A manifesto for a progressive land-grant mission in an authoritarian populist era

In this article, we offer a manifesto for a progressive twenty-first century land-grant mission in an era of rising authoritarian populism in the United States. We explore the historical context of this mode of political engagement, argue that scholars based at land-grant universities are uniquely positioned to address this political moment, and offer examples of land-grant scholars who have embraced this political obligation directly. In the midst of the U.S. Civil War, the federal government provided grants of land to one college in every state to establish universities especially with extension-oriented missions committed to agricultural research and training; today, there are seventy-six land-grant universities. Just as the constitution of these universities at a significant moment in the country’s history served a political purpose, the current political climate demands a robust political response from contemporary land-grant scholars. Given the mandate for land-grant universities to serve their communities, how can a critical land-grant mission respond to the current political moment of emergent authoritarian populism in the United States and internationally? What responsibilities are entailed in the land-grant mission? We consider some strategies that land-grant scholars are employing to engage with communities grappling most directly with economic stagnation, climate change, and agrarian dispossession. We also suggest that, amid the dramatically shifting political climate in the United States, all scholars regardless of land-grant affiliation should be concerned with land-grant institutions’ capacities to engage with the country’s most disenfranchised populations as a means to pushing back against authoritarian populism

Kinesin-II is required for axonal transport of choline acetyltransferase in Drosophila

KLP64D and KLP68D are members of the kinesin-II family of proteins in Drosophila. Immunostaining for KLP68D and ribonucleic acid in situ hybridization for KLP64D demonstrated their preferential expression in cholinergic neurons. KLP68D was also found to accumulate in cholinergic neurons in axonal obstructions caused by the loss of kinesin light chain. Mutations in the KLP64D gene cause uncoordinated sluggish movement and death, and reduce transport of choline acetyltransferase from cell bodies to the synapse. The inviability of KLP64D mutations can be rescued by expression of mammalian KIF3A. Together, these data suggest that kinesin-II is required for the axonal transport of a soluble enzyme, choline acetyltransferase. in a specific subset of neurons in Drosophila. Furthermore, the data lead to the conclusion that the cargo transport requirements of different classes of neurons may lead to upregulation of specific pathways of axonal transport

Territorializing spatial data: Controlling land through One Map projects in Indonesia and Myanmar

Once confined to paper, national cartographic projects increasingly play out through spatial data infrastructures such as software programs and smartphones. Across the Global South, foreign donor-funded digital platforms emphasize transparency, accountability and data sharing while echoing colonial projects that consolidated statebased territorial knowledge. This article brings political geography scholarship on state and counter-mapping together with new work on the political ecology of data to highlight a contemporary dimension of territorialization, one in which state actors seek to consolidate and authorize national geospatial information onto digital platforms. We call attention to the role of data infrastructures in contemporary resource control, arguing that territorializing data both extends state territorialization onto digital platforms and, paradoxically, provides new avenues for non-state actors to claim land. Drawing on interviews, document review, and long-term fieldwork, we compare the origins, institutionalization and realization of Indonesia and Myanmar’s ‘One Map’ projects. Both projects aimed to create a government-managed online spatial data platform, building on national mapping and management traditions while responding to new international incentives, such as climate change mitigation in Indonesia and good democratic governance in Myanmar. While both projects encountered technical difficulties and evolved during implementation, different national histories and political trajectories resulted in the embrace and expansion of the program in Indonesia but reluctant participation and eventual crisis in Myanmar. Together, these cases show how spatial data infrastructures can both extend state control over space and offer opportunities for contesting or reimagining land and nation, even as such infrastructures remain embedded in local power relations

Unlocking "lock-in" and path dependency : a review across disciplines and socio-environmental contexts

Introduced in the early 2000s, the concept of carbon "lock-in" has been widely adopted by think tanks, academics, and civil society trying to break away from the consequences of fossil-fuel induced carbon emissions and climate change. The concept has been instrumental to energy economic policy, energy transitions, and automobile transportation and urban mobility. It has parallels with "path dependency" across sectors, including water governance, fisheries, farmer tenure, and debt. Yet its use has also fallen short in applying it to nontechnical settings beyond infrastructure. In this review article, we argue that the "lock-in" concept is relevant to a much broader range of multi-scalar socio-environmental challenges to development. We expand lock-in to consider granular issues that tend to slip out of macro-level technological and institutional path dependencies, without falling into the 'naturalizing trap' in systems thinking. Broadening and re-engaging the concept of lock-in strengthens our analytical ability to address a range of structurally uneven environmental and societal lock-ins

Dynamic simulation of the THAI heavy oil recovery process

Toe-to-Heel Air Injection (THAI) is a variant of conventional In-Situ Combustion (ISC) that uses a horizontal production well to recover mobilised partially upgraded heavy oil. It has a number of advantages over other heavy oil recovery techniques such as high recovery potential. However, existing models are unable to predict the effect of the most important operational parameters, such as fuel availability and produced oxygen concentration, which will give rise to unsafe designs. Therefore, we have developed a new model that accurately predicts dynamic conditions in the reservoir and also is easily scalable to investigate different field scenarios. The model used a three component direct conversion cracking kinetics scheme, which does not depend on the stoichiometry of the products and, thus, reduces the extent of uncertainty in the simulation results as the number of unknowns is reduced. The oil production rate and cumulative oil produced were well predicted, with the latter deviating from the experimental value by only 4%. The improved ability of the model to emulate real process dynamics meant it also accurately predicted when the oxygen was first produced, thereby enabling a more accurate assessment to be made of when it would be safe to shut-in the process, prior to oxygen breakthrough occurring. The increasing trend in produced oxygen concentration following a step change in the injected oxygen rate by 33 % was closely replicated by the model. The new simulations have now elucidated the mechanism of oxygen production during the later stages of the experiment. The model has allowed limits to be placed on the air injection rates that ensure stability of operation. Unlike previous models, the new simulations have provided better quantitative prediction of fuel laydown, which is a key phenomenon that determines whether, or not, successful operation of the THAI process can be achieved. The new model has also shown that, for completely stable operation, the combustion zone must be restricted to the upper portion of the sand pack, which can be achieved by using higher producer back pressure

Targeted suppression of AR-V7 using PIP5K1α inhibitor overcomes enzalutamide resistance in prostate cancer cells

One mechanism of resistance of prostate cancer (PCa) to enzalutamide (MDV3100) treatment is the increased expression of AR variants lacking the ligand binding-domain, the best characterized of which is AR-V7. We have previously reported that Phosphatidylinositol-4-phosphate 5-kinase alpha (PIP5Kα), is a lipid kinase that links to CDK1 and AR pathways. The discovery of PIP5Kα inhibitor highlight the potential of PIP5K1α as a drug target in PCa. In this study, we show that AR-V7 expression positively correlates with PIP5K1α in tumor specimens from PCa patients. Overexpression of AR-V7 increases PIP5K1α, promotes rapid growth of PCa in xenograft mice, whereas inhibition of PIP5K1α by its inhibitor ISA-2011B suppresses the growth and invasiveness of xenograft tumors overexpressing AR-V7. PIP5K1α is a key co-factor for both AR-V7 and AR, which are present as protein-protein complexes predominantly in the nucleus of PCa cells. In addition, PIP5K1α and CDK1 influence AR-V7 expression also through AKT-associated mechanism dependent on PTEN-status. ISA-2011B disrupts protein stabilization of AR-V7 which is dependent on PIP5K1α, leading to suppression of invasive growth of AR-V7-high tumors in xenograft mice. Our study suggests that combination of enzalutamide and PIP5K1α may have a significant impact on refining therapeutic strategies to circumvent resistance to antiandrogen therapies

Evaluating the Clinical Validity of Gene-Disease Associations: An Evidence-Based Framework Developed by the Clinical Genome Resource

Supplemental Data Supplemental Data include 65 figures and can be found with this article online at http://dx.doi.org/10.1016/j.ajhg.2017.04.015. Supplemental Data Document S1. Figures S1–S65 Download Document S2. Article plus Supplemental Data Download Web Resources ClinGen, https://www.clinicalgenome.org/ ClinGen Gene Curation, https://www.clinicalgenome.org/working-groups/gene-curation/ ClinGen Gene Curation SOP, https://www.clinicalgenome.org/working-groups/gene-curation/projects-initiatives/gene-disease-clinical-validity-sop/ ClinGen Knowledge Base, https://search.clinicalgenome.org/kb/agents/sign_up OMIM, http://www.omim.org/ Orphanet, http://www.orpha.net/consor/cgi-bin/index.php With advances in genomic sequencing technology, the number of reported gene-disease relationships has rapidly expanded. However, the evidence supporting these claims varies widely, confounding accurate evaluation of genomic variation in a clinical setting. Despite the critical need to differentiate clinically valid relationships from less well-substantiated relationships, standard guidelines for such evaluation do not currently exist. The NIH-funded Clinical Genome Resource (ClinGen) has developed a framework to define and evaluate the clinical validity of gene-disease pairs across a variety of Mendelian disorders. In this manuscript we describe a proposed framework to evaluate relevant genetic and experimental evidence supporting or contradicting a gene-disease relationship and the subsequent validation of this framework using a set of representative gene-disease pairs. The framework provides a semiquantitative measurement for the strength of evidence of a gene-disease relationship that correlates to a qualitative classification: “Definitive,” “Strong,” “Moderate,” “Limited,” “No Reported Evidence,” or “Conflicting Evidence.” Within the ClinGen structure, classifications derived with this framework are reviewed and confirmed or adjusted based on clinical expertise of appropriate disease experts. Detailed guidance for utilizing this framework and access to the curation interface is available on our website. This evidence-based, systematic method to assess the strength of gene-disease relationships will facilitate more knowledgeable utilization of genomic variants in clinical and research settings

Organic nitrate chemistry and its implications for nitrogen budgets in an isoprene- and monoterpene-rich atmosphere: constraints from aircraft (SEAC4RS) and ground-based (SOAS) observations in the Southeast US

Formation of organic nitrates (RONO2) during oxidation of biogenic volatile organic compounds (BVOCs: isoprene, monoterpenes) is a significant loss pathway for atmospheric nitrogen oxide radicals (NOx), but the chemistry of RONO2 formation and degradation remains uncertain. Here we implement a new BVOC oxidation mechanism (including updated isoprene chemistry, new monoterpene chemistry, and particle uptake of RONO2) in the GEOS-Chem global chemical transport model with  ∼  25  x  25 km2 resolution over North America. We evaluate the model using aircraft (SEAC4RS) and ground-based (SOAS) observations of NOx, BVOCs, and RONO2 from the Southeast US in summer 2013. The updated simulation successfully reproduces the concentrations of individual gas- and particle-phase RONO2 species measured during the campaigns. Gas-phase isoprene nitrates account for 25-50 % of observed RONO2 in surface air, and we find that another 10 % is contributed by gas-phase monoterpene nitrates. Observations in the free troposphere show an important contribution from long-lived nitrates derived from anthropogenic VOCs. During both campaigns, at least 10 % of observed boundary layer RONO2 were in the particle phase. We find that aerosol uptake followed by hydrolysis to HNO3 accounts for 60 % of simulated gas-phase RONO2 loss in the boundary layer. Other losses are 20 % by photolysis to recycle NOx and 15 % by dry deposition. RONO2 production accounts for 20 % of the net regional NOx sink in the Southeast US in summer, limited by the spatial segregation between BVOC and NOx emissions. This segregation implies that RONO2 production will remain a minor sink for NOx in the Southeast US in the future even as NOx emissions continue to decline

A programme theory for liaison mental health services in England

Background: Mechanisms by which liaison mental health services (LMHS) may bring about improved patient and organisational outcomes are poorly understood. A small number of logic models have been developed, but they fail to capture the complexity of clinical practice. Method: We synthesised data from a variety of sources including a large national survey, 73 in-depth interviews with acute and liaison staff working in hospitals with different types of liaison mental health services, and relevant local, national and international literature. We generated logic models for two common performance indicators used to assess organisational outcomes for LMHS: response times in the emergency department and hospital length of stay for people with mental health problems. Results: We identified 8 areas of complexity that influence performance, and 6 trade-offs which drove the models in different directions depending upon the balance of the trade-off. The logic models we developed could only be captured by consideration of more than one pass through the system, the complexity in which they operated, and the trade-offs that occurred. Conclusions: Our findings are important for commissioners of liaison services. Reliance on simple target setting may result in services that are unbalanced and not patient-centred. Targets need to be reviewed on a regular basis, together with other data that reflect the wider impact of the service, and any external changes in the system that affect the performance of LMHS, which are beyond their control

A nonsynonymous SNP within PCDH15 is associated with lipid traits in familial combined hyperlipidemia

Familial combined hyperlipidemia (FCHL) is a common lipid disorder characterized by the presence of multiple lipoprotein phenotypes that increase the risk of premature coronary heart disease. In a previous study, we identified an intragenic microsatellite marker within the protocadherin 15 (PCDH15) gene to be associated with high triglycerides (TGs) in Finnish dyslipidemic families. In this study we analyzed all four known nonsynonymous SNPs within PCDH15 in 1,268 individuals from Finnish and Dutch multigenerational families with FCHL. Association analyses of quantitative traits for SNPs were performed using the QTDT test. The nonsynonymous SNP rs10825269 resulted in a P = 0.0006 for the quantitative TG trait. Additional evidence for association was observed with the same SNP for apolipoprotein B levels (apo-B) (P = 0.0001) and total cholesterol (TC) levels (P = 0.001). None of the other three SNPs tested showed a significant association with any lipid-related trait. We investigated the expression of PCDH15 in different human tissues and observed that PCDH15 is expressed in several tissues including liver and pancreas. In addition, we measured the plasma lipid levels in mice with loss-of-function mutations in Pcdh15 (Pcdh15av-Tg and Pcdh15av-3J) to investigate possible abnormalities in their lipid profile. We observed a significant difference in plasma TG and TC concentrations for the Pcdh15av-3J carriers when compared with the wild type (P = 0.013 and P = 0.044, respectively). Our study suggests that PCDH15 is associated with lipid abnormalities