ROCK signalling induced gene expression changes in mouse pancreatic ductal adenocarcinoma cells

The RhoA and RhoC GTPases act via the ROCK1 and ROCK2 kinases to promote actomyosin contraction, resulting in directly induced changes in cytoskeleton structures and altered gene transcription via several possible indirect routes. Elevated activation of the Rho/ROCK pathway has been reported in several diseases and pathological conditions, including disorders of the central nervous system, cardiovascular dysfunctions and cancer. To determine how increased ROCK signalling affected gene expression in pancreatic ductal adenocarcinoma (PDAC) cells, we transduced mouse PDAC cell lines with retroviral constructs encoding fusion proteins that enable conditional activation of ROCK1 or ROCK2, and subsequently performed RNA sequencing (RNA-Seq) using the Illumina NextSeq 500 platform. We describe how gene expression datasets were generated and validated by comparing data obtained by RNA-Seq with RT-qPCR results. Activation of ROCK1 or ROCK2 signalling induced significant changes in gene expression that could be used to determine how actomyosin contractility influences gene transcription in pancreatic cancer

MINOS and CPT-violating neutrinos

We review the status of CPT violation in the neutrino sector. Apart from LSND, current data favors three flavors of light stable neutrinos and antineutrinos, with both halves of the spectrum having one smaller mass splitting and one larger mass splitting. Oscillation data for the smaller splitting is consistent with CPT. For the larger splitting, current data favor an antineutrino mass-squared splitting that is an order of magnitude larger than the corresponding neutrino splitting, with the corresponding mixing angle less-than-maximal. This CPT-violating spectrum is driven by recent results from MINOS, but is consistent with other experiments if we ignore LSND. We describe an analysis technique which, together with MINOS running optimized for muon antineutrinos, should be able to conclusively confirm the CPT-violating spectrum proposed here, with as little as three times the current data set. If confirmed, the CPT-violating neutrino mass-squared difference would be an order of magnitude less than the current most-stringent upper bound on CPT violation for quarks and charged leptons.Comment: 18 pages, title change, version to appear in Physical Review

Transcriptomic profiling of human breast and melanoma cells selected by migration through narrow constraints

The metastatic spread of cancer cells is a step-wise process that starts with dissociation from primary tumours and local invasion of adjacent tissues. The ability to invade local tissues is the product of several processes, including degradation of extracellular matrices (ECM) and movement of tumour cells through physically-restricting gaps. To identify properties contributing to tumour cells squeezing through narrow gaps, invasive MDA-MB-231 human breast cancer and MDA-MB-435 human melanoma cells were subjected to three successive rounds of selection using cell culture inserts with highly constraining 3 μm pores. For comparison purposes, flow cytometry was also employed to enrich for small diameter MDA-MB-231 cells. RNA-Sequencing (RNA-seq) using the Illumina NextSeq 500 platform was undertaken to characterize how gene expression differed between parental, invasive pore selected or small diameter cells. Gene expression results obtained by RNA-seq were validated by comparing with RT-qPCR. Transcriptomic data generated could be used to determine how alterations that enable cell passage through narrow spaces contribute to local invasion and metastasis

Complex-network analysis of combinatorial spaces: The NK landscape case

We propose a network characterization of combinatorial fitness landscapes by adapting the notion of inherent networks proposed for energy surfaces. We use the well-known family of NK landscapes as an example. In our case the inherent network is the graph whose vertices represent the local maxima in the landscape, and the edges account for the transition probabilities between their corresponding basins of attraction. We exhaustively extracted such networks on representative NK landscape instances, and performed a statistical characterization of their properties. We found that most of these network properties are related to the search difficulty on the underlying NK landscapes with varying values of K.Comment: arXiv admin note: substantial text overlap with arXiv:0810.3492, arXiv:0810.348

An evolutive computation solution for the TSP: possible application to organizations

This Thesis researches a possible improvement in the performance of the solution of certain NP-hard combinatorial optimization problems . Examples of these are pure sequencing problems. A summary of conventional methods is presented, and a comparison with those belonging to the field of Evolutive Computation is made. Also, a proposal of eventual improvements to the latter is included. The practical applications discussed in this thesis are strongly related to administration, network design in general, and circuit design.Resumen de Tesis de la autora presentada para acceder al título de Magister en Automatización de Oficinas (UNLP).Es revisión de: http://sedici.unlp.edu.ar/handle/10915/4059Facultad de Informátic

An evolutive computation solution for the TSP: possible application to organizations

This Thesis researches a possible improvement in the performance of the solution of certain NP-hard combinatorial optimization problems . Examples of these are pure sequencing problems. A summary of conventional methods is presented, and a comparison with those belonging to the field of Evolutive Computation is made. Also, a proposal of eventual improvements to the latter is included. The practical applications discussed in this thesis are strongly related to administration, network design in general, and circuit design.Es revisión de: http://sedici.unlp.edu.ar/handle/10915/4059Resumen de Tesis de la autora presentada para acceder al título de Magister en Automatización de Oficinas (UNLP).Facultad de Informátic

Diversity Of Short Gamma-Ray Burst Afterglows From Compact Binary Mergers Hosting Pulsars

Short gamma-ray bursts (sGRBs) are widely believed to result from the mergers of compact binaries. This model predicts an afterglow that bears the characteristic signatures of a constant, low density medium, including a smooth prompt-afterglow transition, and a simple temporal evolution. However, these expectations are in conflict with observations for a non-negligible fraction of sGRB afterglows. In particular, the onset of the afterglow phase for some of these events appears to be delayed and, in addition, a few of them exhibit late- time rapid fading in their lightcurves. We show that these peculiar observations can be explained independently of ongoing central engine activity if some sGRB progenitors are compact binaries hosting at least one pulsar. The Poynting flux emanating from the pulsar companion can excavate a bow-shock cavity surround- ing the binary. If this cavity is larger than the shock deceleration length scale in the undisturbed interstellar medium, then the onset of the afterglow will be delayed. Should the deceleration occur entirely within the swept-up thin shell, a rapid fade in the lightcurve will ensue. We identify two types of pulsar that can achieve the conditions necessary for altering the afterglow: low field, long lived pulsars, and high field pulsars. We find that a sizable fraction (~20-50%) of low field pulsars are likely to reside in neutron star binaries based on observations, while their high field counterparts are not. Hydrodynamical calculations motivated by this model are shown to be in good agreement with observations of sGRB afterglow lightcurves.Comment: Accepted to ApjL. Direct comparison to observed X-Ray afterglows now included. 5 Figure