Active Transport of Peptides Across the Intact Human Tympanic Membrane.

We previously identified peptides that are actively transported across the intact tympanic membrane (TM) of rats with infected middle ears. To assess the possibility that this transport would also occur across the human TM, we first developed and validated an assay to evaluate transport in vitro using fragments of the TM. Using this assay, we demonstrated the ability of phage bearing a TM-transiting peptide to cross freshly dissected TM fragments from infected rats or from uninfected rats, guinea pigs and rabbits. We then evaluated transport across fragments of the human TM that were discarded during otologic surgery. Human trans-TM transport was similar to that seen in the animal species. Finally, we found that free peptide, unconnected to phage, was transported across the TM at a rate comparable to that seen for peptide-bearing phage. These studies provide evidence supporting the concept of peptide-mediated drug delivery across the intact TM and into the middle ears of patients

Fulcrum: Flexible Network Coding for Heterogeneous Devices

Producción CientíficaWe introduce Fulcrum, a network coding framework that achieves three seemingly conflicting objectives: 1) to reduce the coding coefficient overhead down to nearly n bits per packet in a generation of n packets; 2) to conduct the network coding using only Galois field GF(2) operations at intermediate nodes if necessary, dramatically reducing computing complexity in the network; and 3) to deliver an end-to-end performance that is close to that of a high-field network coding system for high-end receivers, while simultaneously catering to low-end receivers that decode in GF(2). As a consequence of 1) and 3), Fulcrum has a unique trait missing so far in the network coding literature: providing the network with the flexibility to distribute computational complexity over different devices depending on their current load, network conditions, or energy constraints. At the core of our framework lies the idea of precoding at the sources using an expansion field GF(2 h ), h > 1, to increase the number of dimensions seen by the network. Fulcrum can use any high-field linear code for precoding, e.g., Reed-Solomon or Random Linear Network Coding (RLNC). Our analysis shows that the number of additional dimensions created during precoding controls the trade-off between delay, overhead, and computing complexity. Our implementation and measurements show that Fulcrum achieves similar decoding probabilities as high field RLNC but with encoders and decoders that are an order of magnitude faster.Green Mobile Cloud project (grant DFF-0602-01372B)Colorcast project (grant DFF-0602-02661B)TuneSCode project (grant DFF - 1335-00125)Danish Council for Independent Research (grant DFF-4002-00367)Ministerio de Economía, Industria y Competitividad - Fondo Europeo de Desarrollo Regional (grants MTM2012-36917-C03-03 / MTM2015-65764-C3-2-P / MTM2015-69138-REDT)Agencia Estatal de Investigación - Fondo Social Europeo (grant RYC-2016-20208)Aarhus Universitets Forskningsfond Starting (grant AUFF-2017-FLS-7-1

The Deligne-Simpson problem for connections on Gm\mathbb{G}_m with a maximally ramified singularity

The classical additive Deligne-Simpson problem is the existence problem for Fuchsian connections with residues at the singular points in specified adjoint orbits. Crawley-Boevey found the solution in 2003 by reinterpreting the problem in terms of quiver varieties. A more general version of this problem, solved by Hiroe, allows additional unramified irregular singularities. We apply the theory of fundamental and regular strata due to Bremer and Sage to formulate a version of the Deligne-Simpson problem in which certain ramified singularities are allowed. These allowed singular points are called toral singularities; they are singularities whose leading term with respect to a lattice chain filtration is regular semisimple. We solve this problem in the important special case of connections on $\mathbb{G}_m$ with a maximally ramified singularity at $0$ and possibly an additional regular singular point at infinity. We also give a complete characterization of all such connections which are rigid, under the additional hypothesis of unipotent monodromy at infinity.Comment: 27 pages. Minor correction

Neonatal Cerebral Hypoxia-Ischemia Impairs Plasticity in Rat Visual Cortex

Ocular dominance plasticity (ODP) following monocular deprivation (MD) is a model of activity-dependent neural plasticity that is restricted to an early critical period regulated by maturation of inhibition. Unique developmental plasticity mechanisms may improve outcomes following early brain injury. Our objective was to determine the effects of neonatal cerebral hypoxia–ischemia (HI) on ODP. The rationale extends from observations that neonatal HI results in death of subplate neurons, a transient population known to influence development of inhibition. In rodents subjected to neonatal HI and controls, maps of visual response were derived from optical imaging during the critical period for ODP and changes in the balance of eye-specific response following MD were measured. In controls, MD results in a shift of the ocular dominance index (ODI) from a baseline of 0.15 to −0.10 (p < 0.001). Neonatal HI with moderate cortical injury impairs this shift, ODI = 0.14 (p < 0.01). Plasticity was intact in animals with mild injury and in those exposed to hypoxia alone. Neonatal HI resulted in decreased parvalbumin expression in hemispheres receiving HI compared with hypoxia alone: 23.4 versus 35.0 cells/high-power field (p = 0.01), with no change in other markers of inhibitory or excitatory neurons. Despite abnormal inhibitory neuron phenotype, spontaneous activity of single units and development of orientation selective responses were intact following neonatal HI, while overall visual responses were reduced. Our data suggest that specific plasticity mechanisms are impaired following early brain injury and that the impairment is associated with altered inhibitory neuronal development and cortical activation

Inhibition of Aβ42 aggregation using peptides selected from combinatorial libraries

Increasing evidence suggests that the aggregation of the small peptide Aβ42 plays an important role in the development of Alzheimer’s disease. Inhibiting the initial aggregation of Aβ42 may be an effective treatment for preventing, or slowing, the onset of the disease. Using an in vivo screen based on the enzyme EGFP, we have searched through two combinatorially diverse peptide libraries to identify peptides capable of inhibiting Aβ42 aggregation. From this initial screen, three candidate peptides were selected and characterized. ThT studies indicated that the selected peptides were capable of inhibiting amyloid aggregation. Additional ThT studies showed that one of the selected peptides was capable of disaggregating preformed Aβ42 fibers

Editorial: on the road towards treatment of gastroparesis—accelerating, but do we get closer? Authors' reply

LINKED CONTENTThis article is linked to Kuo et al and Wuestenberghs & Gourcerol papers. To view these articles, visit https://doi.org/10.1111/apt.16344 and https://doi.org/10.1111/apt.1637

Force distributions in 3D granular assemblies: Effects of packing order and inter-particle friction

We present a systematic investigation of the distribution of normal forces at the boundaries of static packings of spheres. A new method for the efficient construction of large hexagonal-close-packed crystals is introduced and used to study the effect of spatial ordering on the distribution of forces. Under uniaxial compression we find that the form for the probability distribution of normal forces between particles does not depend strongly on crystallinity or inter-particle friction. In all cases the distribution decays exponentially at large forces and shows a plateau or possibly a small peak near the average force but does not tend to zero at small forces.Comment: 9 pages including 8 figure