Structure in the optical absorption edge of amorphous selenium technical note no. 8

Temperature measurement of absorption spectrum near band edge of amorphous selenium on evaporated samples with and without substrate

Research in far ultraviolet filtering for space optical systems

Design and fabrication of multilayer interference filters for ultraviole

Evaluating Estradiol as a Novel Therapy for Dry Age-Related Macular Degeneration/Geographic Atrophy

Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the elderly population in the United States and is more prevalent in post-menopausal females than age-matched males. There are no current FDA-approved therapies for dry AMD, which composes 80- 90% of all AMD cases. Late stage dry AMD (geographic atrophy) is characterized by extensive loss of the retinal pigment epithelium (RPE) along with degeneration of the photoreceptors, which cause significant central vision loss. AMD is characterized by drusen, which are extracellular deposits located beneath the retina. Drusen contain proteins associated with the process of inflammation such as activated complement proteins, fragments of the membrane attack complex, vitronectin, cholesterol, C-reactive protein, and amyloid-β. Amyloid-β is a cytotoxic protein associated with various neurodegenerative diseases and is commonly found in plaques of Alzheimer’s disease. Based on these findings, we hypothesized that estradiol may have protective effects against the cytotoxic properties of amyloid-β in RPE cells in vitro

Effects of fluoroquinolones and tetracyclines on mitochondria of human retinal MIO-M1 cells

Our goal was to explore the detrimental impacts of ciprofloxacin (CPFX) and tetracycline (TETRA) on human retinal Müller (MIO-M1) cells in vitro. Cells were exposed to 30, 60 and 120 μg/ml of CPFX and TETRA. The cellular metabolism was measured with the MTT assay. The JC-1 and CM-H2DCFDA assays were used to evaluate the levels of mitochondrial membrane potential (MMP) and ROS (reactive oxygen species), respectively. Mitochondrial DNA (mtDNA) copy number, along with gene expression levels associated with apoptotic (BAX, BCL2-L13, BCL2, CASP-3 and CASP-9), inflammatory (IL-6, IL-1β, TGF-α, TGF-β1 and TGF-β2) and antioxidant pathways (SOD2, SOD3, GPX3 and NOX4) were analyzed via Quantitative Real-Time PCR (qRT-PCR). Bioenergetic profiles were measured using the Seahorse® XF Flux Analyzer. Cells exposed 24 h to 120 μg/ml TETRA demonstrated higher cellular metabolism compared to vehicle-treated cells. At each time points, (i) all TETRA concentrations reduced MMP levels and (ii) ROS levels were reduced by TETRA 120 μg/ml treatment. TETRA caused (i) higher expression of CASP-3, CASP-9, TGF-α, IL-1B, GPX3 and SOD3 but (ii) decreased levels of TGF-B2 and SOD2. ATP production and spare respiratory capacity declined with TETRA treatment. Cellular metabolism was reduced with CPFX 120 μg/ml in all cultures and 60 μg/ml after 72 h. The CPFX 120 μg/ml reduced MMP in all cultures and ROS levels (72 h). CPFX treatment (i) increased expression of CASP-3, CASP-9, and BCL2-L13, (ii) elevated the basal oxygen consumption rate, and (iii) lowered the mtDNA copy numbers and expression levels of TGF-B2, IL-6 and IL-1B compared to vehicle-control cells. We conclude that clinically relevant dosages of bactericidal and bacteriostatic antibiotics can have negative effects on the cellular metabolism and mitochondrial membrane potential of the retinal MIO-M1 cells in vitro. It is noteworthy to mention that apoptotic and inflammatory pathways in exposed cells were affected significantly This is the first study showing the negative impact of fluoroquinolones and tetracyclines on mitochondrial behavior of human retinal MIO-M1 cells

Keratoconus associated with choroidal neovascularization: a case report

<p>Abstract</p> <p>Introduction</p> <p>Keratoconus and choroidal neovascularization can occur as a result of dysfunction of the epithelium and its basement membrane.</p> <p>Case presentation</p> <p>A 17-year-old Asian man, who was diagnosed with myopic choroidal neovascularization in both eyes and who subsequently underwent intravitreal injection of ranibizumab (Lucentis^®) five times over six months, presented with further vision decrease and pain in his right eye. Examination showed corneal steepening and stromal edema in the inferocentral cornea of his right eye, both of which were indicative of advanced keratoconus with acute hydrops. Corneal topography also showed features consistent with keratoconus in his left eye. Fluorescein angiography and optical coherence tomography revealed choroidal neovascularization-associated subretinal hemorrhages and lacquer cracks in both eyes.</p> <p>Conclusion</p> <p>Keratoconus and choroidal neovascularization, possibly resulting from dysfunction of the epithelium and its basement membrane, can occur together in the same individual. This would suggest a possible connection in pathogenesis between these two conditions.</p

Comparing Mutuality and Solidarity in Its Application to Disaster Ethics

Often it has been observed that in disaster situations, people (including victims) become altruistic and are very willing to listen, obey and act in a manner that would help bring an end to the situation. In this chapter, linking disaster ethics and human rights, it is argued that this indeed is how it should be, disaster or otherwise, and that we have moral duties to oneself and to others. An individual exhibiting solidarity, comradery and altruism during a disaster is indeed behaving as a reasonable Self, and exercising ethical individualism as per Gewirthian philosophy. It is the duty of the State and society to act as a supportive State and a caring society. In order to do this, we need to be conditioned for ethical rationality before any whiff of disaster arises, i.e. in our day-to-day conduct and decision-making, at a personal, institutional and transnational level. Our ethical resilience during disasters can only be as robust as our rational moral compass during ‘peace-time’. This chapter argues that Gewirthian solidarity ethics (GSE) should play a role in European policy and action in order to provide a system that conditions ethical rationality and in order to fulfil human rights. This involves addressing our current understanding of human rights as distinct categories of civil, political, economic, social and cultural rights and to effect a shift towards a more holistic understanding of human rights, whereby the hierarchy of fulfilment does not always prioritise civil and political rights.Peer reviewe

Movement variability in stroke patients and controls performing two upper limb functional tasks: a new assessment methodology

Background: In the evaluation of upper limb impairment post stroke there remains a gap between detailed kinematic analyses with expensive motion capturing systems and common clinical assessment tests. In particular, although many clinical tests evaluate the performance of functional tasks, metrics to characterise upper limb kinematics are generally not applicable to such tasks and very limited in scope. This paper reports on a novel, user-friendly methodology that allows for the assessment of both signal magnitude and timing variability in upper limb movement trajectories during functional task performance. In order to demonstrate the technique, we report on a study in which the variability in timing and signal magnitude of data collected during the performance of two functional tasks is compared between a group of subjects with stroke and a group of individually matched control subjects. Methods: We employ dynamic time warping for curve registration to quantify two aspects of movement variability: 1) variability of the timing of the accelerometer signals' characteristics and 2) variability of the signals' magnitude. Six stroke patients and six matched controls performed several trials of a unilateral ('drinking') and a bilateral ('moving a plate') functional task on two different days, approximately 1 month apart. Group differences for the two variability metrics were investigated on both days. Results: For 'drinking from a glass' significant group differences were obtained on both days for the timing variability of the acceleration signals' characteristics (p = 0.002 and p = 0.008 for test and retest, respectively); all stroke patients showed increased signal timing variability as compared to their corresponding control subject. 'Moving a plate' provided less distinct group differences. Conclusion: This initial application establishes that movement variability metrics, as determined by our methodology, appear different in stroke patients as compared to matched controls during unilateral task performance ('drinking'). Use of a user-friendly, inexpensive accelerometer makes this methodology feasible for routine clinical evaluations. We are encouraged to perform larger studies to further investigate the metrics' usefulness when quantifying levels of impairment

Protective Effects of Memantine on Hydroquinone-Treated Human Retinal Pigment Epithelium Cells and Human Retinal Muller Cells

Purpose: Memantine (MEM) acts on the glutamatergic system by blocking N-methyl-d-aspartate (NMDA) glutamate receptors. The role that MEM plays in protecting retinal cells is unknown. Hydroquinone (HQ) is one of the cytotoxic components in cigarette smoke. In the present study, we tested whether pretreatment with MEM could protect against the cytotoxic effects of HQ on human retinal pigment epithelium cells (ARPE-19) and human retinal Müller cells (MIO-M1) in vitro. Methods: Cells were plated, pretreated for 6 h with 30 μM of MEM, and then exposed for 24 h to 200, 100, 50, and 25 μM of HQ while MEM was still present. Cell viability (CV), reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), and lactate dehydrogenase (LDH) release assays were performed. Results: HQ-treated cells showed a dose-dependent decrease in CV and ΔΨm, but an increase in ROS production and LDH levels in both cell lines. MEM pretreatment reversed the CV in 50, 100, and 200 μM doses in ARPE-19 cells and at all HQ concentrations in MIO-M1 cells compared to HQ-treated cultures. ROS production was reversed in all HQ concentrations in both cell lines. ΔΨm was significantly increased after MEM pretreatment only in 50 μM HQ concentration for both cell lines. LDH levels were decreased at 50 and 25 μM HQ in ARPE-19 and MIO-M1 cells, respectively. Conclusion: HQ-induced toxicity is concentration dependent in ARPE-19 and MIO-M1 cultures. MEM exerts protective effects against HQ-induced toxicity on human retinal pigment epithelial and Müller cells in vitro

Hedgehog-mediated regulation of PPARγ controls metabolic patterns in neural precursors and shh-driven medulloblastoma

Sonic hedgehog (Shh) signaling is critical during development and its aberration is common across the spectrum of human malignancies. In the cerebellum, excessive activity of the Shh signaling pathway is associated with the devastating pediatric brain tumor medulloblastoma. We previously demonstrated that exaggerated de novo lipid synthesis is a hallmark of Shh-driven medulloblastoma and that hedgehog signaling inactivates the Rb/E2F tumor suppressor complex to promote lipogenesis. Indeed, such Shh-mediated metabolic reprogramming fuels tumor progression, in an E2F1- and FASN-dependent manner. Here, we show that the nutrient sensor PPARγ is a key component of the Shh metabolic network, particularly its regulation of glycolysis. Our data show that in primary cerebellar granule neural precursors (CGNPs), proposed medulloblastoma cells-of-origin, Shh stimulation elicits a marked induction of PPARγ alongside major glycolytic markers. This is also documented in the actively proliferating Shh-responsive CGNPs in the developing cerebellum, and PPARγ expression is strikingly elevated in Shh-driven medulloblastoma in vivo. Importantly, pharmacological blockade of PPARγ and/or Rb inactivation inhibits CGNP proliferation, drives medulloblastoma cell death and extends survival of medulloblastoma-bearing animals in vivo. This coupling of mitogenic Shh signaling to a major nutrient sensor and metabolic transcriptional regulator define a novel mechanism through which Shh signaling engages the nutrient sensing machinery in brain cancer, controls the cell cycle, and regulates the glycolytic index. This also reveals a dominant role of Shh in the etiology of glucose metabolism in medulloblastoma and underscores the function of the Shh → E2F1 → PPARγ axis in altering substrate utilization patterns in brain cancers in favor of tumor growth. These findings emphasize the value of PPARγ downstream of Shh as a global therapeutic target in hedgehog-dependent and/or Rb-inactivated tumors