Increased adjuvant activity of minimal CD8 T cell peptides incorporated into lipid-core-peptides

A problem facing the use of subunit peptide and protein vaccines is their inability to stimulate protective immune responses. Many different approaches have been utilized to overcome this inefficient immune activation. The approach we have taken is to modify the vaccine antigen so that it now has adjuvant properties. To do this, multiple copies of minimal CD8 T cell epitopes were attached to a poly lysine lipid core. These constructs are known as lipid-core-peptides (LCP). The research presented here examines the adjuvant activity of LCP. Using mouse models, we were able to show that LCP were indeed able to activate antigen-presenting cells in vitro and to activate cytotoxic T-cell responses in vivo. More importantly, LCP were able to stimulate the development of a protective antitumour immune response.

CFD simulations of hydrocyclones with an air core - Comparison between large eddy simulations and a second moment closure

CFD simulations of the 75 mm, hydrocyclone of Hsieh (1988) have been conducted using Fluent TM. The simulations used 3-dimensional body fitted grids. The simulations were two phase simulations where the air core was resolved using the mixture (Manninen et al., 1996) and VOF (Hirt and Nichols, 1981) models. Velocity predictions from large eddy simulations (LES), using the Smagorinsky-Lilly sub grid scale model (Smagorinsky, 1963; Lilly, 1966) and RANS simulations using the differential Reynolds stress turbulence model (Launder et al., 1975) were compared with Hsieh's experimental velocity data. The LES simulations gave very good agreement with Hsieh's data but required very fine grids to predict the velocities correctly in the bottom of the apex. The DRSM/RANS simulations under predicted tangential velocities, and there was little difference between the velocity predictions using the linear (Launder, 1989) and quadratic (Speziale et al., 1991) pressure strain models. Velocity predictions using the DRSM turbulence model and the linear pressure strain model could be improved by adjusting the pressure strain model constants.

Stirring in 3-d spherical models of convection in the Earth's mantle

On a global scale basalts from mid-ocean ridges are strikingly more homogeneous than basalts from intraplate volcanism. The observed geochemical heterogeneity argues strongly for the existence of distinct reservoirs in the Earth's mantle. It is an unresolved problem of Geodynamics as to how these findings can be reconciled with large-scale convection. We review observational constraints, and investigate stirring properties of numerical models of mantle convection. Conditions in the early Earth may have supported layered convection with rapid stirring in the upper layers. Material that has been altered near the surface is transported downwards by small-scale convection. Thereby a layer of homogeneous depleted material develops above pristine mantle. As the mantle cools over Earth history, the effects leading to layering become reduced and models show the large-scale convection favoured for the Earth today. Laterally averaged, the upper mantle below the lithosphere is least affected by material that has experienced near-surface differentiation. The geochemical signature obtained during the previous episode of small-scale convection may be preserved there for the longest time. Additionally, stirring is less effective in the high viscosity layer of the central lower mantle [1, 2], supporting the survival of medium-scale heterogeneities there. These models are the first, using 3-d spherical geometry and mostly Earth-like parameters, to address the suggested change of convective style. Although the models are still far from reproducing our planet, we find that proposal might be helpful towards reconciling geochemical and geophysical constraints.

HRM in context:applicability of HRM models in India

Using the core aspects of five main models of human resource management (HRM), this article investigates the dominant HRM practices in the Indian manufacturing sector. The evaluation is conducted in the context of the recently liberalized economic environment. In response to ever-increasing levels of globalization of business, the article initially highlights the need for more cross-national comparative HRM research. Then it briefly analyzes the five models of HRM (namely, the `Matching model'; the `Harvard model'; the `Contextual model'; the `5-P model'; and the `European model') and identifies the main research questions emerging from these that could be used to reveal and highlight the HRM practices in different national/regional settings. The findings of the research are based on a questionnaire survey of 137 large Indian firms and 24 in-depth interviews in as many firms. The examination not only helped to present the scenario of HRM practices in the Indian context but also the logic dictating the presence of such practices. The article contributes to the fields of cross-national HRM and industrial relations research. It also has key messages for policy makers and opens avenues for further research.

Generic experiments at the sump model "Zittauer Strömungswanne" (ZSW) for the behaviour of mineral wool in the sump and the reactor core

The investigation of insulation debris transport, sedimentation, penetration into the reactor core and head loss build up becomes important to reactor safety research for PWR and BWR, when considering the long-term behaviour of emergency core cooling systems during loss of coolant accidents. Research projects are being performed in cooperation between the University of Applied Sciences Zittau/Görlitz and the Helmholtz-Zentrum Dresden-Rossendorf. The projects include experimental investigations of different processes and phenomena of insulation debris in coolant flow and the development of CFD models. Generic complex experiments serve for building up a data base for the validation of models for single effects and their coupling in CFD codes. This paper includes the description of the experimental facility for complex generic experiments (ZSW), an overview about experimental boundary conditions and results for upstream and down-stream phenomena as well as for the long-time behaviour due to corrosive processes. © Carl Hanser Verlag, München.

Have the GIPSI settled down? Breaks and multivariate stochastic volatility models for, and not against, the European financial integration

We investigate the integration of the European peripheral financial markets with Germany, France, and the UK using a combination of tests for structural breaks and return correlations derived from several multivariate stochastic volatility models. Our findings suggest that financial integration intensified in anticipation of the Euro, further strengthened by the EMU inception, and amplified in response to the 2007/2008 financial crisis. Hence, no evidence is found of decoupling of the equity markets in more troubled European countries from the core. Interestingly, the UK, despite staying outside the EMU, is not worse integrated with the GIPSI than Germany or France. © 2013 Elsevier B.V.

Verification and validation of numerical models of the transport of insulation debris

Damage to insulation materials located near to a primary circuit coolant leak may compromise the operation of the emergency core cooling system (ECCS). Insulation material in the form of mineral wool fiber agglomerates (MWFA) maybe transported to the containment sump strainers, where they may block or penetrate the strainers. Though the impact of MWFA on the pressure drop across the strainers is minimal, corrosion products formed over time may also accumulate in the fiber cakes on the strainers, which can lead to a significant increase in the strainer pressure drop and result in cavitation in the ECCS. An experimental and theoretical study performed by the Helmholtz-Zentrum Dresden-Rossendorf and the Hochschule Zittau/Görlitz is investigating the phenomena that maybe observed in the containment vessel during a primary circuit coolant leak. The study entails the generation of fiber agglomerates, the determination of their transport properties in single and multi-effect experiments and the long-term effect that corrosion and erosion of the containment internals by the coolant has on the strainer pressure drop. The focus of this paper is on the verification and validation of numerical models that can predict the transport of MWFA. A number of pseudo-continuous dispersed phases of spherical wetted agglomerates represent the MWFA. The size, density, the relative viscosity of the fluid-fiber agglomerate mixture and the turbulent dispersion all affect how the fiber agglomerates are transported. In the cases described here, the size is kept constant while the density is modified. This definition affects both the terminal velocity and volume fraction of the dispersed phases. Note that the relative viscosity is only significant at high concentrations. Three single effect experiments were used to provide validation data on the transport of the fiber agglomerates under conditions of sedimentation in quiescent fluid, sedimentation in a horizontal flow and suspension in a horizontal flow. The experiments were performed in a rectangular column for the quiescent fluid and a racetrack type channel that provided a near uniform horizontal flow. The numerical models of sedimentation in the column and the racetrack channel found that the sedimentation characteristics are consistent with the experiments. For channel suspension, the heavier fibers tend to accumulate at the channel base even at high velocities, while lighter phases are more likely to be transported around the channel.

Numerical models used for the modelling of the transport of fibrous insulation debris

Mineral wool insulation material applied to the primary cooling circuit of a nuclear reactor maybe damaged in the course of a loss of coolant accident (LOCA). The insulation material released by the leak may compromise the operation of the emergency core cooling system (ECCS), as it maybe transported together with the coolant in the form of mineral wool fiber agglomerates (MWFA) suspensions to the containment sump strainers, which are mounted at the inlet of the ECCS to keep any debris away from the emergency cooling pumps. In the further course of the LOCA, the MWFA may block or penetrate the strainers. In addition to the impact of MWFA on the pressure drop across the strainers, corrosion products formed over time may also accumulate in the fiber cakes on the strainers, which can lead to a significant increase in the strainer pressure drop and result in cavitation in the ECCS. Therefore, it is essential to understand the transport characteristics of the insulation materials in order to determine the long-term operability of nuclear reactors, which undergo LOCA. An experimental and theoretical study performed by the Helmholtz-Zentrum Dresden-Rossendorf and the Hochschule Zittau/Görlitz1 is investigating the phenomena that maybe observed in the containment vessel during a primary circuit coolant leak. The study entails the generation of fiber agglomerates, the determination of their transport properties in single and multi-effect experiments and the long-term effects that particles formed due to corrosion of metallic containment internals by the coolant medium have on the strainer pressure drop. The focus of this presentation is on the numerical models that are used to predict the transport of MWFA by CFD simulations. A number of pseudo-continuous dispersed phases of spherical wetted agglomerates can represent the MWFA. The size, density, the relative viscosity of the fluid-fiber agglomerate mixture and the turbulent dispersion all affect how the fiber agglomerates are transported. In the cases described here, the size is kept constant while the density is modified. This definition affects both the terminal velocity and volume fraction of the dispersed phases. Only one of the single effect experimental scenarios is described here that are used in validation of the numerical models. The scenario examines the suspension and horizontal transport of the fiber agglomerates in a racetrack type channel. The corresponding experiments will be described in an accompanying presentation (see abstract of Seeliger et al.).

Changing career models and capacity for innovation in professional services

A number of professional sectors have recently moved away from their longstanding career model of up-or-out promotion and embraced innovative alternatives. Professional labor is a critical resource in professional service firms. Therefore, changes to these internal labor markets are likely to trigger other innovations, for example in knowledge management, incentive schemes and team composition. In this chapter we look at how new career models affect the core organizing model of professional firms and, in turn, their capacity for and processes of innovation. We consider how professional firms link the development of human capital and the division of professional labor to distinctive demands for innovation and how novel career systems help them respond to these demands.

Testing competing HRM-performance linkage models:evidence from the Greek manufacturing sector

This paper proposes an integrative framework for the conduct of a more thorough and robust analysis regarding the linkage between Human Resource Management (HRM) and business performance. In order to provide the required basis for the proposed framework, initially, the core aspects of the main HRM models predicting business performance are analysed. The framework proposes both the principle of mediation (i.e. HRM outcomes mediate the relationship between organisational strategies and business performance) and the perspective of simultaneity of decision-making by firms with regard to the consideration of business strategies and HRM policies. In order to empirically test this framework the methodological approach of 'structural equation models' is employed. The empirical research is based on a sample of 178 organisations operating in the Greek manufacturing sector. The paper concludes that both the mediation principle and the simultaneity perspective are supported, emphasising further the positive role of HRM outcomes towards organisational performance.

Verification and validation of numerical models of the transport of insulation debris

A combination of the two-fluid and drift flux models have been used to model the transport of fibrous debris. This debris is generated during loss of coolant accidents in the primary circuit of pressurized or boiling water nuclear reactors, as high pressure steam or water jets can damage adjacent insulation materials including mineral wool blankets. Fibre agglomerates released from the mineral wools may reach the containment sump strainers, where they can accumulate and compromise the long-term operation of the emergency core cooling system. Single-effect experiments of sedimentation in a quiescent rectangular column and sedimentation in a horizontal flow are used to verify and validate this particular application of the multiphase numerical models. The utilization of both modeling approaches allows a number of pseudocontinuous dispersed phases of spherical wetted agglomerates to be modeled simultaneously. Key effects on the transport of the fibre agglomerates are particle size, density and turbulent dispersion, as well as the relative viscosity of the fluid-fibre mixture.

A hydrogen-bonded polar network in the core of the glucagon-like peptide-1 receptor is a fulcrum for biased agonism:lessons from class B crystal structuress

The glucagon-like peptide 1 (GLP-1) receptor is a class B G protein-coupled receptor (GPCR) that is a key target for treatments for type II diabetes and obesity. This receptor, like other class B GPCRs, displays biased agonism, though the physiologic significance of this is yet to be elucidated. Previous work has implicated R2.60190 , N3.43240 , Q7.49394 , and H6.52363 as key residues involved in peptide-mediated biased agonism, with R2.60190 , N3.43240 , and Q7.49394 predicted to form a polar interaction network. In this study, we used novel insight gained from recent crystal structures of the transmembrane domains of the glucagon and corticotropin releasing factor 1 (CRF1) receptors to develop improved models of the GLP-1 receptor that predict additional key molecular interactions with these amino acids. We have introduced E6.53364 A, N3.43240 Q, Q7.49493N, and N3.43240 Q/Q7.49 Q/Q7.49493N mutations to probe the role of predicted H-bonding and charge-charge interactions in driving cAMP, calcium, or extracellular signal-regulated kinase (ERK) signaling. A polar interaction between E6.53364 and R2.60190 was predicted to be important for GLP-1- and exendin-4-, but not oxyntomodulin-mediated cAMP formation and also ERK1/2 phosphorylation. In contrast, Q7.49394 , but not R2.60190 /E6.53364 was critical for calcium mobilization for all three peptides. Mutation of N3.43240 and Q7.49394 had differential effects on individual peptides, providing evidence for molecular differences in activation transition. Collectively, this work expands our understanding of peptide-mediated signaling from the GLP-1 receptor and the key role that the central polar network plays in these events.

Korrupció: mérhetőség és modellezés = In the core of our study we focus on the connection of Foreign Direct Investment and corruption.

Tanulmányunk középpontjában a közvetlen külföldi befektetések és a korrupció kapcsolata áll. Feltételezésünk az, hogy a közvetlen külföldi befektetők a kevésbé korrupt országokat kedvelik, mivel a korrupció egy további kockázati tényezőt jelent a befektetők számára, amely növelheti a befektetések költségeit. Megítélésünk szerint ezt kvantitatív módszerekkel lehet a leginkább vizsgálni, így elemzésünk során 79 országot vizsgálunk meg 10 évre vonatkozó átlagokkal a GRETL program és az OLS becslőfüggvény segítségével. Több modell lefuttatása után azt az eredményt kaptuk, hogy a közvetlen külföldi befektetők döntéseiben a korrupció szignifikáns tényező, a két változó között negatív korrelációt figyelhetünk meg. ____ We assume that investors prefer countries where corruption level is lower, as corruption an additional risk factor that might increase the cost of investment. We believe that the best way to prove the previous statement if we use quantitative methods, so we set up a model where 79 countries are tested for 10 years averages, with the help of the GRETL and OLS estimator. After running several models our finding was that corruption is a significant factor in the decisions of foreign investors, and there is a negative correlation between corruption and FDI.

Realization of Differentiated Quality of Service for Wideband Code Division Multiple Access Core Network

The development of 3G (the 3rd generation telecommunication) value-added services brings higher requirements of Quality of Service (QoS). Wideband Code Division Multiple Access (WCDMA) is one of three 3G standards, and enhancement of QoS for WCDMA Core Network (CN) becomes more and more important for users and carriers. The dissertation focuses on enhancement of QoS for WCDMA CN. The purpose is to realize the DiffServ (Differentiated Services) model of QoS for WCDMA CN. Based on the parallelism characteristic of Network Processors (NPs), the NP programming model is classified as Pool of Threads (POTs) and Hyper Task Chaining (HTC). In this study, an integrated programming model that combines both of the two models was designed. This model has highly efficient and flexible features, and also solves the problems of sharing conflicts and packet ordering. We used this model as the programming model to realize DiffServ QoS for WCDMA CN. ^ The realization mechanism of the DiffServ model mainly consists of buffer management, packet scheduling and packet classification algorithms based on NPs. First, we proposed an adaptive buffer management algorithm called Packet Adaptive Fair Dropping (PAFD), which takes into consideration of both fairness and throughput, and has smooth service curves. Then, an improved packet scheduling algorithm called Priority-based Weighted Fair Queuing (PWFQ) was introduced to ensure the fairness of packet scheduling and reduce queue time of data packets. At the same time, the delay and jitter are also maintained in a small range. Thirdly, a multi-dimensional packet classification algorithm called Classification Based on Network Processors (CBNPs) was designed. It effectively reduces the memory access and storage space, and provides less time and space complexity. ^ Lastly, an integrated hardware and software system of the DiffServ model of QoS for WCDMA CN was proposed. It was implemented on the NP IXP2400. According to the corresponding experiment results, the proposed system significantly enhanced QoS for WCDMA CN. It extensively improves consistent response time, display distortion and sound image synchronization, and thus increases network efficiency and saves network resource.^

Geochemistry and age models of sediments from the Celtic margin

The sedimentary sections of three cores from the Celtic margin provide high-resolution records of the terrigenous fluxes during the last glacial cycle. A total of 21 14C AMS dates allow us to define age models with a resolution better than 100 yr during critical periods such as Heinrich events 1 and 2. Maximum sedimentary fluxes occurred at the Meriadzek Terrace site during the Last Glacial Maximum (LGM). Detailed X-ray imagery of core MD95-2002 from the Meriadzek Terrace shows no sedimentary structures suggestive of either deposition from high-density turbidity currents or significant erosion. Two paroxysmal terrigenous flux episodes have been identified. The first occurred after the deposition of Heinrich event 2 Canadian ice-rafted debris (IRD) and includes IRD from European sources. We suggest that the second represents an episode of deposition from turbid plumes, which precedes IRD deposition associated with Heinrich event 1. At the end of marine isotopic stage 2 (MIS 2) and the beginning of MIS 1 the highest fluxes are recorded on the Whittard Ridge where they correspond to deposition from turbidity current overflows. Canadian icebergs have rafted debris at the Celtic margin during Heinrich events 1, 2, 4 and 5. The high-resolution records of Heinrich events 1 and 2 show that in both cases the arrival of the Canadian icebergs was preceded by a European ice rafting precursor event, which took place about 1-1.5 kyr before. Two rafting episodes of European IRD also occurred immediately after Heinrich event 2 and just before Heinrich event 1. The terrigenous fluxes recorded in core MD95-2002 during the LGM are the highest reported at hemipelagic sites from the northwestern European margin. The magnitude of the Canadian IRD fluxes at Meriadzek Terrace is similar to those from oceanic sites.