288 research outputs found
The epistemological challenge of truth-subversion to the Liberal International Order
Truth-subversion practices, which populist leaders utilize for political domination, are a significant source of current pressure on the Liberal International Order (LIO). Truth-subversion practices include false speak (flagrant lying to subvert the concept of facts), double speak (intentional internal contradictions in speech to erode reason), and flooding (the emission of many messages into the public domain to create confusion). Aiming to destroy liberal truth ideals and practices, truth subversion weakens epistemological security; that is, the experience of orderliness and safety that results from people's and institutionsâ shared understandings of their common-sense reality. It privileges baseless claims over fact-based opinions, thus creating communities of the like-minded between which communication becomes impossible. Truth subversion challenges the LIO's three key institutions: democracy, markets, and multilateralism. If truth-subversion practices prevail, societal polarization, inaccurate information, and emotional inflaming strain democracy and human rights protections. Markets that depend for their functioning on accurate information can falter, and multilateralism that relies on communication and reasoned consensus can decay. International relations (IR) scholarship has recognized knowledge production practices as a key feature underlying the LIO, but has not yet identified challenges to those practices as a threat for the LIO. We discuss what the discipline can do to alleviate its blind spots
Conclusion: Epistemic communities, world order, and the creation of a reflective research program
Este artĂculo se extrae de la revista International Organization, vol. 46, nÂș 1, Knowledge, Power and International Policy Coordination, invierno 1992, ps. 367-390 y ha sido traducido con
permiso de la editorial MIT PressLas Relaciones Internacionales carecen de una teorĂa y un juego de explicaciones creĂble sobre el origen de las instituciones internacionales, los intereses estatales y el comportamiento de los estados en condiciones de incertidumbre. En este volumen no sĂłlo desarrollamos âestudios particulares que (âŠ) pueden iluminar asuntos importantes en la polĂtica internacional,â sino que tambiĂ©n ofrecemos un programa de investigaciĂłn mediante el cual los estudiantes de polĂtica internacional pueden estudiar de modo empĂrico el papel de las ideas en las relaciones internacionalesAccording to this research program, international relations can be seen as an evolutionary process in which epistemic communities play meaningful roles as sources of policy innovation, channels by which these innovations diffuse internationally, and catalysts in the political and institutional processes leading to the selection of their shared goals. International cooperation and, indeed, the development of new world orders based on common meanings and understandings may thus depend on the extent to which nation-states apply their power on behalf of practices that epistemic communities may have helped create, diffuse, and perpetuat
PrĂĄcticas internacionales
En este artĂculo se aborda la polĂtica mundial a travĂ©s de los lentes de sus diversas prĂĄcticas, que son definidas como actuaciones competentes. Estudiar Relaciones Internacionales (RI) desde la perspectiva de las prĂĄcticas internacionales promete tres avances clave. El primero implica que se puede entender la teorĂa de las RI y la polĂtica internacional mejor o de forma diferente. La polĂtica mundial puede ser concebida como estructurada por prĂĄcticas, las que dan significados a las acciones internacionales, hacen posible la interacciĂłn estratĂ©gica, y son reproducidas, cambiadas y reforzadas por las acciones e interacciones internacionales. Este enfoque ayuda a expandir la ontologĂa de la polĂtica mundial, sirve como punto focal sobre el cual estructurar los debates de la teorĂa de RI, y puede ser usado como unidad de anĂĄlisis que transciende el entendimiento tradicional de los niveles de anĂĄlisis. Se ilustra quĂ© es una prĂĄctica internacional revisando el trabajo seminal de Thomas Schelling sobre negociaciones. El segundo avance, con la ayuda de ilustraciones sobre prĂĄcticas de disuasiĂłn y control de armas durante la Guerra FrĂa y la pos-Guerra FrĂa, tales como seguridad cooperativa, muestra como las prĂĄcticas constituyen interacciĂłn estratĂ©gica y negociaciĂłn de modo mĂĄs general. Finalmente, desde la perspectiva de las prĂĄcticas se abre el camino a una innovadora y apasionante agenda de investigaciĂłn que sugiere nuevas preguntas y puzzles, y lleva a revisar conceptos centrales de la disciplina, como el poder, la historia y la estrategi
Water vapor and the dynamics of climate changes
Water vapor is not only Earth's dominant greenhouse gas. Through the release
of latent heat when it condenses, it also plays an active role in dynamic
processes that shape the global circulation of the atmosphere and thus climate.
Here we present an overview of how latent heat release affects atmosphere
dynamics in a broad range of climates, ranging from extremely cold to extremely
warm. Contrary to widely held beliefs, atmospheric circulation statistics can
change non-monotonically with global-mean surface temperature, in part because
of dynamic effects of water vapor. For example, the strengths of the tropical
Hadley circulation and of zonally asymmetric tropical circulations, as well as
the kinetic energy of extratropical baroclinic eddies, can be lower than they
presently are both in much warmer climates and in much colder climates. We
discuss how latent heat release is implicated in such circulation changes,
particularly through its effect on the atmospheric static stability, and we
illustrate the circulation changes through simulations with an idealized
general circulation model. This allows us to explore a continuum of climates,
constrain macroscopic laws governing this climatic continuum, and place past
and possible future climate changes in a broader context.Comment: 22 pages, 11 figure
Key factors in simulating the equatorial Atlantic zonal sea surface temperature gradient in a coupled general circulation model
Causes of the coupled model bias in simulating the zonal sea surface temperature (SST) gradient in the equatorial Atlantic are examined in three versions of the same coupled general circulation model (CGCM) differing only in the cumulus convection scheme. One version of the CGCM successfully simulates the mean zonal SST gradient of the equatorial Atlantic, in contrast to the failure of the Coupled Model Intercomparison Project phase 3 models. The present analysis shows that key factors to be successful are high skills in simulating the meridional location of the Intertropical Convergence Zone, the precipitation over northern South America, and the southerly winds along the west coast of Africa associated with the West African monsoon in boreal spring. Model biases in the Pacific contribute to the weaker precipitation over northern South America. Uncoupled experiments with the atmospheric component further confirm the importance of remote influences on the development of the equatorial Atlantic bias.
Key Points:
The zonal SST gradient of the equatorial Atlantic is well simulated in a CGCM;
Key factors for the realistic simulation of the Atlantic SST are presented;
Remote forcing from the Pacific may contribute to the Atlantic SST bia
In vitro and in vivo effects of Pelargonium sidoides DC. root extract EPsÂź 7630 and selected constituents against SARS-CoV-2 B.1, Delta AY.4/AY.117 and Omicron BA.2
The occurrence of immune-evasive SARS-CoV-2 strains emphasizes the importance to search for broad-acting antiviral compounds. Our previous in vitro study showed that Pelargonium sidoides DC. root extract EPsÂź 7630 has combined antiviral and immunomodulatory properties in SARS-CoV-2-infected human lung cells. Here we assessed in vivo effects of EPsÂź 7630 in SARS-CoV-2-infected hamsters, and investigated properties of EPsÂź 7630 and its functionally relevant constituents in context of phenotypically distinct SARS-CoV-2 variants. We show that EPsÂź 7630 reduced viral load early in the course of infection and displayed significant immunomodulatory properties positively modulating disease progression in hamsters. In addition, we find that EPsÂź 7630 differentially inhibits SARS-CoV-2 variants in nasal and bronchial human airway epithelial cells. Antiviral effects were more pronounced against Omicron BA.2 compared to B.1 and Delta, the latter two preferring TMPRSS2-mediated fusion with the plasma membrane for cell entry instead of receptor-mediated low pH-dependent endocytosis. By using SARS-CoV-2 Spike VSV-based pseudo particles (VSVpp), we confirm higher EPsÂź 7630 activity against Omicron Spike-VSVpp, which seems independent of the serine protease TMPRSS2, suggesting that EPsÂź 7630 targets endosomal entry. We identify at least two molecular constituents of EPsÂź 7630, i.e., (â)-epigallocatechin and taxifolin with antiviral effects on SARS-CoV-2 replication and cell entry. In summary, our study shows that EPsÂź 7630 ameliorates disease outcome in SARS-CoV-2-infected hamsters and has enhanced activity against Omicron, apparently by limiting late endosomal SARS-CoV-2 entry
Protective role of the HSP90 inhibitor, STA-9090, in lungs of SARS-CoV-2-infected Syrian golden hamsters
Introduction The emergence of new SARS-CoV-2 variants, capable of escaping the humoral immunity acquired by the available vaccines, together with waning immunity and vaccine hesitancy, challenges the efficacy of the vaccination strategy in fighting COVID-19. Improved therapeutic strategies are urgently needed to better intervene particularly in severe cases of the disease. They should aim at controlling the hyperinflammatory state generated on infection, reducing lung tissue pathology and inhibiting viral replication. Previous research has pointed to a possible role for the chaperone HSP90 in SARS-CoV-2 replication and COVID-19 pathogenesis. Pharmacological intervention through HSP90 inhibitors was shown to be beneficial in the treatment of inflammatory diseases, infections and reducing replication of diverse viruses.
Methods In this study, we investigated the effects of the potent HSP90 inhibitor Ganetespib (STA-9090) in vitro on alveolar epithelial cells and alveolar macrophages to characterise its effects on cell activation and viral replication. Additionally, the Syrian hamster animal model was used to evaluate its efficacy in controlling systemic inflammation and viral burden after infection.
Results In vitro, STA-9090 reduced viral replication on alveolar epithelial cells in a dose-dependent manner and lowered significantly the expression of proinflammatory genes, in both alveolar epithelial cells and alveolar macrophages. In vivo, although no reduction in viral load was observed, administration of STA-9090 led to an overall improvement of the clinical condition of infected animals, with reduced oedema formation and lung tissue pathology.
Conclusion Altogether, we show that HSP90 inhibition could serve as a potential treatment option for moderate and severe cases of COVID-19
Phase 1-2a multicenter dose-escalation study of ezatiostat hydrochloride liposomes for injection (TelintraÂź, TLK199), a novel glutathione analog prodrug in patients with myelodysplastic syndrome
<p>Abstract</p> <p>Background</p> <p>Ezatiostat hydrochloride liposomes for injection, a glutathione S-transferase P1-1 inhibitor, was evaluated in myelodysplastic syndrome (MDS). The objectives were to determine the safety, pharmacokinetics, and hematologic improvement (HI) rate. Phase 1-2a testing of ezatiostat for the treatment of MDS was conducted in a multidose-escalation, multicenter study. Phase 1 patients received ezatiostat at 5 dose levels (50, 100, 200, 400 and 600 mg/m<sup>2</sup>) intravenously (IV) on days 1 to 5 of a 14-day cycle until MDS progression or unacceptable toxicity. In phase 2, ezatiostat was administered on 2 dose schedules: 600 mg/m<sup>2 </sup>IV on days 1 to 5 or days 1 to 3 of a 21-day treatment cycle.</p> <p>Results</p> <p>54 patients with histologically confirmed MDS were enrolled. The most common adverse events were grade 1 or 2, respectively, chills (11%, 9%), back pain (15%, 2%), flushing (19%, 0%), nausea (15%, 0%), bone pain (6%, 6%), fatigue (0%, 13%), extremity pain (7%, 4%), dyspnea (9%, 4%), and diarrhea (7%, 4%) related to acute infusional hypersensitivity reactions. The concentration of the primary active metabolites increased proportionate to ezatiostat dosage. Trilineage responses were observed in 4 of 16 patients (25%) with trilineage cytopenia. Hematologic Improvement-Erythroid (HI-E) was observed in 9 of 38 patients (24%), HI-Neutrophil in 11 of 26 patients (42%) and HI-Platelet in 12 of 24 patients (50%). These responses were accompanied by improvement in clinical symptoms and reductions in transfusion requirements. Improvement in bone marrow maturation and cellularity was also observed.</p> <p>Conclusion</p> <p>Phase 2 studies of ezatiostat hydrochloride liposomes for injection in MDS are supported by the tolerability and HI responses observed. An oral formulation of ezatiostat hydrochloride tablets is also in phase 2 clinical development.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov: NCT00035867</p
A modeling study of the response of Asian summertime climate to the largest geologic forcings of the past 50Â Ma
The modern Asian summer monsoon is known to be affected by the modern continental geometry, orography, atmospheric composition, interglacial climate state, and orbital configuration. All of these factors, however, have undergone substantial changes since the Indian and Asian continents collided 50 million years ago. Within the framework of one general circulation model we evaluate the relative importance of each of these factors for the spatial patterns of summertime climate fields and precipitationâweighted 18O. We find that the continentalâscale structure of the monsoon circulation remains robust, but there are important impacts on local environmental conditions. The largest differences in climate are associated with changes in orbital configuration and topography because of how those factors influence local gradients in the summer climate variables. Finally, model calculations are consistent with the modern understanding of monsoon dynamics in which the strength of the circulation and the distribution of rainfall are tightly coupled to the spatial patterns of lowâlevel moist static energy and upper tropospheric temperature.Key PointsGeological changes in the Cenozoic have changed summertime climate in AsiaThe continentalâscale structure of the summer monsoon circulation remains robustLarge local climate changes occur, with insolation and local topography having the largest impactsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/122412/1/jgrd52906.pd
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