Representation of Neck Velocity and Neck–Vestibular Interactions in Pursuit Neurons in the Simian Frontal Eye Fields

The smooth pursuit system must interact with the vestibular system to maintain the accuracy of eye movements in space (i.e., gaze-movement) during head movement. Normally, the head moves on the stationary trunk. Vestibular signals cannot distinguish whether the head or whole body is moving. Neck proprioceptive inputs provide information about head movements relative to the trunk. Previous studies have shown that the majority of pursuit neurons in the frontal eye fields (FEF) carry visual information about target velocity, vestibular information about whole-body movements, and signal eye- or gaze-velocity. However, it is unknown whether FEF neurons carry neck proprioceptive signals. By passive trunk-on-head rotation, we tested neck inputs to FEF pursuit neurons in 2 monkeys. The majority of FEF pursuit neurons tested that had horizontal preferred directions (87%) responded to horizontal trunk-on-head rotation. The modulation consisted predominantly of velocity components. Discharge modulation during pursuit and trunk-on-head rotation added linearly. During passive head-on-trunk rotation, modulation to vestibular and neck inputs also added linearly in most neurons, although in half of gaze-velocity neurons neck responses were strongly influenced by the context of neck rotation. Our results suggest that neck inputs could contribute to representing eye- and gaze-velocity FEF signals in trunk coordinates

Topological phase-fluctuations, amplitude fluctuations, and criticality in extreme type-II superconductors

We study the effect of critical fluctuations on the $(B,T)$ phase diagram in extreme type-II superconductors in zero and finite magnetic field using large-scale Monte Carlo simulations on the Ginzburg-Landau model in a frozen gauge approximation. We show that a vortex-loop unbinding gives a correct picture of the zero field superconducting-normal transition even in the presence of amplitude fluctuations, which are far from being critical at $T_c$. We extract critical exponents of the dual model by studying the topological excitations of the original model. From the vortex-loop distribution function we extract the anomalous dimension of the dual field $\eta \simeq -0.18$, and conclude that the charged Ginzburg-Landau model and the neutral 3DXY model belong to different universality classes. We find are two distinct scaling regimes for the vortex-line lattice melting line: a high-field scaling regime and a distinct low-field 3DXY critical scaling regime. We also find indications of an abrupt change in the connectivity of the vortex-tangle in the vortex liquid along a line $T_L \geq T_M$. This is the finite field counter-part of the zero-field vortex-loop blowout. Which at low enough fields appears to coincide with $T_M$. Here, a description of the vortex system only in terms of field induced vortex lines is inadequate at and above the VLL melting temperature.Comment: 30 pages, 14 figure

miR-143 Overexpression Impairs Growth of Human Colon Carcinoma Xenografts in Mice with Induction of Apoptosis and Inhibition of Proliferation

BACKGROUND: MicroRNAs (miRNAs) are aberrantly expressed in human cancer and involved in the (dys)regulation of cell survival, proliferation, differentiation and death. Specifically, miRNA-143 (miR-143) is down-regulated in human colon cancer. In the present study, we evaluated the role of miR-143 overexpression on the growth of human colon carcinoma cells xenografted in nude mice (immunodeficient mouse strain: N: NIH(s) II-nu/nu). METHODOLOGY/PRINCIPAL FINDINGS: HCT116 cells with stable miR-143 overexpression (Over-143) and control (Empty) cells were subcutaneously injected into the flanks of nude mice, and tumor growth was evaluated over time. Tumors arose ∼ 14 days after tumor cell implantation, and the experiment was ended at 40 days after implantation. miR-143 was confirmed to be significantly overexpressed in Over-143 versus Empty xenografts, by TaqMan® Real-time PCR (p<0.05). Importantly, Over-143 xenografts displayed slower tumor growth compared to Empty xenografts from 23 until 40 days in vivo (p<0.05), with final volumes of 928±338 and 2512±387 mm(3), respectively. Evaluation of apoptotic proteins showed that Over-143 versus Empty xenografts displayed reduced Bcl-2 levels, and increased caspase-3 activation and PARP cleavage (p<0.05). In addition, the incidence of apoptotic tumor cells, assessed by TUNEL, was increased in Over-143 versus Empty xenografts (p<0.01). Finally, Over-143 versus Empty xenografts displayed significantly reduced NF-κB activation and ERK5 levels and activation (p<0.05), as well as reduced proliferative index, evaluated by Ki-67 immunohistochemistry (p<0.01). CONCLUSIONS: Our results suggest that reduced tumor volume in Over-143 versus Empty xenografts may result from increased apoptosis and decreased proliferation induced by miR-143. This reinforces the relevance of miR-143 in colon cancer, indicating an important role in the control of in vivo tumor progression, and suggesting that miR-143 may constitute a putative novel therapeutic tool for colon cancer treatment that warrants further investigation

Nature of the Low Field Transition in the Mixed State of High Temperature Superconductors

We have numerically studied the statics and dynamics of a model three-dimensional vortex lattice at low magnetic fields. For the statics we use a frustrated 3D XY model on a stacked triangular lattice. We model the dynamics as a coupled network of overdamped resistively-shunted Josephson junctions with Langevin noise. At low fields, there is a weakly first-order phase transition, at which the vortex lattice melts into a line liquid. Phase coherence parallel to the field persists until a sharp crossover, conceivably a phase transition, near $T_{\ell} > T_m$ which develops at the same temperature as an infinite vortex tangle. The calculated flux flow resistivity in various geometries near $T=T_{\ell}$ closely resembles experiment. The local density of field induced vortices increases sharply near $T_\ell$, corresponding to the experimentally observed magnetization jump. We discuss the nature of a possible transition or crossover at $T_\ell$(B) which is distinct from flux lattice melting.Comment: Updated references. 46 pages including low quality 25 eps figures. Contact [email protected] or visit http://www.physics.ohio-state.edu:80/~ryu/ for better figures and additional movie files from simulations. To be published in Physical Review B1 01Jun9

Extreme Type-II Superconductors in a Magnetic Field: A Theory of Critical Fluctuations

A theory of critical fluctuations in extreme type-II superconductors subjected to a finite but weak external magnetic field is presented. It is shown that the standard Ginzburg-Landau representation of this problem can be recast, with help of a novel mapping, as a theory of a new "superconductor", in an effective magnetic field whose overall value is zero, consisting of the original uniform field and a set of neutralizing unit fluxes attached to $N_{\Phi}$ fluctuating vortex lines. The long distance behavior is related to the anisotropic gauge theory in which the original magnetic field plays the role of "charge". The consequences of this "gauge theory" scenario for the critical behavior in high temperature superconductors are explored in detail, with particular emphasis on questions of 3D XY vs. Landau level scaling, physical nature of the vortex "line liquid" and the true normal state, and fluctuation thermodynamics and transport. A "minimal" set of requirements for the theory of vortex-lattice melting in the critical region is also proposed and discussed.Comment: 28 RevTeX pages, 4 .ps figures; appendix A added, additional references, streamlined Secs. IV and V in response to referees' comment

An Approach to Conceptual and Embodiment Design within a New Product Development Lifecycle Framework

[EN] The design of new innovative products is the result of an accurate and precise management of knowledge sources all over its life cycle, such as technology, market, competitors and suppliers. The work contributes with a framework that shows how the knowledge sources influence in the state-of-the-art and market needs so that they become opportunities for innovating products addressing the whole product life cycle. It provides a systematic path from the early generation of ideas to the production of a new product proposal. Through a deep analysis of previous research works of new product innovation life cycle development frameworks and linking it with knowledge management, strategic planning and scorecards, we came out with a structured contribution. The result considers the concurrent activities and its relationships all the way through the product life cycle that can help in creativity and innovation, combined with a process management proposal. Managing the sources of knowledge in highly dynamic markets and technologies is one of the major difficulties involved in innovative products design and development. The emerging knowledge from external sources is confronted with organisation internal knowledge and experience in order to achieve the first product correct.This work was supported by the Spanish Government and the Universitat Jaume I of Castellon (Spain) through research [project number P11B2009-37], entitled 'Methodologies for Implementing Product lifecycle management tools for mechanical Small and Medium Enterprises'.Vila, C.; Albinana, JC. (2016). An Approach to Conceptual and Embodiment Design within a New Product Development Lifecycle Framework. International Journal of Production Research. 54(10):2856-2874. https://doi.org/10.1080/00207543.2015.1110632S28562874541

MicroRNA-143 targets DNA methyltransferases 3A in colorectal cancer

Background:MicroRNAs (miRNAs) are 19-25-nucleotides regulatory non-protein-coding RNA molecules that regulate the expressions of a wide variety of genes, including some involved in cancer development. In this study, we investigated the possible role of miR-143 in colorectal cancer (CRC).Methods:Expression levels of human mature miRNAs were examined using real-time PCR-based expression arrays on paired colorectal carcinomas and adjacent non-cancerous colonic tissues. The downregulation of miR-143 was further evaluated in colon cancer cell lines and in paired CRC and adjacent non-cancerous colonic tissues by qRT-PCR. Potential targets of miR-143 were defined. The functional effect of miR-143 and its targets was investigated in human colon cancer cell lines to confirm miRNA-target association.Results:Both real-time PCR-based expression arrays and qRT-PCR showed that miR-143 was frequently downregulated in 87.5% (35 of 40) of colorectal carcinoma tissues compared with their adjacent non-cancerous colonic tissues. Using in silico predictions, DNA methyltranferase 3A (DNMT3A) was defined as a potential target of miR-143. Restoration of the miR-143 expression in colon cell lines decreased tumour cell growth and soft-agar colony formation, and downregulated the DNMT3A expression in both mRNA and protein levels. DNMT3A was shown to be a direct target of miR-143 by luciferase reporter assay. Furthermore, the miR-143 expression was observed to be inversely correlated with DNMT3A mRNA and protein expression in CRC tissues.Conclusion:Our findings suggest that miR-143 regulates DNMT3A in CRC. These findings elucidated a tumour-suppressive role of miR-143 in the epigenetic aberration of CRC, providing a potential development of miRNA-based targeted approaches for CRC therapy. © 2009 Cancer Research UK.published_or_final_versio

MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors

BACKGROUND MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with pre-malignant pancreatic tumors. We wished to compare the miRNA expression signatures in pancreatic benign cystic tumors (BCT) of low and high malignant potential with PDAC, in order to identify miRNAs deregulated during PDAC development. The mechanistic consequences of miRNA dysregulation were further evaluated. METHODS Tissue samples were obtained at a tertiary pancreatic unit from individuals with BCT and PDAC. MiRNA profiling was performed using a custom microarray and results were validated using RT-qPCR prior to evaluation of miRNA targets. RESULTS Widespread miRNA down-regulation was observed in PDAC compared to low malignant potential BCT. We show that amongst those miRNAs down-regulated, miR-16, miR-126 and let-7d regulate known PDAC oncogenes (targeting BCL2, CRK and KRAS respectively). Notably, miR-126 also directly targets the KRAS transcript at a "seedless" binding site within its 3'UTR. In clinical specimens, miR-126 was strongly down-regulated in PDAC tissues, with an associated elevation in KRAS and CRK proteins. Furthermore, miR-21, a known oncogenic miRNA in pancreatic and other cancers, was not elevated in PDAC compared to serous microcystic adenoma (SMCA), but in both groups it was up-regulated compared to normal pancreas, implicating early up-regulation during malignant change. CONCLUSIONS Expression profiling revealed 21 miRNAs down-regulated in PDAC compared to SMCA, the most benign lesion that rarely progresses to invasive carcinoma. It appears that miR-21 up-regulation is an early event in the transformation from normal pancreatic tissue. MiRNA expression has the potential to distinguish PDAC from normal pancreas and BCT. Mechanistically the down-regulation of miR-16, miR-126 and let-7d promotes PDAC transformation by post-transcriptional up-regulation of crucial PDAC oncogenes. We show that miR-126 is able to directly target KRAS; re-expression has the potential as a therapeutic strategy against PDAC and other KRAS-driven cancers

No evidence for cardiac dysfunction in Kif6 mutant mice.

A KIF6 variant in man has been reported to be associated with adverse cardiovascular outcomes after myocardial infarction. No clear biological or physiological data exist for Kif6. We sought to investigate the impact of a deleterious KIF6 mutation on cardiac function in mice. Kif6 mutant mice were generated and verified. Cardiac function was assessed by serial echocardiography at baseline, after ageing and after exercise. Lipid levels were also measured. No discernable adverse lipid or cardiac phenotype was detected in Kif6 mutant mice. These data suggest that dysfunction of Kif6 is linked to other more complex biological/biochemical parameters or is unlikely to be of material consequence in cardiac function