Two-photon microperimetry: Sensitivity of human photoreceptors to infrared light

Microperimetry is a subjective ophthalmologic test used to assess retinal function at various specific and focal locations of the visual field. Historically, visible light has been described as ranging from 400 to 720 nm. However, we previously demonstrated that infra-red light can initiate visual transduction in rod photoreceptors by a mechanism of two-photon absorption by visual pigments. Here we introduce a newly designed and constructed two-photon microperimeter. We provide for the first time evidence of the presence of a nonlinear process occurring in the human retina based on psychophysical tests using newly developed instrumentation. Since infra-red light penetrates the aged front of the eye better than visible light, it has the potential for improved functional diagnostics in patients with age-related visual disorders

Age-related changes in geometry and transparency of human crystalline lens revealed by optical signal discontinuity zones in swept-source OCT images

Abstract Background The shape and microstructure of the human crystalline lens alter with ageing, and this has an effect on the optical properties of the eye. The aim of this study was to characterise the age-related differences in the morphology and transparency of the eye lenses of healthy subjects through the optical signal discontinuity (OSD) zones in optical coherence tomography (OCT) images. We also investigated the association of those changes with the optical quality of the eye and visual function. Methods OCT images of the anterior segment of 49 eyes of subjects (9–78 years) were acquired, and the OSD zones (nucleus, C1–C4 cortical zones) were identified. Central thickness, curvature and optical density were measured. The eye’s optical quality was evaluated by the objective scatter index (OSI). Contrast sensitivity and visual acuity tests were performed. The correlation between extracted parameters and age was assessed. Results The increase in lens thickness with age was dominated by the thickening of the cortical zone C3 (0.0146 mm/year). The curvature radii of the anterior lens surface and both anterior and posterior nucleo-cortical interfaces decreased with age (− 0.053 mm/year, − 0.013 mm/year and − 0.006 mm/year, respectively), and no change was observed for the posterior lens radius. OCT-based densitometry revealed significant correlations with age for all zones except for C1β, and the highest increase in density was in the C2–C4 zones (R = 0.45, 0.74, 0.56, respectively, P < 0.001). Increase in OSI was associated with the degradation of visual function. Conclusions OCT enables the identification of OSD zones of the crystalline lens. The most significant age-related changes occur in the C3 zone as it thickens with age at a faster rate and becomes more opaque than other OSD zones. The changes are associated with optical quality deterioration and reduction of visual performance. These findings contribute to a better understanding of the structure–function relationship of the ageing lens and offer insights into both pathological and aging alterations

Two-photon imaging of the mammalian retina with ultrafast pulsing laser

Noninvasive imaging of visual system components in vivo is critical for understanding the causal mechanisms of retinal diseases and for developing therapies for their treatment. However, ultraviolet light needed to excite endogenous fluorophores that participate in metabolic processes of the retina is highly attenuated by the anterior segment of the human eye. In contrast, 2-photon excitation fluorescence imaging with pulsed infrared light overcomes this obstacle. Reducing retinal exposure to laser radiation remains a major barrier in advancing this technology to studies in humans. To increase fluorescence intensity and reduce the requisite laser power, we modulated ultrashort laser pulses with high-order dispersion compensation and applied sensorless adaptive optics and custom image recovery software and observed an over 300% increase in fluorescence of endogenous retinal fluorophores when laser pulses were shortened from 75 fs to 20 fs. No functional or structural changes to the retina were detected after exposure to 2-photon excitation imaging light with 20-fs pulses. Moreover, wide bandwidth associated with short pulses enables excitation of multiple fluorophores with different absorption spectra and thus can provide information about their relative changes and intracellular distribution. These data constitute a substantial advancement for safe 2-photon fluorescence imaging of the human eye

Ohio History Fall 2017

https://kent-islandora.s3.us-east-2.amazonaws.com/node/10123/OH-v124n2-thumb.jpgOHIO HISTORY Contents for Volume 124,&nbsp;Number 2, Fall 2017 Contributors ...... 4 &nbsp; Ladies of Lockbourne: Women Airforce Service Pilots and the Mighty B-17 Flying Fortress Jenny Sage ...... 5 Pathmakers: James and Mary Jane McCleery Lawrence S. Freund ...... 28 From the Parish Hall to the Union Hall: Catholic Labor Education in Cleveland Paul Lubienecki ...... 49 &nbsp; Book Reviews ...... 85 Cover image courtesy of the National Archives.</p

Design, Synthesis, and Evaluation of Novel Hybrid Efflux Pump Inhibitors for Use against Mycobacterium tuberculosis

Efflux pumps are considered a major potential contributor to the development of various forms of resistance in Mycobacterium tuberculosis leading to the emergence of multidrug-resistant tuberculosis (TB). Verapamil (VER) and tricyclic chemosensitizers such as the phenothiazines are known to possess efflux pump inhibition properties and have demonstrated significant efficacy in various TB disease models. Novel hybrid molecules based on fusion of the VER substructure with various tricyclic, as well as nontricyclic, chemosensitizer cores or their structural motifs are described. These hybrid compounds were evaluated in vitro and ex vivo individually for their intrinsic activity and in combination for their potentiating potential with the frontline anti-TB drugs, rifampin and isoniazid. In addition, efflux pump inhibition was assessed in an ethidium bromide assay. This study led to the identification of novel compounds, termed hybrid efflux pump inhibitors, with intrinsic antimycobacterial activities (MIC₉₀ ≤ 3.17 μg/mL) and intracellular activity in macrophages at a low concentration (≤6.25 μg/mL)

Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo

Foxp3(+) CD4(+) T helper cells called regulatory T (T reg) cells play a key role in controlling reactivity to self-antigens and onset of autoimmunity. T reg cells either arise in thymus and are called natural T reg (nT reg) cells or are generated in the periphery through induction of Foxp3 and are called inducible T reg (iT reg) cells. The relative contributions of iT reg cells and nT reg cells in peripheral tolerance remain unclear as a result of an inability to separate these two subsets of T reg cells. Using a combination of novel TCR transgenic mice with a defined self-antigen specificity and conventional mouse models, we demonstrate that a cell surface molecule, neuropilin-1 (Nrp-1), is expressed at high levels on nT reg cells and can be used to separate nT reg versus iT reg cells in certain physiological settings. In addition, iT reg cells generated through antigen delivery or converted under homeostatic conditions lack Nrp-1 expression. Nrp-1(lo) iT reg cells show similar suppressive activity to nT reg cells in controlling ongoing autoimmune responses under homeostatic conditions. In contrast, their activity might be compromised in certain lymphopenic settings. Collectively, our data show that Nrp-1 provides an excellent marker to distinguish distinct T reg subsets and will be useful in studying the role of nT reg versus iT reg cells in different disease settings

Ohio History 2014

https://kent-islandora.s3.us-east-2.amazonaws.com/node/10128/OH-v121-thumb.jpgOHIO HISTORY Contents for Volume 121, 2014 Time Not Ripe: Black Women’s Quest for Citizenship and the Battle for Full Inclusion at Ohio State University Tyran Kai Steward ...... 4 “The Most Free of the Free States”: Politics, Slavery, Race, and Regional Identity in Early Ohio, 1790–1820 John Craig Hammond ...... 35 James A. Shedd to Dr. David Jordon: A Documentary Perspective on the Dayton Mob of 1841 Hans C. Rasmussen ...... 58 The Ohio Constitution of 1803, Jefferson’s Danbury Letter, and Religion in Education David Scott ...... 73 Memories of Work and the Definition of Community: The Making of Italian Americans in the Mahoning Valley Donna M. DeBlasio and Martha I. Pallante ...... 89 Germans, Jubilee Singers, and Axe Men: James A. Garfield and the Original Front-Porch Campaign for the Presidency Jeffrey Normand Bourdon ...... 112 &nbsp; Book Reviews ......&nbsp;130 On the cover: Niles Fire Brick workers, ca. 1896.</p

Evaluation of spiropiperidine hydantoins as a novel class of antimalarial agents

Given the rise of parasite resistance to all currently used antimalarial drugs, the identification of novel chemotypes with unique mechanisms of action is of paramount importance. Since Plasmodium expresses a number of aspartic proteases necessary for its survival, we have mined antimalarial datasets for drug-like aspartic protease inhibitors. This effort led to the identification of spiropiperidine hydantoins, bearing similarity to known inhibitors of the human aspartic protease beta-secretase (BACE), as new leads for antimalarial drug discovery. Spiropiperidine hydantoins have a dynamic structure-activity relationship profile with positions identified as being tolerant of a variety of substitution patterns as well as a key piperidine N-benzyl phenol pharmacophore. Lead compounds 4e (CWHM-123) and 12k (CWHM-505) are potent antimalarials with IC50 values against Plasmodium falciparum 3D7 of 0.310 mu M and 0.099 mu M, respectively, and the former features equivalent potency on the chloroquine-resistant Dd2 strain. Remarkably, these compounds do not inhibit human aspartic proteases BACE, cathepsins D and E, or Plasmodium plasmepsins II and IV despite their similarity to known BACE inhibitors. Although the current leads suffer from poor metabolic stability, they do fit into a drug-like chemical property space and provide a new class of potent antimalarial agents for further study. (C) 2015 Elsevier Ltd. All rights reserved