C/EBPalpha: critical at the origin of leukemic transformation

Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by clonal expansion of myeloid progenitor cells. A major mechanistic theme in AML biology is the extensive collaboration among fusion oncoproteins, transcription factors, and chromatin regulators to initiate and sustain a transformed cellular state. A new study in this issue describes how the C/EBPalpha transcription factor is crucial for the initiation of AML induced by MLL fusion oncoproteins, but is entirely dispensable for the maintenance of established disease. These observations provide a unique glimpse into the pioneer round of regulatory events that are critical at the origin of AML formation. Furthermore, this study implies the existence of oncogene-induced positive feedback loops capable of bypassing the continuous need for certain regulators to propagate disease

Macro-micro feedback links of water management in South Africa : CGE analyses of selected policy regimes

The pressure on an already stressed water situation in South Africa is predicted to increase significantly under climate change, plans for large industrial expansion, observed rapid urbanization, and government programs to provide access to water to millions of previously excluded people. The present study employed a general equilibrium approach to examine the economy-wide impacts of selected macro and water related policy reforms on water use and allocation, rural livelihoods, and the economy at large. The analyses reveal that implicit crop-level water quotas reduce the amount of irrigated land allocated to higher-value horticultural crops and create higher shadow rents for production of lower-value, water-intensive field crops, such as sugarcane and fodder. Accordingly, liberalizing local water allocation in irrigation agriculture is found to work in favor of higher-value crops, and expand agricultural production and exports and farm employment. Allowing for water trade between irrigation and non-agricultural uses fueled by higher competition for water from industrial expansion and urbanization leads to greater water shadow prices for irrigation water with reduced income and employment benefits to rural households and higher gains for non-agricultural households. The analyses show difficult tradeoffs between general economic gains and higher water prices, making irrigation subsidies difficult to justify.Water Supply and Sanitation Governance and Institutions,Town Water Supply and Sanitation,Water Supply and Systems,Water and Industry,Water Conservation

Crystal structure of the catalytic fragment of murine poly(ADP-ribose) polymerase-2.

Poly(ADP-ribose) polymerase-1 (PARP-1) has become an important pharmacological target in the treatment of cancer due to its cellular role as a 'DNA-strand break sensor', which leads in part to resistance to some existing chemo- and radiological treatments. Inhibitors have now been developed which prevent PARP-1 from synthesizing poly(ADP-ribose) in response to DNA-breaks and potentiate the cytotoxicity of DNA damaging agents. However, with the recent discoveries of PARP-2, which has a similar DNA-damage dependent catalytic activity, and additional members containing the 'PARP catalytic' signature, the isoform selectivity and resultant pharmacological effects of existing inhibitors are brought into question. We present here the crystal structure of the catalytic fragment of murine PARP-2, at 2.8 A resolution, and compare this to the catalytic fragment of PARP-1, with an emphasis on providing a possible framework for rational drug design in order to develop future isoform-specific inhibitors

How effective is the Forestry Commission Scotland's woodland improvement programme--'Woods In and Around Towns' (WIAT)--at improving psychological well-being in deprived urban communities? A quasi-experimental study

Introduction: There is a growing body of evidence that suggests that green spaces may positively influence psychological well-being. This project is designed to take advantage of a natural experiment where planned physical and social interventions to enhance access to natural environments in deprived communities provide an opportunity to prospectively assess impacts on perceived stress and mental well-being.<p></p> Study design and methods: A controlled, prospective study comprising a repeat cross-sectional survey of residents living within 1.5 km of intervention and comparison sites. Three waves of data will be collected: prephysical environment intervention (2013); postphysical environment intervention (2014) and postwoodland promotion social intervention (2015). The primary outcome will be a measure of perceived stress (Perceived Stress Scale) preintervention and postintervention. Secondary, self-report outcomes include: mental well-being (Short Warwick-Edinburgh Mental Well-being Scale), changes in physical activity (IPAQ-short form), health (EuroQoL EQ-5D), perception and use of the woodlands, connectedness to nature (Inclusion of Nature in Self Scale), social cohesion and social capital. An environmental audit will complement the study by evaluating the physical changes in the environment over time and recording any other contextual changes over time. A process evaluation will assess the implementation of the programme. A health economics analysis will assess the cost consequences of each stage of the intervention in relation to the primary and secondary outcomes of the study.<p></p> Ethics and dissemination: Ethical approval has been given by the University of Edinburgh, Edinburgh College of Art Research, Ethics and Knowledge Exchange Committee (ref. 19/06/2012). Findings will be disseminated through peer-reviewed publications, national and international conferences and, at the final stage of the project, through a workshop for those interested in implementing environmental interventions.<p></p&gt

Planets opening dust gaps in gas disks

We investigate the interaction of gas and dust in a protoplanetary disk in the presence of a massive planet using a new two-fluid hydrodynamics code. In view of future observations of planet-forming disks we focus on the condition for gap formation in the dust fluid. While only planets more massive than 1 Jupiter mass (MJ) open up a gap in the gas disk, we find that a planet of 0.1 MJ already creates a gap in the dust disk. This makes it easier to find lower-mass planets orbiting in their protoplanetary disk if there is a significant population of mm-sized particles.Comment: 5 pages, 3 figures, accepted for publication in A&A Letter

The Computer-Controlled Oculometer: A Prototype Interactive Eye Movement Tracking System

One kind of eye movement tracking device which has great potential is the digital computer-controlled Oculometer, an instrument which non-invasively measures point of regard of the subject, as well as pupil diameter and blink occurrence. In conjunction with a computer-generated display which can change in real time as a function of the subject's eye motions, the computer-controlled Oculometer makes possible a variety of interactive measurement and control systems. Practical applications of such schemes have had to await the development of an instrument design which does not inconvenience the subject, and which conveniently interfaces with a digital computer (see ref. 1). This report describes an Oculometer subsystem and an eye-tracking/control program designed for use with the PDP-6 computer of the MIT Project MAC Artificial Intelligence Group. The oculometer electro-optic subsystem utilizes near-infrared light reflected specularly off the front surface of the subject's cornea and diffusely off the retina, producing a bright pupil with an overriding corneal highlight. An electro-optic scanning aperture vidissector within the unit, driven by a digital eye-tracking algorithm programmed into the PDP-6 computer, detects and tracks the centers of the corneal highlight and the bright pupil to give eve movement measurements. A computer-controlled, moving mirror head motion tracker directly coupled to the vidissector tracker permits the subject reasonable freedom of movement. Various applications of this system, which are suggested by the work reported here, include; (a) using the eye as a control device, (b) recording eye fixation and exploring patterns, (c) game playing, (d) training machines, and (e) psychophysiological testing and recording

Localizations at infinity and essential spectrum of quantum Hamiltonians: I. General theory

We isolate a large class of self-adjoint operators H whose essential spectrum is determined by their behavior at large x and we give a canonical representation of their essential spectrum in terms of spectra of limits at infinity of translations of H. The configuration space is an arbitrary abelian locally compact not compact group.Comment: 63 pages. This is the published version with several correction

Can Survey-based Scenarios Measure Consumer Values for Improved Food Safety?

Demand and Price Analysis, Food Consumption/Nutrition/Food Safety,