Synthetic lethal targeting of oncogenic transcription factors in acute leukemia by PARP inhibitors

Acute myeloid leukemia (AML) is mostly driven by oncogenic transcription factors, which have been classically viewed as intractable targets using small molecule inhibitor approaches. Here, we demonstrate that AML driven by repressive transcription factors including AML1-ETO and PML-RARα are extremely sensitive to Poly (ADP-ribose) Polymerase (PARP) inhibitor (PARPi), in part due to their suppressed expression of key homologous recombination genes and thus compromised DNA damage response (DDR). In contrast, leukemia driven by MLL fusions with dominant transactivation ability is proficient in DDR and insensitive to PARP inhibition. Intriguing, depletion of an MLL downstream target, Hoxa9 that activates expression of various HR genes, impairs DDR and sensitizes MLL leukemia to PARPi. Conversely, Hoxa9 over-expression confers PARPi resistance to AML1-ETO and PML-RARα transformed cells. Together, these studies describe a potential utility of PARPi-induced synthetic lethality for leukemia treatment and reveal a novel molecular mechanism governing PARPi sensitivity in AML.

Gender Differences in Early Reading Strategies: a Comparison of Synthetic Phonics Only with a Mixed Approach to Teaching Reading to 4-5 Year-Old Children

A survey of primary schools in England found that girls outperform boys in English across all phases (Ofsted in Moving English forward. Ofsted, Manchester, 2012). The gender gap remains an on-going issue in England, especially for reading attainment. This paper presents evidence of gender differences in learning to read that emerged during the development of a reading scheme for 4- and 5-year-old children in which 372 children from Reception classes in sixteen schools participated in 12-month trials. There were three arms per trial: Intervention non-PD (non-phonically decodable text with mixed methods teaching); Intervention PD (phonically decodable text with mixed methods teaching); and a ‘business as usual’ control condition SP (synthetic phonics and decodable text). Assignment to Intervention condition was randomised. Standardised measures of word reading and comprehension were used. The research provides statistically significant evidence suggesting that boys learn more easily using a mix of whole-word and synthetic phonics approaches. In addition, the evidence indicates that boys learn to read more easily using the natural-style language of ‘real’ books including vocabulary which goes beyond their assumed decoding ability. At post-test, boys using the nonphonically decodable text with mixed methods (Intervention A) were 8 months ahead in reading comprehension compared to boys using a wholly synthetic phonics approach.

Applying a synthetic approach to the resilience of Finnish reindeer herding as a changing livelihood

Reindeer herding is an emblematic livelihood for Northern Finland, culturally important for local people and valuable in tourism marketing. We examine the livelihood resilience of Finnish reindeer herding by narrowing the focus of general resilience on social-ecological systems (SESs) to a specific livelihood while also acknowledging wider contexts in which reindeer herding is embedded. The questions for specified resilience can be combined with the applied DPSIR approach (Drivers; Pressures: resilience to what; State: resilience of what; Impacts: resilience for whom; Responses: resilience by whom and how). This paper is based on a synthesis of the authors’ extensive anthropological fieldwork on reindeer herding and other land uses in Northern Finland. Our objective is to synthesize various opportunities and challenges that underpin the resilience of reindeer herding as a viable livelihood. The DPSIR approach, applied here as a three step procedure, helps focus the analysis on different components of SES and their dynamic interactions. First, various land use-related DPSIR factors and their relations (synergies and trade-offs) to reindeer herding are mapped. Second, detailed DPSIR factors underpinning the resilience of reindeer herding are identified. Third, examples of interrelations between DPSIR factors are explored, revealing the key dynamics between Pressures, State, Impacts, and Responses related to the livelihood resilience of reindeer herding. In the Discussion section, we recommend that future applications of the DPSIR approach in examining livelihood resilience should (1) address cumulative pressures, (2) consider the state dimension as more tuned toward the social side of SES, (3) assess both the negative and positive impacts of environmental change on the examined livelihood by a combination of science led top-down and participatory bottom-up approaches, and (4) examine and propose governance solutions as well as local adaptations by reindeer herders as equally relevant responses to enhance livelihood resilience.

Reading comprehension of czech pupils at the beginning of primary school: comparison betweenanalytic-synthetic and genetic methods

In Czech schools two teaching methods of reading are used: the analytic-synthetic (conventional) and genetic (created in the 1990s). They differ in theoretical foundations and in methodology. The aim of this paper is to describe the above mentioned theoretical approaches and present the results of study that followed the differences in the development of initial reading skills between these methods. A total of 452 first grade children (age 6-8) were assessed by a battery of reading tests at the beginning and at the end of the first grade and at the beginning of the second grade. 350 pupils participated all three times. Based on data analysis the developmental dynamics of reading skills in both methods and the main differences in several aspects of reading abilities (e.g. the speed of reading, reading technique, error rate in reading) are described. The main focus is on the reading comprehension development. Results show that pupils instructed using genetic approach scored significantly better on used reading comprehension tests, especially in the first grade. Statistically significant differences occurred between classes independently of each method. Therefore, other factors such as teacher´s role and class composition are discussed.

The synthetic progestin norgestrel modulates Nrf2 signaling and acts as an antioxidant in a model of retinal degeneration

Retinitis pigmentosa (RP) is one of the most common retinal degenerative conditions affecting people worldwide, and is currently incurable. It is characterized by the progressive loss of photoreceptors, in which the death of rod cells leads to the secondary death of cone cells; the cause of eventual blindness. As rod cells die, retinal-oxygen metabolism becomes perturbed, leading to increased levels of reactive oxygen species (ROS) and thus oxidative stress; a key factor in the secondary death of cones. In this study, norgestrel, an FDA-approved synthetic analog of progesterone, was found to be a powerful neuroprotective antioxidant, preventing light-induced ROS in photoreceptor cells, and subsequent cell death. Norgestrel also prevented light-induced photoreceptor morphological changes that were associated with ROS production, and that are characteristic of RP. Further investigation showed that norgestrel acts via post-translational modulation of the major antioxidant transcription factor Nrf2; bringing about its phosphorylation, subsequent nuclear translocation, and increased levels of its effector protein superoxide dismutase 2 (SOD2). In summary, these results demonstrate significant protection of photoreceptor cells from oxidative stress, and underscore the potential of norgestrel as a therapeutic option for RP.

Solar magnetic carpet I: simulation of synthetic magnetograms

This paper describes a new 2D model for the photospheric evolution of the magnetic carpet. It is the first in a series of papers working towards constructing a realistic 3D non-potential model for the interaction of small-scale solar magnetic fields. In the model, the basic evolution of the magnetic elements is governed by a supergranular flow profile. In addition, magnetic elements may evolve through the processes of emergence, cancellation, coalescence and fragmentation. Model parameters for the emergence of bipoles are based upon the results of observational studies. Using this model, several simulations are considered, where the range of flux with which bipoles may emerge is varied. In all cases the model quickly reaches a steady state where the rates of emergence and cancellation balance. Analysis of the resulting magnetic field shows that we reproduce observed quantities such as the flux distribution, mean field, cancellation rates, photospheric recycle time and a magnetic network. As expected, the simulation matches observations more closely when a larger, and consequently more realistic, range of emerging flux values is allowed (4×1016 - 1019 Mx). The model best reproduces the current observed properties of the magnetic carpet when we take the minimum absolute flux for emerging bipoles to be 4×1016 Mx. In future, this 2D model will be used as an evolving photospheric boundary condition for 3D non-potential modeling.

Solar magnetic carpet III: coronal modelling of synthetic magnetograms

This article is the third in a series working towards the construction of a realistic, evolving, non-linear force-free coronal-field model for the solar magnetic carpet. Here, we present preliminary results of 3D time-dependent simulations of the small-scale coronal field of the magnetic carpet. Four simulations are considered, each with the same evolving photospheric boundary condition: a 48-hour time series of synthetic magnetograms produced from the model of Meyer et al. ( Solar Phys. 272, 29, 2011). Three simulations include a uniform, overlying coronal magnetic field of differing strength, the fourth simulation includes no overlying field. The build-up, storage, and dissipation of magnetic energy within the simulations is studied. In particular, we study their dependence upon the evolution of the photospheric magnetic field and the strength of the overlying coronal field. We also consider where energy is stored and dissipated within the coronal field. The free magnetic energy built up is found to be more than sufficient to power small-scale, transient phenomena such as nanoflares and X-ray bright points, with the bulk of the free energy found to be stored low down, between 0.5 - 0.8 Mm. The energy dissipated is currently found to be too small to account for the heating of the entire quiet-Sun corona. However, the form and location of energy-dissipation regions qualitatively agree with what is observed on small scales on the Sun. Future MHD modelling using the same synthetic magnetograms may lead to a higher energy release.

Use of Spirulina platensis micro and nanoparticles for the removal synthetic dyes from aqueous solutions by biosorption

In this research, micro and nanoparticles of Spirulina platensis dead biomass were obtained, characterized and employed to removal FD&C red no. 40 and acid blue 9 synthetic dyes from aqueous solutions. The effects of particle size (micro and nano) and biosorbent dosage (from 50 to 750 mg) were studied. Pseudofirst order, pseudo-second order and Elovich models were used to evaluate the biosorption kinetics. The biosorption nature was verified using energy dispersive X-ray spectroscopy (EDS). The best results for both dyes were found using 250 mg of nanoparticles, in these conditions, the biosorption capacities were 295 mg g−1 and 1450 mg g−1, and the percentages of dye removal were 15.0 and 72.5% for the FD&C red no. 40 and acid blue 9, respectively. Pseudo-first order model was the more adequate to represent the biosorption of both dyes onto microparticles, and Elovich model was more appropriate to the biosorption onto nanoparticles. The EDS results suggested that the dyes biosorption onto microparticles occurred mainly by physical interactions, and for the nanoparticles, chemisorption was dominant.

An electrochemical process for the production of synthetic fuels at low temperatures [Resumo]

Following work exploring the low temperature electrolysis in alkaline media, using graphite consumable anodes, from which syngas was obtained1, laboratory studies have been conducted in acid media pursuing higher efficiency in the production of hydrogen and synthetic fuels. Experiments were conducted in an own designed undivided planar cell with 25 cm2 geometrical area electrodes using a 0.5 M H2SO4 solution with and without Fe(II) additions. Fe2+ oxidizes to Fe3+ at the anode surface. The redox couple Fe3+/ Fe2+ acts as an oxidation mediator not only oxidizing the bulk and detached graphite but also the surface functional groups. The practical experimental potential for graphite oxidation is within the range for the electroxidation of the Fe redox couple giving as a result a 4-fold increase in the amount of produced CO2 at near room temperature, when using 0.025 M FeSO4.

Growth phase-specific promoters of cyanobacteria for synthetic biology applicatations

No abstract available.

Automatic Target Recognition in Synthetic Aperture Radar Imagery: A State-of-the-Art Review

The purpose of this paper is to survey and assess the state-of-the-art in automatic target recognition for synthetic aperture radar imagery (SAR-ATR). The aim is not to develop an exhaustive survey of the voluminous literature, but rather to capture in one place the various approaches for implementing the SAR-ATR system. This paper is meant to be as self-contained as possible, and it approaches the SAR-ATR problem from a holistic end-to-end perspective. A brief overview for the breadth of the SAR-ATR challenges is conducted. This is couched in terms of a single-channel SAR, and it is extendable to multi-channel SAR systems. Stages pertinent to the basic SAR-ATR system structure are defined, and the motivations of the requirements and constraints on the system constituents are addressed. For each stage in the SAR-ATR processing chain, a taxonomization methodology for surveying the numerous methods published in the open literature is proposed. Carefully selected works from the literature are presented under the taxa proposed. Novel comparisons, discussions, and comments are pinpointed throughout this paper. A two-fold benchmarking scheme for evaluating existing SAR-ATR systems and motivating new system designs is proposed. The scheme is applied to the works surveyed in this paper. Finally, a discussion is presented in which various interrelated issues, such as standard operating conditions, extended operating conditions, and target-model design, are addressed. This paper is a contribution toward fulfilling an objective of end-to-end SAR-ATR system design.