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This paper by the Coordinator of the Kamanakao Association reflects upon the Association’s campaign against tribally discriminatory laws, against the social stigma of past serfdom, and for human rights and democracy in Botswana. The campaign made Wayeyi from the North West District highly visible on the national scene. Through litigation up to the High Court, the Kamanakao Association broke new ground for judicial review in the broad public interest. The advance was for the cultural rights of ‘minorities’ in general, and not only in the interest of the Wayeyi. The most favourable High Court ruling recognised Yei cultural distinctness, allowed them to secede from the tribe of their past overlords, the Tawana, and concluded a landmark case in the wider fight against state-backed tribal discrimination and denial of language rights. As an insider’s account mainly about recent events, but seen in a perspective extending to precolonial times, the paper focuses on strategies for and against change. These are the strategies effecting the power relations, in turn, between the Yeyi and the Tawana, former serfs and overlords, the Yeyi and the Government, and the Government and the Tswana speaking tribes unfairly privileged by the tribally discriminatory laws.
The potential use of variola virus, the causative agent of smallpox, as a bioweapon and the endemic presence of monkeypox virus in Africa demonstrate the need for better therapies for orthopoxvirus infections. Chemotherapeutic approaches to control viral infections have been less successful than those targeting bacterial infections. While bacteria commonly reproduce themselves outside of cells and have metabolic functions against which antibiotics can be directed, viruses replicate in the host cells using the cells' metabolic pathways. This makes it very difficult to selectively target the virus without damaging the host. Therefore, the development of antiviral drugs against poxviruses has initially focused on unique properties of the viral replication cycle or of viral proteins that can be selectively targeted. However, recent advances in molecular biology have provided insights into host factors that represent novel drug targets. The latest anti-poxvirus drugs are kinase inhibitors, which were originally developed to treat cancer progression but in addition block egress of poxviruses from infected cells. This review will summarize the current understanding of anti-poxvirus drugs and will give an overview of the development of the latest second generation poxvirus drugs.
Tracing recent bouts of globalised Mugabephobia to Robert Mugabes refusal to be neoimperially penetrated, this book juxtaposes economic liberalisation with the mounting liberalisation of African orifices. Reading land repossession and economic structural adjustment programmes together with what they call neoimperial structural adjustment of African orifices, the authors argue that there has been liberalisation of African orifices in a context where Africans are ironically prevented from repossessing their material resources. Juxtaposing recent bouts of Mugabephobia with discourses on homophobia, the book asks why empire prefers liberalising African orifices rather than attending to African demands for restitution, restoration and reparations. Noting that empire opposes African sovereignty, autonomy, and centralisation of power while paradoxically promoting transnational corporations centralisation of power over African economies, the book challenges contemporary discourses about shared sovereignty, distributed governance, heterarchy, heteronomy and onticology. Arguing that colonialists similarly denied Africans of their human essence, the tome problematises queer sexualities, homosexuality, ecosexuality, cybersexuality and humanoid robotic sexuality all of which complicate supposedly fundamental distinctions between human beings and animals and machines. Provocatively questioning queer sexuality and liberalised orifices that serve to divert African attention from the more serious unfinished business of repossessing material resources, the book insightfully compares Robert Gabriel Mugabe, Thomas Sankara and Julius Kambarage Nyerere who emphasised the imperatives of African autonomy, ownership, control and sovereignty over natural resources. Observing Africans interest in repossessing ownership and control over their resources, the book wonders why so much, queer, international attention is focused on foisting queer sexuality while downplaying more burning issues of resource repossession, human dignity, equality and equity craved by Africans for whom life is not confined to sexuality. With insights for scholars in sociology, development studies, law, politics, African studies, anthropology, transformation, decolonisation and decoloniality, the book argues that liberal democracy is a façade in a world that is actually ruled through criminocracy.
From Antagonism to Re-engagement : Zimbabwe's Trade Negotiations with the European Union, 2000-2016
(2017)
The book interrogates the European Union (EU) - Zimbabwe Economic Partnership Agreement (EPA) negotiations, covering trade in goods, trade-related rules and development cooperation. The negotiations coincided with EUs motives as the dominant development partner, and Zimbabwes state-stakeholder fault-lines, creating dilemmas in the pursuit of a fair EPA outcome. As a result, the economically weak Zimbabwe signed and ratified an asymmetrical interim EPA (iEPA) with an economically powerful EU in 2009 and 2012, respectively. Meanwhile, direct bilateral re-engagement which eluded the Government of National Unity (GNU), became real following ZANU-PF landslide victory on 31 July 2013, that sufficiently altered the power balance to trigger the process between the former nemesis in support of iEPA domestication, and social and economic development. ZANU-PF government stopped blaming the EU and other western nations for the countrys continued economic under-performance, signaling a softening approach on its part. Similarly, the EU and its member states softened its perception on ZANU-PF leadership leading to resumption and intensification of re-engagement despite failure to implement the Global Political Agreement-related constitutional and democratic reforms, agreed by GNU. This re-engagement was firmly endorsed when the EU and Zimbabwe signed an agreement in July 2015 to normalise bilateral relations and start cooperation.
Therapeutic oligonucleotides interact with a target RNA via Watson-Crick complementarity, affecting RNA-processing reactions such as mRNA degradation, pre-mRNA splicing, or mRNA translation. Since they were proposed decades ago, several have been approved for clinical use to correct genetic mutations. Three types of mechanisms of action (MoA) have emerged: RNase H-dependent degradation of mRNA directed by short chimeric antisense oligonucleotides (gapmers), correction of splicing defects via splice-modulation oligonucleotides, and interference of gene expression via short interfering RNAs (siRNAs). These antisense-based mechanisms can tackle several genetic disorders in a gene-specific manner, primarily by gene downregulation (gapmers and siRNAs) or splicing defects correction (exon-skipping oligos). Still, the challenge remains for the repair at the single-nucleotide level. The emerging field of epitranscriptomics and RNA modifications shows the enormous possibilities for recoding the transcriptome and repairing genetic mutations with high specificity while harnessing endogenously expressed RNA processing machinery. Some of these techniques have been proposed as alternatives to CRISPR-based technologies, where the exogenous gene-editing machinery needs to be delivered and expressed in the human cells to generate permanent (DNA) changes with unknown consequences. Here, we review the current FDA-approved antisense MoA (emphasizing some enabling technologies that contributed to their success) and three novel modalities based on post-transcriptional RNA modifications with therapeutic potential, including ADAR (Adenosine deaminases acting on RNA)-mediated RNA editing, targeted pseudouridylation, and 2′-O-methylation.
From Arthouse to Grindhouse - and back? : Wechselbeziehungen zwischen Hoch- und Populärkultur
(2011)
Bericht zur Tagung 'From Arthouse to Grindhouse - and back? Wechselbeziehungen zwischen Hoch- und Populärkultur', Abteilung für Vergleichende Literaturwissenschaft der Universität Wien, Societa - Forum für Ethik, Kunst und Recht, Filmarchiv Austria, 5. bis 7. Mai 2011
Die von Keyvan Sarkhosh (Wien) und Paul Ferstl (Wien) organisierte Tagung, die im Studiokino des Filmarchivs Austria stattfand, widmete sich in dreizehn Vorträgen diesen komplexen, sprach- und medienübergreifenden Wechselbeziehungen von 'Arthouse' und 'Grindhouse' und verband die inhaltliche Thematik mit dem methodischen Ziel einer verstärkten Theoretisierung bei der Betrachtung populärkultureller Phänomene.
In this meeting report, particularly addressing the topic of protection of the cardiovascular system from ischemia/reperfusion injury, highlights are presented that relate to conditioning strategies of the heart with respect to molecular mechanisms and outcome in patients’ cohorts, the influence of co-morbidities and medications, as well as the contribution of innate immune reactions in cardioprotection. Moreover, developmental or systems biology approaches bear great potential in systematically uncovering unexpected components involved in ischemia–reperfusion injury or heart regeneration. Based on the characterization of particular platelet integrins, mitochondrial redox-linked proteins, or lipid-diol compounds in cardiovascular diseases, their targeting by newly developed theranostics and technologies opens new avenues for diagnosis and therapy of myocardial infarction to improve the patients’ outcome.
Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by impaired antimicrobial activity in phagocytic cells. As a monogenic disease affecting the hematopoietic system, CGD is amenable to gene therapy. Indeed in a phase I/II clinical trial, we demonstrated a transient resolution of bacterial and fungal infections. However, the therapeutic benefit was compromised by the occurrence of clonal dominance and malignant transformation demanding alternative vectors with equal efficacy but safety-improved features. In this work we have developed and tested a self-inactivating (SIN) gammaretroviral vector (SINfes.gp91s) containing a codon-optimized transgene (gp91(phox)) under the transcriptional control of a myeloid promoter for the gene therapy of the X-linked form of CGD (X-CGD). Gene-corrected cells protected X-CGD mice from Aspergillus fumigatus challenge at low vector copy numbers. Moreover, the SINfes.gp91s vector generates substantial amounts of superoxide in human cells transplanted into immunodeficient mice. In vitro genotoxicity assays and longitudinal high-throughput integration site analysis in transplanted mice comprising primary and secondary animals for 11 months revealed a safe integration site profile with no signs of clonal dominance.
Understanding the underlying mechanisms that link psychopathology and physical comorbidities in schizophrenia is crucial since decreased physical fitness and overweight pose major risk factors for cardio-vascular diseases and decrease the patients’ life expectancies. We hypothesize that altered reward anticipation plays an important role in this. We implemented the Monetary Incentive Delay task in a MR scanner and a fitness test battery to compare schizophrenia patients (SZ, n = 43) with sex- and age-matched healthy controls (HC, n = 36) as to reward processing and their physical fitness. We found differences in reward anticipation between SZs and HCs, whereby increased activity in HCs positively correlated with overall physical condition and negatively correlated with psychopathology. On the other handy, SZs revealed stronger activity in the posterior cingulate cortex and in cerebellar regions during reward anticipation, which could be linked to decreased overall physical fitness. These findings demonstrate that a dysregulated reward system is not only responsible for the symptomatology of schizophrenia, but might also be involved in physical comorbidities which could pave the way for future lifestyle therapy interventions.
From Brownian motion with a local time drift to Feller's branching diffusion with logistic growth
(2011)
We give a new proof for a Ray-Knight representation of Feller's branching diffusion with logistic growth in terms of the local times of a reflected Brownian motion H with a drift that is affine linear in the local time accumulated by H
at its current level. In Le et al. (2011) such a representation was obtained by an approximation through Harris paths that code the genealogies of particle systems. The present proof is purely in terms of stochastic analysis, and is inspired by previous work of Norris, Rogers and Williams (1988).