Random strategies are nearly optimal for generalized van der Waerden Games

In a (1 : q) Maker-Breaker game, one of the central questions is to find (or at least estimate) the maximal value of q that allows Maker to win the game. Based on the ideas of Bednarska and Luczak [Bednarska, M., and T. Luczak, Biased positional games for which random strategies are nearly optimal, Combinatorica, 20 (2000), 477–488], who studied biased H-games, we prove general winning criteria for Maker and Breaker and a hypergraph generalization of their result. Furthermore, we study the biased version of a strong generalization of the van der Waerden games introduced by Beck [Beck, J., Van der Waerden and Ramsey type games, Combinatorica, 1 (1981), 103–116] and apply our criteria to determine the threshold bias of these games up to constant factor. As in the result of [Bednarska, M., and T. Luczak, Biased positional games for which random strategies are nearly optimal, Combinatorica, 20 (2000), 477–488], the random strategy for Maker is again the best known strategy.Postprint (updated version

Is there an unmet medical need for improved hearing restoration?

Hearing impairment, the most prevalent sensory deficit, affects more than 466 million people worldwide (WHO). We presently lack causative treatment for the most common form, sensorineural hearing impairment; hearing aids and cochlear implants (CI) remain the only means of hearing restoration. We engaged with CI users to learn about their expectations and their willingness to collaborate with health care professionals on establishing novel therapies. We summarize upcoming CI innovations, gene therapies, and regenerative approaches and evaluate the chances for clinical translation of these novel strategies. We conclude that there remains an unmet medical need for improving hearing restoration and that we are likely to witness the clinical translation of gene therapy and major CI innovations within this decade

Mean-field analysis of a dynamical phase transition in a cellular automaton model for collective motion

A cellular automaton model is presented for random walkers with biologically motivated interactions favoring local alignment and leading to collective motion or swarming behavior. The degree of alignment is controlled by a sensitivity parameter, and a dynamical phase transition exhibiting spontaneous breaking of rotational symmetry occurs at a critical parameter value. The model is analyzed using nonequilibrium mean field theory: Dispersion relations for the critical modes are derived, and a phase diagram is constructed. Mean field predictions for the two critical exponents describing the phase transition as a function of sensitivity and density are obtained analytically.Comment: 4 pages, 4 figures, final version as publishe

Overloaded adeno-associated virus as a novel gene therapeutic tool for otoferlin-related deafness

Hearing impairment is the most common sensory disorder in humans. So far, rehabilitation of profoundly deaf subjects relies on direct stimulation of the auditory nerve through cochlear implants. However, in some forms of genetic hearing impairment, the organ of Corti is structurally intact and therapeutic replacement of the mutated gene could potentially restore near natural hearing. In the case of defects of the otoferlin gene (OTOF), such gene therapy is hindered by the size of the coding sequence (~6 kb) exceeding the cargo capacity (<5 kb) of the preferred viral vector, adeno-associated virus (AAV). Recently, a dual-AAV approach was used to partially restore hearing in deaf otoferlin knock-out (Otof-KO) mice. Here, we employed in vitro and in vivo approaches to assess the gene-therapeutic potential of naturally-occurring and newly-developed synthetic AAVs overloaded with the full-length Otof coding sequence. Upon early postnatal injection into the cochlea of Otof-KO mice, overloaded AAVs drove specific expression of otoferlin in ~30% of all IHCs, as demonstrated by immunofluorescence labeling and polymerase chain reaction. Recordings of auditory brainstem responses and a behavioral assay demonstrated partial restoration of hearing. Together, our results suggest that viral gene therapy of DFNB9—using a single overloaded AAV vector—is indeed feasible, reducing the complexity of gene transfer compared to dual-AAV approaches

Sirt2 promotes white matter oligodendrogenesis during development and in models of neonatal hypoxia

Delayed oligodendrocyte (OL) maturation caused by hypoxia (Hx)-induced neonatal brain injury results in hypomyelination and leads to neurological disabilities. Previously, we characterized Sirt1 as a crucial regulator of OL progenitor cell (OPC) proliferation in response to Hx. We now identify Sirt2 as a critical promoter of OL differentiation during both normal white matter development and in a mouse model of Hx. Importantly, we find that Hx reduces Sirt2 expression in mature OLs and that Sirt2 overexpression in OPCs restores mature OL populations. Reduced numbers of Sirt2+ OLs were also observed in the white matter of preterm human infants. We show that Sirt2 interacts with p27Kip1/FoxO1, p21Cip1/Cdk4, and Cdk5 pathways, and that these interactions are altered by Hx. Furthermore, Hx induces nuclear translocation of Sirt2 in OPCs where it binds several genomic targets. Overall, these results indicate that a balance of Sirt1 and Sirt2 activity is required for developmental oligodendrogenesis, and that these proteins represent potential targets for promoting repair following white matter injury

Dislocation-induced structural and luminescence degradation in InAs quantum dot emitters on silicon

We probe the extent to which dislocations reduce carrier lifetimes and alter luminescence and growth morphology in InAs quantum dots (QD) grown on silicon. These heterostructures are key ingredients to achieving a highly reliable monolithically integrated light source on silicon necessary for photonic integrated circuits. We find up to 20-30% shorter carrier lifetimes at spatially resolved individual dislocations from both the QD ground and excited states at room temperature using time-resolved cathodoluminescence spectroscopy. These lifetimes are consistent with differences in the intensity measured under steady-state excitation suggesting that trap-assisted recombination limits the minority carrier lifetime, even away from dislocations. Our techniques also reveal the dramatic growth of misfit dislocations in these structures under carrier injection fueled by recombination-enhanced dislocation glide and III-V/Si residual strain. Beyond these direct effects of increased nonradiative recombination, we find the long-range strain field of misfit dislocations deeper in the defect filter layers employed during III-V/Si growth alter the QD growth environment and introduce a crosshatch-like variation in the QD emission color and intensity when the filter layer is positioned close to the QD emitter layer. Sessile threading dislocations generate even more egregious hillock defects that also reduce emission intensities by altering layer thicknesses, as measured by transmission electron microscopy and atom probe tomography. Our work presents a more complete picture of the impacts of dislocations relevant for the development of light sources for scalable silicon photonic integrated circuits.Comment: 15 pages, 6 figure

Global Diffusion in a Realistic Three-Dimensional Time-Dependent Nonturbulent Fluid Flow

We introduce and study the first model of an experimentally realizable three-dimensional time-dependent nonturbulent fluid flow to display the phenomenon of global diffusion of passive-scalar particles at arbitrarily small values of the nonintegrable perturbation. This type of chaotic advection, termed {\it resonance-induced diffusion\/}, is generic for a large class of flows.Comment: 4 pages, uuencoded compressed postscript file, to appear in Phys. Rev. Lett. Also available on the WWW from http://formentor.uib.es/~julyan/, or on paper by reques

A role of oligodendrocytes in information processing

Myelinating oligodendrocytes enable fast propagation of action potentials along the ensheathed axons. In addition, oligodendrocytes play diverse non-canonical roles including axonal metabolic support and activity-dependent myelination. An open question remains whether myelination also contributes to information processing in addition to speeding up conduction velocity. Here, we analyze the role of myelin in auditory information processing using paradigms that are also good predictors of speech understanding in humans. We compare mice with different degrees of dysmyelination using acute multiunit recordings in the auditory cortex, in combination with behavioral readouts. We find complex alterations of neuronal responses that reflect fatigue and temporal acuity deficits. We observe partially discriminable but similar deficits in well myelinated mice in which glial cells cannot fully support axons metabolically. We suggest a model in which myelination contributes to sus- tained stimulus perception in temporally complex paradigms, with a role of metabolically active oligodendrocytes in cortical information processing