179 research outputs found

    An Analysis of Occupational Pension Provision: From Evaluation to Redesign

    Get PDF
    Around the turn of the 21st century, the “perfect storm” implied by low interest rates, poor stock market returns and an ageing society led collective pension plans into underfunded situations and caused considerable concerns over their financial sustainability. This thesis analyzes the prevailing collective pension plans in the Netherlands and makes suggestions on improving the occupational pension provision in changing demographic, financial and regulatory environments. Chapter 2 probes the pension investment performance at the overall plan level. We find that pension plans on average do not outperform their pre-selected benchmarks, reflecting that trustees fail to select superior asset management strategies. Comparatively, however, large plans outperform their smaller peers. Chapter 3 investigates the strategic asset allocation of pension plans under market consistent valuation. We find that a slight change in the model specification of asset return dynamics can have a significant impact on the optimal mix. In chapter 4, we propose a new generational plan design and find that it provides higher value and welfare to participants when compared with the current collective plan design. This is due to the fact that it allows for risk sharing via time diversification of long-term investments and prevents a-priori value transfers. To allow for intergenerational risk sharing, in Chapter 5 we introduce further design improvements by having generations trade contingent claims among them. Our estimates show that the guarantees are affordable and the surplus call option has substantial value. The option prices also give an indication of value tranfers in traditional collective pension designs

    Large-time Behavior of Solutions to the Inflow Problem of Full Compressible Navier-Stokes Equations

    Full text link
    Large-time behavior of solutions to the inflow problem of full compressible Navier-Stokes equations is investigated on the half line R+=(0,+)R^+ =(0,+\infty). The wave structure which contains four waves: the transonic(or degenerate) boundary layer solution, 1-rarefaction wave, viscous 2-contact wave and 3-rarefaction wave to the inflow problem is described and the asymptotic stability of the superposition of the above four wave patterns to the inflow problem of full compressible Navier-Stokes equations is proven under some smallness conditions. The proof is given by the elementary energy analysis based on the underlying wave structure. The main points in the proof are the degeneracies of the transonic boundary layer solution and the wave interactions in the superposition wave.Comment: 27 page

    Maternal care in rural China: a case study from Anhui province

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Studies on prenatal care in China have focused on the timing and frequency of prenatal care and relatively little information can be found on how maternal care has been organized and funded or on the actual content of the visits, especially in the less developed rural areas. This study explored maternal care in a rural county from Anhui province in terms of care organization, provision and utilization.</p> <p>Methods</p> <p>A total of 699 mothers of infants under one year of age were interviewed with structured questionnaires; the county health bureau officials and managers of township hospitals (n = 10) and county level hospitals (n = 2) were interviewed; the process of the maternal care services was observed by the researchers. In addition, statistics from the local government were used.</p> <p>Results</p> <p>The county level hospitals were well staffed and equipped and served as a referral centre for women with a high-risk pregnancy. Township hospitals had, on average, 1.7 midwives serving an average population of 15,000 people. Only 10–20% of the current costs in county level hospitals and township hospitals were funded by the local government, and women paid for delivery care. There was no systematic organized prenatal care and referrals were not mandatory. About half of the women had their first prenatal visit before the 13th gestational week, 36% had fewer than 5 prenatal visits, and about 9% had no prenatal visits. A major reason for not having prenatal care visits was that women considered it unnecessary. Most women (87%) gave birth in public health facilities, and the rest in a private clinic or at home. A total of 8% of births were delivered by caesarean section. Very few women had any postnatal visits. About half of the women received the recommended number of prenatal blood pressure and haemoglobin measurements.</p> <p>Conclusion</p> <p>Delivery care was better provided than both prenatal and postnatal care in the study area. Reliance on user fees gave the hospitals an incentive to put more emphasis on revenue generating activities such as delivery care instead of prenatal and postnatal care.</p

    Transcriptome analysis of orange-spotted grouper (Epinephelus coioides) spleen in response to Singapore grouper iridovirus

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Orange-spotted grouper (<it>Epinephelus coioides</it>) is an economically important marine fish cultured in China and Southeast Asian countries. The emergence of infectious viral diseases, including iridovirus and betanodavirus, have severely affected food products based on this species, causing heavy economic losses. Limited available information on the genomics of <it>E. coioides </it>has hampered the understanding of the molecular mechanisms that underlie host-virus interactions. In this study, we used a 454 pyrosequencing method to investigate differentially-expressed genes in the spleen of the <it>E. coioides </it>infected with Singapore grouper iridovirus (SGIV).</p> <p>Results</p> <p>Using 454 pyrosequencing, we obtained abundant high-quality ESTs from two spleen-complementary DNA libraries which were constructed from SGIV-infected (V) and PBS-injected fish (used as a control: C). A total of 407,027 and 421,141 ESTs were produced in control and SGIV infected libraries, respectively. Among the assembled ESTs, 9,616 (C) and 10,426 (V) ESTs were successfully matched against known genes in the NCBI non-redundant (nr) database with a cut-off E-value above 10<sup>-5</sup>. Gene ontology (GO) analysis indicated that "cell part", "cellular process" and "binding" represented the largest category. Among the 25 clusters of orthologous group (COG) categories, the cluster for "translation, ribosomal structure and biogenesis" represented the largest group in the control (185 ESTs) and infected (172 ESTs) libraries. Further KEGG analysis revealed that pathways, including cellular metabolism and intracellular immune signaling, existed in the control and infected libraries. Comparative expression analysis indicated that certain genes associated with mitogen-activated protein kinase (MAPK), chemokine, toll-like receptor and RIG-I signaling pathway were alternated in response to SGIV infection. Moreover, changes in the pattern of gene expression were validated by qRT-PCR, including cytokines, cytokine receptors, and transcription factors, apoptosis-associated genes, and interferon related genes.</p> <p>Conclusion</p> <p>This study provided abundant ESTs that could contribute greatly to disclosing novel genes in marine fish. Furthermore, the alterations of predicted gene expression patterns reflected possible responses of these fish to the virus infection. Taken together, our data not only provided new information for identification of novel genes from marine vertebrates, but also shed new light on the understanding of defense mechanisms of marine fish to viral pathogens.</p

    The Changes in Maternal Mortality in 1000 Counties in Mid-Western China by a Government-Initiated Intervention

    Get PDF
    BACKGROUND: Since 2000, the Chinese government has implemented an intervention program to reduce maternal mortality and eliminate neonatal tetanus in accordance with the Millennium Development Goals 5. To assess the effectiveness of this intervention program, we analyzed the level, trend and reasons defining the maternal mortality ratio (MMR) in the 1,000 priority counties before and after implementation of the intervention between 1999 and 2007. METHODOLOGY/PRINCIPAL FINDINGS: The data was obtained from the National Maternal and Child Health Routine Reporting System. The intervention included providing basic and emergency obstetric equipment and supplies to local medical hospitals, and also included providing professional training to local obstetric doctors, development of obstetric emergency centers and "green channel" express referral networks, reducing or waiving the cost of hospital delivery, and conducting community health education. Based on the initiation time of the intervention and the level of poverty, 1,000 counties, containing a total population of 300 million, were categorized into three groups. MMR significantly decreased by about 50%, with an average reduction rate of 9.24%, 16.06%, and 18.61% per year in the three county groups, respectively. The hospital delivery rate significantly increased. Obstetric hemorrhage was the leading cause of maternal deaths and significantly declined, with an average decrease in the MMR of 11.25%, 18.03%, and 24.90% per year, respectively. The magnitude of the MMR, the average reduction rate of the MMR, and the occurrence of the leading causes of death were closely associated with the percentage of poverty. CONCLUSIONS/SIGNIFICANCE: The intervention program implemented by the Chinese government has significantly reduced the MMR in mid-western China, suggesting that well-targeted interventions could be an efficient strategy to reducing MMR in resource-poor areas. Reduction of the MMR not only depends on conducting proven interventions, but also relies on economic development in rural areas with a high burden of maternal death

    Identification of a Novel Marine Fish Virus, Singapore Grouper Iridovirus-Encoded MicroRNAs Expressed in Grouper Cells by Solexa Sequencing

    Get PDF
    BACKGROUND: MicroRNAs (miRNAs) are ubiquitous non-coding RNAs that regulate gene expression at the post-transcriptional level. An increasing number of studies has revealed that viruses can also encode miRNAs, which are proposed to be involved in viral replication and persistence, cell-mediated antiviral immune response, angiogenesis, and cell cycle regulation. Singapore grouper iridovirus (SGIV) is a pathogenic iridovirus that has severely affected grouper aquaculture in China and Southeast Asia. Comprehensive knowledge about the related miRNAs during SGIV infection is helpful for understanding the infection and the pathogenic mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether SGIV encoded miRNAs during infection, a small RNA library derived from SGIV-infected grouper (GP) cells was constructed and sequenced by Illumina/Solexa deep-sequencing technology. We recovered 6,802,977 usable reads, of which 34,400 represented small RNA sequences encoded by SGIV. Sixteen novel SGIV-encoded miRNAs were identified by a computational pipeline, including a miRNA that shared a similar sequence to herpesvirus miRNA HSV2-miR-H4-5p, which suggests miRNAs are conserved in far related viruses. Generally, these 16 miRNAs are dispersed throughout the SGIV genome, whereas three are located within the ORF057L region. Some SGIV-encoded miRNAs showed marked sequence and length heterogeneity at their 3' and/or 5' end that could modulate their functions. Expression levels and potential biological activities of these viral miRNAs were examined by stem-loop quantitative RT-PCR and luciferase reporter assay, respectively, and 11 of these viral miRNAs were present and functional in SGIV-infected GP cells. CONCLUSIONS: Our study provided a genome-wide view of miRNA production for iridoviruses and identified 16 novel viral miRNAs. To the best of our knowledge, this is the first experimental demonstration of miRNAs encoded by aquatic animal viruses. The results provide a useful resource for further in-depth studies on SGIV infection and iridovirus pathogenesis

    Transcriptome and Network Changes in Climbers at Extreme Altitudes

    Get PDF
    Extreme altitude can induce a range of cellular and systemic responses. Although it is known that hypoxia underlies the major changes and that the physiological responses include hemodynamic changes and erythropoiesis, the molecular mechanisms and signaling pathways mediating such changes are largely unknown. To obtain a more complete picture of the transcriptional regulatory landscape and networks involved in extreme altitude response, we followed four climbers on an expedition up Mount Xixiabangma (8,012 m), and collected blood samples at four stages during the climb for mRNA and miRNA expression assays. By analyzing dynamic changes of gene networks in response to extreme altitudes, we uncovered a highly modular network with 7 modules of various functions that changed in response to extreme altitudes. The erythrocyte differentiation module is the most prominently up-regulated, reflecting increased erythrocyte differentiation from hematopoietic stem cells, probably at the expense of differentiation into other cell lineages. These changes are accompanied by coordinated down-regulation of general translation. Network topology and flow analyses also uncovered regulators known to modulate hypoxia responses and erythrocyte development, as well as unknown regulators, such as the OCT4 gene, an important regulator in stem cells and assumed to only function in stem cells. We predicted computationally and validated experimentally that increased OCT4 expression at extreme altitude can directly elevate the expression of hemoglobin genes. Our approach established a new framework for analyzing the transcriptional regulatory network from a very limited number of samples

    Characterization of the Interaction of Full-Length HIV-1 Vif Protein with its Key Regulator CBFβ and CRL5 E3 Ubiquitin Ligase Components

    Get PDF
    Human immunodeficiency virus-1 (HIV-1) viral infectivity factor (Vif) is essential for viral replication because of its ability to eliminate the host's antiviral response to HIV-1 that is mediated by the APOBEC3 family of cellular cytidine deaminases. Vif targets these proteins, including APOBEC3G, for polyubiquitination and subsequent proteasome-mediated degradation via the formation of a Cullin5-ElonginB/C-based E3 ubiquitin ligase. Determining how the cellular components of this E3 ligase complex interact with Vif is critical to the intelligent design of new antiviral drugs. However, structural studies of Vif, both alone and in complex with cellular partners, have been hampered by an inability to express soluble full-length Vif protein. Here we demonstrate that a newly identified host regulator of Vif, core-binding factor-beta (CBFβ), interacts directly with Vif, including various isoforms and a truncated form of this regulator. In addition, carboxyl-terminal truncations of Vif lacking the BC-box and cullin box motifs were sufficient for CBFβ interaction. Furthermore, association of Vif with CBFβ, alone or in combination with Elongin B/C (EloB/C), greatly increased the solubility of full-length Vif. Finally, a stable complex containing Vif-CBFβ-EloB/C was purified in large quantity and shown to bind purified Cullin5 (Cul5). This efficient strategy for purifying Vif-Cul5-CBFβ-EloB/C complexes will facilitate future structural and biochemical studies of Vif function and may provide the basis for useful screening approaches for identifying novel anti-HIV drug candidates

    Relationships between Hematopoiesis and Hepatogenesis in the Midtrimester Fetal Liver Characterized by Dynamic Transcriptomic and Proteomic Profiles

    Get PDF
    In fetal hematopoietic organs, the switch from hematopoiesis is hypothesized to be a critical time point for organogenesis, but it is not yet evidenced. The transient coexistence of hematopoiesis will be useful to understand the development of fetal liver (FL) around this time and its relationship to hematopoiesis. Here, the temporal and the comparative transcriptomic and proteomic profiles were observed during the critical time points corresponding to the initiation (E11.5), peak (E14.5), recession (E15.5), and disappearance (3 ddp) of mouse FL hematopoiesis. We found that E11.5-E14.5 corresponds to a FL hematopoietic expansion phase with distinct molecular features, including the expression of new transcription factors, many of which are novel KRAB (Kruppel-associated box)-containing zinc finger proteins. This time period is also characterized by extensive depression of some liver functions, especially catabolism/utilization, immune and defense, classical complement cascades, and intrinsic blood coagulation. Instead, the other liver functions increased, such as xenobiotic and sterol metabolism, synthesis of carbohydrate and glycan, the alternate and lectin complement cascades and extrinsic blood coagulation, and etc. Strikingly, all of the liver functions were significantly increased at E14.5-E15.5 and thereafter, and the depression of the key pathways attributes to build the hematopoietic microenvironment. These findings signal hematopoiesis emigration is the key to open the door of liver maturation

    Viral Capsid Is a Pathogen-Associated Molecular Pattern in Adenovirus Keratitis

    Get PDF
    Human adenovirus (HAdV) infection of the human eye, in particular serotypes 8, 19 and 37, induces the formation of corneal subepithelial leukocytic infiltrates. Using a unique mouse model of adenovirus keratitis, we studied the role of various virus-associated molecular patterns in subsequent innate immune responses of resident corneal cells to HAdV-37 infection. We found that neither viral DNA, viral gene expression, or viral replication was necessary for the development of keratitis. In contrast, empty viral capsid induced keratitis and a chemokine profile similar to intact virus. Transfected viral DNA did not induce leukocyte infiltration despite CCL2 expression similar to levels in virus infected corneas. Mice without toll-like receptor 9 (Tlr9) signaling developed clinical keratitis upon HAdV-37 infection similar to wild type mice, although the absolute numbers of activated monocytes in the cornea were less in Tlr9−/− mice. Virus induced leukocytic infiltrates and chemokine expression in mouse cornea could be blocked by treatment with a peptide containing arginine glycine aspartic acid (RGD). These results demonstrate that adenovirus infection of the cornea induces chemokine expression and subsequent infiltration by leukocytes principally through RGD contact between viral capsid and the host cell, possibly through direct interaction between the viral capsid penton base and host cell integrins
    corecore