Search

Long-term kidney transplant (KT) allograft outcomes have not improved as expected despite a better understanding of rejection and improved immunosuppression. Previous work had validated a computed rejection score, the tissue common rejection module (tCRM), measured by amplification-based assessment of 11 genes from formalin-fixed paraffin-embedded (FFPE) biopsy specimens, which allows for quantitative, unbiased assessment of immune injury. We applied tCRM in a prospective trial of 124 KT recipients, and contrasted assessment by tCRM and histology reads from 2 independent pathologists on protocol and cause biopsies post-transplant. Four 10-μm shaves from FFPE biopsy specimens were used for RNA extraction and amplification by qPCR of the 11 tCRM genes, from which the tCRM score was calculated. Biopsy diagnoses of either acute rejection (AR) or borderline rejection (BL) were considered to have inflammation present, while stable biopsies had no inflammation. Of the 77 biopsies that were read by both pathologists, a total of 40 mismatches in the diagnosis were present. The median tCRM scores for AR, BL, and stable diagnoses were 4.87, 1.85, and 1.27, respectively, with an overall significant difference among all histologic groups (Kruskal-Wallis, p < 0.0001). There were significant differences in tCRM scores between pathologists both finding inflammation vs. disagreement (p = 0.003), and both finding inflammation vs. both finding no inflammation (p < 0.001), along with overall significance between all scores (Kruskal-Wallis, p < 0.001). A logistic regression model predicting graft inflammation using various clinical predictor variables and tCRM revealed the tCRM score as the only significant predictor of graft inflammation (OR: 1.90, 95% CI: 1.40–2.68, p < 0.0001). Accurate, quantitative, and unbiased assessment of rejection of the clinical sample is critical. Given the discrepant diagnoses between pathologists on the same samples, individuals could utilize the tCRM score as a tiebreaker in unclear situations. We propose that the tCRM quantitative score can provide unbiased quantification of graft inflammation, and its rapid evaluation by PCR on the FFPE shave can become a critical adjunct to help drive clinical decision making and immunosuppression delivery.

The Peruvian Region of Tacna has the highest prevalence of macrosomia (15%), but also the highest arsenic (As) concentration in tap water. The consumption of tap water contaminated with arsenic is associated with low birth weight. To address this discrepancy in this Region, the objective of this study is to evaluate the averages of arsenic concentration in tap water with diferent reproductive outcomes

Inorganic arsenic exposure has been linked to the development of several health conditions, including adverse birth outcomes, and around 150 million of people worldwide are exposed to levels above the WHO suggested limit of 10 μg/L. A recent risk assessment in pregnant women of Tacna, of this same population performed by our group, found that 70.25% were exposed to arsenic concentrations in drinking water ≥ 25 μg/L. The present study aimed to evaluate the relationship between prenatal total urinary arsenic (U-tAs) and inorganic arsenic (U-iAs) with adverse birth outcomes. A total of 147 pregnant women from the province of Tacna, Peru, during February–March, 2019, were evaluated for U-tAs and U-iAs exposure during their second trimester of pregnancy, while the birth records of their children were collected from the local hospital. The geometric mean U-tAs was 43.97 ± 25.88 μg/L (P50 22.30, range 5.99–181.94 μg/L) and U-iAs was 5.27 ± 2.91 μg/L. Controlling for maternal age, pre-pregnancy BMI, parity, mother’s education, and newborn sex, no relationship was observed between tertile of U-tAs and the birth outcomes considered, although we found an apparent but statistically non-significant dose–response relationship for small for gestational age 2.38% (95% CI 0.003, 0.16), versus 7.32% (95% CI 0.02, 0.21%), and versus 8.57% (95% CI 0.03, 0.25%). This finding requires further evaluation considering other factors such as metabolic arsenic species, additional maternal covariates, and ethnicity.

PurposeThe aim of this study was to examine the effect of 17β-estradiol on Benzo(e)pyrene [B(e)P]-induced toxicity in ARPE-19 cells.MethodsWe pretreated ARPE-19 cells with 20 nM and 40 nM 17β-estradiol for 6 hours, followed by addition of 300 μM B(e)P for additional 24 hours. Cell viability was measured using Trypan blue dye-exclusion assay. JC-1 assay was performed to measure mitochondrial membrane potential (ΔΨm). For a quantitative estimation of cell death, apoptotic markers such as caspase-3/7, caspase-9, and caspase-12 were measured.ResultsOur results demonstrated that when treated with B(e)P, the viability and ΔΨm of ARPE-19 cells declined by 25% and 63%, respectively (P < 0.05). However, pretreating with 17β-estradiol increased the viability of ARPE-19 cells by 21% (20 nM) and 10% (40 nM) (P < 0.05). Furthermore, the significantly reduced ΔΨm in βE+B(e)P treated cells ARPE-19 cells was restored by pre-treatment with 17β-estradiol- ΔΨm was increased by 177% (20 nM) and 158% (40 nM) (P < 0.05). We further observed a significant up-regulation in the activity of Caspases-3/7, -9, and -12 in B(e)P-treated ARPE-19 cells. However, 17β-estradiol treatment significantly reduced the activity of all apoptotic markers (P < 0.05).ConclusionIn conclusion, our results demonstrate that 17β-estradiol protects ARPE-19 cells against B(e)P-induced toxicity by decreasing apoptosis, preventing cell death, and restoring mitochondrial membrane potential.

Introducción: El embarazo en adolescentes es un fenómeno bio-psico-social de gran importancia, que frecuentemente se le asocia parto pretermino. El objetivo fue determinar los factores de riesgo asociados a parto pretermino en adolescentes. Material y métodos: Estudio retrospectivo, analítico, de casos y controles. Se comparó 101 adolescentes con parto pretermino atendidas en el hospital Hipólito Unanue de Tacna durante los años 2006 a 2010, con 303 adolescentes de parto a término, seleccionadas al azar 3 controles por caso. Se utilizó OR con intervalos de confianza al 95%. La información se obtuvo de la base de datos del Sistema Informático Perinatal (SIP2000). Resultados: La frecuencia de embarazo en adolescentes fue 21,5%, siendo la frecuencia de parto pretermino en adolescentes del 4,2%. La mayoría de gestantes adolescentes fueron convivientes, con grado de instrucción secundaria, sin hábitos nocivos, sin antecedentes patológicos, primigestas, nulíparas, con menos de 7 controles prenatales y con anemia. Los factores que se asociaron significativamente a parto pretermino en adolescentes fueron: controles prenatales

We present in this paper a revision of three different methods we conceived in the framework of liquid crystal on silicon (LCoS) display optimization and application.We preliminarily demonstrate an LCoS self-calibration technique, from which we can perform a complete LCoS characterization. In particular, two important characteristics of LCoS displays are retrieved by using self-addressed digital holograms. On the one hand, we determine its phase-voltage curve by using the interference pattern generated by a digital two-sectorial split-lens configuration. On the other hand, the LCoS surface profile is also determined by using a self-addressed dynamicmicro-lens array pattern. Second, the implementation of microparticle manipulation through optical traps created by an LCoS display is demonstrated. Finally, an LCoS display based inline (IL) holographic imaging system is described. By using the LCoS display to implement a double-sideband filter configuration, this inline architecture demonstrates the advantage of obtaining dynamic holographic imaging of microparticles independently of their spatial positions by avoiding the non-desired conjugate images. Fil: Zhang, Haolin. Universidad Autonoma de Barcelona. Facultad de Física; España Fil: Lizana, Ángel. Universidad Autonoma de Barcelona. Facultad de Física; España Fil: Van Eeckhout, Albert. Universidad Autonoma de Barcelona. Facultad de Física; España Fil: Turpin, Alex. Universidad Autonoma de Barcelona. Facultad de Física; España Fil: Ramirez, Claudio. Universidad Nacional Autónoma de México; México Fil: Iemmi, Claudio César. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina Fil: Campos, Juan. Universidad Autonoma de Barcelona. Facultad de Física; España

We present a comparison of two experimental methods to measure retardance as a function of applied voltage and as a function of position over the aperture of liquid-crystal variable retarders. These measurements are required for many applications, particularly in polarimetry. One method involves the scan of an unexpanded laser beam over the aperture, and the other uses an expanded beam from a LED and a CCD camera to measure the full aperture with a single measurement. The first method is time consuming, is limited in the measured spatial resolution, and requires more expensive equipment to perform the scan, whereas the second method is low cost, with the spatial resolution of the CCD, and fast, but in principle has variations of the incident beam over the aperture that affect the measured retardance values. The results obtained show good agreement for the average values of retardance for the two methods, but the expanded-beam method shows more noise, particularly close to the voltage values at which the variable-retarder retardance versus voltage curves are unwrapped. These retardance variations can be reduced by smoothing the retardance image, which makes the expanded-beam method an attractive method for polarimetry applications since it gives the complete information in the full aperture of the device with the additional advantages of low cost, simplicity, and being less time consuming.

We present a comparison of the first numerical and experimental results for the scattering of light from rough surfaces using a recently developed variable coherence polarimetry source that permits obtaining information on the object without having to scan over incidence or scatter angle. We present, for the first time, we believe, the application of this source to a 1D rough surface and show how to analyze the scattered field to retrieve useful information about the surface. This source uses a liquid-crystal phase modulator to control the polarization as well as the coherence of the beam illuminating the rough surface. Changing the polarization state distribution at the source plane, by controlling the phase distribution on a spatial light modulator, gives a scan of two source spots over the rough surface. The scattered beam is analyzed with a Stokes polarimeter. The Kirchhoff approximation is used to calculate the scattered Stokes vector using the experimental incident Stokes vector and intensity distribution as a source. Good agreement is obtained between the numerical and experimental results, for a simple calculation of the number of intensity maxima obtained as the two first-order source spots are scanned across the sample.

Background Healthcare-associated infections (HAIs) have a major impact on public health worldwide. Particularly, hospital surfaces contaminated with bacterial pathogens are often the origin of both sporadic cases and outbreaks of HAIs. It has been demonstrated that copper surfaces reduce the microbial burden of high touch surfaces in the hospital environment. Here we report the antimicrobial characterization of a novel composite coating with embedded copper particles, named Copper Armour™. Methods The Copper Armour™ bactericidal activity was evaluated in in vitro assays against several bacterial pathogens, including Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli O157:H7 and Listeria monocytogenes. Additionally, its antimicrobial properties were also evaluated in a pilot study over a nine-week period at an adult intensive care unit. For this, four high touch surfaces, including bed rails, overbed table, bedside table and IV Pole, were coated with Cooper Armour™, and its microbial burden was determined over a nine-week period. Results Copper Armour™ coated samples showed an in vitro reduction in bacterial burden of > 99.9% compared to control samples. Moreover, pilot study results indicate that Copper Armour™ significantly reduces the level of microbial contamination on high-touch surfaces in the hospital environment, as compared with standard surfaces. Conclusions Based on its antimicrobial properties, Copper Armour™ is a novel self-sanitizing coating that exhibits bactericidal activity against important human pathogens and significantly reduces the microbial burden of hospital surfaces. This composite could be used as a self-sanitizing coating to complement infection control strategies in healthcare facilities.

We present an experimental method, based on the use of dynamic split-lens configurations, useful for the trapping and spatial control of microparticles through the photophoretic force. In particular, the concept of split-lens configurations is exploited to experimentally create customized and reconfigurable three-dimensional light structures, in which carbon coated glass microspheres, with sizes in a range of 63–75 μm, can be captured. The generation of light spatial structures is performed by properly addressing phase distributions corresponding to different split-lens configurations onto a spatial light modulator (SLM). The use of an SLM allows a dynamic variation of the light structures geometry just by modifying few control parameters of easy physical interpretation. We provide some examples in video format of particle trapping processes. What is more, we also perform further spatial manipulation, by controlling the spatial position of the particles in the axial direction, demonstrating the generation of reconfigurable three-dimensional photophoretic traps for microscopic manipulation of absorbing particles.

In this paper, a compact optical system for generating arbitrary spatial light polarization patterns is demonstrated. The system uses a single high-resolution liquid crystal (LC) on silicon (LCOS) spatial light modulator. A specialized optical mount is designed and fabricated using a 3D printer, in order to build a compact dual optical architecture, where two different phase patterns are encoded on two adjacent halves of the LCOS screen, with a polarization transformation in between. The final polarization state is controlled via two rotations of the Poincaré sphere. In addition, a relative phase term is added, which is calculated based on spherical trigonometry on the Poincaré sphere. Experimental results are presented that show the effectiveness of the system to produce polarization patterns.

The geographic origins of populations can be identified by their maternally inherited mitochondrial DNA (mtDNA) haplogroups. This study compared human cybrids (cytoplasmic hybrids), which are cell lines with identical nuclei but mitochondria from different individuals with mtDNA from either the H haplogroup or L haplogroup backgrounds. The most common European haplogroup is H while individuals of maternal African origin are of the L haplogroup. Despite lower mtDNA copy numbers, L cybrids had higher expression levels for nine mtDNA-encoded respiratory complex genes, decreased ATP (adenosine triphosphate) turnover rates and lower levels of reactive oxygen species production, parameters which are consistent with more efficient oxidative phosphorylation. Surprisingly, GeneChip arrays showed that the L and H cybrids had major differences in expression of genes of the canonical complement system (5 genes), dermatan/chondroitin sulfate biosynthesis (5 genes) and CCR3 (chemokine, CC motif, receptor 3) signaling (9 genes). Quantitative nuclear gene expression studies confirmed that L cybrids had (a) lower expression levels of complement pathway and innate immunity genes and (b) increased levels of inflammation-related signaling genes, which are critical in human diseases. Our data support the hypothesis that mtDNA haplogroups representing populations from different geographic origins may play a role in differential susceptibilities to diseases.

We present an intuitive and versatile method that can dynamically generate 2D and 3D tailored light patterns. The light structures are generated by dynamically implementing discrete and continuous split lens configurations onto a spatial light modulator. These configurations can be dynamically modified by tuning a reduced number of control parameters with simple physical interpretation. We demonstrate the versatility of the method by experimentally implementing a wide number of structured beams, including optical lattices, a light cone, and vortex beams carrying orbital angular momentum. Compared with other optical illuminators, the advantages of our method are its simple interpretation and control for creating the light structures, and that it is based on a robust, dynamic and easy-to-build optical set-up. The proposed method may be useful in a large number of applications, such as optical trapping, super-resolution imaging or illuminating arrays of photonic switching devices.

On the 20th of December 2013, The United Nations (UN) General Assembly 68th Session proclaimed 2015 as the International Year of Light and Light-based Technologies (IYL 2015). The proclamation of an International Year focusing on the light science and applications recognizes the importance of light in the society, which plays a vital role in our daily lives, being visible in a widespread number of different areas, as for instance, in technology, education, energy, art, agriculture, health, among many others. In this work, the members of the Image Processing Laboratory from the Universitat Autonoma de Barcelona (UAB), analyze the concept of readapting some experiments in optics -usually conducted in different courses at the UAB physics degree- into the artistic context of the MACBA (Museu d’Art Contemporani de Barcelona). This project, called SummerLight, takes place within the framework of the IYL, as part of the activities devised to promote the visibility of light. The readapted experiments are expected to teach and improve the knowledge of high school students with respect to different important physical phenomena related to the wave nature of light as polarization, interferences and diffraction. This study analyzes the suitability of the proposed experiments in terms of student optical skills improvement. In addition, its contextualization into an artistic scenario is also discussed.

Human Molecular Genetics, 2014, Vol. 23, No. 13 doi:10.1093/hmg/ddu065 Advance Access published on February 28, 2014 Inherited mitochondrial DNA variants can affect complement, inflammation and apoptosis pathways: insights into mitochondrial –nuclear interactions M. Cristina Kenney 1,2, ∗ , Marilyn Chwa 1 , Shari R. Atilano 1 , Payam Falatoonzadeh 1 , Claudio Ramirez 1 , Deepika Malik 1 , Mohamed Tarek 1 , Javier Ca´ceres-del-Carpio 1 , Anthony B. Nesburn 1,4 , David S. Boyer 5 , Baruch D. Kuppermann 1 , Marquis Vawter 3 , S. Michal Jazwinski 6 , Michael Miceli 6 , Douglas C. Wallace 7 and Nitin Udar 1 Gavin Herbert Eye Institute, 2 Department of Pathology and Laboratory Medicine, 3 Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA, 4 Cedars-Sinai Medical Center, Los Angeles, CA, USA, 5 Retina-Vitreous Associates Medical Group, Beverly Hills, CA, USA, 6 Tulane Center for Aging, Tulane University, New Orleans, LA, USA and 7 Children’s Hospital of Philadelphia, Center for Mitochondrial and Epigenomic Medicine, Philadelphia, PA, USA Received December 17, 2013; Revised February 3, 2014; Accepted February 10, 2014 Age-related macular degeneration (AMD) is the leading cause of vision loss in developed countries. While linked to genetic polymorphisms in the complement pathway, there are many individuals with high risk alleles that do not develop AMD, suggesting that other ‘modifiers’ may be involved. Mitochondrial (mt) haplogroups, defined by accu- mulations of specific mtDNA single nucleotide polymorphisms (SNPs) which represent population origins, may be one such modifier. J haplogroup has been associated with high risk for AMD while the H haplogroup is protective. It has been difficult to assign biological consequences for haplogroups so we created human ARPE-19 cybrids (cyto- plasmic hybrids), which have identical nuclei but mitochondria of either J or H haplogroups, to investigate their effects upon bioenergetics and molecular pathways. J cybrids have altered bioenergetic profiles compared with H cybrids. Q-PCR analyses show significantly lower expression levels for seven respiratory complex genes encoded by mtDNA. J and H cybrids have significantly altered expression of eight nuclear genes of the alternative complement, inflammation and apoptosis pathways. Sequencing of the entire mtDNA was carried out for all the cybrids to identify haplogroup and non-haplogroup defining SNPs. mtDNA can mediate cellular bioenergetics and expression levels of nuclear genes related to complement, inflammation and apoptosis. Sequencing data sug- gest that observed effects are not due to rare mtDNA variants but rather the combination of SNPs representing the J versus H haplogroups. These findings represent a paradigm shift in our concepts of mt–nuclear interactions. INTRODUCTION Mitochondria (mt) are unique organelles that have their own DNA. Human mtDNA is maternally inherited and forms a circle of double-stranded DNA with 16 569 nucleotide pairs. The non-coding mt-Dloop (also called the control region) con- tains 1121 nucleotides important for replication and transcrip- tion. The coding region of mtDNA encodes for 37 genes, including 13 protein subunits essential for oxidative phosphorylation (OXPHOS), 2 ribosomal RNAs and 22 transfer RNAs (1 – 3). The mtDNA can be categorized into haplogroups that are defined by a group of single nucleotide polymorphism (SNP) variants that have accumulated over tens of thousands of years and correspond to various geographic populations. While some studies have shown that certain mtDNA hap- logroups can be either protective or increase risk for human dis- eases (4–10), others report no haplogroup association with diseases (11– 13). However, many of these studies identified To whom correspondence should be addressed at: Gavin Herbert Eye Institute, Discovery Center for Eye Research, University of California Irvine, Hewitt Hall, Room 2028, 843 Health Science Road, Irvine, CA 92697, USA. Tel: +1 9498247603; Fax: +1 9498249626; Email: mkenney@uci.edu # The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

A polarimetry based method able to characterize optical properties of linear Liquid Crystal Displays (LCDs), even in presence of time-fluctuations of the phase, is proposed in this work. In particular, mean linear retardance, Liquid Crystal (LC) fast axis orientation and phase fluctuation amplitude of LCDs can be obtained with the proposed alternative technique. This technique enables to achieve these important features of LCDs with a set-up significantly less complicated to build up and with faster measurements than previously proposed techniques, which are based on diffraction or interferometry experiments. The validity of the technique is tested by measuring two different LCDs: one monopixel PA-LC panel working in transmission and a reflective PA-LCoS display. The technique provides similar results than those obtained by using previously proposed methods, confirming the validity of our alternative technique.

Mitochondrial DNA Variants Mediate Energy Production and Expression Levels for CFH, C3 and EFEMP1 Genes: Implications for Age-Related Macular Degeneration M. Cristina Kenney 1 *, Marilyn Chwa 1 , Shari R. Atilano 1 , Janelle M. Pavlis 1 , Payam Falatoonzadeh 1 , Claudio Ramirez 1 , Deepika Malik 1 , Tiffany Hsu 1 , Grace Woo 1 , Kyaw Soe 1 , Anthony B. Nesburn 1,2 , David S. Boyer 3 , Baruch D. Kuppermann 1 , S. Michal Jazwinski 4 , Michael V. Miceli 4 , Douglas C. Wallace 5 , Nitin Udar 1 1 Gavin Herbert Eye Institute, University of California Irvine, Irvine, California, United States of America, 2 Cedars-Sinai Medical Center, Los Angeles, California, United States of America, 3 Retina-Vitreous Associates Medical Group, Beverly Hills, California, United States of America, 4 Tulane Center for Aging and Department of Medicine, Tulane University, New Orleans, Louisiana, United States of America, 5 Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America Abstract Background: Mitochondrial dysfunction is associated with the development and progression of age-related macular degeneration (AMD). Recent studies using populations from the United States and Australia have demonstrated that AMD is associated with mitochondrial (mt) DNA haplogroups (as defined by combinations of mtDNA polymorphisms) that represent Northern European Caucasians. The aim of this study was to use the cytoplasmic hybrid (cybrid) model to investigate the molecular and biological functional consequences that occur when comparing the mtDNA H haplogroup (protective for AMD) versus J haplogroup (high risk for AMD). Methodology/Principal Findings: Cybrids were created by introducing mitochondria from individuals with either H or J haplogroups into a human retinal epithelial cell line (ARPE-19) that was devoid of mitochondrial DNA (Rho0). In cybrid lines, all of the cells carry the same nuclear genes but vary in mtDNA content. The J cybrids had significantly lower levels of ATP and reactive oxygen/nitrogen species production, but increased lactate levels and rates of growth. Q-PCR analyses showed J cybrids had decreased expressions for CFH, C3, and EFEMP1 genes, high risk genes for AMD, and higher expression for MYO7A, a gene associated with retinal degeneration in Usher type IB syndrome. The H and J cybrids also have comparatively altered expression of nuclear genes involved in pathways for cell signaling, inflammation, and metabolism. Conclusion/Significance: Our findings demonstrate that mtDNA haplogroup variants mediate not only energy production and cell growth, but also cell signaling for major molecular pathways. These data support the hypothesis that mtDNA variants play important roles in numerous cellular functions and disease processes, including AMD. Citation: Kenney MC, Chwa M, Atilano SR, Pavlis JM, Falatoonzadeh P, et al. (2013) Mitochondrial DNA Variants Mediate Energy Production and Expression Levels for CFH, C3 and EFEMP1 Genes: Implications for Age-Related Macular Degeneration. PLoS ONE 8(1): e54339. doi:10.1371/journal.pone.0054339 Editor: Walter Lukiw, Louisiana State University Health Sciences Center, United States of America Received October 1, 2012; Accepted December 10, 2012; Published January 24, 2013 Copyright: s 2013 Kenney et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Funding provided by The Discovery Eye Foundation www.discoveryeye.org, Lincy Foundation lincyinstitute.unlv.edu/lincy.html, Beckman Macular Research Initiative www.beckmanmacular.org, The Henry Guenther Foundation, Polly and Michael Smith Foundation, Research to Prevent Blindness Foundation www.rpbusa.org, and the National Institute on Aging (AG006168). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: mkenney@uci.edu specific SNP variants that have accumulated over tens of thousands of years and correspond to different geographic populations of the world. The H haplogroup is the most common European haplogroup, while the J haplogroup originates from the Northern European region and is defined by SNP variants that are associated with heat production as an adaptation to colder climates [4]. The mtDNA plays an important role in aging and diseases [4– 6]. Specific haplogroups are associated with a variety of eye diseases including age-related macular degeneration (AMD) [7– 10], diabetic retinopathy [11], pseudoexfoliation glaucoma [12,13], primary open-angle glaucoma [14], keratoconus [15], multiple sclerosis-related optic neuritis [16,17], and Leber Introduction Mitochondria provide critical cellular energy using the tricar- boxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), and beta-oxidation of fatty acids for metabolism, cell division, production of reactive oxygen species (ROS), and apoptosis. Human mitochondrial (mt) DNA forms a circle of double stranded DNA with 16,569 nucleotide pairs. The non-coding mtDNA Dloop contains 1121 nucleotides and is important for replication and transcription. The coding region of mtDNA encodes for 37 genes including 13 protein subunits essential for OXPHOS, 2 ribosomal RNAs, and 22 transfer RNAs [1–3]. The mtDNA can be categorized into haplogroups that are defined by a set of PLOS ONE | www.plosone.org January 2013 | Volume 8 | Issue 1 | e54339

El presente estudio aborda la problematica de la estimacion de precipitaciones areales medias en tres sectores longitudinales de la VII Region de Chile (Cordillera de los Andes, Valle Central y Cordillera de la Costa). Las estimaciones se efectuaron a traves de los siguientes metodos; Media Aritmetica (MA), Poligonos de Thiessen (Th), Isoyetas (Iso), Thiessen Modificado (ThM) e Inverso de la Distancia al Cuadrado (IDC), los que fueron aplicados en dos series extremas de datos pluviales, anos secos y humedos. El analisis y comparacion de los metodos aconseja la aplicacion de cualquiera de ellos para el Valle Central, considerando de antemano la simplicidad de aplicacion que manifiesta la Media Aritmetica (MA). En la Cordillera de la Costa la situacion es similar a la del Valle Central, a excepcion de Thiessen Modificado (ThM). Para el caso de la Cordillera de los Andes, el unico de los metodos estimadores que no se aconseja emplear es el Inverso de la Distancia al Cuadrado (IDC).

In this work a novel point diffraction interferometer based on a variable liquid crystal wave plate (LCWP) has been implemented. The LCWP consists of a 3x3 cm2 monopixel cell with parallel alignment. The monopixel cell was manufactured such that the electrode covers the entire surface except in a centered circular area of 50 μm of diameter. This circle acts as a point perturbation which diffracts the incident wave front giving rise to a spherical reference wave. By applying a voltage to the LCWP we can change the phase of the wave front that passes through the monopixel, except at the center. Phase shifting techniques are used in order to calculate the amplitude and phase distribution of the object wave front. The system allows a digital hologram to be obtained, and by using the Fresnel diffraction integral it is possible to digitally reconstruct the different planes that constitute the three dimensional object. Fil: Ramírez, Claudio. Universidad Autónoma de Barcelona. Departamento de Física; España Fil: Otón, Eva. Universidad Politécnica de Madrid. Escuela Técnica Superior de Ingenieros de Telecomunicación. Centro de Materiales y Dispositivos Avanzados para Tecnologías de Información y Comunicaciones; España Fil: Iemmi, Claudio Cesar. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física. Laboratorio de Procesado de Imágenes; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria; Argentina Fil: Moreno, Ignacio. Universidad Miguel Hernández. Departamento de Ciencia de Materiales, Óptica y Tecnología Electrónica; España Fil: Bennis, Noureddine. Universidad Politécnica de Madrid. Escuela Técnica Superior de Ingenieros de Telecomunicación. Centro de Materiales y Dispositivos Avanzados para Tecnologías de Información y Comunicaciones; España Fil: Otón, José Manuel. Universidad Politécnica de Madrid. Escuela Técnica Superior de Ingenieros de Telecomunicación. Centro de Materiales y Dispositivos Avanzados para Tecnologías de Información y Comunicaciones; España Fil: Campos, Juan. Universidad Autónoma de Barcelona. Departamento de Física; España

PURPOSE To study the inhibitory effects of some agents or drugs (inhibitors) on benzo(e)pyrene (B(e)P)-induced cell death and apoptosis on human retinal pigment epithelial (ARPE-19) cells in vitro. METHODS ARPE-19 cells were pretreated with varying concentrations of different classes of inhibitors (calpain, benzyl isothiocyanate [BITC], simvastatin, epicatechin, genistein, resveratrol, and memantine) before B(e)P exposure. Cell viability (CV) was determined by a trypan blue dye-exclusion assay. Caspase-3/7 and caspase-9 activities were measured by fluorochrome assays. The production of reactive oxygen/nitrogen species (ROS/RNS) was measured with 2',7'-dicholorodihydrofluorescein diacetate dye assay. RESULTS At 30-microM concentrations, the genistein, resveratrol, and memantine inhibitors were able to reverse significantly the loss of cell viability, the activation of caspase-3/7 and caspase-9, and the production of ROS/RNS in ARPE-19 cell cultures. Memantine was the most potent and genistein was the least effective inhibitor in blocking the B(e)P-induced effects. Calpain, BITC, simvastatin, and epicatechin did not reverse the loss of cell viability in B(e)P-treated ARPE-19 cells. As a matter of fact, at the concentrations studied (15, 30, 45 microM), the BITC plus B(e)P-treated cultures showed significantly lower cell viability than the B(e)P-treated culture alone, suggesting BITC-related toxicity. CONCLUSIONS Genistein, resveratrol, and memantine can reverse the apoptosis and oxidant production generated by B(e)P, a toxic element of smoking. These inhibitors may be beneficial against retinal diseases associated with the loss of RPE cells.