Emergent Outcomes of the veToken Model

Decentralised organisations use blockchains as a basis for governance: they use on-chain transactions to allocate voting weight, publish proposals, cast votes, and enact the results. However, blockchain-based governance structures have challenges, mostly notably, the need to align the short-term outlook of pseudononymous voters with the long-term growth and success of the decentralised organisation. The Vote-Escrowed Token (veToken) model attempts to resolve this tension by requiring voters to escrow or lock tokens of value for an extended period in exchange for voting weight. In this paper, we describe the veToken model and analyse its emergent outcomes. We show that voting behaviour follows bribes set by higher-level protocols, and that the cost per vote varies depending on how it is acquired. We describe the implementation of the veToken model by Curve Finance, a popular automated market maker for stablecoins, and the ecosystem of protocols that has arisen on top of this implementation. We show that voting markets such as Votium largely determine the outcome of fortnightly votes held by Convex Finance, and we show that Frax Finance, a stablecoin issuer, plays a central role in the ecosystem even though they directly lock relatively few tokens with Curve. Instead, they indirectly lock tokens through yield aggregators such as Convex Finance and purchase voting weight through voting markets such as Votium. Although the veToken model in isolation is straight-forward and easily explained, it leads to many complex and emergent outcomes. Decentralised organisations should consider these outcomes before adopting the model.Comment: 15 pages, 5 figure

Structural Descriptors of gp120 V3 Loop for the Prediction of HIV-1 Coreceptor Usage

HIV-1 cell entry commonly uses, in addition to CD4, one of the chemokine receptors CCR5 or CXCR4 as coreceptor. Knowledge of coreceptor usage is critical for monitoring disease progression as well as for supporting therapy with the novel drug class of coreceptor antagonists. Predictive methods for inferring coreceptor usage based on the third hypervariable (V3) loop region of the viral gene coding for the envelope protein gp120 can provide us with these monitoring facilities while avoiding expensive phenotypic tests. All simple heuristics (such as the 11/25 rule) as well as statistical learning methods proposed to date predict coreceptor usage based on sequence features of the V3 loop exclusively. Here, we show, based on a recently resolved structure of gp120 with an untruncated V3 loop, that using structural information on the V3 loop in combination with sequence features of V3 variants improves prediction of coreceptor usage. In particular, we propose a distance-based descriptor of the spatial arrangement of physicochemical properties that increases discriminative performance. For a fixed specificity of 0.95, a sensitivity of 0.77 was achieved, improving further to 0.80 when combined with a sequence-based representation using amino acid indicators. This compares favorably with the sensitivities of 0.62 for the traditional 11/25 rule and 0.73 for a prediction based on sequence information as input to a support vector machine and constitutes a statistically significant improvement. A detailed analysis and interpretation of structural features important for classification shows the relevance of several specific hydrogen-bond donor sites and aliphatic side chains to coreceptor specificity towards CCR5 or CXCR4. Furthermore, an analysis of side chain orientation of the specificity-determining residues suggests a major role of one side of the V3 loop in the selection of the coreceptor. The proposed method constitutes the first approach to an improved prediction of coreceptor usage based on an original integration of structural bioinformatics methods with statistical learning

Metallic tube type energy absorbers: a synopsis

This paper presents an overview of energy absorbers in the form of tubes in which the material used is predominantly mild steel and/or aluminium. A brief summary is also made of frusta type energy absorbers. The common modes of deformation such as lateral and axial compression, indentation and inversion are reviewed. Theoretical, numerical and experimental methods which help to understand the behaviour of such devices under various loading conditions are outlined. Although other forms of energy absorbing materials and structures exist such as composites and honeycombs, this is deemed outside the scope of this review. However, a brief description will be given on these materials. It is hoped that this work will provide a useful platform for researchers and design engineers to gain a useful insight into the progress made over the last few decades in the field of tube type energy absorbers

Neo?patrimonialism, Institutions and Economic Growth: The Case of Malawi, 1964–2009

For significant periods Malawi's economy has performed as well or better than might have been expected given its geographical location and natural resource endowments. Underlying these promising episodes is a pattern of centralised, long?horizon rent management and technocratic integrity. This case study of ‘developmental patrimonialism’ found that the period 1965–79 was one of centralised, long?horizon rent management and a vertically disciplined technocracy, and the economy grew healthily; 1980–94, by contrast, was a period in which rent management drifted. Although it remained quite centralised, it became geared more to the short term, while the civil service began to deteriorate as it was politicised. These resulted in a comparatively directionless reform programme. The situation deteriorated still further under President Bakili Muluzi (1994–2004). This was a period of decentralised, short?horizon rent management and a further deterioration of the state bureaucracy. The economy entered a tailspin. A recovery was made during the first term of President Bingu wa Mutharika (2004–09), who reintroduced some aspects of long?horizon rent centralisation and promoted a more vertically disciplined technocracy

MicroRNAs Are Involved in the Development of Morphine-Induced Analgesic Tolerance and Regulate Functionally Relevant Changes in Serpini1.

Long-term opioid treatment results in reduced therapeutic efficacy and in turn leads to an increase in the dose required to produce equivalent pain relief and alleviate break-through or insurmountable pain. Altered gene expression is a likely means for inducing long-term neuroadaptations responsible for tolerance. Studies conducted by our laboratory (Tapocik et al., 2009) revealed a network of gene expression changes occurring in canonical pathways involved in neuroplasticity, and uncovered miRNA processing as a potential mechanism. In particular, the mRNA coding the protein responsible for processing miRNAs, Dicer1, was positively correlated with the development of analgesic tolerance. The purpose of the present study was to test the hypothesis that miRNAs play a significant role in the development of analgesic tolerance as measured by thermal nociception. Dicer1 knockdown, miRNA profiling, bioinformatics, and confirmation of high value targets were used to test the proposition. Regionally targeted Dicer1 knockdown (via shRNA) had the anticipated consequence of eliminating the development of tolerance in C57BL/6J (B6) mice, thus supporting the involvement of miRNAs in the development of tolerance. MiRNA expression profiling identified a core set of chronic morphine-regulated miRNAs (miR\u27s 27a, 9, 483, 505, 146b, 202). Bioinformatics approaches were implemented to identify and prioritize their predicted target mRNAs. We focused our attention on miR27a and its predicted target serpin peptidase inhibitor clade I (Serpini1) mRNA, a transcript known to be intricately involved in dendritic spine density regulation in a manner consistent with chronic morphine\u27s consequences and previously found to be correlated with the development of analgesic tolerance. In vitro reporter assay confirmed the targeting of the Serpini1 3′-untranslated region by miR27a. Interestingly miR27a was found to positively regulateSerpini1 mRNA and protein levels in multiple neuronal cell lines. Lastly, Serpini1 knockout mice developed analgesic tolerance at a slower rate than wild-type mice thus confirming a role for the protein in analgesic tolerance. Overall, these results provide evidence to support a specific role for miR27a and Serpini1 in the behavioral response to chronic opioid administration (COA) and suggest that miRNA expression and mRNA targeting may underlie the neuroadaptations that mediate tolerance to the analgesic effects of morphine

Longitudinal community plasma HIV-1 RNA concentrations and incidence of HIV-1 among injecting drug users: prospective cohort study

Objective To examine the relation between plasma HIV-1 RNA concentrations in the community and HIV incidence among injecting drug users

Balancing the benefits and risks of public–private partnerships to address the global double burden of malnutrition

Objective: Transnational food, beverage and restaurant companies, and their corporate foundations, may be potential collaborators to help address complex public health nutrition challenges. While UN system guidelines are available for private-sector engagement, non-governmental organizations (NGO) have limited guidelines to navigate diverse opportunities and challenges presented by partnering with these companies through public&ndash;private partnerships (PPP) to address the global double burden of malnutrition.Design: We conducted a search of electronic databases, UN system websites and grey literature to identify resources about partnerships used to address the global double burden of malnutrition. A narrative summary provides a synthesis of the interdisciplinary literature identified.Results: We describe partnership opportunities, benefits and challenges; and tools and approaches to help NGO engage with the private sector to address global public health nutrition challenges. PPP benefits include: raising the visibility of nutrition and health on policy agendas; mobilizing funds and advocating for research; strengthening food-system processes and delivery systems; facilitating technology transfer; and expanding access to medications, vaccines, healthy food and beverage products, and nutrition assistance during humanitarian crises. PPP challenges include: balancing private commercial interests with public health interests; managing conflicts of interest; ensuring that co-branded activities support healthy products and healthy eating environments; complying with ethical codes of conduct; assessing partnership compatibility; and evaluating partnership outcomes.Conclusions: NGO should adopt a systematic and transparent approach using available tools and processes to maximize benefits and minimize risks of partnering with transnational food, beverage and restaurant companies to effectively target the global double burden of malnutrition.<br /

Green revolution in Sub-Saharan Africa: Implications of imposed innovation for the wellbeing of rural smallholders

Green Revolution policies are again being pursued to drive agricultural growth and reduce poverty in Sub-Saharan Africa. However conditions have changed since the well-documented successes of the 1960s and 1970s benefited smallholders in southern Asia and beyond. We argue that under contemporary constraints the mechanisms for achieving improvements in the lives of smallholder farmers through such policies are unclear and that both policy rationale and means of governing agricultural innovation are crucial for pro-poor impacts. To critically analyze Rwanda’s Green Revolution policies and impacts from a local perspective, a mixed methods, multidimensional wellbeing approach is applied in rural areas in mountainous western Rwanda. Here Malthusian policy framing has been used to justify imposed rather than ‘‘induced innovation”. The policies involve a substantial transformation for rural farmers from a traditional polyculture system supporting subsistence and local trade to the adoption of modern seed varieties, inputs, and credit in order to specialize in marketable crops and achieve increased production and income. Although policies have been deemed successful in raising yields and conventionally measured poverty rates have fallen over the same period, such trends were found to be quite incongruous with local experiences. Disaggregated results reveal that only a relatively wealthy minority were able to adhere to the enforced modernization and policies appear to be exacerbating landlessness and inequality for poorer rural inhabitants. Negative impacts were evident for the majority of households as subsistence practices were disrupted, poverty exacerbated, local systems of knowledge, trade, and labor were impaired, and land tenure security and autonomy were curtailed. In order to mitigate the effects we recommend that inventive pro-poor forms of tenure and cooperation (none of which preclude improvements to input availability, market linkages, and infrastructure) may provide positive outcomes for rural people, and importantly in Rwanda, for those who have become landless in recent years. We conclude that policies promoting a Green Revolution in Sub-Saharan Africa should not all be considered to be pro-poor or even to be of a similar type, but rather should be the subject of rigorous impact assessment. Such assessment should be based not only on consistent, objective indicators but pay attention to localized impacts on land tenure, agricultural practices, and the wellbeing of socially differentiated people