The Bourbon Reform of Spanish Absolutism: The Government of the Crown of Aragon, 1665-1746

This study of early modern governing practices analyzes the rule of Philip V of Spain (1700-1724, 1724-1746) in relation to his predecessor, the Habsburg Charles II (1665-1700) and his grandfather, Louis XIV of France (1643-1715). Philip creatively engaged the legacy of both monarchs to create a unique set of governing practices that centralized his authority while also maintaining a significant degree of variation in how he related to his subjects based on their social and political standing. Philip followed a particularist model that allowed him to give specific concessions and privileges only to the subjects who requested them. This approach to governing resulted in an ad-hoc administrative and legal patchwork rife with irregularities, but it circumvented the unavoidable problems of replacing multiple complex systems throughout his kingdoms with a uniform legal system. While Philip's reforms left some subjects dissatisfied with his reign, it enabled him to cultivate support among elite groups in his towns and kingdoms, securing his rule in the aftermath of the War of Spanish Succession (1705-1714). The advantages of particularism can be seen in comparison with eighteenth century France, where greater centralization and administrative uniformity created long-term problems that eventually resulted in the French Revolution. The Spanish model, while usually deemed less successful than that of the French, avoided some of the problems that led to the revolution while simultaneously minimizing royal debt. These findings challenge dominant interpretations of state formation in early modern Europe, suggesting that rulers could rationally choose policies that increased administrative and legal fragmentation

A methodology for distinguishing divergent cell fates within a common progenitor population: adenoma- and neuroendocrine-like cells are confounders of rat ileal epithelial cell (IEC-18) culture

BACKGROUND: IEC-18 cells are a non-transformed, immortal cell line derived from juvenile rat ileal crypt cells. They may have experimental advantages over tumor-derived gastrointestinal lineages, including preservation of phenotype, normal endocrine responses and retention of differentiation potential. However, their proclivity for spontaneous differentiation / transformation may be stereotypical and could represent a more profound experimental confounder than previously realized. We hypothesized that IEC-18 cells spontaneously diverge towards a uniform mixture of epigenetic fates, with corresponding phenotypes, rather than persist as a single progenitor lineage. RESULTS: IEC-18 cells were cultured for 72 hours in serum free media (SFM), with and without various insulin-like growth factor agonists to differentially boost the basal rate of proliferation. A strategy was employed to identify constitutive genes as markers of divergent fates through gene array analysis by cross-referencing fold-change trends for individual genes against crypt cell abundance in each treatment. We then confirmed the cell-specific phenotype by immunolocalization of proteins corresponding to those genes. The majority of IEC-18 cells in SFM alone had a loss in expression of the adenomatous polyposis coli (APC) gene at the mRNA and protein levels, consistent with adenoma-like transformation. In addition, a small subset of cells expressed the serotonin receptor 2A gene and had neuroendocrine-like morphology. CONCLUSIONS: IEC-18 cells commonly undergo a change in cell fate prior to reaching confluence. The most common fate switch that we were able to detect correlates with a down regulation of the APC gene and transformation into an adenoma-like phenotype

Women as a Force Multiplier for Bringing Nuclear Forensic Capabilities to the International Stage

In 2009, the US Department of Energy National Nuclear Security Administration’s (NNSA’s) Defense Nuclear Nonproliferation Program initiated a new nuclear forensics outreach effort under its Confidence Building Measures Program. Little did they know that the timing could not have been better. This article focuses on the early years (2009–2015) of the NNSA’s international nuclear forensics outreach, specifically the efforts and experiences of the women who helped establish this program, building it from a fledgling, bilateral effort into an enduring technical capacity provider engaging with dozens of countries and multilateral organizations. At the onset of the program, nuclear forensics was an emerging priority within the US Government and receiving increased focus from international organizations through high-level diplomatic efforts such as the Nuclear Security Summit and Global Initiative to Combat Nuclear Terrorism. Additionally, working-level initiatives were gaining traction through the International Atomic Energy Agency and the Nuclear Forensics International Technical Working Group. Over the next 6 years, a small team comprising a uniquely large number of women NNSA federal, contract, and national laboratory staff served as key leaders engaging with the international community to strengthen global technical nuclear forensics capacity and best practices. The program continues today under the Nuclear Smuggling Detection and Deterrence Program as Investigation Support. The experiences shared here detail a unique time period when the new technical discipline of nuclear forensics was beginning to mature and gain international traction. The authors have made every effort to remember history correctly and be as inclusive as possible. A wealth of training, guidance, and exercise documentation was developed in the 2009–2015 time frame, much of which still serves as the foundation for today’s even more extensive program and community of dedicated technical and diplomatic practitioners

Reducing car-use for leisure: can organised walking groups switch from car travel to bus and train walks?

This paper deals with the significant leisure travel sector, focusing on the attitudes of organised walking groups towards public transport use. A series of interviews with walking group leaders explored the design of organised walks, and factors affecting journeys to and from start points. The themes presented suggest an overlying group culture involving mainly circular walks, reached by car. The research indicates an underlying engrained dependency on cars to reach walks and a degree of opposition to using public transport, which generally contradicts widely–held attitudes towards protecting the environment. Future research should focus more in depth on the long-term removal of psychological barriers to using public transport for leisure, and persuasive measures aimed at groups

Attenuation of Murine Collagen‐Induced Arthritis by Targeting CD6

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156498/2/art41288_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156498/1/art41288.pd

Preferential access to genetic information from endogenous hominin ancient DNA and accurate quantitative SNP-typing via SPEX

The analysis of targeted genetic loci from ancient, forensic and clinical samples is usually built upon polymerase chain reaction (PCR)-generated sequence data. However, many studies have shown that PCR amplification from poor-quality DNA templates can create sequence artefacts at significant levels. With hominin (human and other hominid) samples, the pervasive presence of highly PCR-amplifiable human DNA contaminants in the vast majority of samples can lead to the creation of recombinant hybrids and other non-authentic artefacts. The resulting PCR-generated sequences can then be difficult, if not impossible, to authenticate. In contrast, single primer extension (SPEX)-based approaches can genotype single nucleotide polymorphisms from ancient fragments of DNA as accurately as modern DNA. A single SPEX-type assay can amplify just one of the duplex DNA strands at target loci and generate a multi-fold depth-of-coverage, with non-authentic recombinant hybrids reduced to undetectable levels. Crucially, SPEX-type approaches can preferentially access genetic information from damaged and degraded endogenous ancient DNA templates over modern human DNA contaminants. The development of SPEX-type assays offers the potential for highly accurate, quantitative genotyping from ancient hominin samples