EU pension reform - An overview of the debate and an empirical assessment of the main policy reform options

This paper on European Union (EU) pension reform provides an overview of the debate and, on the basis of a series of model simulations, makes an empirical assessment of the main pension policy reform options at the EU, not the Member State, level. It estimates what it would take to bring the public PAYG pension system back into equilibrium and assesses the case for a shift to funding. The main conclusion of this paper is that the EU pension system should in the very long run (i.e. over more than one generation) be fully funded, with this being achieved using a two-stage optimal transition path. Stage one of this transition process should concentrate on stabilising the PAYG system and achieving a partial shift to funding, with stage two only occurring once circumstances permit. The fully funded system, once established, should have public and private pillars, with the public system in effect replacing the old PAYG system with a similar compulsory, defined benefit, system and with the private pillar being a voluntary, defined contribution, system.pension reform, policy reform options, ageing model, Mc Morrow, R�ger,

A Study of the Language Shifts in the Book of Daniel : A Comparative Narrative Analysis of Daniel 1 and 2, 7 and 8

Problem The problem this dissertation seeks to address is the use of bilingualism in the book of Daniel. Previously, scholars have utilized diachronic methods to explain the phenomenon of bilingualism in Daniel and have concluded that it is the product of compositional redaction. However, such studies have not produced a consensus in scholarship. In the last 40 years, several studies have emerged that conclude the use of bilingualism in the book of Daniel may best be explained as a rhetorical device. In contrast to the diachronic methodologies of prior studies, these examinations utilized methodologies that addressed rhetorical elements. Chapter One of this study briefly addresses the background to the problem of the use of bilingualism in Daniel and reviews five studies that conclude the occurrence of bilingualism is best explained as an intentional rhetorical device. Methodology In response to the positive results of the five studies noted above, this study uses a synchronic method, narrative analysis, to analyze the rhetorical use of bilingualism in the book of Daniel. This analysis seeks to determine whether the language shifts in Daniel affect the narratives that occur before and after the shifts, specifically in Daniel 1 and 2 (Daniel 2:4b; Hebrew to Aramaic) and Daniel 7 and 8 (Daniel 8:1; Aramaic to Hebrew). Chapter Two includes a brief overview of the narrative elements in the book of Daniel and of the prior use of narrative analysis in Old Testament studies and in the study of the book of Daniel. Since there exists a variety of views regarding the elements of narrative analysis, the methodology used in this study follows the narrative analysis outlined in Shimon Bar-Efrat’s book, Narrative Art in the Bible. An outline of this study’s methodology is delineated at the end of the chapter. Analysis In Chapter Three, an analysis of plot and character in the narratives in the chapters located before and after the first language shift at Daniel 2:4b (Daniel 1 and 2) is presented. The results of the analysis are reviewed and the existence of a narrative shift in plot and character that corresponds to the first language shift is identified. Next, the subsequent chapters in Aramaic (Daniel 3-7) are examined to determine whether the narrative shift is repeated throughout the Aramaic section. In Chapter Four, an analysis of plot and character in the narratives located before and after the second language shift at 8:1 (Daniel 7 and 8) is presented. The results of this second analysis are reviewed and the existence of a narrative shift in plot and character that corresponds to the second language shift is identified. Afterwards, the ensuing chapters in Hebrew (Daniel 9-12) are examined to determine whether the narrative shift is repeated throughout the Hebrew section. Findings Chapter Five consists of a discussion of the findings of this study. According to this study’s analysis, the two language shifts at Daniel 2 and Daniel 8 correspond to two narrative shifts at the same location. First, as the language shifts from Hebrew to Aramaic (and as one moves from Daniel 1 to 2), a narrative shift in plot and character emerges. Furthermore, the ensuing chapters in Aramaic (Daniel 3-7) repeat several plot and character elements that emerge in the narrative emphasis identified in Daniel 2. Second, as the language shifts from Aramaic to Hebrew (and as one moves from Daniel 7 to 8), a narrative shift in plot and character emerges. Furthermore, the ensuing chapters in Hebrew (Daniel 9-12) repeat several plot and character elements that emerge in the narrative emphasis identified in Daniel 8. As a consequence of this study’s findings, narrative and theological conclusions may be noted. In a narrative sense, this study suggests three conclusions. First, Daniel 2 and 8 function as points of narrative reconfiguration. Specifically, in Daniel 2 and 8 narrative elements in the previous chapters (Daniel 1 and 7) are appropriated and reconfigured (primarily through the use of a dream/vision) to create a specific narrative emphasis. Second, the narrative emphases identified in Daniel 2 and 8 are repeated in the subsequent chapters, namely Daniel 3-7 in Aramaic and Daniel 9-12 in Hebrew. This repetition creates a complex narrative progression that reaches a climax at the point at which each language concludes, specifically at Daniel 7 for the Aramaic section and at Daniel 12 for the Hebrew section. Thus, the book of Daniel consists of a complex narrative progression that is engendered by the language shifts. Therefore, although the chapters in the book of Daniel are self-contained narratives, the repetition of the narrative elements identified in Daniel 2 and 8 functions as a narrative progression through repetition that reaches a climax at the end of each progression in the respective languages. Third, within the complex narrative progression engendered by the language shifts, Daniel 7 performs three narrative functions. First, it functions as a climax for the Aramaic section, second, it functions as a central point of reconfiguration between Daniel 2 and 8, and third, it functions as the narrative source for the reconfiguration in Daniel 8. Such conclusions are compatible with prior research on the book of Daniel, which notes that Daniel 7 is the center of the book. In a theological sense, this study suggests two conclusions. First, the complex narrative progression that the language shifts engender depict God\u27s resolution to the problem of the divine-human conflict introduced in Daniel 1:1-2. In these programmatic introductory verses, the conflict between kingly-cultic pride and God\u27s sovereignty is broadly presented. Subsequently, the complex narrative progression noted in the language shift-narrative shift correspondence (LS-NSC) depicts God’s resolution to this conflict. In the Aramaic section (Daniel 2 and 3-7) the narrative of conflict between kingly-cultic pride and divine sovereignty emphasizes the kingly context. In the Hebrew section, (Daniel 8 and 9-12) the narrative of conflict between kingly-cultic pride and divine sovereignty emphasizes the cultic context. In both contexts, divine judgment resolves the overriding divine-human conflict. Second, within this overall context of conflict, God\u27s representatives experience religious and mortal threats. However, as they align themselves with God through their faithfulness in the Babylonian exile and in the extended exile depicted in the Hebrew section, they experience the positive results of God’s sovereignty, depicted through his acts of deliverance and judgment. Finally, this study concludes with Chapter 6, which consists of a summary and conclusion, limitations of the study, and recommendations for future research

Discovery and effects of pharmacological inhibition of the E3 ligase Skp2 by small molecule protein-protein interaction disruptors

Skp2 (S-phase kinase-associated protein 2), one component of the SCF E3 ubiquitin ligase complex, directly interacts with Skp1 and indirectly associates with Cullin1 and Rbx1 to bridge the E2 conjugating enzyme with its protein substrate to execute its E3 ligase activity. Skp2 is an Fbox protein (due to it containing an Fbox domain) and it is the rate-limiting component of the SCF complex. Skp2 targets several cell-cycle regulatory proteins for ubiquitination and degradation; most notable and significant for cancer are the cyclin-dependent kinase inhibitor, p27. Skp2 is an oncogene and studies have shown that over-expression of Skp2 leads to increased degradation of p27 and increased proliferation in several tumor types. Additionally, Skp2 is over-expressed in multiple human cancers. Clearly, Skp2 represents an attractive target for attenuating p27 ubiquitination and subsequent cell cycle progression. However, Skp2 does not have an easily identifiable and druggable “pocket” on which small molecules can bind; it interacts with Skp1 through the Fbox domain and binds to an accessory protein called Cks1 to bind to p27. Despite this hurdle, in this study, two selective small molecule inhibitors of the Skp2 SCF complex were discovered via an in silico screen that disrupt two places: the Skp1/Skp2 interaction site and the p27 binding site via targeting hot-spot residues. The Skp1/Skp2 inhibitor disruption resulted in restoring p27 levels in the nucleus and blocks cancer progression and cancer stem cell traits. Additionally, the inhibitors phenocopy the effects of genetic Skp2 deficiency. Two specific residues on Skp2 were predicted to bind to this Skp1/Skp2 inhibitor: Trp97 and Asp98. When these residues were mutated to alanine, the inhibitor lost its ability to bind to Skp2. To investigate the flexibility and understand the conformational change upon inhibitor binding and dynamics of the SCF complex, molecular dynamics simulations, homology models, and structural analysis was carried out on the complex with and without the inhibitors. These simulations showed that the contributions of the N-terminal tail region of Skp2 does not contribute directly to the binding of these inhibitors; but its conformation is important in the context of the other members of the SCF complex. Further dynamics analysis validated the mutagenesis results, showing that the two Skp2 mutants (Trp97Ala, Asp98Ala) that retained Skp1 binding but blocked inhibitor binding were stable, whereas the mutant that was unable to retain Skp1 binding (Trp127Ala) showed destabilization in the Fbox domain. Finally, active recruitment events after post-translational modifications are shown to be possible by the interaction of phosphorylated Ser256 on Skp2 with Lys104 loop region on Cul1 The model shows that this is due to the significant flexibility in the F-box domain of Skp2, making this interaction very likely. These results show that Skp2 is a promising target on which protein-protein interaction disruptors can be designed, and consideration of the dynamics of protein complexes is required to understand ligand binding

Conditional and constitutive expression of a Tbx1-GFP fusion protein in mice.

BACKGROUND: Velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS) is caused by a 1.5-3 Mb microdeletion of chromosome 22q11.2, frequently referred to as 22q11.2 deletion syndrome (22q11DS). This region includes TBX1, a T-box transcription factor gene that contributes to the etiology of 22q11DS. The requirement for TBX1 in mammalian development is dosage-sensitive, such that loss-of-function (LOF) and gain-of-function (GOF) of TBX1 in both mice and humans results in disease relevant congenital malformations. RESULTS: To further gain insight into the role of Tbx1 in development, we have targeted the Rosa26 locus to generate a new GOF mouse model in which a Tbx1-GFP fusion protein is expressed conditionally using the Cre/LoxP system. Tbx1-GFP expression is driven by the endogenous Rosa26 promoter resulting in ectopic and persistent expression. Tbx1 is pivotal for proper ear and heart development; ectopic activation of Tbx1-GFP in the otic vesicle by Pax2-Cre and Foxg1-Cre represses neurogenesis and produces morphological defects of the inner ear. Overexpression of a single copy of Tbx1-GFP using Tbx1Cre/+ was viable, while overexpression of both copies resulted in neonatal lethality with cardiac outflow tract defects. We have partially rescued inner ear and heart anomalies in Tbx1Cre/- null embryos by expression of Tbx1-GFP. CONCLUSIONS: We have generated a new mouse model to conditionally overexpress a GFP-tagged Tbx1 protein in vivo. This provides a useful tool to investigate in vivo direct downstream targets and protein binding partners of Tbx1

The Lisbon Strategy and the EU's structural productivity problem

The structural nature of the EU's productivity downturn is confirmed by the analysis in this paper, with the bulk of the deterioration emanating from an outdated and inflexible industrial structure which has been slow to adapt to the intensifying pressures of globalisation and rapid technological change. The EU's productivity problems are driven by the combined effect ofan excessive focus on low and medium-technology industries (with declining productivity growth rates and a globalisation-induced contraction in investment levels); an inability to seriously challenge the US's dominance in large areas of the ICT industry, as reflected in the relatively small size of its ICT production sector; and finally, its apparent slowness in reaping the productivity enhancing benefits of ICT in a range of ICT-using industries, although measurement issues severely complicate an assessment of the gains from ICT production and diffusion.lisbon strategy, productivity, growth, labour market, Denis, Mc Morrow, R�ger, Veugelers, structural productivity

Design and Implementation of a Measurement-Based Policy-Driven Resource Management Framework For Converged Networks

This paper presents the design and implementation of a measurement-based QoS and resource management framework, CNQF (Converged Networks QoS Management Framework). CNQF is designed to provide unified, scalable QoS control and resource management through the use of a policy-based network management paradigm. It achieves this via distributed functional entities that are deployed to co-ordinate the resources of the transport network through centralized policy-driven decisions supported by measurement-based control architecture. We present the CNQF architecture, implementation of the prototype and validation of various inbuilt QoS control mechanisms using real traffic flows on a Linux-based experimental test bed.Comment: in Ictact Journal On Communication Technology: Special Issue On Next Generation Wireless Networks And Applications, June 2011, Volume 2, Issue 2, Issn: 2229-6948(Online

Bias correction factors for near-Earth asteroids

Knowledge of the population size and physical characteristics (albedo, size, and rotation rate) of near-Earth asteroids (NEA's) is biased by observational selection effects which are functions of the population's intrinsic properties and the size of the telescope, detector sensitivity, and search strategy used. The NEA population is modeled in terms of orbital and physical elements: a, e, i, omega, Omega, M, albedo, and diameter, and an asteroid search program is simulated using actual telescope pointings of right ascension, declination, date, and time. The position of each object in the model population is calculated at the date and time of each telescope pointing. The program tests to see if that object is within the field of view (FOV = 8.75 degrees) of the telescope and above the limiting magnitude (V = +1.65) of the film. The effect of the starting population on the outcome of the simulation's discoveries is compared to the actual discoveries in order to define a most probable starting population

Mutations within the Primer Binding Site of the Human Immunodeficiency Virus Type 1 Define Sequence Requirements Essential for Reverse Transcription

AbstractThe primer binding site (PBS) is involved in two stages during the reverse transcription of the retroviral RNA genome. In the early stage, the PBS provides complementary sequences through which tRNALys,3binds the viral RNA genome to initiate minus-strand DNA synthesis; in the later stages, complementarity between the plus- and minus-strand copies of the PBS is required to facilitate the second template transfer needed to complete reverse transcription. We previously constructed a mutant HIV-1 proviral genome, designated as pHXB2PBS(pheC + 5) (now referred to as pheC + 5), which was used to identify regions of the PBS involved in the initiation and second template transfer steps of reverse transcription. To further define the sequence requirements of the PBS for the initiation of reverse transcription, we have made single nucleotide substitutions within the first six nucleotides of the pheC + 5 PBS. Our results demonstrate that mutations within the first five nucleotides of the PBS which disrupt base paring with tRNALys,3-PBS results in an noninfectious virus; a G-U base pair at position six of the tRNALys,3-PBS complex was tolerated. In contrast to the requirements for initiation, we found that complementary binding between only three base pairs of the plus- and minus-strand PBSs was required for the extension of plus-strand DNA during the second template transfer. Furthermore, regions of the minus-strand DNA of up to 24 nucleotides could be looped-out to facilitate the complementarity required for the completion of plus-strand DNA synthesis. Taken together, the results of our studies demonstrate that different features of the PBS with respect to RNA:RNA and DNA:DNA interactions are required for initiation of reverse transcription and the completion of plus-strand DNA synthesis, respectively

Positive allosteric modulators of the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor

L-glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS) and plays a fundamental role in the control of motor function, cognition and mood. The physiological effects of glutamate are mediated through two functionally distinct receptor families. While activation of metabotropic (G-protein coupled) glutamate receptors results in modulation of neuronal excitability and transmission, the ionotropic glutamate receptors (ligand-gated ion channels) are responsible for mediating the fast synaptic response to extracellular glutamate

Population response of triploid grass carp to declining levels of hydrilla in the Santee Cooper Reservoirs, South Carolina

Approximately 768,500 triploid grass carp ( Ctenopharyngodon idella Valenciennes) were stocked into the Santee Cooper reservoirs, South Carolina between 1989 and 1996 to control hydrilla ( Hydrilla verticillata (L.f.) Royle). Hydrilla coverage was reduced from a high of 17,272 ha during 1994 to a few ha by 1998. During 1997, 1998 and 1999, at least 98 triploid grass carp were collected yearly for population monitoring. Estimates of age, growth, and mortality, as well as population models, were used in the study to monitor triploid grass carp and predict population trends. Condition declined from that measured during a previous study in 1994. The annual mortality rate was estimated at 28% in 1997, 32% in 1998 and 39% in 1999; however, only the 1999 mortality rate was significantly different. Few (2 out of 98) of the triploid grass carp collected during 1999 were older than age 9. We expect increased mortality due to an aging population and sparse hydrilla coverage. During 1999, we estimated about 63,000 triploid grass carp system wide and project less than 3,000 fish by 2004, assuming no future stocking. management, population size Ctenopharyngodon idella, Hydrill