A solute gradient in the tear meniscus I. A hypothesis to explain Marx's line

Marx's line is a line of mucosal staining behind the mucocutaneous junction. It can be demonstrated throughout life in all normal lids by staining with lissamine green and related dyes. Of all the body orifices, only the mucosae of the eye and mouth are directly exposed to the atmosphere. In this paper, we suggest that for the eye, this exposure leads to the formation of Marx's line. The tear meniscus thins progressively toward its apex, where it is pinned at the mucocutaneous junction of the lid. It also thins toward the black line, which segregates the meniscus from the tear film after the blink. We predict that, because of the geometry of the tear meniscus, evaporation generates a solute gradient across the meniscus profile in the anteroposterior plane, which peaks at the meniscus apices at the end of the interblink. One outcome would be to amplify the level of tear molarity at these sites so that they reach hyperosmolar proportions. Preliminary mathematical modeling suggests that dilution of this effect by advection and diffusion of solute away from the meniscus apex at the mucocutaneous junction will be restricted by spatial constraints, the presence of tear and surface mucins at this site, and limited fluid flow. We conclude that evaporative water loss from the tear meniscus may result in a physiological zone of hyperosmolar and related stresses to the occlusal conjunctiva, directly behind the mucocutaneous junction. We hypothesize that this stimulates a high epithelial cell turnover at this site, incomplete epithelial maturation, and a failure to express key molecules such as MUC 16 and galectin-3, which, with the tight junctions between surface epithelial cells, are necessary to seal the ocular surface and prevent penetration of dyes and other molecules into the epithelium. This is proposed as the basis for Marx's line. In Part II of this paper (also published in this issue of The Ocular Surface), we address additional pathophysiological consequences of this mechanism, affecting lid margins

A solute gradient in the tear meniscus II. implications for lid margin disease, including meibomian gland dysfunction

We have hypothesized previously that evaporation from the tears generates a solute gradient across the tear meniscus, which delivers hyperosmolar stress to the mucocutaneous junction (MCJ) of the lid margin. This is proposed as the basis for Marx's line, a line of staining with topically applied dyes that lies directly behind the MCJ. In this article, we consider the implications of this hypothesis for progressive damage to the lid margin as an age-related phenomenon, its amplification in dry eye states, and its possible role in the etiology of meibomian gland dysfunction (MGD). It is suggested that a hyperosmolar or related stimulus, acting behind the MCJ over a lifetime, promotes the anterior migration of the MCJ, which is a feature of the aging lid margin. This mechanism would be amplified in dry eye states, not only by reason of increased tear molarity at the meniscus apex but also by raising the concentration of inflammatory peptides at this site. This could explain the increased width and irregularity of Marx's line in dry eye. While the presence of stem cells at the lid margin may equip this region to respond to such stress, their depletion could be the basis of irreversible lid margin damage. It is further proposed, given the proximity of the MCJ to the meibomian gland orifices, that the solute gradient mechanism could play a role in the initiation of MGD by delivering hyperosmolar and inflammatory stresses to the terminal ducts and orifices of the glands. By the same token, the presence of a zone of increased epithelial permeability in this region may provide a back door route for the delivery of drugs in the treatment of MGD

A mass and solute balance model for tear volume & osmolarity in the normal and the dry eye

Tear hyperosmolarity is thought to play a key role in the mechanism of dry eye, a common symptomatic condition accompanied by visual disturbance, tear film instability, inflammation and damage to the ocular surface. We have constructed a model for the mass and solute balance of the tears, with parameter estimation based on extensive data from the literature which permits the influence of tear evaporation, lacrimal flux and blink rate on tear osmolarity to be explored. In particular the nature of compensatory events has been estimated in aqueous-deficient (ADDE) and evaporative (EDE) dry eye.\ud \ud The model reproduces observed osmolarities of the tear meniscus for the healthy eye and predicts a higher concentration in the tear film than meniscus in normal and dry eye states. The differential is small in the normal eye, but is significantly increased in dry eye, especially for the simultaneous presence of high meniscus concentration and low meniscus radius. This may influence the interpretation of osmolarity values obtained from meniscus samples since they need not fully reflect potential damage to the ocular surface caused by tear film hyperosmolarity.\ud \ud Interrogation of the model suggests that increases in blink rate may play a limited role in compensating for a rise in tear osmolarity in ADDE but that an increase in lacrimal flux, together with an increase in blink rate, may delay the development of hyperosmolarity in EDE. Nonetheless, it is predicted that tear osmolarity may rise to much higher levels in EDE than ADDE before the onset of tear film breakup, in the absence of events at the ocular surface which would independently compromise tear film stability. Differences in the predicted responses of the pre-ocular tears in ADDE compared to EDE or hybrid disease to defined conditions suggest that no single, empirically-accessible variable can act as a surrogate for tear film concentration and the potential for ocular surface damage. This emphasises the need to measure and integrate multiple diagnostic indicators to determine outcomes and prognosis. Modelling predictions in addition show that further studies concerning the possibility of a high lacrimal flux phenotype in EDE are likely to be profitable

Using acoustic waves to induce high-frequency current oscillations in superlattices

We show that GHz acoustic waves in semiconductor superlattices can induce THz electron dynamics that depend critically on the wave amplitude. Below a threshold amplitude, the acoustic wave drags electrons through the superlattice with a peak drift velocity overshooting that produced by a static electric field. In this regime, single electrons perform drifting orbits with THz frequency components. When the wave amplitude exceeds the critical threshold, an abrupt onset of Bloch-like oscillations causes negative differential velocity. The acoustic wave also affects the collective behavior of the electrons by causing the formation of localised electron accumulation and depletion regions, which propagate through the superlattice, thereby producing self-sustained current oscillations even for very small wave amplitudes. We show that the underlying single-electron dynamics, in particular the transition between the acoustic wave dragging and Bloch oscillation regimes, strongly influence the spatial distribution of the electrons and the form of the current oscillations. In particular, the amplitude of the current oscillations depends non-monotonically on the strength of the acoustic wave, reflecting the variation of the single-electron drift velocity.Comment: 10 pages, 8 figure

Development, Characterisation and Application of Monoclonal Antibodies for the Detection and Quantification of Infectious Salmon Anaemia Virus in Plasma Samples Using Luminex Bead Array Technology

Infectious salmon anaemia virus (ISAV) is an orthomyxovirus that has had a significant economic impact on Atlantic salmon farming in Europe, North America and Chile. Monoclonal antibodies (mAbs) were developed against Segment 3 (encoding the viral nucleoprotein, NP) of the virus. Six of the mAbs were shown to be specific to ISAV and recognised all isolates from Scotland, Norway and Canada. They reacted with ISAV in enzyme-linked immunosorbent assay (ELISA), indirect fluorescent antibody technique (IFAT) and western blotting. They were also used to develop a novel detection method based on Luminex (Bio-Plex) bead-based flow cytometric technology for the detection of ISAV in the plasma of Atlantic salmon (Salmo salarL.) smolts experimentally infected with ISAV. Fish were challenged by intraperitoneal (i.p.) injection of virus at 50% Tissue Culture Infective Dose (TCID50) = 2.8 x106per animal. Virus present in plasma of infected fish, collected at 0, 4, 8, 12, 16, 21 and 28 days post infection using a non-lethal sampling method (n = 12 at each time point), was quantified using the optimised Bio-Plex assay. The results obtained with this assay were compared with absolute quantification of the virus by RT-qPCR using SYBR Green I and TaqMan chemistries. The Bio-Plex assay developed using the NP mAbs appears to be a rapid, sensitive method for detecting and quantifying ISAV in small volumes of fish plasma and has the potential to be multiplexed for the detection of other fish pathogens (e.g. during co-infections). To our knowledge this is the first report of the use of Luminex (Bio-Plex) technology for the detection of a fish pathogen

Towards the pressure and material gap in heterogeneous catalysis: hydrogenation of acrolein over silver catalysts

Introduction In recent time, increasing effort has been undertaken in order to answer the question, whether it is justified to transfer results from surface science studies, mostly obtained with idealised surfaces under UHV conditions, to "real" catalysis, i.e. high pressures and complex materials (the so-called pressure and material gaps). The DFG (German research foundation) has initialised a priority program (SPP 1091) in order to bring together experts from surface science, materials science, catalysis and theory with the aim of bridging the two gaps in catalysis. Within this priority program, we are currently studying the hydrogenation of acrolein over silver. Acrolein, an ,-unsaturated aldehyde, can be hydrogenated either to propanal (product of C=C-bond hydrogenation) or to allyl alcohol (product of C=O-bond hydrogenation. Whereas typical hydrogenation catalysts like Pt, Ru or Ni mainly produce the saturated aldehyde, selectivities to allyl alcohol of up to 53 % can be obtained when using monometallic silver (or gold) catalysts [ , ]. The aim of our studies is to clarify the influence of reaction pressure and material on the selectivity distribution in the acrolein hydrogenation. Catalytic experiments have been carried out with differently structured samples from single crystals to disperse Ag/support catalysts in a broad pressure range (few mbar up to 20 bar). Various methods like in situ-XAS and XPS, flow-adsorption calorimetry, infrared spectroscopy, and transient analysis of products (TAP) are performed in order to gain insight into the modes of interaction of acrolein and hydrogen with differently structured silver samples. Effects of particle size and shape are also considered as well as the influence of the support material. Experimental and Results would add a few words about the composition (Ag loading, different supports) / preparation of the catalysts and/or a reference Gas phase hydrogenation of acrolein has been carried out in a flow reaction system allowing a pressure in the range from 150 mbar up to 20 bar. When using silica supported silver catalysts, clear relations can be drawn concerning the pressure and material dependence of the selectivity to allyl alcohol: increasing partial pressure of either reactant (hydrogen or acrolein) leads to increased selectivity to allyl alcohol, also, smaller particles favour its formation. However, when using ZnO-supported catalysts, the situation becomes more complex. Catalysts prepared with the same catalyst loading and the same catalyst preparation technique but with different ZnO support materials yielded different selectivities to allyl alcohol at the same conversion. On the other hand, catalysts prepared from different precursors, but with the same support, lead to different activities but similar selectivities to allyl alcohol. TEM investigations of the Ag/ZnO and Ag/SiO2 catalysts reveal, that the particle sizes of the silica-supported catalysts are much smaller (2 nm and 15 nm in average for the two most intensively studied catalysts) whereas the silver particles in the Ag/ZnO catalysts are surprisingly large (50 nm up to several hundreds of nm). This is even more surprising since the activities of the catalysts are in the same order of magnitude, with the SiO2 catalysts however, being a bit more active. All these results indicate, that the product distribution at supported silver catalysts is governed by a complex interplay between particle size (and/or shape), pressure, and, as the obviously most important factor, the support and the interactions between silver and support. To gain more insight into the reasons for the catalytic behaviour of the Ag/support catalysts, the interaction of hydrogen alone with various silver samples has been studied. TAP (temporal analysis of products) indicates, that hydrogen interacts with nanodisperse Ag/SiO2 samples, but not with larger unsupported silver particles (several mm in size) like those from electrolyte silver. However, as monitored by transmission infrared spectroscopy, not only the Ag nanoparticles but also the SiO2 support interacts with hydrogen. SiO2 and Ag/SiO2 samples, after reduction and exposure to 100 mbar D2, show a reversible H-D-exchange, as monitored by the Si-O-H(D) bands. Time resolved IR spectra indicate, that this H-D-exchange is faster at silver-containing samples. From temperature-dependent measurements, activation energies for the H-D-exchange of ca. 28 kJ/mol for Ag/SiO2 and ca. 38 kJ/mol for SiO2 have been calculated. The interaction of acrolein with silver single crystals as well as with supported catalysts has been studied with in-situ-XAS and in-situ XPS. For both techniques the samples were contacted with mixtures of H2/acrolein in the mbar pressure range. Angular dependent XAS measurements on a Ag(111) single crystal indicated that acrolein is in the lying-down orientation. For all the samples measured the 1π* “C=O” transition is clearly increased compared to the 1π* “C=C”. Consequently, the surface concentration of C=O bonds relative to C=C bonds is higher, which is in line with concomitantly measured mass spectrometric data showing high selectivity towards C=C hydrogenation. In-situ XPS revealed that while silver foil is partly oxidic (~5%) the supported silver particles are completely reduced, as Ag is in the zero valence state. Data indicate also small amount of oxygen removal from the ZnO supported samples during the contact with hydrogen. The combination of different results suggests that metal-support interaction plays an important role in the reaction. The major difference in hydrogen activation between supported catalysts and pure silver/support provides us a hint that the so-called “adlineation sites” (the perimeter interface between silver and support) are the key sites in the mechanism

Dissociative recombination of N2_2H+^+: A revisited study

Dissociative recombination of N$_2$H$^+$ is explored in a two-step theoretical study. In a first step, a diatomic (1D) rough model with frozen NN bond and frozen angles is adopted, in the framework of the multichannel quantum defect theory (MQDT). The importance of the indirect mechanism and of the bending mode is revealed, in spite of the disagreement between our cross section and the experimental one. In a second step, we use our recently elaborated 3D approach based on the normal mode approximation combined with R-matrix theory and MQDT. This approach results in satisfactory agreement with storage-ring measurements, significantly better at very low energy than the former calculations.Comment: 9 pages, 5 figures, 1 tabl

Population of ground and lowest excited states of Sulfur via the dissociative recombination of SH+ in the diffuse interstellar medium

Our previous study on dissociative recombination of ground state SH$^+$ into $^2\Pi$ states of SH is extended by taking into account the contribution of $^4\Pi$ states recently explored by quantum chemistry methods. Multichannel quantum defect theory is employed for the computation of cross sections and rate coefficients for dissociative recombination, but also for vibrational excitation. Furthermore, we produce the atomic yields resulting from recombination, quantifying the generation of sulfur atoms in their ground (\mbox{$^3$P}) and lowest excited (\mbox{$^1$D}) states respectively.Comment: 9 pages, 8 figures, 3 table

Electronic structure of the candidate 2D Dirac semimetal SrMnSb2: a combined experimental and theoretical study

SrMnSb$_2$ is suggested to be a magnetic topological semimetal. It contains square, 2D Sb planes with non-symmorphic crystal symmetries that could protect band crossings, offering the possibility of a quasi-2D, robust Dirac semi-metal in the form of a stable, bulk (3D) crystal. Here, we report a combined and comprehensive experimental and theoretical investigation of the electronic structure of SrMnSb$_2$, including the first ARPES data on this compound. SrMnSb$_2$ possesses a small Fermi surface originating from highly 2D, sharp and linearly dispersing bands (the Y-states) around the (0,$\pi$/a)-point in $k$-space. The ARPES Fermi surface agrees perfectly with that from bulk-sensitive Shubnikov de Haas data from the same crystals, proving the Y$-$states to be responsible for electrical conductivity in SrMnSb$_2$. DFT and tight binding (TB) methods are used to model the electronic states, and both show good agreement with the ARPES data. Despite the great promise of the latter, both theory approaches show the Y-states to be gapped above E$_F$, suggesting trivial topology. Subsequent analysis within both theory approaches shows the Berry phase to be zero, indicating the non-topological character of the transport in SrMnSb$_2$, a conclusion backed up by the analysis of the quantum oscillation data from our crystals.Comment: 26 pages, 10 figures, revised submission to SciPost after including changes requested by referees. All referee reports are open and can be viewed here: https://scipost.org/submissions/1711.07165v2