Profiling Three-Dimensional Nuclear Telomeric Architecture of Myelodysplastic Syndromes and Acute Myeloid Leukemia Defines Patient Subgroups

Purpose: Myelodysplastic syndromes (MDS) are a group of disorders characterized by cytopenias, with a propensity for evolution into acute myeloid leukemias (AML). This transformation is driven by genomic instability, but mechanisms remain unknown. Telomere dysfunction might generate genomic instability leading to cytopenias and disease progression. Experimental Design: We undertook a pilot study of 94 patients with MDS (56 patients) and AML (38 patients). The MDS cohort consisted of refractory cytopenia with multilineage dysplasia (32 cases), refractory anemia (12 cases), refractory anemia with excess of blasts (RAEB) 1 (8 cases), RAEB2 (1 case), refractory anemia with ring sideroblasts (2 cases), and MDS with isolated del(5q) (1 case). The AML cohort was composed of AML-M4 (12 cases), AML-M2 (10 cases), AML-M5 (5 cases), AML-M0 (5 cases), AML-M1 (2 cases), AML-M4eo (1 case), and AML with multidysplasia-related changes (1 case). Three-dimensional quantitative FISH of telomeres was carried out on nuclei from bone marrow samples and analyzed using TeloView. Results: We defined three-dimensional nuclear telomeric profiles on the basis of telomere numbers, telomeric aggregates, telomere signal intensities, nuclear volumes, and nuclear telomere distribution. Using these parameters, we blindly subdivided the MDS patients into nine subgroups and the AML patients into six subgroups. Each of the parameters showed significant differences between MDS and AML. Combining all parameters revealed significant differences between all subgroups. Three-dimensional telomeric profiles are linked to the evolution of telomere dysfunction, defining a model of progression from MDS to AML. Conclusions: Our results show distinct three-dimensional telomeric profiles specific to patients with MDS and AML that help subgroup patients based on the severity of telomere dysfunction highlighted in the profiles. Clin Cancer Res; 18(12); 3293-304. (C) 2012 AACR.

BMP-2 induces the expression of chondrocyte-specific genes in bovine synovium-derived progenitor cells cultured in three-dimensional alginate hydrogel

OBJECTIVE: According to recent reports, the synovial membrane may contain mesenchymal stem cells with the potential to differentiate into chondrocytes under appropriate conditions. In order to assess the usefulness of synovium-derived progenitor cells for the purposes of cartilage tissue engineering, we explored their requirements for the expression of chondrocyte-specific genes after expansion in vitro. DESIGN: Mesenchymal progenitor cells were isolated from the synovial membranes of bovine shoulder joints and expanded in two-dimensions on plastic surfaces. They were then seeded either as micromass cultures or as single cells within alginate gels, which were cultured in serum-free medium. Under these three-dimensional conditions, chondrogenesis is known to be supported and maintained. Cell cultures were exposed either to bone morphogenetic protein-2 (BMP-2) or to isoforms of transforming growth factor-beta (TGF-beta). The levels of mRNA for Sox9, collagen types I and II and aggrecan were determined by RT-PCR. RESULTS: When transferred to alginate gel cultures, the fibroblast-like synovial cells assumed a rounded form. BMP-2, but not isoforms of TGF-beta, stimulated, in a dose-dependent manner, the production of messenger RNAs (mRNAs) for Sox9, type II collagen and aggrecan. Under optimal conditions, the expression levels of cartilage-specific genes were comparable to those within cultured articular cartilage chondrocytes. However, in contrast to cultured articular cartilage chondrocytes, synovial cells exposed to BMP-2 continued to express the mRNA for alpha1(I) collagen. CONCLUSIONS: This study demonstrates that bovine synovium-derived mesenchymal progenitor cells can be induced to express chondrocyte-specific genes. However, the differentiation process is not complete under the chosen conditions. The stimulation conditions required for full transformation must now be delineated.

Three-dimensional primary stability of cementless femoral stems

OBJECTIVE: This study investigates by means of a new bone-prosthesis interface motion detector whether conceptual design differences of femoral stems are reflected in their primary stability pattern. DESIGN: An in vitro experiment using a biaxial materials testing machine in combination with three-dimensional motion measurement devices was performed. BACKGROUND: Primary stability of uncemented total hip replacements is considered to be a prerequisite for the quality of bony ongrowth to the femoral stem. Dynamic motion as a response to loading as well as total motion of the prosthesis have to be considered under quasi-physiological cyclic loading conditions. METHODS: Seven paired fresh cadaveric femora were used for the testing of two types of uncemented femoral stems with different anchoring concepts: CLS stem (Spotorno) and Cone Prosthesis (Wagner). Under sinusoidal cyclic loading mimicking in vivo hip joint forces a new measurement technique was applied allowing for the analysis of the three-dimensional interface motion. RESULTS: Considerable differences between the two prostheses could be detected both in their dynamic motion and total motion behaviour. Whereas the CLS stem, due to the wedge-shaped concept, provides smaller total motions, the longitudinal ribs of the Cone prostheses result in a substantially smaller dynamic motion. CONCLUSIONS: The measuring technique provided reliable and accurate data illustrating the three-dimensional interface motion of uncemented femoral stems.

Molecular-Based Magnetism in High-Spin Molecular Clusters and Three-Dimensional Networks Based on Cyanometalate Building Blocks

The field of molecule-based magnets is a relatively new branch of chemistry, which involves the design and study of molecular compounds that exhibit a spontaneous magnetic ordering below a critical temperature, Tc. One major goal involves the design of materials with tuneable Tc's for specific applications in memory storage devices. Molecule-based magnets with high magnetic ordering temperatures have recently been obtained from bimetallic and mixed-valence transition metal μ-cyanide complexes of the Prussian blue family. Since the μ-cyanide linkages permit an interaction between paramagnetic metal ions, cyanometalate building blocks have found useful applications in the field of molecule-based magnets. Our work involves the use of octacyanometalate building blocks for the self-assembly of two new classes of magnetic materials namely, high-spin molecular clusters which exhibit both ferromagnetic intra- and intercluster coupling, and specific extended network topologies which show long-range ferromagnetic ordering.

Three-Dimensional Analysis of Spiny Dendrites Using Straightening and Unrolling Transforms

Current understanding of the synaptic organization of the brain depends to a large extent on knowledge about the synaptic inputs to the neurons. Indeed, the dendritic surfaces of pyramidal cells (the most common neuron in the cerebral cortex) are covered by thin protrusions named dendritic spines. These represent the targets of most excitatory synapses in the cerebral cortex and therefore, dendritic spines prove critical in learning, memory and cognition. This paper presents a new method that facilitates the analysis of the 3D structure of spine insertions in dendrites, providing insight on spine distribution patterns. This method is based both on the implementation of straightening and unrolling transformations to move the analysis process to a planar, unfolded arrangement, and on the design of DISPINE, an interactive environment that supports the visual analysis of 3D patterns.

Using three-dimensional microfluidic networks for solving computationally hard problems

This paper describes the design of a parallel algorithm that uses moving fluids in a three-dimensional microfluidic system to solve a nondeterministically polynomial complete problem (the maximal clique problem) in polynomial time. This algorithm relies on (i) parallel fabrication of the microfluidic system, (ii) parallel searching of all potential solutions by using fluid flow, and (iii) parallel optical readout of all solutions. This algorithm was implemented to solve the maximal clique problem for a simple graph with six vertices. The successful implementation of this algorithm to compute solutions for small-size graphs with fluids in microchannels is not useful, per se, but does suggest broader application for microfluidics in computation and control.

Three-Dimensional Structure and Disposition of the Air Conducting and Gas Exchange Conduits of the Avian Lung: The Domestic Duck (Cairina moschata)

The anatomy of the domestic duck lung was studied macroscopically, by casting and by light, transmission, and scanning electron microscopy. The lung had four categories of secondary bronchi (SB), namely, the medioventral (MV, 4-5), laterodorsal (LD, 6-10), lateroventral (LV, 2-4), and posterior secondary bronchi (PO, 36-44). The neopulmonic parabronchi formed an intricate feltwork on the ventral third of the lung and inosculated those from the other SB. The lung parenchyma was organized into cylindrical parabronchi separated by thin septa containing blood vessels. Atria were shallow and well-fortified by epithelial ridges reinforced by smooth muscle bundles and gave rise to 2-6 elongate infundibulae. Air capillaries arose either directly from the atria or from infundibulae and were tubular or globular in shape with thin interconnecting branches. The newly described spatial disposition of the conducting air conduits closely resembles that of the chicken. This remarkable similarity between the categories, numbers, and 3D arrangement of the SB in the duck and chicken points to a convergence in function-oriented design. To illuminate airflow dynamics in the avian lung, precise directions of airflow in the various categories of SB and parabronchi need to be characterized.

The influence of cutting tool geometry upon aspects of chip flow and tool wear:a theoretical, three dimensional examination of the cutting geometry and the shape of the twist drill

This work is undertaken in the attempt to understand the processes at work at the cutting edge of the twist drill. Extensive drill life testing performed by the University has reinforced a survey of previously published information. This work demonstrated that there are two specific aspects of drilling which have not previously been explained comprehensively. The first concerns the interrelating of process data between differing drilling situations, There is no method currently available which allows the cutting geometry of drilling to be defined numerically so that such comparisons, where made, are purely subjective. Section one examines this problem by taking as an example a 4.5mm drill suitable for use with aluminium. This drill is examined using a prototype solid modelling program to explore how the required numerical information may be generated. The second aspect is the analysis of drill stiffness. What aspects of drill stiffness provide the very great difference in performance between short flute length, medium flute length and long flute length drills? These differences exist between drills of identical point geometry and the practical superiority of short drills has been known to shop floor drilling operatives since drilling was first introduced. This problem has been dismissed repeatedly as over complicated but section two provides a first approximation and shows that at least for smaller drills of 4. 5mm the effects are highly significant. Once the cutting action of the twist drill is defined geometrically there is a huge body of machinability data that becomes applicable to the drilling process. Work remains to interpret the very high inclination angles of the drill cutting process in terms of cutting forces and tool wear but aspects of drill design may already be looked at in new ways with the prospect of a more analytical approach rather than the present mix of experience and trial and error. Other problems are specific to the twist drill, such as the behaviour of the chips in the flute. It is now possible to predict the initial direction of chip flow leaving the drill cutting edge. For the future the parameters of further chip behaviour may also be explored within this geometric model.

Three-dimensional nitrogen-doped graphene supported molybdenum disulfide nanoparticles as an advanced catalyst for hydrogen evolution reaction

An efficient three-dimensional (3D) hybrid material of nitrogen-doped graphene sheets (N-RGO) supporting molybdenum disulfide (MoS2) nanoparticles with high-performance electrocatalytic activity for hydrogen evolution reaction (HER) is fabricated by using a facile hydrothermal route. Comprehensive microscopic and spectroscopic characterizations confirm the resulting hybrid material possesses a 3D crumpled few-layered graphene network structure decorated with MoS2 nanoparticles. Electrochemical characterization analysis reveals that the resulting hybrid material exhibits efficient electrocatalytic activity toward HER under acidic conditions with a low onset potential of 112 mV and a small Tafel slope of 44 mV per decade. The enhanced mechanism of electrocatalytic activity has been investigated in detail by controlling the elemental composition, electrical conductance and surface morphology of the 3D hybrid as well as Density Functional Theory (DFT) calculations. This demonstrates that the abundance of exposed active sulfur edge sites in the MoS2 and nitrogen active functional moieties in N-RGO are synergistically responsible for the catalytic activity, whilst the distinguished and coherent interface in MoS 2 /N-RGO facilitates the electron transfer during electrocatalysis. Our study gives insights into the physical/chemical mechanism of enhanced HER performance in MoS2/N-RGO hybrids and illustrates how to design and construct a 3D hybrid to maximize the catalytic efficiency.

Next generation high density three-dimensional magnetic recording systems

This work is the first work using patterned soft underlayers in multilevel three-dimensional vertical magnetic data storage systems. The motivation stems from an exponentially growing information stockpile, and a corresponding need for more efficient storage devices with higher density. The world information stockpile currently exceeds 150EB (ExaByte=1x1018Bytes); most of which is in analog form. Among the storage technologies (semiconductor, optical and magnetic), magnetic hard disk drives are posed to occupy a big role in personal, network as well as corporate storage. However; this mode suffers from a limit known as the Superparamagnetic limit; which limits achievable areal density due to fundamental quantum mechanical stability requirements. There are many viable techniques considered to defer superparamagnetism into the 100's of Gbit/in2 such as: patterned media, Heat-Assisted Magnetic Recording (HAMR), Self Organized Magnetic Arrays (SOMA), antiferromagnetically coupled structures (AFC), and perpendicular magnetic recording. Nonetheless, these techniques utilize a single magnetic layer; and can thusly be viewed as two-dimensional in nature. In this work a novel three-dimensional vertical magnetic recording approach is proposed. This approach utilizes the entire thickness of a magnetic multilayer structure to store information; with potential areal density well into the Tbit/in2 regime. ^ There are several possible implementations for 3D magnetic recording; each presenting its own set of requirements, merits and challenges. The issues and considerations pertaining to the development of such systems will be examined, and analyzed using empirical and numerical analysis techniques. Two novel key approaches are proposed and developed: (1) Patterned soft underlayer (SUL) which allows for enhanced recording of thicker media, (2) A combinatorial approach for 3D media development that facilitates concurrent investigation of various film parameters on a predefined performance metric. A case study is presented using combinatorial overcoats of Tantalum and Zirconium Oxides for corrosion protection in magnetic media. ^ Feasibility of 3D recording is demonstrated, and an emphasis on 3D media development is emphasized as a key prerequisite. Patterned SUL shows significant enhancement over conventional "un-patterned" SUL, and shows that geometry can be used as a design tool to achieve favorable field distribution where magnetic storage and magnetic phenomena are involved. ^

Optimization of three-dimensional branching networks of microchannels for thermal management of microelectronics

The aim of this work is to present a methodology to develop cost-effective thermal management solutions for microelectronic devices, capable of removing maximum amount of heat and delivering maximally uniform temperature distributions. The topological and geometrical characteristics of multiple-story three-dimensional branching networks of microchannels were developed using multi-objective optimization. A conjugate heat transfer analysis software package and an automatic 3D microchannel network generator were developed and coupled with a modified version of a particle-swarm optimization algorithm with a goal of creating a design tool for 3D networks of optimized coolant flow passages. Numerical algorithms in the conjugate heat transfer solution package include a quasi-ID thermo-fluid solver and a steady heat diffusion solver, which were validated against results from high-fidelity Navier-Stokes equations solver and analytical solutions for basic fluid dynamics test cases. Pareto-optimal solutions demonstrate that thermal loads of up to 500 W/cm2 can be managed with 3D microchannel networks, with pumping power requirements up to 50% lower with respect to currently used high-performance cooling technologies.

Conceptualising cosmopolitanism and entrepreneurship through the lens of the three-dimensional theory of power

Purpose – The paper aims to conceptualise cosmopolitanism drivers from the third-level power perspective by drawing on Lukes’ (1974; 2005) theory of power. In addition, the paper aims to investigate the relationship between entrepreneurs’ cosmopolitan dispositions and habitus, i.e. a pattern of an individual’s demeanour, as understood by Bourdieu. Design/methodology/approach – This conceptual paper makes use of Bourdieu’s framework (habitus) by extending it to the urban cosmopolitan environment and linking habitus to the three-dimensional theory of power and, importantly, to the power’s third dimension – preference-shaping. Findings – Once cosmopolitanism is embedded in the urban area’s values, this creates multiple endless rounds of mutual influence (by power holders onto entrepreneurs via political and business elites, and by entrepreneurs onto power holders via the same channels), with mutual benefit. Therefore, mutually beneficial influence that transpires in continuous support of a cosmopolitan city’s environment may be viewed as one of the factors that enhances cosmopolitan cities’ resilience to changes in macroeconomic conditions. Originality/value – The paper offers a theoretical model that enriches the understanding of the power-cosmopolitanism-entrepreneurship link, by emphasising the preference-shaping capacity of power, which leads to the embedment of cosmopolitanism in societal values. As a value shared by political and business elites, cosmopolitanism is also actively promoted by entrepreneurs through their disposition and habitus. This ensures not only their willing compliance with power and the environment, but also their enhancement of favourable business conditions. Entrepreneurs depart from mere acquiescence (to power and its explicit dominance), and instead practice their cosmopolitan influence by active preference-shaping.

Three-dimensional slope stability charts for frictional fill materials placed on purely cohesive clay

This paper investigates slope stability and produces a set of stability charts for three-dimensional (3D) slopes for a specific case in which frictional fill materials are placed on purely cohesive clay. As slopes are not usually plane strain in nature and are influenced by physical boundaries, this study uses a 3D analysis using the finite-element LB limit analysis method. Stability charts are convenient tools for geotechnical engineers during design in practice. For comparison purposes, the results from two-dimensional (2D) analyses are also discussed. The results from this study quantify the increase in the factors of safety obtained when 3D conditions are analyzed as opposed to the more traditional 2D.

Three dimensional printing as a way to create an engaging and meaningful context for learning

Three-dimensional (3D) printers are now commonplace in both primary and secondary schools within Australia. As with most new technologies they present a range of challenges to users in terms of technical problems and support, and how to integrate their use into the curriculum in a meaningful way. This research reports on data from a small number of Victorian primary schools from urban and regional areas. A case study methodology has been used to examine how each setting has approached the use of these printers and includes a review of the literature concerning the uptake of new technologies by non-experts. Data include interview transcripts from teachers, principals and technicians and photographic artefacts of 3D printed objects. Teachers reflected on their reasoning behind lesson plans and their aspirations for future use of 3D printers in the classroom. Some of the issues identified were teacher confidence, time to ‘play’ with and become familiar with 3D printers; and technical challenges that arose such as the time taken to print an object and clogging of printer extruders (heads). Recommendations are made concerning possible ways forward.