HDAC inhibitors in acute myeloid leukemia

Acute myeloid leukemia (AML) is a hematological malignancy characterized by uncontrolled proliferation, differentiation arrest, and accumulation of immature myeloid progenitors. Although clinical advances in AML have been made, especially in young patients, long-term disease-free survival remains poor, making this disease an unmet therapeutic challenge. Epigenetic alterations and mutations in epigenetic regulators contribute to the pathogenesis of AML, supporting the rationale for the use of epigenetic drugs in patients with AML. While hypomethylating agents have already been approved in AML, the use of other epigenetic inhibitors, such as histone deacetylases (HDAC) inhibitors (HDACi), is under clinical development. HDACi such as Panobinostat, Vorinostat, and Tricostatin A have been shown to promote cell death, autophagy, apoptosis, or growth arrest in preclinical AML models, yet these inhibitors do not seem to be effective as monotherapies, but rather in combination with other drugs. In this review, we discuss the rationale for the use of different HDACi in patients with AML, the results of preclinical studies, and the results obtained in clinical trials. Although so far the results with HDACi in clinical trials in AML have been modest, there are some encouraging data from treatment with the HDACi Pracinostat in combination with DNA demethylating agents

Incorporating bio-physical sciences into a decision support tool for sustainable urban planning

Deciding upon optimum planning actions in terms of sustainable urban planning involves the consideration of multiple environmental and socio-economic criteria. The transformation of natural landscapes to urban areas affects energy and material fluxes. An important aspect of the urban environment is the urban metabolism, and changes in such metabolism need to be considered for sustainable planning decisions. A spatial Decision Support System (DSS) prototyped within the European FP7-funded project BRIDGE (sustainaBle uRban plannIng Decision support accountinG for urban mEtabolism), enables accounting for the urban metabolism of planning actions, by exploiting the current knowledge and technology of biophysical sciences. The main aim of the BRIDGE project was to bridge the knowledge and communication gap between urban planners and environmental scientists and to illustrate the advantages of considering detailed environmental information in urban planning processes. The developed DSS prototype integrates biophysical observations and simulation techniques with socio-economic aspects in fiveEuropean cities, selected as case studies for the pilot application of the tool. This paper describes the design and implementation of the BRIDGE DSS prototype, illustrates some examples of use, and highlights the need for further research and development in the field

Cost effective manufacturing of the SEA 10X concentrator array

This report describes a low-cost, mass-producible 10X concentrator system that has been claimed to produce electricity at $0.04/kWh. It details changes in manufacturing techniques that could produce a concentrator system at a selling price of$0.71/W. (A simple design and a minimum number of parts and manufacturing steps reduced production costs.) Present production techniques, changes to improve these techniques, impediments to changes, and solutions to the impediments are described. This 10X concentrator system uses available components and manufacturing processes and one-sun solar cells in conjunction with inexpensive plastic lenses to generate about eight times the amount of electricity normally produced by these cells

Symmetry Breakdown in Franckeite: Spontaneous Strain, Rippling, and Interlayer Moire

Franckeite is a naturally occurring layered mineral with a structure composed of alternating stacks of SnS2-like and PbS-like layers. Although this superlattice is composed of a sequence of isotropic two-dimensional layers, it exhibits a spontaneous rippling that makes the material structurally anisotropic. We demonstrate that this rippling comes hand in hand with an inhomogeneous in-plane strain profile and anisotropic electrical, vibrational, and optical properties. We argue that this symmetry breakdown results from a spatial modulation of the van der Waals interaction between layers due to the SnS2-like and PbS-like lattices incommensurability

Differences in Respiratory Symptoms and Lung Structure Between Hispanic and Non-Hispanic White Smokers: A Comparative Study

Background: Prior studies have demonstrated that U.S. Hispanic smokers have a lower risk of decline in lung function and chronic obstructive pulmonary disease (COPD) compared with non-Hispanic whites (NHW). This suggests there might be racial-ethnic differences in susceptibility in cigarette smoke-induced respiratory symptoms, lung parenchymal destruction, and airway and vascular disease, as well as in extra-pulmonary manifestations of COPD. Therefore, we aimed to explore respiratory symptoms, lung function, and pulmonary and extra-pulmonary structural changes in Hispanic and NHW smokers. Methods: We compared respiratory symptoms, lung function, and computed tomography (CT) measures of emphysema-like tissue, airway disease, the branching generation number (BGN) to reach a 2-mm-lumen-diameter airway, and vascular pruning as well as muscle and fat mass between 39 Hispanic and 39 sex-, age- and smoking exposure-matched NHW smokers. Results: Hispanic smokers had higher odds of dyspnea than NHW after adjustment for COPD and asthma statuses (odds ratio[OR] = 2.96; 95% confidence interval [CI] 1.09-8.04), but no significant differences were found in lung function and CT measurements. Conclusions: While lung function and CT measures of the lung structure were similar, dyspnea is reported more frequently by Hispanic than matched-NHW smokers. It seems to be an impossible puzzle but it's easy to solve a Rubik' Cube using a few algorithms

Insights into the Late Mesolithic toolkit: use-wear analysis of the notched blades. Case-studies from the Iberian Peninsula

During the last decades we have gained a considerable amount of data about the Mesolithic lithic toolkit in the Western Mediterranean. A large set of instruments probably existed for a variety of pur-poses: foraging practices (both hunting and fishing), food processing, crafting activities, etc. Dispos-able tools, scarcely elaborated, coexisted with formal and more complex instruments, often com-posed of multiple parts and realized on a variety of raw-materials (e.g. stone, shell or bone inserts; bone or wood hafts, etc.). In this paper we will consider one particular type of tool that appears in the Western Mediterranean starting from the Seventh-Sixth millennia BC: the notched and denticulated blades. We will consider and interpret from a functional viewpoint materials from five different Late Mesolithic contexts: the Cocina Cave and Vallmayor IX in the NE of the Peninsula, Artusia rock-shel-ters in Navarre and Atxoste and Mendandia rock-shelters in the Basque country

Quantum and classical confinement of resonant states in a trilayer graphene Fabry-Pérot interferometer

The advent of few-layer graphene has given rise to a new family of two-dimensional systems with emergent electronic properties governed by relativistic quantum mechanics. The multiple carbon sublattices endow the electronic wavefunctions with pseudospin, a lattice analogue of the relativistic electron spin, whereas the multilayer structure leads to electric-field-effect tunable electronic bands. Here we use these properties to realize giant conductance oscillations in ballistic trilayer graphene Fabry-Pérot interferometers, which result from phase coherent transport through resonant bound states beneath an electrostatic barrier. We confine these states by selectively decoupling them from the leads, resulting in transport via non-resonant states and suppression of the giant oscillations. The confinement is achieved both classically, by manipulating quasiparticle momenta with a magnetic field, and quantum mechanically, by locally varying the pseudospin character of the carrier wavefunctions. Our results illustrate the unique potential of trilayer graphene as a versatile platform for electron optics and pseudospintronics.United States. Office of Naval Research (GATE MURI)National Science Foundation (U.S.) (Career Award DMR-0845287)Conselho Nacional de Pesquisas (Brazil

Quantum and classical confinement of resonant states in a trilayer graphene Fabry-Pérot interferometer

The advent of few-layer graphene has given rise to a new family of two-dimensional systems with emergent electronic properties governed by relativistic quantum mechanics. The multiple carbon sublattices endow the electronic wavefunctions with pseudospin, a lattice analogue of the relativistic electron spin, whereas the multilayer structure leads to electric-field-effect tunable electronic bands. Here we use these properties to realize giant conductance oscillations in ballistic trilayer graphene Fabry-Pérot interferometers, which result from phase coherent transport through resonant bound states beneath an electrostatic barrier. We confine these states by selectively decoupling them from the leads, resulting in transport via non-resonant states and suppression of the giant oscillations. The confinement is achieved both classically, by manipulating quasiparticle momenta with a magnetic field, and quantum mechanically, by locally varying the pseudospin character of the carrier wavefunctions. Our results illustrate the unique potential of trilayer graphene as a versatile platform for electron optics and pseudospintronics.United States. Office of Naval Research (GATE MURI)National Science Foundation (U.S.) (Career Award DMR-0845287)Conselho Nacional de Pesquisas (Brazil

Strain-induced Evolution of Electronic Band Structures in a Twisted Graphene Bilayer

Here we study the evolution of local electronic properties of a twisted graphene bilayer induced by a strain and a high curvature. The strain and curvature strongly affect the local band structures of the twisted graphene bilayer; the energy difference of the two low-energy van Hove singularities decreases with increasing the lattice deformations and the states condensed into well-defined pseudo-Landau levels, which mimic the quantization of massive Dirac fermions in a magnetic field of about 100 T, along a graphene wrinkle. The joint effect of strain and out-of-plane distortion in the graphene wrinkle also results in a valley polarization with a significant gap, i.e., the eight-fold degenerate Landau level at the charge neutrality point is splitted into two four-fold degenerate quartets polarized on each layer. These results suggest that strained graphene bilayer could be an ideal platform to realize the high-temperature zero-field quantum valley Hall effect.Comment: 4 figure