Uveal melanoma is the most common primary intraocular neoplasm in adults. As there are currently no effective methods of treating the disease in the metastatic stage, there is a need to search for ...new prognostic factors that would enable a reliable assessment of the patient’s condition and constitute a possible therapeutic target. In this review, we have prepared the results of English-language studies on new prognostic factors determined with immunohistochemical methods. We found 64 articles in which the expression of various proteins was associated in a statistically significant manner with the histopathological and clinical prognostic factors identified by AJCC. The results of our work clearly show that the biology of uveal melanoma is extraordinarily complex. Numerous studies have shed new light on the complexity of the processes involved in the development of this cancer. Moreover, a careful analysis of the expression of individual proteins may allow the identification of homogeneous groups of patients requiring different treatment regimens.
We collect several useful equivalent conditions for order continuity in F‐normed Köthe spaces. Next, we study uniform monotonicity of Orlicz function (sequence) spaces equipped with the Mazur–Orlicz ...F‐norm. We show necessary and sufficient conditions, separately. Moreover, we study the best dominated approximation problems in F‐normed Köthe spaces showing that order continuity and strict monotonicity are crucial tools in these problems. Finally, we apply the general results in Orlicz spaces. We focus mainly on these methods and techniques which are essentially different and more delicate in comparison to the case of normed Köthe spaces.
The necessary and sufficient conditions for both the Kadec–Klee property as well as the Kadec–Klee property with respect to the coordinatewise convergence in Orlicz–Lorentz sequence spaces equipped ...with the Orlicz norm and generated by arbitrary Orlicz functions as well as any non-increasing weight sequences are given. Moreover, for their subspaces of elements with an order continuous norm the full characterization of the Kadec–Klee property with respect to the coordinatewise convergence is presented. Some tools useful in the proofs of the main results are also provided.
Our paper is devoted to indicating a way of generalizing Mann’s iteration algorithm and a series of fixed point results in the framework of b-metric spaces. First, the concept of a convex b-metric ...space by means of a convex structure is introduced and Mann’s iteration algorithm is extended to this space. Next, by the help of Mann’s iteration scheme, strong convergence theorems for two types of contraction mappings in convex b-metric spaces are obtained. Some examples supporting our main results are also presented. Moreover, the problem of the T-stability of Mann’s iteration procedure for the above mappings in complete convex b-metric spaces is considered. As an application, we apply our main result to approximating the solution of the Fredholm linear integral equation.
The iris, found in many animal species, is a biological tissue that can change the aperture (pupil) size to regulate light transmission into the eye in response to varying illumination conditions. ...The self‐regulation of the eye lies behind its autofocusing ability and large dynamic range, rendering it the ultimate “imaging device” and a continuous source of inspiration in science. In optical imaging devices, adjustable apertures play a vital role as they control the light exposure, the depth of field, and optical aberrations of the systems. Tunable irises demonstrated to date require external control through mechanical actuation, and are not capable of autonomous action in response to changing light intensity without control circuitry. A self‐regulating artificial iris would offer new opportunities for device automation and stabilization. Here, this paper reports the first iris‐like, liquid crystal elastomer device that can perform automatic shape‐adjustment by reacting to the incident light power density. Similar to natural iris, the device closes under increasing light intensity, and upon reaching the minimum pupil size, reduces the light transmission by a factor of seven. The light‐responsive materials design, together with photoalignment‐based control over the molecular orientation, provides a new approach to automatic, self‐regulating optical systems based on soft smart materials.
The iris is a biological tissue that can change the pupil size to stabilize the light transmission into the eye. An iris‐inspired soft device is reported that can automatically adjust aperture size in response to the change of incident light intensity. The device is made of radially photoaligned liquid crystal elastomer, using anisotropic thermal expansion to realize the desired photoactuation mode.
Introduction
Haemophilia therapy has evolved from rudimentary transfusion‐based approaches to an unprecedented level of innovation with glimmers of functional cure brought by gene therapy. After ...decades of misfires, gene therapy has normalized factor (F)VIII and factor (F)IX levels in some individuals in the long term. Several clinical programmes testing adeno‐associated viral (AAV) vector gene therapy are approaching completion with imminent regulatory approvals.
Discussion
Phase 3 studies along with multiyear follow‐up in earlier phase investigations raised questions about efficacy as well as short‐ and long‐term safety, prompting a reappraisal of AAV vector gene therapy. Liver toxicities, albeit mostly low‐grade, occur in the first year in at least some individuals in all haemophilia A and B trials and are poorly understood. Extreme variability and unpredictability of outcome, as well as a slow decline in factor expression (seemingly unique to FVIII gene therapy), are vexing because immune responses to AAV vectors preclude repeat dosing, which could increase suboptimal or restore declining expression, while overexpression may result in phenotoxicity. The long‐term safety will need lifelong monitoring because AAV vectors, contrary to conventional wisdom, integrate into chromosomes at the rate that calls for vigilance.
Conclusions
AAV transduction and transgene expression engage the host immune system, cellular DNA processing, transcription and translation machineries in ways that have been only cursorily studied in the clinic. Delineating those mechanisms will be key to finding mitigants and solutions to the remaining problems, and including individuals who cannot avail of gene therapy at this time.
Most glycosyltransferases show remarkable gross and fine substrate specificity, which is reflected in the old one enzyme-one linkage paradigm. While human Gb3/CD77 synthase is a glycosyltransferase ...that synthesizes the Galα1→4Gal moiety mainly on glycosphingolipids, its pigeon homolog prefers glycoproteins as acceptors. In this study, we characterized two Gb3/CD77 synthase paralogs found in pigeons (Columba livia). We evaluated their specificities in transfected human teratocarcinoma 2102Ep cells by flow cytofluorometry, Western blotting, high-performance thin-layer chromatography, mass spectrometry and metabolic labelling with 14C-galactose. We found that the previously described pigeon Gb3/CD77 synthase (called P) can use predominately glycoproteins as acceptors, while its paralog (called M), which we serendipitously discovered while conducting this study, efficiently synthesizes Galα1→4Gal caps on both glycoproteins and glycosphingolipids. These two paralogs may underlie the difference in expression profiles of Galα1→4Gal-terminated glycoconjugates between neoavians and mammals.
All symptoms of malaria are caused by the intraerythrocytic proliferation of Plasmodium merozoites. Merozoites invade erythrocytes using multiple binding ligands that recognise specific surface ...receptors. It has been suggested that adaptation of Plasmodium parasites to infect specific hosts is driven by changes in genes encoding Plasmodium erythrocyte-binding ligands (EBL) and reticulocyte-binding ligands (RBL). Homologs of both EBL and RBL, including the EBA-140 merozoite ligand, have been identified in P. falciparum and P. reichenowi, which infect humans and chimpanzees, respectively. The P. falciparum EBA-140 was shown to bind human glycophorin C, a minor erythrocyte sialoglycoprotein. Until now, the erythrocyte receptor for the P. reichenowi EBA-140 remained unknown.
The baculovirus expression vector system was used to obtain the recombinant EBA-140 Region II, and flow cytometry and immunoblotting methods were applied to characterise its specificity.
We showed that the chimpanzee glycophorin D is the receptor for the P. reichenowi EBA-140 ligand on chimpanzee red blood cells.
We propose that the development of glycophorin C specificity is spurred by the P. falciparum lineage. We speculate that the P. falciparum EBA-140 evolved to hijack GPC on human erythrocytes during divergence from its ape ancestor.
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