DNA copy number changes define spatial patterns of heterogeneity in colorectal cancer

Genetic heterogeneity between and within tumours is a major factor determining cancer progression and therapy response. Here we examined DNA sequence and DNA copy-number heterogeneity in colorectal cancer (CRC) by targeted high-depth sequencing of 100 most frequently altered genes. In 97 samples, with primary tumours and matched metastases from 27 patients, we observe inter-tumour concordance for coding mutations; in contrast, gene copy numbers are highly discordant between primary tumours and metastases as validated by fluorescent in situ hybridization. To further investigate intra-tumour heterogeneity, we dissected a single tumour into 68 spatially defined samples and sequenced them separately. We identify evenly distributed coding mutations in APC and TP53 in all tumour areas, yet highly variable gene copy numbers in numerous genes. 3D morpho-molecular reconstruction reveals two clusters with divergent copy number aberrations along the proximal–distal axis indicating that DNA copy number variations are a major source of tumour heterogeneity in CRC

The magnetic interactions in spin-glasslike Ge/1-x-y/Sn/x/Mn/y/Te diluted magnetic semiconductor

We investigated the nature of the magnetic phase transition in the Ge/1-x-y/Sn/x/Mn/y/Te mixed crystals with chemical composition changing in the range of 0.083 < x < 0.142 and 0.012 < y < 0.119. The DC magnetization measurements performed in the magnetic field up to 90 kOe and temperature range 2-200 K showed that the magnetic ordering at temperatures below T = 50 K exhibits features characteristic for both spin-glass and ferromagnetic phases. The modified Sherrington - Southern model was applied to explain the observed transition temperatures. The calculations showed that the spin-glass state is preferred in the range of the experimental carrier concentrations and Mn content. The value of the Mn hole exchange integral was estimated to be J/pd/ = 0.45+/-0.05 eV. The experimental magnetization vs temperature curves were reproduced satisfactory using the non-interacting spin-wave theory with the exchange constant J/pd/ values consistent with those calculated using modified Sherrington - Southern model. The magnetization vs magnetic field curves showed nonsaturating behavior at magnetic fields B < 90 kOe indicating the presence of strong magnetic frustration in the system. The experimental results were reproduced theoretically with good accuracy using the molecular field approximation-based model of a disordered ferromagnet with long-range RKKY interaction.Comment: 9 pages, 6 figure

The Role of Mesotocin on Social Bonding in Pinyon Jays

The neuropeptide oxytocin influences mammalian social bonding by facilitating the building and maintenance of parental, sexual, and same‐sex social relationships. However, we do not know whether the function of the avian homologue mesotocin is evolutionarily conserved across birds. While it does influence avian prosocial behavior, mesotocin\u27s role in avian social bonding remains unclear. Here, we investigated whether mesotocin regulates the formation and maintenance of same‐sex social bonding in pinyon jays (Gymnorhinus cyanocephalus), a member of the crow family. We formed squads of four individually housed birds. In the first, “pair‐formation” phase of the experiment, we repeatedly placed pairs of birds from within the squad together in a cage for short periods of time. Prior to entering the cage, we intranasally administered one of three hormone solutions to both members of the pair: mesotocin, oxytocin antagonist, or saline. Pairs received repeated sessions with administration of the same hormone. In the second, “pair‐maintenance” phase of the experiment, all four members of the squad were placed together in a large cage, and no hormones were administered. For both phases, we measured the physical proximity between pairs as our proxy for social bonding. We found that, compared with saline, administering mesotocin or oxytocin antagonist did not result in different proximities in either the pair‐formation or pair‐maintenance phase of the experiment. Therefore, at the dosages and time frames used here, exogenously introduced mesotocin did not influence same‐sex social bond formation or maintenance. Like oxytocin in mammals, mesotocin regulates avian prosocial behavior; however, unlike oxytocin, we do not have evidence that mesotocin regulates social bonds in birds

Understanding the nature of "superhard graphite"

Numerous experiments showed that on cold compression graphite transforms into a new superhard and transparent allotrope. Several structures with different topologies have been proposed for this phase. While experimental data are consistent with these models, the only way to solve this puzzle is to find which structure is kinetically easiest to form. Using state-of-the-art molecular-dynamics transition path sampling simulations, we investigate kinetic pathways of the pressure-induced transformation of graphite to various superhard candidate structures. Unlike hitherto applied methods for elucidating nature of superhard graphite, transition path sampling realistically models nucleation events necessary for physically meaningful transformation kinetics. We demonstrate that nucleation mechanism and kinetics lead to $M$-carbon as the final product. $W$-carbon, initially competitor to $M$-carbon, is ruled out by phase growth. Bct-C$_4$ structure is not expected to be produced by cold compression due to less probable nucleation and higher barrier of formation

Czech Social Reform/Non-reform: Routes, Actors and Problems

In this contribution, the author first considers the characteristics of the Czechoslovak communist welfare state and its theoretical alternatives. Throughout the reform process, dependency on both corporatist and socialist regimes won out, while residualist efforts were promoted in the beginning, but were later held back. The author then considers the possible actors involved in social reforms. In this respect, when proceeding from a general to a more concrete level, thought should first be devoted to the social classes and their ideologies, and second to political parties and their leaders. The author goes on to summarise the particular problems and traps in individual sections of the Czech social system. While no objection to decent standards of social protection and health care could be raised, the poor efficiency of their achievement should evoke concern. The author concludes by reflecting on the possible specificities of Czech social reform in comparison with the other countries undergoing reform and the EU. The current lethargy of the Czech welfare system corresponds to a “frozen edifice”, just as in most Western countries. However, such stagnation is apparently acceptable to both the politicians (who mask it in reformist rhetoric) and the population (which learned to master taking advantage of the generous welfare state) and thus is basically sustainable in the long run.http://deepblue.lib.umich.edu/bitstream/2027.42/40037/3/wp651.pd

Advances in the numerical treatment of grain-boundary migration: Coupling with mass transport and mechanics

This work is based upon a coupled, lattice-based continuum formulation that was previously applied to problems involving strong coupling between mechanics and mass transport; e.g. diffusional creep and electromigration. Here we discuss an enhancement of this formulation to account for migrating grain boundaries. The level set method is used to model grain-boundary migration in an Eulerian framework where a grain boundary is represented as the zero level set of an evolving higher-dimensional function. This approach can easily be generalized to model other problems involving migrating interfaces; e.g. void evolution and free-surface morphology evolution. The level-set equation is recast in a remarkably simple form which obviates the need for spatial stabilization techniques. This simplified level-set formulation makes use of velocity extension and field re-initialization techniques. In addition, a least-squares smoothing technique is used to compute the local curvature of a grain boundary directly from the level-set field without resorting to higher-order interpolation. A notable feature is that the coupling between mass transport, mechanics and grain-boundary migration is fully accounted for. The complexities associated with this coupling are highlighted and the operator-split algorithm used to solve the coupled equations is described.Comment: 28 pages, 9 figures, LaTeX; Accepted for publication in Computer Methods in Applied Mechanics and Engineering. [Style and formatting modifications made, references added.

A participatory physical and psychosocial intervention for balancing the demands and resources among industrial workers (PIPPI): study protocol of a cluster-randomized controlled trial

Background: Need for recovery and work ability are strongly associated with high employee turnover, well-being and sickness absence. However, scientific knowledge on effective interventions to improve work ability and decrease need for recovery is scarce. Thus, the present study aims to describe the background, design and protocol of a cluster randomized controlled trial evaluating the effectiveness of an intervention to reduce need for recovery and improve work ability among industrial workers. Methods/Design: A two-year cluster randomized controlled design will be utilized, in which controls will also receive the intervention in year two. More than 400 workers from three companies in Denmark will be aimed to be cluster randomized into intervention and control groups with at least 200 workers (at least 9 work teams) in each group. An organizational resources audit and subsequent action planning workshop will be carried out to map the existing resources and act upon initiatives not functioning as intended. Workshops will be conducted to train leaders and health and safety representatives in supporting and facilitating the intervention activities. Group and individual level participatory visual mapping sessions will be carried out allowing team members to discuss current physical and psychosocial work demands and resources, and develop action plans to minimize strain and if possible, optimize the resources. At all levels, the intervention will be integrated into the existing organization of work schedules. An extensive process and effect evaluation on need for recovery and work ability will be carried out via questionnaires, observations, interviews and organizational data assessed at several time points throughout the intervention period. Discussion: This study primarily aims to develop, implement and evaluate an intervention based on the abovementioned features which may improve the work environment, available resources and health of industrial workers, and hence their need for recovery and work ability

Multi-Particle Collision Dynamics -- a Particle-Based Mesoscale Simulation Approach to the Hydrodynamics of Complex Fluids

In this review, we describe and analyze a mesoscale simulation method for fluid flow, which was introduced by Malevanets and Kapral in 1999, and is now called multi-particle collision dynamics (MPC) or stochastic rotation dynamics (SRD). The method consists of alternating streaming and collision steps in an ensemble of point particles. The multi-particle collisions are performed by grouping particles in collision cells, and mass, momentum, and energy are locally conserved. This simulation technique captures both full hydrodynamic interactions and thermal fluctuations. The first part of the review begins with a description of several widely used MPC algorithms and then discusses important features of the original SRD algorithm and frequently used variations. Two complementary approaches for deriving the hydrodynamic equations and evaluating the transport coefficients are reviewed. It is then shown how MPC algorithms can be generalized to model non-ideal fluids, and binary mixtures with a consolute point. The importance of angular-momentum conservation for systems like phase-separated liquids with different viscosities is discussed. The second part of the review describes a number of recent applications of MPC algorithms to study colloid and polymer dynamics, the behavior of vesicles and cells in hydrodynamic flows, and the dynamics of viscoelastic fluids

Precise Analysis of Polymer Rotational Dynamics

Through the analysis of individual chain dynamics alongside the corresponding molecular structures under shear via nonequilibrium molecular dynamics simulations of C178H358 linear and short-chain branched polyethylene melts under shear flow, we observed that the conventional method based on the chain end-to-end vector (and/or the gyration tensor of chain) is susceptible to quantitatively inaccurate measurements and often misleading information in describing the rotational dynamics of polymers. Identifying the flaw as attributed to strong irregular Brownian fluctuations inherent to the chain ends associated with their large free volume and strong molecular collisions, we propose a simple, robust way based on the chain center-to-center vector connecting the two centers of mass of the bisected chain, which is shown to adequately describe polymer rotational dynamics without such shortcomings. We present further consideration that the proposed method can be useful in accurately measuring the overall chain structure and dynamics of polymeric materials with various molecular architectures, including branched and ring polymers.open

Modulation-Mode Assignment in SVD-Aided Downlink Multiuser MIMO-OFDM Systems

Multicarrier transmission such as OFDM (orthogonal frequency division multiplexing) is an established technique for radio transmission systems and it can be considered as a promising approach for next generation wireless systems. However, in order to comply with the demand on increasing available data rates in particular in wireless technologies, systems with multiple transmit and receive antennas, also called MIMO (multiple-input multiple-output) systems, have become indispensable for future generations of wireless systems. Due to the strongly increasing demand in high-data rate transmission systems, frequency non-selective MIMO links have reached a state of maturity and frequency selective MIMO links are in the focus of interest. In this field, the combination of MIMO transmission and OFDM can be considered as an essential part of fulfilling the requirements of future generations of wireless systems. However, single-user scenarios have reached a state of maturity. By contrast multiple users' scenarios require substantial further research, where in comparison to ZF (zero-forcing) multiuser transmission techniques, the individual user's channel characteristics are taken into consideration in this contribution. The performed joint optimization of the number of activated MIMO layers and the number of transmitted bits per subcarrier shows that not necessarily all user-specific MIMO layers per subcarrier have to be activated in order to minimize the overall BER under the constraint of a given fixed data throughput