The dual specificity phosphatases M3/6 and MKP-3 are highly selective for inactivation of distinct mitogen-activated protein kinases

The mitogen-activated protein (MAP) kinase family includes extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) and p38/RK/CSBP (p38) as structurally and functionally distinct enzyme classes. Here we describe two new dual specificity phosphatases of the CL100/MKP-1 family that are selective for inactivating ERK or JNK/SAPK and p38 MAP kinases when expressed in COS-7 cells. M3/6 is the first phosphatase of this family to display highly specific inactivation of JNK/SAPK and p38 MAP kinases. Although stress-induced activation of p54 SAPKbeta, p46 SAPKgamma (JNK1) or p38 MAP kinases is abolished upon co-transfection with increasing amounts of M3/6 plasmid, epidermal growth factor-stimulated ERK1 is remarkably insensitive even to the highest levels of M3/6 expression obtained. In contrast to M3/6, the dual specificity phosphatase MKP-3 is selective for inactivation of ERK family MAP kinases. Low level expression of MKP-3 blocks totally epidermal growth factor-stimulated ERK1, whereas stress-induced activation of p54 SAPKbeta and p38 MAP kinases is inhibited only partially under identical conditions. Selective regulation by M3/6 and MKP-3 was also observed upon chronic MAP kinase activation by constitutive p21(ras) GTPases. Hence, although M3/6 expression effectively blocked p54 SAPKbeta activation by p21(rac) (G12V), ERK1 activated by p21(ras) (G12V) was insensitive to this phosphatase. ERK1 activation by oncogenic p21(ras) was, however, blocked totally by co-expression of MKP-3. This is the first report demonstrating reciprocally selective inhibition of different MAP kinases by two distinct dual specificity phosphatases.     

Value creation through project risk management

Risk management is a common and widely adopted project practice. Practitioners use risk management based on a common assumption that risk management adds value to projects. Yet, in the complex and ambiguous environment of a project, value is often subjective. If this is the case, then how do stakeholders perceive project risk management to create value? This paper presents a literature review and an empirical study of project risk management as a means of creating value. The empirical study is based on interviews, analyzed through qualitative analysis, to unravel the subjective value of project risk management. Specifically, we addressed how practitioners perceived the connection between project risk management practices and value creation. We found that stakeholders' perceptions of value played an important role in how value was created through project risk management. What a stakeholder perceives to be important, such as the prospective outcomes of a project, influences the perceived value of a given project risk management practice. The empirical findings indicate the need for a contextualized understanding of the value of project risk management, and thereby provide a more nuanced view of the variety of forms through which project risk management can create value. The findings question the “universal ideal” of PRM value creation portrayed in the academic and practitioner literature.     

Wear Performance of Dental Materials: A Comparison of Substructure Ceramics,Veneering Ceramics,and Non‐Precious Alloys

The aim of this in vitro study was to compare the two‐body wear resistance of different dental ceramics and non‐precious alloys. Two‐body wear tests were performed in a chewing simulator with steatite antagonists. A pin‐on‐block design with a vertical load of 50 N for 1.2 × 10⁵ cycles (f = 1.6 Hz; lateral movement: 1 mm, mouth opening: 2 mm) was used for the wear test. Surface roughness R_a (SP6, Perthen‐Feinprüf, G) and wear depth were determined using a 3D‐Profilometer (Laserscan 3D, Willytec, G). Scanning electron microscopy (Quanta FEG 400, FEI, NL) was applied for evaluating wear performance of both, materials and antagonists. Statistics: one‐way ANOVA (α = 0.05). The in vitro wear test showed that the wear performance of dental materials is strongly influenced by the type of material (ceramic, zirconia, or alloy). Zirconia and alloy provided low wear in contrast to glass‐ceramic systems. In contradiction to common expectations, hard zirconia and alloy systems showed even lower antagonistic wear than glass‐ceramics.     

Effects of the inhomogenous co doping on the magnetoresistance of Zn1-xCo(x)O epitaxial films

A series of Zn1-xCo(x)O epitaxial films around 100 nm with nominal Co concentration from 5% to 15% was prepared by ultra high vacuum (UHV) magnetron reactive sputtering. The optical, magnetic and magneto-transport properties of this series of Zn1-xCo(x)O epitaxial films were investigated, respectively. Resonant Raman spectra indicate the high structural and crystalline quality of these Zn1-xCo(x)O (5 < or = x < or = 15%) films, and confirm a consistent correlation between the substituting Co ions content with the Co doping concentration as well. Paramagnetism, superparamagnetism and ferromagnetism with altered Curie temperature from low temperatures to above room temperatures have been observed in these films by SQUID magnetometry. The broad blocking temperature range indicates the presence of inhomogenous distribution of the magnetic nano-clusters in the superparamagnetic films. However, the magneto-transport behaviors do not strongly respond to the change of the magnetic properties from paramagnetism to ferromagnetism of these Zn1-xCo(x)O films. The lack of efficient coupling between the inhomogenous magnetic nanoclusters and the carrier system in ferromagnetic Zn1-xCo(x)O films highlights the absence of the intrinsic magnetic origins in high structural quality Zn1-xCo(x)O (5 < or = x < or = 15%) epitaxial films. On the other hand, the competition between the spin alignments and the inhomogenous local disorder effect by magnetic ions is suggested to be responsible for the carrier properties and the oberseved magnetoresistance in these Co doping Zn1-xCo(x)O (5 < or = x < or = 15%) epitaxial films.     

Flow induced by ependymal cilia dominates near-wall cerebrospinal fluid dynamics in the lateral ventricles

While there is growing experimental evidence that cerebrospinal fluid (CSF) flow induced by the beating of ependymal cilia is an important factor for neuronal guidance, the respective contribution of vascular pulsation-driven macroscale oscillatory CSF flow remains unclear. This work uses computational fluid dynamics to elucidate the interplay between macroscale and cilia-induced CSF flows and their relative impact on near-wall dynamics. Physiological macroscale CSF dynamics are simulated in the ventricular space using subject-specific anatomy, wall motion and choroid plexus pulsations derived from magnetic resonance imaging. Near-wall flow is quantified in two subdomains selected from the right lateral ventricle, for which dynamic boundary conditions are extracted from the macroscale simulations. When cilia are neglected, CSF pulsation leads to periodic flow reversals along the ventricular surface, resulting in close to zero time-averaged force on the ventricle wall. The cilia promote more aligned wall shear stresses that are on average two orders of magnitude larger compared with those produced by macroscopic pulsatile flow. These findings indicate that CSF flow-mediated neuronal guidance is likely to be dominated by the action of the ependymal cilia in the lateral ventricles, whereas CSF dynamics in the centre regions of the ventricles is driven predominantly by wall motion and choroid plexus pulsation.     

Systemic aspects of R&D policy subsidies for R&D collaborations and their effects on private R&D

This paper analyses how context- and time-dependent factors determine the impact of R&D subsidies on firm behaviour with respect to private R&D expenditures. Based on German R&D survey data, we combine propensity score matching with a difference-in-difference estimator in order to measure the causal influence of public direct R&D project funding on firm behaviour. Our results indicate that (i) repeated participation in R&D projects on average leads to a higher increase in R&D expenditures than once-off funding; (ii) the aggregate effect of R&D funding on R&D expenditures of business firms is somewhat higher for business–business collaboration projects than for science–business collaboration projects; (iii) R&D expenditures of business firms that cooperate with science show a higher share of external R&D spending. Results of one particular cluster programme indicate that at least the short-term development of R&D does not so much depend on which programme direct R&D project funding is applied to.     

Science and technology in the region: The output of regional science and technology, its strengths and its leading institutions

Summary We operationalize scientific output in a region by means of the number of articles (as in the SciSearch database) per year and technology output by means of the number of patent applications (as in the database of the European Patent Office) per priority year. All informetric analyses were done using the DIALOG online-system. The main research questions are the following: Which scientific and technological fields or topics are most influent within a region and which institutions or companies are mainly publishing articles or holding patents? Do the distributions of regional science and technology fields and of publishing institutions follow the well-known informetric function? Are there - as it is expected - only few fields and few institutions which dominate the region? Is there a connection between the economic power of a region and the regional publication and patent output? Examples studied in detail are seven German regions: Aachen, D&uuml;sseldorf, Hamburg, K&ouml;ln (Cologne), Leipzig - Halle - Dessau, M&uuml;nchen (Munich), and Stuttgart. Three different indicators were used, science and technology attraction of a region (number of scientific articles and patents), science and technology intensity (articles and patents per 1,000 inhabitants), and science and technology density (articles and patents per 1 billion EURO gross value added). Top region concerning both attraction and intensity is Munich, concerning density it is Aachen.     

Negative Priming Effects in Children Engaged in Nonspatial Tasks: Evidence for Early Development of an Intact Inhibitory Mechanism.

Three experiments are reported that examined conceptual negative priming effects in children 5 to 12 years of age. Experiment 1 used a negative priming variant of a flanker task requiring the naming of a central color blob flanked by irrelevant distractors. Experiment 2 used a negative priming variant of the Stroop color-word task. Experiment 3 used a same-different matching task with novel 3-D shapes. Results revealed significant and equivalent magnitudes of negative priming across the tested age groups for all 3 tasks. It is concluded that the inhibitory mechanism underlying conceptual (i.e., identity or semantic) negative priming in visual selective attention tasks is intact in young children. Because the findings and conclusions diverge from the developmental literature on negative priming, the authors attempt to reconcile the contradictions by pinning down the reasons for the discrepancies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)