differences among groups were evident in
the food reinforced operant task, pointing to the cocaine specific nature of the effect seen in self administration rather than a general
change in reward processing. Basal brain metabolic activity also changed in CP treated females when compared to their vehicle treated
counterparts with no differences being found in the males; more specifically we observed a hyper activation of the frontal cortex and a
hypo activation of the amygdalo entorhinal cortex. Our results suggest that a chronic exposure to cannabinoids during adolescence alters
the susceptibility to acquire cocaine self administration, in a sex specific fashion. This increased susceptibility could be related to thechanges in brain metabolic activity induced by cannabinoids during adolescenceThis work was supported by Grants FIS G03/05 (Red de Trastornos Adictivos), BSO2001-1099, FIS 01-05-01, Plan Nacional sobre Drogas (PNSD) 2001–2003, PNSD 2004–2007, GR-SAL/0260/2004 to EA and Grants INT/2012/ 2002, CB06/01/0079, and CENIT (2006–2009) to MDPublicad
Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli
Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts. Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins. Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets
Extra-pair parentage and personality in a cooperatively breeding bird
Why so much variation in extra-pair parentage occurs within and among populations remains unclear. Often the fitness costs and benefits of extra-pair parentage are hypothesised to explain its occurrence; therefore, linking extra-pair parentage with traits such as personality (behavioural traits that can be heritable and affect reproductive behaviour) may help our understanding. Here, we investigate whether reproductive outcomes and success are associated with exploratory behaviour in a natural population of cooperatively breeding Seychelles warblers (Acrocephalus sechellensis) on Cousin Island. Exploratory behaviour correlates positively with traits such as risk-taking behaviour and activity in other wild bird species and might promote extra-pair mating by increasing the rate at which potential extra-pair partners are encountered. We therefore predicted that fast-exploring individuals would have more extra-pair offspring. There is also a potential trade-off between pursuing extra-pair parentage and mate guarding in males. We therefore also predicted that fast-exploring males would be more likely to pursue extra-pair parentage and that this would increase the propensity of their mate to gain extra-pair parentage. We found that neither the total number of offspring nor the number of extra-pair offspring were associated with a male’s or female’s exploratory behaviour. However, there was a small but significant propensity for females to have extra-pair fertilisations in pairs that were behaviourally disassortative. Overall, we conclude that, due to the small effect size, the association between exploratory behaviour and extra-pair paternity is unlikely to be biologically relevant. Significance statement: True genetic monogamy is rare, even in socially monogamous systems, and multiple factors, such as behaviour, social structure, morphology and physiology, determined by the biological system can cause variation in extra-pair parentage (EPP). Therefore, investigating the inherent differences in these factors among individuals could be informative. We investigated whether reproductive outcomes/success are associated with differences in the propensity to explore novel environments/objects in a promiscuous, island-dwelling cooperatively breeding bird, the Seychelles warbler. Our results showed that exploratory behaviour was not associated with the number of offspring produced by an individual, and thus the long-term fitness consequences of different exploratory tendencies did not differ. We also found that the propensity to engage in EPP in females was higher in dissimilar behavioural pairs, but due to the small effect size, we hesitate to conclude that there are personality-dependent mating outcomes in the population
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