Influence of topography and moisture and nutrient availability on green alder function on the low arctic tundra, NT

The Arctic has warmed by at least 3°C over the past 50 years and this rapid warming is expected to continue. Climate warming is driving the proliferation of shrubs across the tundra biome with implications for energy balance, climate, hydrology, nutrient cycling, and biodiversity. Changes in tundra plant water use attributable to shrub expansion are predicted to increase evapotranspirative water loss which may amplify local warming and reduce run-off. However, little is known about the extent to which shrubs will enhance evapotranspirative water loss in these systems. Direct measures of shrub water use are needed to accurately predict evapotranspiration rates and the associated hydrological and energetic impacts. In addition, it is crucial that we understand the abiotic factors that drive shrub distribution and physiological function to forecast further changes in tundra ecosystem function. Shrubs are expanding in areas that have a higher potential of accumulating moisture, such as drainage channels and hill slopes. Shrub expansion may be limited by variation in water and nutrient availability across topographic gradients. Nevertheless, the associations between shrub function and abiotic limitations remain understudied. To address these knowledge gaps, we measured sap flow, stem water potential, and a range of functional traits of green alder (Alnus viridis) shrubs and quantified water and nutrient availability in shrub patches on the low arctic tundra of the Northwest Territories. Frost table depth was a significant negative driver of sap flow and underlies decreased surface water availability with thaw. This was further supported through significantly lower stem water potential values as the growing season progressed. Shrubs in upslope locations had significantly lower water potentials relative to shrubs in downslope locations, demonstrating topographic variation in shrub water status. Shrubs in channels and at the tops of patch slopes significantly differed in leaf functional traits representing leaf investment, productivity, and water use efficiency. Channel shrubs reflected traits associated with higher resource availability and productivity whereas shrubs at the tops of patches reflected the opposite. This work provides insight into the abiotic drivers of tall shrub water use and productivity, both of which will be essential for predicting ecosystem function

Freeze-Thaw Resistance of Concrete: Insight from Microstructural Properties

Composite cements offer low carbon alternatives to conventional CEM I. These binders also generally tend to perform better than CEM I in aggressive chemical environments. However, their freeze-thaw resistance, evident through surface scaling and internal damage is usually impaired. Postulated theories on freeze-thaw induced damage do not fully explain the origin of this weakness in composite cement concretes. This paper systematically presents the phase assemblage changes associated with the freeze-thaw of concrete specimen made from composite cements with and without limestone. The freeze-thaw test was performed on concrete according to CIF method based on CEN/TR 15177 and the corresponding cement pastes characterized by X-ray powder diffraction (XRD) and thermogravimetric analysis (TGA). In all investigated composite cements, portlandite was already depleted after the 7d capillary suction. The implications of this and other modified assemblages during the conditioning and the freeze-thaw test are consequently discussed

On Weak Keys and Forgery Attacks Against Polynomial-Based MAC Schemes

Abstract. Universal hash functions are commonly used primitives for fast and secure message authentication in the form of Message Authentication Codes (MACs) or Authenticated Encryption with Associated Data (AEAD) schemes. These schemes are widely used and standardised, the most well known being McGrew and Viega’s Galois/Counter Mode (GCM). In this paper we identify some properties of hash functions based on polynomial evaluation that arise from the underlying algebraic structure. As a result we are able to describe a general forgery attack, of which Saarinen’s cycling attack from FSE 2012 is a special case. Our attack removes the requirement for long messages and applies regardless of the field in which the hash function is evaluated. Furthermore we provide a common description of all published attacks against GCM, by showing that the existing attacks are the result of these algebraic properties of the polynomial-based hash function. We also greatly expand the number of known weak GCM keys and show that almost every subset of the keyspace is a weak key class. Finally, we demonstrate that these algebraic properties and corresponding attacks are highly relevant to GCM/2 +, a variant of GCM designed to increase the efficiency in software

Germline mutations and somatic inactivation of TRIM28 in Wilms tumour

© 2018 Halliday et al. http://creativecommons.org/licenses/by/4.0/ Wilms tumour is a childhood tumour that arises as a consequence of somatic and rare germline mutations, the characterisation of which has refined our understanding of nephrogenesis and carcinogenesis. Here we report that germline loss of function mutations in TRIM28 predispose children to Wilms tumour. Loss of function of this transcriptional co-repressor, which has a role in nephrogenesis, has not previously been associated with cancer. Inactivation of TRIM28, either germline or somatic, occurred through inactivating mutations, loss of heterozygosity or epigenetic silencing. TRIM28-mutated tumours had a monomorphic epithelial histology that is uncommon for Wilms tumour. Critically, these tumours were negative for TRIM28 immunohistochemical staining whereas the epithelial component in normal tissue and other Wilms tumours stained positively. These data, together with a characteristic gene expression profile, suggest that inactivation of TRIM28 provides the molecular basis for defining a previously described subtype of Wilms tumour, that has early age of onset and excellent prognosis

A revised lower estimate of ozone columns during Earth’s oxygenated history

The history of molecular oxygen (O2) in Earth’s atmosphere is still debated; however, geological evidence supports at least two major episodes where O2 increased by an order of magnitude or more: the Great Oxidation Event (GOE) and the Neoproterozoic Oxidation Event. O2 concentrations have likely fluctuated (between 10−3 and 1.5 times the present atmospheric level) since the GOE ∼2.4 Gyr ago, resulting in a time-varying ozone (O3) layer. Using a three-dimensional chemistry-climate model, we simulate changes in O3 in Earth’s atmosphere since the GOE and consider the implications for surface habitability, and glaciation during the Mesoproterozoic. We find lower O3 columns (reduced by up to 4.68 times for a given O2 level) compared to previous work; hence, higher fluxes of biologically harmful UV radiation would have reached the surface. Reduced O3 leads to enhanced tropospheric production of the hydroxyl radical (OH) which then substantially reduces the lifetime of methane (CH4). We show that a CH4 supported greenhouse effect during the Mesoproterozoic is highly unlikely. The reduced O3 columns we simulate have important implications for astrobiological and terrestrial habitability, demonstrating the relevance of three-dimensional chemistry-climate simulations when assessing paleoclimates and the habitability of faraway worlds

The attitude of patients with progressive ataxias towards clinical trials

Background The development of new therapies may rely on the conduct of human experimentation as well as later clinical trials of therapeutic interventions. Ethical considerations seek to protect the patient from risk but few have sought to ascertain the attitude to such risk of patients with progressive debilitating or terminal conditions, for which no mitigating or curative therapies exist. Such understanding is also important if recruitment is to be maximized. We therefore sought to define the motivations for and barriers to trial participation amongst patients with progressive ataxias, as well as their condition-specific trial preferences. Methods We conducted an online survey consisting of 29 questions covering four key domains (demographics, personal motivation, drug therapy and study design) relating to the design of clinical trials. Two major ataxia charities, Ataxia UK and the Friedreich’s Ataxia Research Alliance (FARA) sent the survey to their members. Responses were analysed by disease and by ambulatory status. Results Of 342 respondents, 204 reported a diagnosis of Friedreich’s ataxia (FRDA), 55 inherited cerebellar ataxia (CA) and 70 idiopathic CA. The most important symptoms to be addressed by a trial were considered to be balance problems and ambulation, although these were superseded by speech problems in wheelchair users. Common motivations for participation were potential benefits to self and others. Reasons for non-participation included concerns about side effects, and the burden and cost of travel. Financial reimbursement for expenses was reported to be likely to increase trial engagement, Phase two trials were the most popular to participate in, and the use of a placebo arm was seen as a disincentive. Across all disease subgroups, drug repurposing trials proved popular and just under 70% of participants would be prepared to undergo intrathecal drug administration. Conclusions Knowledge of motivations for and barriers to trial participation as well as the acceptability of investigations, time commitments and routes of drug administration should inform better, more patient focused trial design. This in turn may improve recruitment and retention of participants to future trials

3D time series analysis of cell shape using Laplacian approaches

Background: Fundamental cellular processes such as cell movement, division or food uptake critically depend on cells being able to change shape. Fast acquisition of three-dimensional image time series has now become possible, but we lack efficient tools for analysing shape deformations in order to understand the real three-dimensional nature of shape changes. Results: We present a framework for 3D+time cell shape analysis. The main contribution is three-fold: First, we develop a fast, automatic random walker method for cell segmentation. Second, a novel topology fixing method is proposed to fix segmented binary volumes without spherical topology. Third, we show that algorithms used for each individual step of the analysis pipeline (cell segmentation, topology fixing, spherical parameterization, and shape representation) are closely related to the Laplacian operator. The framework is applied to the shape analysis of neutrophil cells. Conclusions: The method we propose for cell segmentation is faster than the traditional random walker method or the level set method, and performs better on 3D time-series of neutrophil cells, which are comparatively noisy as stacks have to be acquired fast enough to account for cell motion. Our method for topology fixing outperforms the tools provided by SPHARM-MAT and SPHARM-PDM in terms of their successful fixing rates. The different tasks in the presented pipeline for 3D+time shape analysis of cells can be solved using Laplacian approaches, opening the possibility of eventually combining individual steps in order to speed up computations

Cross-species gene expression analysis of species specific differences in the preclinical assessment of pharmaceutical compounds

Animals are frequently used as model systems for determination of safety and efficacy in pharmaceutical research and development. However, significant quantitative and qualitative differences exist between humans and the animal models used in research. This is as a result of genetic variation between human and the laboratory animal. Therefore the development of a system that would allow the assessment of all molecular differences between species after drug exposure would have a significant impact on drug evaluation for toxicity and efficacy. Here we describe a cross-species microarray methodology that identifies and selects orthologous probes after cross-species sequence comparison to develop an orthologous cross-species gene expression analysis tool. The assumptions made by the use of this orthologous gene expression strategy for cross-species extrapolation is that; conserved changes in gene expression equate to conserved pharmacodynamic endpoints. This assumption is supported by the fact that evolution and selection have maintained the structure and function of many biochemical pathways over time, resulting in the conservation of many important processes. We demonstrate this cross-species methodology by investigating species specific differences of the peroxisome proliferatoractivator receptor (PPAR) a response in rat and human

Telomere disruption results in non-random formation of de novo dicentric chromosomes involving acrocentric human chromosomes

Copyright: © 2010 Stimpson et al.Genome rearrangement often produces chromosomes with two centromeres (dicentrics) that are inherently unstable because of bridge formation and breakage during cell division. However, mammalian dicentrics, and particularly those in humans, can be quite stable, usually because one centromere is functionally silenced. Molecular mechanisms of centromere inactivation are poorly understood since there are few systems to experimentally create dicentric human chromosomes. Here, we describe a human cell culture model that enriches for de novo dicentrics. We demonstrate that transient disruption of human telomere structure non-randomly produces dicentric fusions involving acrocentric chromosomes. The induced dicentrics vary in structure near fusion breakpoints and like naturally-occurring dicentrics, exhibit various inter-centromeric distances. Many functional dicentrics persist for months after formation. Even those with distantly spaced centromeres remain functionally dicentric for 20 cell generations. Other dicentrics within the population reflect centromere inactivation. In some cases, centromere inactivation occurs by an apparently epigenetic mechanism. In other dicentrics, the size of the alpha-satellite DNA array associated with CENP-A is reduced compared to the same array before dicentric formation. Extrachromosomal fragments that contained CENP-A often appear in the same cells as dicentrics. Some of these fragments are derived from the same alpha-satellite DNA array as inactivated centromeres. Our results indicate that dicentric human chromosomes undergo alternative fates after formation. Many retain two active centromeres and are stable through multiple cell divisions. Others undergo centromere inactivation. This event occurs within a broad temporal window and can involve deletion of chromatin that marks the locus as a site for CENP-A maintenance/replenishment.This work was supported by the Tumorzentrum Heidelberg/Mannheim grant (D.10026941)and by March of Dimes Research Foundation grant #1-FY06-377 and NIH R01 GM069514