302 research outputs found
Gestionar contradicciones : los dilemas inherentes a la construcción posbélica del estado
Este documento es la traducciĂłn de un policy paper de Roland Paris y Timothy D. Sisk para la International Peace Academy (ahora, International Peace Institute, IPI). La publicaciĂłn original en inglĂ©s es: Managing Contradictions: The Inherent Dilemmas of Postwar Statebuilding. IPA Policy Papers. Nueva York: IPA, 11/2007.La construcciĂłn del estado se ha convertido en un asunto central de las operaciones multi-dimensionales de paz llevadas a cabo en sociedades devastadas por la guerra. Pero los esfuerzos para construir instituciones estatales legĂtimas y efectivas están repletos de tensiones y contradicciones. Entenderlas es esencial para poder anticipar muchos de los problemas prácticos a los que se enfrentan las agencias internacionales en el proceso de la construcciĂłn del estado, asĂ como para vislumbrar estrategias de construcciĂłn del estado mejor adaptadas y más efectivas de cara a misiones futuras
Advanced Materials Technologies / 3D Printing of Hierarchical Porous Silica and -Quartz
The ability to macroscopically shape highly porous oxide materials while concomitantly tailoring the porous network structure as desired by simple and environmentally friendly processes is of great importance in many fields. Here, a purely aqueous printing process toward deliberately shaped, hierarchically organized amorphous silica and the corresponding polycrystalline quartz analogues based on a direct ink writing process (DIW) is presented. The key to success is the careful development of the solgel ink, which is based on an acidic aqueous sol of a glycolated silane and structuredirecting agents. The resulting 3D (DIW) printed silica consists of a macroporous network of struts comprising hexagonally arranged mesopores on a 2D hexagonal lattice. Together with a printed porous superstructure on the millimeter scale, welldefined pore sizes and shapes on at least three hierarchy levels can thus be fabricated. The introduction of devitrifying agents in the printed green part and subsequent heat treatment allows for the transformation of the silica structure into polycrystalline quartz. While small pores (micro and mesopores below 10 nm) are lost, the printed morphology and the macroporous network of struts is preserved during crystallization.1605N20(VLID)266643
Alzheimer's Risk Gene TREM2 Determines Functional Properties of New Type of Human iPSC-Derived Microglia
Microglia are key in the homeostatic well-being of the brain and microglial dysfunction has been implicated in neurodegenerative disorders such as Alzheimer's disease (AD). Due to the many limitations to study microglia in situ or isolated for large scale drug discovery applications, there is a high need to develop robust and scalable human cellular models of microglia with reliable translatability to the disease. Here, we describe the generation of microglia-like cells from human induced pluripotent stem cells (iPSC) with distinct phenotypes for mechanistic studies in AD. We started out from an established differentiation protocol to generate primitive macrophage precursors mimicking the yolk sac ontogeny of microglia. Subsequently, we tested 36 differentiation conditions for the cells in monoculture where we exposed them to various combinations of media, morphogens, and extracellular matrices. The optimized protocol generated robustly ramified cells expressing key microglial markers. Bulk mRNA sequencing expression profiles revealed that compared to cells obtained in co-culture with neurons, microglia-like cells derived from a monoculture condition upregulate mRNA levels for Triggering Receptor Expressed On Myeloid Cells 2 (TREM2), which is reminiscent to the previously described disease-associated microglia. TREM2 is a risk gene for AD and an important regulator of microglia. The regulatory function of TREM2 in these cells was confirmed by comparing wild type with isogenic TREM2 knock-out iPSC microglia. The TREM2-deficient cells presented with stronger increase in free cytosolic calcium upon stimulation with ATP and ADP, as well as stronger migration towards complement C5a, compared to TREM2 expressing cells. The functional differences were associated with gene expression modulation of key regulators of microglia. In conclusion, we have established and validated a work stream to generate functional human iPSC-derived microglia-like cells by applying a directed and neuronal co-culture independent differentiation towards functional phenotypes in the context of AD. These cells can now be applied to study AD-related disease settings and to perform compound screening and testing for drug discoverySG was supported by the Roche Postdoctoral Fellowship (RPF) program and IP by the Roche Internships for Scientific Exchange (RiSE) progra
Recommended from our members
The Internal-External Security Nexus and EU Police/Rule of Law Missions in the Western Balkans
Common Security and Defence Policy (CSDP) police/rule of law missions in the Western Balkans are increasingly guided by externally imposed normative agendas that respond primarily to EU internal security needs rather than functional imperatives or local realities. In line with these needs, EU police reform efforts tend to prioritise effectiveness and crime fighting over longer- term democratic policing and good governance reforms. In practice this means that police reform initiatives are technocratically oriented, yet value ridden fitting EU security concerns and needs. As a result, the police reform process can be—and often is—disconnected from the political and socio-economic reforms necessary for long-term stability and sustainable peace. Police assistance in Bosnia and Herzegovina has been shaped by a determined albeit questionable focus on organised crime and corruption. The focus of EU police reform in Macedonia on primarily crime-fighting aspects of policing has compromised the functioning of the Macedonian police. Similarly, the politics of (non-)recognition of Kosovo's self-proclaimed independence and the intrusiveness of EULEX Kosovo's executive mandate contravene meeting local challenges
Recommended from our members
The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: Baryon Acoustic Oscillations in the Data Release 9 Spectroscopic Galaxy Sample
We present measurements of galaxy clustering from the Baryon Oscillation
Spectroscopic Survey (BOSS), which is part of the Sloan Digital Sky Survey III
(SDSS-III). These use the Data Release 9 (DR9) CMASS sample, which contains
264,283 massive galaxies covering 3275 square degrees with an effective
redshift z=0.57 and redshift range 0.43 < z < 0.7. Assuming a concordance
Lambda-CDM cosmological model, this sample covers an effective volume of 2.2
Gpc^3, and represents the largest sample of the Universe ever surveyed at this
density, n = 3 x 10^-4 h^-3 Mpc^3. We measure the angle-averaged galaxy
correlation function and power spectrum, including density-field reconstruction
of the baryon acoustic oscillation (BAO) feature. The acoustic features are
detected at a significance of 5\sigma in both the correlation function and
power spectrum. Combining with the SDSS-II Luminous Red Galaxy Sample, the
detection significance increases to 6.7\sigma. Fitting for the position of the
acoustic features measures the distance to z=0.57 relative to the sound horizon
DV /rs = 13.67 +/- 0.22 at z=0.57. Assuming a fiducial sound horizon of 153.19
Mpc, which matches cosmic microwave background constraints, this corresponds to
a distance DV(z=0.57) = 2094 +/- 34 Mpc. At 1.7 per cent, this is the most
precise distance constraint ever obtained from a galaxy survey. We place this
result alongside previous BAO measurements in a cosmological distance ladder
and find excellent agreement with the current supernova measurements. We use
these distance measurements to constrain various cosmological models, finding
continuing support for a flat Universe with a cosmological constant.Comment: 33 page
Recommended from our members
UN Peace operations and conflicting legitimacies
Analyses of UN peacekeeping increasingly consider legitimacy a key factor for success, conceiving of it as a resource that operations should seek and use in the pursuit of their goals. However, these analyses rarely break down legitimacy by source. Because the UN is an organization with multiple identities and duties however, different legitimacy sources—in particular output and procedural legitimacy—and the UN’s corresponding legitimation practices come into conflict in the context of peacekeeping. Drawing on a range of examples and a specific case of the UN mission in Congo, this article argues that looking at different legitimacy sources and linking them to the institutional identity of the UN is thus critical and it shows how the UN’s in contradictory legitimation practices can reduce overall legitimacy perceptions
Nucleotide Binding Switches the Information Flow in Ras GTPases
The Ras superfamily comprises many guanine nucleotide-binding proteins (G proteins) that are essential to intracellular signal transduction. The guanine nucleotide-dependent intrinsic flexibility patterns of five G proteins were investigated in atomic detail through Molecular Dynamics simulations of the GDP- and GTP-bound states (SGDP and SGTP, respectively). For all the considered systems, the intrinsic flexibility of SGDP was higher than that of SGTP, suggesting that Guanine Exchange Factor (GEF) recognition and nucleotide switch require higher amplitude motions than effector recognition or GTP hydrolysis. Functional mode, dynamic domain, and interaction energy correlation analyses highlighted significant differences in the dynamics of small G proteins and Gα proteins, especially in the inactive state. Indeed, SGDP of Gαt, is characterized by a more extensive energy coupling between nucleotide binding site and distal regions involved in GEF recognition compared to small G proteins, which attenuates in the active state. Moreover, mechanically distinct domains implicated in nucleotide switch could be detected in the presence of GDP but not in the presence of GTP. Finally, in small G proteins, functional modes are more detectable in the inactive state than in the active one and involve changes in solvent exposure of two highly conserved amino acids in switches I and II involved in GEF recognition. The average solvent exposure of these amino acids correlates in turn with the rate of GDP release, suggesting for them either direct or indirect roles in the process of nucleotide switch. Collectively, nucleotide binding changes the information flow through the conserved Ras-like domain, where GDP enhances the flexibility of mechanically distinct portions involved in nucleotide switch, and favors long distance allosteric communication (in Gα proteins), compared to GTP
Tectonic history of northern New Caledonia Basin from deep offshore seismic reflection: Relation to late Eocene obduction in New Caledonia, southwest Pacific
International audienceNew, high-quality multichannel seismic reflection data from the western New Caledonia offshore domain allow for the first time the direct, continuous connection of seismic reflectors between the Deep Sea Drilling Project 208 drill hole on the Lord Howe Rise and the New Caledonia Basin. A novel seismic interpretation is hence proposed for the northern New Caledonia Basin stratigraphy, which places the Eocene/Oligocene unconformity deeper than previously thought and revisits the actual thickness of the pre-Oligocene sequences. A causal link is proposed between the obduction of the South Loyalty Basin over New Caledonia (NC) and the tectonic history of the northern New Caledonia Basin. Here it is suggested that as the South Loyalty Basin was being obducted during early Oligocene times, the NC Basin subsided under the effect of the overloading and underthrusted to accommodate the compressional deformation, which resulted in (1) the uplift of the northern Fairway Ridge and (2) the sinking of the western flank of New Caledonia. This event also had repercussions farther west with the incipient subsidence of the Lord Howe Rise
- …