Frontal waves and transmissions for temporal laminates and imperfect chiral interfaces.

The analysis of wave patterns in a structure which possesses periodicity in the spatial and temporal dimensions is presented. The topic of imperfect chiral interfaces is also considered. Although causality is fundamental for physical processes, natural wave phenomena can be observed when a wave is split at a temporal interface. A wave split at a spatial interface is a more common occurrence; however, when the coefficients of the governing equations are time-dependent, the temporal interface becomes important. Here, the associated frontal waves are studied, and regimes are analysed where the growth of the solution in time is found. Imperfect interfaces, across which the displacements are discontinuous, are also considered in the vector case of chiral elastic systems. Analytical study and asymptotic approximations are supplied with illustrative numerical examples. This article is part of the theme issue 'Wave generation and transmission in multi-scale complex media and structured metamaterials (part 1)'.

One-way interfacial waves in a flexural plate with chiral double resonators.

In this paper, we demonstrate a new approach to control flexural elastic waves in a structured chiral plate. The main focus is on creating one-way interfacial wave propagation at a given frequency by employing double resonators in a doubly periodic flexural system. The resonators consist of two beams attached to gyroscopic spinners, which act to couple flexural and rotational deformations, hence inducing chirality in the system. We show that this elastic structure supports one-way flexural waves, localized at an interface separating two sub-domains with gyroscopes spinning in opposite directions, but with otherwise identical properties. We demonstrate that a special feature of double resonators is in the directional control of wave propagation by varying the value of the gyricity, while keeping the frequency of the external time-harmonic excitation fixed. Conversely, for the same value of gyricity, the direction of wave propagation can be reversed by tuning the frequency of the external excitation. This article is part of the theme issue 'Modelling of dynamic phenomena and localization in structured media (part 2)'.

Methylomic profiling and replication implicates deregulation of PCSK9 in alcohol use disorder.

Alcohol use disorder (AUD) is a common and chronic disorder with substantial effects on personal and public health. The underlying pathophysiology is poorly understood but strong evidence suggests significant roles of both genetic and epigenetic components. Given that alcohol affects many organ systems, we performed a cross-tissue and cross-phenotypic analysis of genome-wide methylomic variation in AUD using samples from 3 discovery, 4 replication, and 2 translational cohorts. We identified a differentially methylated region in the promoter of the proprotein convertase subtilisin/kexin 9 (PCSK9) gene that was associated with disease phenotypes. Biological validation showed that PCSK9 promoter methylation is conserved across tissues and positively correlated with expression. Replication in AUD datasets confirmed PCSK9 hypomethylation and a translational mouse model of AUD showed that alcohol exposure leads to PCSK9 downregulation. PCSK9 is primarily expressed in the liver and regulates low-density lipoprotein cholesterol (LDL-C). Our finding of alcohol-induced epigenetic regulation of PCSK9 represents one of the underlying mechanisms between the well-known effects of alcohol on lipid metabolism and cardiovascular risk, with light alcohol use generally being protective while chronic heavy use has detrimental health outcomes.

Flexural vibration systems with gyroscopic spinners.

In this paper, we study the spectral properties of a finite system of flexural elements connected by gyroscopic spinners. We determine how the eigenfrequencies and eigenmodes of the system depend on the gyricity of the spinners. In addition, we present a transient numerical simulation that shows how a gyroscopic spinner attached to the end of a hinged beam can be used as a 'stabilizer', reducing the displacements of the beam. We also discuss the dispersive properties of an infinite periodic system of beams with gyroscopic spinners at the junctions. In particular, we investigate how the band-gaps of the structure can be tuned by varying the gyricity of the spinners. This article is part of the theme issue 'Modelling of dynamic phenomena and localization in structured media (part 1)'.

Controlling the motion of gravitational spinners and waves in chiral waveguides.

In this paper we present a mathematical modelling framework for chiral phenomena associated with rotational motions, highlighting the combination of gyroscopic action with gravity. We discuss new ideas of controlling gravity-induced waves by a cluster of gyroscopic spinners. For an elementary gravitational spinner, the transient oscillations are accompanied by a full classification and examples, linked to natural phenomena observed in planetary motion. Applications are presented in the theory of chiral metamaterials, and of the dynamic response of such materials to external loads.

Wave polarization and dynamic degeneracy in a chiral elastic lattice.

This paper addresses fundamental questions arising in the theory of Bloch-Floquet waves in chiral elastic lattice systems. This area has received a significant attention in the context of 'topologically protected' waveforms. Although practical applications of chiral elastic lattices are widely appreciated, especially in problems of controlling low-frequency vibrations, wave polarization and filtering, the fundamental questions of the relationship of these lattices to classical waveforms associated with longitudinal and shear waves retain a substantial scope for further development. The notion of chirality is introduced into the systematic analysis of dispersive elastic waves in a doubly-periodic lattice. Important quantitative characteristics of the dynamic response of the lattice, such as lattice flux and lattice circulation, are used in the analysis along with the novel concept of 'vortex waveforms' that characterize the dynamic response of the chiral system. We note that the continuum concepts of pressure and shear waves do not apply for waves in a lattice, especially in the case when the wavelength is comparable with the size of the elementary cell of the periodic structure. Special critical regimes are highlighted when vortex waveforms become dominant. Analytical findings are accompanied by illustrative numerical simulations.

Localization in semi-infinite herringbone waveguides.

The paper includes novel results for the scattering and localization of a time-harmonic flexural wave by a semi-infinite herringbone waveguide of rigid pins embedded within an elastic Kirchhoff plate. The analytical model takes into account the orientation and spacing of the constituent parts of the herringbone system, and incorporates dipole approximations for the case of closely spaced pins. Illustrative examples are provided, together with the predictive theoretical analysis of the localized waveforms.

Interfacial waveforms in chiral lattices with gyroscopic spinners.

We demonstrate a new method of achieving topologically protected states in an elastic hexagonal system of trusses by attaching gyroscopic spinners, which bring chirality to the system. Dispersive features of this medium are investigated in detail, and it is shown that one can manipulate the locations of stop-bands and Dirac points by tuning the parameters of the spinners. We show that, in the proximity of such points, uni-directional interfacial waveforms can be created in an inhomogeneous lattice and the direction of such waveforms can be controlled. The effect of inserting additional soft internal links into the system, which is thus transformed into a heterogeneous triangular lattice, is also investigated, as the hexagonal lattice represents the limit case of the heterogeneous triangular lattice with soft links. This work introduces a new perspective in the design of periodic media possessing non-trivial topological features.

Gyro-elastic beams for the vibration reduction of long flexural systems.

The paper presents a model of a chiral multi-structure incorporating gyro-elastic beams. Floquet-Bloch waves in periodic chiral systems are investigated in detail, with the emphasis on localization and the formation of standing waves. It is found that gyricity leads to low-frequency standing modes and generation of stop-bands. A design of an earthquake protection system is offered here, as an interesting application of vibration isolation. Theoretical results are accompanied by numerical simulations in the time-harmonic regime.

"Deflecting elastic prism" and unidirectional localisation for waves in chiral elastic systems.

For the first time, a design of a "deflecting elastic prism" is proposed and implemented for waves in a chiral medium. A novel model of an elastic lattice connected to a non-uniform system of gyroscopic spinners is designed to create a unidirectional wave pattern, which can be diverted by modifying the arrangement of the spinners within the medium. This important feature of the gyro-system is exploited to send a wave from a point of the lattice to any other point in the lattice plane, in such a way that the wave amplitude is not significantly reduced along the path. We envisage that the proposed model could be very useful in physical and engineering applications related to directional control of elastic waves.

Cymatics for the cloaking of flexural vibrations in a structured plate.

Based on rigorous theoretical findings, we present a proof-of-concept design for a structured square cloak enclosing a void in an elastic lattice. We implement high-precision fabrication and experimental testing of an elastic invisibility cloak for flexural waves in a mechanical lattice. This is accompanied by verifications and numerical modelling performed through finite element simulations. The primary advantage of our square lattice cloak, over other designs, is the straightforward implementation and the ease of construction. The elastic lattice cloak, implemented experimentally, shows high efficiency.

Dynamic interfacial trapping of flexural waves in structured plates.

The paper presents new results on the localization and transmission of flexural waves in a structured plate containing a semi-infinite two-dimensional array of rigid pins. In particular, localized waves are identified and studied at the interface boundary between the homogeneous part of the flexural plate and the part occupied by rigid pins. A formal connection has been made with the dispersion properties of flexural Bloch waves in an infinite doubly periodic array of rigid pins. Special attention is given to regimes corresponding to standing waves of different types as well as Dirac-like points that may occur on the dispersion surfaces. A single half-grating problem, hitherto unreported in the literature, is also shown to bring interesting solutions.

Sister chromatid exchange induced by X-irradiation of retinoblastoma lymphocytes.

Lymphocyte cultures were employed to assess the degree of spontaneous and induced chromosomal fragility in retinoblastoma. Sister chromatid exchange (SCEs) were scored in metaphases. Three unilateral, three bilateral, eleven family members and controls were studied. Retinoblastoma (RB) lymphocytes did not exhibit increased spontaneous fragility. X-irradiation (25-200 rad) did not significantly increase SCE in unilateral retinoblastoma lymphocytes when compared with controls (P greater than 0.50). However, bilaterally affected subjects and three unaffected relatives demonstrated a statistically significant increase in SCE (P less than 0.01). In conclusion, hereditary retinoblastoma lymphocytes appear more radiosensitive than sporadic retinoblastoma, perhaps, reflecting the increased second malignancies in germinal mutation retinoblastoma. In addition, the analysis of radiation-induced SCE in peripheral blood lymphocytes of RB patients and family members may provide a valuable tool increasing the accuracy of genetic counseling for this disorder. Additional studies of RB patients and families are needed to assess the relevance of this approach to genetic counseling.

Benign epithelioid cell nevi of the iris.

Two benign acquired melanocytic lesions of the iris stroma had distinctive clinical and pathologic features. One tumor was loculated and polypoid, suggesting ectopic glandular tissue, while the other was a flat tumor with a rich surface capillarity. Both lesions histologically were composed of mononucleated, binucleated, and multinucleated hypopigmented epithelioid and elongated "myoid" cells, widely separated in a finely fibrillar eosinophilic stroma. The ultrastructural features of one case included hyperconvoluted nuclei, conspicuous cytoplasmic filaments are rare, filamentary-striated (leptomeric) structures, scant organelles and inclusions except for numerous mitochondria and glycogen granules, small and infrequent melanosomes, and a fibrillary extracellular matrix focally organized into banded basement membrane material.

Orbitofacial angiomatosis.

Two patients with orbital vascular malformation ipsilateral facial nevus flammeus were studied. The literature contains one similar case that interestingly shares with our cases the lack of leptomeningeal angiomatosis. Orbitofacial angiomatosis seems to be a distinct entity from meningofacial angiomatosis because of its true vascular malformation of the orbit.

Radiation retinopathy: electron microscopy of retina and optic nerve.

A 4 1/2 year old female was treated for embryonal rhabdomyosarcoma of the left orbit in 1975 with radiation (59.5 Gy in 5 weeks), followed by chemotherapy. An electroretinogram (ERG) in March, 1988 revealed cone responses 3% of normal and no rod responses in the left eye, and normal responses in the right eye. The eye was enucleated in April 1988. In the fovea no choroidocapillaris was seen at the intact Bruch's membrane, and the pigment epithelium was preserved only in small patches. No photoreceptor cells were seen in the areas devoid of pigment epithelial cells. The parafoveal and peripheral (30 degrees eccentricity) retina was better preserved. The thickness of the layer of rods and cones and of Henle's fiber layer was reduced. Very few outer segments were present. Macrophages had invaded the retinal tissue in moderate numbers. The retinal vessels were ensheathed by several layers of collagen fibrils. The spatial densities of pigment epithelial, cone, rod, and bipolar cells had been reduced. The optic nerve contained a total number of 1,022,000 nerve fibers.

Algernon B. Reese: a biographical sketch.

The contributions of Algernon B. Reese to the understanding of ophthalmic pathology are well known. This biographical sketch combines a historical summary of Reese's many accomplishments with a warm and personal view of Reese as master, teacher, and friend.

Ophthalmic striated muscle neoplasms.

Rhabdomyosarcoma, the most common primary malignant childhood orbital tumor, is composed of neoplastic striated muscle cells (rhabdomyoblasts) in various stages of differentiation and in patterns suggestive of neoplastic analogs of normal muscle embryogenesis. Orbital rhabdomyosarcoma is most commonly seen in children and adolescents, the average age of onset of symptoms being 7.8 years. The tumor usually presents as a rapidly evolving exophthalmos, often associated with drooping of the upper eyelid. A mass is palapable in only 25% of cases, loss of central vision at the time of presentation is uncommon, and laboratory studies are often of little help in diagnosis. The best diagnostic aid is a high index of suspicion whenever one sees a rapidly progressive exophthalamos in a child. Orbital rhabdomyosarcoma is almost always of the embryonal type, believed to originate in the orbital soft tissues from undifferentiated pluripotential embryonic mesenchyme. In the past, orbital exenteration has been the primary therapy. Review of 162 literature cases of orbital rhabdomyosarcoma, generally treated by unassisted surgery, revealed that only 25% of the patients survived 3 or more years. Recently, it has been shown that radiation therapy, alone or combined with chemotherapy, can be successful. A multidisciplinary approach, utilizing surgery, radiation therapy and chemotherapy has also been advocated. Both approaches appear to offer greater survival than unassisted orbital exenteration. The possibility of primary radiation therapy is extremely promising; if it becomes increasingly effective, a mutilating surgical procedure may become obsolete.

Pulsating metastatic tumor of the orbit.

A 47-year-old white man in apparent good health had diplopia and swelling of the right upper eyelid. Ocular examination showed proptosis of the right eye, together with a large, pulsatile, collapsible mass simulating a vascular neoplasm and involving the right temple as well as the right upper outer quadrant of the orbit. Biopsy of the orbital tumor disclosed a clear-cell carcinoma compatible with a renal primary tumor; subsequent laboratory examination revealed the offending tumor in the left kidney. Renal carcinomas may metastasize to the globe or to the orbit before the primary tumor is recognized. Pulsatile exophthalmos acquired in middle life associated with significant bone destruction represents a constellation of findings most consistent with a metastatic tumor, probably renal carcinoma, caused by the exceedingly rich vascularization of these metastatic deposits.

Solitary iris nevus associated with peripheral anterior synechiae and iris endothelialization.

Two middle-aged patients developed pigmented intrastromal iris nevi and an associated loss of the surrounding iris stromal markings suggestive of a surface iris membrane. Because of the fear of malignant melanoma with superficial growth, we excised the lesions. Histopathologic examination of the specimens revealed that the pigmented lesions were benign iris nevi and that the surrounding membrane was caused by endothelial cell growth onto the iris from peripheral anterior synechiae. These synechiae occurred anterior to Schwalbe's line in the same sector as the nevi and had been noted preoperatively at gonioscopic examination, but their diagnostic significance was not appreciated.