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Comparison of Snellen and Early Treatment Diabetic Retinopathy Study charts using a computer simulation

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International Journal of Ophthalmology(English edition) 2016年第1期9卷 119-123页

作者： reuben R.Shamir Yael Friedman Leo Joskowicz Michael Mimouni Eytan Z.Blumenthal School of Engineering and Computer Science the Hebrew University Department of Ophthalmology Hadassah-Hebrew University Medical Center Department of Ophthalmology Rambam Medical Center

AIM：To compare accuracy,reproducibility and test duration for the Snellen and the Early Treatment Diabetic Retinopathy Study（ETDRS）charts,two main tools used to measure visual acuity（VA）.·M ETHODS：A computer simulation was programmed to run multiple virtual patients,each with a unique set of assigned parameters,including VA,false-positive and false-negative error *** each virtual patient,assigned VA was randomly chosen along a continuous scale spanning the range between 1.0 to 0.0 log MAR units（equivalent to 20/200 to 20/20）.Each of 30 000virtual patients were run ten times on each of the two VA charts.·RESULTS：Average test duration（expressed as the total number of characters presented during the test±SD）was12.6±11.1 and 31.2±14.7 characters,for the Snellen and ETDRS,***,defined as the absolute difference（±SD）between the assigned VA and the measured VA,expressed in log MAR units,was superior in the ETDRS charts：0.12±0.14 and 0.08±0.08,for the Snellen and ETDRS charts,***,expressed as test-retest variability,was superior in the ETDRS charts：0.23±0.17 and 0.11±0.09 log MAR units,for the Snellen and ETDRS charts,respectively.·CONCLUSION：A comparison of true（assigned）VA to measured VA,demonstrated,on average,better accuracy and reproducibility of the ETDRS chart,but at the penalty of significantly longer test *** differences were most pronounced in the low VA *** reproducibility using a simulation approach is in line with reproducibility values found in several clinical studies.

关键词： Early Treatment Diabetic RetinopathyStudy Snellen computer simulation visual acuity testing virtual patients

Proinflammatory cytokine TNFα promotes HPV-associated oral carcinogenesis by increasing cancer stemness

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International Journal of Oral Science 2020年第1期12卷 40-49页

作者： Hannah SHong Jonathan Akhavan Sung Hee Lee reuben HKim Mo KKang No-Hee Park Ki-Hyuk Shin The Shapiro Family Laboratory of Viral Oncology and Aging Research UCLA School of DentistryLos AngelesCAUSA UCLA Jonsson Comprehensive Cancer Center Los AngelesCAUSA Department of Medicine David Geffen School of Medicine at UCLALos AngelesCAUSA

High-risk human papillomaviruses(HPVs) are involved in the development of several human cancers, including oropharyngeal squamous cell carcinomas. However, many studies have demonstrated that HPV alone is not sufficient for the oncogenic transformation of normal human epithelial cells, indicating that additional cofactors are required for the oncogenic conversion of HPV-infected cells. Inasmuch as chronic inflammation is also closely associated with carcinogenesis, we investigated the effect of chronic exposure to tumor necrosis factor α(TNFα), the major proinflammatory cytokine, on oncogenesis in two immortalized oral keratinocyte cell lines, namely, HPV16-immortalized and human telomerase reverse transcriptase(h TERT)-immortalized cells. TNFαtreatment led to the acquisition of malignant growth properties in HPV16-immortalized cells, such as(1) calcium resistance,(2)anchorage independence, and(3) increased cell proliferation in vivo. Moreover, TNFα increased the cancer stem cell-like population and stemness phenotype in HPV16-immortalized cells. However, such transforming effects were not observed in h TERTimmortalized cells, suggesting an HPV-specific role in TNFα-promoted oncogenesis. We also generated h TERT-immortalized cells that express HPV16 E6 and E7. Chronic TNFα exposure successfully induced the malignant growth and stemness phenotype in the E6-expressing cells but not in the control and E7-expressing cells. We further demonstrated that HPV16 E6 played a key role in TNFα-induced cancer stemness via suppression of the stemness-inhibiting micro RNAs mi R-203 and mi R-200 c. Overexpression of mi R-203 and mi R-200 c suppressed cancer stemness in TNFα-treated HPV16-immortalized cells. Overall, our study suggests that chronic inflammation promotes cancer stemness in HPV-infected cells, thereby promoting HPV-associated oral carcinogenesis.

关键词： carcinogenesis cytokine cancer

A Simple Traffic Model Including Possibility of Overtaking

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Journal of Electrical Engineering 2018年第3期6卷 156-160页

作者： reuben Thieberger Department of Physics Ben Gurion University Beer Sheva 84105 Israel

Previously we examined different parameters relevant to traffic flow. For illustrative purposes we considered a specific case of approaching a city. The case involves a traffic light where one continues on the main road, into which additional cars are entering at the light. At this intersection an alternative route begins, which is longer but into which no additional cars are entering. In addition to the “Slow to move” model we add here a possibility of “overtaking”, which is quite artificial as our model is one dimensional. Still we think that this gives fair results.

关键词： Cellular automata traffic flux overtaking.

Cellular Automata Model for a Specific Traffic Problem

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Computer Technology and Application 2012年第11期3卷 744-748页

作者： reuben Thieberger Department of Physics Ben Gurion University Beer Sheva 84105 Israel

We examine the possibility of using alternative roads when confronted with traffic congestion. One is the main road; the second alternative is through a secondary road into which additional cars are coming. To keep the total number of vehicles constant, we subtract on the main road the same number of cars as where added to the bypass. We check the Fourier transform of the average on each traffic light cycles of the velocity on the main road and bypass. In the jammed region we obtained different results for the main road and for the bypass. Whereas for the main road we obtained l/f, for the bypass we obtained ＂red noise＂, i.e., 1/f2.

关键词： Elementary cellular automata traffic pink noise.

Periodontitis-induced systemic inflammation exacerbates atherosclerosis partly via endothelial–mesenchymal transition in mice

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International Journal of Oral Science 2019年第3期11卷 201-212页

作者： Jin Sook Suh Sol Kim Kristina I.Bostrom Cun-Yu Wang reuben H.Kim No-Hee Park The Shapiro Family Laboratory of Viral Oncology and Aging Research UCLA School of DentistryLos AngelesCAUSA Department of Medicine David Geffen School of Medicine at UCLALos AngelesCAUSA Division of Oral Biology and Medicine UCLA School of DentistryLos AngelesCAUSA UCLA Jonsson Comprehensive Cancer Center Los AngelesCAUSA Department of Bioengineering UCLA Samueli School of EngineeringLos AngelesCAUSA

Growing evidence suggests close associations between periodontitis and *** further understand the pathological relationships of these associations,we developed periodontitis with ligature placement around maxillary molars or ligature placement in conjunction with Porphyromonas gingivalis lipopolysaccharide injection at the ligature sites (ligature/***) in Apolipoprotein E knock out mice and studied the atherogenesis process in these *** mice were fed with high fat diet for 11 weeks and sacrificed for analyzing periodontitis,systemic inflammation,and *** did not develop periodontitis or systemic inflammation and had minimal lipid deposition in the aortas,but mice receiving ligature or ligature/*** showed severe periodontitis,systemic inflammation,and aortic plaque *** aortic plaque contained abundant macrophages and cells expressing both endothelial and mesenchymal cell *** severity of periodontitis was slightly higher in mice receiving ligature/*** than ligature alone,and the magnitude of systemic inflammation and aortic plaque formation were also notably greater in the mice with ligature/*** observations indicate that the development of atherosclerosis is due to systemic inflammation caused by severe *** vitro,*** enhanced the secretion of pro-inflammatory cytokines from macrophages and increased the adhesion of monocytes to endothelial cells by upregulating the expression of adhesion molecules from endothelial ***,secretory proteins,such as TNF-α,from macrophages induced endothelial–mesenchymal transitions of the endothelial *** together,systemic inflammation induced by severe periodontitis might exacerbate atherosclerosis via,in part,causing aberrant functions of vascular endothelial cells and the activation of macrophages in mice.

关键词： via aortic cells TNF-α did had but was

Long term follow-up of a family with GUCY2D dominant cone dystrophy

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International Journal of Ophthalmology(English edition) 2018年第12期11卷 1945-1950页

作者： Georgios Tsokolas Hussein Almuhtaseb Helen Griffiths Fatima Shawkat reuben J.Pengelly Sarah Ennis Andrew Lotery Clinical and Experimental Sciences University of Southampton Eye Unit University Hospital Southampton Human Genetics & Genomic Medicine Faculty of Medicine University of Southampton

AIM: To describe long term follow-up in a family with GUCY2D dominant cone dystrophy. METHODS: Optical coherence tomography scans and fundus autofluorescence images were obtained. Flash and pattern electroretinograms(ERGs) and occipital pattern reversal visual evoked potentials were recorded. RESULTS: Two members of the same family(father and son) were identified to have the heterozygous R838 C mutation in the GUCY2D gene. The father presented at the age of 45 with bilateral bull’s eye maculopathy and temporal disc pallor. Over 13 y of serial follow up visits, the bull’s eye maculopathy progressed gradually into macular atrophy. Electrophysiological tests were significantly degraded suggesting poor macular function. Spectraldomain optical coherence tomography(SD-OCT) scans showed progressive loss and disruption of the ellipsoid layer at the foveal level. His son presented at the age of 16 with bilateral granular retinal pigment epithelial changes in both maculae. Electrophysiological testing was initially borderline normal but has gradually deteriorated to show reduced cone ERGs and macula function. SD-OCT demonstrated gradual macular thinning and atrophy bilaterally. Unlike his father, there was no disruption of the ellipsoid ***: Both family members exhibited gradual changes in their fundi, electrophysiological testing and multimodal imaging. Changes were milder than those observed in other mutations of the same gene.

关键词： autofluorescence electroretinogram cone dystrophy cone-rod dystrophy GUCY2D spectral-domain optical coherence tomography visual evoked potential

A COVID-19 mathematical model of at-risk populations with non-pharmaceutical preventive measures:The case of Brazil and South Africa

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Infectious Disease Modelling 2022年第1期7卷 45-61页

作者： reuben Asempapa Bismark Oduro Ofosuhene O.Apenteng Vusi M.Magagula School of Behavioral Sciences and Education Penn State UniversityMiddletownPA17057USA Department of Mathematics and Physical Sciences California University of PennsylvaniaCaliforniaPA15419USA Research Group for Genomic Epidemiology National Food InstituteTechnical University of DenmarkKemitorvet2800Kgs.LyngbyDenmark Faculty of Science and Engineering Department of MathematicsUniversity of EswatiniPrivate Bag 4 KwaluseniMatsaphaEswatini

This work examines a mathematical model of COVID-19 among two subgroups:low-risk and high-risk populations with two preventive measures;non-pharmaceutical interventions including wearing masks,maintaining social distance,and washing hands regularly by the low-risk *** addition to the interventions mentioned above,highrisk individuals must take extra precaution measures,including telework,avoiding social gathering or public places,*** reduce the *** with underlying chronic diseases and the elderly(ages 60 and above)were classified as high-risk individuals and the rest as low-risk *** parameter values used in this study were estimated using the available data from the Johns Hopkins University on COVID-19 for Brazil and South *** evaluated the effective reproduction number for the two countries and observed how the various parameters affected the effective reproduction *** also performed numerical simulations and analysis of the *** and infectious populations for both low-risk and high-risk individuals were studied in *** were displayed in both graphical and table forms to show the dynamics of each country being *** observed that non-pharmaceutical interventions by highrisk individuals significantly reduce infections among only high-risk *** contrast,non-pharmaceutical interventions by low-risk individuals have a significant reduction in infections in both ***,low-risk individuals’preventive actions have a considerable effect on reducing infections,even among high-risk individuals.

关键词： COVID-19 disease Low-risk population High-population Effective reproduction number Preventive measures

Combining targeted therapy and immune checkpoint inhibitors in the treatment of metastatic melanoma

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Cancer Biology & Medicine 2014年第4期11卷 237-246页

作者： Teresa Kim Rodabe N.Amaria Christine Spencer Alexandre reuben Zachary A.Cooper Jennifer A.Wargo Department of Surgery Massachusetts General Hospital Harvard Medical School Department of Melanoma Medical Oncology University of Texas M.D.Anderson Cancer Center Department of Genomic Medicine University of Texas M.D.Anderson Cancer Center Department of Surgical Oncology University of Texas M.D.Anderson Cancer Center

Melanoma is the deadliest form of skin cancer and has an incidence that is rising faster than any other solid tumor. Metastatic melanoma treatment has considerably progressed in the past five years with the introduction of targeted therapy(BRAF and MEK inhibitors) and immune checkpoint blockade(anti-CTLA4, anti-PD-1, and anti-PD-L1). However, each treatment modality has limitations. Treatment with targeted therapy has been associated with a high response rate, but with short-term responses. Conversely, treatment with immune checkpoint blockade has a lower response rate, but with longterm responses. Targeted therapy affects antitumor immunity, and synergy may exist when targeted therapy is combined with immunotherapy. This article presents a brief review of the rationale and evidence for the potential synergy between targeted therapy and immune checkpoint blockade. Challenges and directions for future studies are also proposed.

关键词： Melanoma checkpoint blockade BRAF inhibition immunotherapy

Predicting the distribution of the Asian tapir in Peninsular Malaysia using maximum entropy modeling

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Integrative Zoology 2012年第4期7卷 400-406页

作者： Gopalasamy reuben CLEMENTS D.Mark RAYAN Sheema Abdul AZIZ Kae KAWANISHI Carl TRAEHOLT David MAGINTAN Muhammad Fadlli Abdul YAZI Reid TINGLEY Center for Tropical Environmental and Sustainability Science and School of Marine and Tropical Biology James Cook UniversityCairnsAustralia Center for Malaysian Indigenous Studies University of MalayaKuala LumpurMalaysia WWF Malaysia Petaling JayaMalaysia Durrell Institute of Conservation and Ecology University of KentCanterburyUK Malaysian Conservation Alliance for Tigers(MYCAT)Secretariat's Office Petaling JayaMalaysia Copenhagen Zoo CopenhagenDenmark Department of Wldife and National Parks Peninsular Malaysia Kuala LumpurMalaysia School of Biological Sciences University of SydneySydneyAustralia

In 2008,the IUCN threat status of the Asian tapir(Tapirus indicus)was reclasified from‘vulnerable'to‘en-dangered'.The latest distribution map from the IUCN Red List suggests that the tapirs'native range is becom-ing increasingly fragmented in Peninsular Malaysia,but distribution data collected by local researchers sug-gest a more extensive geographical ***,we compile a database of 1261 tapir occurrence records within Peninsular Malaysia,and demonstrate that this species,indeed,has a much broader geographical range than the IUCN range map ***,extreme spatial and temporal bias in these records limits their utility for conservation ***,we used maximum entropy(MaxEnt)modeling to elucidate the potential ex-tent of the Asian tapir's occurrence in Peninsular Malaysia while accounting for bias in existing distribution *** MaxEnt model predicted that the Asian tapir has a wider geographic range than our fine-scale data and the IUCN range map both *** 37%of Peninsular Malaysia contains potentially suit-able tapir *** results justify a revision to the Asian tapir's extent of occurrence in the IUCN Red ***,our modeling demonstrated that selectively logged forests encompass 45%of potentially suitable tapir habitats,underscoring the importance of these habitats for the conservation of this species in Peninsular Malaysia.

关键词： ecological niche IUCN Malayan tapir mammal MaxEnt species distribution model