Reasoning about crowd evacuations as emergent phenomena when using participatory computational models

How do students apply systems thinking to make sense of a computational model of crowd evacuation? We developed a participatory simulation in which users play the role of evacuees that move through a narrow passageway. This simulation demonstrates that when exceeding a certain speed, moving through narrow bottlenecks, is more likely to create clogs, leading to a slower passing rate. The participatory simulation was introduced in a lesson about school evacuation in a group of 9th graders. Their explanations of crowd evacuation, were compared to a similar group of 9th graders who learned the same ideas in a lecture without using the simulation. We found that using the simulation did not improve students’ system thinking about crowd evacuation compared to lecture-based instruction. About 80% of the students in both groups suggested partial/incomplete explanations of the inverse relationship between the desire to move faster as individuals and the opposite consequence of slower evacuation. Interviews with students revealed that some of them perceived the simulation scenario to be different from the organized and coordinated evacuation drills that they partook. Others, were engrossed in their own experiences as evacuees, that obscured their ability to relate the motion of individual evacuees and the overall evacuation rate of the crowd. In a second study, we examined whether prior learning of a different emergent process (spread of a disease) with a computational model, can prepare students for learning the counterintuitive phenomenon of crowd evacuation. We found that introducing a participatory simulation of the spread of a disease in a different group of 9th graders, increased their appreciation of the evacuation simulation as a learning tool, and consequently–their explanations. We conclude that computational models have the potential to enhance systems thinking, but their affordances depend on prior preparation for learning with other complex systems models

Detecting Cancer Gene Networks Characterized by Recurrent Genomic Alterations in a Population

High resolution, system-wide characterizations have demonstrated the capacity to identify genomic regions that undergo genomic aberrations. Such research efforts often aim at associating these regions with disease etiology and outcome. Identifying the corresponding biologic processes that are responsible for disease and its outcome remains challenging. Using novel analytic methods that utilize the structure of biologic networks, we are able to identify the specific networks that are highly significantly, nonrandomly altered by regions of copy number amplification observed in a systems-wide analysis. We demonstrate this method in breast cancer, where the state of a subset of the pathways identified through these regions is shown to be highly associated with disease survival and recurrence

Endogenous siRNAs promote proteostasis and longevity in germline-less Caenorhabditis elegans.

How lifespan and the rate of aging are set is a key problem in biology. Small RNAs are conserved molecules that impact diverse biological processes through the control of gene expression. However, in contrast to miRNAs, the role of endo-siRNAs in aging remains unexplored. Here, by combining deep sequencing and genomic and genetic approaches in Caenorhabditis elegans, we reveal an unprecedented role for endo-siRNA molecules in the maintenance of proteostasis and lifespan extension in germline-less animals. Furthermore, we identify an endo-siRNA-regulated tyrosine phosphatase, which limits the longevity of germline-less animals by restricting the activity of the heat shock transcription factor HSF-1. Altogether, our findings point to endo-siRNAs as a link between germline removal and the HSF-1 proteostasis and longevity-promoting somatic pathway. This establishes a role for endo siRNAs in the aging process and identifies downstream genes and physiological processes that are regulated by the endo siRNAs to affect longevity

Highly sensitive and specific detection of E. coli by a SERS nanobiosensor chip utilizing metallic nanosculptured thin films

A nanobiosensor chip, utilizing surface enhanced Raman spectroscopy (SERS) on nanosculptured thin films (nSTFs) of silver, was shown to detect Escherichia coli (E. coli) bacteria down to the concentration level of a single bacterium. The sensor utilizes highly enhanced plasmonic nSTFs of silver on a silicon platform for the enhancement of Raman bands as checked with adsorbed 4-aminothiophenol molecules. T-4 bacteriophages were immobilized on the aforementioned surface of the chip for the specific capture of target E. coli bacteria. To demonstrate that no significant non-specific immobilization of other bacteria occurs, three different, additional bacterial strains, Chromobacterium violaceum, Paracoccus denitrificans and Pseudomonas aeruginosa were used. Furthermore, experiments performed on an additional strain of E. coli to address the specificity and reusability of the sensor showed that the sensor operates for different strains of E. coli and is reusable. Time resolved phase contrast microscopy of the E. coli-T4 bacteriophage chip was performed to study its interaction with bacteria over time. Results showed that the present sensor performs a fast, accurate and stable detection of E. coli with ultra-small concentrations of bacteria down to the level of a single bacterium in 10 μl volume of the sample

New fermion mass textures from anomalous U(1) symmetries with baryon and lepton number conservation

In this paper, we present solutions to the fermion mass hierarchy problem in the context of the minimal supersymmetric standard theory augmented by an anomalous family-dependent U(1)_X symmetry. The latter is spontaneously broken by non-zero vevs of a pair of singlet fields whose magnitude is determined through the D- and F-flatness conditions of the superpotential. We derive the general solutions to the anomaly cancellation conditions and show that they allow numerous choices for the U(1)_X fermion charges which give several fermion mass textures in agreement with the observed fermion mass hierarchy and mixing. Solutions with U(1)_X fermion charge assignments are found which forbid or substantially suppress the dangerous baryon and lepton number violating operators and the lepton-higgs mixing coupling while a higgs mixing mass (\mu-term) can be fixed at the electroweak level. We give a general classification of the fermion mass textures with respect to the sum of the doublet-higgs U(1)_X-charges and show that suppression of dimension-five operators naturally occurs for various charge assignments. We work out cases which retain a quartic term providing the left-handed neutrinos with Majorana masses in the absence of right-handed neutrino components and consistent with the experimental bounds. Although there exist solutions which naturally combine all the above features with rather natural U(1)_X charges, the suppression of the \mu-term occurs for particular assignments.Comment: 32 page

Hierarchies of R-violating interactions from Family Symmetries

We investigate the possibility of constructing models of R-violating LQD Yukawa couplings using a single U(1) flavour-symmetry group and supermultiplet charge assignments that are compatible with the known hierarchies of quark and lepton masses. The mismatch of mass and current eigenstates inferred from the known charged-current mixing induces the propagation of strong phenomenological constraints on some R-violating couplings to many others. Applying these constraints, we look for flavour-symmetry models that are consistent with different squark-production hypotheses devised to explain the possible HERA large-Q^2 anomaly. The e^+ d -> stop interpretation of the HERA data is accommodated relatively easily, at the price of postulating an extra parity. The e^+ s -> stop interpretation of the events requires models to have only small (2,3) mixing in the down quark sector. The e^+ d -> scharm mechanism cannot be accommodated without large violations of squark-mass universality, due to the very strong experimental constraints on R-violating operators. We display a model in which baryon decay due to dangerous dimension-five operators is automatically suppressed.Comment: 21 pages, Latex file, no figure

SO(10) theory of R-parity and neutrino mass

We study the Higgs sector of a SO(10) grand unified theory which predicts exact conservation of R-parity at all scales and incorporates the see-saw mechanism. We find possible intermediate scales and light states compatible with the constraints coming from the running of the gauge couplings. Such a pattern could lower the SO(10) breaking scale, allowing the d=6 proton decay operators to be comparable in magnitude to the d=5 ones.Comment: 22 pages, 4 figure

Quark and Lepton Mass Matrices from Horizontal U(1) Symmetry

In the simplest model of horizontal U(1) symmetry with one singlet added to the supersymmetric standard model, we systematically reconstruct quark mass matrices from the low-energy data to prove that there are only two mass matrices found by Binetruy et.~al.. The same U(1) symmetry constrains the hierarchical structure of L-violating couplings, from which we build radiative neutrino mass matrices accommodating the solar and hot dark matter neutrino masses and mixing. We find a few patterns of acceptable charged lepton and neutrino mass matrices, most of which are consistent with large $\tan\beta \simeq m_t/m_b$ only.Comment: 15 pages, latex, no figures, version to appear in PL

The linker histone H1.0 generates epigenetic and functional intratumor heterogeneity

Tumors comprise functionally diverse subpopulations of cells with distinct proliferative potential. Here, we show that dynamic epigenetic states defined by the linker histone H1.0 determine which cells within a tumor can sustain the long-term cancer growth. Numerous cancer types exhibit high inter- and intratumor heterogeneity of H1.0, with H1.0 levels correlating with tumor differentiation status, patient survival, and, at the single-cell level, cancer stem cell markers. Silencing of H1.0 promotes maintenance of self-renewing cells by inducing derepression of megabase-sized gene domains harboring downstream effectors of oncogenic pathways. Self-renewing epigenetic states are not stable, and reexpression of H1.0 in subsets of tumor cells establishes transcriptional programs that restrict cancer cells’ long-term proliferative potential and drive their differentiation. Our results uncover epigenetic determinants of tumor-maintaining cells