The Immunological Basis of Dry Eye Disease and Current Topical Treatment Options.

Homeostasis of the lacrimal functional unit is needed to ensure a well-regulated ocular immune response comprising innate and adaptive phases. When the ocular immune system is excessively stimulated and/or immunoregulatory mechanisms are disrupted, the balance between innate and adaptive phases is dysregulated and chronic ocular surface inflammation can result, leading to chronic dry eye disease (DED). According to the Tear Film and Ocular Surface Society Dry Eye Workshop II definition, DED is a multifactorial disorder of the ocular surface characterized by impairment and loss of tear homeostasis (hyperosmolarity), ocular discomfort or pain, and neurosensory abnormalities. Dysregulated ocular immune responses result in ocular surface damage, which is a further contributing factor to DED pathology. Several therapeutics are available to break the vicious circle of DED and prevent chronic disease and progression, including immunosuppressive agents (steroids) and immunomodulators (cyclosporine and lifitegrast). Given the chronic inflammatory nature of DED, each of these agents is commonly used in clinical practice. In this study, we review the immunopathology of DED and the molecular and cellular actions of current topical DED therapeutics to inform clinical decision making

Trellis decoding complexity of linear block codes

In this partially tutorial paper, we examine minimal trellis representations of linear block codes and analyze several measures of trellis complexity: maximum state and edge dimensions, total span length, and total vertices, edges and mergers. We obtain bounds on these complexities as extensions of well-known dimension/length profile (DLP) bounds. Codes meeting these bounds minimize all the complexity measures simultaneously; conversely, a code attaining the bound for total span length, vertices, or edges, must likewise attain it for all the others. We define a notion of “uniform” optimality that embraces different domains of optimization, such as different permutations of a code or different codes with the same parameters, and we give examples of uniformly optimal codes and permutations. We also give some conditions that identify certain cases when no code or permutation can meet the bounds. In addition to DLP-based bounds, we derive new inequalities relating one complexity measure to another, which can be used in conjunction with known bounds on one measure to imply bounds on the others. As an application, we infer new bounds on maximum state and edge complexity and on total vertices and edges from bounds on span lengths

Gauge coupling Unification and SO(10) in 5D

We analyze the gauge unification in minimal supersymmetric SO(10) grand unified theories in 5 dimensions. The single extra spatial dimension is compactified on the orbifold S^1/(Z_2 x Z_2') reducing the gauge group to that of Pati-Salam SU(4)_c x SU(2)_L x SU(2)_R. The Standard Model gauge group is achieved by the further brane-localized Higgs mechanism on one of the fixed points. There are two main different approaches developed in literature. Higgs mechanism can take place on the Pati Salam brane, or on the SO(10) preserving brane. We show, both analytically and numerically, that in the first case a natural and succesfull gauge coupling unification can be achieved, while the second case is highly disfavoured. For completeness, we consider either the case in which the brane breaking scale is near the cutoff scale or the case in which it is lower than the compactification scale.Comment: 18 Pages and 8 PostScript Figure

Hf-based high-k dielectrics for p-Ge MOS gate stacks

The physical and electrical properties of the gate stack high-k/Al2O3/GeO2/p-Ge were studied in detail, where the high-k is either HfO2 or alloyed HfO2 (HfZrOy, HfGdOx, or HfAlOx). Electrical measurements combined with x-ray photoelectron spectroscopy chemical bonding analysis and band alignment determination were conducted in order to assess the suitability of hafnium-based high-k for this kind of gate stacks, with emphasis on low density of interface states and border traps. HfAlOx was found to be the most promising high-k from those studied. The authors have also found that the current- voltage trends for the various systems studied can be explained by the band alignment of the samples obtained by our x-ray photoelectron spectroscopy analysis.Fil: Fadida, Sivan. Technion - Israel Institute of Technology; IsraelFil: Palumbo, Félix Roberto Mario. Technion - Israel Institute of Technology; Israel. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Nyns, Laura. Imec; BélgicaFil: Lin, Dennis. Imec; BélgicaFil: Van Elshocht, Sven. Imec; BélgicaFil: Caymax, Matty. Imec; BélgicaFil: Eizenberg, Moshe. Technion - Israel Institute of Technology; Israe

Nano-to-Submicron Hydroxyapatite Coatings for Magnesium-based Bioresorbable Implants - Deposition, Characterization, Degradation, Mechanical Properties, and Cytocompatibility.

Magnesium (Mg) and its alloys have shown attractive biocompatibility and mechanical strength for medical applications, but low corrosion resistance of Mg in physiological environment limits its broad clinical translation. Hydroxyapatite (HA) nanoparticles (nHA) are promising coating materials for decreasing degradation rates and prolonging mechanical strength of Mg-based implants while enhancing bone healing due to their osteoconductivity and osteoinductivity. Conformal HA coatings with nano-to-submicron structures, namely nHA and mHA coatings, were deposited successfully on Mg plates and rods using a transonic particle acceleration (TPA) process under two different conditions, characterized, and investigated for their effects on Mg degradation in vitro. The nHA and mHA coatings enhanced corrosion resistance of Mg and retained 86-90% of ultimate compressive strength after in vitro immersion in rSBF for 6 weeks, much greater than non-coated Mg that only retained 66% of strength. Mg-based rods with or without coatings showed slower degradation than the respective Mg-based plates in rSBF after 6 weeks, likely because of the greater surface-to-volume ratio of Mg plates than Mg rods. This indicates that Mg-based plate and screw devices may undergo different degradation even when they have the same coatings and are implanted at the same or similar anatomical locations. Therefore, in addition to locations of implantation, the geometry, dimension, surface area, volume, and mass of Mg-based implants and devices should be carefully considered in their design and processing to ensure that they not only provide adequate structural and mechanical stability for bone fixation, but also support the functions of bone cells, as clinically required for craniomaxillofacial (CMF) and orthopedic implants. When the nHA and mHA coated Mg and non-coated Mg plates were cultured with bone marrow derived mesenchymal stem cells (BMSCs) using the in vitro direct culture method, greater cell adhesion densities were observed under indirect contact conditions than that under direct contact conditions for the nHA and mHA coated Mg. In comparison with non-coated Mg, the nHA and mHA coated Mg reduced BMSC adhesion densities directly on the surface, but increased the average BMSC adhesion densities under indirect contact. Further long-term studies in vitro and in vivo are necessary to elucidate the effects of nHA and mHA coatings on cell functions and tissue healing

Novel insights into the Thaumarchaeota in the deepest oceans: their metabolism and potential adaptation mechanisms

Background: Marine Group I (MGI) Thaumarchaeota, which play key roles in the global biogeochemical cycling of nitrogen and carbon (ammonia oxidizers), thrive in the aphotic deep sea with massive populations. Recent studies have revealed that MGI Thaumarchaeota were present in the deepest part of oceans - the hadal zone (depth > 6,000 m, consisting almost entirely of trenches), with the predominant phylotype being distinct from that in the “shallower” deep sea. However, little is known about the metabolism and distribution of these ammonia oxidizers in the hadal water. Results: In this study, metagenomic data were obtained from 0-10,500 m deep seawater samples from the Mariana Trench. The distribution patterns of Thaumarchaeota derived from metagenomics and 16S rRNA gene sequencing were in line with that reported in previous studies: abundance of Thaumarchaeota peaked in bathypelagic zone (depth 1,000 – 4,000 m) and the predominant clade shifted in the hadal zone. Several metagenome-assembled thaumarchaeotal genomes were recovered, including a near-complete one representing the dominant hadal phylotype of MGI. Using comparative genomics we predict that unexpected genes involved in bioenergetics, including two distinct ATP synthase genes (predicted to be coupled with H+ and Na+ respectively), and genes horizontally transferred from other extremophiles, such as those encoding putative di-myo-inositol-phosphate (DIP) synthases, might significantly contribute to the success of this hadal clade under the extreme condition. We also found that hadal MGI have the genetic potential to import a far higher range of organic compounds than their shallower water counterparts. Despite this trait, hadal MDI ammonia oxidation and carbon fixation genes are highly transcribed providing evidence they are likely autotrophic, contributing to the primary production in the aphotic deep sea. Conclusions: Our study reveals potentially novel adaptation mechanisms of deep-sea thaumarchaeotal clades and suggests key functions of deep-sea Thaumarchaeota in carbon and nitrogen cycling

Defeating jamming with the power of silence: a game-theoretic analysis

The timing channel is a logical communication channel in which information is encoded in the timing between events. Recently, the use of the timing channel has been proposed as a countermeasure to reactive jamming attacks performed by an energy-constrained malicious node. In fact, whilst a jammer is able to disrupt the information contained in the attacked packets, timing information cannot be jammed and, therefore, timing channels can be exploited to deliver information to the receiver even on a jammed channel. Since the nodes under attack and the jammer have conflicting interests, their interactions can be modeled by means of game theory. Accordingly, in this paper a game-theoretic model of the interactions between nodes exploiting the timing channel to achieve resilience to jamming attacks and a jammer is derived and analyzed. More specifically, the Nash equilibrium is studied in the terms of existence, uniqueness, and convergence under best response dynamics. Furthermore, the case in which the communication nodes set their strategy and the jammer reacts accordingly is modeled and analyzed as a Stackelberg game, by considering both perfect and imperfect knowledge of the jammer's utility function. Extensive numerical results are presented, showing the impact of network parameters on the system performance.Comment: Anti-jamming, Timing Channel, Game-Theoretic Models, Nash Equilibriu

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