Land Donations and the Gift of Water. On Temple Landlordism and Irrigation Agriculture in Pre-Colonial Bali

The Batur Temple (Pura Ulun Danu Batur) in Kintamani is located at the geographic apex of a so-called ritual water hierarchy and has conventionally been described as a purely religious institution responsible for the coordination and distribution of the irrigation water. However, an analysis of historical palm leaf manuscripts reveals that the temple had a firm economic base with corresponding interests and that it was one of the most important land-owners in late pre-colonial Bali. The article therefore explores from a socio-political and economic perspective the implications of this form of temple landlordism and its combination with ritual water control, particularly for the peasants and the portion of their annual surplus that they were obliged to deliver to this temple

Communications Biophysics

Contains research objectives, summary of research and reports on two research projects.National Institutes of Health (Grant 5 PO1 GM-14940-02)Joint Services Electronics Programs (U. S. Army, U.S. Navy, and U. S. Air Force) under Contract DA 28-043-AMC-02536(E)National Aeronautics and Space Administration (Grant NGL 22-009-304)National Institutes of Health (Grant 5 TO1 GM-01555-02)National Institutes of Health (Grant NB-08082-01

Towards a three-dimensional microfluidic liver platform for predicting drug efficacy and toxicity in humans

Although the process of drug development requires efficacy and toxicity testing in animals prior to human testing, animal models have limited ability to accurately predict human responses to xenobiotics and other insults. Societal pressures are also focusing on reduction of and, ultimately, replacement of animal testing. However, a variety of in vitro models, explored over the last decade, have not been powerful enough to replace animal models. New initiatives sponsored by several US federal agencies seek to address this problem by funding the development of physiologically relevant human organ models on microscopic chips. The eventual goal is to simulate a human-on-a-chip, by interconnecting the organ models, thereby replacing animal testing in drug discovery and development. As part of this initiative, we aim to build a three-dimensional human liver chip that mimics the acinus, the smallest functional unit of the liver, including its oxygen gradient. Our liver-on-a-chip platform will deliver a microfluidic three-dimensional co-culture environment with stable synthetic and enzymatic function for at least 4 weeks. Sentinel cells that contain fluorescent biosensors will be integrated into the chip to provide multiplexed, real-time readouts of key liver functions and pathology. We are also developing a database to manage experimental data and harness external information to interpret the multimodal data and create a predictive platform. © 2013 BioMed Central Ltd

Structural Brain Changes Related to Disease Duration in Patients with Asthma

Dyspnea is the impairing, cardinal symptom patients with asthma repeatedly experience over the course of the disease. However, its accurate perception is also crucial for timely initiation of treatment. Reduced perception of dyspnea is associated with negative treatment outcome, but the underlying brain mechanisms of perceived dyspnea in patients with asthma remain poorly understood. We examined whether increasing disease duration in fourteen patients with mild-to-moderate asthma is related to structural brain changes in the insular cortex and brainstem periaqueductal grey (PAG). In addition, the association between structural brain changes and perceived dyspnea were studied. By using magnetic resonance imaging in combination with voxel-based morphometry, gray matter volumes of the insular cortex and the PAG were analysed and correlated with asthma duration and perceived affective unpleasantness of resistive load induced dyspnea. Whereas no associations were observed for the insular cortex, longer duration of asthma was associated with increased gray matter volume in the PAG. Moreover, increased PAG gray matter volume was related to reduced ratings of dyspnea unpleasantness. Our results demonstrate that increasing disease duration is associated with increased gray matter volume in the brainstem PAG in patients with mild-to-moderate asthma. This structural brain change might contribute to the reduced perception of dyspnea in some patients with asthma and negatively impact the treatment outcome

Correlations, Causes and the Logic of Obscuration: Donor Shaping of Dominant Narratives in Indonesia's Irrigation Development

This article analyses policy trends in Indonesian irrigation, particularly during the last five decades, from the perspective of dominant narratives, as authored, suggested and pushed by international donors. It argues that international donors' adherence to ‘deferred maintenance’ as the core element of irrigation policy problem framing does not match with farmers' and the irrigation agency staff perceptions and practices. The logic of obscuration and the discursive manoeuvers that maintain it are analysed. The article concludes that there is space for more profound conceptual contestation and for alternative actions pathways even within the ‘dominant paradigm’ to address management problems more effectively

Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis

Alcoholic hepatitis (AH) is a life-threatening condition characterized by profound hepatocellular dysfunction for which targeted treatments are urgently needed. Identification of molecular drivers is hampered by the lack of suitable animal models. By performing RNA sequencing in livers from patients with different phenotypes of alcohol-related liver disease (ALD), we show that development of AH is characterized by defective activity of liver-enriched transcription factors (LETFs). TGFβ1 is a key upstream transcriptome regulator in AH and induces the use of HNF4α P2 promoter in hepatocytes, which results in defective metabolic and synthetic functions. Gene polymorphisms in LETFs including HNF4α are not associated with the development of AH. In contrast, epigenetic studies show that AH livers have profound changes in DNA methylation state and chromatin remodeling, affecting HNF4α-dependent gene expression. We conclude that targeting TGFβ1 and epigenetic drivers that modulate HNF4α-dependent gene expression could be beneficial to improve hepatocellular function in patients with AH

The interpretations and uses of fitness landscapes in the social sciences

__Abstract__ This working paper precedes our full article entitled “The evolution of Wright’s (1932) adaptive field to contemporary interpretations and uses of fitness landscapes in the social sciences” as published in the journal Biology & Philosophy (http://link.springer.com/article/10.1007/s10539-014-9450-2). The working paper features an extended literature overview of the ways in which fitness landscapes have been interpreted and used in the social sciences, for which there was not enough space in the full article. The article features an in-depth philosophical discussion about the added value of the various ways in which fitness landscapes are used in the social sciences. This discussion is absent in the current working paper. Th