Trade policy issues in the Wider Europe – that led to war and not yet to peace. CEPS Working Document No. 398, July 2014

This paper looks at the trade policy landscape of the EU and the wider Europe, with a focus on issues arising from the signature on 27 June 2014 of Deep and Comprehensive Free Trade Agreements (DCFTAs) between the EU and three East European countries (Georgia, Moldova and Ukraine), and actual or prospective issues relating to the customs union of Belarus, Russia and Kazakhstan (BRK), and the Eurasian Economic Union whose founding treaty was signed on 29 May 2014. The huge expansion of intercontinental free trade area negotiations currently underway, in which the EU is an active participant alongside much of the Americas and Asia, stands in contrast with Russia’s choice to restrict itself to the Eurasian Economic Union, which is only a marginal extension of its own economy. Alone among the major economies in the world, Russia does not seek to integrate economically with any major economic bloc, which should be a matter of serious concern for Moscow. Within the wider Europe, the EU’s DCFTAs with Ukraine, Moldova and Georgia are a major new development, but Russia now threatens trade sanctions against Ukraine in particular, the economic case for which seems unfounded and whose unilateral application would also impair the customs union. The Belarus-Russia-Kazakhstan customs union itself poses several issues of compatibility with the rules of the WTO, which in turn are viewed by the EU as an impediment to discussing possible free trade scenarios with the customs union, although currently there are far more fundamental political impediments to any consideration of such ideas. Nonetheless, this paper looks at various long-term scenarios, if only as a reminder that there could be much better alternatives to the present context of conflict around Ukraine.

Helpless and lonely: Turkey's attitude towards the war in Syria. OSW Commentary No. 136, 09.05.2014

The conflict in Syria, which has lasted since 2011, has become the most significant test of the efficiency of Turkey’s foreign policy and the biggest challenge to Turkey’s security in recent decades. The lack of a clear prospect of an end to the war does not allow us to come to a final conclusion regarding the Syrian civil war’s importance for Turkey. However, it can be said today that with the exception of the initial phase of the conflict, Ankara’s influence over the course of events in Syria has been limited, and the war itself is evolving in a direction that is unfavourable for Turkey: the hostile regime of Bashar al-Assad is still in power, the opposition has proved to be an unreliable or even a dangerous ally, and in northern Syria militant jihadist groups and Kurds are gaining importance. It is also quite unlikely that the West will take any greater responsibility for stabilising the situation in the region. In response to such an unfortunate situation, and out of fear of risking deeper involvement in the conflict, during the past year Turkey’s policy towards Syria has been restrained, reactive and focused mainly on defending Turkey’s territory. However, this policy offers no security guarantees and does not prevent the country’s regional position from weakening, especially in the context of the reinforcement of the jihadist militants and the Kurdish autonomy in northern Syria. The arguments for Turkey continuing its defensive policy are strong: the country fears the possible results of an open confrontation with Assad’s forces; most probably it could not count on support for such actions from within its own society or its Western allies. It also does not have enough acceptance within the anti-Assad opposition circles. On the other hand, though, the risk of uncontrolled development of events is still present; the risk of confrontations with armed jihadist militants is growing; and the potential operation of Turkish forces, either against the jihadists or against Assad’s army, could be considered as a method of diverting attention from the political problems with which the AKP government has been struggling at home.

War Crimes and Shifting Borders in the Middle East. CEPS Essay No. 14, 11 September 2014

The summer of 2014 saw an explosion of violence in the Middle East: Israel delivered a sledgehammer blow against Gaza, Lebanon was again the scene of terrorist onslaught, and the relentless war in Syria pushed the numbers of casualties and displaced people to record highs. In terms of geopolitical change, however, the advance of the ‘Islamic State’ and the emergence of a de facto independent Iraqi Kurdistan are the most important recent developments in the region. Common to all these conflicts are the levels of barbarity involved in this struggle for a place in the region’s security order.

A quantitative reverse-transcriptase PCR assay for the assessment of drug activities against intracellular Theileria annulata schizonts.

Intracellular schizonts of the apicomplexans Theileria annulata and Theileria parva immortalize bovine leucocytes thereby causing fatal immunoproliferative diseases. Buparvaquone, a hydroxynaphthoquinone related to parvaquone, is the only drug available against Theileria. The drug is only effective at the onset of infection and emerging resistance underlines the need for identifying alternative compounds. Current drug assays employ monitoring of proliferation of infected cells, with apoptosis of the infected host cell as a read-out, but it is often unclear whether active compounds directly impair the viability of the parasite or primarily induce host cell death. We here report on the development of a quantitative reverse transcriptase real time PCR method based on two Theileria genes, tasp and tap104, which are both expressed in schizonts. Upon in vitro treatment of T. annulata infected bovine monocytes with buparvaquone, TaSP and Tap104 mRNA expression levels significantly decreased in relation to host cell actin already within 4 h of drug exposure, while significant differences in host cell proliferation were detectable only after 48-72 h. TEM revealed marked alterations of the schizont ultrastructure already after 2 h of buparvaquone treatment, while the host cell remained unaffected. Expression of TaSP and Tap104 proteins showed a marked decrease only after 24 h. Therefore, the analysis of expression levels of mRNA coding for TaSP and Tap104 allows to directly measuring impairment of parasite viability. We subsequently applied this method using a series of compounds affecting different targets in other apicomplexan parasites, and show that monitoring of TaSP- and Tap104 mRNA levels constitutes a suitable tool for anti-theilerial drug development.

Profound activity of the anti-cancer drug bortezomib against Echinococcus multilocularis metacestodes identifies the proteasome as a novel drug target for cestodes.

A library of 426 FDA-approved drugs was screened for in vitro activity against E. multilocularis metacestodes employing the phosphoglucose isomerase (PGI) assay. Initial screening at 20 µM revealed that 7 drugs induced considerable metacestode damage, and further dose-response studies revealed that bortezomib (BTZ), a proteasome inhibitor developed for the chemotherapy of myeloma, displayed high anti-metacestodal activity with an EC50 of 0.6 µM. BTZ treatment of E. multilocularis metacestodes led to an accumulation of ubiquinated proteins and unequivocally parasite death. In-gel zymography assays using E. multilocularis extracts demonstrated BTZ-mediated inhibition of protease activity in a band of approximately 23 kDa, the same size at which the proteasome subunit beta 5 of E. multilocularis could be detected by Western blot. Balb/c mice experimentally infected with E. multilocularis metacestodes were used to assess BTZ treatment, starting at 6 weeks post-infection by intraperitoneal injection of BTZ. This treatment led to reduced parasite weight, but to a degree that was not statistically significant, and it induced adverse effects such as diarrhea and neurological symptoms. In conclusion, the proteasome was identified as a drug target in E. multilocularis metacestodes that can be efficiently inhibited by BTZ in vitro. However, translation of these findings into in vivo efficacy requires further adjustments of treatment regimens using BTZ, or possibly other proteasome inhibitors.

Activities of fenbendazole in comparison with albendazole against Echinococcus multilocularis metacestodes in vitro and in a murine infection model.

The current chemotherapeutic treatment of alveolar echinococcosis (AE) in humans is based on albendazole and/or mebendazole. However, the costs of treatment, life-long consumption of drugs, parasitostatic rather than parasiticidal activity of chemotherapy, and high recurrence rates after treatment interruption warrant more efficient treatment options. Experimental treatment of mice infected with Echinococcus multilocularis metacestodes with fenbendazole revealed similar efficacy to albendazole. Inspection of parasite tissue from infected and benzimidazole-treated mice by transmission electron microscopy (TEM) demonstrated drug-induced alterations within the germinal layer of the parasites, and most notably an almost complete absence of microtriches. On the other hand, upon in vitro exposure of metacestodes to benzimidazoles, no phosphoglucose isomerase activity could be detected in medium supernatants during treatment with any of these drugs, indicating that in vitro treatment did not severely affect the viability of metacestode tissue. Corresponding TEM analysis also revealed a dramatic shortening/retraction of microtriches as a hallmark of benzimidazole action, and as a consequence separation of the acellular laminated layer from the cellular germinal layer. Since TEM did not reveal any microtubule-based structures within Echinococcus microtriches, this effect cannot be explained by the previously described mechanism of action of benzimidazoles targeting β-tubulin, thus benzimidazoles must interact with additional targets that have not been yet identified. In addition, these results indicate the potential usefulness of fenbendazole for the chemotherapy of AE.

Repurposing of antiparasitic drugs: the hydroxy-naphthoquinone buparvaquone inhibits vertical transmission in the pregnant neosporosis mouse model.

The three anti-malarial drugs artemiside, artemisone, and mefloquine, and the naphthoquinone buparvaquone known to be active against theileriosis in cattle and Leishmania infections in rodents, were assessed for activity against Neospora caninum infection. All four compounds inhibited the proliferation of N. caninum tachyzoites in vitro with IC50 in the sub-micromolar range, but artemisone and buparvaquone were most effective (IC50 = 3 and 4.9 nM, respectively). However, in a neosporosis mouse model for cerebral infection comprising Balb/c mice experimentally infected with the virulent isolate Nc-Spain7, the three anti-malarial compounds failed to exhibit any activity, since treatment did not reduce the parasite burden in brains and lungs compared to untreated controls. Thus, these compounds were not further evaluated in pregnant mice. On the other hand, buparvaquone, shown earlier to be effective in reducing the parasite load in the lungs in an acute neosporosis disease model, was further assessed in the pregnant mouse model. Buparvaquone efficiently inhibited vertical transmission in Balb/c mice experimentally infected at day 7 of pregnancy, reduced clinical signs in the pups, but had no effect on cerebral infection in the dams. This demonstrates proof-of-concept that drug repurposing may lead to the discovery of an effective compound against neosporosis that can protect offspring from vertical transmission and disease.

The case of the German Jews vs. Germany; a legal basis for the claims of the German Jews against Germany,

Bibliography: p. 119-124.

The war of Ormuzd and Ahriman in the nineteenth century.

The Holy alliance.--The conspiracy of Laybach and Verona.--The revolt of France and Poland against the holy conspirators.-- The revolt of Europe in 1848 against the holy conspirators. Germany.--The revolt in Europe in 1848 against the holy conspirators. Hungary.--The dictatorship of Russia in Europe.--The relations of American and English librty to the Russian dictatorship.--The American republic and the last war of freedom and despotism.

Britain's case against Germany; an examination of the historical background of the German action in 1914,

Mode of access: Internet.

Personal recollections and observations of General Nelson A. Miles, embracing a brief view of the Civil War; or, From New England to the Golden gate, and the story of his Indian campaigns, with comments on the exploration, development and progress of our great western empire;

A campaign against Apaches [1885-86] (Captain Maus' narrative): p. 450-471.

Adjudication of claims against Vietnam [microform] : hearing and markup before the Subcommittees on Asian and Pacific Affairs and on International Economic Policy and Trade of the Committee on Foreign Affairs, House of Representatives, Ninety-sixth Congress, first session, on H.R. 2200, July 27 and October 25, 1979.

Reuse of record except for individual research requires license from Congressional Information Service, Inc.

European War pamphlets

A collection of miscellaneous pamphlets on World War I.

The story of the Civil War; a concise account of the war in the United States of America between 1861 and 1865.

No more published?

European War pamphlets

A collection of miscellaneous pamphlets on World War I.