A weak characterization of slow variables in stochastic dynamical systems

We present a novel characterization of slow variables for continuous Markov processes that provably preserve the slow timescales. These slow variables are known as reaction coordinates in molecular dynamical applications, where they play a key role in system analysis and coarse graining. The defining characteristics of these slow variables is that they parametrize a so-called transition manifold, a low-dimensional manifold in a certain density function space that emerges with progressive equilibration of the system's fast variables. The existence of said manifold was previously predicted for certain classes of metastable and slow-fast systems. However, in the original work, the existence of the manifold hinges on the pointwise convergence of the system's transition density functions towards it. We show in this work that a convergence in average with respect to the system's stationary measure is sufficient to yield reaction coordinates with the same key qualities. This allows one to accurately predict the timescale preservation in systems where the old theory is not applicable or would give overly pessimistic results. Moreover, the new characterization is still constructive, in that it allows for the algorithmic identification of a good slow variable. The improved characterization, the error prediction and the variable construction are demonstrated by a small metastable system

Genome wide association mapping of grain arsenic, copper, molybdenum and zinc in rice (Oryza sativa L.) grown at four international field sites

Peer reviewedPublisher PD

The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury

Robot education peers in a situated primary school study: personalisation promotes child learning

The benefit of social robots to support child learning in an educational context over an extended period of time is evaluated. Specifically, the effect of personalisation and adaptation of robot social behaviour is assessed. Two autonomous robots were embedded within two matched classrooms of a primary school for a continuous two week period without experimenter supervision to act as learning companions for the children for familiar and novel subjects. Results suggest that while children in both personalised and non-personalised conditions learned, there was increased child learning of a novel subject exhibited when interacting with a robot that personalised its behaviours, with indications that this benefit extended to other class-based performance. Additional evidence was obtained suggesting that there is increased acceptance of the personalised robot peer over a non-personalised version. These results provide the first evidence in support of peer-robot behavioural personalisation having a positive influence on learning when embedded in a learning environment for an extended period of time

Natural Variation in Arabidopsis thaliana Revealed a Genetic Network Controlling Germination Under Salt Stress

Plant responses to environmental stresses are polygenic and complex traits. In this study quantitative genetics using natural variation in Arabidopsis thaliana was used to investigate the genetic architecture of plant responses to salt stress. Eighty seven A. thaliana accessions were screened and showed a large variation for root development and seed germination under 125 and 200 mM NaCl, respectively. Twenty two quantitative trait loci for these traits have been detected by phenotyping two recombinants inbred line populations, Sha x Col and Sha x Ler. Four QTLs controlling germination under salt were detected in the Sha x Col population. Interestingly, only one allelic combination at these four QTLs inhibits germination under salt stress, implying strong epistatic interactions between them. In this interacting context, we confirmed the effect of one QTL by phenotyping selected heterozygous inbred families. We also showed that this QTL is involved in the control of germination under other stress conditions such as KCl, mannitol, cold, glucose and ABA. Our data highlights the presence of a genetic network which consists of four interacting QTLs and controls germination under limiting environmental conditions

The GCR2 Gene Family Is Not Required for ABA Control of Seed Germination and Early Seedling Development in Arabidopsis

BACKGROUND: The plant hormone abscisic acid (ABA) regulates diverse processes of plant growth and development. It has recently been proposed that GCR2 functions as a G-protein-coupled receptor (GPCR) for ABA. However, the structural relationships and functionality of GCR2 have been challenged by several independent studies. A central question in this controversy is whether gcr2 mutants are insensitive to ABA, because gcr2 mutants were shown to display reduced sensitivity to ABA under one experimental condition (e.g. 22 degrees C, continuous white light with 150 micromol m(-2) s(-1)) but were shown to display wild-type sensitivity under another slightly different condition (e.g. 23 degrees C, 14/10 hr photoperiod with 120 micromol m(-2) s(-1)). It has been hypothesized that gcr2 appears only weakly insensitive to ABA because two other GCR2-like genes in Arabidopsis, GCL1 and GCL2, compensate for the loss of function of GCR2. PRINCIPAL FINDINGS: In order to test this hypothesis, we isolated a putative loss-of-function allele of GCL2, and then generated all possible combinations of mutations in each member of the GCR2 gene family. We found that all double mutants, including gcr2 gcl1, gcr2 gcl2, gcl1 gcl2, as well as the gcr2 gcl1 gcl2 triple mutant displayed wild-type sensitivity to ABA in seed germination and early seedling development assays, demonstrating that the GCR2 gene family is not required for ABA responses in these processes. CONCLUSION: These results provide compelling genetic evidence that GCR2 is unlikely to act as a receptor for ABA in the context of either seed germination or early seedling development

Accelerated partial breast irradiation: the case for current use

The treatment of early stage breast cancer is evolving from traditional breast conservation techniques, employing conventionally fractionated whole breast irradiation, to techniques in which partial breast irradiation is used in an accelerated fractionation scheme. A growing body of evidence exists, including favorable findings. Additional studies are under way that may ultimately prove equivalence. The logic behind this approach is reviewed, and the currently available data are presented to support the current use of carefully applied partial breast irradiation techniques in appropriately selected and informed patients

Variation in Molybdenum Content Across Broadly Distributed Populations of Arabidopsis thaliana Is Controlled by a Mitochondrial Molybdenum Transporter (MOT1)

Molybdenum (Mo) is an essential micronutrient for plants, serving as a cofactor for enzymes involved in nitrate assimilation, sulfite detoxification, abscisic acid biosynthesis, and purine degradation. Here we show that natural variation in shoot Mo content across 92 Arabidopsis thaliana accessions is controlled by variation in a mitochondrially localized transporter (Molybdenum Transporter 1 - MOT1) that belongs to the sulfate transporter superfamily. A deletion in the MOT1 promoter is strongly associated with low shoot Mo, occurring in seven of the accessions with the lowest shoot content of Mo. Consistent with the low Mo phenotype, MOT1 expression in low Mo accessions is reduced. Reciprocal grafting experiments demonstrate that the roots of Ler-0 are responsible for the low Mo accumulation in shoot, and GUS localization demonstrates that MOT1 is expressed strongly in the roots. MOT1 contains an N-terminal mitochondrial targeting sequence and expression of MOT1 tagged with GFP in protoplasts and transgenic plants, establishing the mitochondrial localization of this protein. Furthermore, expression of MOT1 specifically enhances Mo accumulation in yeast by 5-fold, consistent with MOT1 functioning as a molybdate transporter. This work provides the first molecular insight into the processes that regulate Mo accumulation in plants and shows that novel loci can be detected by association mapping

Plant growth environments with programmable relative humidity and homogeneous nutrient availability

We describe the design, characterization, and use of “programmable”, sterile growth environments for individual (or small sets of) plants. The specific relative humidities and nutrient availability experienced by the plant is established (RH between 15% and 95%; nutrient concentration as desired) during the setup of the growth environment, which takes about 5 minutes and <1$ in disposable cost. These systems maintain these environmental parameters constant for at least 14 days with minimal intervention (one minute every two days). The design is composed entirely of off-the-shelf components (e.g., LEGO® bricks) and is characterized by (i) a separation of root and shoot environment (which is physiologically relevant and facilitates imposing specific conditions on the root system, e.g., darkness), (ii) the development of the root system on a flat surface, where the root enjoys constant contact with nutrient solution and air, (iii) a compatibility with root phenotyping. We demonstrate phenotyping by characterizing root systems of Brassica rapa plants growing in different relative humidities (55%, 75%, and 95%). While most phenotypes were found to be sensitive to these environmental changes, a phenotype tightly associated with root system topology – the size distribution of the areas encircled by roots – appeared to be remarkably and counterintuitively insensitive to humidity changes. These setups combine many of the advantages of hydroponics conditions (e.g., root phenotyping, complete control over nutrient composition, scalability) and soil conditions (e.g., aeration of roots, shading of roots), while being comparable in cost and setup time to Magenta® boxes

An Assay to Monitor HIV-1 Protease Activity for the Identification of Novel Inhibitors in T-Cells

The emergence of resistant HIV strains, together with the severe side-effects of existing drugs and lack of development of effective anti-HIV vaccines highlight the need for novel antivirals, as well as innovative methods to facilitate their discovery. Here, we have developed an assay in T-cells to monitor the proteolytic activity of the HIV-1 protease (PR). The assay is based on the inducible expression of HIV-1 PR fused within the Gal4 DNA-binding and transactivation domains. The fusion protein binds to the Gal4 responsive element and activates the downstream reporter, enhanced green fluorescent protein (eGFP) gene only in the presence of an effective PR Inhibitor (PI). Thus, in this assay, eGFP acts as a biosensor of PR activity, making it ideal for flow cytometry based screening. Furthermore, the assay was developed using retroviral technology in T-cells, thus providing an ideal environment for the screening of potential novel PIs in a cell-type that represents the natural milieu of HIV infection. Clones with the highest sensitivity, and robust, reliable and reproducible reporter activity, were selected. The assay is easily adaptable to other PR variants, a multiplex platform, as well as to high-throughput plate reader based assays and will greatly facilitate the search for novel peptide and chemical compound based PIs in T-cells