Wavefronts and the limits of human vision Part 2: applications

The mean values for all the Zernike coefficients are approximately zero, while the individual variability is very high, what means that humans as a species in general have a very good optical system, though individually imperfect. Some temporal instability of higher-order aberrations, whose largest source is accommodation has been described. There arises a new question: will the correction of all the aberrations for the non-accommodated state of the eye be as beneficial for the near sight also? It is possible to modify and decrease the optical aberrations by a process of photo-ablation carried out by a scanning spot LASER with the wavefront data serving as a basis for the customized ablation profile. Perfect alignment of the LASER beam on the eye by means of high frequency eye trackers is fundamental. The theoretical visual benefit by correcting the higher order aberrations is up to 12 times. The main goal of the wavefront-guided treatments is not to allow the decrease in visual acuity after refractive surgical treatments, as may occur nowadays with the traditional LASER treatments; the next step would be treatments aiming at the improvement of visual acuity, as well as the treatments of highly irregular corneas (primary irregular, small or decentered ablations, central islands or irregularities after corneal transplantation). Understanding the new terminology and the bases of the new technological evolution, together with the continuous and critical follow-up of the new results in the literature, is the key of success of the modern approach to the problems related to refraction and refractive surgery.Os valores médios de todos os coeficientes de Zernike são de aproximadamente zero, ao passo que a variabilidade individual é muito grande, o que significa que os seres humanos, como espécie em geral, têm sistema óptico muito bom, mas individualmente imperfeito. Certa instabilidade temporal das aberrações de alta ordem foi descrita em função da acomodação. Este fato leva a uma nova pergunta: a correção de todas as aberrações para visão em estado não acomodado será benéfica para visão de perto também? É possível modificar e diminuir as aberrações ópticas por meio de foto-ablação por scanning spot LASER tendo os dados das frentes de ondas como a base para perfil de ablação individualizado. É fundamental a fixação perfeita do feixe de LASER em relação ao olho, obtida com os eye-trackers de alta freqüência. O benefício visual teórico da correção das aberrações de alta ordem seria de até 12 vezes. A meta principal dos tratamentos guiados pelas frentes de onda é de não permitir a piora da visão depois do tratamento cirúrgico refrativo, como pode ocorrer hoje em dia com os tratamentos tradicionais a LASER; em seguida, a meta se es-tenderia aos melhoramentos visuais, bem como ao tratamento dos casos de córneas extremamente irregulares (ablações primárias irregulares, pequenas ou descentradas, a presença das ilhas centrais ou irregularidades após transplante de córnea). O entendimento da terminologia e das bases da nova evolução tecnológica, bem como o constante acompanhamento crítico dos resultados publicados é fundamental para a abordagem moderna dos problemas relativos à refração e à cirurgia refrativa.UniversitätsSpital ZürichUniversidade Federal de São Paulo (UNIFESP) EPM Departamento de OftalmologiaInstituto de Física AplicadaUNIFESP, EPM, Depto. de OftalmologiaSciEL

Directed Evolution of Gloeobacter violaceus Rhodopsin Spectral Properties

Proton-pumping rhodopsins (PPRs) are photoactive retinal-binding proteins that transport ions across biological membranes in response to light. These proteins are interesting for light-harvesting applications in bioenergy production, in optogenetics applications in neuroscience, and as fluorescent sensors of membrane potential. Little is known, however, about how the protein sequence determines the considerable variation in spectral properties of PPRs from different biological niches or how to engineer these properties in a given PPR. Here we report a comprehensive study of amino acid substitutions in the retinal binding pocket of Gloeobacter violacaeus rhodopsin (GR) that tune its spectral properties. Directed evolution generated 70 GR variants with absorption maxima shifted by up to +/- 80 nm, extending the protein’s light absorption significantly beyond the range of known natural PPRs. While proton pumping activity was disrupted in many of the spectrally shifted variants, we identified single tuning mutations that incurrred blue and red shifts of 42 nm and 22 nm, respectively, that did not disrupt proton pumping. Blue-shifting mutations were distributed evenly along the retinal molecule while red-shifting mutations were clustered near the residue K257, which forms a covalent bond with retinal through a Schiff base linkage. Thirty-four of the identified tuning mutations are not found in known microbial rhodopsins. We discovered a subset of red-shifted GRs that exhibit high levels of fluorescence relative to the wild-type protein

Integrating multi-level values and pro-environmental behavior in a U.S. protected area

Human behavior is influenced by an array of psychological processes such as environmental values. Despite the importance of understanding the reasons why people engage in activities that minimize environmental degradation, empirical research rarely integrates different types of values simultaneously to provide more complete and multi-faceted insights on how values contribute to environmental sustainability. Drawing from on-site survey data collected in Denali National Park and Preserve, Alaska (n = 641), we used two-step structural equation modeling to test how variation in behavioral patterns was explained by the cultural, individual, and social values of visitors to a national park. We fused various disciplinary perspectives on the value concept to demonstrate how individual- and group-level dynamics were integral for predicting behavior and better understanding aggregated preferences for environmental conditions in the context of a U.S. protected area.Peer reviewe

The DO-KB Knowledgebase: a 20-year journey developing the disease open science ecosystem.

In 2003, the Human Disease Ontology (DO, https://disease-ontology.org/) was established at Northwestern University. In the intervening 20 years, the DO has expanded to become a highly-utilized disease knowledge resource. Serving as the nomenclature and classification standard for human diseases, the DO provides a stable, etiology-based structure integrating mechanistic drivers of human disease. Over the past two decades the DO has grown from a collection of clinical vocabularies, into an expertly curated semantic resource of over 11300 common and rare diseases linking disease concepts through more than 37000 vocabulary cross mappings (v2023-08-08). Here, we introduce the recently launched DO Knowledgebase (DO-KB), which expands the DO\u27s representation of the diseaseome and enhances the findability, accessibility, interoperability and reusability (FAIR) of disease data through a new SPARQL service and new Faceted Search Interface. The DO-KB is an integrated data system, built upon the DO\u27s semantic disease knowledge backbone, with resources that expose and connect the DO\u27s semantic knowledge with disease-related data across Open Linked Data resources. This update includes descriptions of efforts to assess the DO\u27s global impact and improvements to data quality and content, with emphasis on changes in the last two years

Money, sex and happiness : an empirical study

The links between income, sexual behavior and reported happiness are studied using recent data on a sample of 16,000 adult Americans. The paper finds that sexual activity enters strongly positively in happiness equations. Higher income does not buy more sex or more sexual partners. Married people have more sex than those who are single, divorced, widowed or separated. The happiness‐maximizing number of sexual partners in the previous year is calculated to be 1. Highly educated females tend to have fewer sexual partners. Homosexuality has no statistically significant effect on happiness

Resistance of Renal Cell Carcinoma to Sorafenib Is Mediated by Potentially Reversible Gene Expression

Purpose: Resistance to antiangiogenic therapy is an important clinical problem. We examined whether resistance occurs at least in part via reversible, physiologic changes in the tumor, or results solely from stable genetic changes in resistant tumor cells. Experimental Design: Mice bearing two human RCC xenografts were treated with sorafenib until they acquired resistance. Resistant 786-O cells were harvested and reimplanted into naïve mice. Mice bearing resistant A498 cells were subjected to a 1 week treatment break. Sorafenib was then again administered to both sets of mice. Tumor growth patterns, gene expression, viability, blood vessel density, and perfusion were serially assessed in treated vs control mice. Results: Despite prior resistance, reimplanted 786-O tumors maintained their ability to stabilize on sorafenib in sequential reimplantation steps. A transcriptome profile of the tumors revealed that the gene expression profile of tumors upon reimplantation reapproximated that of the untreated tumors and was distinct from tumors exhibiting resistance to sorafenib. In A498 tumors, revascularization was noted with resistance and cessation of sorafenib therapy and tumor perfusion was reduced and tumor cell necrosis enhanced with re-exposure to sorafenib. Conclusions: In two RCC cell lines, resistance to sorafenib appears to be reversible. These results support the hypothesis that resistance to VEGF pathway therapy is not solely the result of a permanent genetic change in the tumor or selection of resistant clones, but rather is due to a great extent to reversible changes that likely occur in the tumor and/or its microenvironment

Development of a new tissue injector for subretinal transplantation of human embryonic stem cell derived retinal pigmented epithelium

Background: Subretinal cell transplantation is a challenging surgical maneuver. This paper describes the preliminary findings of a new tissue injector for subretinal implantation of an ultrathin non-absorbable substrate seeded with human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE). Methods: Ultrathin Parylene-C substrates measuring 3.5 mm × 6.0 mm seeded with hESC-RPE (implant referred to as CPCB-RPE1) were implanted into the subretinal space of 12 Yucatan minipigs. Animals were euthanized immediately after the procedure and underwent spectral domain optical coherence tomography (SD-OCT) and histological analysis to assess the subretinal placement of the implant. Evaluation of the hESC-RPE cells seeded on the substrate was carried out before and after implantation using standard cell counting techniques. Results: The tissue injector delivered the CPCB-RPE1 implant through a 1.5 mm sclerotomy and a 1.0–1.5 mm retinectomy. SD-OCT scans and histological examination revealed that substrates were precisely placed in the subretinal space, and that the hESC-RPE cell monolayer continued to cover the surface of the substrate after the surgical procedure. Conclusion: This innovative tissue injector was able to efficiently deliver the implant in the subretinal space of Yucatan minipigs, preventing significant hESC-RPE cell loss, minimizing tissue trauma, surgical complications and postoperative inflammation