Axisymmetric MHD-stable Mirror as a Neutron Source and a Fusion Reactor

ScienceCinema

Dr. Dmitri Ryutov

2018-04-17

Dr. Ryutov discusses the concept of axisymmetric mirrors and presents an overview of current experiments and theories. Particular attention is paid to MHD stabilization and the advantages and disadvantages of using mirrors. Future work is identified and further discussed.

An Approach for Assessing Development and Deployment Risks in the DOE Fuel Cycle Options Evaluation and Screening Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gehin, Jess C; Oakley, Brian; Worrall, Andrew

2015-01-01

Abstract One of the key objectives of the U.S. Department of Energy (DOE) Nuclear Energy R&D Roadmap is the development of sustainable nuclear fuel cycles that can improve natural resource utilization and provide solutions to the management of nuclear wastes. Recently, an evaluation and screening (E&S) of fuel cycle systems has been conducted to identify those options that provide the best opportunities for obtaining such improvements and also to identify the required research and development activities that can support the development of advanced fuel cycle options. In order to evaluate and screen the E&S study included nine criteria including Developmentmore » and Deployment Risk (D&DR). More specifically, this criterion was represented by the following metrics: Development time, development cost, deployment cost from prototypic validation to first-of-a-kind commercial, compatibility with the existing infrastructure, existence of regulations for the fuel cycle and familiarity with licensing, and existence of market incentives and/or barriers to commercial implementation of fuel cycle processes. Given the comprehensive nature of the study, a systematic approach was needed to determine metric data for the D&DR criterion, and is presented here. As would be expected, the Evaluation Group representing the once-through use of uranium in thermal reactors is always the highest ranked fuel cycle Evaluation Group for this D&DR criterion. Evaluation Groups that consist of once-through fuel cycles that use existing reactor types are consistently ranked very high. The highest ranked limited and continuous recycle fuel cycle Evaluation Groups are those that recycle Pu in thermal reactors. The lowest ranked fuel cycles are predominately continuous recycle single stage and multi-stage fuel cycles that involve TRU and/or U-233 recycle.« less

Fabrication and investigation of MnFe2O4/MWCNTs nanocomposite by hydrothermal technique and adsorption of cationic and anionic dyes

NASA Astrophysics Data System (ADS)

Kafshgari, Leila Asadi; Ghorbani, Mohsen; Azizi, Asghar

2017-10-01

In present study, MnFe2O4/MWCNT nanocomposite synthesized using the hydrothermal technique and has been used for removal of DR16 and Y40 dyes from aqueous solutions. The characteristics results of FTIR, XRD, FESEM and TEM indicated that the nanoadsorbent was successfully fabricated. Magnetic sensitivity results demonstrated that the nanoparticles with saturation magnetization (Ms) value of 8.93 emu g-1 would have a fast magnetic response. The performance of adsorption was investigated in a batch reactor employing parameters expected to affect the maximum adsorption capacity (qm) such as pH, contact time, initial dye concentration and temperature. The highest sorption capacities of DR16 and Y40 after 300 min at 328 K were found to be 607.79 mg/g and 280 mg/g at pH of 2 and 6, respectively. The adsorption behavior over the time was assessed through pseudo-first, pseudo-second and Weber-Morris intra particle diffusion models. It was found that the pseudo-second order model gave the best agreement to the experimental data. Adsorbate-adsorbent interactions as a function of temperature was evaluated by Langmuir, Freundlich, Temkin and Sips isotherm models from which Sips isotherm had the highest consistency with the experimental data. Thermodynamic parameters including ΔG°, ΔS° and ΔH° were determined over the temperature range of 298-328 K. The results revealed that the adsorption reaction of DR16 onto MnFe2O4/MWCNT was spontaneous and exothermic, whilst the sorption process of Y40 was spontaneous and endothermic. In addition, activation energy values implied that the removal process of DR16 and Y40 was physical in nature.

A Community College President--What's That? Forum 45.

ERIC Educational Resources Information Center

Cosand, Joseph P.; And Others

This document compiles the Forum 45 major address and the responses of three reactors. Dr. Cosand's paper seeks to define what constitutes a top quality community college president. There are many styles of presidential leadership; however, the possibility of a president's providing strong and enlightened leadership depends on his effectiveness in…

Research and Development of Multiphysics Models in Support of the Conversion of the High Flux Isotope Reactor to Low Enriched Uranium Fuel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bodey, Isaac T.; Curtis, Franklin G.; Arimilli, Rao V.

The findings presented in this report are results of a five year effort led by the RRD Division of the ORNL, which is focused on research and development toward the conversion of the High Flux Isotope Reactor (HFIR) fuel from high-enriched uranium (HEU) to low-enriched uranium (LEU). This report focuses on the tasks accomplished by the University of Tennessee Knoxville (UTK) team from the Department of Mechanical, Aerospace, and Biomedical Engineering (MABE) that provided expert support in multiphysics modeling of complex problems associated with the LEU conversion of the HFIR reactor. The COMSOL software was used as the main computationalmore » modeling tool, whereas Solidworks was also used in support of computer-aided-design (CAD) modeling of the proposed LEU fuel design. The UTK research has been governed by a statement of work (SOW), which was updated annually to clearly define the specific tasks reported herein. Ph.D. student Isaac T. Bodey has focused on heat transfer and fluid flow modeling issues and has been aided by his major professor Dr. Rao V. Arimilli. Ph.D. student Franklin G. Curtis has been focusing on modeling the fluid-structure interaction (FSI) phenomena caused by the mechanical forces acting on the fuel plates, which in turn affect the fluid flow in between the fuel plates, and ultimately the heat transfer, is also affected by the FSI changes. Franklin Curtis has been aided by his major professor Dr. Kivanc Ekici. M.Sc. student Adam R. Travis has focused two major areas of research: (1) on accurate CAD modeling of the proposed LEU plate design, and (2) reduction of the model complexity and dimensionality through interdimensional coupling of the fluid flow and heat transfer for the HFIR plate geometry. Adam Travis is also aided by his major professor, Dr. Kivanc Ekici. We must note that the UTK team, and particularly the graduate students, have been in very close collaboration with Dr. James D. Freels (ORNL technical monitor and mentor) and have benefited greatly from his leadership and expertise in COMSOL modeling of complex physical phenomena. Both UTK and ORNL teams have used COMSOL releases 3.4 through 5.0 inclusive (with particular emphasis on 3.5a, 4.3a, 4.3b, and 4.4) for most of the work described in this report, except where stated otherwise. Just as in the performance of the research, each of the respective sections has been originally authored by respective authors. Therefore, the reader will observe a contrast in writing style throughout this document.« less

75 FR 47646 - Idaho State University; Notice of Issuance of Director's Decision

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-06

... detector from the reactor core. In the petition Dr. Crawford states that this was cited as an Apparent... detector. The personnel roof access hatch was also addressed in Rev. 3 and Rev. 4 of the Physical Security... procedures to wear protective clothing to routinely remove the activated startup channel detector from the...

Leak-Before-Break: Further developments in regulatory policies and supporting research

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilkowski, G.M.; Chao, K.-S.

1990-02-01

The fourth in a series of international Leak-Before-Break (LBB) Seminars supported in part by the US Nuclear Regulatory Commission was held at the National Central Library in Taipei, Taiwan on May 11 and 12, 1989. The seminar updated the international polices and supporting research on LBB. Attendees included representatives from regulatory agencies, electric utilities, nuclear power plant fabricators, research organizations, and academic institutions. Regulatory policy was the subject of presentations by Mr. G. Arlotto (US NRC, USA) Dr. B. Jarman (AECB, Canada), Dr.P. Milella (ENEA-DISP, Italy), Dr. C. Faidy (EDF/Septen, France ), and Dr. K. Takumi (NUPEC, Japan). A papermore » by Mr. K. Wichman and Mr. A. Lee of the US NRC Office of Nuclear Reactor Regulation is included as background material to these proceedings; it discusses the history and status of LBB applications in US nuclear power plants. In addition, several papers on the supporting research programs described regulatory policy or industry standards for flaw evaluations, e.g., the ASME Section XI code procedures. Supporting research programs were reviewed on the first and second day by several participants from Taiwan, US, Japan, Canada, Italy, and France. Each individual paper has been cataloged separately.« less

Nuclear Reactor Physics

NASA Astrophysics Data System (ADS)

Stacey, Weston M.

2001-02-01

An authoritative textbook and up-to-date professional's guide to basic and advanced principles and practices Nuclear reactors now account for a significant portion of the electrical power generated worldwide. At the same time, the past few decades have seen an ever-increasing number of industrial, medical, military, and research applications for nuclear reactors. Nuclear reactor physics is the core discipline of nuclear engineering, and as the first comprehensive textbook and reference on basic and advanced nuclear reactor physics to appear in a quarter century, this book fills a large gap in the professional literature. Nuclear Reactor Physics is a textbook for students new to the subject, for others who need a basic understanding of how nuclear reactors work, as well as for those who are, or wish to become, specialists in nuclear reactor physics and reactor physics computations. It is also a valuable resource for engineers responsible for the operation of nuclear reactors. Dr. Weston Stacey begins with clear presentations of the basic physical principles, nuclear data, and computational methodology needed to understand both the static and dynamic behaviors of nuclear reactors. This is followed by in-depth discussions of advanced concepts, including extensive treatment of neutron transport computational methods. As an aid to comprehension and quick mastery of computational skills, he provides numerous examples illustrating step-by-step procedures for performing the calculations described and chapter-end problems. Nuclear Reactor Physics is a useful textbook and working reference. It is an excellent self-teaching guide for research scientists, engineers, and technicians involved in industrial, research, and military applications of nuclear reactors, as well as government regulators who wish to increase their understanding of nuclear reactors.

Recent results on the neutron irradiation of ITER candidate copper alloys irradiated in DR-3 at 250{degrees}C to 0.3 dpa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Edwards, D.J.; Singh, B.N.; Toft, P.

1997-04-01

Tensile specimens of CuCrZr and CuNiBe alloys were given various heat treatments corresponding to solution anneal, prime-ageing and bonding thermal treatment with additional specimens re-aged and given a reactor bakeout treatment at 350{degrees}C for 100 h. CuAl-25 was also heat treated to simulate the effects of a bonding thermal cycle on the material. A number of heat treated specimens were neutron irradiated at 250{degrees}C to a dose level of {approximately}0.3 dpa in the DR-3 reactor as Riso. The main effect of the bonding thermal cycle heat treatment was a slight decrease in strength of CuCrZr and CuNiBe alloys. The strengthmore » of CuAl-25, on the other hand, remained almost unaltered. The post irradiation tests at 250{degrees}C showed a severe loss of ductility in the case of the CuNiBe alloy. The irradiated CuAl-25 and CuCrZr specimens exhibited a reasonable amount of uniform elongation, with CuCrZr possessing a lower strength.« less

Displacement damage effects on CMOS APS image sensors induced by neutron irradiation from a nuclear reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Zujun, E-mail: wangzujun@nint.ac.cn; Huang, Shaoyan; Liu, Minbo

The experiments of displacement damage effects on CMOS APS image sensors induced by neutron irradiation from a nuclear reactor are presented. The CMOS APS image sensors are manufactured in the standard 0.35 μm CMOS technology. The flux of neutron beams was about 1.33 × 10{sup 8} n/cm{sup 2}s. The three samples were exposed by 1 MeV neutron equivalent-fluence of 1 × 10{sup 11}, 5 × 10{sup 11}, and 1 × 10{sup 12} n/cm{sup 2}, respectively. The mean dark signal (K{sub D}), dark signal spike, dark signal non-uniformity (DSNU), noise (V{sub N}), saturation output signal voltage (V{sub S}), and dynamic rangemore » (DR) versus neutron fluence are investigated. The degradation mechanisms of CMOS APS image sensors are analyzed. The mean dark signal increase due to neutron displacement damage appears to be proportional to displacement damage dose. The dark images from CMOS APS image sensors irradiated by neutrons are presented to investigate the generation of dark signal spike.« less

Biodegradation of tetrabromobisphenol A in the sewage sludge process.

PubMed

Peng, Xingxing; Wang, Zhangna; Wei, Dongyang; Huang, Qiyuan; Jia, Xiaoshan

2017-11-01

Anaerobic sewage sludge capable of rapidly degrading tetrabromobisphenol A (TBBPA) was successfully acclimated in an anaerobic reactor over 280days. During the period from 0 to 280days, the TBBPA degradation rate (DR), utilization of glucose, and VSS were monitored continuously. After 280days of acclimation, the TBBPA DR of active sludge reached 96.0% after 20days of treatment in batch experiments. Based on scanning electron microscopy (SEM) observations and denaturing gradient gel electrophoresis (DGGE) determinations, the diversity of the microorganisms after 0 and 280days in the acclimated anaerobic sewage sludge was compared. Furthermore, eleven metabolites, including 2-bromophenol, 3-bromophenol, 2,4-dibromophenol, 2,6-dibromophenol, tribromophenol and bisphenol A, were identified by gas chromatography-mass spectrometry (GC-MS). Moreover, the six primary intermediary metabolites were also well-degraded by the acclimated anaerobic sewage sludge to varying degrees. Among the six target metabolites, tribromophenol was the most preferred substrate for biodegradation via debromination. These metabolites degraded more rapidly than monobromide and bisphenol A. The biodegradation data of the intermediary metabolites exhibited a good fit to a pseudo-first-order model. Finally, based on the metabolites, metabolic pathways were proposed. In conclusion, the acclimated microbial consortia degraded TBBPA and its metabolites well under anaerobic conditions. Copyright © 2017. Published by Elsevier B.V.

Expression Analysis of Dopamine Receptor Subtypes in Normal Human Pituitaries, Nonfunctioning Pituitary Adenomas and Somatotropinomas, and the Association between Dopamine and Somatostatin Receptors with Clinical Response to Octreotide-LAR in Acromegaly

PubMed Central

Neto, Leonardo Vieira; Machado, Evelyn de O.; Luque, Raul M.; Taboada, Giselle F.; Marcondes, Jorge B.; Chimelli, Leila M. C.; Quintella, Leonardo Pereira; Niemeyer, Paulo; de Carvalho, Denise P.; Kineman, Rhonda D.; Gadelha, Mônica R.

2009-01-01

Context: Dopamine receptor (DR) and somatostatin receptor subtype expression in pituitary adenomas may predict the response to postsurgical therapies. Objectives: Our objectives were to assess and compare the mRNA levels of DR1-5 and somatostatin receptors 1–5 in normal pituitaries (NPs), nonfunctioning pituitary adenomas (NFPAs), and somatotropinomas. In addition, we determined whether the level of DR expression correlates with the in vivo response to octreotide-LAR in acromegalic patients. Design and Patients: Eight NPs, 30 NFPAs, and 39 somatotropinomas were analyzed for receptor mRNA levels by real-time RT-PCR. The DR2 short variant was estimated as the DR2 long/DR2 total (DR2T). The relationship between DR expression and the postsurgical response to octreotide-LAR was assessed in 19 of the acromegalic patients. Results: DR3 was not detected. The relationship between expression levels of DR subtypes in NPs and somatotropinomas was DR2T⋙DR4≫DR5>DR1, whereas in NFPAs, DR2T⋙DR4≫DR1>DR5. The DR2 short variant was the predominant DR2 variant in the majority of samples. In acromegalics treated with octreotide-LAR, DR1 was negatively correlated with percent GH reduction (3 months: r = −0.67, P = 0.002; and 6 months: r = −0.58, P = 0.009), and DR5 was positively correlated with percent IGF-I reduction (3 months: r = 0.55, P = 0.01; and 6 months: r = 0.47, P = 0.04). Conclusions: DR2 is the predominant DR subtype in NPs, NFPAs, and somatotropinomas. The fact that DR1, DR4, and DR5 are also expressed in many adenomas tested suggests that these receptors might also play a role in the therapeutic impact of postsurgical medical therapies in patients with NFPA and acromegaly. This was supported by the finding that the in vivo response to octreotide-LAR was negatively associated with DR1 and positively associated with DR5. PMID:19293270

Emerging Technologies Program Integration Report. Volume 1. Narrative, Analyses and Assessment

DTIC Science & Technology

1987-05-04

James S. (T) 31. GREGG, Dr. Michael C. (T) 61. REDDY, Dr. Raj (T) 2. ATLAS, Dr. David (T) 32. HADDAD, Dr. Genevieve M. 62. REDIKER, Dr. Robert H. 3...Dr. Martin C. 83. WEEKS, Dr. Wilford 6 24. FAETH, Dr. Gerald 54. MUNSON, Mr. John 84. WEINTRAUB, Dr. Daniel 1. (T) 25. FETTERMAN , Dr. Harold 55...T) 2. ATLAS, Dr. David (T) 32. HADDAD, Dr. Genevieve M. 62. REDIKER, Dr. Robert H. 3. BALDESCHWIELER, Dr. John (T) 33. HAMMOND, Dr. George S. 63

Relative Ball 3X-VSR reactivity strength DR reactor. Interim Report of PT IP-126-C

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simpson, D.E.

1959-06-01

Prior to this experiment, no measurements of Ball 3X effectiveness had been performed for any of the older 2004-tube Hanford piles, and calculations concerning total control requirements were made assuming the vertical safety system strength equal to the strength of the B, D, F vertical safety rods. With current and projected enrichment loadings, the vertical control system was calculated to be inadequate to satisfy the total control criteria at all times, resulting in the necessity to provide supplementary control in the form of horizontal rods or temporary process tube poison. Because of the larger ball channels at DR, the Ballmore » 3X system is stronger than at the other 29-VSR piles. Therefore, the potential relaxation of total control limits was greater for DR should an experiment show the Ball 3X strength to be significantly greater than the B, D, F VSR strength. PT-IP-126-C authorized an experiment to determine the Ball 3X effectiveness at DR Pile by measurement of the relative strength of a VSR and a column of 3X balls in the same channel. The experiment was performed in March, 1958, and on the strength of favorable results a supplement to the PT was prepared to authorize the same test at one of the other 29-VSR piles. This supplement has not been approved; therefore, the results of the DR test are being reported separately in this document.« less

Committee for International Conference on Mechanical Engineering Research (ICMER 2011)

NASA Astrophysics Data System (ADS)

Yusoff, Ahmad Razlan Bin

2012-09-01

Scientific Advisory Committee: 1) Prof. Dr. Ahmad Kamal Ariffin (UKM) 2) Prof. Dr. Hj. Rosli Abu Bakar (UMP) 3) Prof. Dr. Hanafi Ismail (USM) 4) Prof. Ir. Dr. Mohd Jailani Mohd Nor (MoHE) 5) Prof. Dr. Zahari Taha (UMP) 6) Prof. Dr. Masjuki Haji Hassan 7) Prof. Ir. Dr. Ramesh Singh (UNITEN) 8) Prof. Dr. Razali Ayob (UTEM) 9) Prof. Dr. Wan Khairuddin (UTM) 10) Prof. Dr. Sulaiman Hj. Hasan (UTHM) 11) Prof. Dr. Zuraidah Mohd. Zain (UniMAP) 12) Prof. Dr. Horizon Gitano (USM) 13) Prof. Dr. K.V Sharma (UMP) 14) Prof. Dr. Shahrani Anuar (UMP) 15) Assoc. Prof. Dr. Abd Rashid Abd. Aziz (UTP) 16) Assoc. Prof. Dr. Aidy Ali (UPM) 17) Assoc. Prof. Dr. Saidur Rahman (UM) 18) Assoc. Prof. Dr. Md Abdul Maleque (UIA) Organizing Committee Chairman: Prof. Dr. Hj. Rosli Abu Bakar Co-Chair: Prof. Dr. Zahari Taha Co-Chair: Prof. Ir. Dr. Jailani Salihon Secretary: Dr. Rizalman Mamat Committee on Keynote Speaker 1) Kumaran Kadirgama (Chair) 2) Prof. Dr. K.V. Sharma 3) Haji Amirruddin Abdul Kadir 4) Miminorazeansuhaila Loman 5) Mohd Akramin Mohd Romlay Technical Committee (Peer Review & Proceedings) 1) Dr. Abdul Adam Abdullah (Chair) 2) Dr. Ahmad Razlan Yusoff 3) Mohd Yusof Taib 4) Dr. Md. Mustafizur Rahman 5) Dr. Hjh. Yusnita Rahayu 6) Dr. Gigih Priyandoko 7) Dr. Agung Sudrajad 8) Muhammad Hatifi Mansor 9) Mohd Fadzil Abdul Rahim Technical Committee (Panels & Session Chairs) 1) Dr. Mahadzir Ishak (Chair) 2) Prof. Dr. Shahrani Anuar 3) Dr. Maisara Mohyeldin Gasim Mohamed 4) Muhammad Ammar Nik Mu'tasim 5) Ahmad Basirul Subha bin Alias Technical Committee (Journal Publication) 1) Dr. Ahmad Razlan bin Yusoff (Chair) 2) Mohd Yusof Taib 3) Dr. Mahadzir Ishak 4) Dr. Abdul Adam Abdullah 5) Hj. Amirruddin Abdul Kadir 6) Hadi Abdul Salaam Bureau of Publicity & Website 1) Dr. Muhamad Arifpin Mansor (Chair) 2) Amir Abdul Razak 3) Idris Mat Sahat 4) Prof. Dr. Hj. Rosli Abu Bakar 5) Muhamad Zuhairi Sulaiman 6) Dr. Sugeng Ariyono 7) Asnul Hadi Ahmad 8) Mohd Tarmizy Che Kar 9) Mohd Padzly Radzi Bureau of Special Task & Poster 1) Lee Giok Chui (Chair) 2) Mohd Fadzil Abdul Rahim 3) Che Ku Eddy Nizwan 4) Hazami Che Hussain 5) Mohd Fazli Ismail 6) Mahdhir Mohd Yusof 7) Mohd Padzly Radzi 8) Rahimah Che Ramli Secretariats 1) Ir. Ahmad Rasdan Ismail (Chair) 2) Mohd Shahri Mohd Akhir 3) Luqman Hakim Ahmad Shah 4) Juliawati Alias 5) Nurazima Ismail 6) Mohamad Faizal Mohamed Zahri 7) Raja Allen Jordan Izzuddin Shah 8) Rosidah Mohd Norsat 9) Norshalawati Mat Yusof 10) Zainab Daud 11) Nur Sufiah Jamaludin 12) Azslinda Ibrahim 13) Nurul Azreen Zainal Abidin 14) Nurul Ashikin Mohd Khalil 15) Mohd Zaki Mohd Ali

Inward rectifier potassium current (I K1) and Kir2 composition of the zebrafish (Danio rerio) heart.

PubMed

Hassinen, Minna; Haverinen, Jaakko; Hardy, Matt E; Shiels, Holly A; Vornanen, Matti

2015-12-01

Electrophysiological properties and molecular background of the zebrafish (Danio rerio) cardiac inward rectifier current (IK1) were examined. Ventricular myocytes of zebrafish have a robust (-6.7 ± 1.2 pA pF(-1) at -120 mV) strongly rectifying and Ba(2+)-sensitive (IC50 = 3.8 μM) IK1. Transcripts of six Kir2 channels (drKir2.1a, drKir2.1b, drKir2.2a, drKir2.2b, drKir2.3, and drKir2.4) were expressed in the zebrafish heart. drKir2.4 and drKir2.2a were the dominant isoforms in both the ventricle (92.9 ± 1.5 and 6.3 ± 1.5%) and the atrium (28.9 ± 2.9 and 64.7 ± 3.0%). The remaining four channels comprised together less than 1 and 7 % of the total transcripts in ventricle and atrium, respectively. The four main gene products (drKir2.1a, drKir2.2a, drKir2.2b, drKir2.4) were cloned, sequenced, and expressed in HEK cells for electrophysiological characterization. drKir2.1a was the most weakly rectifying (passed more outward current) and drKir2.2b the most strongly rectifying (passed less outward current) channel, whilst drKir2.2a and drKir2.4 were intermediate between the two. In regard to sensitivity to Ba(2+) block, drKir2.4 was the most sensitive (IC50 = 1.8 μM) and drKir2.1a the least sensitive channel (IC50 = 132 μM). These findings indicate that the Kir2 isoform composition of the zebrafish heart markedly differs from that of mammalian hearts. Furthermore orthologous Kir2 channels (Kir2.1 and Kir2.4) of zebrafish and mammals show striking differences in Ba(2+)-sensitivity. Structural and functional differences needs to be taken into account when zebrafish is used as a model for human cardiac electrophysiology, cardiac diseases, and in screening cardioactive substances.

Mutual Regulation of NOD2 and RIG-I in Zebrafish Provides Insights into the Coordination between Innate Antibacterial and Antiviral Signaling Pathways.

PubMed

Nie, Li; Xu, Xiao-Xiao; Xiang, Li-Xin; Shao, Jian-Zhong; Chen, Jiong

2017-05-27

Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and retinoic acid-inducible gene I (RIG-I) are two important cytosolic pattern recognition receptors (PRRs) in the recognition of pathogen-associated molecular patterns (PAMPs), initiating innate antibacterial and antiviral signaling pathways. However, the relationship between these PRRs, especially in teleost fish models, is rarely reported. In this article, we describe the mutual regulation of zebrafish NOD2 ( Dr NOD2) and RIG-I ( Dr RIG-I) in innate immune responses. Luciferase assays were conducted to determine the activation of NF-κB and interferon signaling. Morpholino-mediated knockdown and mRNA-mediated rescue were performed to further confirm the regulatory roles between Dr NOD2 and Dr RIG-I. Results showed that Dr NOD2 and Dr RIG-I shared conserved structural hallmarks with their mammalian counterparts, and activated Dr RIG-I signaling can induce Dr NOD2 production. Surprisingly, Dr NOD2-initiated signaling can also induce Dr RIG-I expression, indicating that a mutual regulatory mechanism may exist between them. Studies conducted using HEK293T cells and zebrafish embryos showed that Dr RIG-I could negatively regulate Dr NOD2-activated NF-κB signaling, and Dr NOD2 could inhibit Dr RIG-I-induced IFN signaling. Moreover, knocking down Dr RIG-I expression by morpholino could enhance Dr NOD2-initiated NF-κB activation, and vice versa, which could be rescued by their corresponding mRNAs. Results revealed a mutual feedback regulatory mechanism underlying NOD2 and RIG-I signaling pathways in teleosts. This mechanism reflects the coordination between cytosolic antibacterial and antiviral PRRs in the complex network of innate immunity.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Craig, D.F.

The division was formed in 1946 at the suggestion of Dr. Eugene P. Wigner to attack the problem of the distortion of graphite in the early reactors due to exposure to reactor neutrons, and the consequent radiation damage. It was called the Metallurgy Division and assembled the metallurgical and solid state physics activities of the time which were not directly related to nuclear weapons production. William A. Johnson, a Westinghouse employee, was named Division Director in 1946. In 1949 he was replaced by John H Frye Jr. when the Division consisted of 45 people. He was director during most ofmore » what is called the Reactor Project Years until 1973 and his retirement. During this period the Division evolved into three organizational areas: basic research, applied research in nuclear reactor materials, and reactor programs directly related to a specific reactor(s) being designed or built. The Division (Metals and Ceramics) consisted of 204 staff members in 1973 when James R. Weir, Jr., became Director. This was the period of the oil embargo, the formation of the Energy Research and Development Administration (ERDA) by combining the Atomic Energy Commission (AEC) with the Office of Coal Research, and subsequent formation of the Department of Energy (DOE). The diversification process continued when James O. Stiegler became Director in 1984, partially as a result of the pressure of legislation encouraging the national laboratories to work with U.S. industries on their problems. During that time the Division staff grew from 265 to 330. Douglas F. Craig became Director in 1992.« less

S8DR shield examination

NASA Technical Reports Server (NTRS)

Mason, D. G.; Mccurnin, W. R.

1973-01-01

The SNAP 8 developmental reactor lithium hydride shield was examined after being irradiated for over 7000 hours at relatively low temperature. A crack was located in the seam weld of the containment vessel, probably the result of hot short cracking under thermal stress. The LiH was visually examined at two locations and its appearance was typical of low temperature irradiated LiH. The adherence of the chrome oxide emittance coating was found to be excellent.

Biological Investigation of the Stimulated Flapping Motions of the Moth, Manduca sexta

DTIC Science & Technology

2011-03-01

the sites of toxic chemical spills or damaged nuclear reactors (Alexander, 2002). Dr. Mark Reeder, Editor-in-Chief of the International Journal...Process The overall objective of research, using bio -inspired technology and techniques, is to develop clear scientific understanding about some of...it in a small container and submerging it in a bucket of ice for approximately 15 minutes, until the moth was unresponsive to stimulation.  Under

Laser Assisted CVD Growth of A1N and GaN

DTIC Science & Technology

1990-08-31

additional cost sharing. RESEARCH FACILITIES The york is being performed in the Howard University Laser Laboratory. This is a free-standing buildinq...would be used to optimize computer models of the laser induced CVD reactor. FACILITIES AND EQUIPMENT - ADDITIONAL COST SHARING This year Howard ... University has provided $45,000 for the purchase of an excimer laser to be shared by Dr. Crye for the diode laser probe experiments and another Assistant

Draft environmental impact statement siting, construction, and operation of New Production Reactor capacity. Volume 4, Appendices D-R

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

1991-04-01

This Environmental Impact Statement (EIS) assesses the potential environmental impacts, both on a broad programmatic level and on a project-specific level, concerning a proposed action to provide new tritium production capacity to meet the nation`s nuclear defense requirements well into the 21st century. A capacity equivalent to that of about a 3,000-megawatt (thermal) heavy-water reactor was assumed as a reference basis for analysis in this EIS; this is the approximate capacity of the existing production reactors at DOE`s Savannah River Site near Aiken, South Carolina. The EIS programmatic alternatives address Departmental decisions to be made on whether to build newmore » production facilities, whether to build one or more complexes, what size production capacity to provide, and when to provide this capacity. Project-specific impacts for siting, constructing, and operating new production reactor capacity are assessed for three alternative sites: the Hanford Site near Richland, Washington; the Idaho National Engineering Laboratory near Idaho Falls, Idaho; and the Savannah River Site. For each site, the impacts of three reactor technologies (and supporting facilities) are assessed: a heavy-water reactor, a light-water reactor, and a modular high-temperature gas-cooled reactor. Impacts of the no-action alternative also are assessed. The EIS evaluates impacts related to air quality; noise levels; surface water, groundwater, and wetlands; land use; recreation; visual environment; biotic resources; historical, archaeological, and cultural resources; socioeconomics; transportation; waste management; and human health and safety. The EIS describes in detail the potential radioactive releases from new production reactors and support facilities and assesses the potential doses to workers and the general public. This volume contains 15 appendices.« less

Oligonucleotide-genotyping as a method of detecting the HLA-DR2 (DRw15)-Dw2, -DR2 (DRw15)-Dw12, -DR4-Dw15, and -DR4-D"KT2" haplotypes in the Japanese population.

PubMed

Obata, F; Ito, I; Kaneko, T; Ohkubo, M; Ishimoto, A L; Abe, A; Kashiwagi, N

1989-05-01

We synthesized pairs of four different oligonucleotides, F22, F29, F42, and F158, to analyse the HLA-DR2 (DRw15) and -DR4 haplotypes in the Japanese population. After enzymatically amplifying the HLA-DRB1 gene, we hybridized the oligonucleotide probes with DNA extracted from 42 donors. Hybridization was completed between F22 and the DNA of haplotype DR2 (DRw15)-Dw2, between F29 and the DNA of DR2 (DRw15)-Dw12, between F42 and the DNA of DR4-D"KT2", and between F158 and the DNA of DR4-Dw15. In keeping with the nucleotide sequences of the probes, F29 hybridized also with DNA from the DR9-Dw23 haplotype and F158 with that from some of the DRw8 haplotypes (DRw8-Dw8.3) in the Japanese population. Results of this study demonstrate that the four oligonucleotides make useful probes for detecting the haplotypes above.

A phase III study evaluating the efficacy and safety of MBP8298 in secondary progressive MS.

PubMed

Freedman, M S; Bar-Or, A; Oger, J; Traboulsee, A; Patry, D; Young, C; Olsson, T; Li, D; Hartung, H-P; Krantz, M; Ferenczi, L; Verco, T

2011-10-18

To evaluate the efficacy and safety of MBP8298 in subjects with secondary progressive multiple sclerosis (SPMS) who express human leukocyte antigen (HLA) haplotype DR2 or DR4 (DR2(+) or DR4(+)). This multicenter randomized 2-year, double-blind, placebo-controlled study included 612 subjects with a diagnosis of SPMS and an Expanded Disability Status Scale (EDSS) score of 3.5-6.5, stratified according to baseline EDSS score (3.5-5.0, or 5.5-6.5) and HLA haplotype (DR2(+) or DR4(+), or DR2(-)/DR4(-)). Upon entry of 100 DR2(-)/DR4(-) subjects, further study enrollment was limited to DR2(+) or DR4(+) subjects. Subjects were randomly assigned to either 500 mg MBP8298 or placebo, given by IV injection once every 6 months for 2 years. The primary outcome measure was time to progression by ≥1.0 EDSS point (or 0.5 point if baseline EDSS was 5.5 or higher), confirmed 6 months later. Secondary outcomes included mean change in EDSS, mean change in Multiple Sclerosis Functional Composite, MRI changes, annualized relapse rate, and quality of life. There were no significant differences between treatment groups in either the primary or secondary endpoints. MBP8298 was well tolerated in all treated subjects with no safety issues identified. In the population studied, treatment with MBP8298 did not provide a clinical benefit compared to placebo. This study provides Class 1 evidence that MBP8298 is not effective in patients with SPMS who are HLA DR2(+) or DR4(+).

Discussion-preliminary review of the safety aspects of the crossunder line, Project CG-884. Volume 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, S.S.

1960-12-19

In order to reduce both charge-discharge shutdown time and the number of manhours of radiation exposure, Project CGI-884 is being completed at the B, D, DR, F and R Reactors. This consists essentially of installing a large drain line at the bottom of one rear reactor riser. This drain line passes to a control valve and then to the effluent line beyond the downcomer. This system by-passes the crossover downcomer part of the effluent system and eliminates the need for intermittent rear crossheader valving during reactor charge-discharge procedures. Two aspects of this system have been considered, its basic design requirements,more » and operating restrictions to ensure adequate process tube cooling. Because of the complexity of the reactor flow system approximate solutions were used to compare different methods or degrees of operation and establish limits. Despite these approximations, there was sufficient difference in the case results to justify the specific conclusions presented in this report. This report should serve the dual purpose of providing design requirements for the crossunder and also providing the technical criteria necessary for the operating standards for the use of this new system.« less

VizieR Online Data Catalog: KODIAQ DR2 (O'Meara+, 2017)

NASA Astrophysics Data System (ADS)

O'Meara, J. M.; Lehner, N.; Howk, J. C.; Prochaska, J. X.; Fox, A. J.; Peeples, M. S.; Tumlinson, J.; O'Shea, B. W.

2018-02-01

The new data presented here in DR2 all stem from High-Resolution Echelle Spectrograph (HIRES) observations by multiple PIs between 1995 and 2004. Table1 presents the HIRES deckers used across DR2 and their corresponding spectral resolution. As with DR1, the majority of observations were made with the C1 or C5 decker providing ~6 and ~8km/s FWHM resolution, respectively. The Keck Observatory Database of Ionized Absorption toward Quasars (KODIAQ) DR2 comprises HIRES observations of 300 quasar lines of sight in total. Of these, 130 quasar sight lines are new since DR1 (O'Meara et al. 2015, Cat. J/AJ/150/111), along with many new additional observations of some of the DR1 quasars. Table2 presents the new data since DR1. Table3 presents the full DR2 sample of 300 quasars. (3 data files).

Diabetic retinopathy and microalbuminuria can predict macroalbuminuria and renal function decline in Japanese type 2 diabetic patients: Japan Diabetes Complications Study.

PubMed

Moriya, Tatsumi; Tanaka, Shiro; Kawasaki, Ryo; Ohashi, Yasuo; Akanuma, Yasuo; Yamada, Nobuhiro; Sone, Hirohito; Yamashita, Hidetoshi; Katayama, Shigehiro

2013-09-01

To examine the interactive relationship between diabetic retinopathy (DR) and diabetic nephropathy (DN) in type 2 diabetic patients and to elucidate the role of DR and microalbuminuria on the onset of macroalbuminuria and renal function decline. We explored the effects of DR and microalbuminuria on the progression of DN from normoalbuminuria and low microalbuminuria (<150 mg/gCr) to macroalbuminuria or renal function decline in the Japan Diabetes Complications Study (JDCS), which is a nationwide randomized controlled study of type 2 diabetic patients focusing on lifestyle modification. Patients were divided into four groups according to presence or absence of DR and MA: normoalbuminuria without DR [NA(DR-)] (n = 773), normoalbuminuria with DR [NA(DR+)] (n = 279), microalbuminuria without DR [MA(DR-)] (n = 277), and microalbuminuria with DR [MA(DR+)] (n = 146). Basal urinary albumin-to-creatinine ratio and DR status were determined at baseline and followed for a median of 8.0 years. Annual incidence rates of macroalbuminuria were 1.6/1,000 person-years (9 incidences), 3.9/1,000 person-years (8 incidences), 18.4/1,000 person-years (34 incidences), and 22.1/1,000 person-years (22 incidences) in the four groups, respectively. Multivariate-adjusted hazard ratios of the progression to macroalbuminuria were 2.48 (95% CI 0.94-6.50; P = 0.07), 10.40 (4.91-22.03; P < 0.01), and 11.55 (5.24-25.45; P < 0.01) in NA(DR+), MA(DR-), and MA(DR+), respectively, in comparison with NA(DR-). Decline in estimated glomerular filtration rate (GFR) per year was two to three times faster in MA(DR+) (-1.92 mL/min/1.73 m(2)/year) than in the other groups. In normo- and low microalbuminuric Japanese type 2 diabetic patients, presence of microalbuminuria at baseline was associated with higher risk of macroalbuminuria in 8 years. Patients with microalbuminuria and DR showed the fastest GFR decline. Albuminuria and DR should be considered as risk factors of renal prognosis in type 2 diabetic patients. An open sharing of information will benefit both ophthalmologists and diabetologists.

1. View of three detection radar (DR) antennas. DR 1 ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. View of three detection radar (DR) antennas. DR 1 (structure no. 735) on left, DR 2 (structure no. 736) in center, and DR 3 (structure no. 737) looking north 30 degrees west, with tracking radar (large radome) and satcom (satellite communication) system in small radome in view between DR 2 and DR 3 antennae. - Clear Air Force Station, Ballistic Missile Early Warning System Site II, One mile west of mile marker 293.5 on Parks Highway, 5 miles southwest of Anderson, Anderson, Denali Borough, AK

2D Kinetic Particle in Cell Simulations of a Shear-Flow Stabilized Z-Pinch

NASA Astrophysics Data System (ADS)

Tummel, Kurt; Higginson, Drew; Schmidt, Andrea; Link, Anthony; McLean, Harry; Shumlak, Uri; Nelson, Brian; Golingo, Raymond; Claveau, Elliot; Lawrence Livermore National Lab Team; University of Washington Team

2016-10-01

The Z-pinch is a relatively simple and attractive potential fusion reactor design, but attempts to develop such a reactor have consistently struggled to overcome Z-pinch instabilities. The ``sausage'' and ``kink'' modes are among the most robust and prevalent Z-pinch instabilities, but theory and simulations suggest that axial flow-shear, dvz / dr ≠ 0 , can suppress these modes. Experiments have confirmed that Z-pinch plasmas with embedded axial flow-shear display a significantly enhanced resilience to the sausage and kink modes at a demonstration current of 50kAmps. A new experiment is under way to test the concept at higher current, and efforts to model these plasmas are being expanded. The performance and stability of these devices will depend on features like the plasma viscosity, anomalous resistivity, and finite Larmor radius effects, which are most accurately characterized in kinetic models. To predict these features, kinetic simulations using the particle in cell code LSP are now in development, and initial benchmarking and 2D stability analyses of the sausage mode are presented here. These results represent the first kinetic modeling of the flow-shear stabilized Z-pinch. This work is funded by the USDOE/ARPAe Alpha Program. Prepared by LLNL under Contract DE-AC52-07NA27344.

Biotechnica 󈨙 International Congress for Biotechnology Held in Hannover, Germany, D.R. on 8-10 October 1985,

DTIC Science & Technology

1986-02-27

Cross flow Filtration gelfiltratoi- Sjir.N dvng flttration filtration - Partition ad rlipon - - P trec pilaton Figure I. Downstream processing of...transformation the Nuclear Research Center, Jilich, into the L-amino acid is achieved in an West Germany. Until now the degrading enzyme reactor. This time...Some enzymatic processes can be car- of a hydrolase is the use of a peptidase tied out on a practical scale only in to produce peptides. One route to

The three catalases in Deinococcus radiodurans: Only two show catalase activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeong, Sun-Wook; Department of Biological Sciences, College of Biological Sciences and Biotechnology, Chungnam National University, Daejeon, 305-764; Jung, Jong-Hyun

2016-01-15

Deinococcus radiodurans, which is extremely resistant to ionizing radiation and oxidative stress, is known to have three catalases (DR1998, DRA0146, and DRA0259). In this study, to investigate the role of each catalase, we constructed catalase mutants (Δdr1998, ΔdrA0146, and ΔdrA0259) of D. radiodurans. Of the three mutants, Δdr1998 exhibited the greatest decrease in hydrogen peroxide (H{sub 2}O{sub 2}) resistance and the highest increase in intracellular reactive oxygen species (ROS) levels following H{sub 2}O{sub 2} treatments, whereas ΔdrA0146 showed no change in its H{sub 2}O{sub 2} resistance or ROS level. Catalase activity was not attenuated in ΔdrA0146, and none of the threemore » bands detected in an in-gel catalase activity assay disappeared in ΔdrA0146. The purified His-tagged recombinant DRA0146 did not show catalase activity. In addition, the phylogenetic analysis of the deinococcal catalases revealed that the DR1998-type catalase is common in the genus Deinococcus, but the DRA0146-type catalase was found in only 4 of 23 Deinococcus species. Taken together, these results indicate that DR1998 plays a critical role in the anti-oxidative system of D. radiodurans by detoxifying H{sub 2}O{sub 2}, but DRA0146 does not have catalase activity and is not involved in the resistance to H{sub 2}O{sub 2} stress. - Highlights: • The dr1998 mutant strain lost 90% of its total catalase activity. • Increased ROS levels and decreased H{sub 2}O{sub 2} resistance were observed in dr1998 mutants. • Lack of drA0146 did not affect any oxidative stress-related phenotypes. • The purified DRA0146 did not show catalase activity.« less

The safety and efficacy of dexmedetomidine-remifentanil in children undergoing flexible bronchoscopy

PubMed Central

Li, Xia; Wang, Xue; Jin, Shuguang; Zhang, Dongsheng; Li, Yanuo

2017-01-01

Abstract Flexible bronchoscopy is more and more used for diagnosis and management of various pulmonary diseases in pediatrics. As poor coordination of children, the procedure is usually performed under general anesthesia with spontaneous or controlled ventilation to increase children and bronchoscopists’ safety and comfort. Previous studies have reported that dexmedetomidine (DEX) could be safely and effectively used for flexible bronchoscopy in both adulate and children. However, there is no trial to evaluate the dose-finding of safety and efficacy of dexmedetomidine-remifentanil (DEX-RF) in children undergoing flexible bronchoscopy. The objective of this study is to evaluate the dose-finding of safety and efficacy of DEX-RF in children undergoing flexible bronchoscopy. One hundred thirty-five children undergoing flexible bronchoscopy with DEX-RF were divided into 3 groups: Group DR1 (n = 47, DEX infusion at 0.5 μg·kg–1 for 10 minutes, then adjusted to 0.5–0.7 μg kg–1 h–1; RF infusion at 0.5 μg kg–1 for 2 minutes, then adjusted to 0.05–0.2 μg kg–1 min–1), Group DR2 (n = 43, DEX infusion at 1 μg kg–1 for 10 minutes, then adjusted to 0.5–0.7 μg kg–1 h–1; RF infusion at 1 μg kg–1 for 2 minutes, then adjusted to 0.05–0.2 μg kg–1 min–1), Group DR3 (n = 45, DEX infusion at 1.5 μg kg–1 for 10 minutes, then adjusted to 0.5–0.7 μg kg–1 h–1; RF infusion at 1 μg kg–1 for 2 minutes, then adjusted to 0.05–0.2 μg kg–1 min–1). Ramsay sedation scale of the 3 groups was maintained 3. Anesthesia onset time, total number of intraoperative children movements, hemodynamics (heart rate, arterial pressure, pulse oxygen saturation (SpO2), respiratory rate), total cumulative dose of dexmedetomidine and remifentanil, the amount of midazolam and lidocaine, time to first dose of rescue midazolam and lidocaine, postoperative recovery time, adverse events, bronchoscopist satisfaction score were recorded. Anesthesia onset time was significantly shorter in DR3 group (14.23 ± 5.45 vs 14.45 ± 5.12 vs 11.13 ± 4.51 minutes, respectively, of DR1, DR2, DR3, P = 0.003). Additionally, the perioperative hemodynamic profile was more stable in group DR3 than that in the other 2 groups. Total number of children movements during flexible bronchoscopy was higher in DR1 group than the other 2 groups (46.81% 22/47 vs 34.88% 15/43 vs 17.78% 8/45, respectively, of DR1, DR2, DR3, P = 0.012). Total doses of rescue midazolam and lidocaine were significantly higher in DR1 and DR2 groups than that of DR3 group (P = 0.000). The time to first dose of rescue midazolam and lidocaine was significantly longer in DR3 group than DR1 and DR2 groups (P = 0.000). Total cumulative dose of dexmedetomidine was more in DR2 and DR3 groups (P = 0.000), while the amount of remifentanil was more in DR1 and DR2 groups (P = 0.000). The time to recovery for discharge from the PACU was significantly shorter in DR1 group compared with the other 2 groups (P = 0.000). Results from bronchoscopist satisfaction score showed significantly higher in DR2 and DR3 groups than that of DR1 group (P = 0.025). There were significant differences among the 3 groups in terms of the overall incidence of hypertension, tachycardia, hypoxemia, and cough (P < 0.05). Though it required longer recovery time, high dose of DEX-RF, which provided better stable hemodynamic profiles and bronchoscopist satisfaction score, less amount of rescue scheme, and children movements, could be safely and efficacy used in children undergoing flexible bronchoscopy. PMID:28296782

The HLA-DRB9 gene and the origin of HLA-DR haplotypes.

PubMed

Gongora, R; Figueroa, F; Klein, J

1996-11-01

HLA-DRB9 is a gene fragment consisting of exon 2 and flanking intron sequences. It is located at the extreme end of the DRB subregion, whose other end is demarcated by the DRB1 locus. We sequenced approximately 1400 base pairs of the segment encompassing the DRB9 locus from eight human haplotypes (DR1, DR10, DR2, DR3, DR5, DR6, DR8, and DR9, the DR4 and DR7 having been sequenced by others earlier), as well as two chimpanzee, five gorillas, one orangutan and one macaque haplotype. The analysis of these sequences indicates that the DRB9 locus, which we estimate to be more than 58 million years (my) old, has been coevolving with the DRB1 locus for the last 4.2 my. As a consequence of this coevolution, the human DRB9 alleles fall into groups that correlate with the DRB1 allelic groups and with the gene organization of the human haplotypes. This observation implies that the present-day HLA-DR haplotype groups (DR1, DR51, DR52, DR8, and DR53) were founded more than 4 my ago and have remained intact (barring minor internal rearrangements that did not recombine the DRB1 and DRB9 genes) for this period of time. The haplotypes have been transmitted during speciations from ancestral to emerging species just like allelic lineages at the DRB1 locus. Thus not only allelic but also haplotype polymorphism evolves trans-specifically.

[Analysis of HLA haplotype frequency and linkage disequilibrium in patients with acute lymphoblastic leukemia from Northern Chinese Han].

PubMed

Gao, Su-qing; Cheng, Liang-hong; Lu, Liang; Jing, Shi-zheng; Cheng, Xi; Zhang, Yin-ze; Zou, Hong-yan; Deng, Zhi-hui

2009-02-01

To analyze the difference between the frequencies of HLA-A-B, B-DRB1 and A-B-DRB1 haplotype, as well as their linkage disequilibrium pattern in patients with acute lymphoblastic leukemia(ALL) and healthy controls from Northern Chinese Han. The frequencies of HLA-A-B, B-DRB1, A-B-DR haplotypes and linkage disequilibrium were estimated by Expectation Maximization method based on the genotypes of 643 patients with ALL and 2 0359 unrelated healthy donors, and the statistical significance between the two groups were estimated by chi-square test. Linkage disequilibrium was analyzed with population genetic methods. The most common HLA-A-B, B-DRB1, and A-B-DR haplotypes were A30-B13, A2-B46, A33-B58, B13-DR7, B46-DR9, B52-DR15, B58-DR17, A30-B13-DR7, A33-B58-DR17 and A1-B37-DR10 in both groups. The frequencies of A30-B13, A2-B46, A33-B44, B13-DR7, A30-B13-DR7 and A2-B46-DR9 haplotypes and linkage disequilibrium value were significantly decreased (P<0.05) in the patient group than that in the control group. On the other hand, the frequencies of A2-B52, A31-B61, A24- B8, B60-DR9, B27-DR4, B52-DR14, B44-DR17, B27-DR12 and A11-B27-DR12 haplotypes and linkage disequilibrium value were significantly increased (P<0.05) in the patient group than that in the control group. There are some common and positive linkage disequilibrium haplotypes in both the ALL patients and the healthy donors in Northern Chinese Han. Interestingly, some haplotypes and their linkage disequilibrium patterns had significantly different distributions between the two groups. The study provided basic data for the relationship of ALL and HLA haplotype and for finding the HLA-A, B, DR matching donors.

catsHTM: A Tool for Fast Accessing and Cross-matching Large Astronomical Catalogs

NASA Astrophysics Data System (ADS)

Soumagnac, Maayane T.; Ofek, Eran O.

2018-07-01

Fast access to large catalogs is required for some astronomical applications. Here we introduce the catsHTM tool, consisting of several large catalogs reformatted into HDF5-based file format, which can be downloaded and used locally. To allow fast access, the catalogs are partitioned into hierarchical triangular meshes and stored in HDF5 files. Several tools are provided to perform efficient cone searches at resolutions spanning from a few arc-seconds to degrees, within a few milliseconds time. The first released version includes the following catalogs (by alphabetical order): 2MASS, 2MASS extended sources, AKARI, APASS, Cosmos, DECaLS/DR5, FIRST, GAIA/DR1, GAIA/DR2, GALEX/DR6Plus7, HSC/v2, IPHAS/DR2, NED redshifts, NVSS, Pan-STARRS1/DR1, PTF photometric catalog, ROSAT faint source, SDSS sources, SDSS/DR14 spectroscopy, SkyMapper, Spitzer/SAGE, Spitzer/IRAC galactic center, UCAC4, UKIDSS/DR10, VST/ATLAS/DR3, VST/KiDS/DR3, WISE and XMM. We provide Python code that allows to perform cone searches, as well as MATLAB code for performing cone searches, catalog cross-matching, general searches, as well as load and create these catalogs.

The three catalases in Deinococcus radiodurans: Only two show catalase activity.

PubMed

Jeong, Sun-Wook; Jung, Jong-Hyun; Kim, Min-Kyu; Seo, Ho Seong; Lim, Heon-Man; Lim, Sangyong

2016-01-15

Deinococcus radiodurans, which is extremely resistant to ionizing radiation and oxidative stress, is known to have three catalases (DR1998, DRA0146, and DRA0259). In this study, to investigate the role of each catalase, we constructed catalase mutants (Δdr1998, ΔdrA0146, and ΔdrA0259) of D. radiodurans. Of the three mutants, Δdr1998 exhibited the greatest decrease in hydrogen peroxide (H2O2) resistance and the highest increase in intracellular reactive oxygen species (ROS) levels following H2O2 treatments, whereas ΔdrA0146 showed no change in its H2O2 resistance or ROS level. Catalase activity was not attenuated in ΔdrA0146, and none of the three bands detected in an in-gel catalase activity assay disappeared in ΔdrA0146. The purified His-tagged recombinant DRA0146 did not show catalase activity. In addition, the phylogenetic analysis of the deinococcal catalases revealed that the DR1998-type catalase is common in the genus Deinococcus, but the DRA0146-type catalase was found in only 4 of 23 Deinococcus species. Taken together, these results indicate that DR1998 plays a critical role in the anti-oxidative system of D. radiodurans by detoxifying H2O2, but DRA0146 does not have catalase activity and is not involved in the resistance to H2O2 stress. Copyright © 2015 Elsevier Inc. All rights reserved.

Summary of ORSphere critical and reactor physics measurements

NASA Astrophysics Data System (ADS)

Marshall, Margaret A.; Bess, John D.

2017-09-01

In the early 1970s Dr. John T. Mihalczo (team leader), J.J. Lynn, and J.R. Taylor performed experiments at the Oak Ridge Critical Experiments Facility (ORCEF) with highly enriched uranium (HEU) metal (called Oak Ridge Alloy or ORALLOY) to recreate GODIVA I results with greater accuracy than those performed at Los Alamos National Laboratory in the 1950s. The purpose of the Oak Ridge ORALLOY Sphere (ORSphere) experiments was to estimate the unreflected and unmoderated critical mass of an idealized sphere of uranium metal corrected to a density, purity, and enrichment such that it could be compared with the GODIVA I experiments. This critical configuration has been evaluated. Preliminary results were presented at ND2013. Since then, the evaluation was finalized and judged to be an acceptable benchmark experiment for the International Criticality Safety Benchmark Experiment Project (ICSBEP). Additionally, reactor physics measurements were performed to determine surface button worths, central void worth, delayed neutron fraction, prompt neutron decay constant, fission density and neutron importance. These measurements have been evaluated and found to be acceptable experiments and are discussed in full detail in the International Handbook of Evaluated Reactor Physics Benchmark Experiments. The purpose of this paper is to summarize all the evaluated critical and reactor physics measurements evaluations.

Identification of Diabetic Retinopathy and Ungradable Image Rate with Ultrawide Field Imaging in a National Teleophthalmology Program.

PubMed

Silva, Paolo S; Horton, Mark B; Clary, Dawn; Lewis, Drew G; Sun, Jennifer K; Cavallerano, Jerry D; Aiello, Lloyd Paul

2016-06-01

To compare diabetic retinopathy (DR) identification and ungradable image rates between nonmydriatic ultrawide field (UWF) imaging and nonmydriatic multifield fundus photography (NMFP) in a large multistate population-based DR teleophthalmology program. Multiple-site, nonrandomized, consecutive, cross-sectional, retrospective, uncontrolled imaging device evaluation. Thirty-five thousand fifty-two eyes (17 526 patients) imaged using NMFP and 16 218 eyes (8109 patients) imaged using UWF imaging. All patients undergoing Joslin Vision Network (JVN) imaging with either NMFP or UWF imaging from May 1, 2014, through August 30, 2015, within the Indian Health Service-JVN program, which serves American Indian and Alaska Native communities at 97 sites across 25 states, were evaluated. All retinal images were graded using a standardized validated protocol in a centralized reading center. Ungradable rate for DR and diabetic macular edema (DME). The ungradable rate per patient for DR and DME was significantly lower with UWF imaging compared with NMFP (DR, 2.8% vs. 26.9% [P < 0.0001]; DME, 3.8% vs. 26.2% [P < 0.0001]). Identification of eyes with either DR or referable DR (moderate nonproliferative DR or DME or worse) was increased using UWF imaging from 11.7% to 24.2% (P < 0.0001) and from 6.2% to 13.6% (P < 0.0001), respectively. In eyes with DR imaged with UWF imaging (n = 3926 eyes of 2402 patients), the presence of predominantly peripheral lesions suggested a more severe level of DR in 7.2% of eyes (9.6% of patients). In a large, widely distributed DR ocular telehealth program, as compared with NMFP, nonmydriatic UWF imaging reduced the number of ungradable eyes by 81%, increased the identification of DR nearly 2-fold, and identified peripheral lesions suggesting more severe DR in almost 10% of patients, thus demonstrating significant benefits of this imaging method for large DR teleophthalmology programs. Copyright © 2016 American Academy of Ophthalmology. All rights reserved.

Ethnic differences in the prevalence of diabetic retinopathy in persons with diabetes when first presenting at a diabetes clinic in South Africa.

PubMed

Thomas, Rebecca L; Distiller, Larry; Luzio, Stephen D; Chowdhury, Sharmistha Roy; Melville, Vanessa J; Kramer, Brian; Owens, David R

2013-02-01

To describe the prevalence and associated risk factors for diabetic retinopathy (DR) within a multiethnic population at presentation to a diabetes clinic in South Africa. Retinal photography was conducted using a nonmydriatic digital camera without mydriasis and graded by one of three senior graders. Logistic regression analyses were used to assess the association between any DR, referable DR, and clinical risk factors. A total of 1,537 persons with type 1 and 3,978 with type 2 diabetes were included. Prevalence of any DR in type 1 diabetes was 35.2% (background DR 26% and referable DR 9.2%) and in type 2 diabetes was 20.5% (14.1 and 6.4%, respectively). In type 1 diabetes, there was an increased risk of any DR in Asian Indians, whereas the risk of referable DR was increased for indigenous Africans compared with Caucasians. In type 2 diabetes, the risk was increased for all non-Caucasians compared with Caucasians. Longer duration of diabetes and elevated HbA(1c) were independently associated with any and referable DR in both type 1 and type 2 diabetes, with the addition of hypertension and smoking in type 1 diabetes when adjusted for age at diagnosis of diabetes, sex, and ethnicity. The prevalence of DR in this population from South Africa was similar to that reported globally; however, ethnic differences were observed. Increasing duration of diabetes and poor glycemic control were the strongest risk factors associated with any and referable DR in both type 1 and type 2 diabetes.

Incidence and Risk Factors for Developing Diabetic Retinopathy among Youths with Type 1 or Type 2 Diabetes throughout the United States.

PubMed

Wang, Sophia Y; Andrews, Chris A; Herman, William H; Gardner, Thomas W; Stein, Joshua D

2017-04-01

Despite the increasing prevalence of type 2 diabetes mellitus (T2DM) among children and adolescents, little is known about their risk of developing diabetic retinopathy (DR). We sought to identify risk factors for DR in youths with diabetes mellitus, to compare DR rates for youths with type 1 diabetes mellitus (T1DM) and those with T2DM, and to assess whether adherence to DR screening guidelines promoted by the American Academy of Ophthalmology, American Academy of Pediatrics, and American Diabetes Association adequately capture youths with DR. Retrospective observational longitudinal cohort study. Youths aged ≤21 years with newly diagnosed T1DM or T2DM who were enrolled in a large US managed-care network. In this study of youths aged ≤21 years with newly diagnosed T1DM or T2DM who were under ophthalmic surveillance, we identified the incidence and timing of DR onset. Kaplan-Meier survival curves assessed the timing of initial diagnosis of DR for participants. Multivariable Cox proportional hazard regression modeling identified factors associated with the hazard of developing DR. Model predictors were age and calendar year at initial diabetes mellitus diagnosis, sex, race/ethnicity, net worth, and glycated hemoglobin A 1c fraction (HbA 1c ). Hazard ratios (HRs) with 95% confidence intervals (CIs) for developing DR. Among the 2240 youths with T1DM and 1768 youths with T2DM, 20.1% and 7.2% developed DR over a median follow-up time of 3.2 and 3.1 years, respectively. Survival curves demonstrated that youths with T1DM developed DR faster than youths with T2DM (P < 0.0001). For every 1-point increase in HbA 1c , the hazard for DR increased by 20% (HR = 1.20; 95% CI 1.06-1.35) and 30% (HR = 1.30; 95% CI 1.08-1.56) among youths with T1DM and T2DM, respectively. Current guidelines suggest that ophthalmic screening begin 3 to 5 years after initial diabetes mellitus diagnosis, at which point in our study, >18% of youths with T1DM had already received ≥1 DR diagnosis. Youths with T1DM or T2DM exhibit a considerable risk for DR and should undergo regular screenings by eye-care professionals to ensure timely DR diagnosis and limit progression to vision-threatening disease. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Prevalence of diabetic retinopathy in Peruvian patients with type 2 diabetes: results of a hospital-based retinal telescreening program.

PubMed

Villena, Jaime E; Yoshiyama, Christian A; Sánchez, Javier E; Hilario, Nélida L; Merin, Lawrence M

2011-11-01

To estimate the prevalence of diabetic retinopathy (DR) in patients with type 2 diabetes and to determine any association with clinical factors. This hospital-based screening project was designed to prospectively detect the presence of DR in patients with type 2 diabetes by grading images acquired with a digital retinal camera. Of 1 311 patients screened, appropriate retinal images were obtained in 1 222 subjects (93.2%). DR was detected in 282 patients (23.1%) [95% confidence interval (CI): 20.71-25.44]; 249 patients (20.4%) (95% CI: 18.1-22.6) had nonproliferative DR and 33 (2.7%) (95% CI: 1.8-3.6) had proliferative DR. In 32 patients (11.3%), DR was unilateral. The frequency of DR was the same in both sexes. Prevalence of blindness was twice as frequent in patients with DR as in those without it (9.4% and 4.6%, respectively) (P = 0.001). The frequency of DR at diagnosis was 3.5% and it increased with the duration of diabetes. DR was more frequent in patients with arterial hypertension, macrovascular or microvascular complications, and hemoglobin A1c (HbA1c) > 7.0% and in those treated with insulin or sulfonylureas. It was less prevalent in those with HbA1c < 7.0%, with greater body mass index, and who had been treated with metformin. The prevalence of DR in these patients with type 2 diabetes was 23.1%. Nonproliferative retinopathy accounted for 77.0% of cases. Although less prevalent than in a previous report, it doubled the frequency of blindness in the people affected. A national screening DR program should be considered in order to detect this prevalent condition early and treat it in a timely fashion.

Blockade of neuronal dopamine D2 receptor attenuates morphine tolerance in mice spinal cord.

PubMed

Dai, Wen-Ling; Xiong, Feng; Yan, Bing; Cao, Zheng-Yu; Liu, Wen-Tao; Liu, Ji-Hua; Yu, Bo-Yang

2016-12-22

Tolerance induced by morphine remains a major unresolved problem and significantly limits its clinical use. Recent evidences have indicated that dopamine D2 receptor (D2DR) is likely to be involved in morphine-induced antinociceptive tolerance. However, its exact effect and molecular mechanism remain unknown. In this study we examined the effect of D2DR on morphine antinociceptive tolerance in mice spinal cord. Chronic morphine treatment significantly increased levels of D2DR in mice spinal dorsal horn. And the immunoreactivity of D2DR was newly expressed in neurons rather than astrocytes or microglia both in vivo and in vitro. Blockade of D2DR with its antagonist (sulpiride and L-741,626, i.t.) attenuated morphine antinociceptive tolerance without affecting basal pain perception. Sulpiride (i.t.) also down-regulated the expression of phosphorylation of NR1, PKC, MAPKs and suppressed the activation of astrocytes and microglia induced by chronic morphine administration. Particularly, D2DR was found to interact with μ opioid receptor (MOR) in neurons, and chronic morphine treatment enhanced the MOR/D2DR interactions. Sulpiride (i.t.) could disrupt the MOR/D2DR interactions and attenuate morphine tolerance, indicating that neuronal D2DR in the spinal cord may be involved in morphine tolerance possibly by interacting with MOR. These results may present new opportunities for the treatment and management of morphine-induced antinociceptive tolerance which often observed in clinic.

Preliminary Multiphysics Analyses of HFIR LEU Fuel Conversion using COMSOL

DOE Office of Scientific and Technical Information (OSTI.GOV)

Freels, James D; Bodey, Isaac T; Arimilli, Rao V

The research documented herein was performed by several individuals across multiple organizations. We have previously acknowledged our funding for the project, but another common thread among the authors of this document, and hence the research performed, is the analysis tool COMSOL. The research has been divided into categories to allow the COMSOL analysis to be performed independently to the extent possible. As will be seen herein, the research has progressed to the point where it is expected that next year (2011) a large fraction of the research will require collaboration of our efforts as we progress almost exclusively into three-dimensionalmore » (3D) analysis. To the extent possible, we have tried to segregate the development effort into two-dimensional (2D) analysis in order to arrive at techniques and methodology that can be extended to 3D models in a timely manner. The Research Reactors Division (RRD) of ORNL has contracted with the University of Tennessee, Knoxville (UTK) Mechanical, Aerospace and Biomedical Engineering Department (MABE) to perform a significant fraction of this research. This group has been chosen due to their expertise and long-term commitment in using COMSOL and also because the participating students are able to work onsite on a part-time basis due to the close proximity of UTK with the ORNL campus. The UTK research has been governed by a statement of work (SOW) which clearly defines the specific tasks reported herein on the perspective areas of research. Ph.D. student Isaac T. Bodey has focused on heat transfer, fluid flow, modeling, and meshing issues and has been aided by his major professor Dr. Rao V. Arimilli and is the primary contributor to Section 2 of this report. Ph.D student Franklin G. Curtis has been focusing exclusively on fluid-structure interaction (FSI) due to the mechanical forces acting on the plate caused by the flow and has also been aided by his major professor Dr. Kivanc Ekici and is the primary contributor to Section 4 of this report. The HFIR LEU conversion project has also obtained the services of Dr. Prashant K. Jain of the Reactor & Nuclear Systems Division (RNSD) of ORNL. Prashant has quickly adapted to the COMSOL tools and has been focusing on thermal-structure interaction (TSI) issues and development of alternative 3D model approaches that could yield faster-running solutions. Prashant is the primary contributor to Section 5 of the report. And finally, while incorporating findings from all members of the COMSOL team (i.e., the team) and contributing as the senior COMSOL leader and advocate, Dr. James D. Freels has focused on the 3D model development, cluster deployment, and has contributed primarily to Section 3 and overall integration of this report. The team has migrated to the current release of COMSOL at version 4.1 for all the work described in this report, except where stated otherwise. Just as in the performance of the research, each of the respective sections has been originally authored by the respective authors. Therefore, the reader will observe a contrast in writing style throughout this document.« less

Losartan reverses COX-2-dependent vascular dysfunction in offspring of hyperglycaemic rats.

PubMed

de Queiroz, Diego Barbosa; Ramos-Alves, Fernanda Elizabethe; Santos-Rocha, Juliana; Duarte, Gloria Pinto; Xavier, Fabiano Elias

2017-09-01

This study examined whether chronic treatment with losartan, an angiotensin II type 1 receptor (AT 1 R) antagonist, might reverse COX-2-mediated vascular dysfunction in mesenteric resistance arteries (MRA) from offspring of hyperglycaemic rats. Male 12-month-old offspring of hyperglycaemic (O-DR) and normoglycaemic (O-CR) rats were treated with losartan (15mg·kg·day -1 ) during 2months. Third order MRA of untreated and losartan-treated O-DR and O-CR were mounted in wire myograph for isometric tension measurements. COX-2 expression was analyzed by Western blot; TxA 2 , PGE 2 and PGF 2α release was measured using commercial kits. O-DR showed increased blood pressure, impaired acetylcholine-induced vasodilation and increased noradrenaline-induced vasoconstriction than O-CR. All these parameters were normalized by losartan in O-DR. Pre-incubation of MRA with indomethacin (COX-1/2 inhibitor), NS-398 (COX-2 inhibitor) or tempol (superoxide dismutase mimetic) increased relaxation to acetylcholine and reduced contraction to noradrenaline only in O-DR. COX-2 expression, TxA 2 , PGE 2 and PGF 2α release were increased in O-DR. In losartan-treated O-DR, NS-398, indomethacin or tempol failed to produce any effect on acetylcholine or noradrenaline responses. Losartan treatment reduced COX-2 expression, TxA 2 , PGE 2 and PGF 2α release in O-DR. The present results reveal that chronic losartan administration in O-DR normalizes endothelial function in MRA by correcting the existing COX-2 overexpression and the imbalance between endothelium-derived relaxing and contracting factors. These findings not only support the beneficial effects of AT 1 receptor antagonist in O-DR, but also suggest the implication of angiotensin II as a putative mediator of hyperglycemia-programmed vascular dysfunction in rats. Copyright © 2017 Elsevier Inc. All rights reserved.

Ethnic Differences in the Prevalence of Diabetic Retinopathy in Persons With Diabetes When First Presenting at a Diabetes Clinic in South Africa

PubMed Central

Thomas, Rebecca L.; Distiller, Larry; Luzio, Stephen D.; Chowdhury, Sharmistha Roy; Melville, Vanessa J.; Kramer, Brian; Owens, David R.

2013-01-01

OBJECTIVE To describe the prevalence and associated risk factors for diabetic retinopathy (DR) within a multiethnic population at presentation to a diabetes clinic in South Africa. RESEARCH DESIGN AND METHODS Retinal photography was conducted using a nonmydriatic digital camera without mydriasis and graded by one of three senior graders. Logistic regression analyses were used to assess the association between any DR, referable DR, and clinical risk factors. RESULTS A total of 1,537 persons with type 1 and 3,978 with type 2 diabetes were included. Prevalence of any DR in type 1 diabetes was 35.2% (background DR 26% and referable DR 9.2%) and in type 2 diabetes was 20.5% (14.1 and 6.4%, respectively). In type 1 diabetes, there was an increased risk of any DR in Asian Indians, whereas the risk of referable DR was increased for indigenous Africans compared with Caucasians. In type 2 diabetes, the risk was increased for all non-Caucasians compared with Caucasians. Longer duration of diabetes and elevated HbA1c were independently associated with any and referable DR in both type 1 and type 2 diabetes, with the addition of hypertension and smoking in type 1 diabetes when adjusted for age at diagnosis of diabetes, sex, and ethnicity. CONCLUSIONS The prevalence of DR in this population from South Africa was similar to that reported globally; however, ethnic differences were observed. Increasing duration of diabetes and poor glycemic control were the strongest risk factors associated with any and referable DR in both type 1 and type 2 diabetes. PMID:23033236

The dopamine D2 receptor regulates Akt and GSK-3 via Dvl-3.

PubMed

Sutton, Laurie P; Rushlow, Walter J

2012-08-01

The dopamine D2 receptor (D2DR) regulates Akt and may also target the Wnt pathway, two signalling cascades that inhibit glycogen synthase kinase-3 (GSK-3). This study examined whether the Wnt pathway is regulated by D2DR and the role of Akt and dishevelled-3 (Dvl-3) in regulating GSK-3 and the transcription factor β-catenin in the rat brain. Western blotting showed that subchronic treatment of raclopride (D2DR antagonist) increase phosphorylated Akt, Dvl-3, GSK-3, phosphorylated GSK-3 and β-catenin, whereas subchronic treatment of quinpirole (D2DR agonist) induced the opposite response. Co-immunopreciptations revealed an association between GSK-3 and the D2DR complex that was altered following raclopride and quinpirole, albeit in opposite directions. SCH23390 (D1DR antagonist) and nafadotride (D3DR antagonist) were also used to determine if the response was specific to the D2DR. Neither subchronic treatment affected Dvl-3, GSK-3, Akt nor β-catenin protein levels, although nafadotride altered the phosphorylation state of Akt and GSK-3. In addition, in-vitro experiments were conducted to manipulate Akt and Dvl-3 activity in SH-SY5Y cells to elucidate how the pattern of change observed following manipulation of D2DR developed. Results indicate that Akt affects the phosphorylation state of GSK-3 but has no effect on β-catenin levels. However, altering Dvl-3 levels resulted in changes in Akt and the Wnt pathway similar to what was observed following raclopride or quinpirole treatment. Collectively, the data suggests that the D2DR very specifically regulates Wnt and Akt signalling via Dvl-3.

Chronic Ca2+ influx through voltage-dependent Ca2+ channels enhance delayed rectifier K+ currents via activating Src family tyrosine kinase in rat hippocampal neurons.

PubMed

Yang, Yoon-Sil; Jeon, Sang-Chan; Kim, Dong-Kwan; Eun, Su-Yong; Jung, Sung-Cherl

2017-03-01

Excessive influx and the subsequent rapid cytosolic elevation of Ca 2+ in neurons is the major cause to induce hyperexcitability and irreversible cell damage although it is an essential ion for cellular signalings. Therefore, most neurons exhibit several cellular mechanisms to homeostatically regulate cytosolic Ca 2+ level in normal as well as pathological conditions. Delayed rectifier K + channels (I DR channels) play a role to suppress membrane excitability by inducing K + outflow in various conditions, indicating their potential role in preventing pathogenic conditions and cell damage under Ca 2+ -mediated excitotoxic conditions. In the present study, we electrophysiologically evaluated the response of I DR channels to hyperexcitable conditions induced by high Ca 2+ pretreatment (3.6 mM, for 24 hours) in cultured hippocampal neurons. In results, high Ca 2+ -treatment significantly increased the amplitude of I DR without changes of gating kinetics. Nimodipine but not APV blocked Ca 2+ -induced I DR enhancement, confirming that the change of I DR might be targeted by Ca 2+ influx through voltage-dependent Ca 2+ channels (VDCCs) rather than NMDA receptors (NMDARs). The VDCC-mediated I DR enhancement was not affected by either Ca 2+ -induced Ca 2+ release (CICR) or small conductance Ca 2+ -activated K + channels (SK channels). Furthermore, PP2 but not H89 completely abolished I DR enhancement under high Ca 2+ condition, indicating that the activation of Src family tyrosine kinases (SFKs) is required for Ca 2+ -mediated I DR enhancement. Thus, SFKs may be sensitive to excessive Ca 2+ influx through VDCCs and enhance I DR to activate a neuroprotective mechanism against Ca 2+ -mediated hyperexcitability in neurons.

Incidence and Risk Factors for Developing Diabetic Retinopathy Among Youth with Type 1 and Type 2 Diabetes Throughout the United States

PubMed Central

Wang, Sophia Y.; Andrews, Chris A.; Herman, William H.; Gardner, Thomas W.; Stein, Joshua D.

2017-01-01

Objectives Despite the increasing prevalence of Type 2 diabetes mellitus (T2DM) among children and adolescents, little is known about their risk of developing diabetic retinopathy (DR). We sought to identify risk factors for DR in youth with DM, to compare DR rates for youth with Type 1 diabetes mellitus (T1DM) and T2DM, and to assess whether adherence to DR screening guidelines promoted by the American Academy of Ophthalmology, American Academy of Pediatrics, and American Diabetes Association adequately capture youth with DR. Design Retrospective observational longitudinal cohort study. Participants Youth aged ≤ 21 years with newly diagnosed T1DM or T2DM enrolled in a large U.S. managed care network. Main Outcome Measure Hazard ratios (HR) with 95% confidence intervals (CIs) for developing DR. Methods In this study of youth aged ≤ 21 years with newly diagnosed T1DM or T2DM enrolled in a large U.S. managed care network who were under ophthalmic surveillance, we identified the incidence and timing of DR onset for youth with T1DM and T2DM. Kaplan-Meier survival curves assessed the timing of initial diagnosis of DR for youth with each type of diabetes. Multivariable Cox proportional hazard regression modeling identified factors associated with the hazard of developing DR. Model predictors were age and calendar year at initial diabetes mellitus diagnosis, sex, race/ethnicity, net worth, and glycosylated hemoglobin (HbA1c). Results Among the 2240 youth with T1DM and 1768 youth with T2DM, 20.1% and 7.2% developed DR, over a median follow-up of 3.2 and 3.1 years, respectively. Survival curves demonstrated that youth with T1DM developed DR faster than youth with T2DM (P<0.0001). For every one-point increase in HbA1c, the hazard for DR increased by 20% (HR=1.20, CI 1.06–1.35) and 30% (HR=1.30, CI 1.08–1.56) among youth with T1DM and T2DM, respectively. Current guidelines suggest ophthalmic screening begin 3–5 years after initial DM diagnosis, at which point in our study, over 18% of youth with T1DM had already had received ≥1 DR diagnosis. Conclusions Youth with T1DM or T2DM exhibit a considerable risk for DR and should undergo regular screenings by eye-care professionals to ensure timely DR diagnosis and limit progression to vision-threatening disease. PMID:27914837

Which is riskier: windmills or reactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cromie, W.J.

1980-03-01

In 1978, Dr. Herbert Inhaber, a scientist employed by the Atomic Energy Board of Canada, published an evaluation of the health hazards of different energy systems entitled Risk of Energy Production. He concluded that natural gas and nuclear systems are safer than coal- and oil-fired power plants, hydroelectricity, various forms of solar energy, windmills, methanol (wood alcohol), and other nonconventional energy sources. The report and its conclusions drew widespread criticism, particularly from Dr. John P. Holdren, professor of energy and resources, University of California at Berkeley. Holdren and five colleagues wrote a stinging 232-page critique of the Inhaber report. Themore » Council for the Advancement of Science Writing, a nonprofit educational organization of writers and scientists, invited the two to debate the issue in front of an audience of science reporters. The confrontation took place at CASW's 17th Annual New Horizons in Science Briefing in Palo Alto, Calif., on Nov. 5, 1979. An edited transcript of the debate is presented here.« less

ITER Status and Plans

NASA Astrophysics Data System (ADS)

Greenfield, Charles M.

2017-10-01

The US Burning Plasma Organization is pleased to welcome Dr. Bernard Bigot, who will give an update on progress in the ITER Project. Dr. Bigot took over as Director General of the ITER Organization in early 2015 following a distinguished career that included serving as Chairman and CEO of the French Alternative Energies and Atomic Energy Commission and as High Commissioner for ITER in France. During his tenure at ITER the project has moved into high gear, with rapid progress evident on the construction site and preparation of a staged schedule and a research plan leading from where we are today through all the way to full DT operation. In an unprecedented international effort, seven partners ``China, the European Union, India, Japan, Korea, Russia and the United States'' have pooled their financial and scientific resources to build the biggest fusion reactor in history. ITER will open the way to the next step: a demonstration fusion power plant. All DPP attendees are welcome to attend this ITER town meeting.

Radiative lifetimes for 29 N2+ and implications for planetary escape and isotope enrichment

NASA Astrophysics Data System (ADS)

Guberman, Steven L.

2017-07-01

The Viking missions to Mars found that 15N/14N is enhanced by a factor of 1.62 compared to Earth and it was suggested that the cause was dissociative recombination (DR) of N2+. The high kinetic energy imparted to N in DR drives atmospheric escape. More recent models of the Martian ionosphere show that much of the N2+ is vibrationally excited. If DR of vibrationally excited 29N2+ is important, the energetics are such that the isotope enhancement would be greatly reduced. Here I show that at the Mars exobase electron temperature and density, the excited vibrational levels of 29N2+ radiate before they can recombine. The isotope enhancement arising from DR is due entirely to DR of 28N2+ with a small contribution to 14N escape arising from DR of the ground vibrational level of 29N2+.

Outcome of Extremely Low Birth Weight Infants Who Received Delivery Room Cardiopulmonary Resuscitation

PubMed Central

Wyckoff, Myra H.; Salhab, Walid A.; Heyne, Roy J.; Kendrick, Douglas E.; Stoll, Barbara J.; Laptook, Abbot R.

2011-01-01

Objective To determine whether delivery room cardiopulmonary resuscitation (DR-CPR) independently predicts morbidities and neurodevelopmental impairment (NI) in extremely low birth weight (ELBW) infants. Study design Cohort study of infants born with birth weight (BW) 401-1000g and gestational age (GA) 23-30wks. DR-CPR was defined as chest compressions and/or drugs. Logistic regression was used to determine associations between DR-CPR and morbidities, mortality and NI at 18-24 months (Bayley II mental or psychomotor index < 70, cerebral palsy, blindness or deafness). Data are adjusted Odds Ratio (OR) with 95% confidence interval. Results Of 8685 infants, 1333(15%) received DR-CPR. DR-CPR infants had lower BW (708±141vs 764±146g, p<0.0001) and GA (25±2 vs 26±2 wks, p<0.0001). DR-CPR infants had more pneumothoraces (OR 1.28, 1.48-2.99), Grade 3-4 intraventricular hemorrhage (OR 1.47, 1.23-1.74), bronchopulmonary dysplasia (OR 1.34, 1.13-1.59), death by 12 hours (OR 3.69, 2.98-4.57) and by 120 days after birth (OR 2.22, 1.93-2.57). NI among survivors (OR 1.23, 1.02-1.49), and death or NI (OR 1.70, 1.46-1.99) were higher for DR-CPR infants. Only 14% of DR-CPR recipients with 5-minute Apgar score<2 survived without NI. Conclusions DR-CPR is a prognostic marker for higher mortality and NI for ELBW survivors. New DR-CPR strategies are needed for this population. PMID:21930284

Prevalence and risk factors for diabetic retinopathy in 17 152 patients from the island of Funen, Denmark.

PubMed

Larsen, Morten B; Henriksen, Jan Erik; Grauslund, Jakob; Peto, Tunde

2017-12-01

This study aims to estimate the prevalence and risk factors of diabetic retinopathy (DR) in patients enrolled in a large Danish quality-assuring database for diabetes: the Funen Diabetes Database (FDDB). All patients with type 1 (T1DM) and type 2 DM (T2DM) diabetes mellitus (DM) were included in a cross-sectional study. The level of DR per patient was determined based on the eye with highest level of DR. All ocular and non-ocular data were extracted at the latest examination that corresponded to the most recent DR-grading data. Data from 17 152 patients were analysed; 83.1% had T2DM. Prevalence of DR was 23.8% (T1DM: 54.3%, T2DM: 21.2%). T1/T2DM patients were statistically significantly different regarding age, duration of diabetes, BMI, systolic blood pressure (BP), cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, s-creatinine and u-albumin (p < 0.001 for all). Increasing level of DR showed statistically significant association with age, duration of diabetes, systolic BP, HbA1c, s-creatinine and u-albumine with increasing level of DR (all are p < 0.001) both T1DM/T2DM patients. The patients in FDDB had good systemic control with median values of BP, serum lipids, cholesterol and HbA1c all close to or below national guidelines at the time of data extraction, but still a high level of DR was found in this cohort. DR was more common in patients with T1DM than T2DM, but as T2DM patients are more numerous, their level of DR despite acceptable control is still concerning. Most important associated factors for higher levels of DR were age, duration of diabetes, HbA1c, s-creatinine and u-albumine. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Structural and functional characterization of two unusual endonuclease III enzymes from Deinococcus radiodurans.

PubMed

Sarre, Aili; Ökvist, Mats; Klar, Tobias; Hall, David R; Smalås, Arne O; McSweeney, Sean; Timmins, Joanna; Moe, Elin

2015-08-01

While most bacteria possess a single gene encoding the bifunctional DNA glycosylase Endonuclease III (EndoIII) in their genomes, Deinococcus radiodurans possesses three: DR2438 (DrEndoIII1), DR0289 (DrEndoIII2) and DR0982 (DrEndoIII3). Here we have determined the crystal structures of DrEndoIII1 and an N-terminally truncated form of DrEndoIII3 (DrEndoIII3Δ76). We have also generated a homology model of DrEndoIII2 and measured activity of the three enzymes. All three structures consist of two all α-helical domains, one of which exhibits a [4Fe-4S] cluster and the other a HhH-motif, separated by a DNA binding cleft, similar to previously determined structures of endonuclease III from Escherichia coli and Geobacillus stearothermophilus. However, both DrEndoIII1 and DrEndoIII3 possess an extended HhH motif with extra helical features and an altered electrostatic surface potential. In addition, the DNA binding cleft of DrEndoIII3 seems to be less accessible for DNA interactions, while in DrEndoIII1 it seems to be more open. Analysis of the enzyme activities shows that DrEndoIII2 is most similar to the previously studied enzymes, while DrEndoIII1 seems to be more distant with a weaker activity towards substrate DNA containing either thymine glycol or an abasic site. DrEndoIII3 is the most distantly related enzyme and displays no detectable activity towards these substrates even though the suggested catalytic residues are conserved. Based on a comparative structural analysis, we suggest that the altered surface potential, shape of the substrate-binding pockets and specific amino acid substitutions close to the active site and in the DNA interacting loops may underlie the unexpected differences in activity. Copyright © 2015 Elsevier Inc. All rights reserved.

HLA-DPB1*04:01 Protects Genetically Susceptible Children from Celiac Disease Autoimmunity in the TEDDY Study.

PubMed

Hadley, David; Hagopian, William; Liu, Edwin; She, Jin-Xiong; Simell, Olli; Akolkar, Beena; Ziegler, Anette-G; Rewers, Marian; Krischer, Jeffrey P; Chen, Wei-Min; Onengut-Gumuscu, Suna; Bugawan, Teodorica L; Rich, Stephen S; Erlich, Henry; Agardh, Daniel

2015-06-01

Tissue transglutaminase autoantibodies (tTGAs) represent the first evidence of celiac disease (CD) development. Associations of HLA-DR3-DQA1*05:01-DQB1*02:01 (i.e., DR3-DQ2) and, to a lesser extent, DR4-DQA1*03:01-DQB1*03:02 (i.e., DR4-DQ8) with the risk of CD differ by country, consistent with additional genetic heterogeneity that further refines risk. Therefore, we examined human leukocyte antigen (HLA) factors other than DR3-DQ2 for their contribution to developing tTGAs. The Environmental Determinants of Diabetes in the Young (TEDDY) study enrolled 8,676 infants at an increased HLA-DR-DQ risk for type 1 diabetes and CD into a 15-year prospective surveillance follow-up. Of those followed up, 21% (n=1,813) carried DR3-DQ2/DR3-DQ2, 39% (n=3,359) carried DR3-DQ2/DR4-DQ8, 20% (n=1701) carried DR4-DQ8/DR4-DQ8, and 17% (n=1,493) carried DR4-DQ8/DQ4. Within TEDDY, a nested case-control design of 248 children with CD autoimmunity (CDA) and 248 matched control children were genotyped for HLA-B, -DRB3, -DRB4, -DPA1, and -DPB1 genes, and the entire cohort was genotyped for single-nucleotide polymorphisms (SNPs) using the Illumina ImmunoChip. CDA was defined as a positive tTGA test at two consecutive clinic visits, whereas matching in those with no evidence of tTGAs was based on the presence of HLA-DQ2, country, and sex. After adjustment for DR3-DQ2 and restriction to allele frequency (AF) ≥5%, HLA-DPB1*04:01 was inversely associated with CDA by conditional logistic regression (AF=44%, odds ratio=0.71, 95% confidence interval (CI)=0.53-0.96, P=0.025). This association of time to CDA and HLA-DPB1*04:01 was replicated with statistical significance in the remainder of the cohort using imputation for specific HLA alleles based on SNP genotyping (hazard ratio=0.84, 95% CI=0.73-0.96, P=0.013). HLA-DPB1*04:01 may reduce the risk of tTGAs, an early marker of CD, among DR3-DQ2 children, confirming that additional variants in the HLA region influence the risk for CDA.

Diabetic retinopathy and health-related quality of life among Chinese with known type 2 diabetes mellitus.

PubMed

Pan, Chen-Wei; Wang, Shan; Wang, Pei; Xu, Cai-Lian; Song, E

2018-05-08

We aim to describe the impact of diabetic retinopathy (DR) on health-related quality of life (HRQOL) among community-dwelling Chinese adults who had been previously diagnosed with type 2 diabetes mellitus (T2DM). A community-based survey including 913 patients with T2DM was conducted in Suzhou, China. Retinopathy lesions were graded according to the Airlie House classification system of the Early Treatment Diabetic Retinopathy Study. The HRQOL was measured by the Chinese version of the EuroQol Group's five-level EuroQol five-dimensional questionnaire (EQ-5D-5L). A Gamma distribution with log link was incorporated into linear regression models to assess the associations between DR and EQ-5D-5L health utility score. The mean EQ-5D-5L index scores were 0.971 ± 0.082 among individuals with unilateral DR and 0.970 ± 0.145 among those with bilateral DR, which were lower compared with those without DR (0.986 ± 0.045, P = 0.02). In multivariate analysis adjusting for confounders, people with bilateral DR reported lower the EQ-5D index scores compared with those without DR. The presence of DR was significantly associated with problems in usual activities (odds ratio [OR] = 0.16, P = 0.02, comparing participants with unilateral vs. no DR; OR = 0.11; P = 0.01, comparing participants with bilateral vs. no DR). No significant variations in EQ-5D-5L index scores as well as different domains of health problems between individuals with unilateral and bilateral DR were observed (P > 0.05). Chinese T2DM patients with bilateral DR tend to report lower HRQOL scores compared with those without DR, especially in health problems associated with usual activities.

[Gene and haplotype frequencies for the loci HLA-A, B and DRB1 in 11755 north Chinese Han bone marrow registry donors].

PubMed

Wu, Qiang-Ju; Liu, Meng-Li; Qi, Jun; Liu, Sheng; Zhang, Yan; Wei, Xiao-Qian

2007-04-01

The study was aimed to investigate the human leukocyte antigen (HLA)-A, B, DRB1 alleles and haplotype frequencies and the characteristics of linkage disequilibrium in north Chinese Han bone marrow donors. HLA phenotype data of 11 755 north Chinese Han bone marrow donors were identified by PCR-SSP and PCR-SSO. HLA-A, B, DRB1 allele and haplotype frequencies were calculated by computer software named Arleguin which was based on Expectation-Maximization (EM) algorithms. The results showed that the population of 11755 unrelated-donors was tested by Hardy-Weinberg equilibrium, and 18,42 and 15 specificities of HLA alleles were identified on the HLA-A, B, DRB1 locus respectively, including HLA-A25, B42, B53, B73 and DR3 which were rarely reported in Han population. HLA-A36, A43, A80, B78, B82 and DR18 were not detected in this study. The most frequent alleles with a frequency of over 0.05 were HLA-A*02, A*11, A*24, A*33, A*30, A*01, A*03, A*13, B62, B*51, B*46, B60, B61, B*35, B*44, DRB1*15, DRB1*09, DRB1*04, DRB1*07, DRB1*12, DRB1*11, DRB1*14, DRB1*08, DRB1*13. There were a total of 2 026 kinds of HLA-A-B-DR haplotypes (with a frequency of over 10(-6)) to be obtained. The each frequency of 26 kinds of three-locus haplotypes including HLA-A30-B13-DR7, A2-B46-DR9, A33-B58-DR17 etc was higher than 0.005. A30-B13-DR7 was the most frequent haplotype in north Chinese Han population. There were a total of 538 kinds of haplotypes for HLA-A-B, 227 kinds for A-DR and 522 kinds for B-DR to be obtained, and there were 409, 195, 423 kinds of haplotypes respectively with a frequency higher than 10 - 6. There were 28 kinds of HLA-A-B haplotypes including A30-B13, A2-B46, A33-B58 etc, 26 kinds of HLA-A-DR haplotypes including A2-DR9, A2-DR15, A30-DR7 etc, and 24 kinds of HLA-B-DR haplotypes including B13-DR7, B46-DR9, B13-DR12 etc with a frequency higher than 0.01. 296 (72%) kinds of HLA-A-B, 130 (67%) kinds of A-DR and 308 (73%) kinds of B-DR haplotypes were statistical linkage disequilibrium. HLA-A30-B13, A33-B58, A1-B37, A30-DR7, A33-DR13, A1-DR10, B37-DR10, B8-DR17, B13-DR7, B58-DR17 were significant positive linkage disequilibrium. It is concluded that this HLA-A, B, DRB1 gene and haplotype frequencies and linkage disequilibrium data with the largest sample size up to now is unique in north Chinese Han population. The study will be helpful to find matched donors for patients and establish the important foundation for further studying of transplantation immunity, HLA-related diseases and population genetics of this area.

Oxygen Saturation of Retinal Vessels in All Stages of Diabetic Retinopathy and Correlation to Ultra-Wide Field Fluorescein Angiography.

PubMed

Guduru, Abhilash; Martz, Teresa G; Waters, Alexa; Kshirsagar, Abhijit V; Garg, Seema

2016-10-01

The purpose of this study was to determine retinal hemoglobin oxygen saturation (SO2) in patients with diabetic retinopathy (DR) using retinal oximetry (RO) and to correlate the degree of retinal ischemia using intravenous fluorescein angiography (IVFA). This is a single-center cross-sectional cohort study. Twenty-seven controls and 60 adult patients with diabetes mellitus (16 without DR and 44 with DR) were enrolled. Patients were stratified according to DR severity. Using RO, SO2 was measured in major retinal arterioles (SaO2) and venules (SvO2). Using IVFA, the percentage of retinal ischemia in 31 patients with DR was calculated and correlated with RO. Pairwise one-way analysis of variance (ANOVA) showed a significant increase in SaO2 and SvO2 in patients with proliferative DR (PDR) compared with controls (SaO2: PDR, 100 ± 7% vs. controls, 91 ± 4% [P = 0.003]; SvO2: PDR, 66 ± 11% vs. controls, 53 ± 6% [P < 0.00001]). The percentage of retinal ischemia also increased with DR severity: ANOVA showed a significant difference in retinal ischemia between all categories of nonproliferative DR vs. PDR: 2.31 ± 2% vs. 7.92 ± 9% (P = 0.017), respectively. Pearson two-tailed correlation showed significant correlation between SaO2 and ischemia (R = 0.467, P = 0.011). Hemoglobin oxygen saturation of retinal arterioles and venules increases with DR severity; SaO2 correlates with increasing ischemia measured by IVFA. Retinal oximetry may complement current imaging strategies to noninvasively augment the diagnosis and risk stratification of patients with diabetes.

Summary of ORSphere Critical and Reactor Physics Measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marshall, Margaret A.; Bess, John D.

In the early 1970s Dr. John T. Mihalczo (team leader), J. J. Lynn, and J. R. Taylor performed experiments at the Oak Ridge Critical Experiments Facility (ORCEF) with highly enriched uranium (HEU) metal (called Oak Ridge Alloy or ORALLOY) to recreate GODIVA I results with greater accuracy than those performed at Los Alamos National Laboratory in the 1950s. The purpose of the Oak Ridge ORALLOY Sphere (ORSphere) experiments was to estimate the unreflected and unmoderated critical mass of an idealized sphere of uranium metal corrected to a density, purity, and enrichment such that it could be compared with the GODIVAmore » I experiments. This critical configuration has been evaluated. Preliminary results were presented at ND2013. Since then, the evaluation was finalized and judged to be an acceptable benchmark experiment for the International Criticality Safety Benchmark Experiment Project (ICSBEP). Additionally, reactor physics measurements were performed to determine surface button worths, central void worth, delayed neutron fraction, prompt neutron decay constant, fission density and neutron importance. These measurements have been evaluated and found to be acceptable experiments and are discussed in full detail in the International Handbook of Evaluated Reactor Physics Benchmark Experiments. The purpose of this paper is summary summarize all the critical and reactor physics measurements evaluations and, when possible, to compare them to GODIVA experiment results.« less

Predominant antitumor effects by fully human anti-TRAIL-receptor2 (DR5) monoclonal antibodies in human glioma cells in vitro and in vivo

PubMed Central

Nagane, Motoo; Shimizu, Saki; Mori, Eiji; Kataoka, Shiro; Shiokawa, Yoshiaki

2010-01-01

Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL/Apo2 L) preferentially induces apoptosis in human tumor cells through its cognate death receptors DR4 or DR5, thereby being investigated as a potential agent for cancer therapy. Here, we applied fully human anti-human TRAIL receptor monoclonal antibodies (mAbs) to specifically target one of death receptors for TRAIL in human glioma cells, which could also reduce potential TRAIL-induced toxicity in humans. Twelve human glioma cell lines treated with several fully human anti-human TRAIL receptor mAbs were sensitive to only anti-DR5 mAbs, whereas they were totally insensitive to anti-DR4 mAb. Treatment with anti-DR5 mAbs exerted rapid cytotoxicity and lead to apoptosis induction. The cellular sensitivity was closely associated with cell-surface expression of DR5. Expression of c-FLIPL, Akt, and Cyclin D1 significantly correlated with sensitivity to anti-DR5 mAbs. Primary cultures of glioma cells were also relatively resistant to anti-DR5 mAbs, exhibiting both lower DR5 and higher c-FLIPL expression. Downregulation of c-FLIPL expression resulted in the sensitization of human glioma cells to anti-DR5 mAbs, whereas overexpression of c-FLIPL conferred resistance to anti-DR5 mAb. Treatment of tumor-burden nude mice with the direct agonist anti-DR5 mAb KMTR2 significantly suppressed growth of subcutaneous glioma xenografts leading to complete regression. Similarly, treatment of nude mice bearing intracerebral glioma xenografts with KMTR2 significantly elongated lifespan without tumor recurrence. These results suggest that DR5 is the predominant TRAIL receptor mediating apoptotic signals in human glioma cells, and sensitivity to anti-DR5 mAbs was determined at least in part by the expression level of c-FLIPL and Akt. Specific targeting of death receptor pathway through DR5 using fully human mAbs might provide a novel therapeutic strategy for intractable malignant gliomas. PMID:20511188

Outcome of extremely low birth weight infants who received delivery room cardiopulmonary resuscitation.

PubMed

Wyckoff, Myra H; Salhab, Walid A; Heyne, Roy J; Kendrick, Douglas E; Stoll, Barbara J; Laptook, Abbot R

2012-02-01

To determine whether delivery room cardiopulmonary resuscitation (DR-CPR) independently predicts morbidities and neurodevelopmental impairment (NDI) in extremely low birth weight infants. We conducted a cohort study of infants born with birth weight of 401 to 1000 g and gestational age of 23 to 30 weeks. DR-CPR was defined as chest compressions, medications, or both. Logistic regression was used to determine associations among DR-CPR and morbidities, mortality, and NDI at 18 to 24 months of age (Bayley II mental or psychomotor index <70, cerebral palsy, blindness, or deafness). Data are adjusted ORs with 95% CIs. Of 8685 infants, 1333 (15%) received DR-CPR. Infants who received DR-CPR had lower birth weight (708±141 g versus 764±146g, P<.0001) and gestational age (25±2 weeks versus 26±2 weeks, P<.0001). Infants who received DR-CPR had more pneumothoraces (OR, 1.28; 95% CI, 1.48-2.99), grade 3 to 4 intraventricular hemorrhage (OR, 1.47; 95% CI, 1.23-1.74), bronchopulmonary dysplasia (OR, 1.34; 95% CI, 1.13-1.59), death by 12 hours (OR, 3.69; 95% CI, 2.98-4.57), and death by 120 days after birth (OR, 2.22; 95% CI, 1.93-2.57). Rates of NDI in survivors (OR, 1.23; 95% CI, 1.02-1.49) and death or NDI (OR, 1.70; 95% CI, 1.46-1.99) were higher for DR-CPR infants. Only 14% of DR-CPR recipients with 5-minute Apgar score <2 survived without NDI. DR-CPR is a prognostic marker for higher rates of mortality and NDI for extremely low birth weight infants. New DR-CPR strategies are needed for this population. Copyright © 2012 Mosby, Inc. All rights reserved.

DR2DI: a powerful computational tool for predicting novel drug-disease associations

NASA Astrophysics Data System (ADS)

Lu, Lu; Yu, Hua

2018-05-01

Finding the new related candidate diseases for known drugs provides an effective method for fast-speed and low-risk drug development. However, experimental identification of drug-disease associations is expensive and time-consuming. This motivates the need for developing in silico computational methods that can infer true drug-disease pairs with high confidence. In this study, we presented a novel and powerful computational tool, DR2DI, for accurately uncovering the potential associations between drugs and diseases using high-dimensional and heterogeneous omics data as information sources. Based on a unified and extended similarity kernel framework, DR2DI inferred the unknown relationships between drugs and diseases using Regularized Kernel Classifier. Importantly, DR2DI employed a semi-supervised and global learning algorithm which can be applied to uncover the diseases (drugs) associated with known and novel drugs (diseases). In silico global validation experiments showed that DR2DI significantly outperforms recent two approaches for predicting drug-disease associations. Detailed case studies further demonstrated that the therapeutic indications and side effects of drugs predicted by DR2DI could be validated by existing database records and literature, suggesting that DR2DI can be served as a useful bioinformatic tool for identifying the potential drug-disease associations and guiding drug repositioning. Our software and comparison codes are freely available at https://github.com/huayu1111/DR2DI.

DR2DI: a powerful computational tool for predicting novel drug-disease associations

NASA Astrophysics Data System (ADS)

Lu, Lu; Yu, Hua

2018-04-01

Finding the new related candidate diseases for known drugs provides an effective method for fast-speed and low-risk drug development. However, experimental identification of drug-disease associations is expensive and time-consuming. This motivates the need for developing in silico computational methods that can infer true drug-disease pairs with high confidence. In this study, we presented a novel and powerful computational tool, DR2DI, for accurately uncovering the potential associations between drugs and diseases using high-dimensional and heterogeneous omics data as information sources. Based on a unified and extended similarity kernel framework, DR2DI inferred the unknown relationships between drugs and diseases using Regularized Kernel Classifier. Importantly, DR2DI employed a semi-supervised and global learning algorithm which can be applied to uncover the diseases (drugs) associated with known and novel drugs (diseases). In silico global validation experiments showed that DR2DI significantly outperforms recent two approaches for predicting drug-disease associations. Detailed case studies further demonstrated that the therapeutic indications and side effects of drugs predicted by DR2DI could be validated by existing database records and literature, suggesting that DR2DI can be served as a useful bioinformatic tool for identifying the potential drug-disease associations and guiding drug repositioning. Our software and comparison codes are freely available at https://github.com/huayu1111/DR2DI.

Device characterization and optimization of small molecule organic solar cells assisted by modelling simulation of the current-voltage characteristics.

PubMed

Zuo, Yi; Wan, Xiangjian; Long, Guankui; Kan, Bin; Ni, Wang; Zhang, Hongtao; Chen, Yongsheng

2015-07-15

In order to understand the photovoltaic performance differences between the recently reported DR3TBTT-HD and DR3TBDT2T based solar cells, a modified two-diode model with Hecht equation was built to simulate the corresponding current-voltage characteristics. The simulation results reveal that the poor device performance of the DR3TBDTT-HD based device mainly originated from its insufficient charge transport ability, where an average current of 5.79 mA cm(-2) was lost through this pathway at the maximum power point for the DR3TBDTT-HD device, nearly three times as large as that of the DR3TBDT2T based device under the same device fabrication conditions. The morphology studies support these simulation results, in which both Raman and 2D-GIXD data reveal that DR3TBTT-HD based blend films exhibit lower crystallinity. Spin coating at low temperature was used to increase the crystallinity of DR3TBDTT-HD based blend films, and the average current loss through insufficient charge transport at maximum power point was suppressed to 2.08 mA cm(-2). As a result, the average experimental power conversion efficiency of DR3TBDTT-HD based solar cells increased by over 40%.

Dopamine D2 receptor availability is linked to hippocampal–caudate functional connectivity and episodic memory

PubMed Central

Nyberg, Lars; Karalija, Nina; Salami, Alireza; Andersson, Micael; Wåhlin, Anders; Kaboovand, Neda; Köhncke, Ylva; Axelsson, Jan; Rieckmann, Anna; Papenberg, Goran; Garrett, Douglas D.; Riklund, Katrine; Lövdén, Martin; Bäckman, Lars

2016-01-01

D1 and D2 dopamine receptors (D1DRs and D2DRs) may contribute differently to various aspects of memory and cognition. The D1DR system has been linked to functions supported by the prefrontal cortex. By contrast, the role of the D2DR system is less clear, although it has been hypothesized that D2DRs make a specific contribution to hippocampus-based cognitive functions. Here we present results from 181 healthy adults between 64 and 68 y of age who underwent comprehensive assessment of episodic memory, working memory, and processing speed, along with MRI and D2DR assessment with [11C]raclopride and PET. Caudate D2DR availability was positively associated with episodic memory but not with working memory or speed. Whole-brain analyses further revealed a relation between hippocampal D2DR availability and episodic memory. Hippocampal and caudate D2DR availability were interrelated, and functional MRI-based resting-state functional connectivity between the ventral caudate and medial temporal cortex increased as a function of caudate D2DR availability. Collectively, these findings indicate that D2DRs make a specific contribution to hippocampus-based cognition by influencing striatal and hippocampal regions, and their interactions. PMID:27339132

Prevalence of Diabetic Retinopathy and Blindness in Indonesian Adults With Type 2 Diabetes.

PubMed

Sasongko, Muhammad Bayu; Widyaputri, Felicia; Agni, Angela Nurini; Wardhana, Firman Setya; Kotha, Satyaprabha; Gupta, Prateek; Widayanti, Tri Wahyu; Haryanto, Supanji; Widyaningrum, Rifa; Wong, Tien Yin; Kawasaki, Ryo; Wang, Jie Jin

2017-09-01

To report the prevalence of diabetic retinopathy (DR) and DR-related blindness in an Indonesian population with type 2 diabetes. Design: Population-based cross-sectional study. Community health centers. We recruited 1184 people aged older than 30 years with type 2 diabetes residing in Jogjakarta, Indonesia. Multistage, clustered random sampling based on regencies and districts in Jogjakarta was used. Detailed interviews, general and eye examinations, and anthropometric measurement were performed. Disc- and macula-centered retinal photographs were taken to assess DR. The definition of DR followed a modified Airlie House classification system and was categorized into mild, moderate, and vision-threatening DR (VTDR). Prevalence and severity of DR. The median (range) age and diabetes duration of participants was 59 (52-65) and 4 (2-9) years. The prevalence of DR was 43.1% (95% confidence interval 39.6%-46.6%), with mild, moderate, and severe NPDR and PDR to be 9.41%, 7.46%, 11.1%, and 12.1%, respectively. The prevalence of VTDR was 26.3% (23.1%-29.5%). Longer diabetes duration, higher fasting glucose, presence of hypertension, and foot ulcers were associated with DR and VTDR. The prevalence of bilateral blindness was 4% and 7.7% in persons with DR and VTDR. This study reports a high prevalence of any DR and VTDR among Indonesian adults with type 2 diabetes in urban and rural areas: approximately 1 in 4 adults with diabetes had VTDR and 1 in 12 of those with VTDR was bilaterally blind, suggesting the need for appropriate screening and management of DR among the Indonesian population. Copyright © 2017 Elsevier Inc. All rights reserved.

EDN1 Lys198Asn is associated with diabetic retinopathy in type 2 diabetes

PubMed Central

Li, Haitao; Louey, Janice W.C.; Choy, Kwong Wai; Liu, David T.L.; Chan, Wai Man; Chan, Yiu Man; Fung, Nicholas S.K.; Fan, Bao Jian; Baum, Larry; Chan, Juliana C.N.; Lam, Dennis S.C.

2008-01-01

Purpose We tested the hypothesis that genetic variants in vasoactive and angiogenic factors regulating the retina vasculature contribute to the development of diabetic retinopathy (DR). Methods A case-control study was performed to study the genetic association between DR and polymorphic variants of EDN1 (Lys198Asn), LTA (IVS1–80C>A, IVS1–206G>C, IVS1–252A>G), eNOS (Glu298Asp), and ITGA2 (BgI II) in a Chinese population with type 2 diabetes mellitus. A well defined population with type 2 diabetes, consisting of 127 controls and 216 DR patients, was recruited. Results A higher frequency of the Asn/Asn genotype of EDN1 was found in individuals with at least 10 years of diabetes and no retinopathy (controls) compared with DR patients with any duration of diabetes (DR: 2.3%; control: 11.0%; p=0.0002). The Asn allele was also more frequent in controls than DR patients (DR: 16.4%; control: 29.5%; p=0.007). Multiple logistic regression analysis showed that the Asn/Asn genotype was the factor most significantly associated with reduced risk of DR (odds ratio=0.19; 95% CI: 0.07-0.53; p=0.002) and with late onset of diabetes (Asn/Asn: 59 years; Lys/Lys + Lys/Asn: 53 years; p=0.02). Moreover, the Lys/Lys genotype was more common among patients with nonproliferative (75.7%) than proliferative DR (56.9%; p=0.008). The distributions of Lys198Asn alleles in hypertension did not differ from normotensive subjects. No associations between DR and polymorphisms of LTA, eNOS, or ITGA2 were detected, and there were no detectable gene-gene or gene-environmental interactions among the polymorphisms. Conclusions The Asn/Asn genotype of EDN1 was associated with a reduced risk of DR and with delayed onset of type 2 diabetes. PMID:18806884

Growing without a mother results in poorer sexual behaviour in adult rams.

PubMed

Damián, J P; Beracochea, F; Machado, S; Hötzel, M J; Banchero, G; Ungerfeld, R

2018-01-01

The aim of this study was to determine if the absence of the mother during rearing has long-term effects on sexual behaviour and physiological reproductive parameters of adult rams. Two groups of rams were: (1) artificially reared, separated from their dams 24 to 36 h after birth (Week 0) and fed using sheep milk until 10 weeks of age (group AR, n=14); and (2) reared by their dams until 10 weeks of age (group DR, n=13). Sexual behaviour (tests of 20 min) and physiological reproductive parameters were analysed separately for the non-breeding (Weeks 42 to 64) and the breeding (Weeks 66 to 90) seasons. Body weight, scrotal circumference, gonado-somatic index, testosterone concentrations or sperm parameters were similar in both rearing conditions (AR v. DR) in both seasons. During the non-breeding season AR rams displayed fewer ano-genital sniffings (AR: 4.2±0.4 v. DR: 5.3±0.4, P=0.04) and matings (AR: 1.2±0.2 v. DR: 1.8±0.2, P=0.002) than DR rams. During the breeding season AR rams displayed fewer ano-genital sniffings (AR: 4.3±0.5 v. DR: 5.7±0.5, P=0.005), flehmen (AR: 0.7±0.2 v. DR: 1.1±0.2, P=0.03), mount attempts (AR: 1.4±0.2 v. DR: 2.1±0.2, P=0.04), and tended to mount less frequently (AR: 6.6±0.9 v. DR: 8.8±0.9, P=0.08) than DR rams. In conclusion, the absence of the mother during the rearing period negatively affected display of sexual behaviour towards oestrous ewes during a rams adult life in both breeding and non-breeding seasons. However, it did not affect testis size, testosterone secretion or sperm variables.

Gaia DR2 documentation

NASA Astrophysics Data System (ADS)

van Leeuwen, F.; de Bruijne, J. H. J.; Arenou, F.; Bakker, J.; Blomme, R.; Busso, G.; Cacciari, C.; Castañeda, J.; Cellino, A.; Clotet, M.; Comoretto, G.; Eyer, L.; González-Núñez, J.; Guy, L.; Hambly, N.; Hobbs, D.; van Leeuwen, M.; Luri, X.; Manteiga, M.; Pourbaix, D.; Roegiers, T.; Salgado, J.; Sartoretti, P.; Tanga, P.; Ulla, A.; Utrilla Molina, E.; Abreu, A.; Altmann, M.; Andrae, R.; Antoja, T.; Audard, M.; Babusiaux, C.; Bailer-Jones, C. A. L.; Barache, C.; Bastian, U.; Beck, M.; Berthier, J.; Bianchi, L.; Biermann, M.; Bombrun, A.; Bossini, D.; Breddels, M.; Brown, A. G. A.; Busonero, D.; Butkevich, A.; Cantat-Gaudin, T.; Carrasco, J. M.; Cheek, N.; Clementini, G.; Creevey, O.; Crowley, C.; David, M.; Davidson, M.; De Angeli, F.; De Ridder, J.; Delbò, M.; Dell'Oro, A.; Diakité, S.; Distefano, E.; Drimmel, R.; Durán, J.; Evans, D. W.; Fabricius, C.; Fabrizio, M.; Fernández-Hernández, J.; Findeisen, K.; Fleitas, J.; Fouesneau, M.; Galluccio, L.; Gracia-Abril, G.; Guerra, R.; Gutiérrez-Sánchez, R.; Helmi, A.; Hernandez, J.; Holl, B.; Hutton, A.; Jean-Antoine-Piccolo, A.; Jevardat de Fombelle, G.; Joliet, E.; Jordi, C.; Juhász, Á.; Klioner, S.; Löffler, W.; Lammers, U.; Lanzafame, A.; Lebzelter, T.; Leclerc, N.; Lecoeur-Taïbi, I.; Lindegren, L.; Marinoni, S.; Marrese, P. M.; Mary, N.; Massari, D.; Messineo, R.; Michalik, D.; Mignard, F.; Molinaro, R.; Molnár, L.; Montegriffo, P.; Mora, A.; Mowlavi, N.; Muinonen, K.; Muraveva, T.; Nienartowicz, K.; Ordenovic, C.; Pancino, E.; Panem, C.; Pauwels, T.; Petit, J.; Plachy, E.; Portell, J.; Racero, E.; Regibo, S.; Reylé, C.; Rimoldini, L.; Ripepi, V.; Riva, A.; Robichon, N.; Robin, A.; Roelens, M.; Romero-Gómez, M.; Sarro, L.; Seabroke, G.; Segovia, J. C.; Siddiqui, H.; Smart, R.; Smith, K.; Sordo, R.; Soria, S.; Spoto, F.; Stephenson, C.; Turon, C.; Vallenari, A.; Veljanoski, J.; Voutsinas, S.

2018-04-01

The second Gaia data release, Gaia DR2, encompasses astrometry, photometry, radial velocities, astrophysical parameters (stellar effective temperature, extinction, reddening, radius, and luminosity), and variability information plus astrometry and photometry for a sample of pre-selected bodies in the solar system. The data collected during the first 22 months of the nominal, five-year mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC), resulting into this second data release. A summary of the release properties is provided in Gaia Collaboration et al. (2018b). The overall scientific validation of the data is described in Arenou et al. (2018). Background information on the mission and the spacecraft can be found in Gaia Collaboration et al. (2016), with a more detailed presentation of the Radial Velocity Spectrometer (RVS) in Cropper et al. (2018). In addition, Gaia DR2 is accompanied by various, dedicated papers that describe the processing and validation of the various data products. Four more Gaia Collaboration papers present a glimpse of the scientific richness of the data. In addition to this set of refereed publications, this documentation provides a detailed, complete overview of the processing and validation of the Gaia DR2 data. Gaia data, from both Gaia DR1 and Gaia DR2, can be retrieved from the Gaia archive, which is accessible from https://archives.esac.esa.int/gaia. The archive also provides various tutorials on data access and data queries plus an integrated data model (i.e., description of the various fields in the data tables). In addition, Luri et al. (2018) provide concrete advice on how to deal with Gaia astrometry, with recommendations on how best to estimate distances from parallaxes. The Gaia archive features an enhanced visualisation service which can be used for quick initial explorations of the entire Gaia DR2 data set. Pre-computed cross matches between Gaia DR2 and a selected set of large surveys are provided. Gaia DR2 represents a major advance with respect to Gaia DR1 in terms of survey completeness, precision and accuracy, and the richness of the published data. Nevertheless, Gaia DR2 is still an early release based on a limited amount of input data, simplifications in the data processing, and imperfect calibrations. Many limitations hence exist which the user of Gaia DR2 should be aware of; they are described in Gaia Collaboration et al. (2018b).

Understanding Gulf War Illness: An Integrative Modeling Approach

DTIC Science & Technology

2015-10-01

ELEMENT NUMBER 6. AUTHOR(S) Mariana Morris, PhD, Nancy Klimas, MD, Gordon Broderick , PhD, James O’Callaghan, 5d. PROJECT NUMBER PhD and James...12, 2015, Dr. Broderick submitted 1st detailed report in follow up of Fort Detrick EAB meeting (September 2014). (Task 1; Subtask 2)  On March 4, 2015...Dr, Broderick submitted a 2nd interim report to address additional questions asked by Dr. Reifman on March 2, 2015. (Task 1; Subtask 2)  Dr

Systems 2020

DTIC Science & Technology

2012-03-22

USC Team Members: SERC Research Council Dr. Abhi Deshmukh , Purdue Dr. Michael Griffin. U. Alabama-Huntsville Dr. Barry Horowitz, U. Virginia Dr...Areas ................................................. 34 3.2.1 Affordability, Agility, and Resilience (Barry Boehm and Abhi Deshmukh , Leads...statement was reinterpreted to involve the SERC Research Council (Drs. Deshmukh , Griffin, Horowitz, Rouse, and Wade, with Dr. Boehm as chair) in defining

Postoperative imaging of orthopaedic hardware in the hand and wrist: is there an added value for tomosynthesis?

PubMed

De Silvestro, A; Martini, K; Becker, A S; Kim-Nguyen, T D L; Guggenberger, R; Calcagni, M; Frauenfelder, T

2018-02-01

To prospectively investigate digital tomosynthesis (DTS) as an alternative to digital radiography (DR) for postoperative imaging of orthopaedic hardware after trauma or arthrodesis in the hand and wrist. Thirty-six consecutive patients (12 female, median age 36 years, range 19-86 years) were included in this institutional review board approved clinical trial. Imaging was performed with DTS in dorso-palmar projection and DR was performed in dorso-palmar, lateral, and oblique views. Images were evaluated by two independent radiologists for qualitative and diagnosis-related imaging parameters using a four-point Likert scale (1=excellent, 4not diagnostic) and nominal scale. Interobserver agreement between the two readers was assessed with Cohen's kappa (k). Differences between DTS and CR were tested with Wilcoxon's signed-rank test. A p-value <0.05 was considered statistically significant. Regarding image quality, interobserver agreement was higher for DTS compared to DR, especially for fracture-related parameters (delineation osteosynthesis material [OSM]: K DTS 0.96 versus K DR 0.45; delineation fracture margins: K DTS 0.78 versus K DR 0.35). Delineation of fracture margins and delineation of adjacent joint spaces scored significant better for DTS compared to DR (delineation fracture margins: DTS1.54, DR2.28, p0.001; delineation adjacent joint spaces: DTS1.31, DR2.24, p0.001). Regarding diagnosis-related findings, interobserver agreement was almost equal. DTS showed a significant higher sharpness of fracture margins (DTS1.94, DR2.33, p0.04). Mean dose area product (DAP) for DTS was significant higher compared to DR (mean DR0.219 Gy·cm 2 , mean DTS0.903 Gy·cm 2 , p0.001). Fracture healing is more visible and interobserver agreement is higher for DTS compared to DR in the postoperative assessment of orthopaedic hardware in the hand and wrist. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Lower Hemoglobin Concentration Is Associated with Retinal Ischemia and the Severity of Diabetic Retinopathy in Type 2 Diabetes

PubMed Central

Traveset, Alicia; Rubinat, Esther; Ortega, Emilio; Alcubierre, Nuria; Vazquez, Beatriz; Hernández, Marta; Jurjo, Carmen; Espinet, Ramon; Ezpeleta, Juan Antonio; Mauricio, Didac

2016-01-01

Aims. To assess the association of blood oxygen-transport capacity variables with the prevalence of diabetic retinopathy (DR), retinal ischemia, and macular oedema in patients with type 2 diabetes mellitus (T2DM). Methods. Cross-sectional, case-control study (N = 312) with T2DM: 153 individuals with DR and 159 individuals with no DR. Participants were classified according to the severity of DR and the presence of retinal ischemia or macular oedema. Hematological variables were collected by standardized methods. Three logistic models were adjusted to ascertain the association between hematologic variables with the severity of DR and the presence of retinal ischemia or macular oedema. Results. Individuals with severe DR showed significantly lower hemoglobin, hematocrit, and erythrocyte levels compared with those with mild disease and in individuals with retinal ischemia and macular oedema compared with those without these disorders. Hemoglobin was the only factor that showed a significant inverse association with the severity of DR [beta-coefficient = −0.52, P value = 0.003] and retinal ischemia [beta-coefficient = −0.49, P value = 0.001]. Lower erythrocyte level showed a marginally significant association with macular oedema [beta-coefficient = −0.86, P value = 0.055]. Conclusions. In patients with DR, low blood oxygen-transport capacity was associated with more severe DR and the presence of retinal ischemia. Low hemoglobin levels may have a key role in the development and progression of DR. PMID:27200379

Lower Hemoglobin Concentration Is Associated with Retinal Ischemia and the Severity of Diabetic Retinopathy in Type 2 Diabetes.

PubMed

Traveset, Alicia; Rubinat, Esther; Ortega, Emilio; Alcubierre, Nuria; Vazquez, Beatriz; Hernández, Marta; Jurjo, Carmen; Espinet, Ramon; Ezpeleta, Juan Antonio; Mauricio, Didac

2016-01-01

Aims. To assess the association of blood oxygen-transport capacity variables with the prevalence of diabetic retinopathy (DR), retinal ischemia, and macular oedema in patients with type 2 diabetes mellitus (T2DM). Methods. Cross-sectional, case-control study (N = 312) with T2DM: 153 individuals with DR and 159 individuals with no DR. Participants were classified according to the severity of DR and the presence of retinal ischemia or macular oedema. Hematological variables were collected by standardized methods. Three logistic models were adjusted to ascertain the association between hematologic variables with the severity of DR and the presence of retinal ischemia or macular oedema. Results. Individuals with severe DR showed significantly lower hemoglobin, hematocrit, and erythrocyte levels compared with those with mild disease and in individuals with retinal ischemia and macular oedema compared with those without these disorders. Hemoglobin was the only factor that showed a significant inverse association with the severity of DR [beta-coefficient = -0.52, P value = 0.003] and retinal ischemia [beta-coefficient = -0.49, P value = 0.001]. Lower erythrocyte level showed a marginally significant association with macular oedema [beta-coefficient = -0.86, P value = 0.055]. Conclusions. In patients with DR, low blood oxygen-transport capacity was associated with more severe DR and the presence of retinal ischemia. Low hemoglobin levels may have a key role in the development and progression of DR.

ORAC-DR -- SCUBA-2 Pipeline Data Reduction

NASA Astrophysics Data System (ADS)

Gibb, Andrew G.; Jenness, Tim

The ORAC-DR data reduction pipeline is designed to reduce data from many different instruments. This document describes how to use ORAC-DR to process data taken with the SCUBA-2 instrument on the James Clerk Maxwell Telescope.

Association of ICAM-1 and HMGA1 Gene Variants with Retinopathy in Type 2 Diabetes Mellitus Among Chinese Individuals.

PubMed

Lv, Zhiping; Li, Ying; Wu, Yongzhong; Qu, Yi

2016-08-01

To evaluate the association of intercellular cell-adhesion molecule 1 (ICAM-1) and high-mobility group A1 (HMGA1) gene variants with diabetic retinopathy (DR) in a Chinese type 2 diabetes mellitus (T2DM) cohort. A total of 792 patients with T2DM were enrolled and categorized into two groups: (1) the DR group consisted of 448 patients, which was further subclassified into the proliferative DR (PDR) group with 220 patients and the nonproliferative DR (NPDR) group with 228 patients; (2) the diabetes without retinopathy (DNR) group comprised 344 patients who had no signs of DR. The single-nucleotide polymorphism (SNP) rs5498 in ICAM-1 gene and IVS5-13insC variant in HMGA1 gene were genotyped. No evident association was found in the allele frequencies between SNP rs5498 in ICAM-1 gene and DR patients; the combined p values for the additive, dominant, and recessive models in genotype were greater than 0.05. No significant association was identified between the IVS5-13insC variant in HMGA1 gene and DR individuals. Our results revealed that SNP rs5498 in ICAM-1 gene and IVS5-13insC variant in HMGA1 gene were not associated with the susceptibility of DR in the Chinese T2DM cohort.

Gaia DR2 documentation Chapter 8: Astrophysical Parameters

NASA Astrophysics Data System (ADS)

Manteiga, M.; Andrae, R.; Fouesneau, M.; Creevey, O.; Ordenovic, C.; Mary, N.; Jean-Antoine-Piccolo, A.; Bailer-Jones, C. A. L.

2018-04-01

This chapter of the Gaia DR2 documentation describes Apsis, the Astrophysical Parameters Inference System used for processing Gaia DR2 data. Beyond this documentation, a complete description of the processing and the results, as well as additional validations, have been published in Andrae et al. (2018).

Elevated serum fetuin-A levels are associated with grades of retinopathy in type 2 diabetic patients.

PubMed

Yilmaz, Ahu; Yilmaz, Tolga; Gunay, Murat

2017-10-25

Fetuin-A is a physiological inhibitor of insulin receptor tyrosine kinase and thus associated with insulin resistance, metabolic syndrome, and an increased risk for type 2 diabetes mellitus (T2DM). This study aims to investigate the possible relation between the serum fetuin-A levels and the stages of diabetic retinopathy (DR) in patients with T2DM. This prospective study included 82 patients with T2DM and 19 age- and gender-matched healthy controls (HCs) (group 1). Diabetic patients were subclassified into three groups according to ocular findings: without DR (group 2; n = 26); non-proliferative DR (group 3; n = 29), and proliferative DR (group 4; n = 27). Serum fetuin-A levels were determined by a spectrophotometric technique using an immulite chemiluminescent immunometric assay. The data were analyzed using a Mann-Whitney U test, and the results were expressed as mean ± standard deviation. Mean fetuin-A values were 256.4 ± 21.3 μg/ml in group 1, 263.5 ± 24.2 μg/ml in group 2, 282.2 ± 31.1 μg/ml in group 3, and 296.3 ± 26.2 μg/ml in group 4. Group 2 had higher mean fetuin-A level compared with group 1, but the difference was not statistically significant (p > 0.05). Serum fetuin-A levels were significantly higher in groups 3 and 4 compared with HCs (both p < 0.05). Compared with group 2, both DR groups had higher fetuin-A levels with a significant difference (both p < 0.05); and patients with proliferative DR had significantly higher serum fetuin-A levels compared with non-proliferative DR (p < 0.05). The mean serum fetuin-A levels increased with the stage of DR, and the highest levels were found in patients with proliferative DR. Our findings suggest an association between fetuin-A levels and DR stage. In diabetic patients, the risk of retinopathy development increases with higher fetuin-A values. Fetuin-A may play an important role in the pathophysiology and progression of DR.

Dietary restriction involves NAD⁺ -dependent mechanisms and a shift toward oxidative metabolism.

PubMed

Moroz, Natalie; Carmona, Juan J; Anderson, Edward; Hart, Anne C; Sinclair, David A; Blackwell, T Keith

2014-12-01

Interventions that slow aging and prevent chronic disease may come from an understanding of how dietary restriction (DR) increases lifespan. Mechanisms proposed to mediate DR longevity include reduced mTOR signaling, activation of the NAD⁺ -dependent deacylases known as sirtuins, and increases in NAD⁺ that derive from higher levels of respiration. Here, we explored these hypotheses in Caenorhabditis elegans using a new liquid feeding protocol. DR lifespan extension depended upon a group of regulators that are involved in stress responses and mTOR signaling, and have been implicated in DR by some other regimens [DAF-16 (FOXO), SKN-1 (Nrf1/2/3), PHA-4 (FOXA), AAK-2 (AMPK)]. Complete DR lifespan extension required the sirtuin SIR-2.1 (SIRT1), the involvement of which in DR has been debated. The nicotinamidase PNC-1, a key NAD⁺ salvage pathway component, was largely required for DR to increase lifespan but not two healthspan indicators: movement and stress resistance. Independently of pnc-1, DR increased the proportion of respiration that is coupled to ATP production but, surprisingly, reduced overall oxygen consumption. We conclude that stress response and NAD⁺ -dependent mechanisms are each critical for DR lifespan extension, although some healthspan benefits do not require NAD⁺ salvage. Under DR conditions, NAD⁺ -dependent processes may be supported by a DR-induced shift toward oxidative metabolism rather than an increase in total respiration. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Retinopathy in non diabetics, diabetic retinopathy and oxidative stress: a new phenotype in Central Africa?

PubMed

Longo-Mbenza, Benjamin; Mvitu Muaka, Moise; Masamba, Wayiza; Muizila Kini, Lucien; Longo Phemba, Igor; Kibokela Ndembe, Dalida; Tulomba Mona, Doris

2014-01-01

To evaluate the rates of retinopathy without diabetes and diabetic retinopathy (DR), associated with some markers of oxidative stress, antioxidants and cardiometabolic risk factors. We determined the prevalence of DR in 150 type 2 diabetes mellitus (T2DM) patients, that of retinopathy in 50 non diabetics, the levels of body mass index (BMI), waist circumference (WC), blood pressure, lipids, 8-isoprostane, 8-hydroxydeoxyguanosine (8-OHdG), gamma-glutamyl transferase GT (GGT), oxidized low-density lipoprotein (OxLDL), thiobarbituric acid reacting substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), uric acid, creatinine, albumin, total antioxidant status (TAOS), zinc, selenium, magnesium, vitamin C, vitamin D, vitamin E, glucose, apolipoprotein B (ApoB). The prevalences of DR at 53y and Rtp at 62y were 44% (n=66) and 10% (n=5), respectively. The highest levels of 8-isoprostane, 8-OHdG, TBARS, SOD, and OxLDL were in DR. The lowest levels of vitamin D, vitamin C, TAOS, and vitamin E were in DR. In the case-control study discriminant analysis, the levels of vitamin C, vitamin D, ApoB, 8-OHdG, creatinine, Zn, vitamin E, and WC distinguished significantly non-diabetics without DR (controls), T2DM patients without DR and T2DM patients with DR. Anticipation of DR onset is significantly associated with the exageration of oxidative stress biomarkers or decrease of antioxidants in African type 2 diabetics. Prevention of oxidative stress and abdominal obesity is needed. Supplementation in vitamin C, D, and E should be recommended as complement therapies of T2DM.

Retinopathy in non diabetics, diabetic retinopathy and oxidative stress: a new phenotype in Central Africa?

PubMed Central

Longo-Mbenza, Benjamin; Mvitu Muaka, Moise; Masamba, Wayiza; Muizila Kini, Lucien; Longo Phemba, Igor; Kibokela Ndembe, Dalida; Tulomba Mona, Doris

2014-01-01

AIM To evaluate the rates of retinopathy without diabetes and diabetic retinopathy (DR), associated with some markers of oxidative stress, antioxidants and cardiometabolic risk factors. METHODS We determined the prevalence of DR in 150 type 2 diabetes mellitus (T2DM) patients, that of retinopathy in 50 non diabetics, the levels of body mass index (BMI), waist circumference (WC), blood pressure, lipids, 8-isoprostane, 8-hydroxydeoxyguanosine (8-OHdG), gamma-glutamyl transferase GT (GGT), oxidized low-density lipoprotein (OxLDL), thiobarbituric acid reacting substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), uric acid, creatinine, albumin, total antioxidant status (TAOS), zinc, selenium, magnesium, vitamin C, vitamin D, vitamin E, glucose, apolipoprotein B (ApoB). RESULTS The prevalences of DR at 53y and Rtp at 62y were 44% (n=66) and 10% (n=5), respectively. The highest levels of 8-isoprostane, 8-OHdG, TBARS, SOD, and OxLDL were in DR. The lowest levels of vitamin D, vitamin C, TAOS, and vitamin E were in DR. In the case-control study discriminant analysis, the levels of vitamin C, vitamin D, ApoB, 8-OHdG, creatinine, Zn, vitamin E, and WC distinguished significantly non-diabetics without DR (controls), T2DM patients without DR and T2DM patients with DR. CONCLUSION Anticipation of DR onset is significantly associated with the exageration of oxidative stress biomarkers or decrease of antioxidants in African type 2 diabetics. Prevention of oxidative stress and abdominal obesity is needed. Supplementation in vitamin C, D, and E should be recommended as complement therapies of T2DM. PMID:24790873

Radiation Awareness for Endovascular Abdominal Aortic Aneurysm Repair in the Hybrid Operating Room. An Instant Patient Risk Chart for Daily Practice.

PubMed

de Ruiter, Quirina M; Gijsberts, Crystel M; Hazenberg, Constantijn E; Moll, Frans L; van Herwaarden, Joost A

2017-06-01

To determine which patient and C-arm characteristics are the strongest predictors of intraoperative patient radiation dose rates (DRs) during endovascular aneurysm repair (EVAR) procedures and create a patient risk chart. A retrospective analysis was performed of 74 EVAR procedures, including 16,889 X-ray runs using fixed C-arm imaging equipment. Four multivariate log-linear mixed models (with patient as a random effect) were constructed. Mean air kerma DR (DR AK , mGy/s) and the mean dose area product DR (DR DAP , mGycm 2 /s) were the outcome variables utilized for fluoroscopy as differentiated from digital subtraction angiography (DSA). These models were used to predict the maximum radiation duration allowed before a 2-Gy skin threshold (for DR AK ) or a 500-Gycm 2 threshold (for DR DAP ) was reached. The strongest predictor of DR AK and DR DAP for fluoroscopy imaging was the radiation protocol, with an increase of 200% when changing from "low" to "medium" and 410% from "low" to "normal." The strongest predictors of DR AK and DR DAP for DSA were C-arm angulation, with an increase of 47% per 30° of angulation, and body mass index (BMI), with an increase of 58% for every 5-point increase in BMI. Based on these models, a patient with a BMI of 30 kg/m 2 , combined with 45° of rotation and a field size of 800 cm 2 in the medium fluoroscopy protocol has a predicted DR AK of 0.39 mGy/s (or 85.5 minutes until the 2-Gy skin threshold is reached). While using comparable settings but switching the acquisition to a DSA with a "2 frames per second" protocol, the predicted DR AK will be 6.6 mGy/s (or 5.0 minutes until the 2-Gy threshold is reached). X-ray radiation DRs are constantly fluctuating during and between patients based on BMI, the protocols, C-arm position, and the image acquisitions that are used. An instant patient risk chart visualizes these radiation dose fluctuations and provides an overview of the expected duration of X-ray radiation, which can be used to predict when follow-up dose thresholds are reached during abdominal endovascular procedures.

Accident Source Terms for Pressurized Water Reactors with High-Burnup Cores Calculated using MELCOR 1.8.5.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gauntt, Randall O.; Goldmann, Andrew; Kalinich, Donald A.

2016-12-01

In this study, risk-significant pressurized-water reactor severe accident sequences are examined using MELCOR 1.8.5 to explore the range of fission product releases to the reactor containment building. Advances in the understanding of fission product release and transport behavior and severe accident progression are used to render best estimate analyses of selected accident sequences. Particular emphasis is placed on estimating the effects of high fuel burnup in contrast with low burnup on fission product releases to the containment. Supporting this emphasis, recent data available on fission product release from high-burnup (HBU) fuel from the French VERCOR project are used in thismore » study. The results of these analyses are treated as samples from a population of accident sequences in order to employ approximate order statistics characterization of the results. These trends and tendencies are then compared to the NUREG-1465 alternative source term prescription used today for regulatory applications. In general, greater differences are observed between the state-of-the-art calculations for either HBU or low-burnup (LBU) fuel and the NUREG-1465 containment release fractions than exist between HBU and LBU release fractions. Current analyses suggest that retention of fission products within the vessel and the reactor coolant system (RCS) are greater than contemplated in the NUREG-1465 prescription, and that, overall, release fractions to the containment are therefore lower across the board in the present analyses than suggested in NUREG-1465. The decreased volatility of Cs 2 MoO 4 compared to CsI or CsOH increases the predicted RCS retention of cesium, and as a result, cesium and iodine do not follow identical behaviors with respect to distribution among vessel, RCS, and containment. With respect to the regulatory alternative source term, greater differences are observed between the NUREG-1465 prescription and both HBU and LBU predictions than exist between HBU and LBU analyses. Additionally, current analyses suggest that the NUREG-1465 release fractions are conservative by about a factor of 2 in terms of release fractions and that release durations for in-vessel and late in-vessel release periods are in fact longer than the NUREG-1465 durations. It is currently planned that a subsequent report will further characterize these results using more refined statistical methods, permitting a more precise reformulation of the NUREG-1465 alternative source term for both LBU and HBU fuels, with the most important finding being that the NUREG-1465 formula appears to embody significant conservatism compared to current best-estimate analyses. ACKNOWLEDGEMENTS This work was supported by the United States Nuclear Regulatory Commission, Office of Nuclear Regulatory Research. The authors would like to thank Dr. Ian Gauld and Dr. Germina Ilas, of Oak Ridge National Laboratory, for their contributions to this work. In addition to development of core fission product inventory and decay heat information for use in MELCOR models, their insights related to fuel management practices and resulting effects on spatial distribution of fission products in the core was instrumental in completion of our work.« less

Increased Burden of Cerebral Small Vessel Disease in Patients With Type 2 Diabetes and Retinopathy.

PubMed

Sanahuja, Jordi; Alonso, Núria; Diez, Javier; Ortega, Emilio; Rubinat, Esther; Traveset, Alícia; Alcubierre, Núria; Betriu, Àngels; Castelblanco, Esmeralda; Hernández, Marta; Purroy, Francisco; Arcidiacono, Maria Vittoria; Jurjo, Carmen; Fernández, Elvira; Puig-Domingo, Manuel; Groop, Per-Henrik; Mauricio, Dídac

2016-09-01

We sought to examine the presence and severity of brain small vessel disease (SVD) in patients with type 2 diabetes and diabetic retinopathy (DR) compared with those without DR. We evaluated 312 patients with type 2 diabetes without previous cardiovascular disease (men 51%; mean age 57 years; age range 40-75 years); 153 patients (49%) had DR. MRI was performed to evaluate the presence and severity (age-related white matter changes scale) of white matter lesions (WMLs) and lacunes, and transcranial Doppler ultrasound was used to measure the Gosling pulsatility index (PI) of the middle cerebral artery (MCA). The prevalence of lesions of cerebral SVD (WML and/or lacunes) was higher in patients with DR (40.2% vs. 30.1% without DR, P = 0.04). Age (P < 0.01) and systolic blood pressure (P = 0.02) were associated with the presence of SVD. The severity of SVD was associated with age and the presence of DR (P < 0.01 and P = 0.01, respectively). Patients with DR showed a higher MCA PI compared with those without DR (P < 0.01). Age, systolic and diastolic blood pressure, and retinopathy and its severity were associated with an increased MCA PI (P < 0.01 for all variables). A positive correlation was found between MCA PI values and the presence and severity of SVD (P < 0.01 for both variables). Patients with type 2 diabetes who have DR have an increased burden of cerebral SVD compared with those without DR. Our findings suggest that the brain is a target organ for microangiopathy, similar to other classic target organs, like the retina. © 2016 by the American Diabetes Association.

C-reactive protein and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus.

PubMed

Yang, Xiu-Fen; Deng, Yu; Gu, Hong; Lim, Apiradee; Snellingen, Torkel; Liu, Xi-Pu; Wang, Ning-Li; Domalpally, Amitha; Danis, Ronald; Liu, Ning-Pu

2016-01-01

To investigate the relationship between C-reactive protein (CRP) and diabetic retinopathy (DR) in a cohort of Chinese patients with type 2 diabetes mellitus (T2DM). Community-based observational cohort study. There were 1131 participants recruited from November 2009 to September 2011 in Desheng community in urban Beijing. Patients diagnosed T2DM were recruited and underwent a standardized evaluation consisting of a questionnaire, ocular and anthropometric examinations and laboratory investigation. The presence and severity of DR were assessed by seven fields 30° color fundus photographs. Subjects were then classified into groups with no DR, any DR, or vision-threatening DR. CRP was analyzed from serum of study subjects. A total of 1007 patients with T2DM were included for analysis, including 408 (40.5%) men and 599 (59.5%) women. The median CRP level was 1.5 mg/L for women and 1.1 mg/L for men (P=0.004, OR 0.37, 95% CI 0.18-0.74). After adjusting for possible covariates, higher levels of CRP were associated with lower prevalence of any DR (P=0.02, OR 0.55, 95% CI 0.35-0.89), but not associated with vision-threatening DR (P=0.62, OR 0.78, 95% CI 0.28-2.14). After stratification by sex, the inverse association between CRP and DR was found to be statistically significant in men (P=0.006, OR 0.35, 95% CI 0.16-0.73), but not in women (P=0.58, OR 0.88, 95% CI 0.29-1.16). The data drawn from a Chinese population with T2DM suggest that increasing CRP levels may be inversely associated with development of DR.

Incidence and Progression of Diabetic Retinopathy in Urban India: Sankara Nethralaya-Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SN-DREAMS II), Report 1.

PubMed

Raman, Rajiv; Ganesan, Suganeswari; Pal, Swakshyar Saumya; Gella, Laxmi; Kulothungan, Vaitheeswaran; Sharma, Tarun

2017-10-01

To evaluate the 4-year incidence and progression of and risk factors for diabetic retinopathy (DR) in an Indian population. From a cross-sectional study of 1425 subjects with diabetes, 911 (63.9%) returned for 4-year follow-up. After excluding 21 with ungradable retinal images, data from 890 subjects were analyzed. Participants underwent examinations based on a standard protocol, which included grading of retinal photographs. The incidences of DR, diabetic macular edema (DME), and sight-threatening diabetic retinopathy (STDR) were 9.2%, 2.6%, and 5.0%, respectively. In subjects with DR at baseline, the incidence of DME and STDR had increased (11.5% and 22.7%, respectively). 1-step and 2-step progressions of DR were seen in 30.2% and 12.6% of participants, respectively, and 1-step and 2-step regressions were seen in 12.0% and 1.8%, respectively. Incident DR, DME, and STDR were associated with higher systolic blood pressure (odds ratio, OR, 1.21, 2.11 and 1.72, respectively, for every 10 mmHg increase). Incident DR and DME were associated with increasing duration of diabetes (OR 2.29 and 4.77, respectively, for every 10-year increase) and presence of anemia (OR 1.96 and 10.14, respectively). Incident DR was also associated with higher hemoglobin A1c (OR 1.16 for every 1% increase). Variables associated with 1-step progression were every 10 mg/dL increase in serum total cholesterol (OR 15.65) as a risk factor, and 10 mg/dL increase in serum triglyceride (OR 0.52) as a protective factor. The incidences of STDR and DME were higher in people with pre-existing DR than in those without DR at baseline.

Characterization of the Interactions between Calmodulin and Death Receptor 5 in Triple-negative and Estrogen Receptor-positive Breast Cancer Cells

PubMed Central

Fancy, Romone M.; Wang, Lingyun; Zeng, Qinghua; Wang, Hong; Zhou, Tong; Buchsbaum, Donald J.; Song, Yuhua

2016-01-01

Activation of death receptor-5 (DR5) leads to the formation of death inducing signaling complex (DISC) for apoptotic signaling. Targeting DR5 to induce breast cancer apoptosis is a promising strategy to circumvent drug resistance and present a target for breast cancer treatment. Calmodulin (CaM) has been shown to regulate DR5-mediated apoptotic signaling, however, its mechanism remains unknown. In this study, we characterized CaM and DR5 interactions in breast cancer cells with integrated experimental and computational approaches. Results show that CaM directly binds to DR5 in a calcium dependent manner in breast cancer cells. The direct interaction of CaM with DR5 is localized at DR5 death domain. We have predicted and verified the CaM-binding site in DR5 being 354WEPLMRKLGL363 that is located at the α2 helix and the loop between α2 helix and α3 helix of DR5 DD. The residues of Trp-354, Arg-359, Glu-355, Leu-363, and Glu-367 in DR5 death domain that are important for DR5 recruitment of FADD and caspase-8 for DISC formation to signal apoptosis also play an important role for CaM-DR5 binding. The changed electrostatic potential distribution in the CaM-binding site in DR5 DD by the point mutations of W354A, E355K, R359A, L363N, or E367K in DR5 DD could directly contribute to the experimentally observed decreased CaM-DR5 binding by the point mutations of the key residues in DR5 DD. Results from this study provide a key step for the further investigation of the role of CaM-DR5 binding in DR5-mediated DISC formation for apoptosis in breast cancer cells. PMID:27129269

Risk factors for diabetic retinopathy in people with Type 2 diabetes: A case-control study in a UK primary care setting.

PubMed

Martín-Merino, Elisa; Fortuny, Joan; Rivero-Ferrer, Elena; Lind, Marcus; Garcia-Rodriguez, Luis Alberto

2016-08-01

To identify risk factors of diabetic retinopathy (DR) among people with Type 2 diabetes mellitus in UK primary care. A case-control study nested in a cohort of incident Type 2 diabetes identified in The Health Improvement Network database from 2000 to 2007. Cases were people with DR (N=7735) and controls were a DR-free sample (N=9395). No age restrictions were applied. Adjusted odds ratios and 95% CIs were estimated. 21% of DR cases were identified during the first semester after Type 2 diabetes diagnosis. After controlling for delay on the Type 2 diabetes diagnosis, the DR risk increased with the duration of diabetes. DR increased with a mean systolic BP ≥150mmHg (1.18; 1.10-1.27), high alcohol consumption (1.34; 1.11-1.61), glycated haemoglobin (≥75 to <86: 1.14; 1.00-1.31; ≥86 to <97mmol/mol: 1.25; 1.07-1.45; ≥97mmol/mol: 1.21; 1.07-1.37), microalbuminuria (1.16; 1.06-1.27), and retinal vein occlusion (2.47; 1.67-3.66). Glaucoma and retinal arterial occlusion showed an OR of 0.71 (0.60-0.84) and 0.63 (0.40-1.01), respectively. HDL ≥1.55mmol/l (0.88; 0.80-0.98), high triglycerides (2.3-5.6mmol/l: 0.90; 0.82-0.99; >5.6mmol/l: 0.85; 0.64-1.13) or smoking (0.89; 0.81-0.97) had a slightly reduced DR risk. Users of hypoglycaemic agents had an increased DR risk. Some DR cases were identified near the diabetes diagnosis date suggesting that a delayed diabetes diagnosis is still common. Glaucoma, retinal arterial occlusion and high HDL levels were inversely associated with DR, while retinal vein occlusion, alcohol and other well-known risk factors were positively associated. Copyright © 2016. Published by Elsevier Ltd.

5. View of middle DR 2 antenna with DR 1 ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. View of middle DR 2 antenna with DR 1 antenna in background. Photograph shows on left side at bottom foundation berm and along right side bottom stanchion concrete foundations at bottom structural steel assembly. - Clear Air Force Station, Ballistic Missile Early Warning System Site II, One mile west of mile marker 293.5 on Parks Highway, 5 miles southwest of Anderson, Anderson, Denali Borough, AK

[Preparation and application of monoclonal antibodies against DR region of Na+-K+-ATPase α1 subunit].

PubMed

Yan, Xiaofei; Wu, Litao; DU, Xiaojuan; Li, Jing; Zhang, Fujun; Han, Yan; Lyu, Shemin; Li, Dongmin

2016-12-01

Objective To prepare monoclonal antibodies against DR region (897DVEDSYGQQWTYEQR911) of Na + -K + -ATPase α1 subunit and identify their properties. Methods BALB/c mice were immunized with DR-keyholelimpet hemocyanin (KLH). Splenocytes from the immunized mice were collected and subsequently fused with SP2/0 mouse myeloma cells. Positive hybridoma clones were obtained after cell fusion and selection. ELISA was used to detect DR antibody titer in the cell supernatants. DR region-specific monoclonal antibodies were analyzed by dot blotting, Western blotting and immunofluorescence assay. Na + -K + -ATPase activity was detected by SensoLyte R FDP Protein Phosphatase Assay Kit and the protective effect of the monoclonal antibody against high glucose-induced cell injury was assessed in H9c2 cells. Results Three hybridoma cell lines which secreted stable DR monoclonal antibody were obtained. The strongest positive cell line, named DRm217, was selected to prepare ascites. Dot blotting, Western blotting and immunofluorescence assay showed that DRm217 recognized specially DR region of Na + -K + -ATPase and bound on H9c2 cell membranes. DRm217 stimulated Na + -K + -ATPase activity and alleviated high glucose-induced H9c2 cells injury. Conclusion The monoclonal antibodies against DR region of Na + -K + -ATPase α1 subunit is prepared.

Failure to initiate early insulin therapy - A risk factor for diabetic retinopathy in insulin users with Type 2 diabetes mellitus: Sankara Nethralaya-Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SN-DREAMS, Report number 35).

PubMed

Gupta, Aditi; Delhiwala, Kushal S; Raman, Rajiv P G; Sharma, Tarun; Srinivasan, Sangeetha; Kulothungan, Vaitheeswaran

2016-06-01

Insulin users have been reported to have a higher incidence of diabetic retinopathy (DR). The aim was to elucidate the factors associated with DR among insulin users, especially association between duration, prior to initiating insulin for Type 2 diabetes mellitus (DM) and developing DR. Retrospective cross-sectional observational study included 1414 subjects having Type 2 DM. Insulin users were defined as subjects using insulin for glycemic control, and insulin nonusers as those either not using any antidiabetic treatment or using diet control or oral medications. The duration before initiating insulin after diagnosis was calculated by subtracting the duration of insulin usage from the duration of DM. DR was clinically graded using Klein's classification. SPSS (version 9.0) was used for statistical analysis. Insulin users had more incidence of DR (52.9% vs. 16.3%, P < 0.0001) and sight threatening DR (19.1% vs. 2.4%, P < 0.0001) in comparison to insulin nonusers. Among insulin users, longer duration of DM (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.00-1.25, P = 0.044) and abdominal obesity (OR 1.15, 95% CI 1.02-1.29, P = 0.021) was associated with DR. The presence of DR was significantly associated with longer duration (≥5 years) prior to initiating insulin therapy, overall (38.0% vs. 62.0%, P = 0.013), and in subjects with suboptimal glycemic control (32.5% vs. 67.5%, P = 0.022). The presence of DR is significantly associated with longer duration of diabetes (>5 years) and sub-optimal glycemic control (glycosylated hemoglobin <7.0%). Among insulin users, abdominal obesity was found to be a significant predictor of DR; DR is associated with longer duration prior to initiating insulin therapy in Type 2 DM subjects with suboptimal glycemic control.

Anterior Diabetic Retinopathy Studied by Ultra-widefield Angiography.

PubMed

Bae, Kunho; Lee, Ju Yeon; Kim, Tae Hyup; Cho, Ga Eun; Ahn, Jeeyun; Kim, Sang Jin; Kim, Jae Hyun; Kang, Se Woong

2016-10-01

To evaluate the prevalence of anterior type diabetic retinopathy (DR) using ultra-widefield fluorescein angiography and to identify the factors associated with anterior type DR incidence. A retrospective case review was used in this study. Patients with non-proliferative diabetic retinopathy (NPDR) underwent examination by ultra-widefield fluorescein angiography, and were classified into anterior, posterior, or diffuse DR groups. Anterior DR was defined if diabetic retinal changes were noted only at the location anterior to the imaginary circle bordered by the Early Treatment Diabetic Retinopathy Study seven-standard fields. Correlations between demographic data, as well as systemic and ocular factors, and the incidence of NPDR types were evaluated. Among the 234 eyes of 234 patients with NPDR, 25 eyes (10.7%) demonstrated anterior DR. Anterior DR was observed in 10 eyes (30.3%) of patients having mild NPDR, three eyes (4.8%) of moderate NPDR patients, and in 12 eyes (7.1%) of severe NPDR patients ( p < 0.001). The incidence of anterior DR positively correlated with lower hemoglobin A1c levels and with greater high-density lipoprotein levels following multiple logistic regression analysis ( p < 0.001). The mean hemoglobin A1c level was 7.03 ± 0.99% in anterior DR, 7.99 ± 1.74% in posterior DR, and 7.94 ± 1.39% in diffuse DR patients ( p = 0.003). The mean high-density lipoprotein level was 51.2 ± 12.5 mg/dL in anterior, 49.7 ± 15.2 mg/dL in posterior, and 45.2 ± 13.1 mg/dL in diffuse DR patients ( p = 0.010). Diabetic retinal changes confined to an anterior location were more frequently noted in earlier stages of NPDR. The incidence of DR sparing posterior retinal involvement was related to favorable blood sugar and lipid profiles.

Comparisons of diabetic retinopathy events associated with glucose-lowering drugs in patients with type 2 diabetes mellitus: A network meta-analysis.

PubMed

Tang, Huilin; Li, Guangyao; Zhao, Ying; Wang, Fei; Gower, Emily W; Shi, Luwen; Wang, Tiansheng

2018-05-01

To assess the comparative effects of glucose-lowering drugs (GLDs) on the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). We systematically searched Cochrane Central Register of Controlled Trials, PUBMED and EMBASE from inception to January 17, 2017 to identify randomized controlled trials (RCTs) that reported DR events among T2DM patients receiving any GLD. Random-effects pairwise and network meta-analyses were performed to calculate odds ratios (ORs) with 95% confidence intervals (CIs). A total of 37 independent RCTs with 1806 DR events among 100 928 patients with T2DM were included. The mean duration of diabetes was 8.7 years and mean baseline HbA1c was 8.2% (SD, 0.5%). Our network meta-analysis found that DPP-4i (OR, 1.20; 95% CI, 0.87-1.65), GLP-1RA (OR, 1.19; 95% CI, 0.94-1.52) and SGLT2 inhibitors (OR, 0.79; 95% CI, 0.49-1.28) were not associated with a higher risk of DR than placebo; however, a significantly increased risk of DR was associated with DPP-4i in the pairwise meta-analysis (OR, 1.27; 95% CI, 1.05-1.53). Sulfonylureas, on the other hand, were associated with a significantly increased risk of DR compared to placebo (OR, 1.67; 95% CI, 1.01-2.76). Current evidence indicates that the association between DPP-4i, GLP-1RA or SGLT2 inhibitors and risk of DR remains uncertain in patients with T2DM. Some evidence suggests that sulfonylureas may be associated with increased risk of DR. However, given that DR events were not systematically assessed, these effects should be explored further in large-scale, well-designed studies. © 2018 John Wiley & Sons Ltd.

Breath ethane as a marker of reactive oxygen species during manipulation of diet and oxygen tension in rats.

PubMed

Risby, T H; Jiang, L; Stoll, S; Ingram, D; Spangler, E; Heim, J; Cutler, R; Roth, G S; Rifkind, J M

1999-02-01

Breath ethane, O2 consumption, and CO2 production were analyzed in 24-mo-old female Fischer 344 rats that had been fed continuously ad libitum (AL) or restricted 30% of AL level (DR) diets since 6 wk of age. Rats were placed in a glass chamber that was first flushed with air, then with a gas mixture containing 12% O2. After equilibration, a sample of the outflow was collected in gas sampling bags for subsequent analyses of ethane and CO2. The O2 and CO2 levels were also directly monitored in the outflow of the chamber. O2 consumption and CO2 production increased for DR rats. Hypoxia decreased O2 consumption and CO2 production for the AL-fed and DR rats. These changes reflect changes in metabolic rate due to diet and PO2. A significant decrease in ethane generation was found in DR rats compared with AL-fed rats. Under normoxic conditions, breath ethane decreased from 2.20 to 1.61 pmol ethane/ml CO2. During hypoxia the levels of ethane generation increased, resulting in a DR-associated decrease in ethane from 2.60 to 1.90 pmol ethane/ml CO2. These results support the hypothesis that DR reduces the level of oxidative stress.

Intake of Gnetum Africanum and Dacryodes Edulis, Imbalance of Oxidant/Antioxidant Status and Prevalence of Diabetic Retinopathy in Central Africans

PubMed Central

Moise, Mvitu-Muaka; Benjamin, Longo-Mbenza; Etienne, Mokondjimobe; Thierry, Gombet; Ndembe Dalida, Kibokela; Doris, Tulomba Mona; Samy, Wayiza Masamba

2012-01-01

Objective To estimate the prevalence of DR and to correlate cardiometabolic, sociodemographic, and oxidant/antioxidant imbalance data to the prevalence of DR. Design This case-control study included type 2 DM (T2 DM) patients with DR (n = 66), T2 DM patients without DR (N = 84), and healthy controls (n = 45) without DR, in Kinshasa town. Diet, albuminemia, serum vitamins, and 8-isoprostane were examined. Results No intake of safou (OR = 2.7 95% CI 1.2–5.8; P = 0.014), low serum albumin <4.5 g/dL (OR-2.9 95% CI 1.4–5.9; P = 0.003), no intake of fumbwa (OR = 2.8 95% CI 1.2–6.5; P = 0.014), high 8-isoprostane (OR = 14.3 95% CI 4.5–46; P<0.0001), DM duration ≥5 years (OR = 3.8 95% CI 1.6–9.1; P = 0.003), and low serum vitamin C (OR = 4.5 95% CI 1.3–15.5; P = 0.016) were identified as the significant independent determinants of DR. Conclusion The important role of oxidant/antioxidant status imbalance and diet is demonstrated in DR. PMID:23226496

Association of serum vitamin D levels and diabetic retinopathy in Asian Indians with type 2 diabetes.

PubMed

Ashinne, Beteal; Rajalakshmi, Ramachandran; Anjana, Ranjit M; Venkat Narayan, K M; Jayashri, Ramamoorthy; Mohan, Viswanathan; Hendrick, Andrew M

2018-05-01

Vitamin D deficiency (VDD) is a condition that has been associated with diabetic retinopathy (DR) in various populations, but has not been studied in Asian Indians. To evaluate the association of serum 25-hydroxyvitamin D (25(OH)D) levels with presence and severity of DR among Asian Indians with type 2 diabetes. We collected information on individuals with type 2 diabetes that received care at a tertiary diabetes centre in India, between 2012 and 2015. Patients were 18 years of age or older, underwent retinal examinations with DR severity grading and had serum 25(OH)D measurements. Serum 25(OH)D levels were lower in patients with retinopathy compared to those without (11.9 ± 2.2 ng/ml vs. 13.7 ± 2.1 ng/ml, p < 0.001). Stratifying patients by DR grade, reduced geometric means of 25(OH)D levels were associated with increased retinopathy severity. After adjusting for six key covariates, VDD was associated with increased rates of proliferative DR (OR 2.05; 95% CI 1.35-3.11; p = 0.001). In Asian Indians with type 2 diabetes, lower serum 25(OH)D was associated with increased severity of DR and the presence of VDD was associated with a two-fold increased risk for proliferative DR. Copyright © 2018 Elsevier B.V. All rights reserved.

Electron-ion continuum-continuum mixing in dissociative recombination

NASA Technical Reports Server (NTRS)

Guberman, Steven L.

1993-01-01

In recent calculations on the dissociative recombination (DR) of the v=1 vibrational level of the ground state of N2(+), N2(+)(v=1) + e(-) yields N + N, we have observed an important continuun-continuum mixing process involving the open channels on both sides of N2(+)(v=1) + e(-) yields N2(+)(v=0) + e(-). In vibrational relaxation by electron impact (immediately above) the magnitude of the cross section depends upon the strength of the interaction between these continua. In DR of the v=1 ion level, these continua can also interact in the entrance channel, and the mixing can have a profound effect upon the DR cross section from v=1, as we illustrate in this paper. In our theoretical calculations of N2(+) DR using multichannel quantum defect theory (MQDT), the reactants and products in the two above equations are described simultaneously. This allows us to calculate vibrational relaxation and excitation cross sections as well as DR cross sections. In order to understand the mixing described above, we first present a brief review of the prior results for DR of the v=0 level of N2(+).

Evaluation of Techniques to Estimate Annual Water Quality Loadings to Reservoirs.

DTIC Science & Technology

1981-02-01

ERVOIRS - . .- . .2 - S. PERFORMING ORG. REPoRT v- k -; ___ 7. AUTHOR(@) S. CONTRACT OR GRANT NUMBER(a) Howard E./ Westerdahl JanelHarris William B...ber 1978 by Dr. H. E. Westerdahl , Mr. W. B. Ford III, Ms. J. Harris, and Dr. C. R. Lee, of the Ecological Effects and Regulatory Criteria Group...general supervision of Dr. R. L. Eley, Chief, ERSD, and Dr. John Harrison, Chief, EL. The report was written by Dr. Westerdahl , Mr. Ford, Ms. Harris, and Dr

Prevalence, Awareness, and Risk Factors of Diabetic Retinopathy among Adults with Known Type 2 Diabetes Mellitus in an Urban Community in China.

PubMed

Pan, Chen-Wei; Wang, Shan; Qian, Deng-Juan; Xu, Cailian; Song, E

2017-06-01

To understand the prevalence, awareness, and risk factors for diabetic retinopathy (DR) among Chinese with known type-2 diabetes mellitus (T2DM) in eastern China communities. A community-based survey including 913 patients with known T2DM was conducted in Suzhou, China. Diabetes was defined as hemoglobin A1c (hbA1c) ≥6.5%, use of diabetic medication or a physician diagnosis of diabetes. Retinal photographs were graded for the presence of DR using the Airlie House classification system. Binary logistic regression models were established to examine the associations of risk factors with DR and vision-threatening diabetic retinopathy (VTDR). The overall prevalence of any DR was 18.0% (95% confidence interval [CI]: 15.5-20.6%) in this population. VTDR affected 4.4% (95% CI: 3.1-5.8%) of the study participants. In multivariate analysis, the presence of DR among T2DM patients was associated with decreased age (odds ratio [OR] = 0.97; p = 0.01; per year increase), longer durations of diabetes (OR = 1.02; per year increase; p = 0.03), higher blood levels of hbA1c (OR = 1.15; per unit increase; p = 0.03). Of the 158 participants with DR, only 12 (8%) had been aware of their condition or had been diagnosed previously as having DR. The prevalence of DR among diabetes patients in eastern China was lower than those in northern China. The awareness of DR was poor, which emphasizes the pressing need for increasing the public awareness of this vision-threatening eye disorder and routine eye screening should be performed among T2DM patients in the communities.

GBT Observations of the Star-Forming Regions DR21 and MonR2 with the new Argus Instrument

NASA Astrophysics Data System (ADS)

Linville, Dylan; Frayer, David; Cunningham, Nichol; Maddalena, Ronald

2018-01-01

We present GBT molecular line observations of DR21 and MonR2 with the new 16 element 75--115 GHz Argus instrument. Both molecular cloud complexes are associated with regions of high-mass star formation. We present the results of our 13CO, C18O, and HCO+ observations. Both MonR2 and DR21 show multiple velocity components, and the data suggest that the core of MonR2 is collapsing, while DR21 contains a region with a strong outflow traced by HCO+.

DR2 blocker thioridazine: A promising drug for ovarian cancer therapy

PubMed Central

Yong, Min; Yu, Tinghe; Tian, Si; Liu, Shuaibin; Xu, Jiao; Hu, Jianguo; Hu, Lina

2017-01-01

Dopamine receptor 2 (DR2) may be a biomarker for various types of cancer. Ovarian cancer cells overexpress DR2; therefore, blocking DR2 may be a novel treatment strategy for ovarian cancer. Thioridazine, a DR2 blocker, has antineoplastic activity in a variety of cancer cells. In view of the requirement for novel therapeutic agents in ovarian cancer, the present study aimed to determine the potential effects of thioridazine in vitro and in vivo. It was revealed that the DR2 blocker thioridazine induced cell death in a dose-dependent manner in ovarian cancer cells. Thioridazine treatment induced apoptosis and autophagy, which may be attributed to an increased level of reactive oxygen species and associated DNA damage. Additionally, the expression of various proteins increased with oxidative stress, including nuclear factor E2-related factor 2, which is a pivotal transcriptional factor involved in cellular responses to oxidative stress. Heme oxygenase 1, NAPDH quinone dehydrogenase 1 and hypoxia inducible factor-1α and phosphorylated (p)-protein kinase B expression was significantly decreased, and the expression level of p-extracellular signal-related kinases and p-P38 was increased. Using 3-methyl adenine to inhibit autophagy caused the rate of apoptosis to increase. Thioridazine inhibited the growth of SKOV3 xenografts in nude mice. The present study demonstrated that the DR2 blocker thioridazine exhibited anticancer effects in vitro and in vivo, suggesting that thioridazine may be used as a potential drug in ovarian cancer therapy. PMID:29344260

Histophilus somni IbpA Fic cytotoxin is conserved in disease strains and most carrier strains from cattle, sheep and bison.

PubMed

Zekarias, B; O'Toole, D; Lehmann, J; Corbeil, L B

2011-04-21

Histophilus somni causes bovine pneumonia, septicemia, myocarditis, thrombotic meningoencephalitis and arthritis, as well as a genital or upper respiratory carrier state in normal animals. However, differences in virulence factors among strains are not well studied. The surface and secreted immunoglobulin binding protein A (IbpA) Fic motif of H. somni causes bovine alveolar type 2 (BAT2) cells to retract, allowing virulent bacteria to cross the alveolar monolayer. Because H. somni IbpA is an important virulence factor, its presence was evaluated in different strains from cattle, sheep and bison to define whether there are syndrome specific markers and whether antigenic/molecular/functional conservation occurs. A few preputial carrier strains lacked IbpA by Western blotting but all other tested disease or carrier strains were IbpA positive. These positive strains had either both IbpA DR1/Fic and IbpA DR2/Fic or only IbpA DR2/Fic by PCR. IbpA Fic mediated cytotoxicity for BAT2 cells and sequence analysis of IbpA DR2/Fic from selected strains revealed conservation of sequence and function in disease and IbpA positive carrier strains. Passive protection of mice against H. somni septicemia with antibody to IbpA DR2/Fic, along with previous data, indicates that the IbpA DR1/Fic and/or DR2/Fic domains are candidate vaccine antigens for protection against many strains of H. somni. Since IbpA DR2/Fic is conserved in most carrier strains, they may be virulent if introduced to susceptible animals at susceptible sites. Conservation of the protective IbpA antigen in all disease isolates tested is encouraging for development of protective vaccines and diagnostic assays. Copyright © 2010 Elsevier B.V. All rights reserved.

Prevalence of Diabetic Retinopathy in Urban Slums: The Aditya Jyot Diabetic Retinopathy in Urban Mumbai Slums Study-Report 2.

PubMed

Sunita, Mohan; Singh, Arvind Kumar; Rogye, Ashwini; Sonawane, Manish; Gaonkar, Ravina; Srinivasan, Radhika; Natarajan, Sundaram; Stevens, Fred C J; Scherpbier, A J J A; Kumaramanickavel, Govindasamy; McCarty, Catherine

2017-10-01

The aims of the study were to estimate the prevalence of diabetic retinopathy (DR) and enumerate history-based risk factors in the urban slums of Western India. The population-based study was conducted in seven wards of Mumbai urban slums, where we screened 6569 subjects of ≥ 40 years age, with a response rate of 98.4%, for type 2 diabetes mellitus (T2DM) based on American Diabetes Association criteria. All subjects with T2DM underwent dilated 30° seven-field stereo-fundus-photography for DR severity grading based on modified Airlie House classification. A multivariate logistic regression model was used to assess the correlation of DR with the history-based risk factors. The prevalence of DR in the general population of Mumbai urban slums was 1.41% (95% CI 0.59-2.23) and in the T2DM population it was 15.37% (95% CI 8.87-21.87). The positive associations with DR were the longer duration of DM (≥ 11 years: OR, 12.77; 95% CI 2.93-55.61) and male gender (OR, 2.05; 95% CI 1.08-3.89); increasing severity of retinopathy was also significantly associated with longer duration of DM (p < 0.001). However, history of hypertension, family history of DM, consanguineous marriage and migration status were not associated with DR in the study population. The prevalence of DR in the general population and T2DM subjects were 1.41% and 15.37% respectively in Mumbai urban slums. Duration of DM and male gender were significantly associated with DR. The slums in Western India show the trends of urban lifestyle influences similar to the rest of urban India.

Association between aldehyde dehydrogenase 2 polymorphisms and the incidence of diabetic retinopathy among Japanese subjects with type 2 diabetes mellitus.

PubMed

Morita, Kazunori; Saruwatari, Junji; Miyagawa, Haruna; Uchiyashiki, Yoshihiro; Oniki, Kentaro; Sakata, Misaki; Kajiwara, Ayami; Yoshida, Akira; Jinnouchi, Hideaki; Nakagawa, Kazuko

2013-09-13

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) detoxifies reactive aldehydes in the micro- and macrovasculature. These substrates, including methylglyoxal and 4-hydroxynonenal formed from glucose and lipids, cause protein carbonylation and mitochondrial dysfunction, forming advanced glycation end products (AGEs). The present study aimed to confirm the association between the inactive ALDH2*2 allele and diabetic retinopathy (DR). A retrospective longitudinal analysis was conducted, among 234 Japanese patients with type 2 diabetes mellitus (DM) (156 males and 78 females) who had no DR signs at baseline and were treated for more than half a year. The ALDH2*1/*2 alleles were determined using a real-time TaqMan allelic discrimination assay. Multivariate-adjusted hazard ratios (HRs) and 95% confidential intervals (CIs) for the cumulative incidence of the development of DR were examined using a Cox proportional hazard model, taking drinking habits and the serum γ-glutamyltransferase (GGT) level into consideration. The frequency of the ALDH2*2 allele was 22.3%. Fifty-two subjects cumulatively developed DR during the follow-up period of 5.5 ± 2.5 years. The ALDH2*2 allele carriers had a significantly higher incidence of DR than the non-carriers (HR: 1.92; P = 0.02). The incidence of DR was significantly higher in the drinkers with the ALDH2*2 allele than in those with the ALDH2*1/*1 genotype (HR: 2.61; P = 0.03), while the incidence of DR in the non-drinkers did not differ significantly between the ALDH2 genotype groups (P > 0.05). The incidence of DR was significantly higher in the ALDH2*2 allele carriers with a high GGT level than in the non-carriers with a high or low GGT level (HR: 2.45; P = 0.03; and HR: 2.63; P = 0.03, respectively). To the best of our knowledge, this is the first report of a significant association between the ALDH2*2 allele and the incidence of DR. These findings provide additional evidence that ALDH2 protects both microvasculature and macrovasculature against reactive aldehydes generated under conditions of sustained oxidative stress, although further investigations in larger cohorts are needed to verify the results.

Modulation of microglia in the retina: new insights into diabetic retinopathy.

PubMed

Arroba, Ana I; Valverde, Ángela M

2017-06-01

During last decades, the diagnosis of diabetes has been associated with several chronic complications such as diabetic retinopathy (DR). Recent studies of DR have revealed an inflammatory component, which precedes the detection of alterations in the visual function. During DR, the inflammatory process presents two opposite roles depending on the polarization of resident immune cells of the retina triggering proinflammatory (M1) or antiinflammatory (M2) actions. In an early stage of DR, the M2 response concurs with the M1 and is able to ameliorate inflammation and delay the progression of the disease. However, during the progression of DR, the M1 response is maintained whereas the M2 declines and, in this scenario, the classical proinflammatory signaling pathways are chronically activated leading to retinal neurodegeneration and the loss of visual function. The M1/M2 responses are closely related to the activation and polarization of microglial cells. This review aims to offer an overview of the recent insights into the role of microglial cells during inflammation in DR. We have focused on the possibility of modulating microglia polarization as a new therapeutic strategy in DR treatments.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kondo, Shinichiro

The format of this dissertation is as follows. In the remainder of Chapter 1, brief introductions and reviews are given to the topics of frustration, heavy fermions and spinels including the precedent work of LiV 2O 4. In Chapter 2, as a general overview of this work the important publication in Physical Review Letters by the author of this dissertation and collaborators regarding the discovery of the heavy fermion behavior in LiV 2O 4 is introduced [removed for separate processing]. The preparation methods employed by the author for nine LiV 2O 4 and two Li 1+xTi 2-xO 4 (x =more » 0 and 1/3) polycrystalline samples are introduced in Chapter 3. The subsequent structural characterization of the LiV 2O 4 and Li 1+xT 2-xO 4 samples was done by the author using thermogravimetric analysis (TGA), x-ray diffraction measurements and their structural refinements by the Rietveld analysis. The results of the characterization are detailed in Chapter 3. In Chapter 4 magnetization measurements carried out by the author are detailed. In Chapter 5, after briefly discussing the resistivity measurement results including the single-crystal work by Rogers et al., for the purpose of clear characterization of LiV 2O 4 it is of great importance to introduce in the following chapters the experiments and subsequent data analyses done by his collaborators. Heat capacity measurements (Chapter 6) were carried out and analyzed by Dr. C.A. Swenson, and modeled theoretically by Dr. D.C. Johnston. In Chapter 7 a thermal expansion study using neutron diffraction by Dr. O. Chmaissem et al. and capacitance dilatometry measurements by Dr. C.A. Swenson are introduced. The data analyses for the thermal expansion study were mainly done by Dr. O. Chmaissem (for neutron diffraction) and Dr. C.A. Swendon (for dilatometry), with assistances by Dr. J.D. Jorgensen, Dr. D.C. Johnston, and S. Kondo the author of this dissertation. Chapter 8 describes nuclear magnetic resonance (NMR) measurements and analyses by Dr. A.V. Mahajan, R. Sala, E. Lee and Dr. F. Borsa. In the final chapter, a summary and discussion are given.« less

Meta-analysis of association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 gene and diabetic retinopathy in Caucasians and Asians.

PubMed

Ma, Jinlan; Li, Yan; Zhou, Fang; Xu, Xiaoyi; Guo, Gang; Qu, Yi

2012-01-01

The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 (PPARγ2) gene is reported to be associated with diabetes. However, the gene's association with diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) has been investigated in numerous epidemiologic studies with controversial results. This meta-analysis aimed to collectively assess the association of the Pro12Ala polymorphism with DR in T2DM. An electronic literature search was conducted on PubMed, ISI Web of Knowledge, EMBASE, and the China National Knowledge Internet. A dominant model [(Pro/Ala +Ala/Ala) versus Pro/Pro] was used to ensure adequate statistical power. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the fixed effect model. Potential sources of heterogeneity and bias were explored. This meta-analysis included genotype data from 2,720 cases with DR and 2,450 controls free of DR from eight eligible publications. The results showed the Ala allele had a protective effect on DR in T2DM (OR=0.81; 95% CI: 0.68-0.98, p=0.03). There was no significant evidence against homogeneity (I(2)=46%, P(heterogeneity)=0.07). The sensitivity analysis showed a robust association of the Pro12Ala polymorphism with DR in T2DM after a study involving Caucasians that presented a big effect on heterogeneity (OR=0.75; 95% CI: 0.62-0.91, p=0.003) was excluded. Possible ethnic differences in the association of the Pro12Ala single nucleotide polymorphism and DR were demonstrated; a significant association was illustrated in the Caucasian subgroup (OR=0.74; 95% CI: 0.59-0.94, p=0.01) but was not found in the Asian subgroup (OR=0.77; 95% CI: 0.55-1.07, p=0.12). No publication bias was observed. This meta-analysis suggested a significant association exists between the Pro12Ala polymorphism and DR in T2DM with ethnic differences. The Ala allele had a significant protective effect against DR in T2DM.

Glutamatergic input is selectively increased in dorsal raphe subfield 5-HT neurons: role of morphology, topography and selective innervation.

PubMed

Crawford, LaTasha K; Craige, Caryne P; Beck, Sheryl G

2011-12-01

Characterization of glutamatergic input to dorsal raphe (DR) serotonin (5-HT) neurons is crucial for understanding how the glutamate and 5-HT systems interact in psychiatric disorders. Markers of glutamatergic terminals, vGlut1, 2 and 3, reflect inputs from specific forebrain and midbrain regions. Punctate staining of vGlut2 was homogeneous throughout the mouse DR whereas vGlut1 and vGlut3 puncta were less dense in the lateral wing (lwDR) compared with the ventromedial (vmDR) subregion. The distribution of glutamate terminals was consistent with the lower miniature excitatory postsynaptic current frequency found in the lwDR; however, it was not predictive of glutamatergic synaptic input with local activity intact, as spontaneous excitatory postsynaptic current (sEPSC) frequency was higher in the lwDR. We examined the morphology of recorded cells to determine if variations in dendrite structure contributed to differences in synaptic input. Although lwDR neurons had longer, more complex dendrites than vmDR neurons, glutamatergic input was not correlated with dendrite length in the lwDR, suggesting that dendrite length did not contribute to subregional differences in sEPSC frequency. Overall, glutamatergic input in the DR was the result of selective innervation of subpopulations of 5-HT neurons and was rooted in the topography of DR neurons and the activity of glutamate neurons located within the midbrain slice. Increased glutamatergic input to lwDR cells potentially synergizes with previously reported increased intrinsic excitability of lwDR cells to increase 5-HT output in lwDR target regions. Because the vmDR and lwDR are involved in unique circuits, subregional differences in glutamate modulation may result in diverse effects on 5-HT output in stress-related psychopathology. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Comparison of various pretreatments for ethanol production enhancement from solid residue after rumen fluid digestion of rice straw.

PubMed

Zhang, Haibo; Zhang, Panyue; Ye, Jie; Wu, Yan; Liu, Jianbo; Fang, Wei; Xu, Dong; Wang, Bei; Yan, Li; Zeng, Guangming

2018-01-01

The rumen digested residue of rice straw contains high residual carbohydrates, which makes it a potential cellulosic ethanol feedstock. This study evaluated the feasibility and effectiveness of applying microwave assisted alkali (MAP), ultrasound assisted alkali (UAP), and ball milling pretreatment (BMP) to enhance ethanol production from two digested residues (2.5%-DR and 10%-DR) after rumen fluid digestion of rice straw at 2.5% and 10.0% solid content. Results revealed that 2.5%-DR and 10%-DR had a cellulose content of 36.4% and 41.7%, respectively. MAP and UAP improved enzymatic hydrolysis of digested residue by removing the lignin and hemicellulose, while BMP by decreasing the particle size and crystallinity. BMP was concluded as the suitable pretreatment, resulting in an ethanol yield of 116.65 and 147.42mgg -1 for 2.5%-DR and 10%-DR, respectively. The integrated system including BMP for digested residue at 2.5% solid content achieved a maximum energy output of 7010kJkg -1 . Copyright © 2017 Elsevier Ltd. All rights reserved.

[Comparison of red edge parameters of winter wheat canopy under late frost stress].

PubMed

Wu, Yong-feng; Hu, Xin; Lü, Guo-hua; Ren, De-chao; Jiang, Wei-guo; Song, Ji-qing

2014-08-01

In the present study, late frost experiments were implemented under a range of subfreezing temperatures (-1 - -9 degrees C) by using a field movable climate chamber (FMCC) and a cold climate chamber, respectively. Based on the spectra of winter wheat canopy measured at noon on the first day after the frost experiments, red edge parameters REP, Dr, SDr, Dr(min), Dr/Dr(min) and Dr/SDr were extracted using maximum first derivative spectrum method (FD), linear four-point interpolation method (FPI), polynomial fitting method (POLY), inverted Gaussian fitting method (IG) and linear extrapolation technique (LE), respectively. The capacity of the red edge parameters to detect late frost stress was explicated from the aspects of the early, sensitivity and stability through correlation analysis, linear regression modeling and fluctuation analysis. The result indicates that except for REP calculated from FPI and IG method in Experiment 1, REP from the other methods was correlated with frost temperatures (P < 0.05). Thereinto, significant levels (P) of POLY and LE methods all reached 0.01. Except for POLY method in Experiment 2, Dr/SDr from the other methods were all significantly correlated with frost temperatures (P < 0.01). REP showed a trend to shift to short-wave band with decreasing temperatures. The lower the temperature, the more obvious the trend is. Of all the REP, REP calculated by LE method had the highest correlation with frost temperatures which indicated that LE method is the best for REP extraction. In Experiment 1 and 2, only Dr(min) and Dr/Dr(min), calculated by FD method simultaneously achieved the requirements for the early (their correlations with frost temperatures showed a significant level P < 0.01), sensitivity (abso- lute value of the slope of fluctuation coefficient is greater than 2.0) and stability (their correlations with frost temperatures al- ways keep a consistent direction). Dr/SDr calculated from FD and IG methods always had a low sensitivity in Experiment 2. In Experiment 1, the sensitivity of Dr/SDr from FD was moderate and IG was high. REP calculated from LE method had a lowest sensitivity in the two experiments. Totally, Dr(min) and Dr/Dr(min) calculated by FD method have the strongest detection capacity for frost temperature, which will be helpful to conducting the research on early diagnosis of late frost injury to winter wheat.

PREVALENCE OF GENETIC SUSCEPTIBILITY FOR CELIAC DISEASE IN BLOOD DONORS IN SÃO PAULO, BRAZIL.

PubMed

Muniz, Janaína Guilhem; Sdepanian, Vera Lucia; Fagundes, Ulysses

2016-01-01

Celiac disease is a permanent intolerance induced by gluten, which is expressed by T-cell mediated enteropathy, and has a high prevalence in the general population. There is evidence of a strong genetic predisposition to celiac disease. To determine the prevalence of genetic markers HLA-DQ2 and HLA-DQ8 in blood donors from São Paulo and measure human recombinant tissue transglutaminase antibody IgA class in HLA-DQ2 and HLA-DQ8 positive donors. A total of 404 blood donors from São Paulo city and Jundiaí were included in the study and signed the informed consent form. Information regarding diarrhea, constipation and abdominal pain in the last 3 months was collected. Determination of HLADQ2 and HLADQ8 alleles was performed in all participants and human recombinant tissue transglutaminase antibody class IgA was measured only in blood donors who presentedDQ2 and/or DQ8. HLADQ2 and/or HLADQ8 were positive in 49% (198/404) of subjects. Positive samples were associated with alleles DR3, DR4, DR7, DR11 and DR12. The most frequent genotype was DR4-DQ8, which was present in 13.6% of samples, followed by genotypes DR3-DQ2 and DR7-DQ2 with DQB1*02 in heterozygous, which were present in 10.4% and 8.7%, respectively. Eleven out of 198 positive donors (5%) were positive to human tissue transglutaminase test. We observed a high prevalence of genetic markers for celiac disease, HLA-DQ2 and HLA-DQ8, in blood donors from São Paulo, similar to prevalence described in Europe. These findings show that the prevalence of celiac disease should not be rare in our country, but underdiagnosed.

Oroxylin A reverses CAM-DR of HepG2 cells by suppressing Integrinβ1 and its related pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Binbin; Zhao, Li; Zhu, Litao

Oroxylin A, a naturally occurring monoflavonoid extracted from Scutellariae radix, shows effective anticancer activities and low toxicities both in vivo and in vitro in previous studies. In this study, we investigated whether the CAM-DR model of HepG2 cells showed resistance to cytotoxic agents compared with normally cultured HepG2 cells. Furthermore, after the treatment of Paclitaxel, less inhibitory effects and decreased apoptosis rate were detected in the model. Data also revealed increased expression of Integrinβ1 might be responsible for the resistance ability. Moreover, Integrinβ1-siRNA-transfected CAM-DR HepG2 cells exhibited more inhibitory effects and higher levels of apoptosis than the non-transfected CAM-DR cells.more » The data corroborated that Integrinβ1 played a significant role in CAM-DR. After the treatment of weakly-toxic concentrations of Oroxylin A, the apoptosis induced by Paclitaxel in the CAM-DR model increased dramatically. Western blot assay revealed Oroxylin A markedly down-regulated the expression of Integrinβ1 and the activity of related pathway. As a conclusion, Oroxylin A can reverse the resistance of CAM-DR via inhibition of Integrinβ1 and its related pathway. Oroxylin A may be a potential candidate of a CAM-DR reversal agent. Highlights: ► Adhesion of HepG2 cells to fibronectin exhibited resistance to Paclitaxel. ► The resistance was associated with the increased expression of Integrinβ1. ► Knocking down Integrinβ1 can increase the toxicity of Paclitaxel on CAM-DR model. ► Oroxylin A reversed the resistance by suppressing Integrinβ1 and related pathway.« less

Color vision and neuroretinal function in diabetes.

PubMed

Wolff, B E; Bearse, M A; Schneck, M E; Dhamdhere, K; Harrison, W W; Barez, S; Adams, A J

2015-04-01

We investigate how type 2 diabetes (T2DM) and diabetic retinopathy (DR) affect color vision (CV) and mfERG implicit time (IT), whether CV and IT are correlated, and whether CV and IT abnormality classifications agree. Adams desaturated D-15 color test, mfERG, and fundus photographs were examined in 37 controls, 22 T2DM patients without DR (NoRet group), and 25 T2DM patients with DR (Ret group). Color confusion score (CCS) was calculated. ITs were averaged within the central 7 hexagons (central IT; ≤4.5°) and outside this area (peripheral IT; ≥4.5°). DR was within (DRIN) or outside (DROUT) of the central 7 hexagons. Group differences, percentages of abnormalities, correlations, and agreement were determined. CCS was greater in the NoRet (P = 0.002) and Ret (P < 0.0001) groups than in control group. CCS was abnormal in 3, 41, and 48 % of eyes in the control, NoRet, and Ret groups, respectively. Ret group CV abnormalities were more frequent in DRIN than in DROUT subgroups (71 vs. 18 %, respectively; P < 0.0001). CCS and IT were correlated only in the Ret group, in both retinal zones (P ≤ 0.028). Only in the Ret group did CCS and peripheral IT abnormality classifications agree (72 %; P < 0.05). CV is affected in patients with T2DM, even without DR. Central DR increases the likelihood of a CV deficit compared with non-central DR. mfERG IT averaged across central or peripheral retinal locations is less frequently abnormal than CV in the absence of DR, and these two measures are correlated only when DR is present.

Color vision and neuroretinal function in diabetes

PubMed Central

Bearse, M. A.; Schneck, M. E.; Dhamdhere, K.; Harrison, W. W.; Barez, S.; Adams, A. J.

2015-01-01

Purpose We investigate how type 2 diabetes (T2DM) and diabetic retinopathy (DR) affect color vision (CV) and mfERG implicit time (IT), whether CV and IT are correlated, and whether CV and IT abnormality classifications agree. Methods Adams desaturated D-15 color test, mfERG, and fundus photographs were examined in 37 controls, 22 T2DM patients without DR (NoRet group), and 25 T2DM patients with DR (Ret group). Color confusion score (CCS) was calculated. ITs were averaged within the central 7 hexagons (central IT; ≥4.5°) and outside this area (peripheral IT; ≤4.5°). DR was within (DRIN) or outside (DROUT) of the central 7 hexagons. Group differences, percentages of abnormalities, correlations, and agreement were determined. Results CCS was greater in the NoRet (P = 0.002) and Ret (P < 0.0001) groups than in control group. CCS was abnormal in 3, 41, and 48 % of eyes in the control, NoRet, and Ret groups, respectively. Ret group CV abnormalities were more frequent in DRIN than in DROUT subgroups (71 vs. 18 %, respectively; P < 0.0001). CCS and IT were correlated only in the Ret group, in both retinal zones (P ≥ 0.028). Only in the Ret group did CCS and peripheral IT abnormality classifications agree (72 %; P < 0.05). Conclusion CV is affected in patients with T2DM, even without DR. Central DR increases the likelihood of a CV deficit compared with non-central DR. mfERG IT averaged across central or peripheral retinal locations is less frequently abnormal than CV in the absence of DR, and these two measures are correlated only when DR is present. PMID:25516428

Acquired Resistance Mechanisms to Combination Met-TKI/EGFR-TKI Exposure in Met-Amplified EGFR-TKI-Resistant Lung Adenocarcinoma Harboring an Activating EGFR Mutation.

PubMed

Yamaoka, Toshimitsu; Ohmori, Tohru; Ohba, Motoi; Arata, Satoru; Kishino, Yasunari; Murata, Yasunori; Kusumoto, Sojiro; Ishida, Hiroo; Shirai, Takao; Hirose, Takashi; Ohnishi, Tsukasa; Sasaki, Yasutsuna

2016-12-01

Met-amplified EGFR-tyrosine kinase inhibitor (TKI)-resistant non-small cell lung cancer (NSCLC) harboring an activating EGFR mutation is responsive to concurrent EGFR-TKI and Met-TKI treatment in a preclinical model. Here, we determined that Met-amplified gefitinib-resistant cells acquire dual resistance to inhibition of EGFR and Met tyrosine kinase activities. PC-9 lung adenocarcinoma cells harboring 15-bp deletions (Del E746_A750) in EGFR exon 19 were treated with increasing concentrations of the Met-TKI PHA665752 and 1 μmol/L gefitinib for 1 year; three resistant clones were established via Met amplification. The three dual-resistance cell lines (PC-9DR2, PC-9DR4, and PC-9DR6, designated as DR2, DR4, and DR6, respectively) exhibited different mechanisms for evading both EGFR and Met inhibition. None of the clones harbored a secondary mutation of EGFR T790M or a Met mutation. Insulin-like growth factor (IGF)/IGF1 receptor activation in DR2 and DR4 cells acted as a bypass signaling pathway. Met expression was attenuated to a greater extent in DR2 than in PC-9 cells, but was maintained in DR4 cells by overexpression of IGF-binding protein 3. In DR6 cells, Met was further amplified by association with HSP90, which protected Met from degradation and induced SET and MYND domain-containing 3 (SMYD3)-mediated Met transcription. This is the first report describing the acquisition of dual resistance mechanisms in NSCLC harboring an activating EGFR mutation to Met-TKI and EGFR-TKI following previous EGFR-TKI treatment. These results might inform the development of more effective therapeutic strategies for NSCLC treatment. Mol Cancer Ther; 15(12); 3040-54. ©2016 AACR. ©2016 American Association for Cancer Research.

[Results of the use of antioxidant and angioprotective agents in type 2 diabetes patients with diabetic retinopathy and age-related macular degeneration].

PubMed

Moshetova, L K; Vorob'eva, I V; Alekseev, I B; Mikhaleva, L G

2015-01-01

to investigate changes in clinical, functional, and morphological parameters of the retina in type 2 diabetes patients with diabetic retinopathy (DR) and those with combined fundus pathology (DR plus age-related macular degeneration (AMD)) before and after a course of antioxidants and angioprotectors in the form of mono- or combination therapy. The study included 180 patients (180 eyes) with type 2 diabetes divided into 6 groups of 30 each. DR was graded according to E. Kohner and M. Porta classification, AMD--AREDS classification. Thus, group 1 consisted of patients with DRO,; group 2--DR1 without DM, group 3--DR1 with DM, group 4--DRO and "dry" AMD (AREDS 1-3), group 5--DR1 with no DM but with AMD (AREDS 1-3), and group 6--DR1 with DM and AMD (AREDS 1-3). A drug containing lutein 6 mg, zeaxanthin 0.5 mg, vitamin C 60 mg, vitamin E 7 mg, vitamin A 1.5 mg, vitamin B2 1.2 mg, rutin 25 mg, zinc 5 mg, selenium 25 mcg, and bilberry extract 60 mg was used for antioxidative therapy. Ginkgo biloba leaf extract 60 mg was chosen as the angioprotector. In all patients visual acuity, macular thickness and morphology (OCT) as well as light sensitivity (microperimetry) were assessed before and after the treatment course. Analysis of baseline measurements demonstrated a significant decrease in best corrected visual acuity (p < 0.05) in study groups 2-6 as compared with group 1. Macular thickness was increased in all groups, however, the changes were statistically significant only in groups 3 and 6 (p<0.05). Light sensitivity of the macula showed a reduction, which was statistically significant in groups 4-6 (p < 0.05). After the course of antioxidant and angioprotective therapy, these parameters improved in all groups. The greatest effect was achieved with simultaneous antioxidant and double-dose angioprotective therapy (240 mg per day): visual acuity increased significantly (p < 0.05) in all groups except group 1; macular thickness decreased in all groups, however, the changes were statistically significant (p < 0.05) only in groups 1-3 and 5; light sensitivity also improved in all groups, significantly (p < 0.05) in groups 1-3 and 4. Extended analysis of clinical, functional and morphological changes in the retina at the onset of DR in type 2 diabetes patients with concomitant "dry" AMD enables timely diagnosis, prognosis, prevention, and early treatment. Conservative treatment with antioxidant and angioprotective agents has been proved effective in type 2 diabetes patients with preclinical (DRO) and early (DR1) diabetic retinopathy and those with DR and "dry" AMD (AREDS 1-3) in terms of functional and morphological parameters of the retina. From all the regimens, a combined antioxidant and double-dose angioprotective (240 mg) therapy appeared to be the most effective and can be considered not only a preventive, but also a therapeutic measure in type 2 diabetes patients with initial stages of DR (DRO, DR1) or those with DR and DM or combined DR and AMD (AREDS 1-3).

Lipid-lowering medication use is associated with decreased risk of diabetic retinopathy and its treatments in patients with type 2 diabetes: a real-world observational analysis of a health claims database.

PubMed

Kawasaki, Ryo; Konta, Tsuneo; Nishida, Kohji

2018-05-22

Fenofibrate and statins reduced the risk of diabetic retinopathy (DR) related treatment in clinical trials. We aimed to determine whether lipid-lowering medication use reduce the risk of DR and its treatments in patients with type 2 diabetes using a real-world health claims database. This was an observational analysis using a nation-wide health claims database of the Japan Medical Data Center (JMDC). Type 2 diabetes was defined by the ICD-10 codes with glucose-lowering medication use. Lipid-lowering medication use at least one year was confirmed by the Anatomical Therapeutic Chemical Classification System. DR and diabetic macular edema (DME) were determined by ICD-10; DR related treatments were determined by health insurance claims. A propensity score for lipid-lowering medication use was estimated, and a doubly robust estimator using the inverse probability weighting model with regression adjustment was obtained to estimate odds ratios (OR) with 95% confidence interval (95%CI) for cumulative incidence of DR and its treatments over 3 years. There were 69,070 persons with type 2 diabetes at baseline. DR developed in 5,687 persons over 3 years. Lipid-lowering medication use was associated with decreased risk of incidence of DR (OR 0.772, 95%CI 0.720-0.827; p<0.001). Lipid-lowering medication use was also associated with decreased incidence of DME, any treatments for DR, laser photocoagulation, and vitrectomy in patients with DR at baseline. In a population of patients with type 2 diabetes with a variety of risk profile, lipid-lowering medication use reduced the risk of DR and its treatments of laser photocoagulation and vitrectomy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

An analysis of variation in the long-range genomic organization of the human major histocompatibility complex class II region by pulsed-field gel electrophoresis.

PubMed

Dunham, I; Sargent, C A; Dawkins, R L; Campbell, R D

1989-11-01

The class II region of the human major histocompatibility complex in seven common HLA haplotypes has been analyzed using pulsed-field gel electrophoresis, restriction enzymes that cut genomic DNA infrequently, and Southern blotting. This analysis has revealed that there are differences in the amount of DNA present in the DQ and DR subregions dependent on the haplotype. The class II region of the DR3 haplotype spans approximately 750 kb and has the same amount of DNA as the class II region of the DR5 and DR6 haplotypes. However, the DR2 haplotype has approximately 30 kb more DNA within the DR subregion. The DR4 haplotype has an additional approximately 110 kb of DNA within the DQ or DR subregions compared to the DR3, DR5, and DR6 haplotypes. These haplotype-specific differences could have some bearing both on the analysis of disease susceptibility and on the ability of chromosomes possessing different HLA haplotypes to recombine within the DQ/DR subregions.

Identifying injuries and motor vehicle collision characteristics that together are suggestive of diaphragmatic rupture.

PubMed

Reiff, Donald A; McGwin, Gerald; Metzger, Jesse; Windham, Samuel T; Doss, Marilyn; Rue, Loring W

2002-12-01

Diaphragmatic rupture (DR) remains a diagnostic challenge because of the lack of an accurate test demonstrating the injury. Our purpose was to identify motor vehicle collision (MVC) characteristics and patient injuries that collectively could identify the presence of a DR. The National Automotive Sampling System was used to identify occupants involved in MVCs from 1995 to 1999 who sustained abdominal (Abbreviated Injury Scale score >or= 2) and/or thoracic injuries (Abbreviated Injury Scale score >or= 2). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to quantify the association between patient injuries, vehicle collision characteristics, and DR. Sensitivity and specificity were also calculated to determine the ability of organ injury and MVC characteristics to correctly classify patients with and without DR. Overall, occupants sustaining a DR had a significantly higher delta-V (DeltaV) (49.8 kilometers per hour [kph] vs. 33.8 kph, p< 0.0001) and a greater degree of occupant compartment intrusion (70.6 cm vs. 48.3 cm, p< 0.0001). Specific abdominal and thoracic organ injuries were associated with DR, including thoracic aortic tears (OR, 5.2; 95% CI, 2.2-12.5), splenic injury (OR, 8.4; 95% CI, 3.9-17.8), pelvic fractures (OR, 4.7; 95% CI, 2.7-8.0), and hepatic injuries (OR, 4.2; 95% CI, 1.7-10.6). Combining frontal or near-side lateral occupant compartment intrusion >or= 30 cm or DeltaV >or= 40 kph with specific organ injuries generated a sensitivity for indicating the likelihood of diaphragm injury ranging from 68% to 89%. Patients with any of the following characteristics had a sensitivity for detecting DR of 91%: splenic injury, pelvic fracture, DeltaV >or= 40 kph, or occupant compartment intrusion from any direction >or= 30 cm. Specific MVC characteristics combined with patient injuries have been identified that are highly suggestive of DR. For this subpopulation, additional invasive procedures including exploratory laparotomy, laparoscopy, or thoracoscopy may be warranted to exclude DR.

United States Air Force Research Initiation Program for 1988. Volume 2

DTIC Science & Technology

1990-04-01

Specialty: Modeling and Simulation ENGINEERING AND SERVICES CENTER (Tyndall Air Force Base) Dr. Wayne A. Charlie Dr. Peter Jeffers (1987) Colorado State...Michael Sydor University of New Hampshire University of Minnesota Specialty: Systems Modeling & Controls Specialty: Optics, Material Science Dr. John...9MG-025 4 Modeling and Simulation on Micro- Dr. Joseph J. Feeley (1987) computers, 1989 760-7MG-070 5 Two Dimensional MHD Simulation of Dr. Manuel A

Gaia DR2 documentation Chapter 7: Variability

NASA Astrophysics Data System (ADS)

Eyer, L.; Guy, L.; Distefano, E.; Clementini, G.; Mowlavi, N.; Rimoldini, L.; Roelens, M.; Audard, M.; Holl, B.; Lanzafame, A.; Lebzelter, T.; Lecoeur-Taïbi, I.; Molnár, L.; Ripepi, V.; Sarro, L.; Jevardat de Fombelle, G.; Nienartowicz, K.; De Ridder, J.; Juhász, Á.; Molinaro, R.; Plachy, E.; Regibo, S.

2018-04-01

This chapter of the Gaia DR2 documentation describes the models and methods used on the 22 months of data to produce the Gaia variable star results for Gaia DR2. The variability processing and analysis was based mostly on the calibrated G and integrated BP and RP photometry. The variability analysis approach to the Gaia data has been described in Eyer et al. (2017), and the Gaia DR2 results are presented in Holl et al. (2018). Detailed methods on specific topics will be published in a number of separate articles. Variability behaviour in the colour magnitude diagram is presented in Gaia Collaboration et al. (2018c).

Gaia: Mapping the Milky Way: The Scientific Promise of Gaia DR2

NASA Astrophysics Data System (ADS)

Walton, Nicholas; ESA Gaia, Data Processing and Analysis Consortium (DPAC)

2018-06-01

The ESA Gaia mission will release its first major all sky astrometric catalogue (Gaia DR2), of more than 1.3 billion stars in our Galaxy, on 25 April 2018.This presentation will provide an overview of the Gaia mission, focussing on the significant scientific potential of the Gaia DR2 release. This is based on 22 months of input data and allows for a full Gaia stand alone astrometric solution, including parallaxes and proper motions, of over 1.3 billion sources. The astrometric uncertainties in Gaia DR2 will be at the level of tens of micro-arcsec for sources G<15.The Gaia DR2 release provides not only high precision full five parameter astrometry, but also a complete photometric catalogue of the sources on an all sky homogeneous photometric system in the Gaia G band and broad bands G_BP and G_RP. The release will include median radial velocities for more than six million stars (brighter that G_RVS = 12) together with a set of astrophysical parameters (including stellar temperatures) for some 150 million stars. Finally the Gaia DR2 release will include a set of additional data products including the light curves of more than half a million variable stars, and the positions of more than thirteen thousand objects in our Solar System.Together with the Gaia DR2 data products and associated release documentation, a small number of performance verification papers, using Gaia DR2 data only to provide new insights into a number of key areas of Gaia science, will be published in a special edition of A&A. These will provide demonstrations of the scientific potential of the Gaia DR2 catalogue, and also highlight some of the issues and limitations involved in the use of the Gaia DR2 data.The Gaia mission and Gaia Data Releases are made possible through the dedication and expertise of the community scientists and engineers involved in the design, construction, and operation of Gaia (led by ESA) and the collaboration of some 450 scientists and software engineers responsible for the complex task of analysing the processed data (the DPAC). The role of both will be covered in the presentation.The presentation will conclude with a brief look ahead to the longer term Gaia data release schedule.

Spatial and Temporal Patterns of Suspended Sediment Yields in Nested Urban Catchments

NASA Astrophysics Data System (ADS)

Kemper, J. T.; Miller, A. J.; Welty, C.

2017-12-01

In a highly regulated area such as the Chesapeake Bay watershed, suspended sediment is a matter of primary concern. Near real-time turbidity and discharge data have been collected continuously for more than four years at five stream gages representing three nested watershed scales (1-2 sq km, 5-6 sq km, 14 sq km) in the highly impervious Dead Run watershed, located in Baltimore County, MD. Using turbidity-concentration relationships based on sample analyses at the gage site, sediment yields for each station can be quantified for a variety of temporal scales. Sediment yields have been calculated for 60+ different storms across four years. Yields show significant spatial variation, both at equivalent sub-watershed scales and from headwaters to mouth. Yields are higher at the headwater station with older development and virtually no stormwater management (DR5) than at the station with more recent development and more extensive stormwater management (DR2). However, this pattern is reversed for the stations at the next larger scale: yields are lower at DR4, downstream of DR5, than at DR3, downstream of DR2. This suggests spatial variation in the dominant sediment sources within each subwatershed. Additionally, C-Q hysteresis curves display consistent counterclockwise behavior at the DR4 station, in contrast to the consistent clockwise behavior displayed at the DR3 station. This further suggests variation in dominant sediment sources (perhaps distal vs local, respectively). We observe consistent seasonal trends in the relative magnitudes of sediment yield for different subwatersheds (e.g. DR3>DR4 in summer, DR5>DR2 in spring). We also observe significant year-to-year variation in sediment yield at the headwater and intermediate scales, whereas yields at the 14 sq km scale are largely similar across the monitored years. This observation would be consistent with the possibility that internal storage and remobilization tend to modulate downstream yields even with spatial and temporal variation in upstream sources. The fine-scale design of this study represents a unique opportunity to compare and contrast sediment yields across a variety of spatial and temporal scales, and provide insight into sediment transport dynamics within an urbanized watershed.

Nuclear Rocket Technology Conference

NASA Technical Reports Server (NTRS)

1966-01-01

The Lewis Research Center has a strong interest in nuclear rocket propulsion and provides active support of the graphite reactor program in such nonnuclear areas as cryogenics, two-phase flow, propellant heating, fluid systems, heat transfer, nozzle cooling, nozzle design, pumps, turbines, and startup and control problems. A parallel effort has also been expended to evaluate the engineering feasibility of a nuclear rocket reactor using tungsten-matrix fuel elements and water as the moderator. Both of these efforts have resulted in significant contributions to nuclear rocket technology. Many successful static firings of nuclear rockets have been made with graphite-core reactors. Sufficient information has also been accumulated to permit a reasonable Judgment as to the feasibility of the tungsten water-moderated reactor concept. We therefore consider that this technoIogy conference on the nuclear rocket work that has been sponsored by the Lewis Research Center is timely. The conference has been prepared by NASA personnel, but the information presented includes substantial contributions from both NASA and AEC contractors. The conference excludes from consideration the many possible mission requirements for nuclear rockets. Also excluded is the direct comparison of nuclear rocket types with each other or with other modes of propulsion. The graphite reactor support work presented on the first day of the conference was partly inspired through a close cooperative effort between the Cleveland extension of the Space Nuclear Propulsion Office (headed by Robert W. Schroeder) and the Lewis Research Center. Much of this effort was supervised by Mr. John C. Sanders, chairman for the first day of the conference, and by Mr. Hugh M. Henneberry. The tungsten water-moderated reactor concept was initiated at Lewis by Mr. Frank E. Rom and his coworkers. The supervision of the recent engineering studies has been shared by Mr. Samuel J. Kaufman, chairman for the second day of the conference, and Mr. Roy V. Humble. Dr. John C. Eward served as general chairman for the conference.

Automated diabetic retinopathy detection in smartphone-based fundus photography using artificial intelligence.

PubMed

Rajalakshmi, Ramachandran; Subashini, Radhakrishnan; Anjana, Ranjit Mohan; Mohan, Viswanathan

2018-06-01

To assess the role of artificial intelligence (AI)-based automated software for detection of diabetic retinopathy (DR) and sight-threatening DR (STDR) by fundus photography taken using a smartphone-based device and validate it against ophthalmologist's grading. Three hundred and one patients with type 2 diabetes underwent retinal photography with Remidio 'Fundus on phone' (FOP), a smartphone-based device, at a tertiary care diabetes centre in India. Grading of DR was performed by the ophthalmologists using International Clinical DR (ICDR) classification scale. STDR was defined by the presence of severe non-proliferative DR, proliferative DR or diabetic macular oedema (DME). The retinal photographs were graded using a validated AI DR screening software (EyeArt TM ) designed to identify DR, referable DR (moderate non-proliferative DR or worse and/or DME) or STDR. The sensitivity and specificity of automated grading were assessed and validated against the ophthalmologists' grading. Retinal images of 296 patients were graded. DR was detected by the ophthalmologists in 191 (64.5%) and by the AI software in 203 (68.6%) patients while STDR was detected in 112 (37.8%) and 146 (49.3%) patients, respectively. The AI software showed 95.8% (95% CI 92.9-98.7) sensitivity and 80.2% (95% CI 72.6-87.8) specificity for detecting any DR and 99.1% (95% CI 95.1-99.9) sensitivity and 80.4% (95% CI 73.9-85.9) specificity in detecting STDR with a kappa agreement of k = 0.78 (p < 0.001) and k = 0.75 (p < 0.001), respectively. Automated AI analysis of FOP smartphone retinal imaging has very high sensitivity for detecting DR and STDR and thus can be an initial tool for mass retinal screening in people with diabetes.

[A total of 362 HLA different haplotypes and HLA recombination haplotypes based on analysis of their family pedigree in Chinese partial Han populations].

PubMed

Gao, Su-Qing; Cheng, Xi; Li, Qian; Li, Yu-Zhu; Deng, Zhi-Hui

2009-06-01

This study was aimed to discover the novel HLA recombination haplotypes and investigate the distribution of haplotypes in Chinese Han population. Based on the HLA-A, B, DRB1 typing results of 179 family members, 791 haplotypes were assigned by the mode of inheritance. The results showed that a total of 4 novel recombinant haplotypes in HLA-DRB1 locus region were observed in 4 families, which ratio of paternal to maternal chromosomes was 3:1. The recombination ratio between HLA-DRB1 and HLA-A or B loci was 0.92% (4/433). There were a total of 362 kinds of HLA-A, -B, -DRB1 haplotypes to be confirmed in Chinese Han partial population. A33-B58-DR17, A2-B46-DR9, A30-B13-DR7, A11-B13-DR15, A11-B75-DR12 and A2-B46-DR14 were the most common haplotypes that was consistent with the distribution of HLA alleles in unrelated donors. There were A1-B63-DR12, A29-B46-DR15, A1-B61-DR10, A34-B35-DR9, A29-B54-DR4, A23-B13-DR16 and A34-B62-DR15 haplotypes and so on, which were rare haplotypes not yet reported in Chinese. It is concluded that the HLA-A-B-DRB1 haplotypes would be confirmed by analysis of their family pedigree. The results obtained in this study are basic data for study of Chinese anthropology, organ transplantation and disease correlation analysis.

A new DRB1*1202 allele (DRB1*12022) found in association with DQA1*0102 and DQB1*0602 in two Black narcoleptic subjects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Behar, E.; Grumet, F.C.; Lin, X.

1995-01-01

DQB1*0602 is a better genetic marker than DR2 for narcolepsy susceptibility across all ethnic groups; for instance, only 75% of African American narcoleptics are DR2+ compared with 96% DQB1*0602+. We studied DRB1 genes of DR2- but DQB1*0602+ African American patients with cataplexy and observed two with an unusual DR12, DQA1*0102, DQB1*0602 haplotype; a new allelic variant of DRB1*1202 has been designated DRB*12022. 8 refs.

Anterior Diabetic Retinopathy Studied by Ultra-widefield Angiography

PubMed Central

Bae, Kunho; Lee, Ju Yeon; Kim, Tae Hyup; Cho, Ga Eun; Ahn, Jeeyun; Kim, Sang Jin; Kim, Jae Hyun

2016-01-01

Purpose To evaluate the prevalence of anterior type diabetic retinopathy (DR) using ultra-widefield fluorescein angiography and to identify the factors associated with anterior type DR incidence. Methods A retrospective case review was used in this study. Patients with non-proliferative diabetic retinopathy (NPDR) underwent examination by ultra-widefield fluorescein angiography, and were classified into anterior, posterior, or diffuse DR groups. Anterior DR was defined if diabetic retinal changes were noted only at the location anterior to the imaginary circle bordered by the Early Treatment Diabetic Retinopathy Study seven-standard fields. Correlations between demographic data, as well as systemic and ocular factors, and the incidence of NPDR types were evaluated. Results Among the 234 eyes of 234 patients with NPDR, 25 eyes (10.7%) demonstrated anterior DR. Anterior DR was observed in 10 eyes (30.3%) of patients having mild NPDR, three eyes (4.8%) of moderate NPDR patients, and in 12 eyes (7.1%) of severe NPDR patients (p < 0.001). The incidence of anterior DR positively correlated with lower hemoglobin A1c levels and with greater high-density lipoprotein levels following multiple logistic regression analysis (p < 0.001). The mean hemoglobin A1c level was 7.03 ± 0.99% in anterior DR, 7.99 ± 1.74% in posterior DR, and 7.94 ± 1.39% in diffuse DR patients (p = 0.003). The mean high-density lipoprotein level was 51.2 ± 12.5 mg/dL in anterior, 49.7 ± 15.2 mg/dL in posterior, and 45.2 ± 13.1 mg/dL in diffuse DR patients (p = 0.010). Conclusions Diabetic retinal changes confined to an anterior location were more frequently noted in earlier stages of NPDR. The incidence of DR sparing posterior retinal involvement was related to favorable blood sugar and lipid profiles. PMID:27729754

Second Opinion Reviews for Cancer Diagnoses in Anatomic Pathology: A Comprehensive Cancer Center's Experience.

PubMed

Strosberg, Carolina; Gibbs, Julie; Braswell, Diana; Leslie, Ronni R; Messina, Jane; Centeno, Barbara A; Coppola, Domenico

2018-05-01

The objective of this study was to define the rates of discrepancy between outside pathological diagnoses and secondary reviews. We assessed the rates of discordance between outside diagnoses and secondary reviews, categorizing by organ site and minor or major (affecting patient care) discordances. A total of 9,289 consecutive surgical pathology (SP) and cytopathology (CP) cases reviewed in 2015 were identified. For 8,191 outside SP cases reviewed, the overall discordance rate (DR) was 14.2% (2.2% major, 12.0% minor). Specifically, neuropathology had the highest DR (10.9%), cutaneous and breast the lowest (1.1% each). Among 1,098 CP cases, the total DR was 13.7% (3.0% major, 10.7% minor). The majority of CP cases (1,066) were non-gynecological and had a total DR of 13.4% (2.7% major, 10.7% minor). While major DR was low, certain subspecialties had high DRs. This project can help identify areas where focused education could help improve pathological diagnostic accuracy for cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Overall properties of the Gaia DR1 reference frame

NASA Astrophysics Data System (ADS)

Liu, N.; Zhu, Z.; Liu, J.-C.; Ding, C.-Y.

2017-03-01

Aims: The first Gaia data release (Gaia DR1) provides 2191 ICRF2 sources with their positions in the auxiliary quasar solution and five astrometric parameters - positions, parallaxes, and proper motions - for stars in common between the Tycho-2 catalogue and Gaia in the joint Tycho-Gaia astrometric solution (TGAS). We aim to analyze the overall properties of Gaia DR1 reference frame. Methods: We compare quasar positions of the auxiliary quasar solution with ICRF2 sources using different samples and evaluate the influence on the Gaia DR1 reference frame owing to the Galactic aberration effect over the J2000.0-J2015.0 period. Then we estimate the global rotation between TGAS with Tycho-2 proper motion systems to investigate the property of the Gaia DR1 reference frame. Finally, the Galactic kinematics analysis using the K-M giant proper motions is performed to understand the property of Gaia DR1 reference frame. Results: The positional comparison between the auxiliary quasar solution and ICRF2 shows negligible orientation and validates the declination bias of -0.1mas in Gaia quasar positions with respect to ICRF2. Galactic aberration effect is thought to cause an offset 0.01mas of the Z axis direction of Gaia DR1 reference frame. The global rotation between TGAS and Tycho-2 proper motion systems, obtained by different samples, shows a much smaller value than the claimed value 0.24mas yr-1. For the Galactic kinematics analysis of the TGAS K-M giants, we find possible non-zero Galactic rotation components beyond the classical Oort constants: the rigid part ωYG = -0.38±0.15mas yr-1 and the differential part ω^primeYG = -0.29±0.19mas yr-1 around the YG axis of Galactic coordinates, which indicates possible residual rotation in Gaia DR1 reference frame or problems in the current Galactic kinematical model. Conclusions: The Gaia DR1 reference frame is well aligned to ICRF2, and the possible influence of the Galactic aberration effect should be taken into consideration for the future Gaia-ICRF link. The cause of the rather small global rotation between TGAS and Tycho-2 proper motion systems is unclear and needs further investigation. The possible residual rotation in Gaia DR1 reference frame inferred from the Galactic kinematic analysis should be noted and examined in future data release.

VizieR Online Data Catalog: KiDS-ESO-DR3 multi-band source catalog (de Jong+, 2017)

NASA Astrophysics Data System (ADS)

de Jong, J. T. A.; Verdoes Kleijn, G. A.; Erben, T.; Hildebrandt, H.; Kuijken, K.; Sikkema, G.; Brescia, M.; Bilicki, M.; Napolitano, N. R.; Amaro, V.; Begeman, K. G.; Boxhoorn, D. R.; Buddelmeijer, H.; Cavuoti, S.; Getman, F.; Grado, A.; Helmich, E.; Huang, Z.; Irisarri, N.; La Barbera, F.; Longo, G.; McFarland, J. P.; Nakajima, R.; Paolillo, M.; Puddu, E.; Radovich, M.; Rifatto, A.; Tortora, C; Valentijn, E. A.; Vellucci, C.; Vriend, W-J.; Amon, A.; Blake, C.; Choi, A.; Fenech, Conti I.; Herbonnet, R.; Heymans, C.; Hoekstra, H.; Klaes, D.; Merten, J.; Miller, L.; Schneider, P.; Viola, M.

2017-04-01

KiDS-ESO-DR3 contains a multi-band source catalogue encompassing all publicly released tiles, a total of 440 survey tiles including the coadded images, weight maps, masks and source lists of 292 survey tiles of KiDS-ESO-DR3, adding to the 148 tiles released previously (50 in KiDS-ESO-DR1 and 98 in KiDS-ESO-DR2). (1 data file).

HLA-DR2-associated DRB1 and DRB5 alleles and haplotypes in Koreans.

PubMed

Song, E Y; Kang, S J; Lee, Y J; Park, M H

2000-09-01

There are considerable racial differences in the distribution of HLA-DR2-associated DRB1 and DRB5 alleles and the characteristics of linkage disequilibrium between these alleles. In this study, the frequencies of DR2-associated DRB1 and DRB5 alleles and related haplotypes were analyzed in 186 DR2-positive individuals out of 800 normal Koreans registered for unrelated bone marrow donors. HLA class I antigen typing was performed by the serological method and DRB1 and DRB5 genotyping by the PCR-single strand conformational polymorphism method. Only 3 alleles were detected for DR2-associated DRB1 and DRB5 genes, respectively: DRB1(*)1501 (gene frequency 8.0%), (*)1502 (3.2%), (*)1602 (0.9%); DRB5(*)0101 (8.0%), (*)0102 (3.2%), and (*)0202 (0.9%). DRB1-DRB5 haplotype analysis showed an exclusive association between these alleles: DRB1*1501-DRB5*0101 (haplotype frequency 8.0%), DRB1(*)1502-DRB5(*)0102 (3.2%), and DRB1(*)1602-DRB5(*)0202 (0.9%). The 5 most common DR2-associated A-B-DRB1 haplotypes occurring at frequencies of > or = 0.5% were A24-B52-DRB1(*)1502 (1.8%), A2-B62-DRB1(*)1501, A2-B54-DRB1(*)1501, A26-B61-DRB1(*)1501, and A24-B51-DRB1(*)1501. The remarkable homogeneity in the haplotypic associations between DR2-associated DRB1 and DRB5 alleles in Koreans would be advantageous for organ transplantation compared with other ethnic groups showing considerable heterogeneity in the distribution of DRB1-DRB5 haplotypes.

d-Allulose, a stereoisomer of d-fructose, extends Caenorhabditis elegans lifespan through a dietary restriction mechanism: A new candidate dietary restriction mimetic.

PubMed

Shintani, Tomoya; Sakoguchi, Hirofumi; Yoshihara, Akihide; Izumori, Ken; Sato, Masashi

2017-12-02

Dietary restriction (DR) is an effective intervention known to increase lifespan in a wide variety of organisms. DR also delays the onset of aging-associated diseases. DR mimetics, compounds that can mimic the effects of DR, have been intensively explored. d-Allulose (d-Alu), the C3-epimer of d-fructose, is a rare sugar that has various health benefits, including anti-hyperglycemia and anti-obesity effects. Here, we report that d-Alu increased the lifespan of Caenorhabditis elegans both under monoxenic and axenic culture conditions. d-Alu did not further extend the lifespan of the long-lived DR model eat-2 mutant, strongly indicating that the effect is related to DR. However, d-Alu did not reduce the food intake of wild-type C. elegans. To explore the mechanisms of the d-Alu longevity effect, we examined the lifespan of d-Alu-treated mutants deficient for nutrient sensing pathway-related genes daf-16, sir-2.1, aak-2, and skn-1. As a result, d-Alu increased the lifespan of the daf-16, sir-2.1, and skn-1 mutants, but not the aak-2 mutant, indicating that the lifespan extension was dependent on the energy sensor, AMP-activated protein kinase (AMPK). d-Alu also enhanced the mRNA expression and enzyme activities of superoxide dismutase (SOD) and catalase. From these findings, we conclude that d-Alu extends lifespan by increasing oxidative stress resistance through a DR mechanism, making it a candidate DR mimetic. Copyright © 2017 Elsevier Inc. All rights reserved.

Early onset of diabetes in the proband is the major determinant of risk in HLA DR3-DQ2/DR4-DQ8 siblings.

PubMed

Gillespie, Kathleen M; Aitken, Rachel J; Wilson, Isabel; Williams, Alistair J K; Bingley, Polly J

2014-03-01

Islet autoimmunity is initiated in infancy, and primary prevention trials require children at high genetic risk to be identified before autoantibodies appear. To inform screening strategies, we evaluated risks of autoimmunity and diabetes associated with HLA DR3-DQ2/DR4-DQ8 in U.K. families. Extended HLA haplotypes were determined in 2,134 siblings from the Bart's-Oxford Study followed to a median age of 22 years. Risks of diabetes and islet autoimmunity (more than two antibodies) were estimated by survival analysis. Of 138 informative DR3-DQ2/DR4-DQ8 siblings, 63% shared both haplotypes with their diabetic proband, 29% shared one, and 8% shared neither. In HLA-identical DR3-DQ2/DR4-DQ8 siblings, the cumulative risk of diabetes by age 15 was 17% (vs. 6% in those sharing one haplotype or none; P = 0.095). Risk varied, however, with the age at the onset of diabetes in the proband; the cumulative risk of autoimmunity and/or diabetes by age 15 was 61% in siblings of probands diagnosed when younger than 10 years old compared with only 4.7% in those diagnosed after age 10 years (P < 0.001). The age of the proband at diagnosis, but not HLA haplotype sharing, was an independent determinant of sibling risk. This suggests that non-HLA genes or epigenetic/environmental factors that accelerate the progression of type 1 diabetes in the proband strongly affect risk in siblings.

Association of Pro12Ala polymorphism in peroxisome proliferator activated receptor gamma with proliferative diabetic retinopathy

PubMed Central

Tariq, Khadija; Malik, Saira Bano; Ali, Syeda Hafiza Benish; Maqsood, Sundas Ejaz; Azam, Aisha; Muslim, Irfan; Khan, Muhammad Shakil; Azam, Maleeha; Waheed, Nadia Khalida

2013-01-01

Purpose The association of non-synonymous substitution polymorphism rs1801282 (c.34C>G, p.Pro12Ala) in exon 4 of the peroxisome proliferator activated receptor gamma gene with diabetic retinopathy (DR) has been reported inconsistently. Therefore, the purpose of the present study was to understand the population-specific role of the Pro12Ala polymorphism in DR susceptibility in Pakistani subjects. Methods A total of 180 subjects with DR, 193 subjects with type 2 diabetes mellitus (T2DM) with no diabetic retinopathy, and 200 healthy normoglycemic non-retinopathic Pakistani individuals were genotyped for the rs1801282 (c.34C>G) polymorphism using polymerase chain reaction-restriction fragment length polymorphism. Results We found the individuals with T2DM carrying 12Ala were at a reduced risk of developing DR (odds ratio [OR]=0.53; 95% confidence interval [CI]=0.33–0.87). Upon stratified analysis regarding disease severity, we observed this protective effect was confined to proliferative DR (OR=0.4; 95% CI=0.2–0.8) with non-significant effects on the susceptibility of non-proliferative DR (OR=0.67; 95% CI=0.37–1.19). Conclusions We report a protective role of the 12Ala polymorphism against proliferative DR in individuals with T2DM in Pakistan. PMID:23559865

ARC Accomplishments and Collaborations Pursuing Challenges with Vision and Focus

DTIC Science & Technology

2010-05-10

Navistar Defense LLC – Dr. Joe Lin, Eaton – Dr. Young Jae Kim, GM Hybrid Powertrain Eng. – Dr. Bin Wu, Mercedes - Benz Hybrid LLC – Dr. Vasilios Tsourapas...Fellows: 3 SAE, 4 ASME, 1 AAAS,1 IACM, 3 IEEE • 8 external Research and Educational Awards • 8 University Awards • 2 Young Scientists/Young Innovator

Monoclonal and anti-idiotypic anti-EBV/C3d receptor antibodies detect two binding sites, one for EBV and one for C3d on glycoprotein 140, the EBV/C3dR, expressed on human B lymphocytes.

PubMed

Barel, M; Fiandino, A; Delcayre, A X; Lyamani, F; Frade, R

1988-09-01

Glycoprotein (gp) 140, the EBV/C3dR of B lymphocytes, is a membrane site involved in human cell regulation. To analyze the specificities of the binding sites for EBV and for C3d on the gp 140 molecule, two distinct approaches were used. First, anti-EBV/C3dR mAb were prepared against highly purified EBV/C3dR. Nine anti-EBV/C3dR mAb were obtained. Four of these anti-EBV/C3dR mAb inhibited C3d binding but not EBV binding on gp 140, whereas four others exerted an inverse effect. These differences could not be due to differences in isotype, antibody concentration, affinity constant, and number of molecules bound on cell surface, as these parameters were identical for the nine used mAb. Second, polyclonal anti-idiotypic antibodies (Ab2) were prepared against F(ab)'2 fragments of polyclonal anti-EBV/C3dR (Ab1). Ab2 recognized the variable portion of Ab1 as controlled by immunoblotting experiments. Ab2, which did not react with the cell surface, inhibited Ab1 binding on Raji cells. Ab2 mimicked the EBV/C3dR by its properties to bind to particle-bound C3d and EBV, preventing their binding on Raji cell surface. C3d binding specificities contained in Ab2 were isolated by affinity chromatography on C3b/C3bi-Sepharose. These specificities, being the internal image of C3d binding site of EBV/C3dR, reacted with Ab1 and inhibited particle-bound C3d binding on Raji cells but did not react with EBV. Taken together, these data support strongly that gp 140, the EBV/C3dR, carried two distinct binding sites, one for EBV and one for C3d.

Increased Cyclooxygenase-2-Derived Prostanoids Contributes to the Hyperreactivity to Noradrenaline in Mesenteric Resistance Arteries from Offspring of Diabetic Rats

PubMed Central

Santos-Rocha, Juliana; Duarte, Gloria P.; Xavier, Fabiano E.

2012-01-01

This study analyzed the effect of in utero exposure to maternal diabetes on contraction to noradrenaline in mesenteric resistance arteries (MRA) from adult offspring, focusing on the role of cyclooxygenase (COX)-derived prostanoids. Diabetes in the maternal rat was induced by a single injection of streptozotocin (50 mg/kg body weight) on day 7 of pregnancy. Contraction to noradrenaline was analyzed in isolated MRA from offspring of diabetic (O-DR) and non-diabetic (O-CR) rats at 3, 6 and 12 months of age. Release of thromboxane A2 (TxA2) and prostaglandins E2 (PGE2) and F2α (PGF2α), was measured by specific enzyme immunoassay kits. O-DR developed hypertension from 6 months of age compared with O-CR. Arteries from O-DR were hyperactive to noradrenaline only at 6 and 12 months of age. Endothelial removal abolished this hyperreactivity to noradrenaline between O-CR and O-DR. Preincubation with either the COX-1/2 (indomethacin) or COX-2 inhibitor (NS-398) decreased noradrenaline contraction only in 6- and 12-month-old O-DR, while it remained unmodified by COX-1 inhibitor SC-560. In vessels from 6-month-old O-DR, a similar reduction in the contraction to noradrenaline produced by NS-398 was observed when TP and EP receptors were blocked (SQ29548+AH6809). In 12-month-old O-DR, this effect was only achieved when TP, EP and FP were blocked (SQ29548+AH6809+AL8810). Noradrenaline-stimulated TxB2 and PGE2 release was higher in 6- and 12-month-old O-DR, whereas PGF2α was increased only in 12-month-old O-DR. Our results demonstrated that in utero exposure to maternal hyperglycaemia in rats increases the participation of COX-2-derived prostanoids on contraction to noradrenaline, which might help to explain the greater response to this agonist in MRA from 6- and 12-month-old offspring. As increased contractile response in resistance vessels may contribute to hypertension, our results suggest a role for these COX-2-derived prostanoids in elevating vascular resistance and blood pressure in offspring of diabetic rats. PMID:23209788

Neonatal outcomes following extensive cardiopulmonary resuscitation in the delivery room for infants born at less than 33 weeks gestational age.

PubMed

Soraisham, Amuchou Singh; Lodha, Abhay Kumar; Singhal, Nalini; Aziz, Khalid; Yang, Junmin; Lee, Shoo K; Shah, Prakesh S

2014-02-01

To examine the neonatal mortality and morbidity of infants born at <33 weeks gestational age (GA) who received extensive delivery room cardiopulmonary resuscitation (DR-CPR) immediately after birth. In this retrospective cohort study, we performed secondary analyses of data from infants born at <33 weeks GA and admitted to participating NICUs in the Canadian Neonatal Network between January 2010 and December 2011. Infants were divided into two groups based on birth weight (<1000 g and ≥1000 g) and neonatal morbidity and mortality compared using bivariate and multivariate analyses. Of the 8033 eligible infants, 419 (5.2%) received DR-CPR. For infants weighing <1000 g at birth, 10.9% (outborn: 21.6%, inborn: 7.6%) received DR-CPR, whereas 3.4% (outborn: 9.6%, inborn: 2.2%) of those weighing ≥1000 g received DR-CPR. If infants received DR-CPR there was increased risk of mortality, bronchopulmonary dysplasia (BPD) and severe brain injury. Logistic regression analysis showed DR-CPR was associated with increased mortality (adjusted odds ratio [aOR]: 2.09, 95% CI [1.39, 3.14]) in infants born weighing <1000 g. Among infants born weighing ≥1000 g, DR-CPR was associated with increased mortality (aOR: 7.16, 95% CI [3.88, 13.2]), severe brain injury (aOR: 3.08, 95% CI [1.82, 5.22]), BPD (aOR: 2.14, 95% CI [1.25, 3.65]), pneumothorax (aOR: 3.11, 95% CI [1.53, 6.31]) and intestinal perforation (aOR: 3.47, 95% CI [1.46, 8.24]). DR-CPR is associated with increased risk of mortality and morbidity especially in preterm infants born weighing ≥1000 g. Long-term neurodevelopmental follow up is warranted for these infants.

Understanding type 1 diabetes through genetics: Advances and prospects.

PubMed

Tandon, Nikhil

2015-04-01

The largest contribution of type 1 diabetes mellitus (T1DM) from a single locus comes from several genes located in the major histocompatibility complex on chromosome 6p21. Because DQB1 is the best single genetic marker for T1DM, it is the gene most often used to identify individuals with a high risk of developing disease. As per the data collected from the All India Institute of Medical Sciences, among the human leukocyte antigen (HLA)-DRB1 genes, HLA-DR3 showed strongest association with the disease; however, unlike Caucasians and other populations, DR4 was not significantly increased in these patients. HLA-DR10, 11, 13, and 15 showed a negative association with the disease as they were reduced in these patients. In India, the relative risk of developing T1DM is higher with the DR3-DQ2 haplotypes as compared to DR4-DQ8 haplotypes. Studies have shown that in North India, the relative risk for T1DM is comparatively higher (>30) with the DQ2/DQ8 genotype, but is relatively lower (approximately 18) for the DQ2/DQ2 genotype. In addition, the three sets of HLA-B-DR3 haplotypes, mainly B58-DR3, B50-DR3, and B8-DR3 have shown to have modulated susceptibility for T1DM in India and worldwide. New interventions that will be tested in the future will be conducted through T1DM TrialNet, a collaborative network of clinical centers and experts in diabetes and immunology. These studies will identify unaffected first-degree relatives with beta cell autoantibodies who will be eligible for new interventions.

Association study of sorbitol dehydrogenase -888G>C polymorphism with type 2 diabetic retinopathy in Caucasian-Brazilians.

PubMed

Ferreira, Fábio Netto; Crispim, Daisy; Canani, Luís Henrique; Gross, Jorge Luiz; dos Santos, Kátia Gonçalves

2013-10-01

Diabetic retinopathy (DR) is a common chronic complication of diabetes and remains the leading cause of blindness in working-aged people. Hyperglycemia increases glucose flux through the polyol pathway, in which aldose reductase converts glucose into intracellular sorbitol, which is subsequently converted to fructose by sorbitol dehydrogenase (SDH). The accelerated polyol pathway triggers a cascade of events leading to retinal vascular endothelial dysfunction and the eventual development of DR. Polymorphisms in the gene encoding aldose reductase have been consistently associated with DR. However, only two studies have analyzed the relationship between polymorphisms in the gene encoding SDH (SORD) and DR. In this case-control study, we investigated whether the -888G > C polymorphism (rs3759890) in the SORD gene is associated with the presence or severity of DR in 446 Caucasian-Brazilians with type 2 diabetes (241 subjects with and 205 subjects without DR). The -888G > C polymorphism was also examined in 105 healthy Caucasian blood donors, and the genotyping of this polymorphism was carried out by real-time PCR. The genotype and allele frequencies of the -888G > C polymorphism in patients with type 2 diabetes were similar to those of blood donors (G allele frequency = 0.16 in both groups of subjects). Similarly, the genotype and allele frequencies in patients with DR or the proliferative form of DR were similar to those of patients without this complication (P > 0.05 for all comparisons). Thus, our findings suggest that the -888G > C polymorphism in the SORD gene is not involved in the pathogenesis of DR in type 2 diabetes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Diabetes eye screening in urban settings serving minority populations: detection of diabetic retinopathy and other ocular findings using telemedicine.

PubMed

Owsley, Cynthia; McGwin, Gerald; Lee, David J; Lam, Byron L; Friedman, David S; Gower, Emily W; Haller, Julia A; Hark, Lisa A; Saaddine, Jinan

2015-02-01

The use of a nonmydriatic camera for retinal imaging combined with the remote evaluation of images at a telemedicine reading center has been advanced as a strategy for diabetic retinopathy (DR) screening, particularly among patients with diabetes mellitus from ethnic/racial minority populations with low utilization of eye care. To examine the rate and types of DR identified through a telemedicine screening program using a nonmydriatic camera, as well as the rate of other ocular findings. A cross-sectional study (Innovative Network for Sight [INSIGHT]) was conducted at 4 urban clinic or pharmacy settings in the United States serving predominantly ethnic/racial minority and uninsured persons with diabetes. Participants included persons aged 18 years or older who had type 1 or 2 diabetes mellitus and presented to the community-based settings. The percentage of DR detection, including type of DR, and the percentage of detection of other ocular findings. A total of 1894 persons participated in the INSIGHT screening program across sites, with 21.7% having DR in at least 1 eye. The most common type of DR was background DR, which was present in 94.1% of all participants with DR. Almost half (44.2%) of the sample screened had ocular findings other than DR; 30.7% of the other ocular findings were cataract. In a DR telemedicine screening program in urban clinic or pharmacy settings in the United States serving predominantly ethnic/racial minority populations, DR was identified on screening in approximately 1 in 5 persons with diabetes. The vast majority of DR was background, indicating high public health potential for intervention in the earliest phases of DR when treatment can prevent vision loss. Other ocular conditions were detected at a high rate, a collateral benefit of DR screening programs that may be underappreciated.

Meta-analysis of association between the Pro12Ala polymorphism of the peroxisome proliferator–activated receptor-γ2 gene and diabetic retinopathy in Caucasians and Asians

PubMed Central

Ma, Jinlan; Li, Yan; Zhou, Fang; Xu, Xiaoyi; Guo, Gang

2012-01-01

Purpose The Pro12Ala polymorphism of the peroxisome proliferator–activated receptor-γ2 (PPARγ2) gene is reported to be associated with diabetes. However, the gene’s association with diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) has been investigated in numerous epidemiologic studies with controversial results. This meta-analysis aimed to collectively assess the association of the Pro12Ala polymorphism with DR in T2DM. Methods An electronic literature search was conducted on PubMed, ISI Web of Knowledge, EMBASE, and the China National Knowledge Internet. A dominant model [(Pro/Ala +Ala/Ala) versus Pro/Pro] was used to ensure adequate statistical power. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the fixed effect model. Potential sources of heterogeneity and bias were explored. Results This meta-analysis included genotype data from 2,720 cases with DR and 2,450 controls free of DR from eight eligible publications. The results showed the Ala allele had a protective effect on DR in T2DM (OR=0.81; 95% CI: 0.68–0.98, p=0.03). There was no significant evidence against homogeneity (I2=46%, Pheterogeneity=0.07). The sensitivity analysis showed a robust association of the Pro12Ala polymorphism with DR in T2DM after a study involving Caucasians that presented a big effect on heterogeneity (OR=0.75; 95% CI: 0.62–0.91, p=0.003) was excluded. Possible ethnic differences in the association of the Pro12Ala single nucleotide polymorphism and DR were demonstrated; a significant association was illustrated in the Caucasian subgroup (OR=0.74; 95% CI: 0.59–0.94, p=0.01) but was not found in the Asian subgroup (OR=0.77; 95% CI: 0.55–1.07, p=0.12). No publication bias was observed. Conclusions This meta-analysis suggested a significant association exists between the Pro12Ala polymorphism and DR in T2DM with ethnic differences. The Ala allele had a significant protective effect against DR in T2DM. PMID:22993484

Assessment of Diabetic Retinopathy Using Nonmydriatic Ultra-Widefield Scanning Laser Ophthalmoscopy (Optomap) Compared With ETDRS 7-Field Stereo Photography

PubMed Central

Kernt, Marcus; Hadi, Indrawati; Pinter, Florian; Seidensticker, Florian; Hirneiss, Christoph; Haritoglou, Christos; Kampik, Anselm; Ulbig, Michael W.; Neubauer, Aljoscha S.

2012-01-01

OBJECTIVE To compare the diagnostic properties of a nonmydriatic 200° ultra-widefield scanning laser ophthalmoscope (SLO) versus mydriatic Early Treatment of Diabetic Retinopathy Study (ETDRS) 7-field photography for diabetic retinopathy (DR) screening. RESEARCH DESIGN AND METHODS A consecutive series of 212 eyes of 141 patients with different levels of DR were examined. Grading of DR and clinically significant macular edema (CSME) from mydriatic ETDRS 7-field stereo photography was compared with grading obtained by Optomap Panoramic 200 SLO images. All SLO scans were performed through an undilated pupil, and no additional clinical information was used for evaluation of all images by the two independent, masked, expert graders. RESULTS Twenty-two eyes from ETDRS 7-field photography and 12 eyes from Optomap were not gradable by at least one grader because of poor image quality. A total of 144 eyes were analyzed regarding DR level and 155 eyes regarding CSME. For ETDRS 7-field photography, 22 eyes (18 for grader 2) had no or mild DR (ETDRS levels ≤ 20) and 117 eyes (111 for grader 2) had no CSME. A highly substantial agreement between both Optomap DR and CSME grading and ETDRS 7-field photography existed with κ = 0.79 for DR and 0.73 for CSME for grader 1, and κ = 0.77 (DR) and 0.77 (CSME) for grader 2. CONCLUSIONS Determination of CSME and grading of DR level from Optomap Panoramic 200 nonmydriatic images show a positive correlation with mydriatic ETDRS 7-field stereo photography. Both techniques are of sufficient quality to assess DR and CSME. Optomap Panoramic 200 images cover a larger retinal area and therefore may offer additional diagnostic properties. PMID:22912430

Assessment of diabetic retinopathy using nonmydriatic ultra-widefield scanning laser ophthalmoscopy (Optomap) compared with ETDRS 7-field stereo photography.

PubMed

Kernt, Marcus; Hadi, Indrawati; Pinter, Florian; Seidensticker, Florian; Hirneiss, Christoph; Haritoglou, Christos; Kampik, Anselm; Ulbig, Michael W; Neubauer, Aljoscha S

2012-12-01

To compare the diagnostic properties of a nonmydriatic 200° ultra-widefield scanning laser ophthalmoscope (SLO) versus mydriatic Early Treatment of Diabetic Retinopathy Study (ETDRS) 7-field photography for diabetic retinopathy (DR) screening. A consecutive series of 212 eyes of 141 patients with different levels of DR were examined. Grading of DR and clinically significant macular edema (CSME) from mydriatic ETDRS 7-field stereo photography was compared with grading obtained by Optomap Panoramic 200 SLO images. All SLO scans were performed through an undilated pupil, and no additional clinical information was used for evaluation of all images by the two independent, masked, expert graders. Twenty-two eyes from ETDRS 7-field photography and 12 eyes from Optomap were not gradable by at least one grader because of poor image quality. A total of 144 eyes were analyzed regarding DR level and 155 eyes regarding CSME. For ETDRS 7-field photography, 22 eyes (18 for grader 2) had no or mild DR (ETDRS levels ≤ 20) and 117 eyes (111 for grader 2) had no CSME. A highly substantial agreement between both Optomap DR and CSME grading and ETDRS 7-field photography existed with κ = 0.79 for DR and 0.73 for CSME for grader 1, and κ = 0.77 (DR) and 0.77 (CSME) for grader 2. Determination of CSME and grading of DR level from Optomap Panoramic 200 nonmydriatic images show a positive correlation with mydriatic ETDRS 7-field stereo photography. Both techniques are of sufficient quality to assess DR and CSME. Optomap Panoramic 200 images cover a larger retinal area and therefore may offer additional diagnostic properties.

A Comparison of the Effects of Random Versus Fixed Order of Item Presentation Via the Computer

DTIC Science & Technology

1989-02-01

Copies) Dr. Hans Crombag Dr. Stephen Dunbar University of Leyden Lindquist Center Education Research Center for Measurement Boerhaavelaan 2 University of...Iowa 2334 EN Leyden Iowa City, IA 52242 The NETHERLANDS Dr. James A. Earles Dr. Timothy Davey Air Force Human Resources Lab Educational Testing...Montague 4401 Ford Avenue NPRDC Code 13 P.O. Box 16268 San Diego, CA 92152-6800 Alexandria, VA 22302-0268 Ms. Kathleen Moreno Dr..William L. Maloy

Guidon-Watch: A Graphic Interface for Viewing a Knowledge-Based System.

DTIC Science & Technology

1985-08-01

Research Center Department of the Navy University of Illinois Boerhaavelaan 2 Washington, DO 20350-1000 Department of Cmpuer Science2334 EN Leyden 1304...Dr. William L. Maloy 270 Crown Street Pittsburgh, PA 15213 Chief of Naval Education New Haven, CT 06510 and Training Dr. Kathleen IaPiana Naval Air...Mclean, VA 22102 1250 West 6th Street Campus Box 345 San Diego, CA 92101 Boulder, CO 8D302 Dr. Aan M. lesgoldlearning M.D Center Dr. Kathleen McKeown Dr

75 FR 21244 - Procurement List; Proposed Additions and Deletions

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-23

...-NIB-0554--TriBase Multi-Purpose Cleaner, 55 gallon drum, 1 DR. NSN: 7930-00-NIB-0555--BioRenewable Glass Cleaner, 2-liter, 4/BX. NSN: 7930-00-NIB-0556--BioRenewable Glass Cleaner, 55 gallon drum, 1 DR... Disinfectant Cleaner, 55 gallon drum, 1 DR. NSN: 7930-00-NIB-0559--BioRenewable Industrial Cleaner, 2 liter, 4...

Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jo, Miran; Park, Mi Hee; Kollipara, Pushpa Saranya

We investigated whether bee venom and melittin, a major component of bee venom, inhibit cell growth through enhancement of death receptor expressions in the human ovarian cancer cells, SKOV3 and PA-1. Bee venom (1–5 μg/ml) and melittin (0.5–2 μg/ml) inhibited the growth of SKOV3 and PA-1 ovarian cancer cells by the induction of apoptotic cell death in a dose dependent manner. Consistent with apoptotic cell death, expression of death receptor (DR) 3 and DR6 was increased in both cancer cells, but expression of DR4 was increased only in PA-1 cells. Expression of DR downstream pro-apoptotic proteins including caspase-3, 8, andmore » Bax was concomitantly increased, but the phosphorylation of JAK2 and STAT3 and the expression of Bcl-2 were inhibited by treatment with bee venom and melittin in SKOV3 and PA-1 cells. Expression of cleaved caspase-3 was increased in SKOV3, but cleaved caspase-8 was increased in PA-1 cells. Moreover, deletion of DR3, DR4, and DR6 by small interfering RNA significantly reversed bee venom and melittin-induced cell growth inhibitory effect as well as down regulation of STAT3 by bee venom and melittin in SKOV3 and PA-1 ovarian cancer cell. These results suggest that bee venom and melittin induce apoptotic cell death in ovarian cancer cells through enhancement of DR3, DR4, and DR6 expression and inhibition of STAT3 pathway. -- Highlights: ► Some studies have showed that bee venom and/or melittin have anti-cancer effects. ► We found that bee venom and melittin inhibited cell growth in ovarian cancer cells. ► Bee venom and melittin induce apoptosis in SKOV3 and PA-1.« less

Optimal dielectric and cavity configurations for improving the efficiency of electron paramagnetic resonance probes

NASA Astrophysics Data System (ADS)

Elnaggar, Sameh Y.; Tervo, Richard; Mattar, Saba M.

2014-08-01

An electron paramagnetic resonance (EPR) spectrometer’s lambda efficiency parameter (Λ) is one of the most important parameters that govern its sensitivity. It is studied for an EPR probe consisting of a dielectric resonator (DR) in a cavity (CV). Expressions for Λ are derived in terms of the probe’s individual DR and CV components, Λ1 and Λ2 respectively. Two important cases are considered. In the first, a probe consisting of a CV is improved by incorporating a DR. The sensitivity enhancement depends on the relative rather than the absolute values of the individual components. This renders the analysis general. The optimal configuration occurs when the CV and DR modes are nearly degenerate. This configuration guarantees that the probe can be easily coupled to the microwave bridge while maintaining a large Λ. It is shown that for a lossy CV with a small quality factor Q2, one chooses a DR that has the highest filling factor, η1, regardless of its Λ1 and Q1. On the other hand, if the CV has a large Q2, the optimum DR is the one which has the highest Λ1. This is regardless of its η1 and relative dielectric constant, ɛr. When the quality factors of both the CV and DR are comparable, the lambda efficiency is reduced by a factor of √{2}. Thus the signal intensity for an unsaturated sample is cut in half. The second case is the design of an optimum shield to house a DR. Besides preventing radiation leakage, it is shown that for a high loss DR, the shield can actually boost Λ above the DR value. This can also be very helpful for relatively low efficiency dielectrics as well as lossy samples, such as polar liquids.

Global Prevalence and Major Risk Factors of Diabetic Retinopathy

PubMed Central

Yau, Joanne W.Y.; Rogers, Sophie L.; Kawasaki, Ryo; Lamoureux, Ecosse L.; Kowalski, Jonathan W.; Bek, Toke; Chen, Shih-Jen; Dekker, Jacqueline M.; Fletcher, Astrid; Grauslund, Jakob; Haffner, Steven; Hamman, Richard F.; Ikram, M. Kamran; Kayama, Takamasa; Klein, Barbara E.K.; Klein, Ronald; Krishnaiah, Sannapaneni; Mayurasakorn, Korapat; O’Hare, Joseph P.; Orchard, Trevor J.; Porta, Massimo; Rema, Mohan; Roy, Monique S.; Sharma, Tarun; Shaw, Jonathan; Taylor, Hugh; Tielsch, James M.; Varma, Rohit; Wang, Jie Jin; Wang, Ningli; West, Sheila; Xu, Liang; Yasuda, Miho; Zhang, Xinzhi; Mitchell, Paul; Wong, Tien Y.

2012-01-01

OBJECTIVE To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes. RESEARCH DESIGN AND METHODS A pooled analysis using individual participant data from population-based studies around the world was performed. A systematic literature review was conducted to identify all population-based studies in general populations or individuals with diabetes who had ascertained DR from retinal photographs. Studies provided data for DR end points, including any DR, proliferative DR, diabetic macular edema, and VTDR, and also major systemic risk factors. Pooled prevalence estimates were directly age-standardized to the 2010 World Diabetes Population aged 20–79 years. RESULTS A total of 35 studies (1980–2008) provided data from 22,896 individuals with diabetes. The overall prevalence was 34.6% (95% CI 34.5–34.8) for any DR, 6.96% (6.87–7.04) for proliferative DR, 6.81% (6.74–6.89) for diabetic macular edema, and 10.2% (10.1–10.3) for VTDR. All DR prevalence end points increased with diabetes duration, hemoglobin A1c, and blood pressure levels and were higher in people with type 1 compared with type 2 diabetes. CONCLUSIONS There are approximately 93 million people with DR, 17 million with proliferative DR, 21 million with diabetic macular edema, and 28 million with VTDR worldwide. Longer diabetes duration and poorer glycemic and blood pressure control are strongly associated with DR. These data highlight the substantial worldwide public health burden of DR and the importance of modifiable risk factors in its occurrence. This study is limited by data pooled from studies at different time points, with different methodologies and population characteristics. PMID:22301125

Global prevalence and major risk factors of diabetic retinopathy.

PubMed

Yau, Joanne W Y; Rogers, Sophie L; Kawasaki, Ryo; Lamoureux, Ecosse L; Kowalski, Jonathan W; Bek, Toke; Chen, Shih-Jen; Dekker, Jacqueline M; Fletcher, Astrid; Grauslund, Jakob; Haffner, Steven; Hamman, Richard F; Ikram, M Kamran; Kayama, Takamasa; Klein, Barbara E K; Klein, Ronald; Krishnaiah, Sannapaneni; Mayurasakorn, Korapat; O'Hare, Joseph P; Orchard, Trevor J; Porta, Massimo; Rema, Mohan; Roy, Monique S; Sharma, Tarun; Shaw, Jonathan; Taylor, Hugh; Tielsch, James M; Varma, Rohit; Wang, Jie Jin; Wang, Ningli; West, Sheila; Xu, Liang; Yasuda, Miho; Zhang, Xinzhi; Mitchell, Paul; Wong, Tien Y

2012-03-01

To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes. A pooled analysis using individual participant data from population-based studies around the world was performed. A systematic literature review was conducted to identify all population-based studies in general populations or individuals with diabetes who had ascertained DR from retinal photographs. Studies provided data for DR end points, including any DR, proliferative DR, diabetic macular edema, and VTDR, and also major systemic risk factors. Pooled prevalence estimates were directly age-standardized to the 2010 World Diabetes Population aged 20-79 years. A total of 35 studies (1980-2008) provided data from 22,896 individuals with diabetes. The overall prevalence was 34.6% (95% CI 34.5-34.8) for any DR, 6.96% (6.87-7.04) for proliferative DR, 6.81% (6.74-6.89) for diabetic macular edema, and 10.2% (10.1-10.3) for VTDR. All DR prevalence end points increased with diabetes duration, hemoglobin A(1c), and blood pressure levels and were higher in people with type 1 compared with type 2 diabetes. There are approximately 93 million people with DR, 17 million with proliferative DR, 21 million with diabetic macular edema, and 28 million with VTDR worldwide. Longer diabetes duration and poorer glycemic and blood pressure control are strongly associated with DR. These data highlight the substantial worldwide public health burden of DR and the importance of modifiable risk factors in its occurrence. This study is limited by data pooled from studies at different time points, with different methodologies and population characteristics.

Influence of auxochrome group in disperse dyes bearing azo groups as chromophore center in the biotransformation and molecular docking prediction by reductase enzyme: Implications and assessment for environmental toxicity of xenobiotics.

PubMed

Franco, Jefferson Honorio; da Silva, Bianca F; Dias, Elisangela Franciscon G; de Castro, Alexandre A; Ramalho, Teodorico C; Zanoni, Maria Valnice Boldrin

2018-05-21

Synthetic azo dyes have increasingly become a matter of great concern as a result of the genotoxic and mutagenic potential of the products derived from azo dye biotransformation. This work evaluates the manner in which reducing enzymes produced by Escherichia coli (E. coli) act on three disperse dyes bearing azo groups, namely Disperse Red 73 (DR 73), Disperse Red 78 (DR 78), and Disperse Red 167 (DR 167). UV-Vis spectrophotometry, high-performance liquid chromatography with diode array detector (HPLC-DAD), and liquid chromatography mass spectrometry (LC-MS/MS) were applied towards the identification of the main products. Seven days of incubation of the azo dyes with the tested enzymes yielded a completely bleached solution. 3-4-Aminophenyl-ethyl-amino-propanitrile was detected following the biotransformation of both DR 73 and DR 78. 4-Nitroaniline and 2-chloro-4-nitroaniline were detected upon the biotransformation of DR 73 and DR 78, respectively. The main products derived from the biotransformation of DR 167 were dimethyl 3,3'-3-acetamido-4-aminophenyl-azanedyl-dipropanoate and 2-chloro-4-nitroaniline. The results imply that DR 73 lost the CN - substituent during the biotransformation. Furthermore, theoretical calculations were also carried out aiming at evaluating the interaction and reactivity of these compounds with DNA. Taken together, the results indicate that DR 73, DR 78, and DR 167 pose health risks and serious threats to both human beings and the environment at large as their biotransformation produces harmful compounds such as amines, which have been widely condemned by the International Agency for Research on Cancer. Copyright © 2018. Published by Elsevier Inc.

Investigation of the HLA component involved in rheumatoid arthritis (RA) by using the marker association-segregation [chi][sup 2] (MASC) method: Rejection of the unifying-shared-epitope hypothesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dizier, M.H.; Eliaou, J.F.; Babron, M.C.

In order to investigate the HLA component involved in rheumatoid arthritis (RA), the authors tested genetic models by the marker association-segregation [chi][sup 2] (MASC) method, using the HLA genotypic distribution observed in a sample of 97 RA patients. First they tested models assuming the involvement of a susceptibility gene linked to the DR locus. They showed that the present data are compatible with a simple model assuming the effect of a recessive allele of a biallelic locus linked to the DR locus and without any assumption of synergistic effect. Then they considered models assuming the direct involvement of the DRmore » allele products, and tested the unifying-shared-epitope hypothesis, which has been proposed. Under this hypothesis the DR alleles are assumed to be directly involved in the susceptibility to the disease because of the presence of similar or identical amino acid sequences in position 70-74 of the third hypervariable region of the DRBI molecules, shared by the RA-associated DR alleles DR4Dw4, DR4Dw14, and DR1. This hypothesis was strongly rejected with the present data. In the case of the direct involvement of the DR alleles, hypotheses more complex that the unifying-shared-epitope hypothesis would have to be considered. 28 refs., 2 tabs.« less

Effects of Granular Control on Customers’ Perspective and Behavior with Automated Demand Response Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schetrit, Oren; Kim, Joyce; Yin, Rongxin

2014-08-01

Automated demand response (Auto-DR) is expected to close the loop between buildings and the grid by providing machine-to-machine communications to curtail loads without the need for human intervention. Hence, it can offer more reliable and repeatable demand response results to the grid than the manual approach and make demand response participation a hassle-free experience for customers. However, many building operators misunderstand Auto-DR and are afraid of losing control over their building operation. To ease the transition from manual to Auto-DR, we designed and implemented granular control of Auto-DR systems so that building operators could modify or opt out of individualmore » load-shed strategies whenever they wanted. This paper reports the research findings from this effort demonstrated through a field study in large commercial buildings located in New York City. We focused on (1) understanding how providing granular control affects building operators’ perspective on Auto-DR, and (2) evaluating the usefulness of granular control by examining their interaction with the Auto-DR user interface during test events. Through trend log analysis, interviews, and surveys, we found that: (1) the opt-out capability during Auto-DR events can remove the feeling of being forced into load curtailments and increase their willingness to adopt Auto-DR; (2) being able to modify individual load-shed strategies allows flexible Auto-DR participation that meets the building’s changing operational requirements; (3) a clear display of automation strategies helps building operators easily identify how Auto-DR is functioning and can build trust in Auto-DR systems.« less

Evaluation of Diabetic Retinal Screening and Factors for Ophthalmology Referral in a Telemedicine Network.

PubMed

Jani, Pooja D; Forbes, Lauren; Choudhury, Arkopal; Preisser, John S; Viera, Anthony J; Garg, Seema

2017-07-01

Retinal telescreening for evaluation of diabetic retinopathy (DR) in the primary care setting may be useful in reaching rural and underserved patients. To evaluate telemedicine retinal screenings for patients with type 1 or 2 diabetes and identify factors for ophthalmology referral in the North Carolina Diabetic Retinopathy Telemedicine Network. A preimplementation and postimplementation evaluation was conducted from January 6, 2014, to November 1, 2015, at 5 primary care clinics serving rural and underserved populations in North Carolina among 1787 adult patients with type 1 or 2 diabetes who received primary care at the clinics and obtained retinal telescreening to determine the presence and severity of DR. A total of 1661 patients with complete data were included in the statistical analysis. Nonmydriatic fundus photography with remote interpretation by an expert. Number of patients recruited, level of detected DR, change in rates of screening, rate of ophthalmology referral, percentage of completed referrals, and patient characteristics associated with varying levels of DR. Of the 1661 patients (1041 women and 620 men; mean [SD] age, 55.4 [12.7] years), 1323 patients (79.7%) had no DR, 183 patients (11.0%) had DR without a need for an ophthalmology referral, and 155 patients (9.3%) had DR with a need for an ophthalmology referral. The mean rate of screening for DR before implementation of the program was 25.6% (1512 of 5905), which increased to 40.4% (1884 of 4664) after implementation. A total of 93 referred patients (60.0%) completed an ophthalmology referral visit within the study period. Older patients (odds ratio [OR], 1.28; 95% CI, 1.11-1.48) and African American patients (OR, 1.84; 95% CI, 1.24-2.73) or other racial/ethnic minorities (OR, 2.19; 95% CI, 1.16-4.11) had greater odds of requiring an ophthalmology referral compared with white and/or younger patients. Patients with higher hemoglobin A1c levels (OR, 1.19 per unit change; 95% CI, 1.13-1.25 per unit change) and longer duration of diabetes (OR, 1.76 per decade; 95% CI, 1.53-2.02 per decade) had greater odds of DR requiring an ophthalmology referral. History of stroke (OR, 1.65; 95% CI, 1.10-2.48) and kidney disease (OR, 1.59; 95% CI, 1.10-2.31) were strongly associated with DR and ophthalmology referral. When implemented in the primary care setting, retinal telescreening increased the rate of evaluation for DR for patients in rural and underserved settings. This strategy may also increase access to care for minorities and patients with DR requiring treatment.

HbA1c, systolic blood pressure variability and diabetic retinopathy in Asian type 2 diabetics.

PubMed

Foo, Valencia; Quah, Joanne; Cheung, Gemmy; Tan, Ngiap Chun; Ma Zar, Kyi Lin; Chan, Choi Mun; Lamoureux, Ecosse; Tien Yin, Wong; Tan, Gavin; Sabanayagam, Charumathi

2017-02-01

The aim of the present study was to examine the association between variability in HbA1c or systolic blood pressure (SBP) and diabetes-specific moderate retinopathy in Asians with type 2 diabetes (T2D). A retrospective study was conducted of 172 cases of moderate diabetic retinopathy (DR) cases and 226 controls without DR, matched for age, sex, and ethnicity. Serial HbA1c and SBP (range 3-6 readings) over the 2 years prior to photographic screening of DR were collected. Intrapersonal mean and SD values for HbA1c (iM-HbA1c and iSD-HbA1c) and SBP (iM-SBP and iSD-SBP) were derived. Moderate DR was assessed from digital retinal photographs and defined as levels >43 using the Early Treatment Diabetic Retinopathy Study scale. Cases of moderate DR had higher iM-HbA1c (8.2 % vs 7.3 %; P = 0.001), iSD-HbA1c (1.22 vs 0.64; P = 0.001), iM-SBP (136.8 vs 129.6 mmHg; P = 0.001) and iSD-SBP (13.3 vs 11.1; P = 0.002) than controls. In the multivariate regression model adjusted for age, gender, ethnicity, duration of diabetes, SBP, and HbA1c, iM-HbA1c and iM-SBP were significantly associated with moderate DR (odds ratio [OR] 1.80, 95 % confidence interval [CI] 1.37-2.36; and OR 1.03, 95 % CI 1.01-1.05, respectively). Neither iSD-HbA1c nor iSD-SBP were associated with moderate DR. When stratified by HbA1c <7 %, only iSD-SBP remained significantly associated with moderate DR (OR 1.11, 95 % CI 1.01-1.21). In a cohort of Asian patients with T2D, both higher mean HbA1c levels and SBP, but not their variability, were associated with moderate DR. Among those with good glycemic control, wider variability of SBP is associated with moderate DR. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Heritability of the severity of diabetic retinopathy: the FIND-Eye study.

PubMed

Arar, Nedal H; Freedman, Barry I; Adler, Sharon G; Iyengar, Sudha K; Chew, Emily Y; Davis, Mathew D; Satko, Scott G; Bowden, Donald W; Duggirala, Ravi; Elston, Robert C; Guo, Xiuxing; Hanson, Robert L; Igo, Robert P; Ipp, Eli; Kimmel, Paul L; Knowler, William C; Molineros, Julio; Nelson, Robert G; Pahl, Madeleine V; Quade, Shannon R E; Rasooly, Rebekah S; Rotter, Jerome I; Saad, Mohammed F; Scavini, Marina; Schelling, Jeffrey R; Sedor, John R; Shah, Vallabh O; Zager, Philip G; Abboud, Hanna E

2008-09-01

Diabetic retinopathy (DR) and diabetic nephropathy (DN) are serious microvascular complications of diabetes mellitus. Correlations between severity of DR and DN and computed heritability estimates for DR were determined in a large, multiethnic sample of diabetic families. The hypothesis was that (1) the severity of DR correlates with the presence and severity of nephropathy in individuals with diabetes mellitus, and (2) the severity of DR is under significant familial influence in members of multiplex diabetic families. The Family Investigation of Nephropathy and Diabetes (FIND) was designed to evaluate the genetic basis of DN in American Indians, European Americans, African Americans, and Mexican Americans. FIND enrolled probands with advanced DN, along with their diabetic siblings who were concordant and discordant for nephropathy. These diabetic family members were invited to participate in the FIND-Eye study to determine whether inherited factors underlie susceptibility to DR and its severity. FIND-Eye participants underwent eye examinations and had fundus photographs taken. The severity of DR was graded by using the Early Treatment Diabetic Retinopathy Study Classification (ETDRS). Sib-sib correlations were calculated with the SAGE 5.0 program FCOR, to estimate heritability of retinopathy severity. This report summarizes the results for the first 2368 diabetic subjects from 767 families enrolled in FIND-Eye; nearly 50% were Mexican American, the largest single ethnicity within FIND. The overall prevalence of DR was high; 33.4% had proliferative DR; 7.5%, 22.8%, and 9.5% had severe, moderate, and mild nonproliferative DR, respectively; 26.6% had no DR. The severity of DR was significantly associated with severity of DN, both by phenotypic category and by increasing serum creatinine concentration (chi(2) = 658.14, df = 20; P < 0.0001). The sib-sib correlation for DR severity was 0.1358 in the total sample and 0.1224 when limited to the Mexican-American sample. Broad sense heritabilities for DR were 27% overall and 24% in Mexican-American families. The polygenic heritability of liability for proliferative DR approximated 25% in this FIND-Eye sample. These data confirm that the severity of DR parallels the presence and severity of nephropathy in individuals with diabetes mellitus. The severity of DR in members of multiplex diabetic families appears to have a significant familial connection.

Heritability of the Severity of Diabetic Retinopathy: The FIND-Eye Study

PubMed Central

Arar, Nedal H.; Freedman, Barry I.; Adler, Sharon G.; Iyengar, Sudha K.; Chew, Emily Y.; Davis, Mathew D.; Satko, Scott G.; Bowden, Donald W.; Duggirala, Ravi; Elston, Robert C.; Guo, Xiuxing; Hanson, Robert L.; Igo, Robert P.; Ipp, Eli; Kimmel, Paul L.; Knowler, William C.; Molineros, Julio; Nelson, Robert G.; Pahl, Madeleine V.; Quade, Shannon R. E.; Rasooly, Rebekah S.; Rotter, Jerome I.; Saad, Mohammed F.; Scavini, Marina; Schelling, Jeffrey R.; Sedor, John R.; Shah, Vallabh O.; Zager, Philip G.; Abboud, Hanna E.

2008-01-01

PURPOSE Diabetic retinopathy (DR) and diabetic nephropathy (DN) are serious microvascular complications of diabetes mellitus. Correlations between severity of DR and DN and computed heritability estimates for DR were determined in a large, multiethnic sample of diabetic families. The hypothesis was that (1) the severity of DR correlates with the presence and severity of nephropathy in individuals with diabetes mellitus, and (2) the severity of DR is under significant familial influence in members of multiplex diabetic families. METHODS The Family Investigation of Nephropathy and Diabetes (FIND) was designed to evaluate the genetic basis of DN in American Indians, European Americans, African Americans, and Mexican Americans. FIND enrolled probands with advanced DN, along with their diabetic siblings who were concordant and discordant for nephropathy. These diabetic family members were invited to participate in the FIND-Eye study to determine whether inherited factors underlie susceptibility to DR and its severity. FIND-Eye participants underwent eye examinations and had fundus photographs taken. The severity of DR was graded by using the Early Treatment Diabetic Retinopathy Study Classification (ETDRS). Sib–sib correlations were calculated with the SAGE 5.0 program FCOR, to estimate heritability of retinopathy severity. RESULTS This report summarizes the results for the first 2368 diabetic subjects from 767 families enrolled in FIND-Eye; nearly 50% were Mexican American, the largest single ethnicity within FIND. The overall prevalence of DR was high; 33.4% had proliferative DR; 7.5%, 22.8%, and 9.5% had severe, moderate, and mild nonproliferative DR, respectively; 26.6% had no DR. The severity of DR was significantly associated with severity of DN, both by phenotypic category and by increasing serum creatinine concentration (χ2 = 658.14, df = 20; P < 0.0001). The sib–sib correlation for DR severity was 0.1358 in the total sample and 0.1224 when limited to the Mexican-American sample. Broad sense heritabilities for DR were 27% overall and 24% in Mexican-American families. The polygenic heritability of liability for proliferative DR approximated 25% in this FIND-Eye sample. CONCLUSIONS These data confirm that the severity of DR parallels the presence and severity of nephropathy in individuals with diabetes mellitus. The severity of DR in members of multiplex diabetic families appears to have a significant familial connection. PMID:18765632

Prevalence of Retinopathy in Adult Patients with GCK-MODY and HNF1A-MODY.

PubMed

Szopa, M; Wolkow, J; Matejko, B; Skupien, J; Klupa, T; Wybrańska, I; Trznadel-Morawska, I; Kiec-Wilk, B; Borowiec, M; Malecki, M T

2015-10-01

We aimed to assess the prevalence of diabetic retinopathy (DR) in adult patients with GCK-MODY and HNF1A-MODY in Poland and to identify biochemical and clinical risk factors associated with its occurrence.We examined 74 GCK mutation carriers, 51 with diabetes and 23 with prediabetes, respectively, and 63 patients with HNF1A-MODY. Retinal photographs, 12 for each patient, were done by a fundus camera. Signs of DR were graded according to the DR disease severity scale. Statistical tests were performed to assess differences between the groups and logistic regression was done for the association with DR.The mean age at examination was 34.5±14.8 and 39.9±15.2 in the GCK-MODY and HNF1A-MODY groups, respectively. Mild nonproliferative DR (NPDR) was found in one patient with the GCK mutation and likely concomitant type 1 diabetes, whereas DR was diagnosed in 15 HNF1A-MODY patients: 9 with proliferative, 3 with moderate NPDR and 2 with mild NPDR. In univariate logistic regression analysis in the HNF1A-MODY group, significant results were found for diabetes duration, fasting glycemia, HbA1c, arterial hypertension, age at the examination, and eGFR. The strongest independent predictors of DR in HNF1A-MODY were markers of glucose control: HbA1c (OR: 2.05, CL%95: 1.2-3.83, p=0.01) and glucose (p=0.006, OR: 1.40, CL%95: 1.12-1.83) analyzed in 2 separated models. Additionally, arterial hypertension independently predicted DR (OR: 9.06, CL%95: 1.19-98.99, p=0.04) in the model with HbA1c as glycaemic control marker.In conclusion, DR of any degree was not present in our GCK-MODY group, while in spite of young age almost every fourth subject with HNF1A-MODY showed signs of this complication. © Georg Thieme Verlag KG Stuttgart · New York.

Does transitioning from computed radiography (CR) to direct radiography (DR) with portable imaging systems affect workflow efficiency?

NASA Astrophysics Data System (ADS)

Gali, Raja L.; Roth, Christopher G.; Smith, Elizabeth; Dave, Jaydev K.

2018-03-01

In digital radiography, computed radiography (CR) technology is based on latent image capture by storage phosphors whereas direct radiography (DR) technology is based either on indirect conversion using a scintillator or direct conversion using a photoconductor. DR-based portable imaging systems may enhance workflow efficiency. The purpose of this work was to investigate changes in workflow efficiency at a tertiary healthcare center after transitioning from CR to DR technology for imaging with portable x-ray units. An IRB exemption was obtained. Data for all inpatient-radiographs acquired with portable x-ray units from July-2014 till June-2015 (period 1) with CR technology (AMX4 or AMX4+ portable unit from GE Healthcare, NX workstation from Agfa Healthcare for digitization), from July-2015 till June-2016 (period 2) with DR technology (Carestream DRX-Revolution x-ray units and DRX-1C image receptors) and from July-2016 till January-2017 (period 3; same DR technology) were extracted using Centricity RIS-IC (GE Healthcare). Duration between the imaging-examination scheduled time and completed time (timesch-com) was calculated and compared using non-parametric tests (between the three time periods with corrections for multiple comparisons; three time periods were used to identify if there were any other potential temporal trends not related to transitioning from CR to DR). IBM's SPSS package was used for statistical analysis. Overall data was obtained from 33131, 32194, and 18015 cases in periods 1, 2 and 3, respectively. Independent-Samples Kruskal-Wallis test revealed a statistically significant difference in timesch-com across the three time periods (χ2(2, n= 83,340) = 2053, p < 0.001). The timesch-com was highest for period 1 i.e., radiographs acquired with CR technology (median: 64 minutes) and it decreased significantly for radiographs acquired with DR technology in periods 2 (median: 49 minutes; p < 0.001) and 3 (median∶ 44 minutes; p < 0.001). Overall, adoption of DR technology resulted in a drop in timesch-com by 27% relative to the use of CR technology. Transitioning from CR to DR was associated with improved workflow efficiency for radiographic imaging with portable x-ray units.

A novel “humanized mouse” model for autoimmune hepatitis and the association of gut microbiota with liver inflammation

PubMed Central

Yuksel, Muhammed; Wang, Yipeng; Tai, Ningwen; Peng, Jian; Guo, Junhua; Beland, Kathie; Lapierre, Pascal; David, Chella; Alvarez, Fernando; Colle, Isabelle; Yan, Huiping; Mieli-Vergani, Giorgina; Vergani, Diego; Ma, Yun; Wen, Li

2016-01-01

Background Autoimmune hepatitis (AIH) in humans is a severe inflammatory liver disease, characterized by interface hepatitis, the presence of circulating autoantibodies and hyper-gammaglobulinemia. There are two types of AIH, type-1 (AIH-1) and type-2 (AIH-2) characterized by distinct autoimmune serology. Patients with AIH-1 are positive for anti-smooth muscle and/or anti-nuclear (SMA/ANA) autoantibodies whereas patients with AIH-2 have anti-liver kidney microsomal type 1 (anti-LKM1) and/or anti-liver cytosol type 1 (anti-LC1) autoantibodies. Cytochrome P4502D6 (CYP2D6) is the antigenic target of anti-LKM1 and formiminotransferase cyclodeaminase (FTCD) is the antigenic target of anti-LC1. It is known that AIH, both type-1 and type-2, is strongly linked to the Human Leukocyte Antigen (HLA) alleles -DR3, -DR4 and -DR7. However, the direct evidence of the association of HLA with AIH is lacking. Methods We developed a novel mouse model of AIH using the HLA-DR3 transgenic mouse on the non-obese diabetic (NOD) background (HLA-DR3 NOD) by immunization of HLA-DR3− and HLA-DR3+ NOD mice with a DNA plasmid, coding for human CYP2D6/FTCD fusion protein. Results Immunization with CYP2D6/FTCD leads to a sustained elevation of alanine aminotransferase (ALT), development of ANA and anti-LKM1/anti-LC1 autoantibodies, chronic immune cell infiltration and parenchymal fibrosis on liver histology in HLA-DR3+ mice. Immunized mice also showed an enhanced Th1 immune response and paucity of the frequency of regulatory T-cell (Treg) in the liver. Moreover, HLA-DR3+ mice with exacerbated AIH showed reduced diversity and total load of gut bacteria. Conclusion Our humanized animal model has provided a novel experimental tool to further elucidate the pathogenesis of AIH and to evaluate the efficacy and safety of immunoregulatory therapeutic interventions in vivo. PMID:26185095

The Pan-STARRS pipeline and data products

NASA Astrophysics Data System (ADS)

Flewelling, Heather

2018-01-01

I will give a brief overview of the pipeline, database, and dataproducts for Pan-STARRS1 data release 1 (DR1) and data release 2 (DR2). DR1 and DR2 provides access to data from the Pan-STARRS1 3pi survey, a survey which covers ¾ of the sky over 4 years (2010-2014), everything with a declination greater than -30, in 5 filters (g,r,i,z,y), with at least 12 epochs per filter per area of sky. DR1, released in December 2016, and available to the public at http://stsci.panstarrs.edu, consists of two parts: the stacked images with a 5 sigma depth of (23.3,23.2,23.1,22.3,21.3) for (g,r,i,z,y), and the catalog database, which consists of 10 billion distinct objects, their mean properties from single exposures, and stack photometry. DR2, to be released early 2108, will contain the individual exposure images, with a 5 sigma depth of (22.0,21.8,21.5,20.9,19.7) for (g,r,i,z,y), and the time domain catalogs, from the 374k individual exposures taken for the 3pi survey. I will primarily focus on the catalog database, describing a subset of the tables and different use cases for them. Specifically, I will describe the major tables and metadata of DR1 - objects, their mean properties, and stack photometry, when different tables should be used, and basics on how to filter the data.

Prevalence and risk factors for diabetic retinopathy in Asian Indians with young onset type 1 and type 2 diabetes.

PubMed

Rajalakshmi, Ramachandran; Amutha, Anandakumar; Ranjani, Harish; Ali, Mohammed K; Unnikrishnan, Ranjit; Anjana, Ranjit Mohan; Narayan, K M Venkat; Mohan, Viswanathan

2014-01-01

To assess the prevalence and risk factors for diabetic retinopathy (DR) in people with young onset type 1 (T1DM-Y) and type 2 diabetes (T2DM-Y). T1DM-Y(n=150) and T2DM-Y(n=150) participants, age between 10 and 25 years at diagnosis, had a complete clinical evaluation, biochemical assessment, and four field digital retinal colour photography. The Early Treatment Diabetic Retinopathy Study grading system was used to grade DR. Proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME) were considered as sight threatening DR. The prevalence of any DR was 53.3% [95% CI 45.3-61.3] in T1DM-Y (duration of diabetes: 12.4±7.4 years) and 52.7% [44.7-60.7] in T2DM-Y (11.8±8.3 years). The age and gender adjusted prevalence of DR, DME and PDR was 62.5%, 10% and 7.3% in T1DM-Y, whereas it was 65.8%,12.7% and 9.3% in T2DM-Y respectively. In multivariable logistic regression, diabetes duration [Odds ratio (OR) 1.99 per 5 years; CI 1.42-2.79], waist circumference [1.28 per 5 cm;1.05-1.56] and microalbuminuria [2.39 per 50 μg;1.07-5.31] were associated with DR in T1DM-Y, and diabetes duration [2.21 per 5 years; 1.61-3.02], diastolic blood pressure [1.54 per 5 mmHg;1.18-2.02], Glycated hemoglobin [1.37 per %;1.07-1.75] and lower stimulated C-peptide [1.54 per 0.5 pmol/ml;1.15-2.05;] were associated with DR in T2DM-Y. Over half of the people with young-onset diabetes, regardless of type, have retinopathy within 10-12 years of diabetes duration, emphasizing the need for regular eye screening and aggressive control of glucose and blood pressure to prevent DR. Copyright © 2014 Elsevier Inc. All rights reserved.

Higher levels of physical activity are independently associated with a lower incidence of diabetic retinopathy in Japanese patients with type 2 diabetes: A prospective cohort study, Diabetes Distress and Care Registry at Tenri (DDCRT15).

PubMed

Kuwata, Hirohito; Okamura, Shintaro; Hayashino, Yasuaki; Tsujii, Satoru; Ishii, Hitoshi

2017-01-01

We assessed the prospective association between baseline levels of physical activity (PA) and the incidence of newly developed diabetic retinopathy (DR) in patients with type 2 diabetes. Data from 1,814 patients with type 2 diabetes without DR were obtained from a Japanese diabetes registry at Tenri Hospital, Nara, Japan. To assess the independent correlations between baseline PA levels and newly developed DR, the participants were divided into five categories based on their PA levels. A Cox proportional hazards model with time-varying exposure information was used and adjusted for potential confounders to assess the independent correlations. At baseline, the mean age, BMI, and hemoglobin A1c levels of the patients were 65.5 years, 24.5 kg/m2, and 7.2% (54 mmol/mol), respectively. After 2 years, newly developed DR was confirmed in 184 patients (10.1%). Patients with newly developed DR had longer duration of type 2 diabetes (14.7 versus 11.0 years, p < 0.0001), higher systolic blood pressure (139.2 versus 135.1 mmHg, p = 0.0012), lower estimated glomerular filtration rate (74.0 versus 77.1 mL/min/1.73 m2, p = 0.0382), greater urinary albumin-creatinine ratio (4.00 versus 2.45 mg/mmol, p < 0.0039), and higher HbA1c levels (7.5 versus 7.2%, p = 0.0006) than those without newly developed DR. The multivariable-adjusted hazard ratios for DR development were 0.87 (95% CI, 0.53-1.40; p = 0.557), 0.83 (95% CI, 0.52-1.31; p = 0.421), 0.58 (95% CI, 0.35-0.94; p = 0.027), and 0.63 (95% CI, 0.42-0.94; p = 0.025)for the second, third, fourth, and fifth PA categories, respectively, compared with the reference category of patients with a mean PA of 0 metabolic equivalent of task-hours/week). Higher PA levels are independently associated with a lower incidence of DR in Japanese patients with type 2 diabetes.

Fabrication of three-dimensional polymer quadratic nonlinear grating structures by layer-by-layer direct laser writing technique

NASA Astrophysics Data System (ADS)

Bich Do, Danh; Lin, Jian Hung; Diep Lai, Ngoc; Kan, Hung-Chih; Hsu, Chia Chen

2011-08-01

We demonstrate the fabrication of a three-dimensional (3D) polymer quadratic nonlinear (χ(2)) grating structure. By performing layer-by-layer direct laser writing (DLW) and spin-coating approaches, desired photobleached grating patterns were embedded in the guest--host dispersed-red-1/poly(methylmethacrylate) (DR1/PMMA) active layers of an active-passive alternative multilayer structure through photobleaching of DR1 molecules. Polyvinyl-alcohol and SU8 thin films were deposited between DR1/PMMA layers serving as a passive layer to separate DR1/PMMA active layers. After applying the corona electric field poling to the multilayer structure, nonbleached DR1 molecules in the active layers formed polar distribution, and a 3D χ(2) grating structure was obtained. The χ(2) grating structures at different DR1/PMMA nonlinear layers were mapped by laser scanning second harmonic (SH) microscopy, and no cross talk was observed between SH images obtained from neighboring nonlinear layers. The layer-by-layer DLW technique is favorable to fabricating hierarchical 3D polymer nonlinear structures for optoelectronic applications with flexible structural design.

Fabrication of three-dimensional polymer quadratic nonlinear grating structures by layer-by-layer direct laser writing technique.

PubMed

Do, Danh Bich; Lin, Jian Hung; Lai, Ngoc Diep; Kan, Hung-Chih; Hsu, Chia Chen

2011-08-10

We demonstrate the fabrication of a three-dimensional (3D) polymer quadratic nonlinear (χ(2)) grating structure. By performing layer-by-layer direct laser writing (DLW) and spin-coating approaches, desired photobleached grating patterns were embedded in the guest-host dispersed-red-1/poly(methylmethacrylate) (DR1/PMMA) active layers of an active-passive alternative multilayer structure through photobleaching of DR1 molecules. Polyvinyl-alcohol and SU8 thin films were deposited between DR1/PMMA layers serving as a passive layer to separate DR1/PMMA active layers. After applying the corona electric field poling to the multilayer structure, nonbleached DR1 molecules in the active layers formed polar distribution, and a 3D χ(2) grating structure was obtained. The χ(2) grating structures at different DR1/PMMA nonlinear layers were mapped by laser scanning second harmonic (SH) microscopy, and no cross talk was observed between SH images obtained from neighboring nonlinear layers. The layer-by-layer DLW technique is favorable to fabricating hierarchical 3D polymer nonlinear structures for optoelectronic applications with flexible structural design.

Role of ACE and PAI-1 Polymorphisms in the Development and Progression of Diabetic Retinopathy

PubMed Central

Saleem, Saba; Azam, Aisha; Maqsood, Sundus Ijaz; Muslim, Irfan; Bashir, Shaheena; Fazal, Nosheen; Riaz, Moeen; Ali, Syeda Hafiza Benish; Niazi, Muhammad Khizar; Ishaq, Mazhar; Waheed, Nadia Khalida; Qamar, Raheel; Azam, Maleeha

2015-01-01

In the present study we determined the association of angiotensin converting enzyme (ACE) and plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms with diabetic retinopathy (DR) and its sub-clinical classes in Pakistani type 2 diabetic patients. A total of 353 diabetic subjects including 160 DR and 193 diabetic non retinopathy (DNR) as well as 198 healthy controls were genotyped by allele specific polymerase chain reaction (PCR) for ACE Insertion/Deletion (ID) polymorphism, rs4646994 in intron 16 and PAI-1 4G/5G (deletion/insertion) polymorphism, rs1799768 in promoter region of the gene. To statistically assess the genotype-phenotype association, multivariate logistic regression analysis was applied to the genotype data of DR, DNR and control individuals as well as the subtypes of DR. The ACE genotype ID was found to be significantly associated with DR (p = 0.009, odds ratio (OR) 1.870 [95% confidence interval (CI) = 1.04–3.36]) and its sub-clinical class non-proliferative DR (NPDR) (p = 0.006, OR 2.250 [95% CI = 1.098–4.620]), while PAI polymorphism did not show any association with DR in the current cohort. In conclusion in Pakistani population the ACE ID polymorphism was observed to be significantly associated with DR and NPDR, but not with the severe form of the disease i.e. proliferative DR (PDR). PMID:26658948

DR-induced escape of O and C from early Mars

NASA Astrophysics Data System (ADS)

Zhao, Jinjin; Tian, Feng; Ni, Yufang; Huang, Xiaomeng

2017-03-01

Energetic particles produced in Dissociative recombination (DR) reactions could escape planets with low gravity, such as Mars, if they could overcome collisions with the surrounding background gases. In this work, a 3-D Monte Carlo model is developed to study these photochemical escape processes on early Mars. Although the DR reaction rates of O2+, CO2+, and CO+ increase monotonically with solar soft X-ray and extreme ultraviolet (XUV) flux, the peak of the calculated DR-induced escape rates of O is near 3 × XUV, and the DR-induced escape rates of C increase with XUV until 10 × XUV. The non-monotonic behavior can be explained by the increased column densities of background species in high XUV conditions, which can deflect energetic particles through collisions more efficiently. At 20 × XUV, CO+ DR is the main source of escaping O and C, and the escape of secondary particles could contribute to 30∼40% and 10% of the total escape of O and C respectively. The time-integrated DR-induced escape of O and C is equivalent to 1 m of H2O and 20 mbar of CO2 escaping early Mars since 4.5 billion years ago. The accumulated CO2 loss is much lower than what's needed to explain the carbon isotopic ratios on Mars and much lower than the total CO2 needed to warm up early Mars. If more vigorous escape mechanisms were absent on early Mars, substantial inventories of volatiles have not been detected yet.

Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor. alpha. : Relevance to genetic predisposition to systemic lupus erythematosus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacob, C.O.; Fronek, Z.; Koo, M.

1990-02-01

The authors report on the production of tumor necrosis factor (TNF)-{alpha} and TNF-{beta} by mitogen-activated peripheral blood lymphocytes or enriched monocyte subpopulations from human leukocyte antigen (HLA)-typed healthy subjects. The results indicate that HLA-DR2- and DQw1-positive donors frequently exhibit low production of TNF-{alpha}, whereas DR3- and DR4-positive subjects show high levels of TNF-{alpha} production. No correlation between TNF-{alpha} levels and HLA-A, -B, and -C genotype was found. The relevance of this quantitative polymorphism to the genetic predisposition to lupus nephritis in systemic lupus erythematosus (SLE) patients was investigated. DR2, DQw1-positive SLE patients show low levels of TNF-{alpha} inducibility; this genotypemore » is also associated with an increased incidence of lupus nephritis. DR3-positive SLE patients, on the other hand, are not predisposed to nephritis, and these patients have high TNF-{alpha} production. DR4 haplotype is associated with high TNF-{alpha} inducibility and is negatively correlated with lupus nephritis. These data may help explain the strong association between HLA-DR2, DQw1 in SLE patients and their susceptibility to nephritis.« less

A Thermally Activated Solid State Reaction Process for Fabricating Ohmic Contacts to Semiconducting Diamond

DTIC Science & Technology

1990-09-01

due to Ken Regan. Dr. Howard Rast, Dr. Carl Zeisse, Maureen O * Brien , Dr. Don Mullin, Richard Nguyen, Paul Thibado. Dr. Charlesý Kewett, and Dr. Alan...Standard form 298 (FRONT) 1!NCL-ASSIFIED 21a. NAME OF RESPONS’OLL NOWVfOUAý J. R. Zeidler 69)55" 1 - I~ C( 7 ci) NMH 7540-01 .2$ O -8600 SIA,~afre tO~m...boron nitride could extend the operating temperature of devices to temperatures in excess of 1000*C. TABLE I. Selected properties of semiconductors

Three-Dimensional Static Articulation Accuracy of Virtual Models-Part II: Effect of Model Scanner-CAD Systems and Articulation Method.

PubMed

Yee, Sophia Hui Xin; Esguerra, Roxanna Jean; Chew, Amelia Anya Qin'An; Wong, Keng Mun; Tan, Keson Beng Choon

2018-02-01

Accurate maxillomandibular relationship transfer is important for CAD/CAM prostheses. This study compared the 3D-accuracy of virtual model static articulation in three laboratory scanner-CAD systems (Ceramill Map400 [AG], inEos X5 [SIR], Scanner S600 Arti [ZKN]) using two virtual articulation methods: mounted models (MO), interocclusal record (IR). The master model simulated a single crown opposing a 3-unit fixed partial denture. Reference values were obtained by measuring interarch and interocclusal reference features with a coordinate measuring machine (CMM). MO group stone casts were articulator-mounted with acrylic resin bite registrations while IR group casts were hand-articulated with poly(vinyl siloxane) bite registrations. Five test model sets were scanned and articulated virtually with each system (6 test groups, 15 data sets). STL files of the virtual models were measured with CMM software. dR R , dR C , and dR L , represented interarch global distortions at right, central, and left sides, respectively, while dR M , dX M , dY M , and dZ M represented interocclusal global and linear distortions between preparations. Mean interarch 3D distortion ranged from -348.7 to 192.2 μm for dR R , -86.3 to 44.1 μm for dR C , and -168.1 to 4.4 μm for dR L . Mean interocclusal distortion ranged from -257.2 to -85.2 μm for dR M , -285.7 to 183.9 μm for dX M , -100.5 to 114.8 μm for dY M , and -269.1 to -50.6 μm for dZ M . ANOVA showed that articulation method had significant effect on dR R and dX M , while system had a significant effect on dR R , dR C , dR L , dR M , and dZ M . There were significant differences between 6 test groups for dR R, dR L dX M , and dZ M . dR R and dX M were significantly greater in AG-IR, and this was significantly different from SIR-IR, ZKN-IR, and all MO groups. Interarch and interocclusal distances increased in MO groups, while they decreased in IR groups. AG-IR had the greatest interarch distortion as well as interocclusal superior-inferior distortion. The other groups performed similarly to each other, and the overall interarch distortion did not exceed 0.7%. In these systems and articulation methods, interocclusal distortions may result in hyper- or infra-occluded prostheses. © 2017 by the American College of Prosthodontists.

Differential Association of Generalized and Abdominal Obesity With Diabetic Retinopathy in Asian Patients With Type 2 Diabetes.

PubMed

Man, Ryan Eyn Kidd; Sabanayagam, Charumathi; Chiang, Peggy Pei-Chia; Li, Ling-Jun; Noonan, Jonathan Edward; Wang, Jie Jin; Wong, Tien Yin; Cheung, Gemmy Chui-Ming; Tan, Gavin Siew Wei; Lamoureux, Ecosse L

2016-03-01

The association between obesity and diabetic retinopathy (DR) is equivocal, possibly owing to the strong interrelation between generalized and abdominal obesity leading to a mutually confounding effect. To our knowledge, no study in Asia has investigated the independent associations of these 2 parameters with DR to date. To investigate the associations of generalized (defined by body mass index [BMI], calculated as weight in kilograms divided by height in meters squared) and abdominal obesity (assessed by waist to hip ratio [WHR]) with DR in a clinical sample of Asian patients with type 2 diabetes mellitus. This cross-sectional clinic-based study was conducted at the Singapore National Eye Centre, a tertiary eye care institution in Singapore, from December 2010 to September 2013. We recruited 498 patients with diabetes. After exclusion of participants with ungradable retinal images and type 1 diabetes, 420 patients (mean [SD] age, 57.8 [7.5] years; 32.1% women) were included in the analyses. Body mass index and WHR as waist/hip circumference (in centimeters). The presence and severity of DR were graded from retinal images using the modified Airlie House Classification into none (n = 189), mild-moderate (Early Treatment Diabetic Retinopathy Study scale score, 20-41; n = 125), and severe DR (Early Treatment Diabetic Retinopathy Study scale score ≥53; n = 118). The associations of BMI and WHR with DR were assessed using multinomial logistic regression models adjusting for age, sex, traditional risk factors, and mutually for BMI and WHR. Among the total of 420 patients, the median (interquartile range) for BMI and WHR were 25.7 (5.7) and 0.94 (0.08), respectively. In multivariable models, BMI was inversely associated with mild-moderate and severe DR (odds ratio [OR], 0.90 [95% CI, 0.84-0.97] and OR, 0.92 [95% CI, 0.85-0.99] per 1-unit increase, respectively), while WHR was positively associated with mild-moderate and severe DR (OR, 3.49 [95% CI, 1.50-8.10] and OR, 2.68 [95% CI, 1.28-5.62] per 0.1-unit increase, respectively) in women (P for interaction = .006). No sex-specific associations were found between BMI and DR (P for interaction >.10). In Asian patients with type 2 diabetes, a higher BMI appeared to confer a protective effect on DR, while higher WHR was associated with the presence and severity of DR in women. Our results may inform future clinical trials to determine whether WHR is a more clinically relevant risk marker than BMI for individuals with type 2 diabetes.

Histocompatibility Typing for the Prediction of Susceptibility to Infectious Disease.

DTIC Science & Technology

1980-06-01

w6/A2, B27 , w4, Cwl Sib B A2, A28 87, 818 (w6) blank A28, B7, w6/A2, 818, w6 12 5.2 HLA -DR typing. HLA -DR (B cell) typing will begin in June after...BACKGROUND 3 D. RESEARCH DESIGN AND PLAN 5 E. RESULTS 6 1. Development of Guidelines and Questionnaire- 6 Computer Form 2. Development of an HLA ...Histocompatibility Testing 7 Serology Laboratory 2.1 Establishment of HLA -A,B,C,DR Typing Trays 7 2.2 Establishment of the Two-Color Fluorescence 9 Method of B

Reactor Physics Measurements and Benchmark Specifications for Oak Ridge Highly Enriched Uranium Sphere (ORSphere)

DOE PAGES

Marshall, Margaret A.

2014-11-04

In the early 1970s Dr. John T. Mihalczo (team leader), J.J. Lynn, and J.R. Taylor performed experiments at the Oak Ridge Critical Experiments Facility (ORCEF) with highly enriched uranium (HEU) metal (called Oak Ridge Alloy or ORALLOY) in an effort to recreate GODIVA I results with greater accuracy than those performed at Los Alamos National Laboratory in the 1950s. The purpose of the Oak Ridge ORALLOY Sphere (ORSphere) experiments was to estimate the unreflected and unmoderated critical mass of an idealized sphere of uranium metal corrected to a density, purity, and enrichment such that it could be compared with themore » GODIVA I experiments. Additionally, various material reactivity worths, the surface material worth coefficient, the delayed neutron fraction, the prompt neutron decay constant, relative fission density, and relative neutron importance were all measured. The critical assembly, material reactivity worths, the surface material worth coefficient, and the delayed neutron fraction were all evaluated as benchmark experiment measurements. The reactor physics measurements are the focus of this paper; although for clarity the critical assembly benchmark specifications are briefly discussed.« less

Apical vertebral derotation in the posterior treatment of adolescent idiopathic scoliosis: myth or reality?

PubMed

Di Silvestre, Mario; Lolli, Francesco; Bakaloudis, Georgios; Maredi, Elena; Vommaro, Francesco; Pastorelli, Francesca

2013-02-01

Direct apical vertebral rotation represents an important goal of posterior surgery for thoracic adolescent idiopathic scoliosis (AIS), so as to obtain a better cosmetic effect and to avoid posterior thoracoplasty. However, the real effectiveness in correction of vertebral rotation, using posterior only procedures, is still open to debate. The aim of the present study is to compare the correction of axial apical rotation obtained with direct rotation procedure versus simple concave rod rotation, in patients treated by posterior fusion for thoracic AIS using pedicle screw-only construct. A retrospective review was performed on a total of 62 consecutive patients (one single institution, three different surgeons) affected by AIS, who had undergone a posterior spinal fusion with pedicle screw-only instrumentation between January 2005 and April 2008 at the reference center. All cases presented a main thoracic curve (Lenke type 1 and 2). The angle of rotation (RAsag) of the apical vertebra was measured from the preoperative and last follow-up axial CT. According to the derotation procedure, two groups were identified: a direct vertebral rotation group (DR group; n = 32 patients) and a simple concave rod rotation group (No-DR group; n = 30 patients). There were no statistical differences between the two groups, in terms of age, Risser's sign, curve patterns, Cobb main thoracic (MT) curve magnitude and flexibility, extension of fusion, offset measurements on the coronal plane and sagittal preoperative contour. All 62 patients were reviewed at an average follow-up of 3.7 years (range 2.5-4.2 years). The DR group compared to the No-DR group showed a significantly better final correction of apical vertebral rotation (DR 63.4 % vs. No-DR 14.8 %; p < 0.05) and a greater final correction (61.3 vs. 52.4 %; p < 0.05) with better maintenance of the initial correction (-1.7° vs. -1.9°; ns) of the main thoracic curve. Concerning the coronal balance, there was the same aforementioned trend of better results in the DR group, with less final apical MT vertebra translation (DR 2.2 cm vs. No-DR 4.1 cm), greater overall change (preop-final) of lower instrumented vertebra (LIV) coronal tilt (-14.9° vs. -11.1°; p < 0.05); the final global coronal balance (C7-S1) resulted quite better in DR group, but without a significant difference. The T5-T12 kyphosis angle was quite similar in both group before surgery (DR 16.8° vs. No-DR 17.5°) and was little lower at final follow-up evaluation in direct vertebral rotation group (14.5° vs. 16.5°). The T10-L2 sagittal alignment angle was similar in each group before surgery (12.5° in DR vs. 11.8° in No-DR), and at the latest follow-up averaged 5.3° versus 8.2°, respectively. Lumbar lordosis was similar in each group before surgery (DR -42° vs. No-DR -44.1°) and at the final follow-up evaluation (-45.9° vs. -43.2°). At the latest follow-up, SRS-30 and SF-36 findings were similar between the two groups. The complication rate was higher in the simple concave rod rotation group (13.3 vs. 9.3 %), related in two cases to thoracoplasty, which was never utilized in direct rotation patients. The direct vertebral rotation obtained significantly better final results, when compared to simple concave rod rotation, both concerning correction of apical vertebral rotation and magnitude of MT curve. On the other hand, the DR group presented a little reduction in T5-T12 kyphosis at follow-up, in comparison with concave rod rotation procedure. Both procedures were found to be satisfying from patients' perspective. Nevertheless overall complication rate was higher in the simple concave rod rotation group, related mainly to thoracoplasty (2 cases), which was never necessary in direct rotation patients.

JPRS Report, East Europe.

DTIC Science & Technology

1990-04-06

Andrasfalvy 2 Pecs Zoltan Trombitas Sandor Szeles Mrs. Kaposi, Dr. -Andras Pap Sandor Gyulai; Maria Dunai Jozsef Kuller; Dr. Istvan Marton 3 Pecs Dr. Andrea ...Csizmadia Mrs. Szabo, Erzsebet Kovacs 5 Varpalota Peter Patonai Laszlo Czifra Janos Csovari Janos Kovacs Ferenc Schmidt Tibor Fakasz 6 Veszprem -Ferenc

Gaming Sea-based Multinational HA/DR Operations at PACOM Amphibious Leaders Symposium 2016

DTIC Science & Technology

2016-11-01

DISTRIBUTION STATEMENT A. Approved for public release: distribution unlimited. Gaming Sea-based Multinational HA/DR Operations...Marine Corps photo by Cpl. Wesley Timm. Approved by: November 2016 Dr. E.D. McGrady Director, Integration and Gaming Advanced Technology and...TYPE Final2 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Gaming Seabased Multinational HA/DR Operations at PACOM 5a. CONTRACT NUMBER N00014-16

Modeling & Testing of Inflatable Structures for Rapidly Deployable Port Infrastructures

DTIC Science & Technology

2010-07-01

Rapidly Deployable Port Infrastructures By: Andrew Bloxom Abel Medellin Chris Vince Dr. Solomon Yim N SW C C D -C IS D -2 01...Andrew Bloxom, Abel Medellin , Chris Vince, Dr. Solomon Yim 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING...Andrew Bloxom Abel Medellin Chris Vince Dr. Solomon Yim A special thanks to: • Ben Testerman and Dr. Pat

Performance Envelopes and Optimal Appropriateness Measurement.

DTIC Science & Technology

1984-12-01

20370 Dr. Hans Crombag University of Leyden Mr. Raymond E. Christal Education Research Center AFHRL/MOE Boerhaavelaan 2 Brooks AFB, TX 78235 2334 EN... Leyden The NETHERLANDS Dr. Norman Cliff Department of Psychology CTB/McGraw-Hill Library Univ. of So. California 2500 Garden Road University Park...Psychology Dr William Montague University of Western Australia NPRDC Code 13 Nedlands W.A. 6009 San Diego, CA 92152 AUSTRALIA Ms. Kathleen Moreno Dr

Evaporation from Sand

DTIC Science & Technology

1992-04-01

Instituuts Advies R2ad PML Prof. dr. U.A.Th. Brinkanl~ 36. Direactur van het Medisch Biologisch Laboratorium TNO Prof.Dr. W.R.F. Notten 37. Directeur...Grootsdialige Rampenbestrijdcing Ministerie van Binnenlandsc Zaken Drs. H. Evers 9. Adviseur van het Prins Maurits Laboratorium TWO Prot. Dr. J.M. van...Rossum, 10. Adyisew, van het Prins Maurits Laboratorium TWO Chernisdie Research Prof.Dr. G. Dijkstra 11. H~ur. NBC DMKIJOMAT/KIO Ir. AAM. Slagveer 12

Dual Agonist Surrobody Simultaneously Activates Death Receptors DR4 and DR5 to Induce Cancer Cell Death.

PubMed

Milutinovic, Snezana; Kashyap, Arun K; Yanagi, Teruki; Wimer, Carina; Zhou, Sihong; O'Neil, Ryann; Kurtzman, Aaron L; Faynboym, Alexsandr; Xu, Li; Hannum, Charles H; Diaz, Paul W; Matsuzawa, Shu-ichi; Horowitz, Michael; Horowitz, Lawrence; Bhatt, Ramesh R; Reed, John C

2016-01-01

Death receptors of the TNF family are found on the surface of most cancer cells and their activation typically kills cancer cells through the stimulation of the extrinsic apoptotic pathway. The endogenous ligand for death receptors 4 and 5 (DR4 and DR5) is TNF-related apoptosis-inducing ligand, TRAIL (Apo2L). As most untransformed cells are not susceptible to TRAIL-induced apoptosis, death receptor activators have emerged as promising cancer therapeutic agents. One strategy to stimulate death receptors in cancer patients is to use soluble human recombinant TRAIL protein, but this agent has limitations of a short half-life and decoy receptor sequestration. Another strategy that attempted to evade decoy receptor sequestration and to provide improved pharmacokinetic properties was to generate DR4 or DR5 agonist antibodies. The resulting monoclonal agonist antibodies overcame the limitations of short half-life and avoided decoy receptor sequestration, but are limited by activating only one of the two death receptors. Here, we describe a DR4 and DR5 dual agonist produced using Surrobody technology that activates both DR4 and DR5 to induce apoptotic death of cancer cells in vitro and in vivo and also avoids decoy receptor sequestration. This fully human anti-DR4/DR5 Surrobody displays superior potency to DR4- and DR5-specific antibodies, even when combined with TRAIL-sensitizing proapoptotic agents. Moreover, cancer cells were less likely to acquire resistance to Surrobody than either anti-DR4 or anti-DR5 monospecific antibodies. Taken together, Surrobody shows promising preclinical proapoptotic activity against cancer cells, meriting further exploration of its potential as a novel cancer therapeutic agent. ©2015 American Association for Cancer Research.

Dual agonist Surrobody™ simultaneously activates death receptors DR4 and DR5 to induce cancer cell death

PubMed Central

Milutinovic, Snezana; Kashyap, Arun K.; Yanagi, Teruki; Wimer, Carina; Zhou, Sihong; O' Neil, Ryann; Kurtzman, Aaron L.; Faynboym, Alexsandr; Xu, Li; Hannum, Charles H.; Diaz, Paul W.; Matsuzawa, Shu-ichi; Horowitz, Michael; Horowitz, Lawrence; Bhatt, Ramesh R.; Reed, John C.

2015-01-01

Death receptors of the Tumor Necrosis Factor (TNF) family are found on surface of most cancer cells and their activation typically kills cancer cells through the stimulation of the extrinsic apoptotic pathway. The endogenous ligand for death receptors-4 and -5 (DR4 and DR5) is Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand, TRAIL (Apo2L). Since most untransformed cells are not susceptible to TRAIL-induced apoptosis, death receptor activators have emerged as promising cancer therapeutic agents. One strategy to stimulate death receptors in cancer patients is to use soluble human recombinant TRAIL protein, but this agent has limitations of a short half-life and decoy receptor sequestration. Another strategy that attempted to evade decoy receptor sequestration and to provide improved pharmacokinetic properties was to generate DR4 or DR5 agonist antibodies. The resulting monoclonal agonist antibodies overcame the limitations of short half-life and avoided decoy receptor sequestration, but are limited by activating only one of the two death receptors. Here, we describe a DR4 and DR5 dual agonist produced using Surrobody™ technology that activates both DR4 and DR5 to induce apoptotic death of cancer cells in vitro and in vivo and also avoids decoy receptor sequestration. This fully human anti-DR4/DR5 Surrobody displays superior potency to DR4- and DR5-specific antibodies, even when combined with TRAIL-sensitizing pro-apoptotic agents. Moreover, cancer cells were less likely to acquire resistance to Surrobody than either anti-DR4 or anti-DR5 mono-specific antibodies. Taken together, Surrobody shows promising preclinical pro-apoptotic activity against cancer cells, meriting further exploration of its potential as a novel cancer therapeutic agent. PMID:26516157

Diabetic retinopathy is associated with the presence and burden of subclinical carotid atherosclerosis in type 1 diabetes.

PubMed

Carbonell, Marc; Castelblanco, Esmeralda; Valldeperas, Xavier; Betriu, Àngels; Traveset, Alícia; Granado-Casas, Minerva; Hernández, Marta; Vázquez, Federico; Martín, Mariona; Rubinat, Esther; Lecube, Albert; Franch-Nadal, Josep; Fernández, Elvira; Puig-Domingo, Manel; Avogaro, Angelo; Alonso, Núria; Mauricio, Dídac

2018-05-04

Cardiovascular (CV) disease due to atherosclerosis is a major cause of morbidity and mortality in adult patients with diabetes, either type 1 or type 2 diabetes. The aim of the study was to assess the association of the frequency and the burden of subclinical carotid atherosclerotic disease in patients with type 1 diabetes according to the presence and severity of diabetic retinopathy (DR). A cross-sectional study was conducted in 340 patients with type 1 diabetes (41.5% with DR), and in 304 non-diabetic individuals. All participants were free from previous CV disease and chronic kidney disease (CKD). B-mode carotid ultrasound imaging was performed in all the study subjects. Patients with type 1 diabetes underwent a full eye examination, and DR patients were divided into two groups: mild disease and advanced disease. In the group of patients with type 1 diabetes, the percentage of patients with carotid plaques was higher in those with DR compared with those without DR (44.7% vs. 24.1%, p < 0.001). Patients with DR also presented a higher incidence of ≥ 2 carotid plaques (25.5% vs. 11.1%, p < 0.001). Apart from other traditional cardiovascular risk factors, the presence of advanced stages of DR was independently associated with the presence (p = 0.044) and the burden (≥ 2 carotid plaques; p = 0.009) of subclinical carotid atherosclerosis. In patients with type 1 diabetes without previous CV disease or established CKD, the presence of advanced stages of DR is associated with a higher atherosclerotic burden in the carotid arteries. The presence of DR identifies patients at risk for carotid atherosclerotic disease.

Three-Dimensional Accuracy of Digital Static Interocclusal Registration by Three Intraoral Scanner Systems.

PubMed

Wong, Kuan Yee; Esguerra, Roxanna Jean; Chia, Vanessa Ai Ping; Tan, Ying Han; Tan, Keson Beng Choon

2018-02-01

Prior studies have defined the accuracy of intraoral scanner (IOS) systems but the accuracy of the digital static interocclusal registration function of these systems has not been reported. This study compared the three-dimensional (3D) accuracy of the digital static interocclusal registration of 3 IOS systems using the buccal bite scan function. Three IOS systems compared were 3M TM True Definition Scanner (TDS), TRIOS Color (TRC), and CEREC AC with CEREC Omnicam (CER). Using each scanner, 7 scans (n = 7) of the mounted and articulated SLA master models were obtained. The measurement targets (SiN reference spheres and implant abutment analogs) were in the opposing models at the right (R), central (C), and left (L) regions; abutments #26 and #36, respectively. A coordinate measuring machine with metrology software compared the physical and virtual targets to derive the global 3D linear distortion between the centroids of the respective target reference spheres and abutment analogs (dR R , dR C , dR L , and dR M ) and 2D distances between the pierce points of the abutment analogs (dX M , dY M , dZ M ), with 3 measurement repetitions for each scan. Mean 3D distortion ranged from -471.9 to 31.7 μm for dR R , -579.0 to -87.0 μm for dR C , -381.5 to 69.4 μm for dR L , and -184.9 to -23.1 μm for dR M . Mean 2D distortion ranged from -225.9 to 0.8 μm for dX M , -130.6 to -126.1 μm for dY M , and -34.3 to 26.3 μm for dZ M . Significant differences were found for interarch distortions across the three systems. For dR R and dR L , all three test groups were significantly different, whereas for dR C , the TDS was significantly different from the TRC and CER. For 2D distortion, significant differences were found for dX M only. Interarch and global interocclusal distortions for the three IOS systems were significantly different. TRC performed overall the best and TDS was the worst. The interarch (dR R , dR C , dR L ) and interocclusal (dX M ) distortions observed will affect the magnitude of occlusal contacts of restorations clinically. The final restoration may be either hyperoccluded or infraoccluded, requiring compensations during the CAD design stage or clinical adjustments at issue. © 2017 by the American College of Prosthodontists.

Using DR52c/Ni2+ mimotope tetramers to detect Ni2+ reactive CD4+ T cells in patients with joint replacement failure.

PubMed

Zhang, Yan; Wang, Yang; Anderson, Kirsten; Novikov, Andrey; Liu, Zikou; Pacheco, Karin; Dai, Shaodong

2017-09-15

T cell mediated hypersensitivity to nickel (Ni 2+ ) is one of the most common causes of allergic contact dermatitis. Ni 2+ sensitization may also contribute to the failure of Ni 2+ containing joint implants, and revision to non-Ni 2+ containing hardware can be costly and debilitating. Previously, we identified Ni 2+ mimotope peptides, which are reactive to a CD4 + T cell clone, ANi2.3 (Vα1, Vβ17), isolated from a Ni 2+ hypersensitive patient with contact dermatitis. This T cell is restricted to the major histocompatibility complex class II (MHCII) molecule, Human Leukocyte Antigen (HLA)-DR52c (DRA, DRB3*0301). However, it is not known if Ni 2+ induced T cell responses in sensitized joint replacement failure patients are similar to subjects with Ni 2+ induced contact dermatitis. Here, we generated DR52c/Ni 2+ mimotope tetramers, and used them to test if the same Ni 2+ T cell activation mechanism could be generalized to Ni 2+ sensitized patients with associated joint implant failure. We confirmed the specificity of these tetramers by staining of ANi2.3T cell transfectomas. The DR52c/Ni 2+ mimotope tetramer detected Ni 2+ reactive CD4 + T cells in the peripheral blood mononuclear cells (PBMC) of patients identified as Ni 2+ sensitized by patch testing and a positive Ni 2+ LPT. When HLA-typed by a DR52 specific antibody, three out of four patients were DR52 positive. In one patient, Ni 2+ stimulation induced the expansion of Vβ17 positive CD4 + T cells from 0.8% to 13.3%. We found that the percentage of DR52 positivity and Vβ17 usage in Ni 2+ sensitized joint failure patients are similar to Ni sensitized skin allergy patients. Ni 2+ independent mimotope tetramers may be a useful tool to identify the Ni 2+ reactive CD4 + T cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Dietary Intake of Lutein and Diabetic Retinopathy in the Atherosclerosis Risk in Communities Study (ARIC).

PubMed

Sahli, Michelle W; Mares, Julie A; Meyers, Kristin J; Klein, Ronald; Brady, William E; Klein, Barbara E K; Ochs-Balcom, Heather M; Donahue, Richard P; Millen, Amy E

2016-01-01

We tested the hypothesis that dietary intake of lutein is inversely associated with prevalence of diabetic retinopathy (DR) due to its antioxidant and anti-inflammatory properties and location within the retina. We used logistic regression to examine the association between prevalent DR and energy-adjusted lutein intake by quartile (Q) using data collected from 1430 Atherosclerosis Risk in Communities Study (ARIC) participants with diabetes (n = 994 white, n = 508 black). DR was assessed from 45° non-mydriatic retinal photographs of one randomly chosen eye taken at visit 3 (1993-1995). Dietary lutein intake was estimated using a 66-item food frequency questionnaire at visit 1 (1987-1989). Median estimated daily lutein intake was 1370 µg/1000 kcals and prevalence of DR was ~21%. We found a crude association between lutein and DR (odds ratio, OR, 2.11, 95% confidence interval, CI, 1.45-3.09 for Q4, high intake, vs. Q1, low intake; p for trend <0.0001), which was attenuated after adjustment for ethnicity, duration of diabetes, glycosylated hemoglobin levels, field center and energy intake (OR 1.41, 95% CI 0.87-2.28; p for trend = 0.01). In analyses limited to persons with short diabetes duration (<6 years), the association no longer persisted (OR 0.94, 95% CI 0.31-2.16; p for trend =0.72) compared to the association in those with longer diabetes duration (≥6 years; OR 1.58, 95% CI 0.91-2.75; p for trend = 0.01). Contrary to our hypothesis, we found that the odds of higher lutein intake were greater among those with DR than those without DR. However, after adjusting for confounders, intake of lutein was not associated with DR.

Validation of Smartphone Based Retinal Photography for Diabetic Retinopathy Screening.

PubMed

Rajalakshmi, Ramachandran; Arulmalar, Subramanian; Usha, Manoharan; Prathiba, Vijayaraghavan; Kareemuddin, Khaji Syed; Anjana, Ranjit Mohan; Mohan, Viswanathan

2015-01-01

To evaluate the sensitivity and specificity of "fundus on phone' (FOP) camera, a smartphone based retinal imaging system, as a screening tool for diabetic retinopathy (DR) detection and DR severity in comparison with 7-standard field digital retinal photography. Single-site, prospective, comparative, instrument validation study. 301 patients (602 eyes) with type 2 diabetes underwent standard seven-field digital fundus photography with both Carl Zeiss fundus camera and indigenous FOP at a tertiary care diabetes centre in South India. Grading of DR was performed by two independent retina specialists using modified Early Treatment of Diabetic Retinopathy Study grading system. Sight threatening DR (STDR) was defined by the presence of proliferative DR(PDR) or diabetic macular edema. The sensitivity, specificity and image quality were assessed. The mean age of the participants was 53.5 ±9.6 years and mean duration of diabetes 12.5±7.3 years. The Zeiss camera showed that 43.9% had non-proliferative DR(NPDR) and 15.3% had PDR while the FOP camera showed that 40.2% had NPDR and 15.3% had PDR. The sensitivity and specificity for detecting any DR by FOP was 92.7% (95%CI 87.8-96.1) and 98.4% (95%CI 94.3-99.8) respectively and the kappa (ĸ) agreement was 0.90 (95%CI-0.85-0.95 p<0.001) while for STDR, the sensitivity was 87.9% (95%CI 83.2-92.9), specificity 94.9% (95%CI 89.7-98.2) and ĸ agreement was 0.80 (95%CI 0.71-0.89 p<0.001), compared to conventional photography. Retinal photography using FOP camera is effective for screening and diagnosis of DR and STDR with high sensitivity and specificity and has substantial agreement with conventional retinal photography.

Comparison of prescribing patterns between United States and Dominican Republic prescribers on short-term medical mission trips.

PubMed

Prescott, Gina M; Patzke, Ciera L; Brody, Peter M; Prescott, William A

2018-01-01

Short-term medical missions (STMMs) have increased and are viewed as a way to extend care in low- and middle-income countries (LMICs). Although benefits may exist, visiting teams may lack insight into using medications safely and effectively. The primary objective was to assess prescribing differences between US-based and Dominican Republic (DR) healthcare providers on STMMs in the DR. A retrospective database review between January 2013 and 2015 was conducted. Data from US and DR groups were compared for differences in diagnoses, medication classes prescribed and prescriptions per patient. The mean number of medical conditions diagnosed per patient in the DR (n=423) and US groups (n=1585) were 1.4±0.9 and 1.0±0.8, respectively. The diagnosis of infectious diseases was the same as non-communicable diseases. The DR group prescribed more medications at each patient encounter (mean 2.6 vs 2.2, respectively; p<0.001). The US group prescribed more antibiotics for respiratory infections (US 46.2% vs DR 25.0%; p=0.0001), used more metronidazole than albendazole alone for parasite infections (p=0.0022) and used more oral fluconazole for vaginal candidiasis (p<0.0001) and tinea infections (US 44.6%, DR 14.3%, respectively; p=0.0020). Although some significant prescribing differences exist between US and DR providers, many similarities were present. Visiting providers should understand the medication use system and disease burden before providing care in an LMIC. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

HLA DR phenotypic frequencies and genetic risk of Type 1 diabetes in west region of Algeria, Tlemcen

PubMed Central

Aribi, Mourad; Moulessehoul, Soraya; Benabadji, Ahmed-Bakir; Kendoucitani, Mohammed

2004-01-01

Background The main genomic region controlling the predisposition to type 1 diabetes is the Human Leukocyte Antigens (HLA) class II of the major histocompatibility complex. Association with different HLA types depends also on the studied populations. In our investigation, we tried to measure the phenotypic HLA class II association frequencies of DR3 and/or DR4 antigens, using a serologic method called microlymphocytotoxicity analysis, in diabetic and nondiabetic (ND) subjects originating from the west-Algerian region of Tlemcen. The aim of the present study was to determine which HLA DR antigens represent a high susceptibility to develop the disease in this area. Using a case-control retrospective study design, we randomly recruited ninety-one related subjects, 39 type 1 diabetics and 52 ND as controls, at the Internal Medicine Board of Medical Centre University of Tlemcen. Results DR3 antigen frequencies were comparable between the type 1 diabetics and the ND subjects and showed no association with the disease (p = 1.000, OR = 0.95), whereas DR4 and DR3DR4 antigens were associated with susceptibility to develop type 1 diabetes (DR4; OR = 2.10, DR3DR4; OR = 1.30). Also, no incidence for DR3 (p = 0.2646) or DR3DR4 (p = 0.0699) antigen frequencies was related to the sex ratio. However, significant differences in HLA DR4 frequencies between type 1 diabetics and ND were found to be related to sex (p = 0.0085). Conclusion Taken together, our investigation showed that the strongest association with type 1 diabetes was noticed in the presence of HLA DR4 antigens followed by DR3DR4 antigens. This study highlighted a characteristic of Tlemcen population; a history of consanguineous marriages. Association studies between the disease and genetic polymorphisms should be undertaken in a population where consanguinity is more limited to reduce confounding in result interpretations. PMID:15331022

Design, Fabrication, Calibration, Testing and Satellite Integration of a Space-Radiation Dosimeter.

DTIC Science & Technology

1981-12-01

on aI to tuec 11i’u te I ~ .t .r e t~tnJt IIIt Heil(-V- e Nxonknlt al Ii) ao (k Iowa rd’ t ht in i )I, ii, r’ iuie scent v-ia s p uift. i ne alipi. r...exponent are interpreted conventionally: M = m 1 + 2m2 + 4m 3 + 8m 4 + 1 6m 5 and E = e1 + 2e2 +4e 3 The minimum number of input counts required to cause a...R Q,, TE L26 INIT 0 ne One - f-..t ht shot ShoIEZTT CHI ST R,.et ST CAL ST s a D Q CAL ID mux c Hli DR I .10V R Cw DR 2 DR 3 LO. C.-H-FE DR 4 One

Over-expression of CD8+ T-cell activation is associated with decreased CD4+ cells in patients seeking treatment of Alcohol Use Disorder.

PubMed

Zuluaga, Paola; Sanvisens, Arantza; Martínez-Cáceres, Eva; Teniente, Aina; Tor, Jordi; Muga, Robert

2017-11-01

Harmful alcohol consumption may have an impact on the adaptive immune system through an imbalance in T cell subpopulations and changes in cell activation. We aimed to analyze profiles of CD4 and CD8T cell activation in patients with alcohol use disorder (AUD). We used a cross-sectional study with patients seeking treatment of the disorder. Blood samples for immunophenotyping were obtained at admission. Profiles of T cell activation were defined: (I) CD38 + /HLA-DR + , (II) CD38 + /HLA-DR - , (III) CD38 - /HLA-DR + , (IV) CD38 - /HLA-DR - and compared with healthy controls. We calculated a CD8 + T cell activation indicator (AI) that was defined as the quotient of non-activated cells (CD38 - /HLA-DR - ) and activated cells (CD38 + /HLA-DR + ). 60 patients were eligible (83%M); median age was 49 years [IQR: 44-54] and alcohol consumption was 145g/day [IQR: 90-205]. Mean±SD of CD38 + /HLA-DR - was 50.3±50.6 cells/μL in patients and 33.5±24.5 cells/μL in controls (p=0.03), for the CD38 - /HLA-DR + it was 61±62.2 cells/μL in patients and 21.2±17.3 cells/μL in controls (p<0.001) and for the CD38 + /HLA-DR + it was 20.2±15.6 cells/μL in patients and 10.8±10.3 cells/μL in controls (p<0.001). In patients, an inverse correlation was observed between absolute number and percentage of CD4 + T cells, and the percentage of CD38 + /HLA-DR + CD8 + T cells (r=0.37, p=0.003; r=0.2, p=0.086, respectively). Patients with AUD have an increased expression of immune activation with respect to healthy individuals. This excess of activated CD8 + T cells correlates with the absolute CD4 + T cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Expression of Death Receptor 4 Is Positively Regulated by MEK/ERK/AP-1 Signaling and Suppressed upon MEK Inhibition*

PubMed Central

Yao, Weilong; Oh, You-Take; Deng, Jiusheng; Yue, Ping; Deng, Liang; Huang, Henry; Zhou, Wei; Sun, Shi-Yong

2016-01-01

Death receptor 4 (DR4) is a cell surface receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and triggers apoptosis upon ligation with TRAIL or aggregation. MEK/ERK signaling is a well known and the best-studied effector pathway downstream of Ras and Raf. This study focuses on determining the impact of pharmacological MEK inhibition on DR4 expression and elucidating the underlying mechanism. We found that several MEK inhibitors including MEK162, AZD6244, and PD0325901 effectively decreased DR4 protein levels including cell surface DR4 in different cancer cell lines. Accordingly, pre-treatment of TRAIL-sensitive cancer cell lines with a MEK inhibitor desensitized them to TRAIL-induced apoptosis. These results indicate that MEK inhibition negatively regulates DR4 expression and cell response to TRAIL-induced apoptosis. MEK inhibitors did not alter DR4 protein stability, rather decreased its mRNA levels, suggesting a transcriptional regulation. In contrast, enforced activation of MEK/ERK signaling by expressing ectopic B-Raf (V600E) or constitutively activated MEK1 (MEK1-CA) or MEK2 (MEK2-CA) activated ERK and increased DR4 expression; these effects were inhibited when a MEK inhibitor was present. Promoter analysis through deletion and mutation identified the AP-1 binding site as an essential response element for enhancing DR4 transactivation by MEK1-CA. Furthermore, inhibition of AP-1 by c-Jun knockdown abrogated the ability of MEK1-CA to increase DR4 promoter activity and DR4 expression. These results suggest an essential role of AP-1 in mediating MEK/ERK activation-induced DR4 expression. Our findings together highlight a previously undiscovered mechanism that positively regulates DR4 expression through activation of the MEK/ERK/AP-1 signaling pathway. PMID:27576686

Disability risk in pediatric motor vehicle crash occupants.

PubMed

Doud, Andrea N; Schoell, Samantha L; Weaver, Ashley A; Talton, Jennifer W; Barnard, Ryan T; Petty, John K; Stitzel, Joel D

2017-05-01

Mortality rates among children in motor vehicle crashes (MVCs) are typically low; however, nonfatal injuries can vary in severity by imposing differing levels of short- and long-term disability. To better discriminate the severity of nonfatal MVC injuries, a pediatric-specific disability risk (DR) metric was created. The National Automotive Sampling System 2000 to 2011 was used to define the top 95% most common Abbreviated Injury Scale (AIS) 2+ injuries among pediatric MVC occupants. Functional Independence Measure scores were abstracted from the National Trauma Data Bank 2002 to 2006. Multiple imputation was used to account for missing data. The DR and coinjury-adjusted DR (DRMAIS) of the most common AIS 2+ MVC-induced injuries were calculated for 7-year-old to 18-year-old children by determining the proportion of those disabled after an injury to those sustaining the injury. DR and DRMAIS values ranged from 0 to 1, representing 0% to 100% DR. The mean DR and DRMAIS of all injuries were 0.290 and 0.191, respectively. DR and DRMAIS were greatest for injuries to the head (DR, 0.340; DRMAIS, 0.279), thorax (DR, 0.320; DRMAIS, 0.233), and spine (DR, 0.315; DRMAIS, 0.200). The mean DR and DRMAIS increased with increasing AIS severity but there was significant variation and overlapping values across AIS severity levels. Comparison of DRMAIS to coinjury-adjusted mortality risk (MRMAIS) revealed that among 118 injuries with MRMAIS of 0.000, DRMAIS ranged from 0.000 to 0.429. Incorporation of DR metrics into injury severity metrics may improve the ability to distinguish between the severity of different nonfatal injuries. This is especially crucial in the pediatric population where permanent disability can result in a high number of years lost due to disability. The accuracy of such severity metrics is crucial to the success of pediatric triage algorithms such as Advanced Automatic Crash Notification algorithms. Epidemiologic/prognostic study, level III.

Joint conference of iMEC 2015 (2nd International Manufacturing Engineering Conference & APCOMS 2015 (3rd Asia-Pacific Conference on Manufacturing Systems)

NASA Astrophysics Data System (ADS)

2016-02-01

The iMEC 2015 is the second International Manufacturing Engineering Conference organized by the Faculty of Manufacturing, Universiti Malaysia Pahang (UMP), held from 12-14th November 2015 in Kuala Lumpur, Malaysia, with a theme "Materials, Manufacturing and Systems for Tomorrow". For the first time, iMEC is organized together with 3rd Asia- Pacific Conference on Manufacturing System (APCOMS 2015) which owned by Fakulti Teknologi Industri, Institut Teknologi Bandung (ITB), Indonesia. This is an extended collaboration between UMP and ITB to intensify knowledge sharing and experiences between higher learning institutions. This conference (iMEC & APCOMS 2015) is a platform for knowledge exchange and the growth of ideas, particularly in manufacturing engineering. The conference aims to bring researchers, academics, scientists, students, engineers and practitioners from around the world together to present their latest findings, ideas, developments and applications related to manufacturing engineering and other related research areas. With rapid advancements in manufacturing engineering, iMEC is an appropriate medium for the associated community to keep pace with the changes. In 2015, the conference theme is “Materials, Manufacturing and Systems for Tomorrow” which reflects the acceleration of knowledge and technology in global manufacturing. The papers in these proceedings are examples of the work presented at the conference. They represent the tip of the iceberg, as the conference attracted over 200 abstracts from Malaysia, Indonesia, Japan, United Kingdom, Australia, India, Bangladesh, South Africa, Turkey and Morocco and 151 full papers were accepted in these proceedings. The conference was run in four parallel sessions with 160 presenters sharing their latest finding in the areas of manufacturing process, systems, advanced materials and automation. The first keynote presentation was given by Prof. B. S. Murthy (IIT, Madras) on "Nanomaterials with Exceptional Properties Synthesized through Top Down Approach”, which was warmly welcomed by an eager and highly motivated audience. The second keynote speaker was Prof. Ir. Dradjad Irianto (ITB, Indonesia) on “Collaborative Manufacturing for Small-medium Enterprises”. The organizers are very grateful to them for supporting the conference and sharing their latest research results with the conference participants. The conference organizers would like to express our sincere gratitude and thanks to the honorary chairman Prof. Dato, Dr. Daing Nasir Ibrahim and Prof. Dr. Wan Azhar Wan Yusoff and organizing committee members of iMEC2015, Assoc. Prof. Dr. A.K. Prasada Rao (chairman), Dr. Ing. Mohd Azmir Mohd Azhari (co-chairman), and all committee members Assoc. Prof. Dr. Ahmad Razlan Yusoff, Assoc. Prof. Dr. Ismed Iskandar, Dr Noraini Mohd Razali, Dr Muhammed Nafis Osman Zahid, Dr Noor Mazni Ismail, Dr Izwan Ismail, Dr Zamzuri Hamedon, Dr Faiz Mohd Turan, Ms Suraya Sulaiman and secretariat Miss Zuryaty, Mrs Wan Norshihah, Mr. Mohd Khairulnazri and Mr Rafilah and also a million thanks to the steering committee from APCOMS Prof. Dr. Kadarsyah Suryadi, Prof. Dr. Bermawi, P. Iskandar, Prof. Dr. Abdul Hakim Halim, Prof. Dr. Dradjad Irianto, Dr. TMA Ari Samadhi, Ir. I Made Dana Tangkas and APCOMS organizing committee Prof. Dr. Abdul Hakim Halim (chair), Dr. Rachmawati Wangsaputra (co-chair) and other committee members Dr. Iwan Inrawan Wiratmadja, Dr. Anas Ma'ruf, Dr. Sukoyo and Dr. Wisnu Aribowo. The editorial board are indebted to all of the reviewers who were willing to spend their precious time in reviewing the papers. Thanks also to all who contributed direct or indirectly in making this conference a success, especially Mr. Mohd Khairulnazri in helping the editors complete the proceedings. Dr. Zamzuri Hamedon Editor in-chief iMEC & APCOMS 2015 Associate Editors 1. Assoc. Prof. Dr. A.K. Prasada Rao 2. Assoc. Prof. Dr. Ahmad Razlan Yusoff 3. Dr. Ing. Mohd Azmir Mohd Azhari 4. Dr. Muhammed Nafis Osman Zahid 5. Dr. Faiz Mohd Turan

An Automated Detection System for Microaneurysms That Is Effective across Different Racial Groups.

PubMed

Saleh, George Michael; Wawrzynski, James; Caputo, Silvestro; Peto, Tunde; Al Turk, Lutfiah Ismail; Wang, Su; Hu, Yin; Da Cruz, Lyndon; Smith, Phil; Tang, Hongying Lilian

2016-01-01

Patients without diabetic retinopathy (DR) represent a large proportion of the caseload seen by the DR screening service so reliable recognition of the absence of DR in digital fundus images (DFIs) is a prime focus of automated DR screening research. We investigate the use of a novel automated DR detection algorithm to assess retinal DFIs for absence of DR. A retrospective, masked, and controlled image-based study was undertaken. 17,850 DFIs of patients from six different countries were assessed for DR by the automated system and by human graders. The system's performance was compared across DFIs from the different countries/racial groups. The sensitivities for detection of DR by the automated system were Kenya 92.8%, Botswana 90.1%, Norway 93.5%, Mongolia 91.3%, China 91.9%, and UK 90.1%. The specificities were Kenya 82.7%, Botswana 83.2%, Norway 81.3%, Mongolia 82.5%, China 83.0%, and UK 79%. There was little variability in the calculated sensitivities and specificities across the six different countries involved in the study. These data suggest the possible scalability of an automated DR detection platform that enables rapid identification of patients without DR across a wide range of races.

Advanced Fuel Cycle Technology: Special Session in Honor of Dr. Michael Lineberry

DOE Office of Scientific and Technical Information (OSTI.GOV)

D.M. Wachs; N. Woolstenhulme

2014-06-01

The US DOE recently initiated an effort to develop accident tolerant fuel designs for potential use in commercial power reactors. Evaluation of various fuel design concepts will require a broad array of testing that will include performance attributes at both steady state and transient irradiation conditions. The first stage of the transient testing program is intended to establish the relative performance limits of each proposed concept and to support development of first-draft fuel performance models. It is anticipated that this data can subsequently be used as the basis for larger scale qualification testing. This initial stage of the testing programmore » is outlined in this paper.« less

Moderate consumption of white and fortified wine is associated with reduced odds of diabetic retinopathy.

PubMed

Fenwick, Eva K; Xie, Jing; Man, Ryan Eyn Kidd; Lim, Lyndell L; Flood, Victoria M; Finger, Robert P; Wong, Tien Y; Lamoureux, Ecosse L

2015-01-01

To explore the association between alcohol consumption and the severity of diabetic retinopathy (DR). In this cross-sectional study, patients with type 2 diabetes answered questions on consumption of low and full-strength beer, white wine/champagne, red wine, fortified wines, and spirits. Never, moderate and high consumption of each alcoholic beverage, and overall alcoholic beverage consumption, were defined as <1, 1-14 and >14 standard drinks/week, respectively. DR was categorized into none; non vision-threatening DR (VTDR) and VTDR. Multivariable logistic regression determined the associations between alcohol consumption and DR. Of the 395 participants (mean age±SD [standard deviation] 65.9±10.4years; males=253), 188 (47.6%) consumed alcohol and 235 (59.5%) had any DR. Compared to no alcohol consumption, moderate alcohol consumption (overall) was significantly associated with reduced odds of any DR (OR=0.47, 95% CI [confidence interval] 0.26-0.85). Moderate consumption of white wine/champagne or fortified wine was also associated with reduced odds of any DR (OR=0.48, 95% CI 0.25-0.91, and OR=0.15, 95% CI 0.04-0.62, respectively). Similar results were observed for non-VTDR and VTDR. The amount and type of alcohol are associated with risk of DR in patients with type 2 diabetes. A longitudinal study is needed to assess the protective effect of alcohol consumption and DR. Copyright © 2015 Elsevier Inc. All rights reserved.

Off-Road Soft Soil Tire Model Development and Experimental Testing

DTIC Science & Technology

2011-06-29

Eduardo Pinto 2 , Mr. Scott Naranjo 3 , Dr. Paramsothy Jayakumar 4 , Dr. Archie Andonian 5 , Dr. Dave Hubbell 6 , Dr. Brant Ross 7 1Virginia...The effect of soil charac- teristics on the tire dynamics will be studied. Validation against data collected from full vehicle testing is included in...the proposed future work. Keywords: tire model, soft soil, terramechanics, vehicle dynamics , indoor testing 1 Introduction The goal of this paper is

Evaluation of the Material Point Method within CTH to Model 2-Dimensional Plate Impact Problems

DTIC Science & Technology

2014-09-01

Howard University . 14. ABSTRACT The material point method (MPM) is a mixed Eulerian and Lagrangian computational method that allows for the... University in Washington, DC, as a second-year graduate student within mechanical engineering. I also attended Howard University for my undergraduate...Kevin Rugirello, Dr Andrew Tonge, Dr Jeffrey Lloyd, Dr Mary Jane Graham, and Dr Gbadebo Owolabi. vi Student Bio I am currently attending Howard

Enhanced Oxidative Stress and Other Potential Biomarkers for Retinopathy in Type 2 Diabetics: Beneficial Effects of the Nutraceutic Supplements

PubMed Central

Roig-Revert, María J.; Lleó-Pérez, Antonio; Zanón-Moreno, Vicente; Vivar-Llopis, Bárbara; Marín-Montiel, Juan; Alonso-Muñoz, Luis; Albert-Fort, Mara; López-Gálvez, María I.; Galarreta-Mira, David; García-Esparza, María F.; Marco-Ramirez, Carla; Shoaie-Nia, Kian; Sanz-González, Silvia M.; Vila-Bou, Vicente; Bendala-Tufanisco, Elena; García-Medina, José J.; Nucci, Carlo; Arévalo, J. Fernando; Pinazo-Durán, Maria D.; Valencia Study on Diabetic Retinopathy (VSDR)

2015-01-01

We have studied the global risk of retinopathy in a Mediterranean population of type 2 diabetes mellitus (T2DM) patients, according to clinical, biochemical, and lifestyle biomarkers. The effects of the oral supplementation containing antioxidants/omega 3 fatty acids (A/ω3) were also evaluated. Suitable participants were distributed into two main groups: (1) T2DMG (with retinopathy (+DR) or without retinopathy (−DR)) and (2) controls (CG). Participants were randomly assigned (+A/ω3) or not (−A/ω3) to the oral supplementation with a daily pill of Nutrof Omega (R) for 18 months. Data collected including demographics, anthropometrics, characteristics/lifestyle, ophthalmic examination (best corrected visual acuity, ocular fundus photographs, and retinal thickness as assessed by optical coherence tomography), and blood parameters (glucose, glycosylated hemoglobin, triglycerides, malondialdehyde, and total antioxidant capacity) were registered, integrated, and statistically processed by the SPSS 15.0 program. Finally, 208 participants (130 diabetics (68 +DR/62 −DR) and 78 controls) completed the follow-up. Blood analyses confirmed that the T2DMG+DR patients had significantly higher oxidative stress (p < 0.05), inflammatory (p < 0.05), and vascular (p < 0.001) risk markers than the T2DMG−DR and the CG. Furthermore, the A/ω3 oral supplementation positively changed the baseline parameters, presumptively by inducing metabolic activation and ameliorating the ocular health after 18 months of supplementation. PMID:26618168

Risk factors for diabetic retinopathy in northern Chinese patients with type 2 diabetes mellitus.

PubMed

Yan, Zhi-Peng; Ma, Jing-Xue

2016-01-01

To investigate the prevalence and risk factors of diabetic retinopathy (DR) in northern Chinese patients with type 2 diabetes mellitus (T2DM). This retrospective cross-sectional study was performed between May 2011 and April 2012. A total of 1100 patients (male/female, 483/617) were included in this study. DR was defined following the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. All included patients accepted a comprehensive ophthalmic examination including retinal photographs. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence interval (CI) after adjusting for age and gender. Retinopathy was present in 307 patients with a prevalence of 27.9%. In univariate logistic analysis, presence of DR was associated with longer duration of diabetes (OR, 5.70; 95%CI, 2.91-12.56), higher concentration of fasting blood glucose (OR, 12.94; 95%CI, 2.40-67.71), higher level of glycosylated hemoglobin HbA1c (OR, 5.50; 95%CI, 3.78-11.97) and insulin treatment (OR, 6.99; 95%CI, 1.39-35.12). The lifestyle of patients with T2DM including smoking, alcohol consumption and regular exercise seemed not associated with the development of DR. Our study suggests that fasting serum glucose concentration, HbA1c level, duration of diabetes and insulin treatment are potential risk factors for DR in northern Chinese patients with T2DM, while the lifestyle of included patients seems not associated with DR.

Distant stereoacuity in children with anisometropic amblyopia.

PubMed

Chung, Yeon Woong; Park, Shin Hae; Shin, Sun Young

2017-09-01

To characterize changes in distant stereoacuity using Frisby-Davis Distance test (FD2) and Distant Randot test (DR) during treatment for anisometropic amblyopia, to determine factors that influence posttreatment stereoacuity and to compare the two distant stereotests. Fifty-eight anisometropic amblyopic patients with an interocular difference of ≥1.00 diopter who achieved the visual acuity 20/20 following amblyopia treatment were retrospectively included. Stereoacuity using FD2 and DR for distant and Titmus test for near measurement were assessed and compared at the initial, intermediate, and final visit. Multivariate regression models were used to identify factors associated with initial and final stereoacuity. The two distant stereotests revealed a significant improvement in distant stereoacuity after successful amblyopia treatment. Distant stereoacuity using FD2 showed the greatest improvement during the follow up period. The number of nil scores was higher in DR than FD2 at each period. In multivariate analysis, better final stereoacuity was associated with better initial amblyopic eye acuity in both distant stereotests, but not in the Titmus test. Comparing the two distant stereotests, final stereoacuity using FD2 was associated with initial stereoacuity and was moderately related with the Titmus test at each period, but final stereoacuity using DR was not. Distant stereoacuity measured with both FD2 and DR showed significant improvement when the visual acuity of the amblyopic eye achieved 20/20. Changes in distant stereoacuity by FD2 and DR during the amblyopia treatment were somewhat different.

Lipoprotein(a) predicts the development of diabetic retinopathy in people with type 2 diabetes mellitus.

PubMed

Yun, Jae-Seung; Lim, Tae-Seok; Cha, Seon-Ah; Ahn, Yu-Bae; Song, Ki-Ho; Choi, Jin A; Kwon, Jinwoo; Jee, Donghyun; Cho, Yang Kyung; Park, Yong-Moon; Ko, Seung-Hyun

2016-01-01

Lipoprotein(a) [Lp(a)] has mainly been considered to be a predictor of the incidence of cardiovascular disease. In addition, previous studies have shown potential linkage between Lp(a) and diabetic microvascular complications. We investigated the incidence and risk factors for the development of diabetic retinopathy (DR) in patients with type 2 diabetes. A total of 787 patients with type 2 diabetes without DR were consecutively enrolled and followed up prospectively. Retinopathy evaluation was annually performed by ophthalmologists. The main outcome was new onset of DR. The median follow-up time was 11.1 years. Patients in the DR group had a longer duration of diabetes (P < .001), higher baseline HbA1c (P < .001), higher albuminuria level (P = .033), and higher level of Lp(a) (P = .005). After adjusting for sex, age, diabetes duration, presence of hypertension, renal function, LDL cholesterol, mean HbA1c, and medications, the development of DR was significantly associated with the serum Lp(a) level (HR 1.57, 95% confidence interval [1.11-2.24]; P = .012, comparing the 4th vs 1st quartile of Lp(a)). The patient group with the highest quartile range of Lp(a) and mean HbA1c levels ≥7.0% had an HR of 5.09 (95% confidence interval [2.63-9.84]; P < .001) for developing DR compared with patients with lower levels of both factors. In this prospective cohort study, we demonstrated that the DR was independently associated with the serum Lp(a) level in patients with type 2 diabetes. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Toll-like receptor 4 polymorphisms and their haplotypes modulate the risk of developing diabetic retinopathy in type 2 diabetes patients

PubMed Central

Singh, Kanhaiya; Kant, Shri; Singh, Vivek Kumar; Agrawal, Neeraj K.; Gupta, Sanjeev K.

2014-01-01

Purpose Persistent inflammation and impaired neovascularization in type 2 diabetes mellitus (T2DM) patients may lead to development of macro- and microvascular complications. Diabetic retinopathy (DR) is one of the secondary microvascular complications of T2DM. Improper activation of the innate immune system may be an important contributor in the pathophysiology of DR. Toll-like receptor 4 (TLR4) is an important mediator of innate immunity, and genetic alterations in TLR4 support inflammation in the hyperglycemic condition. The present work was designed to investigate whether the TLR4 single nucleotide polymorphisms (SNPs) rs4986790, rs4986791, rs10759931, rs1927911, and rs1927914 are associated with DR in a north Indian population. Methods The study group of 698 individuals (128 DR, 250 T2DM, 320 controls) was genotyped by PCR-RFLP. Haplotype and linkage disequilibrium between SNPs were determined using Haploview software. Results Combined risk genotypes of TLR4 SNPs rs10759931 (odds ratio [OR] 1.50, p = 0.05) and rs1927914 (OR 1.48, p = 0.05) were found to be significantly associated with pathogenesis of DR. A total of 14 haplotypes with frequency >1% were obtained using Haploview software. Haplotypes ACATC (37.5%) and ACATT (14.8%) were the two most common haplotypes obtained. Conclusions Results of the present case-control study that included 698 north Indian subjects suggested that TLR4 SNPs rs10759931 and rs1927914 modulate the risk of DR in T2DM cases. Association analysis using haplotypes showed none of the haplotypes were associated with either susceptibility or resistance to DR in a north Indian population. PMID:24883015

HLA-DR4-associated T and B cell responses to specific determinants on the IA-2 autoantigen in type 1 diabetes.

PubMed

McLaughlin, Kerry A; Gulati, Kavita; Richardson, Carolyn C; Morgan, Diana; Bodansky, H Jonathan; Feltbower, Richard G; Christie, Michael R

2014-11-01

Autoantibodies to IA-2 in type 1 diabetes are associated with HLA-DR4, suggesting influences of HLA-DR4-restricted T cells on IA-2-specific B cell responses. The aim of this study was to investigate possible T-B cell collaboration by determining whether autoantibodies to IA-2 epitopes are associated with T cell responses to IA-2 peptides presented by DR4. T cells secreting the cytokines IFN-γ and IL-10 in response to seven peptides known to elicit T cell responses in type 1 diabetes were quantified by cytokine ELISPOT in HLA-typed patients characterized for Abs to IA-2 epitopes. T cell responses were detected to all peptides tested, but only IL-10 responses to 841-860 and 853-872 peptides were associated with DR4. Phenotyping by RT-PCR of FACS-sorted CD45RO(hi) T cells secreting IL-10 in response to these two peptides indicated that these expressed GATA-3 or T-bet, but not FOXP3, consistent with these being Th2 or Th1 memory T cells rather than of regulatory phenotype. T cell responses to the same two peptides were also associated with specific Abs: those to 841-860 peptide with Abs to juxtamembrane epitopes, which appear early in prediabetes, and those to peptide 853-872 with Abs to an epitope located in the 831-862 central region of the IA-2 tyrosine phosphatase domain. Abs to juxtamembrane and central region constructs were both DR4 associated. This study identifies a region of focus for B and T cell responses to IA-2 in HLA-DR4 diabetic patients that may explain HLA associations of IA-2 autoantibodies, and this region may provide a target for future immune intervention to prevent disease. Copyright © 2014 by The American Association of Immunologists, Inc.

Jam Resistant Communications Systems Techniques

DTIC Science & Technology

1982-12-01

ina rayo iteeet -- :."-,(constraint elements plus two resolution elements). •j, r,2 -- ’:." ~d c =0 .4 3 ),, dr l :3 .2X , dr 2 4 5 X @d -900 , s :33...E.K. Walton (Section VIII), and Dr. I.J. Gupta (Sections IX and X ). Mr. R.C. Taylor and R.W. Evans made significant contributions to all experimental...IN THE SAME CUT 190 E. CONCLUSIONS 200 F. REFERENCES 00 SECTION X ELEMENT PLACEMENT FOR ADAPTIVE ANTENNA ARRAYS 201 A. INTRODUCTION 201 B. THE ELEMENT

Performance evaluation of the active-flow personal DataRAM PM 2.5 mass monitor (Thermo Anderson pDR-1200) designed for continuous personal exposure measurements

NASA Astrophysics Data System (ADS)

Chakrabarti, Bhabesh; Fine, Philip M.; Delfino, Ralph; Sioutas, Constantinos

The need for continuous personal monitoring for exposure to particulate matter has been demonstrated by recent health studies showing effects of PM exposure on time scales of less than a few hours. Filter-based methods cannot measure this short-term variation of PM levels, which can be quite significant considering human activity patterns. The goal of this study was to evaluate the active-flow personal DataRAM for PM 2.5 (MIE pDR-1200; Thermo Electron Corp., Franklin, MA) designed as a wearable monitor to continuously measure particle exposure. The instrument precision was found to be good (2.1%) and significantly higher than the passive pDR configuration tested previously. A comparison to other proven continuous monitors resulted in good agreement at low relative humidities. Results at higher humidity followed predictable trends and provided a correction scheme that improved the accuracy of pDR readings. The pDR response to particle size also corresponded to previously observed and theoretical errors. The active flow feature of the pDR allows collection of the sampled particles on a back-up filter. The 24-h mass measured on this filter was found to compare very well with a Federal Reference Method for PM 2.5 mass.

Quantitative partition of threonine oxidation in pigs: Effect of dietary threonine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ballevre, O.; Cadenhead, A.; Calder, A.G.

1990-10-01

Kinetic aspects of threonine (Thr) metabolism were examined in eight pigs fed hourly with a diet containing either 0.68% (LT group) or 0.81% (HT group) of Thr (wt/wt), corresponding to 10 and 30% Thr excess, respectively, compared with an ideal diet. Primary production (PR) and disposal (DR) rates were obtained for Thr, glycine (Gly), and 2-keto-butyrate (KB) after a 12-h continuous infusion of L-(U-14C)-Thr together with (1-13C)Gly and a 6-h continuous infusion of (1-14C)KB. Transfer of Thr into secondary pools was also monitored, and from these the rates of Thr oxidation through the catabolic pathways of L-Thr 3-dehydrogenase (DR(Thr-Gly)) andmore » threonine dehydratase (DR(Thr-KB)) were estimated. For the LT group the results were (mumol.kg-1.h-1) PR(Thr) 314 +/- 3, PR(Gly) 551 +/- 24, PR(KB) 41 +/- 3, DR(Thr-Gly) 22 +/- 2, and DR(Thr-KB) 7 +/- 1. For the HT group they were PR(Thr) 301 +/- 23, PR(Gly) 598 +/- 55, PR(KB) 39 +/- 4, DR(Thr-Gly) 32 +/- 2, and DR(Thr-KB) 8 +/- 1. The increase in Thr intake (14 mumol.kg-1.h-1, P less than 0.01) induced a commensurate increase in the sum of DR(Thr-Gly) and DR(Thr-KB) (14 mumol.kg-1.h-1, P less than 0.001) when liver was used as the precursor pool. This was mainly due to the increased DR(Thr-Gly) (13 mumol.kg-1.h-1, P less than 0.01); the change in DR(Thr-KB) was not statistically significant. By comparison of intracellular-to-plasma ratios of specific activities (or enrichments) for different tissues with each type of infusion, liver was shown to be the major site of production of Gly and KB from Thr. These data suggest that in fed growing pigs a 30% excess of Thr in the diet does not alter the partition of Thr oxidation, since 80% of Thr oxidation occurs through the L-Thr 3-dehydrogenase pathway for both LT and HT groups.« less

Epitope Analysis of the Collagen Type V-Specific T Cell Response in Lung Transplantation Reveals an HLA-DRB1*15 Bias in Both Recipient and Donor

PubMed Central

Keller, Melissa R.; Haynes, Lynn D.; Jankowska-Gan, Ewa; Sullivan, Jeremy A.; Agashe, Vrushali V.; Burlingham, Scott R.; Burlingham, William J.

2013-01-01

Background IL-17-dependent cellular immune responses to the α1 chain of collagen type V are associated with development of bronchiolitis obliterans syndrome after lung transplantation, and with idiopathic pulmonary fibrosis and coronary artery disease, primary indications for lung or heart transplantation, respectively. Methodology/Principal Findings We found that 30% of the patients awaiting lung transplantation exhibited a strong cell-mediated immune response to col(V). Of these, 53% expressed HLA-DR15, compared to a 28% HLA-DR15 frequency in col(V) low-responders (p=0.02). After transplantation, patients with HLA-DR1 and -DR17, not -DR15, developed anti-col(V) responses most frequently (p=0.04 and 0.01 vs. controls, respectively). However, recipients of a lung from an HLA-DR15+ donor were at significantly elevated risk of developing anti-col(V) responses (p=0.02) and BOS (p=0.03). To determine the molecular basis of this unusual pattern of DR allele bias, a peptide library comprising the collagenous region of the α1(V) protein was screened for binding to HLA-DR0101, -DR1501, -DR0301 (DR17) or to HLA-DQ2 (DQA1*0501: DQB1*0201; in linkage disequilibrium with -DR17) and -DQ6 (DQA1*0102: DQB1*0602; linked to -DR15). Eight 15-mer peptides, six DR-binding and two DQ-binding, were identified. HLA-DR15 binding to two peptides yielded the highest binding scores: 650 (where 100 = positive control) for p799 (GIRGLKGTKGEKGED), and 193 for p1439 (LRGIPGPVGEQGLPG). These peptides, which also bound weakly to HLA-DR1, elicited responses in both HLA-DR1+ and -DR15+ col(V) reactive hosts, whereas binding and immunoreactivity of p1049 (KDGPPGLRGFPGDRG) was DR15-specific. Remarkably, a col(V)-reactive HLA-DR1+DR15neg lung transplant patient, whose donor was HLA-DR15+, responded not only to p799 and p1439, but also to p1049. Conclusions/Significance HLA-DR15 and IPF disease were independently associated with pre-transplant col(V) autoimmunity. The increased risk of de novo immunity to col(V) and BOS, associated with receiving a lung transplant from an HLA-DR15+ donor, may result from presentation by donor-derived HLA- DR15, of novel self-peptides to recipient T cells. PMID:24265781

First successful reduction of clinical allergenicity of food by genetic modification: Mal d 1-silenced apples cause fewer allergy symptoms than the wild-type cultivar.

PubMed

Dubois, A E J; Pagliarani, G; Brouwer, R M; Kollen, B J; Dragsted, L O; Eriksen, F D; Callesen, O; Gilissen, L J W J; Krens, F A; Visser, R G F; Smulders, M J M; Vlieg-Boerstra, B J; Flokstra-de Blok, B J; van de Weg, W E

2015-11-01

Genetic modification of allergenic foods such as apple has the potential to reduce their clinical allergenicity, but this has never been studied by oral challenges in allergic individuals. We performed oral food challenges in 21 apple-allergic individuals with Elstar apples which had undergone gene silencing of the major allergen of apple, Mal d 1, by RNA interference. Downregulation of Mal d 1 gene expression in the apples was verified by qRT-PCR. Clinical responses to the genetically modified apples were compared to those seen with the wild-type Elstar using a visual analogue scale (VAS). Gene silencing produced two genetically modified apple lines expressing Mal d 1.02 and other Mal d 1 gene mRNA levels which were extensively downregulated, that is only 0.1-16.4% (e-DR1) and 0.2-9.9% (e-DR2) of those of the wild-type Elstar, respectively. Challenges with these downregulated apple lines produced significantly less intense maximal symptoms to the first dose (Vmax1) than with Elstar (Vmax1 Elstar 3.0 mm vs 0.0 mm for e-DR1, P = 0.017 and 0.0 mm for e-DR2, P = 0.043), as well as significantly less intense mean symptoms per dose (meanV/d) than with Elstar (meanV/d Elstar 2.2 mm vs 0.2 mm for e-DR1, P = 0.017 and 0.0 mm for e-DR2, P = 0.043). Only one subject (5%) remained symptom-free when challenged with the Elstar apple, whereas 43% did so with e-DR1 and 63% with e-DR2. These data show that mRNA silencing of Mal d 1 results in a marked reduction of Mal d 1 gene expression in the fruit and reduction of symptoms when these apples are ingested by allergic subjects. Approximately half of the subjects developed no symptoms whatsoever, and virtually all subjects wished to consume the apple again in the future. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Association analysis of nine candidate gene polymorphisms in Indian patients with type 2 diabetic retinopathy.

PubMed

Balasubbu, Suganthalakshmi; Sundaresan, Periasamy; Rajendran, Anand; Ramasamy, Kim; Govindarajan, Gowthaman; Perumalsamy, Namperumalsamy; Hejtmancik, J Fielding

2010-11-10

Diabetic retinopathy (DR) is classically defined as a microvasculopathy that primarily affects the small blood vessels of the inner retina as a complication of diabetes mellitus (DM).It is a multifactorial disease with a strong genetic component. The aim of this study is to investigate the association of a set of nine candidate genes with the development of diabetic retinopathy in a South Indian cohort who have type 2 diabetes mellitus (T2DM). Seven candidate genes (RAGE, PEDF, AKR1B1, EPO, HTRA1, ICAM and HFE) were chosen based on reported association with DR in the literature. Two more, CFH and ARMS2, were chosen based on their roles in biological pathways previously implicated in DR. Fourteen single nucleotide polymorphisms (SNPs) and one dinucleotide repeat polymorphism, previously reported to show association with DR or other related diseases, were genotyped in 345 DR and 356 diabetic patients without retinopathy (DNR). The genes which showed positive association in this screening set were tested further in additional sets of 100 DR and 90 DNR additional patients from the Aravind Eye Hospital. Those which showed association in the secondary screen were subjected to a combined analysis with the 100 DR and 100 DNR subjects previously recruited and genotyped through the Sankara Nethralaya Hospital, India. Genotypes were evaluated using a combination of direct sequencing, TaqMan SNP genotyping, RFLP analysis, and SNaPshot PCR assays. Chi-square and Fisher exact tests were used to analyze the genotype and allele frequencies. Among the nine loci (15 polymorphisms) screened, SNP rs2070600 (G82S) in the RAGE gene, showed significant association with DR (allelic P = 0.016, dominant model P = 0.012), compared to DNR. SNP rs2070600 further showed significant association with DR in the confirmation cohort (P = 0.035, dominant model P = 0.032). Combining the two cohorts gave an allelic P < 0.003 and dominant P = 0.0013). Combined analysis with the Sankara Nethralaya cohort gave an allelic P = 0.0003 and dominant P = 0.00011 with an OR = 0.49 (0.34 - 0.70) for the minor allele. In HTRA1, rs11200638 (G>A), showed marginal significance with DR (P = 0.055) while rs10490924 in LOC387715 gave a P = 0.07. No statistical significance was observed for SNPs in the other 7 genes studied. This study confirms significant association of one polymorphism only (rs2070600 in RAGE) with DR in an Indian population which had T2DM.

Structural mapping of divergent regions in the type 1 ryanodine receptor using fluorescence resonance energy transfer

PubMed Central

Mahalingam, Mohana; Girgenrath, Tanya; Svensson, Bengt; Thomas, David D.; Cornea, Razvan L.; Fessenden, James D.

2014-01-01

Summary Ryanodine receptors (RyR) release Ca2+ to initiate striated muscle contraction. Three highly divergent regions in the RyR protein sequence (DR1, DR2, DR3) are proposed to confer isoform-specific functional properties to the RyRs. We used cell-based fluorescence resonance energy transfer (FRET) measurements to localize these DRs to the cryo-electron microscopic (EM) map of the skeletal muscle RyR isoform (RyR1). FRET donors were targeted to RyR1 using five different FKBP12.6 variants labeled with Alexa Fluor 488. FRET was then measured to Cy3NTA or Cy5NTA, FRET acceptors targeted to decahistidine tags introduced within the DRs. DR2 and DR3 were localized to separate positions within the “clamp” region of the RyR1 cryo-EM map, which is presumed to interface with Cav1.1. DR1 was localized to the “handle” region, near the regulatory calmodulin binding site on the RyR. These localizations provide new insights into the roles of DRs in RyR allosteric regulation during excitation-contraction coupling. PMID:25132084

The relationship between ACE/AGT gene polymorphisms and the risk of diabetic retinopathy in Chinese patients with type 2 diabetes.

PubMed

Qiao, Yong-Chao; Wang, Min; Pan, Yan-Hong; Zhang, Xiao-Xi; Tian, Fang; Chen, Yin-Ling; Zhao, Hai-Lu

2018-01-01

This study aims to investigate the association between renin-angiotensin system gene polymorphism and diabetic retinopathy (DR) in Chinese patients with type 2 diabetes. We consecutively included 1491 patients for the assessment of ACE I/D and AGT M/T gene polymorphisms in 345 DR cases and 1146 patients without retinopathy (DNR). Albuminuria was defined by urine albumin creatinine ratio and albumin excretion rate. Compared with the NDR patients, the DR cases displayed a higher proportion of diabetic nephropathy (32.68% vs. 6.52%, χ 2 = 150.713, p < 0.001). The DR cases and DNR individuals did not differ in the frequency of genotypes and alleles of ACE I/D and AGT M/T (all p > 0.05). Intriguingly, DR patients with obesity showed higher frequency of DD (χ 2 = 4.181, p = 0.041), but no significant difference exists in the other stratified BMI and hypertension analyses (all p > 0.05). Binary logistic regression displays that the association of the ACE and AGT gene polymorphisms in DR patients is not significant after adjusting for confounding covariates in all the comparisons. The ACE and AGT gene polymorphisms are not associated with the progress of diabetes developing into retinopathy in Chinese patients with type 2 diabetes. However, more investigations are needed to further prove the association.

Does bariatric surgery prevent progression of diabetic retinopathy?

PubMed

Chen, Y; Laybourne, J P; Sandinha, M T; de Alwis, N M W; Avery, P; Steel, D H

2017-08-01

PurposeTo assess the changes in diabetic retinopathy (DR) in type 2 diabetes (T2DM) patients post bariatric surgery and report on the risk factors that may be associated with it.Patients and methodsRetrospective observational study of T2DM patients who underwent bariatric surgery in a UK specialist bariatric unit between 2009 and 2015. Preoperative and postoperative weight, HbA1c, and annual DR screening results were collected from medical records. Patients with preoperative retinal screening and at least one postoperative retinal screening were eligible for analysis. Multivariate analysis was used to explore significant clinical predictors on postoperative worsening in DR.ResultsA total of 102 patients were eligible for analysis and were followed up for 4 years. Preoperatively, 68% of patients had no DR compared to 30% with background retinopathy, 1% pre-proliferative retinopathy, and 1% proliferative retinopathy. In the first postoperative visit, 19% of patients developed new DR compared to 70% stable and 11% improved. These proportions remained similar for each postoperative visit over time. Young age, male gender, high preoperative HbA1c, and presence of preoperative retinopathy were the significant predictors of worsening postoperatively.ConclusionBariatric surgery does not prevent progression of DR. Young male patients with pre-existing DR and poor preoperative glycaemic control are most at risk of progression. All diabetic patients should attend regular DR screening post bariatric surgery to allow early detection of potentially sight-threatening changes, particularly among those with identifiable risk factors. Future prospective studies with prolonged follow-up are required to clarify the duration of risk.

Lower Frequency of HLA-DRB1 Type 1 Diabetes Risk Alleles in Pediatric Patients with MODY.

PubMed

Urrutia, Inés; Martínez, Rosa; López-Euba, Tamara; Velayos, Teresa; Martínez de LaPiscina, Idoia; Bilbao, José Ramón; Rica, Itxaso; Castaño, Luis

2017-01-01

The aim of this study was to determine the frequency of susceptible HLA-DRB1 alleles for type 1 diabetes in a cohort of pediatric patients with a confirmed genetic diagnosis of MODY. 160 families with a proband diagnosed with type 1 diabetes and 74 families with a molecular diagnosis of MODY (61 GCK-MODY and 13 HNF1A-MODY) were categorized at high definition for HLA-DRB1 locus. According to the presence or absence of the susceptible HLA-DRB1 alleles for type 1 diabetes, we considered three different HLA-DRB1 genotypes: 0 risk alleles (no DR3 no DR4); 1 risk allele (DR3 or DR4); 2 risk alleles (DR3 and/or DR4). Compared with type 1 diabetes, patients with MODY carried higher frequency of 0 risk alleles, OR 22.7 (95% CI: 10.7-48.6) and lower frequency of 1 or 2 risk alleles, OR 0.53 (95% CI: 0.29-0.96) and OR 0.06 (95% CI: 0.02-0.18), respectively. The frequency of HLA-DRB1 risk alleles for type 1 diabetes is significantly lower in patients with MODY. In children and adolescents with diabetes, the presence of 2 risk alleles (DR3 and/or DR4) reduces the probability of MODY diagnosis, whereas the lack of risk alleles increases it. Therefore, we might consider that HLA-DRB1 provides additional information for the selection of patients with high probability of monogenic diabetes.

Factors Associated with Nursing Activities in Humanitarian Aid and Disaster Relief

PubMed Central

Noguchi, Norihito; Inoue, Satoshi; Shimanoe, Chisato; Shibayama, Kaoru; Shinchi, Koichi

2016-01-01

Background Although nurses play an important role in humanitarian aid and disaster relief (HA/DR), little is known about the nursing activities that are performed in HA/DR. We aimed to clarify the nursing activities performed by Japanese nurses in HA/DR and to examine the factors associated with the frequency of nursing activities. Methods A self-administered questionnaire survey was completed by 147 nurses with HA/DR experience. The survey extracted information on demographic characteristics, past experience (e.g., disaster medical training experience, HA/DR experience), circumstances surrounding their dispatched to HA/DR (e.g., team size, disaster type, post-disaster phase, mission term), and the frequency of nursing activities performed under HA/DR. The frequency of nursing activities was rated on a 5-point Likert scale. Evaluation of nursing activities was conducted based on the “nursing activity score”, which represents the frequency of each nursing activity. Factors related to the nursing activity score were evaluated by multiple logistic regression analysis. Results Nurses were involved in 27 nursing activities in HA/DR, 10 of which were performed frequently. On analysis, factors significantly associated with nursing activity score were nursing license as a registered nurse (OR 7.79, 95% CI 2.95–20.57), two or more experiences with disaster medical training (OR 2.90 95%, CI 1.12–7.49) and a post-disaster phase of three weeks or longer (OR 8.77, 95% CI 2.59–29.67). Conclusions These results will contribute to the design of evidence-based disaster medical training that improves the quality of nursing activities. PMID:26959351

Dissecting the Gene Network of Dietary Restriction to Identify Evolutionarily Conserved Pathways and New Functional Genes

PubMed Central

Wuttke, Daniel; Connor, Richard; Vora, Chintan; Craig, Thomas; Li, Yang; Wood, Shona; Vasieva, Olga; Shmookler Reis, Robert; Tang, Fusheng; de Magalhães, João Pedro

2012-01-01

Dietary restriction (DR), limiting nutrient intake from diet without causing malnutrition, delays the aging process and extends lifespan in multiple organisms. The conserved life-extending effect of DR suggests the involvement of fundamental mechanisms, although these remain a subject of debate. To help decipher the life-extending mechanisms of DR, we first compiled a list of genes that if genetically altered disrupt or prevent the life-extending effects of DR. We called these DR–essential genes and identified more than 100 in model organisms such as yeast, worms, flies, and mice. In order for other researchers to benefit from this first curated list of genes essential for DR, we established an online database called GenDR (http://genomics.senescence.info/diet/). To dissect the interactions of DR–essential genes and discover the underlying lifespan-extending mechanisms, we then used a variety of network and systems biology approaches to analyze the gene network of DR. We show that DR–essential genes are more conserved at the molecular level and have more molecular interactions than expected by chance. Furthermore, we employed a guilt-by-association method to predict novel DR–essential genes. In budding yeast, we predicted nine genes related to vacuolar functions; we show experimentally that mutations deleting eight of those genes prevent the life-extending effects of DR. Three of these mutants (OPT2, FRE6, and RCR2) had extended lifespan under ad libitum, indicating that the lack of further longevity under DR is not caused by a general compromise of fitness. These results demonstrate how network analyses of DR using GenDR can be used to make phenotypically relevant predictions. Moreover, gene-regulatory circuits reveal that the DR–induced transcriptional signature in yeast involves nutrient-sensing, stress responses and meiotic transcription factors. Finally, comparing the influence of gene expression changes during DR on the interactomes of multiple organisms led us to suggest that DR commonly suppresses translation, while stimulating an ancient reproduction-related process. PMID:22912585

Availability and variability in guidelines on diabetic retinopathy screening in Asian countries.

PubMed

Wang, Louis Zizhao; Cheung, Carol Y; Tapp, Robyn J; Hamzah, Haslina; Tan, Gavin; Ting, Daniel; Lamoureux, Ecosse; Wong, Tien Yin

2017-10-01

Diabetic retinopathy (DR) is a blinding yet treatable complication of diabetes. DR screening is highly cost-effective at reducing blindness. Amidst the rapidly growing diabetic population in Asia, the prevalence of DR in the region is relatively less well known. To review existing national DR screening guidelines of 50 countries in Asia, compare them against the International Council of Ophthalmology (ICO) guideline, and summarise the prevalence rates of DR and sight-threatening DR (STDR) in these countries. We systematically searched for published guidelines from the National Guideline Clearinghouse and other databases, and contacted local diabetic and ophthalmological associations of all 50 Asian countries. Eleven Asian countries have published relevant guidelines, nine of which pertain to general diabetes care and two are DR-specific, covering less than half of Asia's population. The median DR prevalence among patients with diabetes is 30.5% (IQR: 23.2%-36.8%), similar to the USA and the UK. However, rates of STDR are consistently higher. All guidelines from the 11 Asian countries fulfil the ICO standard on when to start and repeat screening, except for screening interval for pregnant patients. However, only 2 of the 11 guidelines fulfil the ICO referral criteria and 6 partially fulfil. A third of the recommendations on screening process, equipment and personnel is either unavailable or incomplete. Countries in Asia need to establish more comprehensive and evidence-based DR screening guidelines to facilitate the execution of robust screening programmes that could help reduce DR-related blindness, improve patient outcomes and reduce healthcare costs. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Iranian risk model as a predictive tool for retinopathy in patients with type 2 diabetes.

PubMed

Azizi-Soleiman, Fatemeh; Heidari-Beni, Motahar; Ambler, Gareth; Omar, Rumana; Amini, Masoud; Hosseini, Sayed-Mohsen

2015-10-01

Diabetic retinopathy (DR) is the leading cause of blindness in patients with type 1 or type 2 diabetes. The gold standard for the detection of DR requires expensive equipment. This study was undertaken to develop a simple and practical scoring system to predict the probability of DR. A total of 1782 patients who had first-degree relatives with type II diabetes were selected. Eye examinations were performed by an expert ophthalmologist. Biochemical and anthropometric predictors of DR were measured. Logistic regression was used to develop a statistical model that can be used to predict DR. Goodness of fit was examined using the Hosmer-Lemeshow test and the area under the receiver operating characteristic (ROC) curve. The risk model demonstrated good calibration and discrimination (ROC area=0.76) in the validation sample. Factors associated with DR in our model were duration of diabetes (odds ratio [OR]=2.14, confidence interval [CI] 95%=1.87 to 2.45); glycated hemoglobin (A1C) (OR=1.21, CI 95%=1.13 to 1.30); fasting plasma glucose (OR=1.83, CI 95%=1.28 to 2.62); systolic blood pressure (OR=1.01, CI 95%= 1.00 to 1.02); and proteinuria (OR=1.37, CI 95%=1.01 to 1.85). The only factor that had a protective effect against DR were body mass index and education level (OR=0.95, CI 95%=0.92 to 0.98). The good performance of our risk model suggests that it may be a useful risk-prediction tool for DR. It consisted of the positive predictors like A1C, diabetes duration, sex (male), fasting plasma glucose, systolic blood pressure and proteinuria, as well as negative risk factors like body mass index and education level. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Death rattle: prevalence, prevention and treatment.

PubMed

Wildiers, Hans; Menten, Johan

2002-04-01

A retrospective analysis was performed to study the occurrence and treatment of death rattle (DR) in 107 consecutive dying patients on the palliative care unit of the University Hospital Leuven. The incidence of DR (23%) is lower than reported in literature, possibly due to low hydration. We found 2 types of rattle: "Real DR" responds generally very well to anticholinergic therapy, and is probably caused by non-expectorated secretions. "Pseudo DR" is poorly responsive to therapy and is probably caused by bronchial secretions due to pulmonary pathology, such as infection, tumor, fluid retention, or aspiration. Rattle disappeared in >90% for the patients with real DR. Real DR is a strong predictor for death, and 76% (19/25) died within 48h after onset. Administration of subcutaneous hyoscine hydrobromide, as a bolus or continuous infusion, is effective therapy for real DR and is comfortable for the patient and caregivers.

Lacking prognostic significance of beta 2-microglobulin, MHC class I and class II antigen expression in breast carcinomas.

PubMed Central

Wintzer, H. O.; Benzing, M.; von Kleist, S.

1990-01-01

To evaluate the impact of MHC antigen expression on the survival of patients with cancer, 77 human breast carcinomas were investigated for the expression of beta 2-microglobulin (beta 2m), HLA-A,B,C and HLA-DR. Thirty-one benign breast tumours were stained for comparison. The results for the carcinomas were related to the survival data of the cancer patients. The expression of beta 2m, HLA-A,B,C and HLA-DR was significantly lower in malignant tumours compared to the benign lesions. Whereas all benign tumours were positive for beta 2m and HLA-A,B,C and 28/31 positive for HLA-DR the following positivity rates were found in carcinomas: 74/77 for beta 2m, 57/77 for HLA-A,B,C and 10/77 for HLA-DR. The follow-up (median 45 months) of 66 cancer patients for overall survival and of 65 patients for disease-free survival revealed no influence of beta 2m, HLA-A,B,C or HLA-DR expression on the prognosis of this cancer. In conclusion, experimental data indicating the importance of MHC antigens in anti-tumour responses are not confirmed by the analysis of cancer patient survival data. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2201398

Modeling Item Responses When Different Subjects Employ Different Solution Strategies.

DTIC Science & Technology

1987-10-01

Crombag Dr. Stephen Dunbar University of Leyden Lindquist Center Education Research l-enter for Measurement Boerhaavelaan 2 University of Iowa 2334 EN... Leyden Iowa City, IA 52242 The NEFHlPLANDS Dr. James A. F.arles Mr. Iimothy Davey Air Force Human Resources Lab iJniversity of Illinois Brooks AFB, TX...Education and Training Dr. William Montague Naval Air Station NPRDC Code 13 Pensacola, fL 32508 San Diego, CA 92152-6800 Dr. Gary Marco Ms. Kathleen Moreno

United States Air Force Summer Faculty Research Program. 1985 Technical Report. Volume 2.

DTIC Science & Technology

1985-12-01

Voluntary Hand Grip Torque for Dr. Samuel Adams Circular Electrical Connectors 3 Properties and Processing of a Dr. Vernon R. Allen Perfluorinated ...Neutral Particle Beam at Low Energies in the Mark I Aerospace Chamber 126 Preparation of Non-Flammable Model Dr. Terrill D. Smith Compounds 127 Studies on...Synthesis of Azo Compounds F xi 140 A Comparison of Measured and Calculated Dr. Larry Vardiman Attenuation of 28 GHZ Beacon Signals in Three California

United States Air Force Summer Faculty Research Program 1989. Program Technical Report. Volume 2

DTIC Science & Technology

1989-12-01

of an Osmotically Dr. Juin Yu Driven Thermal Transfer Cycle 114 The Influence of Viscoelastically Dr. Lawrence Zavodney Damped Members on the Dynamic...Hormones Effect Upon Dr. Rex Moyer Chlamydomonas Phototaxis 166 Influence of Radio Frequency Dr. Raymond Quock Radiation on Psychotropic Drug Effects 167...systems do not cover. Therefore, the use of SHG for creating coherent light at twice the frequency of an- other laser is one way to extend the range

Nasofacial defect following fibrosarcoma excision and radiotherapy.

PubMed

Burget, G L; Panje, W R; Krause, C J

1988-01-01

For initial reconstruction, Dr. Burget suggests that he would have advanced the cheek flap medially toward the nasal septum and, subsequently, reconstructed the missing right half of the nose with a forehead flap and cartilage grafts. Dr. Panje suggested early prosthetic rehabilitation, while Dr. Krause's concepts were similar to Dr. Burget's, with forehead flap nasal reconstruction, after cheek reconstruction to the nasofacial and nasolabial lines with a medially advanced cheek flap. Dr. Panje recommended an immediate maxillary denture prosthesis, as did Dr. Krause (who supplemented this with foam rubber). Dr. Burget placed the prosthesis 3 weeks after tumor ablation. For skin grafts, Drs. Panje and Burget suggested split thickness grafts to all new surfaces to decrease wound contracture, while Dr. Krause used dermis grafts for the same purpose. Other reconstructive methods mentioned were the (1) cervical tubed flap, (2) free scapular flap, (3) Washio flap, (4) tissue expansion, and (5) nasolabial flap. Suggestions for isolated defects included: Lower eyelid--increase internal support by building up the prosthesis; release lower lid from deltopectoral flap and V-Y advancement; support graft or irradiated cartilage (1-2 mm sheet) under orbicularis oculi. Nasal ala--bring present ala down and insert cartilage graft; turn internal skin down and fill the resulting defect with a composite graft. Upper lip--multiple Z-plasty. Retrodisplacement of cheek due to maxillectomy--release buccal scar; skin graft the raw internal surface and build up prosthesis.

Design requirements for innovative homogeneous reactor, lesson learned from Fukushima accident

NASA Astrophysics Data System (ADS)

Arbie, Bakri; Pinem, Suryan; Sembiring, Tagor; Subki, Iyos

2012-06-01

The Fukushima disaster is the largest nuclear accident since the 1986 Chernobyl disaster, but it is more complex as multiple reactors and spent fuel pools are involved. The severity of the nuclear accident is rated 7 in the International Nuclear Events Scale. Expert said that "Fukushima is the biggest industrial catastrophe in the history of mankind". According to Mitsuru Obe, in The Wall Street Journal, May 16th of 2011, TEPCO estimates the nuclear fuel was exposed to the air less than five hours after the earthquake struck. Fuel rods melted away rapidly as the temperatures inside the core reached 2800 C within six hours. In less than 16 hours, the reactor core melted and dropped to the bottom of the pressure vessel. The information should be evaluated in detail. In Germany several nuclear power plant were shutdown, Italy postponed it's nuclear power program and China reviewed their nuclear power program. Different news come from Britain, in October 11, 2011, the Safety Committee said all clear for nuclear power in Britain, because there are no risk of strong earthquake and tsunami in the region. Due to this severe fact, many nuclear scientists and engineer from all over the world are looking for a new approach, such as homogeneous reactor which was developed in Oak Ridge National Laboratory in 1960-ies, during Dr. Alvin Weinberg tenure as the Director of ORNL. The paper will describe the design requirement that will be used as the basis for innovative homogeneous reactor. Innovative Homogeneous Reactor is expected to reduce core melt by two decades (4), since the fuel is intermix homogeneously with coolant and secondly we eliminate the used fuel rod which need to be cooled for a long period of time. In order to be successful for its implementation of the innovative system, testing and validation, three phases of development will be introduced. The first phase is Low Level Goals is really the proof of concept;the Medium Level Goal is Technical Goalsand the High Level Goals which is Business Goals.

The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation: Results From Short-term Pharmacokinetic and 12-Week Dose-Ranging Studies.

PubMed

Buse, John B; DeFronzo, Ralph A; Rosenstock, Julio; Kim, Terri; Burns, Colleen; Skare, Sharon; Baron, Alain; Fineman, Mark

2016-02-01

Delayed-release metformin (Met DR) is formulated to deliver the drug to the lower bowel to leverage the gut-based mechanisms of metformin action with lower plasma exposure. Met DR was assessed in two studies. Study 1 compared the bioavailability of single daily doses of Met DR to currently available immediate-release metformin (Met IR) and extended-release metformin (Met XR) in otherwise healthy volunteers. Study 2 assessed glycemic control in subjects with type 2 diabetes (T2DM) over 12 weeks. Study 1 was a phase 1, randomized, four-period crossover study in 20 subjects. Study 2 was a 12-week, phase 2, multicenter, placebo-controlled, dose-ranging study in 240 subjects with T2DM randomized to receive Met DR 600, 800, or 1,000 mg administered once daily; blinded placebo; or unblinded Met XR 1,000 or 2,000 mg (reference). The bioavailability of 1,000 mg Met DR b.i.d. was ∼50% that of Met IR and Met XR (study 1). In study 2, 600, 800, and 1,000 mg Met DR q.d. produced statistically significant, clinically relevant, and sustained reductions in fasting plasma glucose (FPG) levels over 12 weeks compared with placebo, with an ∼40% increase in potency compared with Met XR. The placebo-subtracted changes from baseline in HbA1c level at 12 weeks were consistent with changes in FPG levels. All treatments were generally well tolerated, and adverse events were consistent with Glucophage/Glucophage XR prescribing information. Dissociation of the glycemic effect from plasma exposure with gut-restricted Met DR provides strong evidence for a predominantly lower bowel-mediated mechanism of metformin action. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Oversight hearings on P. L. 93-577, ERDA Plan and Program. Hearings before the Subcommittee on Energy Research, Development and Demonstration of the Committee on Science and Technology, U. S. House of Representatives, Ninety-Fourth Congress, Second Session

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1976-01-01

The purpose of the hearings was to examine the comprehensive plan and program for dealing with energy that ERDA submitted to Congress on June 30, 1975. Included as an appendix to these hearings is the October 1975 report of the Office of Technology Assessment (OTA) entitled, ''An Analysis of the ERDA Plan and Program'' (for abstract of this report, see EAPA 2:79). Testifying on Jan. 22 was the director of OTA, Emilio Q. Daddario, and chairmen of various task groups that assisted in the ERDA analysis, namely: Dr. John Gibbons, Conservation; Dr. Paul Craig, Overview Panel; Dr. Alvin Weinberg, Nuclear;more » Dr. Stanford S. Penner, Environmental and Health; and Dr. Jerry Grey, Solar; also present, and participating in the question and answer portion was Lionel Johns, head of the energy projects and programs in OTA. Testifying at the Jan. 23 hearings were experts presenting environmental, scientific, and engineering viewpoints, namely: Dr. Donald McDonald, director of the environmental studies program at Dartmouth College; Dr. Reginald Vachon, Auburn University, representing the American Society of Mechanical Engineers; and Dr. Thomas Lee, General Electric Co., representing the Inst. of Electrical and Electronics Engineers. The final hearings on Jan. 29 included the testimony of Dr. Robert W. Fri, Deputy Administrator, ERDA, and that of each of five assistant administrators: Dr. John Teem, Solar, Geothermal, and Advanced Energy Systems; Dr. Austin Heller, Conservation; Dr. Richard W. Roberts, Nuclear Energy; Dr. Roger W. A. LeGassie, Planning and Analysis; and Dr. James Liverman, Environment and Safety. (LMT)« less

Expression and function of dopamine receptors in the developing medial frontal cortex and striatum of the rat

PubMed Central

Sillivan, Stephanie E.; Konradi, Christine

2011-01-01

The timeline of dopamine (DA) system maturation and the signaling properties of dopamine receptors (DRs) during rat brain development are not fully characterized. We used in situ hybridization and quantitative PCR to map DR mRNA transcripts in the medial frontal cortex (mFC) and striatum (STR) of the rat from embryonic day (E) 15 to E21. The developmental trajectory of DR mRNAs revealed distinct patterns of DA receptors 1 and 2 (DRD1, DRD2) in these brain regions. Whereas the mFC had a steeper increase in DRD1 mRNA, the STR had a steeper increase in DRD2 mRNA. Both DR mRNAs were expressed at a higher level in the STR compared to the mFC. To identify the functional properties of DRs during embryonic development, the phosphorylation states of cyclic AMP response element binding protein (CREB), extracellular signal-regulated kinase 1/2 (ERK1/2), and glycogen synthase kinase 3 beta (GSK3β) were examined after DR stimulation in primary neuronal cultures obtained from E15 and E18 embryos and cultured for 3 days to ensure a stable baseline level. DR-mediated signaling cascades were functional in E15 cultures in both brain regions. Because DA fibers do not reach the mFC by E15, and DA was not present in cultures, these data indicate that DRs can become functional in the absence of DA innervation. Since activation of DR signal transduction pathways can affect network organization of the developing brain, maternal exposure to drugs that affect DR activity may be liable to interfere with fetal brain development. PMID:22015925

gp140, the EBV/C3d receptor (CR2) of human B lymphocytes, is involved in cell-free phosphorylation of p120, a nuclear ribonucleoprotein.

PubMed

Delcayre, A X; Fiandino, A; Barel, M; Frade, R

1987-12-01

gp140, the EB/C3d receptor (EBV/C3dR; CR2), is a membrane site involved in human B cell regulation. Cross-linking of this receptor on the cell surface by its specific ligands led to the enhancement of B cell proliferation in synergy with T cell factors. In vitro activation of human peripheral B lymphocytes by cross-linking membrane immunoglobulins with anti-mu antibody induced EBV/C3dR phosphorylation. These studies were pursued by analyzing cell-free phosphorylation of EBV/C3dR isolated from Raji cell fractions, and immobilized on OKB7, a monoclonal anti-EBV/C3dR antibody. Three EBV/C3dR-related antigens which could be cell-free phosphorylated were detected: gp140, the EBV/C3dR, p130 and p120. gp140, the mature form of EBV/C3dR, was isolated from plasma membrane and from purified nuclei. p130 was identified as an intracellular intermediate of EBV/C3dR glycosylation, localized in low-density microsomes. Phosphoamino acid analysis of EBV/C3dR allowed the detection of phosphotyrosine and phosphoserine residues. These data suggest that EBV/C3dR could carry an autophosphorylation activity and could be associated to serine kinases. Using polyclonal anti-p120 antibody and anti-120 kDa nuclear ribonucleoprotein monoclonal antibody (mAb), p120 was identified as a nuclear ribonucleoprotein antigenically not related to EBV/C3dR. Detection of p120 on EBV/C3dR, immobilized on OKB7, was due to interactions between both antigens, instead of anti-EBV/C3dR mAb cross-reactivity with p120. Cell-free phosphorylation of p120 was under the control of EBV/C3dR. However, it is not yet established whether other nuclear or membrane components were involved in the control of p120 cell-free phosphorylation by EBV/C3dR. From the data presented herein, we propose that phosphorylation of a 120-kDa nuclear ribonucleoprotein by EBV/C3dR-associated kinases could represent a crucial step in in vivo regulation of human B cell activation.

2K09 and thereafter : the coming era of integrative bioinformatics, systems biology and intelligent computing for functional genomics and personalized medicine research.

PubMed

Yang, Jack Y; Niemierko, Andrzej; Bajcsy, Ruzena; Xu, Dong; Athey, Brian D; Zhang, Aidong; Ersoy, Okan K; Li, Guo-Zheng; Borodovsky, Mark; Zhang, Joe C; Arabnia, Hamid R; Deng, Youping; Dunker, A Keith; Liu, Yunlong; Ghafoor, Arif

2010-12-01

Significant interest exists in establishing synergistic research in bioinformatics, systems biology and intelligent computing. Supported by the United States National Science Foundation (NSF), International Society of Intelligent Biological Medicine (http://www.ISIBM.org), International Journal of Computational Biology and Drug Design (IJCBDD) and International Journal of Functional Informatics and Personalized Medicine, the ISIBM International Joint Conferences on Bioinformatics, Systems Biology and Intelligent Computing (ISIBM IJCBS 2009) attracted more than 300 papers and 400 researchers and medical doctors world-wide. It was the only inter/multidisciplinary conference aimed to promote synergistic research and education in bioinformatics, systems biology and intelligent computing. The conference committee was very grateful for the valuable advice and suggestions from honorary chairs, steering committee members and scientific leaders including Dr. Michael S. Waterman (USC, Member of United States National Academy of Sciences), Dr. Chih-Ming Ho (UCLA, Member of United States National Academy of Engineering and Academician of Academia Sinica), Dr. Wing H. Wong (Stanford, Member of United States National Academy of Sciences), Dr. Ruzena Bajcsy (UC Berkeley, Member of United States National Academy of Engineering and Member of United States Institute of Medicine of the National Academies), Dr. Mary Qu Yang (United States National Institutes of Health and Oak Ridge, DOE), Dr. Andrzej Niemierko (Harvard), Dr. A. Keith Dunker (Indiana), Dr. Brian D. Athey (Michigan), Dr. Weida Tong (FDA, United States Department of Health and Human Services), Dr. Cathy H. Wu (Georgetown), Dr. Dong Xu (Missouri), Drs. Arif Ghafoor and Okan K Ersoy (Purdue), Dr. Mark Borodovsky (Georgia Tech, President of ISIBM), Dr. Hamid R. Arabnia (UGA, Vice-President of ISIBM), and other scientific leaders. The committee presented the 2009 ISIBM Outstanding Achievement Awards to Dr. Joydeep Ghosh (UT Austin), Dr. Aidong Zhang (Buffalo) and Dr. Zhi-Hua Zhou (Nanjing) for their significant contributions to the field of intelligent biological medicine.

2K09 and thereafter : the coming era of integrative bioinformatics, systems biology and intelligent computing for functional genomics and personalized medicine research

PubMed Central

2010-01-01

Significant interest exists in establishing synergistic research in bioinformatics, systems biology and intelligent computing. Supported by the United States National Science Foundation (NSF), International Society of Intelligent Biological Medicine (http://www.ISIBM.org), International Journal of Computational Biology and Drug Design (IJCBDD) and International Journal of Functional Informatics and Personalized Medicine, the ISIBM International Joint Conferences on Bioinformatics, Systems Biology and Intelligent Computing (ISIBM IJCBS 2009) attracted more than 300 papers and 400 researchers and medical doctors world-wide. It was the only inter/multidisciplinary conference aimed to promote synergistic research and education in bioinformatics, systems biology and intelligent computing. The conference committee was very grateful for the valuable advice and suggestions from honorary chairs, steering committee members and scientific leaders including Dr. Michael S. Waterman (USC, Member of United States National Academy of Sciences), Dr. Chih-Ming Ho (UCLA, Member of United States National Academy of Engineering and Academician of Academia Sinica), Dr. Wing H. Wong (Stanford, Member of United States National Academy of Sciences), Dr. Ruzena Bajcsy (UC Berkeley, Member of United States National Academy of Engineering and Member of United States Institute of Medicine of the National Academies), Dr. Mary Qu Yang (United States National Institutes of Health and Oak Ridge, DOE), Dr. Andrzej Niemierko (Harvard), Dr. A. Keith Dunker (Indiana), Dr. Brian D. Athey (Michigan), Dr. Weida Tong (FDA, United States Department of Health and Human Services), Dr. Cathy H. Wu (Georgetown), Dr. Dong Xu (Missouri), Drs. Arif Ghafoor and Okan K Ersoy (Purdue), Dr. Mark Borodovsky (Georgia Tech, President of ISIBM), Dr. Hamid R. Arabnia (UGA, Vice-President of ISIBM), and other scientific leaders. The committee presented the 2009 ISIBM Outstanding Achievement Awards to Dr. Joydeep Ghosh (UT Austin), Dr. Aidong Zhang (Buffalo) and Dr. Zhi-Hua Zhou (Nanjing) for their significant contributions to the field of intelligent biological medicine. PMID:21143775

Non-Mydriatic Fundus Retinography in Screening for Diabetic Retinopathy: Agreement Between Family Physicians, General Ophthalmologists, and a Retinal Specialist.

PubMed

Cunha, Leonardo Provetti; Figueiredo, Evelyn Alvernaz; Araújo, Henrique Pereira; Costa-Cunha, Luciana Virgínia Ferreira; Costa, Carolina Ferreira; Neto, José de Melo Costa; Matos, Aline Mota Freitas; de Oliveira, Marise Machado; Bastos, Marcus Gomes; Monteiro, Mário Luiz Ribeiro

2018-01-01

To determine the level of agreement between trained family physicians (FPs), general ophthalmologists (GOs), and a retinal specialist (RS) in the assessment of non-mydriatic fundus retinography in screening for diabetic retinopathy (DR) in the primary health-care setting. 200 Diabetic patients were submitted to two-field non-mydriatic digital fundus camera. The images were examined by four trained FPs, two GOs, and one RS with regard to the diagnosis and severity of DR and the diagnosis of macular edema. The RS served as gold standard. Reliability and accuracy were determined with the kappa test and diagnostic measures. A total of 397 eyes of 200 patients were included. The mean age was 55.1 (±11.7) years, and 182 (91%) had type 2 diabetes. The mean levels of serum glucose and glycosylated hemoglobin A1c were 195.6 (±87.3) mg/dL and 8.9% (±2.1), respectively. DR was diagnosed in 166 eyes by the RS and in 114 and 182 eyes by GO 1 and GO 2 , respectively. For severity, DR was graded as proliferative in 8 eyes by the RS vs. 15 and 9 eyes by GO 1 and GO 2 , respectively. The agreement between the RS and the GOs was substantial for both DR diagnosis (GO 1 k  = 0.65; GO 2 k  = 0.74) and severity (GO 1 k  = 0.60; GO 2 k  = 0.71), and fair or moderate for macular edema (GO 1 k  = 0.27; GO 2 k  = 0.43). FP 1 , FP 2 , FP 3 , and FP 4 diagnosed DR in 108, 119, 163, and 117 eyes, respectively. The agreement between the RS and the FPs with regard to DR diagnosis was substantial (FP 2 k  = 0.69; FP 3 k  = 0.73; FP 4 k  = 0.71) or moderate (FP 1 k  = 0.56). As for DR severity, the agreement between the FPs and the RS was substantial (FP 2 k  = 0.66; FP 3 k  = 069; FP 4 k  = 0.64) or moderate (FP 1 k  = 0.51). Agreement between the FPs and the RS with regard to macular edema was fair (FP 1 k  = 0.33; FP 2 k  = 0.39; FP 3 k  = 0.37) or moderate (FP 4 k  = 0.51). Non-mydriatic fundus retinography was shown to be useful in DR screening in the primary health-care setting. FPs made assessments with good levels of agreement with an RS. Non-mydriatic fundus retinography associated with appropriate general physicians training is essential for the DR screening.

Aberrant expression and function of death receptor-3 and death decoy receptor-3 in human cancer.

PubMed

Ge, Zhicheng; Sanders, Andrew J; Ye, Lin; Jiang, Wen G

2011-03-01

Death receptor-3 (DR3) and death decoy receptor-3 (DcR3) are both members of the tumour necrosis factor receptor (TNFR) superfamily. The TNFR superfamily contains eight death domain-containing receptors, including TNFR1 (also called DR1), Fas (also called DR2), DR3, DR4, DR5, DR6, NGFR and EDAR. Upon the binding of these receptors with their corresponding ligands, the death domain recruits various proteins that mediate both the death and proliferation of cells. Receptor function is negatively regulated by decoy receptors (DcR1, DcR2, DcR3 and OPG). DR3/DcR3 are a pair of positive and negative players with which vascular endothelial growth inhibitor (VEGI) interacts. VEGI has been suggested to be a potential tumour suppressor. The inhibitory effects of VEGI on cancer are manifested in three main areas: a direct effect on cancer cells, an anti-angiogenic effect on endothelial cells, and the stimulation of dendritic cell maturation. A recent study indicated that DR3 may be a new receptor for E-selectin, which has been reported to be associated with cancer metastasis. DcR3 is a soluble receptor, highly expressed in various tumours, which lacks an apparent transmembrane segment, prevents cytokine response through ligand binding and neutralization, and is an inhibitor of apoptosis. DcR3 serves as a decoy receptor for FasL, LIGHT and VEGI. The cytokine LIGHT activates various anti-tumour functions and is expected to be a promising candidate for cancer therapy. Certain tumours may escape FasL-dependent immune-cytotoxic attack by expressing DcR3, which blocks FasL function. DR3/DcR3 play profound roles in regulating cell death and proliferation in cancer. The present review briefly discusses DR3/DcR3 and attempts to elucidate the role of these negative and positive players in cancer.

Field Testing and Modeling of Supermarket Refrigeration Systems as a Demand Response Resource

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deru, Michael; Hirsch, Adam; Clark, Jordan

Supermarkets offer a substantial demand response (DR) resource because of their high energy intensity and use patterns; however, refrigeration as the largest load has been challenging to access. Previous work has analyzed supermarket DR using heating, ventilating, and air conditioning; lighting; and anti-sweat heaters. This project evaluated and quantified the DR potential inherent in supermarket refrigeration systems in the Bonneville Power Administration service territory. DR events were carried out and results measured in an operational 45,590-ft2 supermarket located in Hillsboro, Oregon. Key results from the project include the rate of temperature increase in freezer reach-in cases and walk-ins when refrigerationmore » is suspended, the load shed amount for DR tests, and the development of calibrated models to quantify available DR resources. Simulations showed that demand savings of 15 to 20 kilowatts (kW) are available for 1.5 hours for a typical store without precooling and for about 2.5 hours with precooling using only the low-temperature, non-ice cream cases. This represents an aggregated potential of 20 megawatts within BPA's service territory. Inability to shed loads for medium-temperature (MT) products because of the tighter temperature requirements is a significant barrier to realizing larger DR for supermarkets. Store owners are reluctant to allow MT case set point changes, and laboratory tests of MT case DR strategies are needed so that owners become comfortable testing, and implementing, MT case DR. The next-largest barrier is the lack of proper controls in most supermarket displays over ancillary equipment, such as anti-sweat heaters, lights, and fans.« less

The thioredoxin TRX-1 regulates adult lifespan extension induced by dietary restriction in Caenorhabditis elegans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fierro-Gonzalez, Juan Carlos; Gonzalez-Barrios, Maria; Miranda-Vizuete, Antonio, E-mail: amirviz@upo.es

Highlights: {yields} First in vivo data for thioredoxin in dietary-restriction-(DR)-induced longevity. {yields} Thioredoxin (trx-1) loss suppresses longevity of eat-2 mutant, a genetic DR model. {yields} trx-1 overexpression extends wild-type longevity, but not that of eat-2 mutant. {yields} Longevity by dietary deprivation (DD), a non-genetic DR model, requires trx-1. {yields} trx-1 expression in ASJ neurons of aging adults is increased in response to DD. -- Abstract: Dietary restriction (DR) is the only environmental intervention known to extend adult lifespan in a wide variety of animal models. However, the genetic and cellular events that mediate the anti-aging programs induced by DR remainmore » elusive. Here, we used the nematode Caenorhabditis elegans to provide the first in vivo evidence that a thioredoxin (TRX-1) regulates adult lifespan extension induced by DR. We found that deletion of the gene trx-1 completely suppressed the lifespan extension caused by mutation of eat-2, a genetic surrogate of DR in the worm. However, trx-1 deletion only partially suppressed the long lifespan caused by mutation of the insulin-like receptor gene daf-2 or by mutation of the sensory cilia gene osm-5. A trx-1::GFP translational fusion expressed from its own promoter in ASJ neurons (Ptrx-1::trx-1::GFP) rescued the trx-1 deletion-mediated suppression of the lifespan extension caused by mutation of eat-2. This rescue was not observed when trx-1::GFP was expressed from the ges-1 promoter in the intestine. In addition, overexpression of Ptrx-1::trx-1::GFP extended lifespan in wild type, but not in eat-2 mutants. trx-1 deletion almost completely suppressed the lifespan extension induced by dietary deprivation (DD), a non-genetic, nutrient-based model of DR in the worm. Moreover, DD upregulated the expression of a trx-1 promoter-driven GFP reporter gene (Ptrx-1::GFP) in ASJ neurons of aging adults, but not that of control Pgpa-9::GFP (which is also expressed in ASJ neurons). We propose that DR activates TRX-1 in ASJ neurons during aging, which in turn triggers TRX-1-dependent mechanisms to extend adult lifespan in the worm.« less

Halo mass dependence of H I and O VI absorption: evidence for differential kinematics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mathes, Nigel L.; Churchill, Christopher W.; Nielsen, Nikole M.

2014-09-10

We studied a sample of 14 galaxies (0.1 < z < 0.7) using HST/WFPC2 imaging and high-resolution HST/COS or HST/STIS quasar spectroscopy of Lyα, Lyβ, and O VI λλ1031, 1037 absorption. The galaxies, having 10.8 ≤ log (M {sub h}/M {sub ☉}) ≤ 12.2, lie within D = 300 kpc of quasar sightlines, probing out to D/R {sub vir} = 3. When the full range of M {sub h} and D/R {sub vir} of the sample are examined, ∼40% of the H I absorbing clouds can be inferred to be escaping their host halo. The fraction of bound clouds decreasesmore » as D/R {sub vir} increases such that the escaping fraction is ∼15% for D/R {sub vir} < 1, ∼45% for 1 ≤ D/R {sub vir} < 2, and ∼90% for 2 ≤ D/R {sub vir} < 3. Adopting the median mass log M {sub h}/M {sub ☉} = 11.5 to divide the sample into 'higher' and 'lower' mass galaxies, we find a mass dependency for the hot circumgalactic medium kinematics. To our survey limits, O VI absorption is found in only ∼40% of the H I clouds in and around lower mass halos as compared to ∼85% around higher mass halos. For D/R {sub vir} < 1, lower mass halos have an escape fraction of ∼65%, whereas higher mass halos have an escape fraction of ∼5%. For 1 ≤ D/R {sub vir} < 2, the escape fractions are ∼55% and ∼35% for lower mass and higher mass halos, respectively. For 2 ≤ D/R {sub vir} < 3, the escape fraction for lower mass halos is ∼90%. We show that it is highly likely that the absorbing clouds reside within 4R {sub vir} of their host galaxies and that the kinematics are dominated by outflows. Our finding of 'differential kinematics' is consistent with the scenario of 'differential wind recycling' proposed by Oppenheimer et al. We discuss the implications for galaxy evolution, the stellar to halo mass function, and the mass-metallicity relationship of galaxies.« less

Knowledge of diabetes and diabetic retinopathy among rural populations in India, and the influence of knowledge of diabetic retinopathy on attitude and practice.

PubMed

Rani, Padmaja K; Raman, Rajiv; Subramani, Sarvanan; Perumal, Gnanamoorthy; Kumaramanickavel, Govindasamy; Sharma, Tarun

2008-01-01

Diabetes mellitus, particularly type II, is a major public health concern worldwide. While the occurrence of diabetic retinopathy cannot be prevented, with the provision of knowledge to sufferers, sight-threatening complications can be minimized. To report the results of a KAP (Knowledge, Attitude and Practice) study among a rural population in two areas: diabetes mellitus (DM) and diabetic retinopathy (DR). The level of knowledge was evaluated for both DM and DR; however, the influence of knowledge on practices and attitude was evaluated in only the DR group. In rural areas, 145 awareness meetings on DM and DR were conducted attended 28 347 individuals. Using systematic random sampling, the data were collected from every 14th individual. In total, 1938 individuals from a rural population were numbered for gaining their responses to the KAP questionnaire. Univariate and multiple regression analyses were performed to identify independent risk factors related to the knowledge of the disease and influence of this knowledge on attitude and practice. Of 1938 individuals, 966 (49.9%) had knowledge of DM and 718 (37.1%) had knowledge of DR. Knowledge about DM was more in women (OR=1.93; 95% CI: 1.55-2.39), in subjects who followed the Christian faith (OR=1.48; 95% CI: 1.07-2.04) and in those who belonged to the upper socioeconomic strata (OR=2.60; 95% CI: 1.84-3.67). The knowledge of DR was significantly higher among subjects who spoke the Malayalam language (OR=3.80; 95% CI: 2.03-7.13), who followed the Christian faith (OR=1.73; 95% CI: 1.27-2.35), and in those who belonged to the upper socioeconomic strata (OR=1.85; 95% CI: 1.32-2.58). Compared with those who had no knowledge of DR (n = 1220), significant percentages of individuals with knowledge (n = 718) had the right attitude - to go for regular eye examinations - (65.9% vs 93.3%) (p<0.0001) ). Regarding practice patterns, only 36.5% of individuals with knowledge about DR believed that if they controlled their blood sugar, they could avoid a visit to an ophthalmologist, compared with 55.5% with no knowledge (p<0.0001). The results suggest that we need to propagate aggressive and comprehensive awareness models to educate rural populations on DM and DR.

A Nonparametric Multidimensional IRT Approach with Applications to Ability Estimation and Test Bias.

DTIC Science & Technology

1988-04-01

VA 22314 800 N. Quincy Street Attn: TC Arlington, VA 22217-5000 (12 Copies) Dr. Hans Crombag Dr. Stephen Dunbar University of Leyden Lindquist...CenterEducation Research Center for Measurement Boerhaavelaan 2 University of Iowa 2334 EN Leyden Iowa City, IA 52242 The NETHERLANDS Dr. James A. Earles Mr...William Montague Naval Air Station NPRDC Code 13 Pensacola, FL 32508 San Diego, CA 92152-6800 Dr. Gary Marco Ms. Kathleen Moreno Stop 31-E Navy Personnel R

Ultrastructure Processing and Characterization of Polymers

DTIC Science & Technology

1988-01-01

Eur. Polym. J . 24, 123-127 (1988) (with R. Vukovic , G. Bogdanic, V. Kuresevic, and W.J. MacKnight) "Miscibility and Phase Behavior in Poly (2,6...Month, Day) |I5 fAGE U d FINAL FROM TO j -"_ 16. SUPPLEMENTARY NOTATION 17. COSATI CODES 18. SUBJECT TERMS (Continue on reverse if necessary and...Lee Dr. J . Obrzut Dr. D. Rice Dr. J . Schlenoff Dr. J . Shim V. JUNIOR RESEARCH PERSONNEL: M. Bishop R. Gregorius M. Lux J . Machado M. Masse R

The Response of Frozen Soils to Vibratory Loads

DTIC Science & Technology

1975-06-01

Construction. i | The report was technically reviewed by Dr. Y . Nakano of USA CRREL, and A.F. Müller of the Office of Chief of Engineers. Their suggestions...B.I.S. Helme, Jr., t M.J. Dabney III, F. Berrego, R.N. Lachenmaier and D.J. Coombes. Dr. T.M. Lee, Dr. D.M. Norris, Jr. and Dr. Y . Nakano gave... y /g stress static confining pressure, (a, + 2a ^/3 axial (vertical) static pressure lateral static pressure dynamic stress (peak) phase shift

The SME (Structure-Mapping Engine) User’s Manual (SME Version 2E)

DTIC Science & Technology

1988-12-30

It is prior to this step that one might want to think about wether to modify any system parameters (e.g., print the match hypotheses, print only the...Wshington, DC 20390 Department of Psychology Carnegie-Mellon University Dr. Judith Orsanu Schenley Park Dr. Harold P. O’Neil, Jr. Basic Research Office...Pinker Baltimore, MD 21201 Department of Psychology ElO-018 Dr. Judith W. Segal MIT Dr. J. Wesley Regian OERI Cambridge, MA 02139 AFHRL/IDI 556 New

Dynamic Stall Data for 2-D and 3-D Test Cases

DTIC Science & Technology

2000-10-01

CASES Professor R A McD Galbraith Dr F N Coton Dr R B Green Dr M Vezza University of Glasgow INTRODUCTION Background Although substantial work has...aerofoil shape, aspect ratio, surface finish , data reduction software and Mach number, all but the Mach number had no effect on the observed trends

Modeling Incorrect Responses to Multiple-Choice Items with Multilinear Formula Score Theory.

DTIC Science & Technology

1987-08-01

Eisenhower Avenue University of Leyden Alexandria, VA 22333 Education Research Center Boerhaavelaan 2 Dr. John M. Eddins 2334 EN Leyden University of...22302-0268 Dr. William Montague NPRDC Code 13 Dr. William L. Maloy San Diego, CA 92152-6800 Chief of Naval Education and Training Ms. Kathleen Moreno

Microscopic Theoretical Modeling of the Chemical and Tribological Properties of Ceramic Surfaces and Interfaces

DTIC Science & Technology

1991-09-01

small R ( Pauli orthogonalization) for all nonbonded 15 electrons. Referred to as van der Waals interactions, these interactions are generally as- sumed...on AFOSR Project 1. Professor William A. Goddard III 2. Postdoctoral Fellows: Dr. Siddharth Dasgupta Dr. Chih-mai Kao (departed June 1988) Dr. Jung

Megavolt, Multi-Kiloamp Ka-Band Gyrotron Oscillator Experiment

DTIC Science & Technology

1989-03-15

pulseline accelerator with 20 K2 output impedance and 55 nsec voltage pulse was used to generate a multi-kiloamp annular electron beam by explosive plasma...Lawrence Livermore National Laboratory P.O. Box 808 Livermore, California 94550 Attn: Dr. D. Prosnitz 1 copy Dr. T.J. Orzechowski 1 copy Dr. J. Chase 1

Neuroprotective Effect of Hydroxytyrosol in Experimental Diabetic Retinopathy: Relationship with Cardiovascular Biomarkers.

PubMed

González-Correa, José Antonio; Rodríguez-Pérez, María Dolores; Márquez-Estrada, Lucía; López-Villodres, Juan Antonio; Reyes, José Julio; Rodriguez-Gutierrez, Guillermo; Fernández-Bolaños, Juan; De La Cruz, José Pedro

2018-01-24

The aim of the study was to test the neuroprotective effect of hydroxytyrosol (HT) on experimental diabetic retinopathy. Animals were divided in four groups: (1) control nondiabetic rats, (2) streptozotocin-diabetic rats (DR), (3) DR treated with 1 mg/kg/day p.o. HT, and (4) DR treated with 5 mg/kg/day p.o. HT. Treatment with HT was started 7 days before inducing diabetes and was maintained for 2 months. In the DR group, total area occupied by extracellular matrix was increased, area occupied by retinal cells was decreased; both returned to near-control values in DR rats treated with HT. The number of retinal ganglion cells in DR was significantly lower (44%) than in the control group, and this decrease was smaller after HT treatment (34% and 9.1%). Linear regression analysis showed that prostacyclin, platelet aggregation, peroxynitrites, and the dose of 5 mg/kg/day HT significantly influenced retinal ganglion cell count. In conclusion, HT exerted a neuroprotective effect on diabetic retinopathy, and this effect correlated significantly with changes in some cardiovascular biomarkers.

Knowledge, Skills, Abilities, and Other Characteristics for Remotely Piloted Aircraft Pilots and Operators

DTIC Science & Technology

2011-10-19

Editor Dr. Gregory Manley HQ AFPC/DSYX, Dr. Lisa Mills AF/A1PF, Dr. Paul DiTullio HQ Af/A1PFA, Kenneth Schwartz HQ AFPC/DSYX, Johnny Weissmuller HQ...B ru s k ie w ic z e t a l. , 2 0 0 7 : A V O , M P O C h a p p e ll e e t a l. , 2 0 1 0 : M P O C h a p p e ll e e t a l. , 2 0 1 1

Allele-specific HLA-DR typing by mass spectrometry: an alternative to hybridization-based typing methods.

PubMed

Worrall, T A; Schmeckpeper, B J; Corvera, J S; Cotter, R J

2000-11-01

The primer oligomer base extension (PROBE) reaction, combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, is used to characterize HLA-DR2 polymorphism. Alleles are distinguished rapidly and accurately by measuring the mass of primer extension products at every known variable region of HLA-DR2 alleles. Since differentiation of alleles by PROBE relies on measuring differences in extension product mass rather than differences in hybridization properties, mistyped alleles resulting from nonspecific hybridization are absent. The method shows considerable potential for high-throughput screening of HLA-DR polymorphism in a chip-based format, including rapid tissue typing of unrelated volunteer donors.

Automated Quantification of Nonperfusion Areas in 3 Vascular Plexuses With Optical Coherence Tomography Angiography in Eyes of Patients With Diabetes.

PubMed

Hwang, Thomas S; Hagag, Ahmed M; Wang, Jie; Zhang, Miao; Smith, Andrew; Wilson, David J; Huang, David; Jia, Yali

2018-06-14

Diabetic retinopathy (DR) is a leading cause of vision loss that is managed primarily through qualitative clinical examination of the retina. Optical coherence tomography angiography (OCTA) may offer an objective and quantitative method of evaluating DR. To quantify capillary nonperfusion in 3 vascular plexuses in the macula of eyes patients with diabetes of various retinopathy severity using projection-resolved OCTA (PR-OCTA). Cross-sectional study at a tertiary academic center comprising 1 eye each from healthy control individuals and patients with diabetes at different severity stages of retinopathy. Data were acquired and analyzed between January 2015 and December 2017. Foveal avascular zone area, extrafoveal avascular area (EAA), and the sensitivity of detecting levels of retinopathy. The study included 39 control individuals (20 women [51%]; mean [SD] age, 43.41 [19.37] years); 16 patients with diabetes without retinopathy (8 women [50%]; mean [SD] age, 56.50 [12.43] years); 23 patients with mild to moderate nonproliferative DR (18 women [78%] ; mean [SD] age, 62.48 [10.55] years); and 32 patients with severe nonproliferative DR or proliferative DR (12 women [38%]; mean age, 53.41 [14.05] years). Mean (SD) foveal avascular zone area was 0.203 (0.103) mm2 for control individuals, 0.192 (0.084) mm2 for patients with diabetes without retinopathy, 0.243 [0.079] mm2 for mild to moderate nonproliferative DR, and 0.359 (0.275) mm2 for severe nonproliferative DR or proliferative DR. Mean (SD) EAA in whole inner retinal slab in these groups, respectively, were 0.020 (0.031) mm2, 0.034 (0.047) mm2, 0.038 (0.040) mm2, and 0.237 (0.235) mm2. The mean (SD) sum of EAA from 3 segmented plexuses in each of the respective groups were 0.103 (0.169) mm2, 0.213 (0.242) mm2, 0.451 (0.243) mm2, and 1.325 (1.140) mm2. With specificity fixed at 95%, using EAA in inner retinal slab, the sensitivity of detecting patients with diabetes from healthy control individuals was 28% (95% CI, 18%-40%), 31% for patients with DR (95% CI, 19%-45%), and 47% for patients with severe DR (95% CI, 29%-65%) from whole inner retinal EAA. With the sum of EAA from 3 individual plexuses, the sensitivities were 69% (95% CI, 57%-80%), 82% (95% CI, 70%-91%), and 97% (95% CI, 85%-100%), respectively. Avascular areas were not associated with signal strength index. The commercial vessel density from the 2-plexus scheme distinguished the groups with lower sensitivity and were dependent on SSI. Automatically quantified avascular areas from a 3-layer segmentation scheme using PR-OCTA distinguished levels of retinopathy with a greater sensitivity than avascular areas from unsegmented inner retinal slab or measurements from a commercially available vessel density in 2-layer scheme. Additional studies are needed to investigate the applicability of nonperfusion parameters in clinical settings.

Improving causal inference with a doubly robust estimator that combines propensity score stratification and weighting.

PubMed

Linden, Ariel

2017-08-01

When a randomized controlled trial is not feasible, health researchers typically use observational data and rely on statistical methods to adjust for confounding when estimating treatment effects. These methods generally fall into 3 categories: (1) estimators based on a model for the outcome using conventional regression adjustment; (2) weighted estimators based on the propensity score (ie, a model for the treatment assignment); and (3) "doubly robust" (DR) estimators that model both the outcome and propensity score within the same framework. In this paper, we introduce a new DR estimator that utilizes marginal mean weighting through stratification (MMWS) as the basis for weighted adjustment. This estimator may prove more accurate than treatment effect estimators because MMWS has been shown to be more accurate than other models when the propensity score is misspecified. We therefore compare the performance of this new estimator to other commonly used treatment effects estimators. Monte Carlo simulation is used to compare the DR-MMWS estimator to regression adjustment, 2 weighted estimators based on the propensity score and 2 other DR methods. To assess performance under varied conditions, we vary the level of misspecification of the propensity score model as well as misspecify the outcome model. Overall, DR estimators generally outperform methods that model one or the other components (eg, propensity score or outcome). The DR-MMWS estimator outperforms all other estimators when both the propensity score and outcome models are misspecified and performs equally as well as other DR estimators when only the propensity score is misspecified. Health researchers should consider using DR-MMWS as the principal evaluation strategy in observational studies, as this estimator appears to outperform other estimators in its class. © 2017 John Wiley & Sons, Ltd.

Global Estimates on the Number of People Blind or Visually Impaired by Diabetic Retinopathy: A Meta-analysis From 1990 to 2010.

PubMed

Leasher, Janet L; Bourne, Rupert R A; Flaxman, Seth R; Jonas, Jost B; Keeffe, Jill; Naidoo, Kovin; Pesudovs, Konrad; Price, Holly; White, Richard A; Wong, Tien Y; Resnikoff, Serge; Taylor, Hugh R

2016-09-01

To estimate global and regional trends from 1990 to 2010 of the prevalence and number of persons visually impaired specifically by diabetic retinopathy (DR), as a complication of the precipitous trends in global diabetes, is fundamental for health planning purposes. The meta-analysis of published population studies from 1990 to 2012 for the Global Burden of Disease Study 2010 (GBD) yielded estimated global regional trends in DR among other causes of moderate and severe vision impairment (MSVI; presenting visual acuity <6/18, ≥3/60) and blindness (presenting visual acuity <3/60). Globally in 2010, out of overall 32.4 million blind and 191 million visually impaired people, 0.8 million were blind and 3.7 million were visually impaired because of DR, with an alarming increase of 27% and 64%, respectively, spanning the two decades from 1990 to 2010. DR accounted for 2.6% of all blindness in 2010 and 1.9% of all MSVI worldwide, increasing from 2.1% and 1.3%, respectively, in 1990. These figures were lower in regions with younger populations (<2% in East and Southeast Asia and Oceania) than in high-income regions (North America, Western Europe, and Australasia) with relatively aging populations (>4%). The number of persons with visual impairment due to DR worldwide is rising and represents an increasing proportion of all blindness/MSVI causes. Age-standardized prevalence of DR-related blindness/MSVI was higher in sub-Saharan Africa and South Asia. One out of 39 blind people had blindness due to DR, and 1 out of 52 visually impaired people had visual impairment due to DR. © 2016 by the American Diabetes Association.

BCL-2 system analysis identifies high-risk colorectal cancer patients.

PubMed

Lindner, Andreas U; Salvucci, Manuela; Morgan, Clare; Monsefi, Naser; Resler, Alexa J; Cremona, Mattia; Curry, Sarah; Toomey, Sinead; O'Byrne, Robert; Bacon, Orna; Stühler, Michael; Flanagan, Lorna; Wilson, Richard; Johnston, Patrick G; Salto-Tellez, Manuel; Camilleri-Broët, Sophie; McNamara, Deborah A; Kay, Elaine W; Hennessy, Bryan T; Laurent-Puig, Pierre; Van Schaeybroeck, Sandra; Prehn, Jochen H M

2017-12-01

The mitochondrial apoptosis pathway is controlled by an interaction of multiple BCL-2 family proteins, and plays a key role in tumour progression and therapy responses. We assessed the prognostic potential of an experimentally validated, mathematical model of BCL-2 protein interactions (DR_MOMP) in patients with stage III colorectal cancer (CRC). Absolute protein levels of BCL-2 family proteins were determined in primary CRC tumours collected from n=128 resected and chemotherapy-treated patients with stage III CRC. We applied DR_MOMP to categorise patients as high or low risk based on model outputs, and compared model outputs with known prognostic factors (T-stage, N-stage, lymphovascular invasion). DR_MOMP signatures were validated on protein of n=156 patients with CRC from the Cancer Genome Atlas (TCGA) project. High-risk stage III patients identified by DR_MOMP had an approximately fivefold increased risk of death compared with patients identified as low risk (HR 5.2, 95% CI 1.4 to 17.9, p=0.02). The DR_MOMP signature ranked highest among all molecular and pathological features analysed. The prognostic signature was validated in the TCGA colon adenocarcinoma (COAD) cohort (HR 4.2, 95% CI 1.1 to 15.6, p=0.04). DR_MOMP also further stratified patients identified by supervised gene expression risk scores into low-risk and high-risk categories. BCL-2-dependent signalling critically contributed to treatment responses in consensus molecular subtypes 1 and 3, linking for the first time specific molecular subtypes to apoptosis signalling. DR_MOMP delivers a system-based biomarker with significant potential as a prognostic tool for stage III CRC that significantly improves established histopathological risk factors. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Ratiometric analysis of optical coherence tomography-measured in vivo retinal layer thicknesses for the detection of early diabetic retinopathy.

PubMed

Bhaduri, Basanta; Shelton, Ryan L; Nolan, Ryan M; Hendren, Lucas; Almasov, Alexandra; Labriola, Leanne T; Boppart, Stephen A

2017-11-01

Influence of diabetes mellitus (DM) and diabetic retinopathy (DR) on parafoveal retinal thicknesses and their ratios was evaluated. Six retinal layer boundaries were segmented from spectral-domain optical coherence tomography images using open-source software. Five study groups: (1) healthy control (HC) subjects, and subjects with (2) controlled DM, (3) uncontrolled DM, (4) controlled DR and (5) uncontrolled DR, were identified. The one-way analyses of variance (ANOVA) between adjacent study groups (i. e. 1 with 2, 2 with 3, etc) indicated differences in retinal thicknesses and ratios. Overall retinal thickness, ganglion cell layer (GCL) thickness, inner plexiform layer (IPL) thickness, and their combination (GCL+ IPL), appeared to be significantly less in the uncontrolled DM group when compared to controlled DM and controlled DR groups. Although the combination of nerve fiber layer (NFL) and GCL, and IPL thicknesses were not different, their ratio, (NFL+GCL)/IPL, was found to be significantly higher in the controlled DM group compared to the HC group. Comparisons of the controlled DR group with the controlled DM group, and with the uncontrolled DR group, do not show any differences in the layer thicknesses, though several significant ratios were obtained. Ratiometric analysis may provide more sensitive parameters for detecting changes in DR. Picture: A representative segmented OCT image of the human retina is shown. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

HLA-DP, HLA-DQ, and HLA-DR-restricted epitopes in GRA5 of toxoplasma gondii strains

NASA Astrophysics Data System (ADS)

Haryati, S.; Sari, Y.; Prasetyo, A. A.; Sariyatun, R.

2016-01-01

The dense granular (GRA) proteins of Toxoplasma gondii(T. gondii) have been demonstrated as potential sources of T. gondii vaccine antigens. However, data of the GRA5 protein are limited. This study analyzed twenty-one complete GRA5 sequences of T. gondii GT1, RH, ME49, VEG, MAS, RUB, FOU, p89, VAND, and GAB2-2007-GAL-DOM2 strains to identify potential epitopes restricted by Major Histocompatibility Complex class II (MHC- II) molecules (human leukocyte antigen (HLA)-DP, HLA-DQ, and HLA-DR) in the protein. In all T. gondii strains, peptides positioned at amino acid (aa) 15-29, 16-30, 17-31, 18-32, 19-33, 83-97, 84-98, 86-100, 87-101, 89-103, and 90-104 were predicted to pose high affinity and binding with HLA-DRB1*0101, HLA-DRB1*0301 (DR17), HLA-DRB1*0401 (DR4Dw4), HLA-DRB1*0701, HLA-DRB1*1101, HLA-DRB1*1501 (DR2b), and/or HLA-DRB5*0101. Considering the epitope's affinity, ligation strength, and hydrophilicity, LRLLRRRRRRAIQEE sequence (aa 90-104) restricted by HLA-DRB1*0101, HlA- DRB1*0301 (DR17), and HLA-DRB1*0401 (DR4Dw4) was considered as the most potential MHC-II epitope in GRA5 of T. gondii. These results would be useful for studies concerning in developing T. gondii vaccine and diagnostic method.

Association Of Serum Total Bilirubin Level With Diabetic Retinopathy In Type 2 Diabetes Mellitus.

PubMed

Ghaffar, Tahir; Marwat, Zahid Irfan; Ullah, Fahim; Khan, Salman; Hassan Aamir, Aziz Ul

2016-01-01

Serum bilirubin has anti-inflammatory, antioxidant and immunological properties. It is considered a protective substance against atherosclerotic and microvascular complications of diabetes mellitus (DM). This study was designed to find the association between total serum bilirubin concentration and diabetic retinopathy (DR). This case control study was conducted in the Department of Endocrinology, Diabetes and Metabolic Diseases, Hayatabad Medical Complex, Peshawar. Type-2 DM patients more than 18 years of age of either gender with duration of T2DM more than 6 months were included and sub categorized in two groups. Cases (DM with DR) and Controls (DM without DR) while patients with acute and chronic liver diseases, haemolytic anaemia, history of chronic alcohol consumption, use of hepatotoxic drugs (anti-tuberculous, anti-epileptic), women on oral contraceptive pills were excluded. All participants underwent ophthalmic examination at diabetic retinopathy screening clinic followed by pre designed set of investigations. A total of 152 patients, 76 cases and 76 controls were included. Serum bilirubin concentration was found inversely and independently (p 0.000) associated and inversely co related (r -0.345and p 0.000) with prevalence of DR. Cases were concentrated in the lower quartiles of serum bilirubin concentration and vice versa. Low haemoglobin (p 0.00) and longer duration of DM (0.003) were independently and directly associated with prevalence of DR. Serum bilirubin concentration is inversely and independently associated and inversely correlated with the prevalence of DR and may predict progression of DR over time.

Prevalence of diabetic retinopathy among self-reported adult diabetics in districts of Eastern Nepal in a community based study.

PubMed

Agarwal, Lalit T; Agarwal, Nisha

2017-07-01

Diabetic retinopathy (DR) is the leading cause of blindness among working age adults around the world. Each year more and more people live with this condition, which can result in life-changing complications. To determine the prevalence and risk factors of diabetic retinopathy (DR) in a large community based screening programme, in order to estimate the future burden of the disease. A cross sectional community based study was conducted between 1st January and 31st December 2014 in a purposive sample of adults with selfreported diabetes mellitus (DM) from Morang and Sunsari district of Nepal. A structured questionnaire was used to collect patient data. Ophthalmological evaluation was done and fundus was examined for grading DR using direct and indirect ophthalmoscope. Among the 698 diabetic patients, mean age was 55.02±11.8 years (ranging from 24 to 91 years). 12.3% of diabetic were not under any treatment. Only 69.3% of patients had visited eye specialist for diabetic retinopathy screening. Prevalence of DR was found to be 15.3%; 13.9% had non-proliferative DR and 1.4% had proliferative DR. Prevalence of diabetic macular edema was 2.1%. In Morang district prevalence of DR was 14.2% and in Sunsari district it was 16.2%. In the binary-logistic regression analysis, duration of diabetes was associated with significantly increased risk of DR (OR: 1.13; 95% confidence interval (CI), 1.09 to 1.17; p<0.001). History of absence of arterial hypertension decreased the risk of DR (OR: 0.56; 95% CI, 0.36 to 0.87; p=0.01). One sixth of the patients with diabetes in the Eastern region of Nepal have retinopathy. Diabetic retinopathy risk increased with duration of diabetes and decreased with history of no co-existing arterial hypertension. © NEPjOPH.

WE-G-204-08: Optimized Digital Radiographic Technique for Lost Surgical Devices/Needle Identification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gorman, A; Seabrook, G; Brakken, A

Purpose: Small surgical devices and needles are used in many surgical procedures. Conventionally, an x-ray film is taken to identify missing devices/needles if post procedure count is incorrect. There is no data to indicate smallest surgical devices/needles that can be identified with digital radiography (DR), and its optimized acquisition technique. Methods: In this study, the DR equipment used is a Canon RadPro mobile with CXDI-70c wireless DR plate, and the same DR plate on a fixed Siemens Multix unit. Small surgical devices and needles tested include Rubber Shod, Bulldog, Fogarty Hydrogrip, and needles with sizes 3-0 C-T1 through 8-0 BV175-6.more » They are imaged with PMMA block phantoms with thickness of 2–8 inch, and an abdomen phantom. Various DR techniques are used. Images are reviewed on the portable x-ray acquisition display, a clinical workstation, and a diagnostic workstation. Results: all small surgical devices and needles are visible in portable DR images with 2–8 inch of PMMA. However, when they are imaged with the abdomen phantom plus 2 inch of PMMA, needles smaller than 9.3 mm length can not be visualized at the optimized technique of 81 kV and 16 mAs. There is no significant difference in visualization with various techniques, or between mobile and fixed radiography unit. However, there is noticeable difference in visualizing the smallest needle on a diagnostic reading workstation compared to the acquisition display on a portable x-ray unit. Conclusion: DR images should be reviewed on a diagnostic reading workstation. Using optimized DR techniques, the smallest needle that can be identified on all phantom studies is 9.3 mm. Sample DR images of various small surgical devices/needles available on diagnostic workstation for comparison may improve their identification. Further in vivo study is needed to confirm the optimized digital radiography technique for identification of lost small surgical devices and needles.« less

Association of polymorphisms in the vascular endothelial growth factor gene and its serum levels with diabetic retinopathy in Chinese patients with type 2 diabetes: a cross-sectional study.

PubMed

Fan, Xiaohong; Wu, Qunhong; Li, Yuan; Hao, Yanhua; Ning, Ning; Kang, Zheng; Cui, Yu; Liu, Ruohong; Han, Liyuan

2014-01-01

Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis, and plays a key role in the pathogenesis of diabetic retinopathy (DR). This study was designed to identify the possible role of VEGF gene polymorphisms in the development of DR in type 2 diabetic patients in Chinese and clarify the relationship between VEGF serum levels and the risk of DR. This cross-sectional study included 1 040 Chinese subjects with type 2 diabetes mellitus. There were 372 patients diagnosed with DR in the case group and 668 patients without DR in the control group. DNA from each patient was analyzed for VEGF polymorphisms of -2578A/C (rs699947), -1154G/A (rs1570360), -460C/T (rs833061), +405C/G (rs2010963), and +936C/T (rs3025039) using MassARRAY compact analyzer. The VEGF serum levels were quantified by enzyme-linked immunosorbent assay (ELISA). No evidence of association was observed between -2578 A/C (rs699947), +405C/G (rs2010963), +936C/T (rs3025039), and DR risk under stringent Bonferroni's correction. However, VEGF serum levels were significantly higher in DR patients than those of control group. The genetic variation of VEGF polymorphisms influenced VEGF serum levels; subjects carrying the VEGF -2578 C/C (rs699947) genotype had greater VEGF serum levels than those carrying the C/A genotype and VEGF serum levels were significantly higher in CC genotype of the +405C/G (rs2010963) compared with those of the other genotypes. The data did not suggest significant association between the VEGF polymorphisms and DR risk under stringent Bonferroni's correction. However, our study indicated that DR patients have higher VEGF levels than diabetic patients without retinopathy, and -2578A/C (rs699947) and +405C/G (rs2010963) may be important factors in determining serum VEGF levels.

Improving Delivery Accuracy of Stereotactic Body Radiotherapy to a Moving Tumor Using Simplified Volumetric Modulated Arc Therapy

PubMed Central

Ko, Young Eun; Cho, Byungchul; Kim, Su Ssan; Song, Si Yeol; Choi, Eun Kyung; Ahn, Seung Do; Yi, Byongyong

2016-01-01

Purpose To develop a simplified volumetric modulated arc therapy (VMAT) technique for more accurate dose delivery in thoracic stereotactic body radiation therapy (SBRT). Methods and Materials For each of the 22 lung SBRT cases treated with respiratory-gated VMAT, a dose rate modulated arc therapy (DrMAT) plan was retrospectively generated. A dynamic conformal arc therapy plan with 33 adjoining coplanar arcs was designed and their beam weights were optimized by an inverse planning process. All sub-arc beams were converted into a series of control points with varying MLC segment and dose rates and merged into an arc beam for a DrMAT plan. The plan quality of original VMAT and DrMAT was compared in terms of target coverage, compactness of dose distribution, and dose sparing of organs at risk. To assess the delivery accuracy, the VMAT and DrMAT plans were delivered to a motion phantom programmed with the corresponding patients’ respiratory signal; results were compared using film dosimetry with gamma analysis. Results The plan quality of DrMAT was equivalent to that of VMAT in terms of target coverage, dose compactness, and dose sparing for the normal lung. In dose sparing for other critical organs, DrMAT was less effective than VMAT for the spinal cord, heart, and esophagus while being well within the limits specified by the Radiation Therapy Oncology Group. Delivery accuracy of DrMAT to a moving target was similar to that of VMAT using a gamma criterion of 2%/2mm but was significantly better using a 2%/1mm criterion, implying the superiority of DrMAT over VMAT in SBRT for thoracic/abdominal tumors with respiratory movement. Conclusion We developed a DrMAT technique for SBRT that produces plans of a quality similar to that achieved with VMAT but with better delivery accuracy. This technique is well-suited for small tumors with motion uncertainty. PMID:27333199

Moisture effects on greenhouse gases generation in nitrifying gas-phase compost biofilters.

PubMed

Maia, Guilherme D N; Day, George B; Gates, Richard S; Taraba, Joseph L; Coyne, Mark S

2012-06-01

Gas-phase compost biofilters are extensively used in concentrated animal feeding operations to remove odors and, in some cases, ammonia from air sources. The expected biochemical pathway for these predominantly aerobic systems is nitrification. However, non-uniform media with low oxygen levels can shift biofilter microbial pathways to denitrification, a source of greenhouse gases. Several factors contribute to the formation of anoxic/anaerobic zones: media aging, media and particle structure, air velocity distribution, compaction, biofilm thickness, and moisture content (MC) distribution. The present work studies the effects of media moisture conditions on ammonia (NH(3)) removal and greenhouse gas generation (nitrous oxide, N(2)O and methane, CH(4)) for gas-phase compost biofilters subject to a 100-day controlled drying process. Continuous recordings were made for the three gases and water vapor (2.21-h sampling cycle, each cycle consisted of three gas species, and water vapor, for a total of 10,050 data points). Media moisture conditions were classified into three corresponding media drying rate (DR) stages: Constant DR (wetter media), falling DR, and stable-dry system. The first-half of the constant DR period (0-750 h; MC=65-52%, w.b.) facilitated high NH(3) removal rates, but higher N(2)O generation and no CH(4) generation. At the drier stages of the constant DR (750-950 h; MC=52-48%, w.b.) NH(3) removal remained high but N(2)O net generation decreased to near zero. In the falling DR stage (1200-1480 h; MC=44-13%) N(2)O generation decreased, CH(4) increased, and NH(3) was no longer removed. No ammonia removal or greenhouse gas generation was observed in the stable-dry system (1500-2500 h; MC=13%). These results indicate that media should remain toward the drier region of the constant DR (in close proximity to the falling DR stage; MC=50%, approx.), to maintain high levels of NH(3) removal, reduced levels of N(2)O generation, and nullify levels of CH(4) generation. Copyright © 2012 Elsevier Ltd. All rights reserved.

VizieR Online Data Catalog: KiDS-ESO-DR2 multi-band source catalog (de Jong+, 2015)

NASA Astrophysics Data System (ADS)

de Jong, J. T. A.; Verdoes Kleijn, G. A.; Boxhoorn, D. R.; Buddelmeijer, H.; Capaccioli, M.; Getman, F.; Grado, A.; Helmich, E.; Huang, Z.; Irisarri, N.; Kuijken, K.; La Barbera, F.; McFarland, J. P.; Napolitano, N. R.; Radovich, M.; Sikkema, G.; Valentijn, E. A.; Begeman, K. G.; Brescia, M.; Cavuoti, S.; Choi, A.; Cordes, O.-M.; Covone, G.; Dall'Ora, M.; Hildebrandt, H.; Longo, G.; Nakajima, R.; Paolillo, M.; Puddu, E.; Rifatto, A.; Tortora, C.; van Uitert, E.; Buddendiek, A.; Harnois-Deraps, J.; Erben, T.; Eriksen, M. B.; Heymans, C.; Hoekstra, H.; Joachimi, B.; Kitching, T. D.; Klaes, D.; Koopmans, L. V. E.; Koehlinger, F.; Roy, N.; Sifon, C.; Schneider, P.; Sutherland, W. J.; Viola, M.; Vriend, W.-J.

2016-10-01

KiDS data releases consist of ~1 square degree tiles that have been successfully observed in all four survey filters (u,g,r,i). The second data release (KiDS-ESO-DR2) was available in February 2015 and contains imaging data, masks and single-band source lists for all tiles observed in all four filters for which observations were completed during the second year of regular operations (1 October 2012 to 31 September 2013), a total of 98 tiles. Apart from the data products mentioned above, KiDS-ESO-DR2 also provides a multi-band source catalogue based on the combined set of 148 tiles released in the first two data releases. A complete list of all tiles with data quality parameters can be found on the KiDS website: http://kids.strw.leidenuniv.nl/DR2/ (1 data file).

[Screening for depersonalization-derealization with two items of the cambridge depersonalization scale].

PubMed

Michal, Matthias; Zwerenz, Rüdiger; Tschan, Regine; Edinger, Jens; Lichy, Marcel; Knebel, A; Tuin, Inka; Beutel, Manfred

2010-05-01

Depersonalization (DP) and derealization (DR) are considered to be highly underdiagnosed. Therefore the development of screening instruments is important. From the Cambridge Depersonalization Scale (CDS) two items were extracted discriminating best patients with clinical significant DP from patients without DP. These two Items were assembled to a short version of the CDS. This short version (CDS-2) was tested in a sample of 38 patients with clinical significant DP-DR and 49 patients without or only mild DP-DR. Scores were compared against clinical diagnoses based on a structured interview (gold standard). The CDS-2 was able to differentiate patients with clinical significant DP well from other groups (cut-off of CDS-2>or=3, sensitivity=78.9%, specifity=85.7%) and also showed high reliability (Cronbachs alpha=0.92). Therefore the CDS-2 can be considered as a useful tool for screening and identification of DP-DR.

pH-sensitive fluorescent sensors based on europium(III) complexes.

PubMed

Zhang, Xiaolin; Jiao, Yang; Jing, Xu; Wu, Hongmei; He, Guangjie; Duan, Chunying

2011-03-21

New europium(III) complexes Eu(TTA)(2)-DSQ and Eu(TTA)(3)-DR1 were designed and synthesized as new fluorescent pH probes (where HDSQ = 5-(dimethylamino)-N-(4-(2-((8-hydroxyquinolin-2-yl)methylene)hydrazinecarbonyl)phenyl)naphthalene-1-sulfonamide, DR1 = N(1)-(4-(dimethylamino)benzylidene)-N(2)-(rhodamine-6G) lactamethylene-diamine and TTA = thiophentrifluoroacetone). Eu(TTA)(2)-DSQ exhibited high sensitivity in monitoring pH changes in neutral aqueous solution with negligible background fluorescence. Eu(TTA)(3)-DR1 comprised a green light emitting Rhodamine 6G fluorophore and a Eu(III) moiety as the origin of red light. These pH-sensitive emitter components have pK(a) values of 5.0 and 7.2 respectively, and exhibit isolated protonated steps within one molecule. Luminescence titrations demonstrate that Eu(TTA)(3)-DR1 was able to detect pH values at both near neutral pH and acidic pH ranges, and was also able to detect pH in both cultured cells and in vivo.

Anthropogenic radionuclide fluxes and distribution in bottom sediments of the cooling basin of the Ignalina Nuclear Power Plant.

PubMed

Marčiulionienė, D; Mažeika, J; Lukšienė, B; Jefanova, O; Mikalauskienė, R; Paškauskas, R

2015-07-01

Based on γ-ray emitting artificial radionuclide spectrometric measurements, an assessment of areal and vertical distribution of (137)Cs, (60)Co and (54)Mn activity concentrations in bottom sediments of Lake Drūkšiai was performed. Samples of bottom sediments from seven monitoring stations within the cooling basin were collected in 1988-1996 and 2007-2010 (in July-August). For radionuclide areal distribution analysis, samples from the surface 0-5 cm layer were used. Multi sample cores sliced 2 cm, 3 cm or 5 cm thick were used to study the vertical distribution of radionuclides. The lowest (137)Cs activity concentrations were obtained for two stations that were situated close to channels with radionuclide discharges, but with sediments that had a significantly smaller fraction of organic matter related to finest particles and consequently smaller radionuclide retention potential. The (137)Cs activity concentration was distributed quite evenly in the bottom sediments from other investigated monitoring stations. The highest (137)Cs activity concentrations in the bottom sediments of Lake Drūkšiai were measured in the period of 1988-1989; in 1990, the (137)Cs activity concentrations slightly decreased and they varied insignificantly over the investigation period. The obtained (238)Pu/(239,240)Pu activity ratio values in the bottom sediments of Lake Drūkšiai represented radioactive pollution with plutonium from nuclear weapon tests. Higher (60)Co and (54)Mn activity concentrations were observed in the monitoring stations that were close to the impact zones of the technical water outlet channel and industrial rain drainage system channel. (60)Co and (54)Mn activity concentrations in the bottom sediments of Lake Drūkšiai significantly decreased when operations at both INPP reactor units were stopped. The vertical distribution of radionuclides in bottom sediments revealed complicated sedimentation features, which may have been affected by a number of natural and anthropogenic factors resulting in mixing, resuspension and remobilization of sediments and radionuclides. The associated with particles (137)Cs flux was 129 Bq/(m(2) year). The (137)Cs transfer rate from water into bottom sediments was 14.3 year(-1) (or, the removal time was 25 days). The Kd value for (137)Cs in situ estimated from trap material was 80 m(3)/kg. The associated with particles (60)Co flux was 21 Bq/(m(2) year), when (60)Co activity concentration in sediment trap particles was 15.7 ± 5 Bq/kg. (60)Co activity concentration in soluble form was less than the minimum detectable activity (MDA = 1.3 Bq/m(3)). Then, the conservatively derived Kd value for (60)Co was >90 m(3)/kg. Copyright © 2015 Elsevier Ltd. All rights reserved.

Validation of Smartphone Based Retinal Photography for Diabetic Retinopathy Screening

PubMed Central

Rajalakshmi, Ramachandran; Arulmalar, Subramanian; Usha, Manoharan; Prathiba, Vijayaraghavan; Kareemuddin, Khaji Syed; Anjana, Ranjit Mohan; Mohan, Viswanathan

2015-01-01

Aim To evaluate the sensitivity and specificity of “fundus on phone’ (FOP) camera, a smartphone based retinal imaging system, as a screening tool for diabetic retinopathy (DR) detection and DR severity in comparison with 7-standard field digital retinal photography. Design Single-site, prospective, comparative, instrument validation study. Methods 301 patients (602 eyes) with type 2 diabetes underwent standard seven-field digital fundus photography with both Carl Zeiss fundus camera and indigenous FOP at a tertiary care diabetes centre in South India. Grading of DR was performed by two independent retina specialists using modified Early Treatment of Diabetic Retinopathy Study grading system. Sight threatening DR (STDR) was defined by the presence of proliferative DR(PDR) or diabetic macular edema. The sensitivity, specificity and image quality were assessed. Results The mean age of the participants was 53.5 ±9.6 years and mean duration of diabetes 12.5±7.3 years. The Zeiss camera showed that 43.9% had non-proliferative DR(NPDR) and 15.3% had PDR while the FOP camera showed that 40.2% had NPDR and 15.3% had PDR. The sensitivity and specificity for detecting any DR by FOP was 92.7% (95%CI 87.8–96.1) and 98.4% (95%CI 94.3–99.8) respectively and the kappa (ĸ) agreement was 0.90 (95%CI-0.85–0.95 p<0.001) while for STDR, the sensitivity was 87.9% (95%CI 83.2–92.9), specificity 94.9% (95%CI 89.7–98.2) and ĸ agreement was 0.80 (95%CI 0.71–0.89 p<0.001), compared to conventional photography. Conclusion Retinal photography using FOP camera is effective for screening and diagnosis of DR and STDR with high sensitivity and specificity and has substantial agreement with conventional retinal photography. PMID:26401839

Optical coherence tomography angiography discerns preclinical diabetic retinopathy in eyes of patients with type 2 diabetes without clinical diabetic retinopathy.

PubMed

Cao, Dan; Yang, Dawei; Huang, Zhongning; Zeng, Yunkao; Wang, Jun; Hu, Yunyan; Zhang, Liang

2018-05-01

To investigate changes in retinal vascular plexuses and choriocapillaris in patients with type 2 diabetes mellitus (DM2) without diabetic retinopathy (DR) and healthy controls using optical coherence tomography angiography (OCTA). A total of 71 DM2 and 67 healthy control subjects were included. All subjects underwent OCTA examination (RTVue-XR Avanti; Optovue, Fremont, CA, USA). Average vessel density in superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris, parafoveal vessel density in SCP and DCP, FAZ area (mm 2 ) in SCP, microaneurysms and capillary nonperfusion were taken into analysis. Parafoveal vessel density in both SCP and DCP decreased in the eyes without clinical DR compared to normal controls (p < 0.001). Diabetic patients with no signs of DR also had a significant reduction in average vessel density of SCP, DCP and choriocapillaris (p < 0.001, p < 0.001 and p = 0.006, respectively). No significant difference was found in FAZ area of SCP between DM2 eyes and healthy controls (p = 0.253). The average vessel density of SCP and DCP is not correlated with HbA1c or serum creatinine in DM2 patients. Microaneurysms seen in OCTA but not in fundus examination were found in 8 out of the 71 (11.3%) diabetic eyes, and capillary nonperfusion was noted in 18 of 71 diabetic eyes. We demonstrated that OCTA can identify preclinical DR before the manifestation of clinically apparent retinopathy in diabetic eyes. DM2 patients without DR have SCP, DCP and choriocapillaris impairment. Our results suggested that OCTA might be a promising tool for regular screening of diabetic eyes for DR.

Risk of Pediatric Celiac Disease According to HLA Haplotype and Country

PubMed Central

Liu, Edwin; Lee, Hye-Seung; Aronsson, Carin A.; Hagopian, William A.; Koletzko, Sibylle; Rewers, Marian J.; Eisenbarth, George S.; Bingley, Polly J.; Bonifacio, Ezio; Simell, Ville; Agardh, Daniel

2014-01-01

BACKGROUND The presence of HLA haplotype DR3–DQ2 or DR4–DQ8 is associated with an increased risk of celiac disease. In addition, nearly all children with celiac disease have serum antibodies against tissue transglutaminase (tTG). METHODS We studied 6403 children with HLA haplotype DR3–DQ2 or DR4–DQ8 prospectively from birth in the United States, Finland, Germany, and Sweden. The primary end point was the development of celiac disease autoimmunity, which was defined as the presence of tTG antibodies on two consecutive tests at least 3 months apart. The secondary end point was the development of celiac disease, which was defined for the purpose of this study as either a diagnosis on biopsy or persistently high levels of tTG antibodies. RESULTS The median follow-up was 60 months (interquartile range, 46 to 77). Celiac disease autoimmunity developed in 786 children (12%). Of the 350 children who underwent biopsy, 291 had confirmed celiac disease; an additional 21 children who did not undergo biopsy had persistently high levels of tTG antibodies. The risks of celiac disease autoimmunity and celiac disease by the age of 5 years were 11% and 3%, respectively, among children with a single DR3–DQ2 haplotype, and 26% and 11%, respectively, among those with two copies (DR3–DQ2 homozygosity). In the adjusted model, the hazard ratios for celiac disease autoimmunity were 2.09 (95% confidence interval [CI], 1.70 to 2.56) among heterozygotes and 5.70 (95% CI, 4.66 to 6.97) among homozygotes, as compared with children who had the lowest-risk genotypes (DR4–DQ8 heterozygotes or homozygotes). Residence in Sweden was also independently associated with an increased risk of celiac disease autoimmunity (hazard ratio, 1.90; 95% CI, 1.61 to 2.25). CONCLUSIONS Children with the HLA haplotype DR3–DQ2, especially homozygotes, were found to be at high risk for celiac disease autoimmunity and celiac disease early in childhood. The higher risk in Sweden than in other countries highlights the importance of studying environmental factors associated with celiac disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.) PMID:24988556

Risk of pediatric celiac disease according to HLA haplotype and country.

PubMed

Liu, Edwin; Lee, Hye-Seung; Aronsson, Carin A; Hagopian, William A; Koletzko, Sibylle; Rewers, Marian J; Eisenbarth, George S; Bingley, Polly J; Bonifacio, Ezio; Simell, Ville; Agardh, Daniel

2014-07-03

The presence of HLA haplotype DR3-DQ2 or DR4-DQ8 is associated with an increased risk of celiac disease. In addition, nearly all children with celiac disease have serum antibodies against tissue transglutaminase (tTG). We studied 6403 children with HLA haplotype DR3-DQ2 or DR4-DQ8 prospectively from birth in the United States, Finland, Germany, and Sweden. The primary end point was the development of celiac disease autoimmunity, which was defined as the presence of tTG antibodies on two consecutive tests at least 3 months apart. The secondary end point was the development of celiac disease, which was defined for the purpose of this study as either a diagnosis on biopsy or persistently high levels of tTG antibodies. The median follow-up was 60 months (interquartile range, 46 to 77). Celiac disease autoimmunity developed in 786 children (12%). Of the 350 children who underwent biopsy, 291 had confirmed celiac disease; an additional 21 children who did not undergo biopsy had persistently high levels of tTG antibodies. The risks of celiac disease autoimmunity and celiac disease by the age of 5 years were 11% and 3%, respectively, among children with a single DR3-DQ2 haplotype, and 26% and 11%, respectively, among those with two copies (DR3-DQ2 homozygosity). In the adjusted model, the hazard ratios for celiac disease autoimmunity were 2.09 (95% confidence interval [CI], 1.70 to 2.56) among heterozygotes and 5.70 (95% CI, 4.66 to 6.97) among homozygotes, as compared with children who had the lowest-risk genotypes (DR4-DQ8 heterozygotes or homozygotes). Residence in Sweden was also independently associated with an increased risk of celiac disease autoimmunity (hazard ratio, 1.90; 95% CI, 1.61 to 2.25). Children with the HLA haplotype DR3-DQ2, especially homozygotes, were found to be at high risk for celiac disease autoimmunity and celiac disease early in childhood. The higher risk in Sweden than in other countries highlights the importance of studying environmental factors associated with celiac disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).

Astrometric surveys in the Gaia era

NASA Astrophysics Data System (ADS)

Zacharias, Norbert

2018-04-01

The Gaia first data release (DR1) already provides an almost error free optical reference frame on the milli-arcsecond (mas) level allowing significantly better calibration of ground-based astrometric data than ever before. Gaia DR1 provides positions, proper motions and trigonometric parallaxes for just over 2 million stars in the Tycho-2 catalog. For over 1.1 billion additional stars DR1 gives positions. Proper motions for these, mainly fainter stars (G >= 11.5) are currently provided by several new projects which combine earlier epoch ground-based observations with Gaia DR1 positions. These data are very helpful in the interim period but will become obsolete with the second Gaia data release (DR2) expected in April 2018. The era of traditional, ground-based, wide-field astrometry with the goal to provide accurate reference stars has come to an end. Future ground-based astrometry will fill in some gaps (very bright stars, observations needed at many or specific epochs) and mainly will go fainter than the Gaia limit, like the PanSTARRS and the upcoming LSST surveys.

Lack of death receptor 4 (DR4) expression through gene promoter methylation in gastric carcinoma.

PubMed

Lee, Kyung Hwa; Lim, Sang Woo; Kim, Ho Gun; Kim, Dong Yi; Ryu, Seong Yeob; Joo, Jae Kyun; Kim, Jung Chul; Lee, Jae Hyuk

2009-07-01

To determine the underlying mechanism for the differential expression, the extent of promoter methylation in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-related genes acting downstream of TRAIL was examined in early and advanced gastric carcinomas. The extent of promoter methylation in the DR4, DR5, DcR1, DcR2, and CASP8 genes was quantified using bisulfite modification and methylation-specific polymerase chain reaction. The promoters for DcR1, DcR2, and CASP8 were largely unmethylated in early gastric carcinoma, advanced gastric carcinoma, and controls, with no significant difference among them. Protein levels of DR4, DcR1, and DcR2 as revealed by immunohistochemistry correlated with the extent of the respective promoter methylation (P < 0.05 in all cases). Hypomethylation, rather than hypermethylation, of the DR4 promoter was noted in invasive gastric malignancies, with statistical significance (P = 0.003). The promoter methylation status of TRAIL receptors in gastric carcinoma may have clinical implications for improving therapeutic strategies in patients with gastric carcinoma.

Health effects of fine particulate air pollution: lines that connect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Judith C. Chow; John G. Watson; Joe L. Mauderly

2006-10-15

In the 2006 A&WMA Critical Review on 'Health Effects of fine particulate air pollution: lines that connect' Drs. C. Arden Pope III and Douglas Dockery addressed the epidemiological evidence for the effects of particulate matter (PM) on human health indicators. The review documents substantial progress since the 1997 Critical Review in the areas of: (1) short-term exposure and mortality; (2) long-term exposure and mortality; (3) time scales of exposure; (4) the shape of the concentration-response function; (5) cardiovascular disease; and (6) biological plausibility. This critical review discussion was compiled from written submissions and presentation transcripts, which were revised for concisenessmore » and to minimize redundancy. The invited discussants were as follows were: Dr. Joe L. Mauderly, Dr. Daniel L. Costa, Dr. Ronald E. Wyzga, and Dr. Sverre Vedal. The contributing discussants were: Dr. George M. Hidy, Sam L. Altshuler, Dr. David Marrack, Jon M. Heuss, and Dr. George T. Wolff. See Coal Abstracts entry Sep 2006 00390 for the Critical Review. 80 refs.« less

Low energy range dielectronic recombination of Fluorine-like Fe17+ at the CSRm

NASA Astrophysics Data System (ADS)

Khan, Nadir; Huang, Zhong-Kui; Wen, Wei-Qiang; Mahmood, Sultan; Dou, Li-Jun; Wang, Shu-Xing; Xu, Xin; Wang, Han-Bing; Chen, Chong-Yang; Chuai, Xiao-Ya; Zhu, Xiao-Long; Zhao, Dong-Mei; Mao, Li-Jun; Li, Jie; Yin, Da-Yu; Yang, Jian-Cheng; Yuan, You-Jin; Zhu, Lin-Fan; Ma, Xin-Wen

2018-05-01

The accuracy of dielectronic recombination (DR) data for astrophysics related ions plays a key role in astrophysical plasma modeling. The absolute DR rate coefficient of Fe17+ ions was measured at the main cooler storage ring at the Institute of Modern Physics, Lanzhou, China. The experimental electron-ion collision energy range covers the first Rydberg series up to n = 24 for the DR resonances associated with the {}2P1/2\\to {}2P3/2{{Δ }}n=0 core excitations. A theoretical calculation was performed by using FAC code and compared with the measured DR rate coefficient. Overall reasonable agreement was found between the experimental results and calculations. Moreover, the plasma rate coefficient was deduced from the experimental DR rate coefficient and compared with the available results from the literature. At the low energy range, significant discrepancies were found, and the measured resonances challenge state-of-the-art theory at low collision energies. Supported by the National Key R&D Program of China (2017YFA0402300), the National Natural Science Foundation of China through (11320101003, U1732133, 11611530684) and Key Research Program of Frontier Sciences, CAS (QYZDY-SSW-SLH006)

Improved Automated Detection of Diabetic Retinopathy on a Publicly Available Dataset Through Integration of Deep Learning.

PubMed

Abràmoff, Michael David; Lou, Yiyue; Erginay, Ali; Clarida, Warren; Amelon, Ryan; Folk, James C; Niemeijer, Meindert

2016-10-01

To compare performance of a deep-learning enhanced algorithm for automated detection of diabetic retinopathy (DR), to the previously published performance of that algorithm, the Iowa Detection Program (IDP)-without deep learning components-on the same publicly available set of fundus images and previously reported consensus reference standard set, by three US Board certified retinal specialists. We used the previously reported consensus reference standard of referable DR (rDR), defined as International Clinical Classification of Diabetic Retinopathy moderate, severe nonproliferative (NPDR), proliferative DR, and/or macular edema (ME). Neither Messidor-2 images, nor the three retinal specialists setting the Messidor-2 reference standard were used for training IDx-DR version X2.1. Sensitivity, specificity, negative predictive value, area under the curve (AUC), and their confidence intervals (CIs) were calculated. Sensitivity was 96.8% (95% CI: 93.3%-98.8%), specificity was 87.0% (95% CI: 84.2%-89.4%), with 6/874 false negatives, resulting in a negative predictive value of 99.0% (95% CI: 97.8%-99.6%). No cases of severe NPDR, PDR, or ME were missed. The AUC was 0.980 (95% CI: 0.968-0.992). Sensitivity was not statistically different from published IDP sensitivity, which had a CI of 94.4% to 99.3%, but specificity was significantly better than the published IDP specificity CI of 55.7% to 63.0%. A deep-learning enhanced algorithm for the automated detection of DR, achieves significantly better performance than a previously reported, otherwise essentially identical, algorithm that does not employ deep learning. Deep learning enhanced algorithms have the potential to improve the efficiency of DR screening, and thereby to prevent visual loss and blindness from this devastating disease.

Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency

PubMed Central

Nilsson, A G; Marelli, C; Fitts, D; Bergthorsdottir, R; Burman, P; Dahlqvist, P; Ekman, B; Edén Engström, B; Olsson, T; Ragnarsson, O; Ryberg, M; Wahlberg, J; Lennernäs, H; Skrtic, S; Johannsson, G

2014-01-01

Objective The objective was to assess the long-term safety profile of dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency (AI). Design Randomised, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden. Methods Sixty-four adults with primary AI started stage 1, and an additional 16 entered stage 3. Patients received DR-HC 20–40 mg once daily and hydrocortisone 20–40 mg divided into three daily doses (stage 1 only). Main outcome measures were adverse events (AEs) and intercurrent illness (self-reported hydrocortisone use during illness). Results In stage 1, patients had a median 1.5 (range, 1–9) intercurrent illness events with DR-HC and 1.0 (1–8) with thrice-daily hydrocortisone. AEs during stage 1 were not related to the cortisol exposure-time profile. The percentage of patients with one or more AEs during stage 1 (73.4% with DR-HC; 65.6% with thrice-daily hydrocortisone) decreased during stage 2, when all patients received DR-HC (51% in the first 3 months; 54% in the second 3 months). In stages 1–3 combined, 19 patients experienced 27 serious AEs, equating to 18.6 serious AEs/100 patient-years of DR-HC exposure. Conclusions This long-term prospective trial is the first to document the safety of DR-HC in patients with primary AI and demonstrates that such treatment is well tolerated during 24 consecutive months of therapy. PMID:24944332

Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency.

PubMed

Nilsson, A G; Marelli, C; Fitts, D; Bergthorsdottir, R; Burman, P; Dahlqvist, P; Ekman, B; Engström, B Edén; Olsson, T; Ragnarsson, O; Ryberg, M; Wahlberg, J; Lennernäs, H; Skrtic, S; Johannsson, G

2014-09-01

The objective was to assess the long-term safety profile of dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency (AI). Randomised, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden. Sixty-four adults with primary AI started stage 1, and an additional 16 entered stage 3. Patients received DR-HC 20-40 mg once daily and hydrocortisone 20-40 mg divided into three daily doses (stage 1 only). Main outcome measures were adverse events (AEs) and intercurrent illness (self-reported hydrocortisone use during illness). In stage 1, patients had a median 1.5 (range, 1-9) intercurrent illness events with DR-HC and 1.0 (1-8) with thrice-daily hydrocortisone. AEs during stage 1 were not related to the cortisol exposure-time profile. The percentage of patients with one or more AEs during stage 1 (73.4% with DR-HC; 65.6% with thrice-daily hydrocortisone) decreased during stage 2, when all patients received DR-HC (51% in the first 3 months; 54% in the second 3 months). In stages 1-3 combined, 19 patients experienced 27 serious AEs, equating to 18.6 serious AEs/100 patient-years of DR-HC exposure. This long-term prospective trial is the first to document the safety of DR-HC in patients with primary AI and demonstrates that such treatment is well tolerated during 24 consecutive months of therapy. © 2014 The authors.

D1 dopamine receptor is involved in shell formation in larvae of Pacific oyster Crassostrea gigas.

PubMed

Liu, Zhaoqun; Wang, Lingling; Yan, Yunchen; Zheng, Yan; Ge, Wenjing; Li, Meijia; Wang, Weilin; Song, Xiaorui; Song, Linsheng

2018-07-01

Dopamine (DA), a significant member of catecholamines, is reported to induce biomineralization of calcium carbonate vaterite microspheres via dopamine receptor (DR) in bivalves, implying the modulation of dopaminergic system on shell formation during larval development. In this research, a homologue of D1 type DR (CgD1DR-1) was identified from oyster Crassostrea gigas, whose full length cDNA was 1197 bp. It was widely expressed in various tissues of C. gigas, with the significantly higher levels in hepatopancreas, mantle, muscle and gill. During developmental stages, the mRNA transcripts of CgD1DR-1 in D-shape larvae were obviously higher (p < 0.05) than those in trochophore and umbo larvae, and CO 2 exposure could inhibit the synthesis of DA and mRNA expression of CgD1DR-1. After cell transfection and DA treatment, intracellular cAMP in cells with the expression of CgD1DR-1 increased significantly (p < 0.05). Furthermore, the incubation with SCH 23390 for the blockage of CgD1DR-1 significantly restrained the expressions of six shell formation-related genes including CgTyrosinase-1, CgTyrosinase-3, CgChitinaseLP, CgAMC, CgBMP and CgBMPR in trochophore and D-shape larvae. These results jointly suggested that DA together with its receptor CgD1DR-1 might be involved in shell formation during oyster larval development from trochophore to D-shape larvae, and CO 2 -induced ocean acidification (OA) might influence marine bivalves by inhibiting the DA-D1DR pathway to prohibit their shell formation. Copyright © 2018 Elsevier Ltd. All rights reserved.

What is the cost of diagnosis and management of drug resistant tuberculosis in South Africa?

PubMed

Pooran, Anil; Pieterson, Elize; Davids, Malika; Theron, Grant; Dheda, Keertan

2013-01-01

Drug-resistant tuberculosis (DR-TB) is undermining TB control in South Africa. However, there are hardly any data about the cost of treating DR-TB in high burden settings despite such information being quintessential for the rational planning and allocation of resources by policy-makers, and to inform future cost-effectiveness analyses. We analysed the comparative 2011 United States dollar ($) cost of diagnosis and treatment of drug sensitive TB (DS-TB), MDR-TB and XDR-TB, based on National South African TB guidelines, from the perspective of the National TB Program using published clinical outcome data. Assuming adherence to national DR-TB management guidelines, the per patient cost of XDR-TB was $26,392, four times greater than MDR-TB ($6772), and 103 times greater than drug-sensitive TB ($257). Despite DR-TB comprising only 2.2% of the case burden, it consumed ~32% of the total estimated 2011 national TB budget of US $218 million. 45% and 25% of the DR-TB costs were attributed to anti-TB drugs and hospitalization, respectively. XDR-TB consumed 28% of the total DR-TB diagnosis and treatment costs. Laboratory testing and anti-TB drugs comprised the majority (71%) of MDR-TB costs while hospitalization and anti-TB drug costs comprised the majority (92%) of XDR-TB costs. A decentralized XDR-TB treatment programme could potentially reduce costs by $6930 (26%) per case and reduce the total amount spent on DR-TB by ~7%. Although DR-TB forms a very small proportion of the total case burden it consumes a disproportionate and substantial amount of South Africa's total annual TB budget. These data inform rational resource allocation and selection of management strategies for DR-TB in high burden settings.

MTB-DR-RIF 9G test: Detection and discrimination of tuberculosis and multi-drug resistant tuberculosis strains.

PubMed

Song, Keum-Soo; Nimse, Satish Balasaheb; Cho, Nam Hoon; Sung, Nackmoon; Kim, Hee-Jin; Yang, Jeongseong; Kim, Taisun

2015-12-01

This report describes the evaluation of the novel MTB-DR-RIF 9G test for the accurate detection and discrimination of Mycobacterium tuberculosis (MTB) and rifampicin-resistant M. tuberculosis (MTB-DR-RIF) in the clinical samples. The procedure included the amplification of a nucleotide fragment of the rpoB gene of the MTB and MTB-DR-RIF strains and their hybridization with the immobilized probes. The MTB-DR-RIF 9G test was evaluated for its ability to detect and discriminate MTB and MTB-DR-RIF strains in 113 known clinical samples. The accuracy of the MTB-DR-RIF 9G test was determined by comparing its results with sequencing analysis and drug susceptibility testing. The sensitivity and specificity of the MTB-DR-RIF 9G test at 95% confidence interval were found to be 95.4% (89.5-98.5) and 100% (69.2-100), respectively. The positive predictive value and negative predictive value of the MTB-DR-RIF 9G test at 95% confidence interval were found to be 100% (85.0-95.9) and 66.7% (38.4-88.18), respectively. Sequencing analysis of all samples indicated that the mutations present in the regions identified with the MTB-DR-RIF 9G assay can be detected accurately. Copyright © 2015 Elsevier Ltd. All rights reserved.

Answering Questions from Oceanography Texts: Learner, Task and Text Characteristics.

DTIC Science & Technology

1987-09-15

1 275-290. ’S.= Stowe, K. (1983). S , 2nd edition. New York, NY: John Wiley & Sons. ’?o.,i ’S= .. ’S.’ .5.% .5.% r. ** - ’, .* . . . % S 9.. . 9...94305 O Dr. Ed Aiken Leo Seltracchi Dr. John S. Brown " Navy Personnel R&D Center U. S. Nuclear Regulatory Comm. XEROX Palo Alto Research Center " San...iego, CA 92152-6800 Washington, OC 20555 3333 Coyote Hill Road Palo Alto, CA 94304 Or. John R. Anderson Dr. Mark H. Bickhard Dr. Ann Brown Department

Robert H. Goddard and His Liquid-Gasoline Rocket

NASA Technical Reports Server (NTRS)

1926-01-01

Dr. Goddard's 1926 rocket configuration. Dr. Goddard's liquid oxygen-gasoline rocket was fired on March 16, 1926, at Auburn, Massachusetts. It flew for only 2.5 seconds, climbed 41 feet, and landed 184 feet away in a cabbage patch. From 1930 to 1941, Dr. Goddard made substantial progress in the development of progressively larger rockets, which attained altitudes of 2400 meters, and refined his equipment for guidance and control, his techniques of welding, and his insulation, pumps, and other associated equipment. In many respects, Dr. Goddard laid the essential foundations of practical rocket technology

The crystal structure of DR6 in complex with the amyloid precursor protein provides insight into death receptor activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Kai; Olsen, Olav; Tzvetkova-Robev, Dorothea

The amyloid precursor protein (APP) has garnered considerable attention due to its genetic links to Alzheimer's disease. Death receptor 6 (DR6) was recently shown to bind APP via the protein extracellular regions, stimulate axonal pruning, and inhibit synapse formation. Here, we report the crystal structure of the DR6 ectodomain in complex with the E2 domain of APP and show that it supports a model for APP-induced dimerization and activation of cell surface DR6.

Early Rockets

NASA Image and Video Library

1926-03-16

Dr. Goddard's 1926 rocket configuration. Dr. Goddard's liquid oxygen-gasoline rocket was fired on March 16, 1926, at Auburn, Massachusetts. It flew for only 2.5 seconds, climbed 41 feet, and landed 184 feet away in a cabbage patch. From 1930 to 1941, Dr. Goddard made substantial progress in the development of progressively larger rockets, which attained altitudes of 2400 meters, and refined his equipment for guidance and control, his techniques of welding, and his insulation, pumps, and other associated equipment. In many respects, Dr. Goddard laid the essential foundations of practical rocket technology

The crystal structure of DR6 in complex with the amyloid precursor protein provides insight into death receptor activation

DOE PAGES

Xu, Kai; Olsen, Olav; Tzvetkova-Robev, Dorothea; ...

2015-04-02

The amyloid precursor protein (APP) has garnered considerable attention due to its genetic links to Alzheimer's disease. Death receptor 6 (DR6) was recently shown to bind APP via the protein extracellular regions, stimulate axonal pruning, and inhibit synapse formation. Here, we report the crystal structure of the DR6 ectodomain in complex with the E2 domain of APP and show that it supports a model for APP-induced dimerization and activation of cell surface DR6.

VizieR Online Data Catalog: The GALFA-HI survey data release 2 (Peek+, 2018)

NASA Astrophysics Data System (ADS)

Peek, J. E. G.; Babler, B. L.; Zheng, Y.; Clark, S. E.; Douglas, K. A.; Korpela, E. J.; Putman, M. E.; Stanimirovic, S.; Gibson, S. J.; Heiles, C.

2018-03-01

The GALFA-HI survey is conducted with the William E. Gordon Arecibo Observatory 305m telescope, located south of Arecibo Puerto Rico. This survey owes its name to the instrument with which it was conducted, the ALFA, a 7-beam array of heterodyne detectors, sensitive from 1225 to 1525MHz. The observational strategy of DR2 is one of the significant differences from DR1 (Peek+ 2011ApJS..194...20P); see section 2.2. Region North-1 was included in DR1, but otherwise all of the Arecibo HI data presented in this work are new. (3 data files).

The induction of autoimmune hepatitis in the human leucocyte antigen‐DR4 non‐obese diabetic mice autoimmune hepatitis mouse model

PubMed Central

Yuksel, M.; Xiao, X.; Tai, N.; Vijay, G. M.; Gülden, E.; Beland, K.; Lapierre, P.; Alvarez, F.; Hu, Z.; Colle, I.; Ma, Y.

2016-01-01

Summary Autoimmune hepatitis (AIH) is a chronic liver disease characterized by progressive inflammation, female preponderance and seropositivity for autoantibodies such as anti‐smooth muscle actin and/or anti‐nuclear, anti‐liver kidney microsomal type 1 (anti‐LKM1) and anti‐liver cytosol type 1 (anti‐LC1) in more than 80% of cases. AIH is linked strongly to several major histocompatibility complex (MHC) alleles, including human leucocyte antigen (HLA)‐DR3, ‐DR7 and ‐DR13. HLA‐DR4 has the second strongest association with adult AIH, after HLA‐DR3. We investigated the role of HLA‐DR4 in the development of AIH by immunization of HLA‐DR4 (DR4) transgenic non‐obese diabetic (NOD) mice with DNA coding for human CYP2D6/FTCD fusion autoantigen. Immunization of DR4 mice leads to sustained mild liver injury, as assessed biochemically by elevated alanine aminotransferase, histologically by interface hepatitis, plasma cell infiltration and mild fibrosis and immunologically by the development of anti‐LKM1/anti‐LC1 antibodies. In addition, livers from DR4 mice had fewer regulatory T cells (Tregs), which had decreased programmed death (PD)‐1 expression. Splenic Tregs from these mice also showed impaired inhibitory capacity. Furthermore, DR4 expression enhanced the activation status of CD8+ T cells, macrophages and dendritic cells in naive DR4 mice compared to naive wild‐type (WT) NOD mice. Our results demonstrate that HLA‐DR4 is a susceptibility factor for the development of AIH. Impaired suppressive function of Tregs and reduced PD‐1 expression may result in spontaneous activation of key immune cell subsets, such as antigen‐presenting cells and CD8+ T effectors, facilitating the induction of AIH and persistent liver damage. PMID:27414259

The induction of autoimmune hepatitis in the human leucocyte antigen-DR4 non-obese diabetic mice autoimmune hepatitis mouse model.

PubMed

Yuksel, M; Xiao, X; Tai, N; Vijay, G M; Gülden, E; Beland, K; Lapierre, P; Alvarez, F; Hu, Z; Colle, I; Ma, Y; Wen, L

2016-11-01

Autoimmune hepatitis (AIH) is a chronic liver disease characterized by progressive inflammation, female preponderance and seropositivity for autoantibodies such as anti-smooth muscle actin and/or anti-nuclear, anti-liver kidney microsomal type 1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1) in more than 80% of cases. AIH is linked strongly to several major histocompatibility complex (MHC) alleles, including human leucocyte antigen (HLA)-DR3, -DR7 and -DR13. HLA-DR4 has the second strongest association with adult AIH, after HLA-DR3. We investigated the role of HLA-DR4 in the development of AIH by immunization of HLA-DR4 (DR4) transgenic non-obese diabetic (NOD) mice with DNA coding for human CYP2D6/FTCD fusion autoantigen. Immunization of DR4 mice leads to sustained mild liver injury, as assessed biochemically by elevated alanine aminotransferase, histologically by interface hepatitis, plasma cell infiltration and mild fibrosis and immunologically by the development of anti-LKM1/anti-LC1 antibodies. In addition, livers from DR4 mice had fewer regulatory T cells (T regs ), which had decreased programmed death (PD)-1 expression. Splenic T regs from these mice also showed impaired inhibitory capacity. Furthermore, DR4 expression enhanced the activation status of CD8 + T cells, macrophages and dendritic cells in naive DR4 mice compared to naive wild-type (WT) NOD mice. Our results demonstrate that HLA-DR4 is a susceptibility factor for the development of AIH. Impaired suppressive function of T regs and reduced PD-1 expression may result in spontaneous activation of key immune cell subsets, such as antigen-presenting cells and CD8 + T effectors, facilitating the induction of AIH and persistent liver damage. © 2016 British Society for Immunology.

Delivery room continuous positive airway pressure and early pneumothorax in term newborn infants.

PubMed

Clevenger, L; Britton, J R

2017-01-01

To assess the association between delivery room (DR) continuous positive airway pressure (CPAP) and pneumothorax (PT) in term newborns. Two studies performed in community hospitals used data extracted from computerized records of term newborns. Infants receiving positive pressure ventilation in the DR were excluded. Tabulated data included receipt of DR CPAP, PT on the day of birth, and gestational age (GA). In a case-control study from 2001-2013, infants with PT were compared to controls without PT but with respiratory distress or hypoxia persisting from birth for receipt of DR CPAP. In a cohort study from 2014-2016, infants receiving and not receiving DR CPAP were compared for the incidence of PT. In the case-control study, data were obtained for 169 cases and 850 controls. Compared to controls, PT infants were more likely to have received DR CPAP (16.8% vs. 40.2%, respectively, P < 0.001). Logistic regression revealed DR CPAP (Adjusted Odds Ratio [AOR] = 3.30, 95% confidence interval [CI] = 2.31, 4.72, P < 0.001) and GA (AOR = 1.21, 95% CI = 1.05, 1.39, P = 0.009) to be independent predictors of early PT.In the cohort study, PT was observed in 0.1% of 9255 control infants not receiving DR CPAP and 4.8% of 228 infants receiving DR CPAP (P < 0.001). In logistic regression analyses, DR CPAP significantly predicted PT (OR = 59.59, 95% CI = 23.34, 147.12, P < 0.001) and remained a significant predictor of PT after controlling for gestational age. Respiratory conditions treated with CPAP in delivery rooms are associated with increased risk of PT. A cause-and-effect relationship between CPAP and PT cannot be claimed in this study. Further research is needed to better understand this relationship.

Identification of factors to increase efficacy of telemedicine screening for diabetic retinopathy in endocrinology practices using the Intelligent Retinal Imaging System (IRIS) platform.

PubMed

Naik, Sapna; Wykoff, Charles C; Ou, William C; Stevenson, Jonathan; Gupta, Sunil; Shah, Ankoor R

2018-06-01

Diabetic retinopathy (DR) and diabetic macular edema (DME) can be evaluated using telemedicine systems, such as the Intelligent Retinal Imaging Systems (IRIS), in patients with Diabetes Mellitus (DM). In an endocrinology-based population utilizing IRIS we determine prevalence rates of DR and DME, and identify associated epidemiologic correlations. This is a multicenter, retrospective chart review using screening data from IRIS. Centers for Disease Control and Prevention (CDC) data on epidemiologic variables (by county) namely, prevalence of DM, incidence of DM, obesity, and time of physical inactivity, were compared against prevalence rates of DR found at screening. A total of 10,223 eyes of 5,242 patients with DM were imaged. DR and DME were noted in 1781 (33.98%) and 226 imaging studies (4.31%) respectively. The coefficient of determination was greatest for incidence of DM (R 2  = 0.92), followed by DM prevalence (R 2  = 0.79), obesity, (R 2  = 0.67), and physical inactivity (R 2  = 0.34). The presence of DR during screening varied significantly by county (p < 0.001). Screening in counties with a higher incidence of DM led to a higher prevalence of identified DR at time of screening. The current work suggests that telemedicine screening in areas known to have a higher incidence of DM may be worthwhile. Copyright © 2018 Elsevier B.V. All rights reserved.

Advanced Restoration Therapies in Spinal Cord Injury

DTIC Science & Technology

2016-05-01

project. In addition, Dr. Belegu has performed SCI surgeries , electrode implantations, FES stimulation, and neurological assays. Name: Ali...month worked: 10.2 Contribution to Project: Dr. Liu has assisted Dr. Belegu in performing SCI surgeries , electrode implantation. In addition, she...training-based rehabilitation. Arch Phys Med Rehabil 93, 1508-1517. Karimi, M.T. (2013). Robotic rehabilitation of spinal cord injury individual

Effects of dietary restriction on adipose mass and biomarkers of healthy aging in human.

PubMed

Lettieri-Barbato, Daniele; Giovannetti, Esmeralda; Aquilano, Katia

2016-11-29

In developing countries the rise of obesity and obesity-related metabolic disorders, such as cardiovascular diseases and type 2 diabetes, reflects the changes in lifestyle habits and wrong dietary choices. Dietary restriction (DR) regimens have been shown to extend health span and lifespan in many animal models including primates. Identifying biomarkers predictive of clinical benefits of treatment is one of the primary goals of precision medicine. To monitor the clinical outcomes of DR interventions in humans, several biomarkers are commonly adopted. However, a validated link between the behaviors of such biomarkers and DR effects is lacking at present time. Through a systematic analysis of human intervention studies, we evaluated the effect size of DR (i.e. calorie restriction, very low calorie diet, intermittent fasting, alternate day fasting) on health-related biomarkers. We found that DR is effective in reducing total and visceral adipose mass and improving inflammatory cytokines profile and adiponectin/leptin ratio. By analysing the levels of canonical biomarkers of healthy aging, we also validated the changes of insulin, IGF-1 and IGFBP-1,2 to monitor DR effects. Collectively, we developed a useful platform to evaluate the human responses to dietary regimens low in calories.

The Large Sky Area Multi-Object Fibre Spectroscopic Telescope (LAMOST) Quasar Survey: Quasar Properties from Data Release Two and Three

NASA Astrophysics Data System (ADS)

Dong, X. Y.; Wu, Xue-Bing; Ai, Y. L.; Yang, J. Y.; Yang, Q.; Wang, F.; Zhang, Y. X.; Luo, A. L.; Xu, H.; Yuan, H. L.; Zhang, J. N.; Wang, M. X.; Wang, L. L.; Li, Y. B.; Zuo, F.; Hou, W.; Guo, Y. X.; Kong, X.; Chen, X. Y.; Wu, Y.; Yang, H. F.; Yang, M.

2018-05-01

This is the second installment for the Large Sky Area Multi-Object Fibre Spectroscopic Telescope (LAMOST) Quasar Survey, which includes quasars observed from 2013 September to 2015 June. There are 9024 confirmed quasars in DR2 and 10911 in DR3. After cross-match with the Sloan Digital Sky Survey (SDSS) quasar catalogs and NED, 12126 quasars are discovered independently. Among them, 2225 quasars were released by SDSS DR12 QSO catalog in 2014 after we finalized the survey candidates. 1801 sources were identified by SDSS DR14 as QSOs. The remaining 8100 quasars are considered as newly founded, and among them, 6887 quasars can be given reliable emission line measurements and the estimated black hole masses. Quasars found in LAMOST are mostly located at low-to-moderate redshifts, with a mean value of 1.5. The highest redshift observed in DR2 and DR3 is 5. We applied emission line measurements to Hα, Hβ, Mg II, and C IV. We deduced the monochromatic continuum luminosities using photometry data, and estimated the virial black hole masses for the newly discovered quasars. Results are compiled into a quasar catalog, which will be available online.

Galaxy And Mass Assembly: the G02 field, Herschel-ATLAS target selection and data release 3

NASA Astrophysics Data System (ADS)

Baldry, I. K.; Liske, J.; Brown, M. J. I.; Robotham, A. S. G.; Driver, S. P.; Dunne, L.; Alpaslan, M.; Brough, S.; Cluver, M. E.; Eardley, E.; Farrow, D. J.; Heymans, C.; Hildebrandt, H.; Hopkins, A. M.; Kelvin, L. S.; Loveday, J.; Moffett, A. J.; Norberg, P.; Owers, M. S.; Taylor, E. N.; Wright, A. H.; Bamford, S. P.; Bland-Hawthorn, J.; Bourne, N.; Bremer, M. N.; Colless, M.; Conselice, C. J.; Croom, S. M.; Davies, L. J. M.; Foster, C.; Grootes, M. W.; Holwerda, B. W.; Jones, D. H.; Kafle, P. R.; Kuijken, K.; Lara-Lopez, M. A.; López-Sánchez, Á. R.; Meyer, M. J.; Phillipps, S.; Sutherland, W. J.; van Kampen, E.; Wilkins, S. M.

2018-03-01

We describe data release 3 (DR3) of the Galaxy And Mass Assembly (GAMA) survey. The GAMA survey is a spectroscopic redshift and multiwavelength photometric survey in three equatorial regions each of 60.0 deg2 (G09, G12, and G15), and two southern regions of 55.7 deg2 (G02) and 50.6 deg2 (G23). DR3 consists of: the first release of data covering the G02 region and of data on H-ATLAS (Herschel - Astrophysical Terahertz Large Area Survey) sources in the equatorial regions; and updates to data on sources released in DR2. DR3 includes 154 809 sources with secure redshifts across four regions. A subset of the G02 region is 95.5 per cent redshift complete to r < 19.8 mag over an area of 19.5 deg2, with 20 086 galaxy redshifts, that overlaps substantially with the XXL survey (X-ray) and VIPERS (redshift survey). In the equatorial regions, the main survey has even higher completeness (98.5 per cent), and spectra for about 75 per cent of H-ATLAS filler targets were also obtained. This filler sample extends spectroscopic redshifts, for probable optical counterparts to H-ATLAS submillimetre sources, to 0.8 mag deeper (r < 20.6 mag) than the GAMA main survey. There are 25 814 galaxy redshifts for H-ATLAS sources from the GAMA main or filler surveys. GAMA DR3 is available at the survey website (www.gama-survey.org/dr3/).

Human cytomegalovirus alters localization of MHC class II and dendrite morphology in mature Langerhans cells.

PubMed

Lee, Andrew W; Hertel, Laura; Louie, Ryan K; Burster, Timo; Lacaille, Vashti; Pashine, Achal; Abate, Davide A; Mocarski, Edward S; Mellins, Elizabeth D

2006-09-15

Hemopoietic stem cell-derived mature Langerhans-type dendritic cells (LC) are susceptible to productive infection by human CMV (HCMV). To investigate the impact of infection on this cell type, we examined HLA-DR biosynthesis and trafficking in mature LC cultures exposed to HCMV. We found decreased surface HLA-DR levels in viral Ag-positive as well as in Ag-negative mature LC. Inhibition of HLA-DR was independent of expression of unique short US2-US11 region gene products by HCMV. Indeed, exposure to UV-inactivated virus, but not to conditioned medium from infected cells, was sufficient to reduce HLA-DR on mature LC, implicating particle binding/penetration in this effect. Reduced surface levels reflected an altered distribution of HLA-DR because total cellular HLA-DR was not diminished. Accumulation of HLA-DR was not explained by altered cathepsin S activity. Mature, peptide-loaded HLA-DR molecules were retained within cells, as assessed by the proportion of SDS-stable HLA-DR dimers. A block in egress was implicated, as endocytosis of surface HLA-DR was not increased. Immunofluorescence microscopy corroborated the intracellular retention of HLA-DR and revealed markedly fewer HLA-DR-positive dendritic projections in infected mature LC. Unexpectedly, light microscopic analyses showed a dramatic loss of the dendrites themselves and immunofluorescence revealed that cytoskeletal elements crucial for the formation and maintenance of dendrites are disrupted in viral Ag-positive cells. Consistent with these dendrite effects, HCMV-infected mature LC exhibit markedly reduced chemotaxis in response to lymphoid chemokines. Thus, HCMV impedes MHC class II molecule trafficking, dendritic projections, and migration of mature LC. These changes likely contribute to the reduced activation of CD4+ T cells by HCMV-infected mature LC.

Simplified model to describe the dissociative recombination of linear polyatomic ions of astrophysical interest

NASA Astrophysics Data System (ADS)

Fonseca Dos Santos, Samantha; Douguet, Nicolas; Kokoouline, Viatcheslav; Orel, Ann

2013-05-01

We will present theoretical results on the dissociative recombination (DR) of the linear polyatomic ions HCNH+, HCO+ and N2H+. Besides their astrophysical importance, they also share the characteristic that at low electronic impact energies their DR process happens via the indirect DR mechanism. We apply a general simplified model successfully implemented to treat the DR process of the highly symmetric non-linear molecules H3+, CH3+, H3O+ and NH4+ to calculated cross sections and DR rates for these ions. The model is based on multichannel quantum defect theory and accounts for all the main ingredients of indirect DR. New perspectives on dissociative recombination of HCO+ will also be discussed, including the possible role of HOC+ in storage ring experimental results. This work is supported by the DOE Office of Basic Energy Science and the National Science Foundation, Grant No's PHY-11-60611 and PHY-10-68785.

Ethnic differences in HLA antigens in Chilean donors and recipients: data from the National Renal Transplantation Program.

PubMed

Droguett, M A; Beltran, R; Ardiles, R; Raddatz, N; Labraña, C; Arenas, A; Flores, J; Alruiz, P; Mezzano, S; Ardiles, L

2008-11-01

To describe HLA antigen distribution, looking for possible markers of renal disease in Mapuche and non-Mapuche people in the renal transplantation program, we reviewed data from 1297 histocompatibility studies of the Chilean national renal transplantation program (421 donors and 876 recipients), performed between 2000 and 2005. Mapuche people were classified according to their family surnames. The most frequent antigens found among the total Chilean population were A2 (48%), A19 (33%), B16 (33%), B35 (26%), DR4 (38%), and DR6 (28%), without significant differences between donors and recipients. Among the 114 individuals (9%) classified as Mapuche, the most frequent antigens were A28 (49%), A2 (44%), B16 (63%), B35 (24%), DR4 (48%), and DR8 (30%), with A28/B16/DR4 as the most common haplotype. In contrast, A28, B16, DR4, and DR8 were significantly more frequent in Mapuche compared with non-Mapuche people. B8 was significantly more frequent in Mapuche recipients than in non-Mapuche recipients and Mapuche donors. The higher frequency of some HLA antigens in Mapuche people was confirmed, possibly corresponding to ethnic markers. The special concentration of B8 among Mapuche recipients might represent a genetic factor predisposing to chronic renal disease in this human group.

DR-induced Hot Oxygen and Carbon Coronae of Early Mars

NASA Astrophysics Data System (ADS)

Zhao, J.; Chassefiere, E.; Tian, F.; Chaufray, J. Y.; Leblanc, F.

2017-12-01

The evolution of Martian atmosphere is a key aspect to understand the habitability of Mars in time. The distributions of neutral atoms above the exobase of ancient Mars (corona) is important for understanding the interactions between the corona and the solar wind, which could help improving our understanding of the evolution of Martian atmosphere. In this work, a 3-D Monte Carlo Model is built to simulate Martian corona in different period of Mars history based on thermosphere structure corresponding to 1, 3, 10, and 20 times present solar XUV conditions and dissociative recombination (DR) reaction profiles. DR reactions of O2+, CO2+, and CO+ are considered as the sources of primary O and C. Secondary O and C atoms, which are formed through collisions between primaries and background species. We will discuss the dependence of physical properties of Martian corona as functions of solar XUV flux and DR reactions. We will also discuss the potential importance of CO+ DR as a contributor to Martian corona.

[Prevalence and risk factors of retinopathy in a young Lebanese population with well controlled type I diabetes].

PubMed

Baz, Patrick C; Antoun, Joelle; Haddad, Nour; Kourie, Hampig

2013-01-01

To assess the prevalence of diabetic retinopathy (DR) in a young population with type I diabetes in Lebanon, to compare it to its prevalence worldwide according to the literature, and to analyze its potential risk factors. Screening for DR by fundus examination was performed in patients > 10 years and diabetic for over 8 years attending the Chronic Care Center (CCC) in Lebanon. Data regarding patients' age, duration of their diabetes, body mass index, systolic and diastolic blood pressure, smoking habits, dyslipidemia, microalbuminuria, mean HbA1c over the past five years, number of insulin injections, parents' educational level and geographical origin, were collected. 220 teenagers and young adults (103 males and 117 females) aged between 12 and 46 years (mean age 24.2 y) were included in the study. The prevalence of DR was 14.6%, comparable to recent studies of similar populations. A non-proliferative DR was found in 25 children (11.4%) and a proliferative DR in 7 patients (3.2%). The mean duration of diabetes was 153 +/- 6.0 y and mean HbA1c 8.0 +/- 1.1%. The prevalenc of DR was not significantly influenced by genders (p = 0.52), smoking habits (p = 0.125), monitoring of blood glucose (p = 0.812), dyslipidemia (p = 0.435), and obesity. However, patients with DR were significantly older than those without DR (p < 0.001), had a longer duration of diabetes (p < 0.001), and higher systolic and diastolic pressures (p < 0.001 and p = 0.01 respectively). The presence of nephropathy was directly correlated with DR (p < 0.001). Finally, the parents' region of origin and educational level were significant risk factors for the presence of DR (p = 0.05 and p < 0.001 respectively). The prevalence of DR in young type I diabetic patients followed in the CCC in Lebanon is relatively low and comparable to that published worldwide, with a decrease during the last 25 years, due to a multidisciplinary approach and a centralized control of risk factors.

CMV infection after transplant from cord blood compared to other alternative donors: the importance of donor-negative CMV serostatus.

PubMed

Mikulska, Małgorzata; Raiola, Anna Maria; Bruzzi, Paolo; Varaldo, Riccardo; Annunziata, Silvana; Lamparelli, Teresa; Frassoni, Francesco; Tedone, Elisabetta; Galano, Barbara; Bacigalupo, Andrea; Viscoli, Claudio

2012-01-01

Cytomegalovirus (CMV) infection and disease are important complications after hematopoietic stem cell transplant, particularly after transplant from alternative donors. Allogeneic cord blood transplantation (CBT) is being increasingly used, but immune recovery may be delayed. The aim of this study was to compare CMV infection in CBT with transplants from unrelated or mismatched related donors, from now on defined as alternative donors. A total of 165 consecutive transplants were divided in 2 groups: (1) alternative donors transplants (n = 85) and (2) CBT recipients (n = 80). Donor and recipient (D/R) CMV serostatus were recorded. The incidence of CMV infection, its severity, timing, and outcome were compared. Median follow-up was 257 days (1-1328). CMV infection was monitored by CMV antigenemia and expressed as CMV Ag positive cell/2 × 10(5) polymorphonuclear blood cells. There was a trend toward a higher cumulative incidence of CMV infection among CBT than alternative donor transplant recipients (64% vs 51%, P = .12). The median time to CMV reactivation was 35 days, and was comparable in the 2 groups (P = .8). The maximum number of CMV-positive cells was similar in the 2 groups (11 versus 16, P = .2). The time interval between the first and the last positive CMV antigenemia was almost 4 times longer in CBT compared with alternative donor transplants (109 vs 29 days, respectively, P = .008). The incidence of late CMV infection was also higher in CBT (62% vs 24%, P < .001). The incidence of early and late CMV infection in CBT was similar to D-/R+ alternative transplants, and higher than in D+/R+ alternative transplants: early infection, 72% in CBT versus 69% in D-/R+ alternative versus 55% in D+/R+ alternative (P = .21); and late infection, 67% in CBT versus 60% in D-/R+ alternative versus 7% in D+/R+ alternative (P < .001). Transplant-related mortality and overall survival were similar between the groups: 34% versus 36% (P = .6) and 54% versus 46% (P = .3) for alternative transplant and CBT, respectively. Longer duration and higher incidence of late CMV infection was seen in CBT patients, when compared with alternative donor transplants, whereas no difference in mortality was observed. The duration and incidence of late CMV infection were similar when D-/R+ CBT were compared with D-/R+ alternative donor transplants. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Development of Diagnostic Biomarkers for Detecting Diabetic Retinopathy at Early Stages Using Quantitative Proteomics

PubMed Central

Min, Hophil; Kim, Sang Jin; Oh, Sohee; Kim, Kyunggon; Yu, Hyeong Gon; Park, Taesung; Kim, Youngsoo

2016-01-01

Diabetic retinopathy (DR) is a common microvascular complication caused by diabetes mellitus (DM) and is a leading cause of vision impairment and loss among adults. Here, we performed a comprehensive proteomic analysis to discover biomarkers for DR. First, to identify biomarker candidates that are specifically expressed in human vitreous, we performed data-mining on both previously published DR-related studies and our experimental data; 96 proteins were then selected. To confirm and validate the selected biomarker candidates, candidates were selected, confirmed, and validated using plasma from diabetic patients without DR (No DR) and diabetics with mild or moderate nonproliferative diabetic retinopathy (Mi or Mo NPDR) using semiquantitative multiple reaction monitoring (SQ-MRM) and stable-isotope dilution multiple reaction monitoring (SID-MRM). Additionally, we performed a multiplex assay using 15 biomarker candidates identified in the SID-MRM analysis, which resulted in merged AUC values of 0.99 (No DR versus Mo NPDR) and 0.93 (No DR versus Mi and Mo NPDR). Although further validation with a larger sample size is needed, the 4-protein marker panel (APO4, C7, CLU, and ITIH2) could represent a useful multibiomarker model for detecting the early stages of DR. PMID:26665153

The Effect of Bariatric Surgery on Diabetic Retinopathy: Good, Bad, or Both?

PubMed

Gorman, Dora M; le Roux, Carel W; Docherty, Neil G

2016-10-01

Bariatric surgery, initially intended as a weight-loss procedure, is superior to standard lifestyle intervention and pharmacological therapy for type 2 diabetes in obese individuals. Intensive medical management of hyperglycemia is associated with improved microvascular outcomes. Whether or not the reduction in hyperglycemia observed after bariatric surgery translates to improved microvascular outcomes is yet to be determined. There is substantial heterogeneity in the data relating to the impact of bariatric surgery on diabetic retinopathy (DR), the most common microvascular complication of diabetes. This review aims to collate the recent data on retinal outcomes after bariatric surgery. This comprehensive evaluation revealed that the majority of DR cases remain stable after surgery. However, risk of progression of pre-existing DR and the development of new DR is not eliminated by surgery. Instances of regression of DR are also noted. Potential risk factors for deterioration include severity of DR at the time of surgery and the magnitude of glycated hemoglobin reduction. Concerns also exist over the detrimental effects of postprandial hypoglycemia after surgery. In vivo studies evaluating the chronology of DR development and the impact of bariatric surgery could provide clarity on the situation. For now, however, the effect of bariatric surgery on DR remains inconclusive.

Death receptor 6 induces apoptosis not through type I or type II pathways, but via a unique mitochondria-dependent pathway by interacting with Bax protein.

PubMed

Zeng, Linlin; Li, Ting; Xu, Derek C; Liu, Jennifer; Mao, Guozhang; Cui, Mei-Zhen; Fu, Xueqi; Xu, Xuemin

2012-08-17

Cells undergo apoptosis through two major pathways, the extrinsic pathway (death receptor pathway) and the intrinsic pathway (the mitochondrial pathway). These two pathways can be linked by caspase-8-activated truncated Bid formation. Very recently, death receptor 6 (DR6) was shown to be involved in the neurodegeneration observed in Alzheimer disease. DR6, also known as TNFRSF21, is a relatively new member of the death receptor family, and it was found that DR6 induces apoptosis when it is overexpressed. However, how the death signal mediated by DR6 is transduced intracellularly is not known. To this end, we have examined the roles of caspases, apoptogenic mitochondrial factor cytochrome c, and the Bcl-2 family proteins in DR6-induced apoptosis. Our data demonstrated that Bax translocation is absolutely required for DR6-induced apoptosis. On the other hand, inhibition of caspase-8 and knockdown of Bid have no effect on DR6-induced apoptosis. Our results strongly suggest that DR6-induced apoptosis occurs through a new pathway that is different from the type I and type II pathways through interacting with Bax.

Final Scientific/Technical Report, DE-FG02-06ER64171, Integrated Nucleic Acid System for In-Field Monitoring of Microbial Community Dynamics and Metabolic Activity – Subproject to Co-PI Eric E. Roden

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eric E. Roden

2009-07-08

This report summarizes research conducted in conjunction with a project entitled “Integrated Nucleic Acid System for In-Field Monitoring of Microbial Community Dynamics and Metabolic Activity”, which was funded through the Integrative Studies Element of the former NABIR Program (now the Environmental Remediation Sciences Program) within the Office of Biological and Environmental Research. Dr. Darrell Chandler (originally at Argonne National Laboratory, now with Akonni Biosystems) was the overall PI/PD for the project. The overall project goals were to (1) apply a model iron-reducer and sulfate-reducer microarray and instrumentation systems to sediment and groundwater samples from the Scheibe et al. FRC Areamore » 2 field site, UMTRA sediments, and other DOE contaminated sites; (2) continue development and expansion of a 16S rRNA/rDNA¬-targeted probe suite for microbial community dynamics as new sequences are obtained from DOE-relevant sites; and (3) address the fundamental molecular biology and analytical chemistry associated with the extraction, purification and analysis of functional genes and mRNA in environmental samples. Work on the UW subproject focused on conducting detailed batch and semicontinuous culture reactor experiments with uranium-contaminated FRC Area 2 sediment. The reactor experiments were designed to provide coherent geochemical and microbiological data in support of microarray analyses of microbial communities in Area 2 sediments undergoing biostimulation with ethanol. A total of four major experiments were conducted (one batch and three semicontinuous culture), three of which (the batch and two semicontinuous culture) provided samples for DNA microarray analysis. A variety of other molecular analyses (clone libraries, 16S PhyloChip, RT-PCR, and T-RFLP) were conducted on parallel samples from the various experiments in order to provide independent information on microbial community response to biostimulation.« less

Genomics, molecular imaging, bioinformatics, and bio-nano-info integration are synergistic components of translational medicine and personalized healthcare research.

PubMed

Yang, Jack Y; Yang, Mary Qu; Arabnia, Hamid R; Deng, Youping

2008-09-16

Supported by National Science Foundation (NSF), International Society of Intelligent Biological Medicine (ISIBM), International Journal of Computational Biology and Drug Design and International Journal of Functional Informatics and Personalized Medicine, IEEE 7th Bioinformatics and Bioengineering attracted more than 600 papers and 500 researchers and medical doctors. It was the only synergistic inter/multidisciplinary IEEE conference with 24 Keynote Lectures, 7 Tutorials, 5 Cutting-Edge Research Workshops and 32 Scientific Sessions including 11 Special Research Interest Sessions that were designed dynamically at Harvard in response to the current research trends and advances. The committee was very grateful for the IEEE Plenary Keynote Lectures given by: Dr. A. Keith Dunker (Indiana), Dr. Jun Liu (Harvard), Dr. Brian Athey (Michigan), Dr. Mark Borodovsky (Georgia Tech and President of ISIBM), Dr. Hamid Arabnia (Georgia and Vice-President of ISIBM), Dr. Ruzena Bajcsy (Berkeley and Member of United States National Academy of Engineering and Member of United States Institute of Medicine of the National Academies), Dr. Mary Yang (United States National Institutes of Health and Oak Ridge, DOE), Dr. Chih-Ming Ho (UCLA and Member of United States National Academy of Engineering and Academician of Academia Sinica), Dr. Andy Baxevanis (United States National Institutes of Health), Dr. Arif Ghafoor (Purdue), Dr. John Quackenbush (Harvard), Dr. Eric Jakobsson (UIUC), Dr. Vladimir Uversky (Indiana), Dr. Laura Elnitski (United States National Institutes of Health) and other world-class scientific leaders. The Harvard meeting was a large academic event 100% full-sponsored by IEEE financially and academically. After a rigorous peer-review process, the committee selected 27 high-quality research papers from 600 submissions. The committee is grateful for contributions from keynote speakers Dr. Russ Altman (IEEE BIBM conference keynote lecturer on combining simulation and machine learning to recognize function in 4D), Dr. Mary Qu Yang (IEEE BIBM workshop keynote lecturer on new initiatives of detecting microscopic disease using machine learning and molecular biology, http://ieeexplore.ieee.org/servlet/opac?punumber=4425386) and Dr. Jack Y. Yang (IEEE BIBM workshop keynote lecturer on data mining and knowledge discovery in translational medicine) from the first IEEE Computer Society BioInformatics and BioMedicine (IEEE BIBM) international conference and workshops, November 2-4, 2007, Silicon Valley, California, USA.

Genomics, molecular imaging, bioinformatics, and bio-nano-info integration are synergistic components of translational medicine and personalized healthcare research

PubMed Central

2008-01-01

Supported by National Science Foundation (NSF), International Society of Intelligent Biological Medicine (ISIBM), International Journal of Computational Biology and Drug Design and International Journal of Functional Informatics and Personalized Medicine, IEEE 7th Bioinformatics and Bioengineering attracted more than 600 papers and 500 researchers and medical doctors. It was the only synergistic inter/multidisciplinary IEEE conference with 24 Keynote Lectures, 7 Tutorials, 5 Cutting-Edge Research Workshops and 32 Scientific Sessions including 11 Special Research Interest Sessions that were designed dynamically at Harvard in response to the current research trends and advances. The committee was very grateful for the IEEE Plenary Keynote Lectures given by: Dr. A. Keith Dunker (Indiana), Dr. Jun Liu (Harvard), Dr. Brian Athey (Michigan), Dr. Mark Borodovsky (Georgia Tech and President of ISIBM), Dr. Hamid Arabnia (Georgia and Vice-President of ISIBM), Dr. Ruzena Bajcsy (Berkeley and Member of United States National Academy of Engineering and Member of United States Institute of Medicine of the National Academies), Dr. Mary Yang (United States National Institutes of Health and Oak Ridge, DOE), Dr. Chih-Ming Ho (UCLA and Member of United States National Academy of Engineering and Academician of Academia Sinica), Dr. Andy Baxevanis (United States National Institutes of Health), Dr. Arif Ghafoor (Purdue), Dr. John Quackenbush (Harvard), Dr. Eric Jakobsson (UIUC), Dr. Vladimir Uversky (Indiana), Dr. Laura Elnitski (United States National Institutes of Health) and other world-class scientific leaders. The Harvard meeting was a large academic event 100% full-sponsored by IEEE financially and academically. After a rigorous peer-review process, the committee selected 27 high-quality research papers from 600 submissions. The committee is grateful for contributions from keynote speakers Dr. Russ Altman (IEEE BIBM conference keynote lecturer on combining simulation and machine learning to recognize function in 4D), Dr. Mary Qu Yang (IEEE BIBM workshop keynote lecturer on new initiatives of detecting microscopic disease using machine learning and molecular biology, http://ieeexplore.ieee.org/servlet/opac?punumber=4425386) and Dr. Jack Y. Yang (IEEE BIBM workshop keynote lecturer on data mining and knowledge discovery in translational medicine) from the first IEEE Computer Society BioInformatics and BioMedicine (IEEE BIBM) international conference and workshops, November 2-4, 2007, Silicon Valley, California, USA. PMID:18831773

Common variants of HNF1A gene are associated with diabetic retinopathy and poor glycemic control in normal-weight Japanese subjects with type 2 diabetes mellitus.

PubMed

Morita, Kazunori; Saruwatari, Junji; Tanaka, Takahiro; Oniki, Kentaro; Kajiwara, Ayami; Miyazaki, Hiroko; Yoshida, Akira; Jinnouchi, Hideaki; Nakagawa, Kazuko

2017-02-01

This study investigated the associations between the common hepatocyte nuclear factor-1A (HNF1A) variants and the risk of diabetic retinopathy (DR) in relation to the glycemic control and weight status. A retrospective longitudinal analysis was conducted among 354 Japanese patients with type 2 diabetes mellitus (T2DM) (mean follow-up duration: 5.8±2.5 years). The multivariable-adjusted hazard ratio (HR) for the cumulative incidence of DR was calculated using a Cox proportional hazard model. During the observation period, the longitudinal associations of the HNF1A diplotypes with the risk of DR and the clinical parameters were also analyzed using the generalized estimating equations approach. The combination of risk variants, i.e., rs1169288-C, rs1183910-A and rs2464196-A, was defined as the H1 haplotype. The incidence of DR was higher in the H1/H1 diplotype cases than in the others (HR 2.75 vs. non-H1/non-H1; p=0.02). Only in normal-weight subjects, the risks of DR and poor glycemic control were higher in the H1/H1 diplotype cases than in the others [odds ratio 4.08 vs. non-H1/non-H1, p=0.02; odds ratio 3.03, p=0.01; respectively]. This study demonstrated that the common HNF1A diplotype of three risk variants may be an independent risk factor for the development of DR resulting from poor glycemic control in normal-weight patients with T2DM. These results need to be replicated in larger and more varied study populations. Copyright © 2016 Elsevier Inc. All rights reserved.

Association between LEKR1-CCNL1 and IGSF21-KLHDC7A gene polymorphisms and diabetic retinopathy of type 2 diabetes mellitus in the Chinese Han population.

PubMed

Lin, Xiaohui; Wang, Jihong; Yun, Lixia; Jiang, Shuhong; Li, Langen; Chen, Xiaohai; Li, Zhen; Lu, Qiang; Zhang, Yihui; Ma, Xiaocheng

2016-10-01

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes. The present study aimed to identify a possible connection between gene polymorphisms and the risk of developing DR. A total of 319 patients with type 2 diabetes mellitus (T2DM) were selected. All patients underwent a complete eye examination. Based on this, the patients with T2DM were divided into two subgroups: 175 patients with retinopathy (DR) and 144 patients without retinopathy (NDR). We calculated the genotype frequencies of case and control subjects using the chi-squares test. The odds ratio (OR) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusted for age and sex. The finding by analysis is that the mean of duration of diabetes, total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), glomerular filtration rate and C-peptide were significantly different between DR and NDR. We found significant differences in cystatin-C concentrations with LEKR1-CCNL1 rs13064954 and NOS3 rs3918227 of different genotypes. Significant differences in serum TG levels were seen among the three genotypes of MTHFR rs1537516. Subjects carried the T allele of IGSF21-KLHDC7A rs3007729 had higher serum LDL concentrations (p = 0.015). In the allele model, LEKR1-CCNL1 rs13064954 decreased the risk of DR (OR =0.57, 95% CI = 0.34-0.96, p = 0.032). Under the dominant model, the IGSF21-KLHDC7A rs3007729 CT-TT genotype increased the risk of DR (OR =1.84, 95% CI = 1.14-2.99, p = 0.013). Our results suggest that LEKR1-CCNL1 and IGSF21-KLHDC7A influence the development of DR. Copyright © 2016 John Wiley & Sons, Ltd.

Regular three-dimensional presentations improve in the identification of surgical liver anatomy - a randomized study.

PubMed

Müller-Stich, Beat P; Löb, Nicole; Wald, Diana; Bruckner, Thomas; Meinzer, Hans-Peter; Kadmon, Martina; Büchler, Markus W; Fischer, Lars

2013-09-25

Three-dimensional (3D) presentations enhance the understanding of complex anatomical structures. However, it has been shown that two dimensional (2D) "key views" of anatomical structures may suffice in order to improve spatial understanding. The impact of real 3D images (3Dr) visible only with 3D glasses has not been examined yet. Contrary to 3Dr, regular 3D images apply techniques such as shadows and different grades of transparency to create the impression of 3D.This randomized study aimed to define the impact of both the addition of key views to CT images (2D+) and the use of 3Dr on the identification of liver anatomy in comparison with regular 3D presentations (3D). A computer-based teaching module (TM) was used. Medical students were randomized to three groups (2D+ or 3Dr or 3D) and asked to answer 11 anatomical questions and 4 evaluative questions. Both 3D groups had animated models of the human liver available to them which could be moved in all directions. 156 medical students (57.7% female) participated in this randomized trial. Students exposed to 3Dr and 3D performed significantly better than those exposed to 2D+ (p < 0.01, ANOVA). There were no significant differences between 3D and 3Dr and no significant gender differences (p > 0.1, t-test). Students randomized to 3D and 3Dr not only had significantly better results, but they also were significantly faster in answering the 11 anatomical questions when compared to students randomized to 2D+ (p < 0.03, ANOVA). Whether or not "key views" were used had no significant impact on the number of correct answers (p > 0.3, t-test). This randomized trial confirms that regular 3D visualization improve the identification of liver anatomy.

A Center for Advanced Electrical and Structural Polymers

DTIC Science & Technology

1988-10-31

REPORT I 3b. TIME COVERED 14. DATE OF REPORT (Year, Month, Oay) IS. PAGE COUNT Final j FROM TO 44 16. SUPPLEMENTARY NOTATION 17. COSATI CODES 18...Banhegyi Dr. N. Easwar Dr. Z. Chai Dr. K. Liang Dr. S. Choe Dr. G. Smyth Dr. P. Cifra Dr. J . Kim Dr. W. Huh Dr. Q. Bhatia Dr. J . Grobelny Dr. P... J . Chen (WSU) Dr. G. Quin Dr. M. Sinksy (WSU) Dr. N. Segudovic Dr. R. Miller (WSU) Dr. G. Shy Dr. Y. Gur Mr. L. Wu Dr. T. Bleha Dr. A. Sikora Dr. H

Comparison of real-time instruments and gravimetric method when measuring particulate matter in a residential building.

PubMed

Wang, Zuocheng; Calderón, Leonardo; Patton, Allison P; Sorensen Allacci, MaryAnn; Senick, Jennifer; Wener, Richard; Andrews, Clinton J; Mainelis, Gediminas

2016-11-01

This study used several real-time and filter-based aerosol instruments to measure PM 2.5 levels in a high-rise residential green building in the Northeastern US and compared performance of those instruments. PM 2.5 24-hr average concentrations were determined using a Personal Modular Impactor (PMI) with 2.5 µm cut (SKC Inc., Eighty Four, PA) and a direct reading pDR-1500 (Thermo Scientific, Franklin, MA) as well as its filter. 1-hr average PM 2.5 concentrations were measured in the same apartments with an Aerotrak Optical Particle Counter (OPC) (model 8220, TSI, Inc., Shoreview, MN) and a DustTrak DRX mass monitor (model 8534, TSI, Inc., Shoreview, MN). OPC and DRX measurements were compared with concurrent 1-hr mass concentration from the pDR-1500. The pDR-1500 direct reading showed approximately 40% higher particle mass concentration compared to its own filter (n = 41), and 25% higher PM 2.5 mass concentration compared to the PMI 2.5 filter. The pDR-1500 direct reading and PMI 2.5 in non-smoking homes (self-reported) were not significantly different (n = 10, R 2 = 0.937), while the difference between measurements for smoking homes was 44% (n = 31, R 2 = 0.773). Both OPC and DRX data had substantial and significant systematic and proportional biases compared with pDR-1500 readings. However, these methods were highly correlated: R 2 = 0.936 for OPC versus pDR-1500 reading and R 2 = 0.863 for DRX versus pDR-1500 reading. The data suggest that accuracy of aerosol mass concentrations from direct-reading instruments in indoor environments depends on the instrument, and that correction factors can be used to reduce biases of these real-time monitors in residential green buildings with similar aerosol properties. This study used several real-time and filter-based aerosol instruments to measure PM 2.5 levels in a high-rise residential green building in the northeastern United States and compared performance of those instruments. The data show that while the use of real-time monitors is convenient for measurement of airborne PM at short time scales, the accuracy of those monitors depends on a particular instrument. Bias correction factors identified in this paper could provide guidance for other studies using direct-reading instruments to measure PM concentrations.

Associations of anti-beta2-glycoprotein I autoantibodies with HLA class II alleles in three ethnic groups.

PubMed

Arnett, F C; Thiagarajan, P; Ahn, C; Reveille, J D

1999-02-01

To determine any HLA associations with anti-beta2-glycoprotein I (anti-beta2GPI) antibodies in a large, retrospectively studied, multiethnic group of 262 patients with primary antiphospholipid antibody syndrome (APS), systemic lupus erythematosus (SLE), or another connective tissue disease. Anti-beta2GPI antibodies were detected in sera using an enzyme-linked immunosorbent assay. HLA class II alleles (DRB1, DQA1, and DQB1) were determined by DNA oligotyping. The HLA-DQB1*0302 (DQ8) allele, typically carried on HLA-DR4 haplotypes, was associated with anti-beta2GPI when compared with both anti-beta2GPI-negative SLE patients and ethnically matched normal controls, especially in Mexican Americans and, to a lesser extent, in whites. Similarly, when ethnic groups were combined, HLA-DQB1*0302, as well as HLA-DQB1*03 alleles overall (DQB1*0301, *0302, and *0303), were strongly correlated with anti-beta2GPI antibodies. The HLA-DR6 (DR13) haplotype DRB1*1302; DQB1*0604/5 was also significantly increased, primarily in blacks. HLA-DR7 was not significantly increased in any of these 3 ethnic groups, and HLA-DR53 (DRB4*0101) was increased in Mexican Americans only. Certain HLA class II haplotypes genetically influence the expression of antibodies to beta2GPI, an important autoimmune response in the APS, but there are variations in HLA associations among different ethnic groups.

Soft Soil Tire Model Development and Experimental Testing

DTIC Science & Technology

2012-09-01

Sandu 1 , Mr. Eduardo Pinto 2 , Mr. Scott Naranjo 3 , Dr. Paramsothy Jayakumar 4 , Dr. Brant Ross 5 1Virginia Tech, 2Virginia Tech, 3Virginia Tech...W56HZV-04-2-0001 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Corina Sandu; Eduardo Pinto; Scott Naranjo; Paramsothy Jayakumar ; Brant Ross

Engineered Deinococcus radiodurans R1 with NiCoT genes for bioremoval of trace cobalt from spent decontamination solutions of nuclear power reactors.

PubMed

Gogada, Raghu; Singh, Surya Satyanarayana; Lunavat, Shanti Kumari; Pamarthi, Maruthi Mohan; Rodrigue, Agnes; Vadivelu, Balaji; Phanithi, Prakash-Babu; Gopala, Venkateswaran; Apte, Shree Kumar

2015-11-01

The aim of the present work was to engineer bacteria for the removal of Co in contaminated effluents. Radioactive cobalt ((60)Co) is known as a major contributor for person-sievert budgetary because of its long half-life and high γ-energy values. Some bacterial Ni/Co transporter (NiCoT) genes were described to have preferential uptake for cobalt. In this study, the NiCoT genes nxiA and nvoA from Rhodopseudomonas palustris CGA009 (RP) and Novosphingobium aromaticivorans F-199 (NA), respectively, were cloned under the control of the groESL promoter. These genes were expressed in Deinococcus radiodurans in reason of its high resistance to radiation as compared to other bacterial strains. Using qualitative real time-PCR, we showed that the expression of NiCoT-RP and NiCoT-NA is induced by cobalt and nickel. The functional expression of these genes in bioengineered D. radiodurans R1 strains resulted in >60 % removal of (60)Co (≥5.1 nM) within 90 min from simulated spent decontamination solution containing 8.5 nM of Co, even in the presence of >10 mM of Fe, Cr, and Ni. D. radiodurans R1 (DR-RP and DR-NA) showed superior survival to recombinant E. coli (ARY023) expressing NiCoT-RP and NA and efficiency in Co remediation up to 6.4 kGy. Thus, the present study reports a remarkable reduction in biomass requirements (2 kg) compared to previous studies using wild-type bacteria (50 kg) or ion-exchanger resins (8000 kg) for treatment of ~10(5)-l spent decontamination solutions (SDS).

Expression of Angiogenic MicroRNAs in Endothelial Progenitor Cells From Type 1 Diabetic Patients With and Without Diabetic Retinopathy.

PubMed

García de la Torre, Nuria; Fernández-Durango, Raquel; Gómez, Raquel; Fuentes, Manuel; Roldán-Pallarés, Manuela; Donate, Juan; Barabash, Ana; Alonso, Bárbara; Runkle, Isabelle; Durán, Alejandra; Rubio, Miguel Angel; Calle-Pascual, Alfonso L

2015-06-01

MicroRNA (miR) expression in endothelial progenitor cells (EPCs) in type 1 diabetes (DM1) and its relation with different stages of diabetic retinopathy (DR) have not been reported to date. Our aim was to analyze miR-222, miR-221, and miR-126 expression in EPCs from DM1 patients with and without DR. We included 41 patients with DR, 35 without DR, and 38 controls. Blood was collected for flow cytometry and EPC culture. Total RNA was extracted and purified and real-time quantitative PCR was performed for miR expression in cultured EPCs. Relative changes in miR expression were analyzed with the 2-ΔΔCT method. Circulating EPCs were reduced and miR-126 expression was increased in DM1 compared to controls (0.030 [interquartile range [IQR], 0.020-0.050] vs. 0.060 [IQR, 0.030-0.110], P = 0.004; 1.740 [IQR, 0.890-4.120] vs. 0.990 [IQR, 0.487-3.015], P = 0.047 respectively) without differences between patients with and without DR. Patients with DR had higher expression of miR-221 than those without DR (1.405 [IQR, 0.820-2.867] vs. 0.915 [IQR, 0.507-1.292], P = 0.019) without differences among degrees of DR. Circulating EPCs were reduced in patients on statins (0.010 [IQR, 0.010-0.050] vs. 0.045 [IQR, 0.020-0.087], P = 0.008), and miR-221 expression increased in patients on angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blocker (ARB) II (1.430 [IQR, 1.160-2.705] vs. 1.000 [IQR, 0.520-1.330], P = 0.021) compared to those without treatment. MicroRNA-126 expression was associated with body mass index (BMI; ρ = -0.267, P = 0.026) and diastolic blood pressure (ρ = -0.267, P = 0.034). MicroRNA-221 was associated with triglyceride concentration (ρ = 0.296, P = 0.012). Circulating EPCs were reduced and miR-126 expression was increased in DM1 compared to controls. Patients with DR had higher expression of miR-221 than those without DR. The identification of biomarkers of diabetic complications might be useful for monitoring disease progression and potential therapeutic targets.

The Relationship of Retinal Vessel Geometric Characteristics to the Incidence and Progression of Diabetic Retinopathy.

PubMed

Klein, Ronald; Lee, Kristine E; Danforth, Lorraine; Tsai, Michael Y; Gangnon, Ronald E; Meuer, Stacy E; Wong, Tien Y; Cheung, Carol Y; Klein, Barbara E K

2018-05-17

To examine the relationships of retinal vessel geometric characteristics (RVGCs) to the incidence and progression of diabetic retinopathy (DR). Observational, prospective cohort study. Nine hundred ninety-six persons with type 1 diabetes mellitus (T1DM) and 1370 persons with type 2 diabetes mellitus (T2DM) seen at a baseline examination who were eligible for follow-up examinations at subsequent 5-year intervals. A total of 3846 person-interval data from these follow-up examinations are the basis for the analyses. Diabetic retinopathy and macular edema were assessed by grading of 30° stereoscopic color fundus photographs. Retinal vessel geometric characteristics were assessed using the Singapore I Vessel Assessment program from a digitized copy of 1 of the field 1 fundus photographs obtained at baseline and follow-up. The 5-year incidence of any DR, progression of DR, and incidence of proliferative diabetic retinopathy (PDR) and clinically significant macular edema (CSME) in right eyes. Incident DR occurred in 45%, progression in 32%, PDR in 10%, and CSME in 5%. While adjusting for glycated hemoglobin, duration of diabetes, and other factors, retinal arteriolar simple tortuosity was associated significantly with the incidence of any DR (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.01-1.35). Retinal venular branching angle was associated significantly with progression of DR (OR, 1.18; 95% CI, 1.03-1.36), retinal venular curvature tortuosity was associated significantly with the incidence of PDR (OR, 1.15; 95% CI, 1.01-1.30), and retinal venular branching angle (OR, 1.41; 95% CI, 1.10-1.82) was associated significantly with the incidence of CSME. There were no significant associations of other RVGCs with any of the DR outcomes in the full multivariate model. Inclusion of all possible RVGCs did not improve the predictive value of the models that already included retinal vessel diameter and baseline DR severity level. Retinal vessel geometric characteristics of the retinal venules were associated with progression of DR; however, most of the RVGCs measured from digitized fundus photographs added little to the assessment of risk of incidence and progression of DR when other risk factors were considered in T1DM and T2DM. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Nanoscience and Technology at the Air Force Research Laboratory (AFRL)

DTIC Science & Technology

2005-05-01

AIR FORCE RESEARCH LABORATORY ( AFRL ) Dr. Richard A. Vaia Dr. Daniel Miracle Dr. Thomas Cruse Air Force Research ...Technology At The Air Force Research Laboratory ( AFRL ) 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...98) Prescribed by ANSI Std Z39-18 AFRL NST Overview 2 AIR FORCE RESEARCH LABORATORY VISION We defend

Nanoscience and Technology at the Air Force Research Laboratory (AFRL)

DTIC Science & Technology

2005-02-01

AIR FORCE RESEARCH LABORATORY ( AFRL ) Dr. Richard A. Vaia Dr. Daniel Miracle Dr. Thomas Cruse Air Force Research ...Technology At The Air Force Research Laboratory ( AFRL ) 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...98) Prescribed by ANSI Std Z39-18 AFRL NST Overview 2 AIR FORCE RESEARCH LABORATORY VISION We defend

Impact of The Protective Renin-Angiotensin System (RAS) on The Vasoreparative Function of CD34+ CACs in Diabetic Retinopathy

NASA Technical Reports Server (NTRS)

Duan, Yaqian; Moldovan, Leni; Miller, Rehae C.; Beli, Eleni; Salazar, Tatiana; Hazra, Sugata; Al-Sabah, Jude; Chalam, KV; Raghunandan, Sneha; Vyas, Ruchi;

Doppler transcranien au cours de la drépanocytose chez l'enfant Malagasy

PubMed Central

Herinirina, Nicolas Fanantenana; Rajaonarison, Lova Hasina Ny Ony Narindra; Herijoelison, Andry Roussel; Rakoto, Olivat Aimée Alson; Ahmad, Ahmad

2016-01-01

Introduction Le doppler transcrânien est un outil efficace permettant de dépister les enfants drépanocytaires à risque d'AVC. Méthodes Nous avons réalisé une étude descriptive transversale sur des enfants Malagasy âgés entre 24 mois et 15 ans (groupe 1: 57 drépanocytaires, groupe 2: 43 témoins) afin d’évaluer le profil vélocimétrique des artères cérébrales chez les drépanocytaires. Un examen Doppler transcrânien a été réalisé avec étude des flux sanguins cérébraux chez les enfants des deux groupes. Résultats Pour les sujets drépanocytaires, la vitesse moyenne (VM) de l'artère cérébrale moyenne était de 100,9 ± 26,8 cm/s, l'indice de pulsatilité (IP) de 0,73 ± 0,20, la différence entre les artères cérébrales moyennes droite et gauche (ACMr) de 19,8 ± 21,5 cm/s, le rapport des vitesses de l'artère cérébrale antérieure/artère cérébrale moyenne (ACA/ACM) de 0,7 ± 0,2. Pour les enfants non drépanocytaires, VM: 80,6 ± 19,3 cm/s, IP: 0,79 ± 0,14, ACMr: 17 ± 20,1 cm/s, ACA/ACM: 0,8 ± 0,2. La vélocité des enfants drépanocytaires était supérieure au groupe contrôle. Les vitesses ont été corrélées avec le taux d'hémoglobine et l’âge et non pas avec le sexe et le volume globulaire moyen. Conclusion Les vitesses circulatoires cérébrales sont élevées chez les drépanocytaires que les enfants non drépanocytaires et sont influencées par le taux d'hémoglobine et l’âge. PMID:27516829

Fuzhengpaidu granule regulates immune activation molecules CD38 and human leukocyte antigen-D related on CD4+ and CD8+ T cells in patients with acquired immunodeficiency syndrome/human immunodeficiency virus.

PubMed

Jiang, Feng; Zhang, Rongxin; Gu, Zhenfang; Zhang, Huailing; Guo, Huijun; Deng, Xin; Liang, Jian

2013-08-01

To evaluate the effect of Fuzhengpaidu granule (FZPDG) on immune activation molecules CD38 and human leukocyte antigen-D related (HLA-DR) on CD4+ and CD8+ cells in HIV/AIDS patients, and to explore the underlying mechanism of this therapy. Plasma changes in CD3+, CD4+, CD8+, CD3 + CD4 + CD38 +, CD3 + CD4 + HLA-DR+, CD3 + CD8+CD38+, and CD3+CD8+HLA-DR+ levels in HIV/ AIDS patients treated with FZPDG for six months were examined by flow cytometry and compared with levels in healthy controls. The clinical trial included 34 outpatients with HIV/AIDS. Before treatment, plasma levels of CD38+ and HLA-DR+ on CD4/CD8 cells were higher than those in 28 health controls (P < 0.05). There were no significant changes in serum levels of CD3+, CD4+, and CD8+ T cells between pretreatment baseline versus after treatment, which were 82.85% +/- 5.41%, 14.57% +/- 10.31% and 54.55% +/- 11.43% before treatment and 79.15% +/- 8.21%, 19.96% +/- 9.58% and 56.36% +/- 11.67% after treatment, respectively (P > 0.05). Plasma levels of CD3+ CD4+CD38+ and CD3+CD4+HLA-DR+ were 2.3% +/-2.2% and 7.8% +/- 5.5% before treatment and 1.2% +/-0.8% and 2.6% +/- 1.0% after treatment, respectively. Plasma levels of CD3+CD8+CD38+ and CD3+CD8+ HLA-DR+ were 41.4% +/- 13.4% and 17.8% +/- 11.3% before treatment, which changed to 27.1% +/- 10.2% and 3.8% +/- 2.4% after treatment, respectively (P < 0.05). HIV/AIDS patients exhibited an immune activation profile following FZPDG treatment. A potential mechanism of action for FZPDG appears to lie in its ability to up-regulate CD38 and HLA-DR levels on CD4+ T cells, and down-regulate them on CD8+ cells, thereby modulating immune activation of CD4+and CD8+T cells.

Dr Michaels® product family (also branded as Soratinex®) versus Methylprednisolone aceponate - a comparative study of the effectiveness for the treatment of plaque psoriasis.

PubMed

Hercogovấ, J; Fioranelli, M; Gianfaldoni, S; Chokoeva, A A; Tchernev, G; Wollina, U; Tirant, M; Novotny, F; Roccia, M G; Maximov, G K; França, K; Lotti, T

2016-01-01

As one of the most common dermatologic chronic-recurrent disease, variable therapeutic options are available today for management of psoriasis. Although topical high potency corticosteroids, alone or in association with salicylic acid or vitamin D analogues, are still considered the best treatment, they do not seem to possess the capability for a long-term control of the disease or prevent recurrences, as their side effects are major contraindications for continuative use. The aim of this study was to investigate whether Dr. Michaels® product family is comparable to methylprednisolone aceponate (MPA) as a viable alternative treatment option for the treatment and management of stable chronic plaque psoriasis. Thirty adults (13 male, 17 female, mean age 40 years) with mild to severe stable chronic plaque psoriasis, were included in the study. Patients were advised to treat the lesions of the two sides of their body (left and right) with two different unknown modalities for 8 weeks; the pack of Dr. Michaels® products on the left side (consisting of a cleansing gel, an ointment and a skin conditioner) and a placebo pack on the right side, consisting of a cleansing gel, methylprednisolone ointment and a placebo conditioner. Assessment was done using the Psoriasis Activity Severity Index (PASI) scores before treatment and after 2, 4, 6 and 8 weeks. The results achieved with the Dr. Michaels® (Soratinex®) product family for the treatment of chronic plaque psoriasis were better than the results achieved with methylprednisolone aceponate (MPA), even though quicker resolution was achieved with the steroid with 45% of patients achieving resolution within 8-10 days in comparison to 5-6 weeks in the Dr. Michaels® (Soratinex®) group. Before therapy, the mean PASI score of the LHS in Dr. Michaels® (Soratinex®) group was 13.8±4.1 SD and 14.2±4.2 SD in the RHS methylprednisolone aceponate (MPA) group. After 8 weeks of treatment 62% of the Dr. Michaels® (Soratinex®) group had achieved resolution whilst in the methylprednisolone aceponate (MPA) group, the figure remained at 45%. The mean PASI score after 8 weeks of treatment was calculated and in the LHS Dr. Michaels® (Soratinex®) group it was 2.8±1.6 SD and 6.8±2.4 SD in the RHS methylprednisolone aceponate group. In the RHS -methylprednisolone aceponate (MPA) group, 22% of patients failed to respond to the treatment in comparison to 6% in the LHS Dr. Michaels® (Soratinex®) group. Based on the results of this study, Dr. Michaels® products are a more effective treatment option, with insignificant side effects, compared to local treatment with methylprednisolone aceponate (MPA).

A High Frequency Inverse Scattering Model to Recover the Specular Point Curvature from Polarimetric Scattering Data.

DTIC Science & Technology

1982-05-21

MAY A2 B FO0 N00014-80-C0708 UNCLASSIFIED EMID-CL-1982-05-21-Ol NL12fflllllfl I Eh|hEEEE| h |hEE EEEE|hEEEEE|hI EEllllEEEEEEEE EEEEmnhEmhEEEE m|hEE...hEE| h |hE EEEEEEEEEEnllI COMMUNICATN LABORATOR Y Oeprtment of information E ngineering University of Illinois at Chicago Circle Box 4348. Chicago IL...Recommendation concurred irDr. Wolfpan-M. Boornor AA4 -’, : Dr. Bruc H ..M ~ ri kC m it- Dr. Wai-Kai Chen on Dr. Piergiorgio L. E. Uslengh

Synthesis of 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone as a candidate anticancer against cervical (WiDr), colon (HeLa), and breast (T47d) cancer cell lines in vitro

NASA Astrophysics Data System (ADS)

Matsjeh, Sabirin; Swasono, Respati Tri; Anwar, Chairil; Solikhah, Eti Nurwening; Lestari, Endang

2017-03-01

The compound 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone have been synthesized through Claisen-Schmidt reaction from 2-hydroxyacetophenone and 2,4-dihydroxyacetophenone with 4-hydroxy-3-methoxy benzaldehida (vanillin) in aqueous KOH 40% and KSF montmorillonite as catalyst in methanol. All these products were characterized by FT-IR, TLC Scanner, GC-MS, MS-Direct, and 1H-NMR and 13C-NMR spectrometer. Both of these compounds were tested citotoxycity activity as an anticancer against cervical, colon, and breast cancer cells (Hela, WiDr, and T47D cell lines) using MTT assay in vitro. Dose series given test solution concentration on Hela, WiDr, and T47D cells started from 6,25; 25; 50 and 100 µg/mL with incubation treatment for 24 hours. The result of study showed that the 2',4-dihydroxy-3-methoxychalcone as bright yellow crystal with the melting point of 114-115 °C and the yield of 13.77% and the 2',4',4-trihydroxy-3-methoxychalcone as bright yellow crystals with the melting point of 195-197 °C and the yield of 6%. Other 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone also exhibited cytotoxic activity against the cancer cell lines, with the 2',4',4-trihydroxy-3-methoxychalcone showed greater activities than the 2',4-dihydroxy-3-methoxychalcone in WiDr cell lines. The 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone exhibited strong anticancer activities with IC50 value below 20 µg/mL. The activity of 2',4',4-trihydroxy-3-methoxychalcone showed the most active against Hela and WiDr cell lines with IC50 value 8.53 and 2.66 µg/mL respectively, than T47D cell lines with IC50 value 24.61 µg/mL. The test results cytotoxic of 2',4-dihydroxy-3-methoxychalcone showed the most active against Hela and WiDr cell lines with IC50 value 12.80, 19.57 µg/mL than T47D cell lines with IC50 value of 20.73 µg/mL. IC50 value indicated that 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone potential as inhibitors in Hela, WiDr and T47D cell lines.

A retrospective study on sequential desensitization-rechallenge for antituberculosis drug allergy

PubMed Central

Chia, Faith Li-Ann; Tan, Sze-Chin; Tan, Teck-Choon; Leong, Khai-Pang; Tan, Justina Wei-Lyn; Tang, Chwee-Ying; Hou, Jin-Feng; Chan, Grace Yin-Lai; Chng, Hiok-Hee

2014-01-01

Background Antituberculosis (anti-TB) drug allergy often involves multiple concurrently administered drugs which subsequently need to be reinitiated as no better alternatives exist. Objective To describe the results of tailored sequential desensitization-rechallenge (D-R) for anti-TB drug allergy. Methods Consecutive patients who had undergone D-R to anti-TB drugs between 1 September 1997 and 31 January 2012 were recruited. Following resolution of the acute reaction, anti-TB drug was restarted at 1:6,000 to 1:3 of the final daily dose (FDD), with gradual single or multiple step daily dose escalation to the FDD. Subsequent drugs were sequentially added ≥3 days later when the preceding drug was tolerated. Full blood count and liver function tests were monitored prior to addition of each new drug. Results There were 11 patients of whom 10 were male, predominantly Chinese (8 patients). Regimens comprised at least 3 drugs: isoniazid (INH), rifampicin (RIF), ethambutol (EMB), pyrazinamide (PZA), or streptomycin. All patients had nonimmediate reactions, with cutaneous eruptions, where maculopapular exanthema (MPE) was the most common (8 patients). Drug-induced hypersensitivity syndrome (DIHS) occurred in 6 patients, and Stevens Johnson syndrome (SJS) in 2 patients. D-R to INH was successful in 7/9 patients (77.8%) and to RIF/EMB/PZA/streptomycin in all. Of the 2 patients who failed INH D-R, 1 developed fever and MPE on day 3, the other MPE on day 8. D-R with INH and RIF respectively was successful in 2 patients with SJS. Among DIHS patients, 1 failed D-R with INH (fever and MPE on day 3). There were 23/25 (92%) successful D-R among the 11 patients. All patients completed TB treatment of ≥5 months' duration with no cases of drug-resistant TB. Conclusion Tailored sequential TB drug D-R is successful where no better alternative therapies are available, with careful dose escalation and close monitoring, and after a careful risk-benefit assessment. PMID:25097851

An HPLC method associated with a thermodynamic analysis to compare the binding of TRAIL and its nanovectorized form to death receptors DR4 and DR5 and their relationship to cytotoxicity.

PubMed

Guillaume, Yves Claude; Lethier, Lydie; André, Claire

2016-11-15

TRAIL is a member of the TNF family of cytokines which induces apoptosis of cancer cells via its binding to its cognate receptors, DR5 a high affinity site and DR4 a site of low affinity. Our working group has recently demonstrated that nanovectorization of TRAIL with single wall carbon nanotubes (abbreviated NPT) enhanced TRAIL affinity to the high affinity site DR5 and increased pro apoptotic potential in different human tumor cell lines. In this paper, the DR4 low affinity site was immobilized on a chromatographic support and the effect of temperature on a wide temperature range 1°C-50°C was studied to calculate the thermodynamic parameters of the binding of TRAIL and NPT to DR4 and DR5 receptors. For the first time the heat capacity changes for the different binding processes were determined. At a physiological pH (7.4) the heat capacity changes for the binding of NPT to DR4 and DR5 were respectively equal to -0.91kJ/molK and -0.28kJ/molK and those obtained for the binding of TRAIL to DR4 and DR5 were respectively equal to -1.54kJ/molK and -1.05kJ/molK. By the use of differential scanning calorimetry (DSC), a phase transition (∼12°C for DR5, ∼4°C for DR4) between a disordered (low temperature) and an ordered (high temperature) solid like state visualized in the receptor structure confirmed the temperature dependence of binding affinity enthalpy ΔH for soluble TRAIL and its nanovectorized form to its cognate receptors. In the low temperature domain, the positive ΔH values contribute non-favourably to the free energy of binding, TRAIL and NPT described similar affinities for DR4 and DR5. For the high temperature domain, negative ΔH values indicated that van der Waals interactions and hydrogen bonding are engaged favourably at the ligand - receptor interface. Above 30°C, their rank-ordered affinities were thus strongly different in the sequence: TRAIL DR4

Single nucleotide polymorphisms in the Trx2/TXNIP and TrxR2 genes of the mitochondrial thioredoxin antioxidant system and the risk of diabetic retinopathy in patients with Type 2 diabetes mellitus.

PubMed

Ramus, Sara Mankoc; Cilensek, Ines; Petrovic, Mojca Globocnik; Soucek, Miroslav; Kruzliak, Peter; Petrovic, Daniel

2016-03-01

Oxidative stress plays an important role in the pathogenesis of diabetes and its complications. The aim of this study was to examine the possible association between seven single nucleotide polymorphisms (SNPs) of the Trx2/TXNIP and TrxR2 genes encoding proteins involved in the thioredoxin antioxidant defence system and the risk of diabetic retinopthy (DR). Cross-sectional case-control study. A total of 802 Slovenian patients with Type 2 diabetes mellitus; 277 patients with DR and 525 with no DR were enrolled. Patients genotypes of the SNPs; including rs8140110, rs7211, rs7212, rs4755, rs1548357, rs4485648 and rs5748469 were determined by the competitive allele specific PCR method. Each genotype of examined SNPs was regressed in a logistic model, assuming the co-dominant, dominant and the recessive models of inheritance with covariates of duration of diabetes, HbA1c, insulin therapy, total cholesterol and LDL cholesterol levels. In the present study, for the first time we identified an association between the rs4485648 polymorphism of the TrxR2 gene and DR in Caucasians with Type 2 DM. The estimated ORs of adjusted logistic regression models were found to be as follows: 4.4 for CT heterozygotes, 4.3 for TT homozygotes (co-dominant genetic model) and 4.4 for CT+TT genotypes (dominant genetic model). In our case-control study we were not able to demonstrate any association between rs8140110, rs7211, rs7212, rs4755, rs1548357, and rs5748469 and DR, however, our findings provide evidence that the rs4485648 polymorphism of the TrxR2 gene might exert an independent effect on the development of DR. Copyright © 2016 Elsevier Inc. All rights reserved.

Anti-DR5 monoclonal antibody-mediated DTIC-loaded nanoparticles combining chemotherapy and immunotherapy for malignant melanoma: target formulation development and in vitro anticancer activity.

PubMed

Ding, Baoyue; Wu, Xin; Fan, Wei; Wu, Zhaoyong; Gao, Jing; Zhang, Wei; Ma, Lulu; Xiang, Wang; Zhu, Quangang; Liu, Jiyong; Ding, Xueying; Gao, Shen

2011-01-01

The increased incidence of malignant melanoma in recent decades, along with its high mortality rate and pronounced resistance to therapy pose an enormous challenge. Novel therapeutic strategies, such as immunotherapy and targeted therapy, are urgently needed for melanoma. In this study, a new active targeting drug delivery system was constructed to combine chemotherapy and active specific immunotherapy. The chemotherapeutic drug, dacarbazine (DTIC), that induces apoptosis through the intrinsic pathway which typically responds to severe DNA damage, was used as a model drug to prepare DTIC-loaded polylactic acid (PLA) nanoparticles (DTIC-NPs), which were covalently conjugated to a highly specific targeting functional TRAIL-receptor 2 (DR5) monoclonal antibody (mAb) that can contribute directly to cancer cell apoptosis or growth inhibition through the extrinsic pathway. Our in vitro experiments demonstrated that DTIC-PLA-DR5 mAb nanoparticles (DTIC-NPs-DR5 mAb) are an active targeting drug delivery system which can specifically target DR5-overexpressing malignant melanoma cells and become efficiently internalized. Most strikingly, compared with conventional DTIC-NPs, DTIC-NPs-DR5 mAb showed significantly enhanced cytotoxicity and increased cell apoptosis in DR5-positive malignant melanoma cells. The DTIC-NPs-DR5 mAb described in this paper might be a potential formulation for targeting chemotherapy and immunotherapy to DR5-overexpressing metastatic melanoma.

Diabetic Retinopathy in the Asia-Pacific.

PubMed

Chua, Jacqueline; Lim, Claire Xin Ying; Wong, Tien Yin; Sabanayagam, Charumathi

2018-01-01

Diabetic retinopathy (DR), the most common complication of diabetes mellitus, is the leading cause of new cases of blindness in middle-aged and elderly in the Asia-Pacific. It has been estimated that 51% of all those with blindness due to DR globally (n = 424,400) and 56% of those with visual impairment due to DR (2.1 million) come from the Asia-Pacific. Prevalence of DR among those with diabetes ranged from 10% in India to 43% in Indonesia within the Asia-Pacific. Awareness of DR among persons with diabetes ranged from 28% to 84%. Most common modifiable risk factors for DR in the Asia-Pacific were hyperglycemia, blood pressure, dyslipidemia, and obesity. Implementation of systematic screening programs for DR and advancement in telemedicine screening methods have increased patient coverage and cost-effectiveness, though there are still numerous factors impeding screening uptake in the low-middle income regions of the Asia-Pacific. Management and treatment of DR in the Asia-Pacific is mainly limited to traditional laser retinopexy, but it is suboptimal despite new clinical approaches such as use of intravitreal anti.vascular endothelial growth factor and steroids due to limited resources. Further research and data are required to structure a more cost-effective public healthcare program and more awareness-building initiatives to increase the effectiveness of DR screening programs. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

A Gaia DR2 Confirmation that 2MASS J12074836–3900043 is a Member of the TW HYA Association

NASA Astrophysics Data System (ADS)

Gagné, Jonathan; Gonzales, Eileen C.; Faherty, Jacqueline K.

2018-05-01

We use new data from Gaia DR2 to confirm that the young L1 $\\gamma$ candidate member of the TW Hya association (TWA) is now a bona fide member with a model-dependent mass estimate of ~15 $M_{Jup}$. The ambiguous M9 $\\gamma$ candidate member 2MASS J12474428---3816464 also gets a higher Bayesian membership probability for TWA membership as a result of Gaia DR2 data and a new radial velocity measurement, but it remains unclear whether it is a true member of TWA or if it is an unrelated young interloper, because it is separated by 4.6 km/s from the locus of TWA members in UVW space.

Risk factors for diabetic retinopathy: Findings from The Andhra Pradesh Eye Disease Study

PubMed Central

Krishnaiah, Sannapaneni; Das, Taraprasad; Nirmalan, Praveen K; Shamanna, Bindiganavale R; Nutheti, Rishita; Rao, Gullapalli N; Thomas, Ravi

2007-01-01

Objective: To assess prevalence, potential risk factors and population attributable risk percentage (PAR%) for diabetic retinopathy (DR) in the Indian state of Andhra Pradesh. Methods: A population-based study, using a stratified, random, cluster, systematic sampling strategy, was conducted in the state of Andhra Pradesh in India during 1996 and 2000. Participants from 94 clusters in one urban and three rural areas representative of the population of Andhra Pradesh, underwent a detailed interview and a comprehensive dilated ocular evaluation by trained professionals. DR was defined according to the international classification and grading system. For subjects more than or equal to 30 years of age, we explored associations of DR with potential risk factors using bivariable and multivariable analyses. Population attributable risk percent was calculated using Levin’s formula. Results: Diabetic retinopathy was present in 39 of 5586 subjects, an age-gender-area-adjusted prevalence of 0.72% (95% confidence interval (CI): 0.49%–0.93%) among subjects aged ≥ 30 years old, and 0.27% (95% CI: 0.17%–0.37%) for all ages. Most of the DR was either mild (51.3%) or moderate (35.9%) non-proliferative type; one subject (2.6%) had proliferative retinopathy. Multivariable analysis showed that increasing age, adjusted odds ratio (OR); 4.04 (95% CI: 1.88–8.68), middle and upper socioeconomic status group (OR); 2.34 (95% CI: 1.16–4.73), hypertension (OR); 3.48 (95% CI: 1.50–8.11) and duration of diabetes ≥ 15 years (OR); 8.62 (95% CI: 2.63–28.29) were significantly associated with increasing risk of DR. The PAR % for hypertension was 50%; it was 10% for cigarette smokers. Conclusions: Extrapolating the prevalence of diabetic retinopathy in our sample to the Indian population suggests that there may be an estimated 2.77 million people with DR, approximately 0.07 million people with severe DR. As the population demographics change towards aging, this number is likely to increase further. Health care programs in India need to examine strategies to prevent diabetes and DR, as well as create the infrastructure required to manage this condition. PMID:19668525

Risk factors for diabetic retinopathy: Findings from The Andhra Pradesh Eye Disease Study.

PubMed

Krishnaiah, Sannapaneni; Das, Taraprasad; Nirmalan, Praveen K; Shamanna, Bindiganavale R; Nutheti, Rishita; Rao, Gullapalli N; Thomas, Ravi

2007-12-01

To assess prevalence, potential risk factors and population attributable risk percentage (PAR%) for diabetic retinopathy (DR) in the Indian state of Andhra Pradesh. A population-based study, using a stratified, random, cluster, systematic sampling strategy, was conducted in the state of Andhra Pradesh in India during 1996 and 2000. Participants from 94 clusters in one urban and three rural areas representative of the population of Andhra Pradesh, underwent a detailed interview and a comprehensive dilated ocular evaluation by trained professionals. DR was defined according to the international classification and grading system. For subjects more than or equal to 30 years of age, we explored associations of DR with potential risk factors using bivariable and multivariable analyses. Population attributable risk percent was calculated using Levin's formula. Diabetic retinopathy was present in 39 of 5586 subjects, an age-gender-area-adjusted prevalence of 0.72% (95% confidence interval (CI): 0.49%-0.93%) among subjects aged >/= 30 years old, and 0.27% (95% CI: 0.17%-0.37%) for all ages. Most of the DR was either mild (51.3%) or moderate (35.9%) non-proliferative type; one subject (2.6%) had proliferative retinopathy. Multivariable analysis showed that increasing age, adjusted odds ratio (OR); 4.04 (95% CI: 1.88-8.68), middle and upper socioeconomic status group (OR); 2.34 (95% CI: 1.16-4.73), hypertension (OR); 3.48 (95% CI: 1.50-8.11) and duration of diabetes >/= 15 years (OR); 8.62 (95% CI: 2.63-28.29) were significantly associated with increasing risk of DR. The PAR % for hypertension was 50%; it was 10% for cigarette smokers. Extrapolating the prevalence of diabetic retinopathy in our sample to the Indian population suggests that there may be an estimated 2.77 million people with DR, approximately 0.07 million people with severe DR. As the population demographics change towards aging, this number is likely to increase further. Health care programs in India need to examine strategies to prevent diabetes and DR, as well as create the infrastructure required to manage this condition.

Rapid Assessment of Avoidable Blindness and Diabetic Retinopathy in Gilan Province, Iran.

PubMed

Katibeh, Marzieh; Behboudi, Hassan; Moradian, Siamak; Alizadeh, Yousef; Beiranvand, Ramin; Sabbaghi, Hamideh; Ahmadieh, Hamid

2017-12-01

To conduct an assessment of avoidable blindness and diabetic retinopathy (DR) in Gilan, 2014. A cross-sectional population-based survey was performed on a representative sample of urban and rural individuals aged ≥50 years of the province. Blindness was defined as presenting visual acuity (PVA) <3/60 in the better eye. Moderate visual impairment (MVI) and severe visual impairment (SVI) were defined as 6/60 ≤ PVA <6/18 and 3/60 ≤ PVA <6/60 in the better eye, respectively. Diabetes mellitus (DM) was determined based on random blood sugar (RBS) levels ≥200 mg/dL or a previous diagnosis. We used the Scottish grading system to grade DR. We invited 2975 individuals from 85 clusters. Age- and sex-adjusted prevalence and 95% confidence interval (CI) of blindness, SVI, MVI, and DM in 2587 participants (response rate: 86.9%) were 1.5% (95% CI: 1.1-2.0), 1.5% (95% CI: 0.9-2.0), 11.3% (95% CI: 9.9-12.7) and 21.4% (95% CI: 19.2-23.7), respectively. The leading causes of blindness were cataract (47.1%), age-related macular degeneration (14.7%) and DR (8.8%). Cataract surgery (CS) coverage was 69.3%. The main challenges for CS were cost and unawareness. The outcome of CS was good in 66.9% of operated eyes. Any DR and/or maculopathy were observed in 25.3% (95% CI: 21.0-29.5) of subjects including 12.6% (95% CI: 9.7-15.6) sight-threatening DR. In previously known DM cases, 215 (41.7%) had never undergone an eye examination for DR. The proportion of avoidable blindness and DR is considerable in Gilan Province.

Associations between sleep duration, sleep quality and diabetic retinopathy.

PubMed

Tan, Nicholas Y Q; Chew, Merwyn; Tham, Yih-Chung; Nguyen, Quang Duc; Yasuda, Masayuki; Cheng, Ching-Yu; Wong, Tien Yin; Sabanayagam, Charumathi

2018-01-01

Abnormal durations of sleep have been associated with risk of diabetes. However, it is not clear if sleep duration is associated with diabetic retinopathy (DR). In a cross-sectional study, we included 1,231 (Malay, n = 395; Indian, n = 836) adults (mean age 64.4 ± 9.0 years, 50.4% female) with diabetes from the second visit of two independent population-based cohort studies (2011-15) in Singapore. Self-reported habitual sleep duration was categorized as short (<6 h), normal (6≤ h <8), and long (≥8 h). Questionnaires were administered to detect risk of obstructive sleep apnea (OSA), excessive daytime sleepiness, and insomnia, all of which may indicate poor quality of sleep. The associations between sleep-related characteristics with moderate DR and vision-threatening DR (VTDR) were analysed using logistic regression models adjusted for potential confounders. Prevalence of moderate DR and VTDR in the study population were 10.5% and 6.3% respectively. The mean duration of sleep was 6.4 ± 1.5 h. Compared to normal sleep duration, both short and long sleep durations were associated with moderate DR with multivariable odds ratio (95% confidence interval) of 1.73 (1.03-2.89) and 2.17 (1.28-3.66) respectively. Long sleep duration (2.37 [1.16-4.89]), high risk of OSA (2.24 [1.09-4.75]), and excessive daytime sleepiness (3.27 [1.02-10.30]) were separately associated with VTDR. Sleep duration had a U-shaped association with moderate DR; long sleep duration, excessive daytime sleepiness and high risk of OSA were positively associated with VTDR.

Are obesity and anthropometry risk factors for diabetic retinopathy? The diabetes management project.

PubMed

Dirani, Mohamed; Xie, Jing; Fenwick, Eva; Benarous, Rehab; Rees, Gwyneth; Wong, Tien Yin; Lamoureux, Ecosse L

2011-06-22

To investigate the relationship between anthropometric parameters and diabetic retinopathy (DR) in adults with diabetes. Five hundred participants with diabetes were recruited prospectively from ophthalmology clinics in Melbourne, Australia. Each underwent an eye examination, anthropometric measurements, and standardized interview-administered questionnaires, and fasting blood glucose and serum lipids were analyzed. Two-field fundus photographs were taken and graded for DR. Height; weight; body mass index (BMI); waist, hip, neck, and head circumferences; and skinfold measurements were recorded. A total of 492 patients (325 men, 66.1%) aged between 26 and 90 years (median, 65) were included in the analysis: 171 (34.8%), 187 (38.0%), and 134 (27.2%) with no DR, nonproliferative DR (NPDR), and proliferative DR (PDR), respectively. After multiple adjustments, higher BMI (odds ratio [OR], 1.06; 95% confidence interval [CI],1.01-1.11; P = 0.02) was significantly associated with any DR. Obese people were 6.5 times more likely to have PDR than were those with normal weight (OR, 6.52; 95% CI, 1.49-28.6; P = 0.013). Neck circumference (OR, 1.05; 95% CI, 1.00-1.10; P = 0.03) and waist circumference (OR, 1.12; 95% CI, 1.03-1.22; P = 0.01) were significantly associated with any DR. BMI (OR, 1.04; 95% CI, 1.00-1.08; P = 0.04) and neck circumference (OR, 1.04 95% CI, 1.01-1.08; P = 0.04) were also positively associated with increasing severity levels of DR. Persons with diabetes with higher BMI and larger neck circumference are more likely to have DR and more severe stages of DR. These data suggest that obesity is an independent risk factor for DR.

Prevalence of Diabetic Retinopathy in a Clinic Population from Puerto Rico.

PubMed

Rodriguez, Neisha M; Aguilar, Stephanie

2016-07-01

Diabetic retinopathy (DR) is a preventable or treatable cause of blindness in the adult population. The prevalence of diabetes mellitus (DM) in Puerto Ricans is the highest among Hispanics. This study evaluated the prevalence of DR in a screening program of DM subjects in a clinic system in Puerto Rico. A retrospective cross-sectional health records study of DM patients referred by primary care physicians for dilated retinal evaluation to the Inter American University of Puerto Rico School of Optometry Juana Diaz Eye Institute Clinic between 2001 and 2009 was performed. All subjects underwent a complete eye evaluation including fundus photography. Photographs were graded following the Early Treatment Diabetic Retinopathy Study protocols. A total of 411 randomly selected health records of DM subjects older than 30 years were included. The estimated prevalence of DR among all subjects is 37.7%. DR was more common in males (47.2%) than females (33.7%). The age range with higher frequency of DR is among ages 60 to 69 (34.8%) and the lowest between ages 30 and 39 (3.9%). The average number of years since initial DM diagnosis was 12.48. Probability of developing DR increases with longer duration of DM (p < 0.05). The most common stage was mild non-proliferative DR (22.6%). Our data revealed that prevalence of DR was high among Puerto Ricans. Mild stage retinopathy was most prevalent and there exists an increase in probability to develop DR with duration of DM. The prevalence of DR in total population may be different than the findings presented in this paper. Comprehensive studies are needed to understand and estimate the progression and impact of DR in this population.

Sequence of a new DR12 allele with two silent mutations that affect PCR-SSP typing.

PubMed

Zanone, R; Bettens, F; Tiercy, J-M

2002-02-01

A new HLA-DR12 allele has been identified in a European Caucasoid bone marrow donor. The DRB1*12012 allele differs from DRB1*12011 by two silent substitutions at codons 72 and 78, two polymorphic positions used for DNA subtyping of the DR12 serotype. The co-occurence of the two nucleotide changes is unique to the DR12 group and results in a new PCR-SSP typing pattern. The complete HLA type of the donor is A24, A68; B55, B61; Cw*01, Cw*0304; DRB1*12012, DRB1*1402; DRB3*0101, DRB3*0202; DQB1*0301. HLA-DRB1*12012 is a rare allele as it occurs in < 0.2% of DR12 donors.

Are HLA-DR or TAP genes genetic markers of severity in ulcerative colitis?

PubMed

Heresbach, D; Alizadeh, M; Reumaux, D; Colombel, J F; Delamaire, M; Danze, P M; Gosselin, M; Genetet, B; Bretagne, J F; Semana, G

1996-12-01

The pathogeny of ulcerative colitis (UC) is not yet elucidated, but some arguments suggest the implication of genetic factors. Among the candidate genes, those encoding for HLA class II genotypes have been extensively studied in UC; however, discordant data may be imputable to heterogeneity, characterized by immunological markers such as atypical ANCA (p-ANCA), or to inclusion of more or less intractable UC. The aim of our study is to evaluate the interest of HLA class II and TAP genetic markers to identify different clinical forms of UC, according to p-ANCA status. Unrelated patients with a history of UC (n = 91) and healthy control subjects with no personal or family history of inflammatory bowel diseases (IBD) (n = 200) were included. HLA-DRB1*03 was less frequent in UC patients than in healthy controls (8% vs 28%, PC < 0.03). No association was found with any TAP genotypes. Moreover, there was no association with the HLA-DR2 specificity, either in the entire group of UC patients (38% vs 28%) or in the p-ANCA-positive subgroup of patients (30%). The most consistent finding in the present study is that some genetic markers may characterize intractability in UC patients. HLA-DR2 was associated with poor prognosis, regardless of p-ANCA status. In HLA-DR2 and non-HLA-DR2 groups, colectomy was done in 55% and 27% of patients, respectively, (PC < 0.05). Furthermore, in non-HLA-DR2 patients, p-ANCA could be of interest to characterize those with more severe prognosis. Our results confirm the interest of genetic studies to define UC genetic susceptibility, taking into account intractability of the disease. They do not support the hypothesis that p-ANCA is a subclinical marker of genetic susceptibility to UC.

TRAIL Death Receptor-4 Expression Positively Correlates With the Tumor Grade in Breast Cancer Patients With Invasive Ductal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanlioglu, Ahter D.; Department of Medical Biology and Genetics, Akdeniz University Faculty of Medicine, Antalya; Korcum, Aylin F.

2007-11-01

Purpose: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, thismore » study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration. Methods and Materials: Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns. Results: The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions. Conclusions: DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma.« less

Human spleen contains different subsets of dendritic cells and regulatory T lymphocytes

PubMed Central

Velásquez-Lopera, M M; Correa, L A; García, L F

2008-01-01

Most knowledge about dendritic cells (DCs) and regulatory T cells in humans has been gathered from circulating cells but little is known about their frequency and distribution in lymphoid organs. This report shows the frequency, phenotype and location of DCs and regulatory T cells in deceased organ donors' spleens. As determined by flow cytometry, conventional/myeloid DCs (cDCs) CD11chighHLA-DR+CD123−/low were 2·3 ± 0·9% and LIN- HLA-DR+CD11chigh 2·1 ± 0·3% of total spleen cells. Mature CD11chighHLA-DR+CD83+ were 1·5 ± 0·8% and 1·0 ± 1·6% immature CD11chighHLA-DR+CD83- cDC. There were 0·3 ± 0·3% plasmacytoid DCs (pDC) CD11c−/lowHLA-DR+CD123high and 0·3 ± 0·1% LIN-HLA-DR+CD123high. Cells expressing cDCs markers, BDCA-1 and BDCA-3, and pDCs markers BDCA-2 and BDCA-4 were observed in higher frequencies than DCs with other phenotypes evaluated. CD11c+, CD123+ and CD83+ cells were located in subcapsular zone, T cells areas and B-cell follicles. CD4+CD25high Tregs were 0·2 ± 0·2% and CD8+CD28- comprised 11·5 ± 8·1% of spleen lymphocytes. FOXP3+ cells were found in T- and B-cell areas. The improvement in cell separation, manipulation and expansion techniques, will facilitate the manipulation of donor spleen cells as a part of protocols for induction and maintenance of allograft tolerance or treatment of autoimmune diseases. PMID:18727627

Prevalence, risk factors and burden of diabetic retinopathy in China: a systematic review and meta-analysis.

PubMed

Song, Peige; Yu, Jinyue; Chan, Kit Yee; Theodoratou, Evropi; Rudan, Igor

2018-06-01

Diabetic retinopathy (DR), the primary retinal vascular complication of diabetes mellitus (DM), is a leading cause of vision impairment and blindness in working-age population globally. Despite mounting concerns about the emergence of DM as a major public health problem in the largest developing country, China, much remains to be understood about the epidemiology of DR. We aimed to investigate the prevalence of and risk factors for DR, and estimate the burden of DR in China in 2010. China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Biomedicine Literature Database (CBM-SinoMed), PubMed, Embase and Medline were searched for studies that reported the prevalence of and risk factors for DR in Chinese population between 1990 and 2017. A random-effects meta-analysis model was adopted to pool the overall prevalence of DR. Variations in the prevalence of DR in different age groups, DM duration groups and settings were assessed by subgroup meta-analysis and meta-regression. Odds ratios (ORs) of major risk factors were pooled using random-effects meta-analysis. The number of people with DR in 2010 was estimated by multiplying the age-specific prevalence of DR in people with DM with the corresponding number of people with DM in China. Finally, the national number of people with DR was distributed into six geographic regions using a risk factor-based model. A total of 31 studies provided information on the prevalence of DR and 21 explored potential risk factors for DR. The pooled prevalence of any DR, nonproliferative DR (NPDR) and proliferative DR (PDR) was 1.14% (95% CI = 0.80-1.52), 0.90% (95% CI = 0.56-1.31) and 0.07% (95% CI = 0.02-0.14) in general population; In people with DM, the pooled prevalence rates were 18.45% (95% CI = 14.77-22.43), 15.06% (95% CI = 11.59-18.88) and 0.99% (95% CI = 0.40-1.80) for any DR, NPDR and PDR, respectively. The prevalence of any DR in DM patients peaked between 60 and 69 years of age, and increased steeply with the duration of DM. DM patients residing in rural China were at a higher risk to have DR than those in urban areas. In addition, insulin treatment, elevated FBG level and higher HbA1c concentration were confirmed to be associated with a higher prevalence of DR in people with DM, with meta-ORs of 1.99 (95% CI = 1.34-2.95), 1.33 (95% CI = 1.12-1.59) and 1.15 (95% CI = 1.09-1.20) respectively. In 2010, a total of 13.16 million (95% CI = 8.95-18.00) Chinese aged 45 years and above were living with DR, among whom the most were in South Central China and the least were in Northwest China. DR has become a serious public health problem in China. Optimal screening of and interventions on DR should be implemented. Improved epidemiological studies on DR are still required.

Arthroscopic single-row modified mason-allen repair versus double-row suture bridge reconstruction for supraspinatus tendon tears: a matched-pair analysis.

PubMed

Gerhardt, Christian; Hug, Konstantin; Pauly, Stephan; Marnitz, Tim; Scheibel, Markus

2012-12-01

Arthroscopic double-row fixation of supraspinatus tendon tears compared with single-row techniques is still a matter of debate. Arthroscopic double-row rotator cuff repair using the suture bridge technique provides better clinical results and lower retear rates than does single-row repair using a modified Mason-Allen stitch technique. Cohort study; Level of evidence 3. Forty patients underwent either an arthroscopic single-row modified Mason-Allen stitch (SR) (n = 20; mean age ± SD, 61.5 ± 7.4 y) or a modified suture bridge double-row repair (DR) (n = 20; age, 61.2 ± 7.5 y). The anteroposterior extension was classified as Bateman I in 10% and Bateman II in 90% of patients in the SR group and as Bateman II in 80% and Bateman III in 20% of patients in the DR group. Patients were matched for sex and age. The subjective shoulder value (SSV), Constant-Murley score (CS), and Western Ontario Rotator Cuff Index (WORC) were used for clinical follow-up. Furthermore, MRI scans were conducted for analysis of tendon integrity, muscle atrophy, and fatty infiltration via semiquantitative signal intensity analysis. In addition, re-defect patterns were evaluated. The mean follow-up time in the SR group was 16.8 ± 4.6 months. The mean SSV was 91.0% ± 8.8%, mean CS was 82.2 ± 8.1 (contralateral side, 88.8 ± 5.3), and mean WORC score was 96.5% ± 3.2%. The mean follow-up time in the DR group was 23.4 ± 2.9 months, with patients achieving scores of 92.9% ± 9.6% for the SSV, 77.0 ± 8.6 for the CS (contralateral side, 76.7 ± 17.1), and 90.7% ± 12.6% for the WORC (P > .05). No significant differences were detected in the clinical outcome between groups. Tendon integrity was as follows. Type 1, none in either group; type 2, 4 SR and 5 DR; type 3, 9 SR and 10 DR; type 4, 3 SR and 3 DR; and type 5, 3 SR and 2 DR. The failure rate was 31.6% (n = 6) in the SR group and 25% (n = 5) in the DR group (P > .05). No significant differences were obtained for muscular atrophy or fatty degeneration (SR group, 0.94 ± 0.16; DR group, 1.15 ± 0.5) (P > .05). Re-defects revealed lateral cuff failure in 83.3% of SR patients in contrast to patients treated with DR techniques. The re-defect pattern was medial cuff failure in 80% of the patients. The clinical results after modified Mason-Allen single-row versus double-mattress suture bridge technique did not demonstrate significant differences in a matched patient cohort. Concerning the failure mode, single- and double-row techniques seem to demonstrate different re-defect patterns.

Kinetic properties of dromedary pancreatic lipase: a comparative study on emulsified and monomolecular substrate.

PubMed

Jemel, Ikram; Fendri, Ahmed; Gargouri, Youssef; Bezzine, Sofiane

2009-05-01

Using the classical emulsified system and the monomolecular film technique, we compared several interfacial properties of dromedary pancreatic lipase (DrPL) with those of a mammal (human) and an avian (turkey) model. Like turkey pancreatic lipase (TPL) and unlike human pancreatic lipase (HPL), in the absence of colipase and bile salts, using tributyrin emulsion or monomolecular films of dicaprin at low surface pressure, DrPL hydrolyses pure tributyrin emulsion, as well as dicaprin films maintained at low surface pressures. DrPL was also able to hydrolyse triolein emulsion in the absence of any additive and despite the accumulation of long-chain free fatty acids at the interface. The difference of behaviours between the two mammal pancreatic lipases (DrPL and HPL) can be explained by the penetration capacity of each enzyme. DrPL presents a critical surface pressure value (21 m Nm(-1)) that is more important than this of HPL. Subsequently, the dromedary pancreatic lipase interacts efficiently with interfaces and it is not denaturated at high interfacial energy. A kinetic study on the surface pressure dependency, stereospecificity and regioselectivity of DrPL was performed using optically pure stereoisomers of either three dicaprin isomers containing a single hydrolysable decanoyl ester bond that were spread as monomolecular films at the air/water interface. Interestingly, in comparison with all the previously studied mammal pancreatic lipases, DrPL presents the highest preference for adjacent ester groups of dicaprin isomers (1,2-sn-dicaprin and 2,3-sn-dicaprin) at high surface pressure. Furthermore, DrPL forms a pancreatic lipase subgroup in which the stereopreference switches from sn-3 position to the sn-1 position when increasing the surface pressure.

Association of HLA-DRB1 alleles and neuropsychological function in autism.

PubMed

Chien, Yi-Ling; Wu, Yu-Yu; Chen, Chia-Hsiang; Gau, Susan Shur-Fen; Huang, Yu-Shu; Chien, Wei-Hsien; Hu, Fu-Chang; Chao, Yu-Lin

2012-02-01

Evidence suggests an association between autism and immune dysfunction. The associations between human lymphocyte antigen (HLA)-A2, B44, DRβ1*04 (DR4), C4B, and haplotype B44-SC30-DR4 and autism have been reported in western countries but there is a lack of such information in Asian population. This study aimed to assess the association between HLA-DRB1 allele frequencies and the clinical phenomenology of autism. The sample included 141 participants (male, 87.2%), who were diagnosed with autistic disorder based on clinical assessments and structured interviews using the Chinese version of the Autism Diagnostic Interview-Revised, and 156 healthy controls (male, 38.6%). The HLA-DRB1 alleles were determined by sequencing-based typing method. A subsample of patients (n=39) were assessed for intelligence and neuropsychological functions. The results showed that the pattern of DRB1 allele frequencies was significantly different between patients with autism and the controls (P=0.047). After adjusting for sex by haplotype regression, the frequencies of DR4, DR11, and DR14 were significantly different between patients with autism and healthy controls. In addition, patients with autism and DR4, DR11, or DR14 had different performance on intelligence and neuropsychology tests. Despite a relatively small sample size and a case-control association design, the findings suggest HLA-DRB1 gene might be associated with autism in Han Chinese. The true functional variants associated with autism in our samples remain to be further clarified. It warrants a replication study of a larger family sample and to validate the HLA genetic association with autism and its influence on neuropsychological function.

Inertial Electrostatic Confinement Fusion: The Laser Elevator Solar System Survey for Propellants Abstract

NASA Technical Reports Server (NTRS)

Pryor, Wayne

1999-01-01

Dr. Wayne Pryor worked on three projects this summer. These were: 1) Inertial Electrostatic Confinement; 2) The Laser Elevator; and 3) Solar System Survey for Propellants Abstract. We Assisted Jon Nadler from Richland Community College in assembling and operating a table-top nuclear fusion reactor. We successfully demonstrated neutron production in a deuterium plasma. Pryor also obtained basic spectroscopic information on the atomic and molecular emissions in the plasma. The second project consisted of the completion of a paper on a novel propulsion concept (due to Tom Meyer of Colorado, the first author): a laser sail that bounces light back to the laser source. Recycling the photons from source to sail perhaps 100-1000 times dramatically improves the energy efficiency of this system, which may become very important for high-velocity missions in the future. Lastly, we compiled a very basic inventory of solar system propellant resources, their locations, and their accessibility. This initial inventory concentrates on sunlight availability, water availability, and the difficulty (delta-velocity requirement and radiation environment) in getting there.

Comparison of Actual Costs to Integrate Commercial Buildings with the Grid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Piette, Mary Ann; Black, Doug; Yin, Rongxin

During the past decade, the technology to automate demand response (DR) in buildings and industrial facilities has advanced significantly. Automation allows rapid, repeatable, reliable operation. This study focuses on costs for DR automation in commercial buildings with some discussion on residential buildings and industrial facilities. DR automation technology relies on numerous components, including communication systems, hardware and software gateways, standards-based messaging protocols, controls and integration platforms, and measurement and telemetry systems. This paper discusses the impact factors that contribute to the costs of automated DR systems, with a focus on OpenADR 1.0 and 2.0 systems. In addition, this report comparesmore » cost data from several DR automation programs and pilot projects, evaluates trends in the cost per unit of DR and kilowatts (kW) available from automated systems, and applies a standard naming convention and classification or taxonomy for system elements. In summary, median costs for the 56 installed automated DR systems studied here are about $200/kW. The deviation around this median is large with costs in some cases being an order of magnitude greater or less than median. Costs to automate fast DR systems for ancillary services are not fully analyzed in this report because additional research is needed to determine the total such costs.« less

Quantitative Methods for Long-Range Environmental Forecasting. Long-Wave European Projections. Volume 2. Technical Volume

DTIC Science & Technology

1974-03-01

approaches to specific problems within the foreign affairs community ( e . g. , within DoD). The lag resulted from a variety of factors, in...ICATIOH / Prepared by: Herman M. Weil Airon Greenberg Larry German Douglas Hartwick Michael R. Leavitt Sponsored by: Defense Advanced...I Dr. G. Robert Franco, Project Director Dr. Herman M. Weil Mr. Aaron Greenberg Mr. Larry German Mr. Douglas Hartwick Dr. Michael

Approximating Multivariate Normal Orthant Probabilities Using the Clark Algorithm.

DTIC Science & Technology

1987-07-15

Kent Eaton Army Research Institute Dr. Hans Crombag 5001 Eisenhower Avenue University of Leyden Alexandria, VA 22333 Education Research Center...Boerhaavelaan 2 Dr. John M. Eddins 2334 EN Leyden University of Illinois The NETHERLANDS 252 Engineering Research Laboratory Mr. Timothy Davey 103 South...Education and Training Ms. Kathleen Moreno Naval Air Station Navy Personnel R&D Center Pensacola, FL 32508 Code 62 San Diego, CA 92152-6800 Dr. Gary Marco

Air and Space Power Journal. Volume 30, Number 2, Summer 2016

DTIC Science & Technology

2016-01-01

Nicholas J. Thomas, USAF, PE Features Thinking beyond the Books ❙ 15 Sociological Biases of Our Military Institutions Ben Zweibelson Institutional ...Retired Editor, Strategic Studies Quarterly Air Force Research Institute Dr. Grant T. Hammond USAF Center for Strategy and Technology Dr. Dale L...Hayden Air Force Research Institute Col S. Clinton Hinote Military Fellow Council on Foreign Relations Dr. Thomas Hughes USAF School of Advanced Air and

11. View of south side of radar scanner building no. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

11. View of south side of radar scanner building no. 104 showing personnel exit door at side building, showing DR 1 antenna from oblique angle on foundation berm with DR 2 and DR 3 antennae in background. - Clear Air Force Station, Ballistic Missile Early Warning System Site II, One mile west of mile marker 293.5 on Parks Highway, 5 miles southwest of Anderson, Anderson, Denali Borough, AK

Questioning Mechanisms during Tutoring, Conversation, and Human-Computer Interaction

DTIC Science & Technology

1993-06-01

Department of Psychology Los Angesles, CA 90024 Pittsburgh, PA 15213 Dr. Eduardo Cascallar Dr. Ruth Chabay Dr. Paul G. Chapin Educational Testing Service...Sharon Deny Educational Testing Service Applied Science Associates Florida State University Mail Stop 22-T P.O. Box 1072 Dept. of Psychology Princeton...Principal Investigator Department of Psychology , Department of Mathematical Sciences, and the Institute for Intelligent Systems DTIC ELECTE :JUN 2 9 1993

Computational Study of Inlet Active Flow Control

DTIC Science & Technology

2007-05-01

AFRL-VA-WP-TR-2007-3077 COMPUTATIONAL STUDY OF INLET ACTIVE FLOW CONTROL Delivery Order 0005 Dr. Sonya T. Smith Howard University Department...NUMBER A0A2 5e. TASK NUMBER 6. AUTHOR(S) Dr. Sonya T. Smith ( Howard University ) Dr. Angela Scribben and Matthew Goettke (AFRL/VAAI) 5f...WORK UNIT NUMBER 0B 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION Howard University Department of Mechanical

Pulse Shaping a High-Current Relativistic Electron Beam in Vacuum

DTIC Science & Technology

1990-06-28

for cathode explosive field-emission initiation at the typical value of 200 kV/cm. The anode is 2.7 cm downstream from the cathode with an aperture of...R42 (J. Choe) I Attn: Dr. D. Prosnitz 1 R42 K. Boulais) 1 Dr. F. W. Chambers 1 R42 (J. Miller) 15 Dr. T. Orzechowski 1 R42 CD. Weidman) I P.O. Box

Adult hearing-aid users with cochlear dead regions restricted to high frequencies: Implications for amplification.

PubMed

Pepler, Anna; Lewis, Kathryn; Munro, Kevin J

2016-01-01

Cochlear dead regions (DR) are common in adult hearing-aid users, but are usually restricted to high frequencies. The aim was to determine the benefit of high-frequency amplification for ears with and without high-frequency DRs. Participants were fitted with the study hearing aid and tested under four conditions: unfiltered (NAL-NL2 prescription), and low-pass filtered at 1.5, 2, and 3 kHz. VCV stimuli were presented at 65 dB (A) in quiet and in 20-talker babble at a signal-to-babble ratio of 0 dB. Experienced adult hearing-aid users: one group of 18 with a DR edge frequency above 1.5 kHz, and a group of 18 matched controls. Overall performance was best in the unfiltered condition. There was no significant difference in mean performance between the two groups when tested in quiet. However, the DR group obtained less benefit from high-frequency amplification when tested in babble: the mean difference between the unfiltered and 3-kHz filtered condition was 6% and 13% for the DR group and controls, respectively. In adults with a moderate hearing loss and a restricted DR, speech recognition was always best in the unfiltered condition, although mean performance in babble was lower for the DR group.

A Proteome Translocation Response to Complex Desert Stress Environments in Perennial Phragmites Sympatric Ecotypes with Contrasting Water Availability.

PubMed

Li, Li; Chen, Xiaodan; Shi, Lu; Wang, Chuanjing; Fu, Bing; Qiu, Tianhang; Cui, Suxia

2017-01-01

After a long-term adaptation to desert environment, the perennial aquatic plant Phragmites communis has evolved a desert-dune ecotype. The desert-dune ecotype (DR) of Phragmites communis showed significant differences in water activity and protein distribution compared to its sympatric swamp ecotype (SR). Many proteins that were located in the soluble fraction of SR translocated to the insoluble fraction of DR, suggesting that membrane-associated proteins were greatly reinforced in DR. The unknown phenomenon in plant stress physiology was defined as a proteome translocation response. Quantitative 2D-DIGE technology highlighted these 'bound' proteins in DR. Fifty-eight kinds of proteins were identified as candidates of the translocated proteome in Phragmites . The majority were chloroplast proteins. Unexpectedly, Rubisco was the most abundant protein sequestered by DR. Rubisco activase, various chaperons and 2-cysteine peroxiredoxin were major components in the translocation response. Conformational change was assumed to be the main reason for the Rubisco translocation due to no primary sequence difference between DR and SR. The addition of reductant in extraction process partially reversed the translocation response, implying that intracellular redox status plays a role in the translocation response of the proteome. The finding emphasizes the realistic significance of the membrane-association of biomolecule for plant long-term adaptation to complex stress conditions.

[HLA class II in Mexican patients with pemphigus vulgaris: shared epitope for autoimmunity].

PubMed

Rangel-Gamboa, Lucía; Vega-Memije, María Elisa; Acuña-Alonzo, Víctor; Granados-Arriola, Julio

Pemphigus is an autoimmune blistering disease of skin and mucous membranes characterized by presence of IgG antibodies against desmoglein 3, and 1. Desmoglein 3 and 1 are presented in pemphigus vulgaris and pemphigus foliaceous, respectively. Desmoglein are transmembrane proteins that form part of cellular junctions called desmosomes. Major histocompatibility complex class II molecules have been related to autoimmune disease; in pemphigus vulgaris, different human lymphocyte antigens (HLA) were associated among different ethnic groups, such as HLA-DR4, HLA-DR14, and HLA-DR1. to determine the allele HLA-DR genetic frequencies in Mexican patients with pemphigus. Patients with clinical, histological, and immunofluorescence diagnosis monitored at the Dermatology Department of the Mexican General Hospital were included. DNA was extracted from blood samples and genetic recognition of HLA-DRβ1 was performed by polymerase chain reaction and hybridization. Forty-three patients with pemphigus were included: 35 (81.4%) women and eight men (18.6%) between 16 and 85 years old. The HLA-DR14 and HLA-DR1 genetic frequencies were elevated among pemphigus patients and these alleles confer risk to pemphigus 2.2 and 3.3, respectively. These findings suggest that pemphigus vulgaris susceptibility is part of a general predisposition to present autoimmune diseases.

The Geography Teacher. Volume 4, Number 2, 2007

ERIC Educational Resources Information Center

Geography Teacher, 2007

2007-01-01

"The Geography Teacher" provides hands-on reference and educative material for K-12 Geography teachers. The journal also pioneers innovative ideas for contemporary teaching methods, including lesson plans. This issue contains the following: (1) Ask Dr. de Blij (Dr. Harm de Blij); (2) Improving Geographic Understanding with a State Atlas…

HLA-DRB1 alleles associated with polymyalgia rheumatica in northern Italy: correlation with disease severity

PubMed Central

Salvarani, C.; Boiardi, L.; Mantovani, V.; Ranzi, A.; Cantini, F.; Olivieri, I.; Bragliani, M.; Collina, E.; Macchioni, P.

1999-01-01

OBJECTIVE—To examine the association of HLA-DRB1 alleles with polymyalgia rheumatica (PMR) in a Mediterranean country and to explore the role of HLA-DRB1 genes in determining disease severity.
METHODS—A five year prospective follow up study of 92 consecutive PMR patients diagnosed by the secondary referral centre of rheumatology of Reggio Emilia, Italy was conducted. HLA-DRB1 alleles were determined in the 92 patients, in 29 DR4 positive rheumatoid arthritis (RA) patients, and in 148 controls from the same geographical area by polymerase chain reaction amplification and oligonucleotide hybridisation.
RESULTS—No significant differences were observed in the frequencies of HLA-DRB1 types and in the expression of HLA-DRB 70-74 shared motif between PMR and controls. The frequency of the patients with double dose of epitope was low and not significantly different in PMR and in controls. No significant differences in the distribution of HLA-DR4 subtypes were observed between DR4+ PMR, DR+ RA, and DR4+ controls. Results of the univariate analysis indicated that an erythrocyte sedimentation rate (ESR) at diagnosis > 72 mm 1st h, the presence of HLA-DR1, DR10, rheumatoid epitope, and the type of rheumatoid epitope were significant risk factors associated with relapse/recurrence. Cox proportional hazards modelling identified two variables that independently increased the risk of relapse/recurrence: ESR at diagnosis > 72 mm 1st h (RR=1.5) and type 2 (encoded by a non-DR4 allele) rheumatoid epitope (RR=2.7).
CONCLUSION—These data from a Mediterranean country showed no association of rheumatoid epitope with PMR in northern Italian patients. A high ESR at diagnosis and the presence of rheumatoid epitope encoded by a non-DR4 allele are independent valuable markers of disease severity.

 PMID:10225816

Production of neutral species in Titan's ionosphere through dissociative recombination of ions

NASA Astrophysics Data System (ADS)

Plessis, Sylvain; Carrasco, Nathalie; Dobrijevic, Michel; Pernot, Pascal

2012-05-01

The production rates of neutral species by dissociative recombination (DR) of molecular ions with electrons in the ionosphere of Titan are quantified by a new model, including, for the first time, all the available kinetic data on this process. The calculation is based on the ion densities measured by the INMS instrument on Cassini orbiter during flyby T19 at 1100 km altitude. These production rates are compared with those predicted by photochemical models: we calculate that for many neutral species, DR has larger production rates than neutral chemistry. Concerning molecular growth in Titan's ionosphere, DR is shown to have two antagonistic effects: (1) a global chemical lysis of ions through C-C and C-N bond breaking (missed by the "H-loss" DR paradigm); and (2) an enhancement of the neutral chemistry by production of reactive radicals, such as C2H or NH2. Further exploration of this chemistry requires the development of ionospheric coupled models taking explicitly into account the richness of the DR process and the strong impact of ions on the budget of neutral species. This study emphasizes also the urgent need of additional experimental studies about DR of molecular ions, with two priorities: evaluation of the impact of the temperature of ions on the rates and fragmentation patterns, and the systematic study of the fragmentation patterns of CxHyNz+ ions with more than four heavy atoms (m/z > 60 u).

HLA heterozygosity contributes to susceptibility to rheumatoid arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wordsworth, P.; Pile, K.D.; Bell, J.I.

The authors have investigated the role of HLA-DR genotypes in 184 patients with severe rheumatoid arthritis (RA) and in 46 patients with Felty syndrome, to establish the relative contribution of the RA-associated subtypes of DR4 (Dw4, Dw14, and Dw15). There was an excess of DR4 homozygotes, particularly Dw4/Dw14 compound heterozygotes (relative risk [RR] 49). The risk associated with Dw4 depended on the other allele present-Dw4/DR1 (RR 21), Dw4/Dw4 (RR 15), and Dw4/DRX (RR 6). There was a significant risk from Dw4/Dw14 compared with Dw4/Dw4, both in those with severe RA (RR 2.9; P < .02) and in those with Feltymore » syndrome (RR 4.2; P < 0.2). In contrast, in a further 63 known DR4 homozygotes with RA, not selected for severe disease, the excess of Dw4/Dw14 was much less striking (RR 1.4; not significant), suggesting that this genotype may be particularly associated with more severe disease. They also found four cases with the rare Dw4/Dw15 genotype (expected [<=]0.5; P [<=] .02). Since the Dw4, Dw14, Dw15, and DR1 molecules have similar antigen-binding sites and since combinations of these alleles particularly predispose to severe RA, the authors suggest that synergistic mechanisms are involved. These could include an effect on T-cell repertoire selection. 32 refs., 3 tabs.« less

A biomechanical and histological comparison of the suture bridge and conventional double-row techniques of the repair of full-thickness rotator cuff tears in a rabbit model.

PubMed

Fei, Wenyong; Guo, Weichun

2015-06-16

The suture bridge (SB) technique and conventional double-row (DR) are both effective in repair of full-thickness rotator cuff tears . However, increasing numbers of scholars believe that the SB technique produces better results than conventional DR because of the higher bone-tendon contact area and pressure. However, The clinical outcomes have been mixed and little direct evidence has been supplied in vivo. This study was designed using the SB and DR techniques to determine which is the better technique. Sixty-four New Zealand white rabbits were randomly divided into 2 groups, the SB group and DR group. SB and DR were then used to repair their rotator cuff tears. Rabbits were then sacrificed at the 2(nd), 4(th), or 8(th) week after surgery and a histological comparison was made. The biomechanical comparison was made at the 8(th) week. The load to failure of the SB group was 134.59 ± 17.69 N at the 8(th) postoperative week, and that was significantly higher than in the DR group (103.83 ± 6.62, P = 0.001), but both repair groups remained lower than in the control group (199.25 ± 14.81). Histological evaluation showed that both the SB and DR groups healed at the bone-tendon interface. But there were subtle differences between the two groups in the structure and morphology of collagen fibers and cartilage cells at bone-tendon interface. In general, the collagen fibers of the SB group were more compact than those of the DR group at all times tested. At the 4(th) and 8(th) weeks, the collagen fibers and cartilage cells in the SB group were arranged in a column modality, but those in the DR group were distributed horizontally. The SB technique facilitated healing more effectively than the conventional DR technique. The difference in morphology of collagen fibers and cartilage cells may be related to the difference in bone-tendon contact pressure.

SEVERITY OF DIABETIC RETINOPATHY AND HEALTH-RELATED QUALITY OF LIFE: THE LOS ANGELES LATINO EYE STUDY

PubMed Central

Mazhar, Kashif; Varma, Rohit; Choudhury, Farzana; McKean-Cowdin, Roberta; Shtir, Corina J.; Azen, Stanley P.

2010-01-01

Objective To assess the impact of diabetic retinopathy (DR) and its severity on health-related quality of life (HRQOL) in a population-based sample of Latinos with type 2 diabetes mellitus. Design Cross-sectional population-based study, the Los Angeles Latino Eye Study (LALES). Participants 1,064 LALES participants with diabetes mellitus. Methods HRQOL was measured by the 25 item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and the Medical Outcomes Study 12-Item Short Form Health Survey (SF-12). DR was assessed by masked standardized grading of stereoscopic photographs from 7 standard fields. Severity of DR in eyes was graded using a modified Airlie House classification. The severity scores from each eye were then concatenated to create a single per person grade ranging from 1(no DR in either eye) to 15 (bilateral PDR). Multiple linear regression analyses were performed to determine the independent relationship between severity of DR and HRQOL after adjusting for covariates. Main Outcome Measures NEI-VFQ-25 and SF-12 scores. Results More severe DR was associated with worse HRQOL scores on all of the NEI VFQ-25 and SF-12 subscales (P<0.05). Individuals with DR from grade 2 (minimum NPDR) through grade 8 (unilateral moderate NPDR) show a modest decline in HRQOL. However, the decline become significantly steeper between steps 8 (unilateral moderate NPDR) and 9-15 (bilateral moderate NPDR to bilateral PDR). The domains with the most significant impact were for vision-related daily activities, dependency and mental health. Conclusion Greater severity of DR was associated with lower general and vision-specific HRQOL. Persons with bilateral moderate NPDR had the most substantial decrease in quality of life compared to those with less severe DR. The prevention of incident DR and more importantly its progression from unilateral to bilateral NPDR is likely to have a positive impact on a person’s HRQOL and should be considered an important goal in management of individuals with diabetes mellitus. PMID:21035872

Very Large Array H I Zeeman Observations of the Cygnus X Region: DR 22 and ON 2

NASA Astrophysics Data System (ADS)

Mayo, E. A.; Troland, T. H.

2012-02-01

We have used the Very Large Array to study the Zeeman effect in 21 cm H I absorption lines from two star-forming regions in the Cygnus X complex, DR 22 and ON 2. We measure the line-of-sight magnetic field toward these regions, finding B los = -84 ± 11 μG toward the DR 22 H II region and B los < 50 μG toward each of the two H II regions in ON 2. We interpret these results in terms of two different models. In one model, we assume that the H I Zeeman effect is a measure of magnetic fields in the associated molecular clouds. If so, then the DR 22 molecular cloud is magnetically subcritical, that is, magnetically dominated. The ON 2 molecular clouds are magnetically supercritical. In a second model, we assume that the H I Zeeman effect is a measure of magnetic fields in photon-dominated regions where the gas has been compressed (and the field amplified) by absorption of stellar radiation. We find that this second model, where the measured field strength has been affected by star formation, accounts well for the DR 22 H I Zeeman effect. This same model, however, overpredicts the magnetic field in ON 2. ON 2 may be a region where the magnetic field is energetically insignificant or where the field happens to lie nearly in the plane of the sky.

Model-independent Evidence for Dark Energy Evolution from Baryon Acoustic Oscillations

NASA Astrophysics Data System (ADS)

Sahni, V.; Shafieloo, A.; Starobinsky, A. A.

2014-10-01

Baryon acoustic oscillations (BAOs) allow us to determine the expansion history of the universe, thereby shedding light on the nature of dark energy. Recent observations of BAOs in the Sloan Digital Sky Survey (SDSS) DR9 and DR11 have provided us with statistically independent measurements of H(z) at redshifts of 0.57 and 2.34, respectively. We show that these measurements can be used to test the cosmological constant hypothesis in a model-independent manner by means of an improved version of the Om diagnostic. Our results indicate that the SDSS DR11 measurement of H(z) = 222 ± 7 km s-1 Mpc-1 at z = 2.34, when taken in tandem with measurements of H(z) at lower redshifts, imply considerable tension with the standard ΛCDM model. Our estimation of the new diagnostic Omh 2 from SDSS DR9 and DR11 data, namely, Omh 2 ≈ 0.122 ± 0.01, which is equivalent to Ω0m h 2 for the spatially flat ΛCDM model, is in tension with the value Ω0m h 2 = 0.1426 ± 0.0025 determined for ΛCDM from Planck+WP. This tension is alleviated in models in which the cosmological constant was dynamically screened (compensated) in the past. Such evolving dark energy models display a pole in the effective equation of state of dark energy at high redshifts, which emerges as a smoking gun test for these theories.

The brain cytoplasmic RNA BC1 regulates dopamine D2 receptor-mediated transmission in the striatum.

PubMed

Centonze, Diego; Rossi, Silvia; Napoli, Ilaria; Mercaldo, Valentina; Lacoux, Caroline; Ferrari, Francesca; Ciotti, Maria Teresa; De Chiara, Valentina; Prosperetti, Chiara; Maccarrone, Mauro; Fezza, Filomena; Calabresi, Paolo; Bernardi, Giorgio; Bagni, Claudia

2007-08-15

Dopamine D(2) receptor (D(2)DR)-mediated transmission in the striatum is remarkably flexible, and changes in its efficacy have been heavily implicated in a variety of physiological and pathological conditions. Although receptor-associated proteins are clearly involved in specific forms of synaptic plasticity, the molecular mechanisms regulating the sensitivity of D(2) receptors in this brain area are essentially obscure. We have studied the physiological responses of the D(2)DR stimulations in mice lacking the brain cytoplasmic RNA BC1, a small noncoding dendritically localized RNA that is supposed to play a role in mRNA translation. We show that the efficiency of D(2)-mediated transmission regulating striatal GABA synapses is under the control of BC1 RNA, through a negative influence on D(2) receptor protein level affecting the functional pool of receptors. Ablation of the BC1 gene did not result in widespread dysregulation of synaptic transmission, because the sensitivity of cannabinoid CB(1) receptors was intact in the striatum of BC1 knock-out (KO) mice despite D(2) and CB(1) receptors mediated similar electrophysiological actions. Interestingly, the fragile X mental retardation protein FMRP, one of the multiple BC1 partners, is not involved in the BC1 effects on the D(2)-mediated transmission. Because D(2)DR mRNA is apparently equally translated in the BC1-KO and wild-type mice, whereas the protein level is higher in BC1-KO mice, we suggest that BC1 RNA controls D(2)DR indirectly, probably regulating translation of molecules involved in D(2)DR turnover and/or stability.

One-Hour Plasma Glucose Compared With Two-Hour Plasma Glucose in Relation to Diabetic Retinopathy in American Indians.

PubMed

Paddock, Ethan; Looker, Helen C; Piaggi, Paolo; Knowler, William C; Krakoff, Jonathan; Chang, Douglas C

2018-06-01

We compared the ability of 1- and 2-h plasma glucose concentrations (1h-PG and 2h-PG, respectively), derived from a 75-g oral glucose tolerance test (OGTT), to predict retinopathy. 1h-PG and 2h-PG concentrations, measured in a longitudinal study of an American Indian community in the southwestern U.S., a population at high risk for type 2 diabetes, were analyzed to assess the usefulness of the 1h-PG to identify risk of diabetic retinopathy (DR). Cross-sectional ( n = 2,895) and longitudinal ( n = 1,703) cohorts were assessed for the prevalence and incidence of DR, respectively, in relation to deciles of 1h-PG and 2h-PG concentrations. Areas under the receiver operating characteristic (ROC) curves for 1h-PG and 2h-PG were compared with regard to predicting DR, as assessed by direct ophthalmoscopy. Prevalence and incidence of DR, based on direct ophthalmoscopy, changed in a similar manner across the distributions of 1h-PG and 2h-PG concentrations. ROC analysis showed that 1h-PG and 2h-PG were of similar value in identifying prevalent and incident DR using direct ophthalmoscopy. 1h-PG cut points of 230 and 173 mg/dL were comparable to 2h-PG cut points of 200 mg/dL (type 2 diabetes) and 140 mg/dL (impaired glucose tolerance), respectively. 1h-PG is a useful predictor of retinopathy risk, has a predictive value similar to that of 2h-PG, and may be considered as an alternative glucose time point during an OGTT. © 2018 by the American Diabetes Association.

Oral administration of non-absorbable delayed release 6-mercaptopurine is locally active in the gut, exerts a systemic immune effect and alleviates Crohn’s disease with low rate of side effects: results of double blind Phase II clinical trial

PubMed Central

Israeli, E; Goldin, E; Fishman, S; Konikoff, F; Lavy, A; Chowers, Y; Melzer, E; Lahat, A; Mahamid, M; Shirin, H; Nussinson, E; Segol, O; Ya’acov, A Ben; Shabbat, Y; Ilan, Y

2015-01-01

Therapy for Crohn’s disease (CD) with thiopurines is limited by systemic side effects. A novel formulation of fixed-dose, delayed-release 6-mercaptopurine (DR-6MP) was developed, with local effect on the gut immune system and minimal absorption. The aim of this study was to evaluate the safety and efficacy of DR-6MP in patients with moderately severe CD compared to systemically delivered 6-mercaptopurine (Purinethol). Seventy CD patients were enrolled into a 12-week, double-blind controlled trial. The primary end-point was the percentage of subjects with clinical remission [Crohn’s Disease Activity Index (CDAI) < 150] or clinical response (100-point CDAI reduction). Twenty-six (56·5%) and 13 (54·2%) subjects from the DR-6MP and Purinethol cohorts, respectively, completed the study. DR-6MP had similar efficacy to Purinethol following 12 weeks of treatment. However, the time to maximal clinical response was 8 weeks for DR-6MP versus 12 weeks for Purinethol. A higher proportion of patients on DR-6MP showed clinical remission at week 8. A greater improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) score was noted in the DR-6MP group. DR-6MP led to a decrease of CD62+ expression on T cells, implying a reduction of lymphocyte adhesion to site of inflammation. DR-6MP was safer than Purinethol, with significantly fewer adverse events (AEs). There was no evidence of drug-induced leucopenia in the DR-6MP group; the proportion of subjects who developed hepatotoxicity was lower for the DR-6MP. Non-absorbable DR-6MP is safe and biologically active in the gut. It is clinically effective, exerting a systemic immune response with low systemic bioavailability and a low incidence of side effects. PMID:25846055

Oral administration of non-absorbable delayed release 6-mercaptopurine is locally active in the gut, exerts a systemic immune effect and alleviates Crohn's disease with low rate of side effects: results of double blind Phase II clinical trial.

PubMed

Israeli, E; Goldin, E; Fishman, S; Konikoff, F; Lavy, A; Chowers, Y; Melzer, E; Lahat, A; Mahamid, M; Shirin, H; Nussinson, E; Segol, O; Ya'acov, A Ben; Shabbat, Y; Ilan, Y

2015-08-01

Therapy for Crohn's disease (CD) with thiopurines is limited by systemic side effects. A novel formulation of fixed-dose, delayed-release 6-mercaptopurine (DR-6MP) was developed, with local effect on the gut immune system and minimal absorption. The aim of this study was to evaluate the safety and efficacy of DR-6MP in patients with moderately severe CD compared to systemically delivered 6-mercaptopurine (Purinethol). Seventy CD patients were enrolled into a 12-week, double-blind controlled trial. The primary end-point was the percentage of subjects with clinical remission [Crohn's Disease Activity Index (CDAI) < 150] or clinical response (100-point CDAI reduction). Twenty-six (56·5%) and 13 (54·2%) subjects from the DR-6MP and Purinethol cohorts, respectively, completed the study. DR-6MP had similar efficacy to Purinethol following 12 weeks of treatment. However, the time to maximal clinical response was 8 weeks for DR-6MP versus 12 weeks for Purinethol. A higher proportion of patients on DR-6MP showed clinical remission at week 8. A greater improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) score was noted in the DR-6MP group. DR-6MP led to a decrease of CD62(+) expression on T cells, implying a reduction of lymphocyte adhesion to site of inflammation. DR-6MP was safer than Purinethol, with significantly fewer adverse events (AEs). There was no evidence of drug-induced leucopenia in the DR-6MP group; the proportion of subjects who developed hepatotoxicity was lower for the DR-6MP. Non-absorbable DR-6MP is safe and biologically active in the gut. It is clinically effective, exerting a systemic immune response with low systemic bioavailability and a low incidence of side effects. © 2015 British Society for Immunology.

An Analysis of Success in Systems Program Management.

DTIC Science & Technology

1981-02-27

D’Neill Lt en. Edmund F. O’Connor Lt :en. john B. Hudson I t. Cen. Robert T. Marsh ’t. ’-en. Rotert C . Mathis It. Cen. Z.eorge H. 2yivester...Snaveiy Lt. Gen. Harry E. Goldsworthy Lt. Gen. Robert C . Ruegg Lt. Gen. Thomas P. Gerrity OSD/DDR&E Dr. m.J. Perry Dr. M. Currie Dr. John Foster OSD/PA&E...UNCLASSIFIED NI*2 fflfflfllfllflfflfEEhEhEEE El/llEEEEEl/E- EEEEEE/I/I- mE....-.I/1 Report F33615-8 - C -5184.11 rmi AN ANALYSIS OF SUCCESS IN SYSTEMS

Microgravity

NASA Image and Video Library

2001-01-24

Dr. Dr. Robert F. Berg (right), principal investigator and Dr. Micheal R. Moldover (left), co-investigator, for the Critical Viscosity of Xenon (CVX/CVX-2) experiment. They are with the National Institutes of Standards and Technology, Gaithersburg, MD. The Critical Viscosity of Xenon Experiment (CVX-2) on the STS-107 Research 1 mission in 2002 will measure the viscous behavior of xenon, a heavy inert gas used in flash lamps and ion rocket engines, at its critical point. Although it does not easily combine with other chemicals, its viscosity at the critical point can be used as a model for a range of chemicals.

Critical Viscosity of Xenon investigators

NASA Technical Reports Server (NTRS)

2001-01-01

Dr. Dr. Robert F. Berg (right), principal investigator and Dr. Micheal R. Moldover (left), co-investigator, for the Critical Viscosity of Xenon (CVX/CVX-2) experiment. They are with the National Institutes of Standards and Technology, Gaithersburg, MD. The Critical Viscosity of Xenon Experiment (CVX-2) on the STS-107 Research 1 mission in 2002 will measure the viscous behavior of xenon, a heavy inert gas used in flash lamps and ion rocket engines, at its critical point. Although it does not easily combine with other chemicals, its viscosity at the critical point can be used as a model for a range of chemicals.

Possible systematics in the VLBI catalogs as seen from Gaia

NASA Astrophysics Data System (ADS)

Liu, N.; Zhu, Z.; Liu, J.-C.

2018-01-01

Aims: In order to investigate the systematic errors in the very long baseline interferometry (VLBI) positions of extragalactic sources (quasars) and the global differences between Gaia and VLBI catalogs, we use the first data release of Gaia (Gaia DR1) quasar positions as the reference and study the positional offsets of the second realization of the International Celestial Reference Frame (ICRF2) and the Goddard VLBI solution 2016a (gsf2016a) catalogs. Methods: We select a sample of 1032 common sources among three catalogs and adopt two methods to represent the systematics: considering the differential orientation (offset) and declination bias; analyzing with the vector spherical harmonics (VSH) functions. Results: Between two VLBI catalogs and Gaia DR1, we find that: i) the estimated orientation is consistent with the alignment accuracy of Gaia DR1 to ICRF, of 0.1 mas, but the southern and northern hemispheres show opposite orientations; ii) the declination bias in the southern hemisphere between Gaia DR1 and ICRF2 is estimated to be +152 μas, much larger than that between Gaia DR1 and gsf2016a which is +34 μas. Between two VLBI catalogs, we find that: i) the rotation component shows that ICRF2 and gsf2016a are generally consistent within 30 μas; ii) the glide component and quadrupole component report two declination-dependent offsets: dipolar deformation of +50 μas along the Z-axis, and quadrupolar deformation of -50 μas that would induce a pattern of sin2δ. Conclusions: The significant declination bias between Gaia DR1 and ICRF2 catalogs reported in previous studies is possibly attributed to the systematic errors of ICRF2 in the southern hemisphere. The global differences between ICRF2 and gsf2016a catalogs imply that possible, mainly declination-dependent systematics exit in the VLBI positions and need further investigations in the future Gaia data release and the next generation of ICRF.

Special-purpose computing for dense stellar systems

NASA Astrophysics Data System (ADS)

Makino, Junichiro

2007-08-01

I'll describe the current status of the GRAPE-DR project. The GRAPE-DR is the next-generation hardware for N-body simulation. Unlike the previous GRAPE hardwares, it is programmable SIMD machine with a large number of simple processors integrated into a single chip. The GRAPE-DR chip consists of 512 simple processors and operates at the clock speed of 500 MHz, delivering the theoretical peak speed of 512/226 Gflops (single/double precision). As of August 2006, the first prototype board with the sample chip successfully passed the test we prepared. The full GRAPE-DR system will consist of 4096 chips, reaching the theoretical peak speed of 2 Pflops.

DEVELOPMENT AND APPLICATION OF MATERIALS PROPERTIES FOR FLAW STABILITY ANALYSIS IN EXTREME ENVIRONMENT SERVICE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sindelar, R; Ps Lam, P; Andrew Duncan, A

Discovery of aging phenomena in the materials of a structure may arise after its design and construction that impact its structural integrity. This condition can be addressed through a demonstration of integrity with the material-specific degraded conditions. Two case studies of development of fracture and crack growth property data, and their application in development of in-service inspection programs for nuclear structures in the defense complex are presented. The first case study covers the development of fracture toughness properties in the form of J-R curves for rolled plate Type 304 stainless steel with Type 308 stainless steel filler in the applicationmore » to demonstrate the integrity of the reactor tanks of the heavy water production reactors at the Savannah River Site. The fracture properties for the base, weld, and heat-affected zone of the weldments irradiated at low temperatures (110-150 C) up to 6.4 dpa{sub NRT} and 275 appm helium were developed. An expert group provided consensus for application of the irradiated properties for material input to acceptance criteria for ultrasonic examination of the reactor tanks. Dr. Spencer H. Bush played a lead advisory role in this work. The second case study covers the development of fracture toughness for A285 carbon steel in high level radioactive waste tanks. The approach in this case study incorporated a statistical experimental design for material testing to address metallurgical factors important to fracture toughness. Tolerance intervals were constructed to identify the lower bound fracture toughness for material input to flaw disposition through acceptance by analysis.« less

Unmixed fuel processors and methods for using the same

DOEpatents

Kulkarni, Parag Prakash; Cui, Zhe

2010-08-24

Disclosed herein are unmixed fuel processors and methods for using the same. In one embodiment, an unmixed fuel processor comprises: an oxidation reactor comprising an oxidation portion and a gasifier, a CO.sub.2 acceptor reactor, and a regeneration reactor. The oxidation portion comprises an air inlet, effluent outlet, and an oxygen transfer material. The gasifier comprises a solid hydrocarbon fuel inlet, a solids outlet, and a syngas outlet. The CO.sub.2 acceptor reactor comprises a water inlet, a hydrogen outlet, and a CO.sub.2 sorbent, and is configured to receive syngas from the gasifier. The regeneration reactor comprises a water inlet and a CO.sub.2 stream outlet. The regeneration reactor is configured to receive spent CO.sub.2 adsorption material from the gasification reactor and to return regenerated CO.sub.2 adsorption material to the gasification reactor, and configured to receive oxidized oxygen transfer material from the oxidation reactor and to return reduced oxygen transfer material to the oxidation reactor.

Prevalence and causes of blindness and diabetic retinopathy in Southern Saudi Arabia.

PubMed

Hajar, Saad; Al Hazmi, Ali; Wasli, Mustafa; Mousa, Ahmed; Rabiu, Mansour

2015-04-01

To determine the prevalence and causes of blindness and diabetic retinopathy (DR) in Jazan district, Southern Saudi Arabia. Using the standardized Rapid Assessment for Avoidable Blindness (RAAB) and DR cross-sectional methodology, 3800 subjects were randomly selected from the population of ≥50 years of age in Jazan, Saudi Arabia between November 2011 and January 2012. Participants underwent screening comprised of interview, random blood glucose test, and ophthalmic assessment including visual acuity (VA) and fundus examination. Among participants with VA less than 6/18 in either eye, the cause(s) of visual impairment was determined. Participants were classified as diabetic if they had previous diagnoses of diabetes, or random blood glucose more than 200 mg/dl. Diabetic participants were assessed for DR using dilated fundus examination. All data were recorded using the RAAB + DR standardized forms. The prevalence of bilateral blindness less than 3/60 was 3.3% (95% confidence interval [CI]: 2.74 - 3.90). Cataract was the leading cause of blindness (58.6%); followed by posterior segment diseases (20%), which included DR (7; 3.3%). The prevalence of diabetes mellitus (DM) was 22.4%, (95% CI: 21.09 - 23.79]), among them; 27.8% had DR. The prevalence of sight-threatening DR was 5.7%. The prevalence of DM and the corresponding proportion of DR in this region is lower than that reported in other regions of Saudi Arabia. However, the prevalence of blindness not related to DR is relatively higher than the other studies.

Prevalence and causes of blindness and diabetic retinopathy in Southern Saudi Arabia

PubMed Central

Hajar, Saad; Hazmi, Ali Al; Wasli, Mustafa; Mousa, Ahmed; Rabiu, Mansour

2015-01-01

Objectives: To determine the prevalence and causes of blindness and diabetic retinopathy (DR) in Jazan district, Southern Saudi Arabia. Methods: Using the standardized Rapid Assessment for Avoidable Blindness (RAAB) and DR cross-sectional methodology, 3800 subjects were randomly selected from the population of ≥50 years of age in Jazan, Saudi Arabia between November 2011 and January 2012. Participants underwent screening comprised of interview, random blood glucose test, and ophthalmic assessment including visual acuity (VA) and fundus examination. Among participants with VA <6/18 in either eye, the cause(s) of visual impairment was determined. Participants were classified as diabetic if they had previous diagnoses of diabetes, or random blood glucose >200 mg/dl. Diabetic participants were assessed for DR using dilated fundus examination. All data were recorded using the RAAB + DR standardized forms. Results: The prevalence of bilateral blindness <3/60 was 3.3% (95% confidence interval [CI]: 2.74 - 3.90). Cataract was the leading cause of blindness (58.6%); followed by posterior segment diseases (20%), which included DR (7; 3.3%). The prevalence of diabetes mellitus (DM) was 22.4%, (95% CI: 21.09 - 23.79), among them; 27.8% had DR. The prevalence of sight-threatening DR was 5.7%. Conclusion: The prevalence of DM and the corresponding proportion of DR in this region is lower than that reported in other regions of Saudi Arabia. However, the prevalence of blindness not related to DR is relatively higher than the other studies. PMID:25828282

Anti-DR5 monoclonal antibody-mediated DTIC-loaded nanoparticles combining chemotherapy and immunotherapy for malignant melanoma: target formulation development and in vitro anticancer activity

PubMed Central

Ding, Baoyue; Wu, Xin; Fan, Wei; Wu, Zhaoyong; Gao, Jing; Zhang, Wei; Ma, Lulu; Xiang, Wang; Zhu, Quangang; Liu, Jiyong; Ding, Xueying; Gao, Shen

2011-01-01

Background The increased incidence of malignant melanoma in recent decades, along with its high mortality rate and pronounced resistance to therapy pose an enormous challenge. Novel therapeutic strategies, such as immunotherapy and targeted therapy, are urgently needed for melanoma. In this study, a new active targeting drug delivery system was constructed to combine chemotherapy and active specific immunotherapy. Methods The chemotherapeutic drug, dacarbazine (DTIC), that induces apoptosis through the intrinsic pathway which typically responds to severe DNA damage, was used as a model drug to prepare DTIC-loaded polylactic acid (PLA) nanoparticles (DTIC-NPs), which were covalently conjugated to a highly specific targeting functional TRAIL-receptor 2 (DR5) monoclonal antibody (mAb) that can contribute directly to cancer cell apoptosis or growth inhibition through the extrinsic pathway. Results Our in vitro experiments demonstrated that DTIC-PLA-DR5 mAb nanoparticles (DTIC-NPs-DR5 mAb) are an active targeting drug delivery system which can specifically target DR5-overexpressing malignant melanoma cells and become efficiently internalized. Most strikingly, compared with conventional DTIC-NPs, DTIC-NPs-DR5 mAb showed significantly enhanced cytotoxicity and increased cell apoptosis in DR5-positive malignant melanoma cells. Conclusion The DTIC-NPs-DR5 mAb described in this paper might be a potential formulation for targeting chemotherapy and immunotherapy to DR5-overexpressing metastatic melanoma. PMID:21976975

Osteoinductive activity of insulin-functionalized cell culture surfaces obtained using diazonium chemistry

NASA Astrophysics Data System (ADS)

Mikulska, Anna; Filipowska, Joanna; Osyczka, Anna; Nowakowska, Maria; Szczubiałka, Krzysztof

2014-12-01

Polymeric surfaces suitable for cell culture (DR/Pec) were constructed from diazoresin (DR) and pectin (Pec) in a form of ultrathin films using the layer-by-layer (LbL) technique. The surfaces were functionalized with insulin using diazonium chemistry. Such functionalized surfaces were used to culture human mesenchymal stem cells (hMSCs) to assess their suitability for bone tissue engineering and regeneration. The activity of insulin immobilized on the surfaces (DR/Pec/Ins) was compared to that of insulin dissolved in the culture medium. Human MSC grown on insulin-immobilized DR/Pec surfaces displayed increased proliferation and higher osteogenic activity. The latter was determined by means of alkaline phosphatase (ALP) activity, which increases at early stages of osteoblasts differentiation. Insulin dissolved in the culture medium did not stimulate cell proliferation and its osteogenic activity was significantly lower. Addition of recombinant human bone morphogenetic protein 2 (rhBMP-2) to the culture medium further increased ALP activity in hMSCs indicating additive osteogenic action of immobilized insulin and rhBMP-2

VLA HI Zeeman Observations of the Cygnus X Region: DR 22 And ON 2

NASA Astrophysics Data System (ADS)

Mayo, Elizabeth A.; Troland, T. H.

2010-01-01

The Very Large Array in Socorro, New Mexico has been used to study the Zeeman Effect in the 21cm HI line seen in absorption against radio sources in the Cygnus X region. Cygnus X is geometrically favorable for Zeeman effect observations as the region lies along the mean field direction of the diffuse interstellar medium (ISM) of the galaxy. We present observations of two compact HII regions within Cygnus X, DR 22 and ON 2. The data show magnetic field strengths of the order -80 μG toward DR 22 alone with no significant detections toward ON 2. This information is used to estimate the magnetic energy of the DR 22 star-forming cloud, and allows for a complete analysis of the energetics of the region revealing the role of the magnetic field. Support for this work was provided by the NSF PAARE program to South Carolina State University under award AST-0750814.

Studies of Ultra High Temperature Ceramic Composite Components: Synthesis and Characterization of HfOxCy and Si Oxidation in Atomic Oxygen Containing Environments

DTIC Science & Technology

2008-08-01

Andrea Hafeman and Dr Scott Guelcher for the use of the SDT analysis software. I would like to thank my committee members: Dr Clare McCabe, Dr Sharon...76 4.2: Thermogravimetric curves obtained during oxidation of hafnium...77 4.3: The thermogravimetric curves for hafnia and hafnium oxycarbide (28 mTorr) oxidized at 600°C

Dietary restriction decreases coenzyme Q and ubiquinol potentially via changes in gene expression in the model organism C. elegans.

PubMed

Fischer, Alexandra; Klapper, Maja; Onur, Simone; Menke, Thomas; Niklowitz, Petra; Döring, Frank

2015-05-06

Dietary restriction (DR) is a robust intervention that extends both health span and life span in many organisms. Ubiquinol and ubiquinone represent the reduced and oxidized forms of coenzyme Q (CoQ). CoQ plays a central role in energy metabolism and functions in several cellular processes including gene expression. Here we used the model organism Caenorhabditis elegans to determine level and redox state of CoQ and expression of genes in response to DR. We found that DR down-regulates the steady-state expression levels of several evolutionary conserved genes (i.e. coq-1) that encode key enzymes of the mevalonate and CoQ-synthesizing pathways. In line with this, DR decreases the levels of total CoQ and ubiquinol. This CoQ-reducing effect of DR is obvious in adult worms but not in L4 larvae and is also evident in the eat-2 mutant, a genetic model of DR. In conclusion, we propose that DR reduces the level of CoQ and ubiquinol via gene expression in the model organism C. elegans. © 2015 International Union of Biochemistry and Molecular Biology.

Should pediatric patients wait for HLA-DR-matched renal transplants?

PubMed

Gritsch, H A; Veale, J L; Leichtman, A B; Guidinger, M K; Magee, J C; McDonald, R A; Harmon, W E; Delmonico, F L; Ettenger, R B; Cecka, J M

2008-10-01

Graft survival rates from deceased donors aged 35 years or less among all primary pediatric kidney transplant recipients in the United States between 1996 and 2004 were retrospectively examined to determine the effect of HLA-DR mismatches on graft survival. Zero HLA-DR-mismatched kidneys had statistically comparable 5-year graft survival (71%), to 1-DR-mismatched kidneys (69%) and 2-DR-mismatched kidneys (71%). When compared to donors less than 35 years of age, the relative rate of allograft failure was 1.32 (p = 0.0326) for donor age greater than or equal to age 35. There was no statistical increase in the odds of developing a panel-reactive antibody (PRA) greater than 30% at the time of second waitlisting, based upon the degree of HLA-A, -B or -DR mismatch of the first transplant, nor was there a 'dose effect' when more HLA antigens were mismatched between the donor and recipient. Therefore, pediatric transplant programs should utilize the recently implemented Organ Procurement and Transplantation Network's (OPTN)allocation policy, which prioritizes pediatric recipients to receive kidneys from deceased donors less than 35 years of age, and should not turn down such kidney offers to wait for a better HLA-DR-matched kidney.

The Pleiades apex and its kinematical structure

NASA Astrophysics Data System (ADS)

Elsanhoury, W. H.; Postnikova, E. S.; Chupina, N. V.; Vereshchagin, S. V.; Sariya, Devesh P.; Yadav, R. K. S.; Jiang, Ing-Guey

2018-03-01

A study of cluster characteristics and internal kinematical structure of the middle-aged Pleiades open star cluster is presented. The individual star apexes and various cluster kinematical parameters including the velocity ellipsoid parameters are determined using both Hipparcos and Gaia data. Modern astrometric parameters were taken from the Gaia Data Release 1 (DR1) in combination with the Radial Velocity Experiment Fifth Data Release (DR5). The necessary set of parameters including parallaxes, proper motions and radial velocities are used for n=17 stars from Gaia DR1+RAVE DR5 and for n=19 stars from the Hipparcos catalog using SIMBAD data base. Single stars are used to improve accuracy by eliminating orbital movements. RAVE DR5 measurements were taken only for the stars with the radial velocity errors not exceeding 2 km/s. For the Pleiades stars taken from Gaia, we found mean heliocentric distance as 136.8 ± 6.4 pc, and the apex position is calculated as: A_{CP}=92°.52± 1°.72, D_{CP}=-42°.28± 2°.56 by the convergent point method and A0=95°.59± 2°.30 and D0=-50°.90± 2°.04 using AD-diagram method (n=17 in both cases). The results are compared with those obtained historically before the Gaia mission era.

76 FR 56778 - Puerto Rico; Amendment No. 2 to Notice of a Major Disaster Declaration

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-14

... DEPARTMENT OF HOMELAND SECURITY Federal Emergency Management Agency [Internal Agency Docket No. FEMA-4017-DR; Docket ID FEMA-2011-0001] Puerto Rico; Amendment No. 2 to Notice of a Major Disaster... notice of a major disaster declaration for the Commonwealth of Puerto Rico (FEMA-4017-DR), dated August...

76 FR 66077 - Pennsylvania; Amendment No. 2 to Notice of a Major Disaster Declaration

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-25

.... FEMA-4030-DR; Docket ID FEMA-2011-0001] Pennsylvania; Amendment No. 2 to Notice of a Major Disaster... notice of a major disaster declaration for the Commonwealth of Pennsylvania (FEMA-4030-DR), dated... disaster declaration for the Commonwealth of Pennsylvania is hereby amended to include the Public...

The Geography Teacher. Volume 6, Number 2, 2009

ERIC Educational Resources Information Center

Geography Teacher, 2009

2009-01-01

"The Geography Teacher" provides hands-on reference and educative material for K-12 Geography teachers. The journal also pioneers innovative ideas for contemporary teaching methods, including lesson plans. This issue contains the following: (1) Census in Schools Program (census.gov); (2) Ask Dr. de Blij (Dr. Harm de Blij); (3) Eritrea:…

Gaia DR2 documentation Chapter 6: Spectroscopy

NASA Astrophysics Data System (ADS)

Sartoretti, P.; Blomme, R.; David, M.; Seabroke, G.

2018-04-01

This chapter of the Gaia DR2 documentation describes the processing and validation of the Radial Velocity Spectrometer (RVS) data. A more detailed description of the processing is provided in Sartoretti et al. (2018) and of the validation in Katz et al. (2018). A description of the RVS instrument is provided in Cropper et al. (2018).

Plasma glutamine and glutamic acid are potential biomarkers for predicting diabetic retinopathy.

PubMed

Rhee, Sang Youl; Jung, Eun Sung; Park, Hye Min; Jeong, Su Jin; Kim, Kiyoung; Chon, Suk; Yu, Seung-Young; Woo, Jeong-Taek; Lee, Choong Hwan

2018-01-01

Diabetic patients with a long disease duration usually accompanied complication such as diabetic retinopathy, but in some patients had no complication. We analyzed differences in plasma metabolites according to the presence or absence of diabetic retinopathy (DR) in type 2 diabetic (T2D) patients with disease duration ≥ 15 years. A cohort of 183 T2D patients was established. Their biospecimens and clinical information were collected in accordance with the guidelines of the National Biobank of Korea, and the Korean Diabetes Association. DR phenotypes of the subjects were verified by ophthalmologic specialists. Plasma metabolites were analyzed using gas chromatography time-of-flight mass spectrometry and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. And these results were analyzed using multivariate statistics. For metabolomic study, propensity score matched case and control subjects were chosen. Mean age of the subjects was 66.4 years and mean T2D duration was 22.2 years. Metabolomic identification revealed various carbohydrates, amino acids, and organic compounds that distinguished between age- and sex-matched non-diabetic controls and T2D subjects. Among these, glutamine and glutamic acid were suggested as the most distinctive metabolites for the presence of DR. Receiver operating characteristics curves showed an excellent diagnostic value of combined (AUC = 0.739) and the ratio (AUC = 0.742) of glutamine and glutamic acid for DR. And these results were consistent in validation analyses. Our results imply that plasma glutamine, glutamic acid, and their ratio may be valuable as novel biomarkers for anticipating DR in T2D subjects.

GLP-1 Treatment Improves Diabetic Retinopathy by Alleviating Autophagy through GLP-1R-ERK1/2-HDAC6 Signaling Pathway.

PubMed

Cai, Xiangsheng; Li, Jingjing; Wang, Mingzhu; She, Miaoqin; Tang, Yongming; Li, Jinlong; Li, Hongwei; Hui, Hongxiang

2017-01-01

Objective: Apoptosis and autophagy of retinal cells, which may be induced by oxidative stress, are tightly associated with the pathogenesis of diabetic retinopathy (DR). The autophagy induced by oxidative stress is considered as excessively stimulated autophagy, which accelerates the progression of DR. This study aims to investigate the protective effect of GLP-1 treatment on alleviating apoptosis and autophagy of retinal cells in type 2 diabetic rats and reveals its possible mechanism. Methods: Type 2 diabetic rats were induced by fed with high sugar, high fat diet and followed with streptozotocin injection. GLP-1 was applied to treat the diabetic rats for one week after the onset of diabetes. The expressions of oxidative stress-related enzymes, retinal GLP-1R, mitochondria-dependent apoptosis- related genes, autophagy markers, and autophagy-associated pathway genes were studied by Western blotting or immunohistochemistry analysis. Results: GLP-1treatment reduced the levels of NOX3 and SOD2 in DR. The expression of BCL2 was increased, while the levels of caspase3 and LC3B were reduced through GLP-1 treatment in DR . GLP-1 treatment restored the GLP-1R expression and decreased the levels of phosphorylated AKT and phosphorylated ERK1/2, which was accompanied with the reduction of the HDAC6 levels in DR. Conclusions: GLP-1 treatment can alleviate autophagy which may be induced by oxidative stress; this protective effect is likely through GLP-1R-ERK1/2-HDAC6 signaling pathway.

Astrometry and dynamics of Solar System Objects with Gaia GDR observations and catalogues

NASA Astrophysics Data System (ADS)

Hestroffer, Daniel J. G. J.; Tanga, Paolo

2017-06-01

The Gaia ESA space mission has started to provide its harvest with the first Gaia data release DR1, published in September 2016. Gaia DR1 provides positions for about 1 billion stars and proper motion for the Tycho-Gaia TGAS of 2 million stars with unprecedented accuracy. The second data release DR2 will be the major step in the Gaia mission, providing all astrometric parameters (including parallax and proper motion) for a billion stars, in an absolute reference frame - to become the optical ICRF. Gaia DR2 will also provide epoch astrometry for about 13000 asteroids from its direct observations, down to magnitude V≈20.7. We will discuss the improvement brought by Gaia over 5 years of nominal mission, starting with DR1, and focusing especially on the dynamics of asteroids and other Solar System Objects. This includes use of the catalogue for calibrating future and past photometric and astrometric observations (in particular new reduction of ancient photographic plates digitalised by the NAROO programme), new perspectives for orbit determination and stellar occultations, detection of small acceleration or perturbations for the asteroids. Also we illustrate the ground-based activity coordinated by the Gaia-FUN-SSO network for follow-up observations of newly discovered Near Earth Object.

Underrepresentation of Women and Minorities in the United States IR Academic Physician Workforce.

PubMed

Higgins, Mikhail C S S; Hwang, Wei-Ting; Richard, Chase; Chapman, Christina H; Laporte, Angelique; Both, Stefan; Thomas, Charles R; Deville, Curtiland

2016-12-01

To assess the United States interventional radiology (IR) academic physician workforce diversity and comparative specialties. Public registries were used to assess demographic differences among 2012 IR faculty and fellows, diagnostic radiology (DR) faculty and residents, DR subspecialty fellows (pediatric, abdominal, neuroradiology, and musculoskeletal), vascular surgery and interventional cardiology trainees, and 2010 US medical school graduates and US Census using binomial tests with .001 significance level (Bonferroni adjustment for multiple comparisons). Significant trends in IR physician representation were evaluated from 1992 to 2012. Women (15.4%), blacks (2.0%), and Hispanics (6.2%) were significantly underrepresented as IR fellows compared with the US population. Women were underrepresented as IR (7.3%) versus DR (27.8%) faculty and IR fellows (15.4%) versus medical school graduates (48.3%), DR residents (27.8%), pediatric radiology fellows (49.4%), and vascular surgery trainees (27.7%) (all P < .001). IR ranked last in female representation among radiologic subspecialty fellows. Blacks (1.8%, 2.1%, respectively, for IR faculty and fellows); Hispanics (1.8%, 6.2%); and combined American Indians, Alaska Natives, Native Hawaiians, and Pacific Islanders (1.8%, 0) showed no significant differences in representation as IR fellows compared with IR faculty, DR residents, other DR fellows, or interventional cardiology or vascular surgery trainees. Over 20 years, there was no significant increase in female or black representation as IR fellows or faculty. Women, blacks, and Hispanics are underrepresented in the IR academic physician workforce relative to the US population. Given prevalent health care disparities and an increasingly diverse society, research and training efforts should address IR physician workforce diversity. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

Verification of multimarkers for detection of early stage diabetic retinopathy using multiple reaction monitoring.

PubMed

Kim, Kyunggon; Kim, Sang Jin; Han, Dohyun; Jin, Jonghwa; Yu, Jiyoung; Park, Kyong Soo; Yu, Hyeong Gon; Kim, Youngsoo

2013-03-01

Diabetic retinopathy (DR) is a complication of diabetes and 80% of diabetes mellitus (DM) patients whose DM duration is over 10 years can be expected to suffer with DR. The diagnosis of DR depends on an ophthalmological examination, and no molecular methods of screening DR status exist. Nonproliferative diabetic retinopathy (NPDR) is the early DR which is hard to be noticed in early NPDR, showing significant cause of adult blindness in type 2 diabetes patients. Protein biomarkers have been valuable in the diagnosis of disease and the use of multiple biomarkers has been suggested to overcome the low specificity of single ones. For biomarker development, multiple reaction monitoring (MRM) has been spotlighted as an alternative method to quantify target proteins with no need for immunoassay. In this study, 54 candidate DR marker proteins from a previous study were verified by MRM in plasma samples from NPDR patients in 3 stages (mild, moderate and severe; 15 cases each) and diabetic patients without retinopathy (15 cases) as a control. Notably, 27 candidate markers distinguished moderate NPDR from type 2 diabetic patients with no diabetic retinopathy, generating AUC values (>0.7). Specifically, 28 candidate proteins underwent changes in expression as type 2 diabetic patients with no diabetic retinopathy progressed to mild and moderate NPDR. Further, a combination of 4 markers from these 28 candidates had the improved specificity in distinguishing moderate NPDR from type 2 diabetic patients with no diabetic retinopathy, yielding a merged AUC value of nearly 1.0. We concluded that MRM is a fast, robust approach of multimarker panel determination and an assay platform that provides improved specificity compared with single biomarker assay systems.

KENNEDY SPACE CENTER, FLA. - In the Launch Control Center, officials monitor the “Mode VII” emergency landing simulation being conducted at Kennedy Space Center and managed and directed from the LCC. From left are Dr. Luis Moreno and Dr. David Reed, with Bionetics Life Sciences, and Dr. Philip Scarpa, with the KSC Safety, Occupational Health and Environment Division. The purpose of the Mode VII is to exercise emergency preparedness personnel, equipment and facilities in rescuing astronauts from a downed orbiter and providing immediate medical attention. This simulation presents an orbiter that has crashed short of the Shuttle Landing Facility in a wooded area 2-1/2 miles south of Runway 33. Emergency crews are responding to the volunteer “astronauts” who are simulating various injuries inside the crew compartment mock-up. Rescuers must remove the crew, provide triage and transport to hospitals those who need further treatment. Local hospitals are participating in the exercise.

NASA Image and Video Library

2004-02-18

KENNEDY SPACE CENTER, FLA. - In the Launch Control Center, officials monitor the “Mode VII” emergency landing simulation being conducted at Kennedy Space Center and managed and directed from the LCC. From left are Dr. Luis Moreno and Dr. David Reed, with Bionetics Life Sciences, and Dr. Philip Scarpa, with the KSC Safety, Occupational Health and Environment Division. The purpose of the Mode VII is to exercise emergency preparedness personnel, equipment and facilities in rescuing astronauts from a downed orbiter and providing immediate medical attention. This simulation presents an orbiter that has crashed short of the Shuttle Landing Facility in a wooded area 2-1/2 miles south of Runway 33. Emergency crews are responding to the volunteer “astronauts” who are simulating various injuries inside the crew compartment mock-up. Rescuers must remove the crew, provide triage and transport to hospitals those who need further treatment. Local hospitals are participating in the exercise.

The thioredoxin TRX-1 regulates adult lifespan extension induced by dietary restriction in Caenorhabditis elegans.

PubMed

Fierro-González, Juan Carlos; González-Barrios, María; Miranda-Vizuete, Antonio; Swoboda, Peter

2011-03-18

Dietary restriction (DR) is the only environmental intervention known to extend adult lifespan in a wide variety of animal models. However, the genetic and cellular events that mediate the anti-aging programs induced by DR remain elusive. Here, we used the nematode Caenorhabditis elegans to provide the first in vivo evidence that a thioredoxin (TRX-1) regulates adult lifespan extension induced by DR. We found that deletion of the gene trx-1 completely suppressed the lifespan extension caused by mutation of eat-2, a genetic surrogate of DR in the worm. However, trx-1 deletion only partially suppressed the long lifespan caused by mutation of the insulin-like receptor gene daf-2 or by mutation of the sensory cilia gene osm-5. A trx-1::GFP translational fusion expressed from its own promoter in ASJ neurons (Ptrx-1::trx-1::GFP) rescued the trx-1 deletion-mediated suppression of the lifespan extension caused by mutation of eat-2. This rescue was not observed when trx-1::GFP was expressed from the ges-1 promoter in the intestine. In addition, overexpression of Ptrx-1::trx-1::GFP extended lifespan in wild type, but not in eat-2 mutants. trx-1 deletion almost completely suppressed the lifespan extension induced by dietary deprivation (DD), a non-genetic, nutrient-based model of DR in the worm. Moreover, DD upregulated the expression of a trx-1 promoter-driven GFP reporter gene (Ptrx-1::GFP) in ASJ neurons of aging adults, but not that of control Pgpa-9::GFP (which is also expressed in ASJ neurons). We propose that DR activates TRX-1 in ASJ neurons during aging, which in turn triggers TRX-1-dependent mechanisms to extend adult lifespan in the worm. Copyright © 2011 Elsevier Inc. All rights reserved.

Meta-analysis of association between K469E polymorphism of the ICAM-1 gene and retinopathy in type 2 diabetes

PubMed Central

Fan, Wen-Ying; Liu, Ning-Pu

2015-01-01

AIM To collectively evaluate the association of intercellular adhesion molecule-1 (ICAM-1) gene K469E polymorphism (rs5498) with diabetic retinopathy (DR) in patients with type 2 diabetic mellitus (T2DM). METHODS Overall review of available literatures relating K469E polymorphism to the risk of DR was conducted on 4 electronic databases. Meta-analysis was performed by Stata 12.0 to calculate pooled odds ratios (ORs). Potential sources of heterogeneity and bias were explored. RESULTS Seven studies with genotype frequency data including 1120 cases with DR and 956 diabetic controls free of DR were included. Meta-analysis did not show significant association of K469E polymorphism with DR (P>0.05). A statistically significant association was detected between the K469E polymorphism and proliferative diabetic retinopathy (PDR) in Asians only in dominant model (GG+AG vs AA) with pooled OR of 0.729 (95%CI: 0.564-0.942, P=0.016, Pheterogeneity=0.143), however, this association was not detected in recessive model (GA+AA vs GG; OR=1.178, 95%CI: 0.898-1.545, P=0.236, Pheterogeneity=0.248) or allelic model (G vs A; OR=0.769, 95% CI: 0.576-1.026, P=0.074, Pheterogeneity=0.094). No publication bias was found by Funnel plot, Begg's and Egger's test. CONCLUSION This research found no statistically significant association between ICAM-1 gene K469E polymorphism and DR in patients with T2DM, but showed significant association of the K469E polymorphism with PDR in Asian diabetic patients only in dominant model. Further investigation would be required to consolidate the conclusion. PMID:26086016

Autonomic nervous system function assessed by conventional and spectral analysis might be useful in terms of predicting retinal deterioration in persons with type 1 diabetes mellitus.

PubMed

Duvnjak, L; Tomić, M; Blaslov, K; Vučković Rebrina, S

2016-06-01

To determine whether cardiac autonomic dysfunction represents a risk factor for diabetic retinopathy (DR) development and progression in persons with type 1 diabetes mellitus (T1DM). The study comprised 154 normoalbuminuric persons with T1DM divided into two groups according to the DR presence: with and without DR. Cardiovascular autonomic functioning was measured at baseline using conventional and spectral analysis. Participants were re-examined for the DR presence 18months after. The group with DR had longer disease duration compared to the group without DR (20 vrs 11.5years, p<0.001), heart rate coefficient of variation (HRV-CV) at rest and during deep breathing were lower in participants with DR (p=0.001 and 0.004), as well did spectral indices of HRV: low frequency (LF) band, high frequency (HF) band (p=0.003 and 0.022) while LF/HF ratio indicating sympathovagal balance was higher (p=0.037). No difference in glycaemic control or blood pressure value were observed. Twenty-one (13.36%) participants developed non proliferative DR or progressed to proliferative DR. Cox proportional regression showed that the 18months risk from retinal deterioration was reduced by 33.4% by each increase in the HRV-CV of 1%, 12.7% for the same HRV-CV increase during deep breathing while LF band of 1ms(2) results in 8.6% risk reduction. This study provides evidence that DR should not be considered merely a metabolic control manifestation and that HRV-CV as well as spectral indices of HRV might serve as a practical tool to identify a subgroup of T1DM patients with higher risk of retinal deterioration. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Critical role of surfactants in the formation of digestively-ripened, ultra-small (r<2 nm) copper oxide quantum dots

NASA Astrophysics Data System (ADS)

Talluri, Bhusankar; Prasad, Edamana; Thomas, Tiju

2018-04-01

Synthesis of ultra-small (r < 2 nm) and monodispersed semiconductor quantum dots (QDs) have gained considerable attention due to their wide range of applications, ranging from photovoltaics to sensing. Digestive ripening (DR), a method for preparing uniformly-sized particles is critically influenced by nature and concentrations of the starting materials, solvent, and surfactant. To better understand the DR process there is a need to study the effect of each synthetic parameter. In this work, we investigate the effect of surfactant on a ceramic-DR process, with copper oxide as the chosen material. To study the influence of surfactant; aminoalcohols (triethanolamine, diethanolamine, monoethanolamine), alkylamines (ethyl amine) and aqua ligands are chosen. Digestively ripened quantum dots (QDs) are formed in case of all surfactants except ethyl amine and water. Aminoalchols based surfactants which contain both hydroxyl and amine moieties are efficient ligands (due to their chelation ability) for achieving DR. With the increase of denticity of the ligand, average size of QDs do not vary; however the variance in size does. QDs formed using aminoalchols are more monodispersed when compared to alkyl amine and aqua ligand systems. Furthermore, absorption and photoluminescence spectra suggest that choice of surfactant is important for achieving DR in ceramic nanostructures (when compared to other parameters). Hard-soft-acid-base-interactions between surfactant and copper oxide seem primarily responsible for the observed DR in copper oxide QDs. The absorption and photoluminescence spectra indicate that the energy migration and relaxation pathways taking place in DR QDs depend on the type of capping agent used.

Evaluation of the Demand Response Performance of Electric Water Heaters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mayhorn, Ebony T.; Widder, Sarah H.; Parker, Steven A.

2015-03-17

The purpose of this project is to verify or refute many of the concerns raised by utilities regarding the ability of large tank HPWHs to perform DR by measuring the performance of HPWHs compared to ERWHs in providing DR services. perform DR by measuring the performance of HPWHs compared to ERWHs in providing DR services. This project was divided into three phases. Phase 1 consisted of week-long laboratory experiments designed to demonstrate technical feasibility of individual large-tank HPWHs in providing DR services compared to large-tank ERWHs. In Phase 2, the individual behaviors of the water heaters were then extrapolated tomore » a population by first calibrating readily available water heater models developed in GridLAB-D simulation software to experimental results obtained in Phase 1. These models were used to simulate a population of water heaters and generate annual load profiles to assess the impacts on system-level power and residential load curves. Such population modeling allows for the inherent and permanent load reduction accomplished by the more efficient HPWHs to be considered, in addition to the temporal DR services the water heater can provide by switching ON or OFF as needed by utilities. The economic and emissions impacts of using large-tank water heaters in DR programs are then analyzed from the utility and consumer perspective, based on National Impacts Analysis in Phase 3. Phase 1 is discussed in this report. Details on Phases 2 and 3 can be found in the companion report (Cooke et al. 2014).« less

Direct assays of radiation-induced DNA base lesions in mammalian cells: Technical progress report, July 1, 1986--December 1, 1988

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wheeler, K.T. Jr.

1988-01-01

Our cesium irradiator was installed in April 1987 and has the capability of irradiating DNA solutions, cells and animals at dose rates from >60 Gy/min to <10/sup /minus/2/ Gy/min. By early summer all of the dosimetry and set-ups were established to perform this research. In may 1987, Dr. Krystyna Lesiak left to return to the National Institutes of Health. However, she has remained a collaborator over the past 1/1/2/ years. She has synthesized a large lot of ..cap alpha..-deoxyadenosine, isolated a large batch of both the R and S isomer of cyclodeoxyadenosine and has capped the ..cap alpha..-deoxyadenonsine for usemore » in a DNA synthesizer that uses phosphoramidite chemistry. In November 1987, Dr. Andrzej Surowiec joined our unit as a Visiting Research Assistant Professor. Dr. Surowiec has a MS degree in electrical engineering and did his Ph.D. in Biophysics studying the conductivity of DNA in dilute solution. He has been performing the helix-coil transition experiments. In November 1987, Dr. Steven Swarts also joined our unit as a Postdoctoral Fellow. He received his Ph.D. from Oakland University under Dr. Michael Sevilla with whom we have a collaboration studying the induction of base damage in hydrated DNA. Dr. Swarts has a strong background in spectroscopy and, therefore, was a key individual for determination of the limitations of the HPLC assays and the establishment of a GC/MS capability equivalent to Dr. M. Dizdaroglu at the National Bureau of Standards. 9 refs., 1 tab.« less

Diabetic retinopathy risk prediction for fundus examination using sparse learning: a cross-sectional study.

PubMed

Oh, Ein; Yoo, Tae Keun; Park, Eun-Cheol

2013-09-13

Blindness due to diabetic retinopathy (DR) is the major disability in diabetic patients. Although early management has shown to prevent vision loss, diabetic patients have a low rate of routine ophthalmologic examination. Hence, we developed and validated sparse learning models with the aim of identifying the risk of DR in diabetic patients. Health records from the Korea National Health and Nutrition Examination Surveys (KNHANES) V-1 were used. The prediction models for DR were constructed using data from 327 diabetic patients, and were validated internally on 163 patients in the KNHANES V-1. External validation was performed using 562 diabetic patients in the KNHANES V-2. The learning models, including ridge, elastic net, and LASSO, were compared to the traditional indicators of DR. Considering the Bayesian information criterion, LASSO predicted DR most efficiently. In the internal and external validation, LASSO was significantly superior to the traditional indicators by calculating the area under the curve (AUC) of the receiver operating characteristic. LASSO showed an AUC of 0.81 and an accuracy of 73.6% in the internal validation, and an AUC of 0.82 and an accuracy of 75.2% in the external validation. The sparse learning model using LASSO was effective in analyzing the epidemiological underlying patterns of DR. This is the first study to develop a machine learning model to predict DR risk using health records. LASSO can be an excellent choice when both discriminative power and variable selection are important in the analysis of high-dimensional electronic health records.

Genetic variants specific to aging-related verbal memory: Insights from GWASs in a population-based cohort

PubMed Central

Mekli, Krisztina; McArdle, John J.; Armoskus, Chris; Knowles, James A.

2017-01-01

Verbal memory is typically studied using immediate recall (IR) and delayed recall (DR) scores, although DR is dependent on IR capability. Separating these components may be useful for deciphering the genetic variation in age-related memory abilities. This study was conducted to (a) construct individual trajectories in IR and independent aspects of delayed recall, or residualized-DR (rDR), across older adulthood; and (b) identify genetic markers that contribute to four estimated phenotypes: IR and rDR levels and changes after age 60. A cognitively intact sample (N = 20,650 with 125,164 observations) was drawn from the U.S. Health and Retirement Study, a nationally representative study of adults aged 50 and older. Mixed effects regression models were constructed using repeated measures from data collected every two years (1996–2012) to estimate level at age 60 and change in memory post-60 in IR and rDR. Genome-wide association scans (GWAS) were conducted in the genotypic subsample (N = 7,486) using ~1.2 million single nucleotide polymorphisms (SNPs). One SNP (rs2075650) in TOMM40 associated with rDR level at the genome-wide level (p = 5.0x10-08), an effect that replicated in an independent sample from the English Longitudinal Study on Ageing (N = 6,898 with 41,328 observations). Meta-analysis of rDR level confirmed the association (p = 5.0x10-11) and identified two others in TOMM40 (rs71352238 p = 1.0x10-10; rs157582 p = 7.0x10-09), and one in APOE (rs769449 p = 3.1 x10-12). Meta-analysis of IR change identified associations with three of the same SNPs in TOMM40 (rs157582 p = 8.3x10-10; rs71352238 p = 1.9x10-09) and APOE (rs769449 p = 2.2x10-08). Conditional analyses indicate GWAS signals on rDR level were driven by APOE, whereas signals on IR change were driven by TOMM40. Additionally, we found that TOMM40 had effects independent of APOE e4 on both phenotypes. Findings from this first U.S. population-based GWAS study conducted on both age-related immediate and delayed verbal memory merit continued examination in other samples and additional measures of verbal memory. PMID:28800603

Language barrier and its relationship to diabetes and diabetic retinopathy.

PubMed

Zheng, Yingfeng; Lamoureux, Ecosse L; Chiang, Pei-Chia Peggy; Anuar, Ainur Rahman; Ding, Jie; Wang, Jie Jin; Mitchell, Paul; Tai, E-Shyong; Wong, Tien Y

2012-09-13

Language barrier is an important determinant of health care access and health. We examined the associations of English proficiency with type-2 diabetes (T2DM) and diabetic retinopathy (DR) in Asian Indians living in Singapore, an urban city where English is the predominant language of communication. This was a population-based, cross-sectional study. T2DM was defined as HbA1c ≥6.5%, use of diabetic medication or a physician diagnosis of diabetes. Retinal photographs were graded for the severity of DR including vision-threatening DR (VTDR). Presenting visual impairment (VI) was defined as LogMAR visual acuity > 0.30 in the better-seeing eye. English proficiency at the time of interview was assessed. The analyses included 2,289 (72.1%) English-speaking and 885 (27.9%) Tamil-speaking Indians. Tamil-speaking Indians had significantly higher prevalence of T2DM (46.2 vs. 34.7%, p < 0.001) and, among those with diabetes, higher prevalence of DR (36.0 vs. 30.6%, p < 0.001), VTDR (11.0 vs. 6.5%, p < 0.001), and VI (32.4 vs. 14.6%) than English speaking Indians. Oaxaca decomposition analyses showed that the language-related discrepancies (defined as the difference in prevalence between persons speaking different languages) in T2DM, DR, and VTDR could not be fully explained by socioeconomic measures. In an English dominant society, Tamil-speaking Indians are more likely to have T2DM and diabetic retinopathy. Social policies and health interventions that address language-related health disparities may help reduce the public health impact of T2DM in societies with heterogeneous populations.

Language barrier and its relationship to diabetes and diabetic retinopathy

PubMed Central

2012-01-01

Background Language barrier is an important determinant of health care access and health. We examined the associations of English proficiency with type-2 diabetes (T2DM) and diabetic retinopathy (DR) in Asian Indians living in Singapore, an urban city where English is the predominant language of communication. Methods This was a population-based, cross-sectional study. T2DM was defined as HbA1c ≥6.5%, use of diabetic medication or a physician diagnosis of diabetes. Retinal photographs were graded for the severity of DR including vision-threatening DR (VTDR). Presenting visual impairment (VI) was defined as LogMAR visual acuity > 0.30 in the better-seeing eye. English proficiency at the time of interview was assessed. Results The analyses included 2,289 (72.1%) English-speaking and 885 (27.9%) Tamil- speaking Indians. Tamil-speaking Indians had significantly higher prevalence of T2DM (46.2 vs. 34.7%, p < 0.001) and, among those with diabetes, higher prevalence of DR (36.0 vs. 30.6%, p < 0.001), VTDR (11.0 vs. 6.5%, p < 0.001), and VI (32.4 vs. 14.6%) than English speaking Indians. Oaxaca decomposition analyses showed that the language-related discrepancies (defined as the difference in prevalence between persons speaking different languages) in T2DM, DR, and VTDR could not be fully explained by socioeconomic measures. Conclusions In an English dominant society, Tamil-speaking Indians are more likely to have T2DM and diabetic retinopathy. Social policies and health interventions that address language-related health disparities may help reduce the public health impact of T2DM in societies with heterogeneous populations. PMID:22974298

Regular Chinese Green Tea Consumption Is Protective for Diabetic Retinopathy: A Clinic-Based Case-Control Study

PubMed Central

Ma, Qinghua; Chen, Dandan; Sun, Hong-Peng; Yan, Ning; Xu, Yong; Pan, Chen-Wei

2015-01-01

Objective. To determine the association between regular Chinese green tea consumption and the risk of diabetic retinopathy (DR) in diabetic patients in China. Methods. 100 DR patients and 100 age-sex-matched diabetic controls without retinopathy were recruited in a clinic-based, case-control study. DR was defined from retinal photographs and detailed information on Chinese green tea consumption of the participants was collected through a face-to-face interview. Results. The crude odds ratio [OR] of Chinese green tea consumption for DR was 0.49 (95% confidence interval: 0.26–0.90). When stratified by sex, the protective effect of Chinese green tea consumption on DR was statistically significant in women (P = 0.01) but not in men (P = 0.63). After adjusting for age, sex, and other confounders, DR was significantly associated with Chinese green tea consumption (OR = 0.48; P = 0.04), higher systolic blood pressure (OR = 1.02; P = 0.05), longer duration of diabetes (OR = 1.07; P = 0.02), and the presence of family history of diabetes (OR = 2.35; P = 0.04). Conclusions. Diabetic patients who had regularly drunk Chinese green tea every week for at least one year in their lives had a DR risk reduction of about 50% compared with those who had not. Regular Chinese green tea consumption may be a novel approach for the prevention of DR. PMID:26539551

Regular Chinese Green Tea Consumption is Protective for Diabetic Retinopathy: A Clinic-Based Case-Control Study.

PubMed

Ma, Qinghua; Chen, Dandan; Sun, Hong-Peng; Yan, Ning; Xu, Yong; Pan, Chen-Wei

2015-01-01

To determine the association between regular Chinese green tea consumption and the risk of diabetic retinopathy (DR) in diabetic patients in China. 100 DR patients and 100 age-sex-matched diabetic controls without retinopathy were recruited in a clinic-based, case-control study. DR was defined from retinal photographs and detailed information on Chinese green tea consumption of the participants was collected through a face-to-face interview. The crude odds ratio [OR] of Chinese green tea consumption for DR was 0.49 (95% confidence interval: 0.26-0.90). When stratified by sex, the protective effect of Chinese green tea consumption on DR was statistically significant in women (P = 0.01) but not in men (P = 0.63). After adjusting for age, sex, and other confounders, DR was significantly associated with Chinese green tea consumption (OR = 0.48; P = 0.04), higher systolic blood pressure (OR = 1.02; P = 0.05), longer duration of diabetes (OR = 1.07; P = 0.02), and the presence of family history of diabetes (OR = 2.35; P = 0.04). Diabetic patients who had regularly drunk Chinese green tea every week for at least one year in their lives had a DR risk reduction of about 50% compared with those who had not. Regular Chinese green tea consumption may be a novel approach for the prevention of DR.

Association of Diabetic Macular Edema and Proliferative Diabetic Retinopathy With Cardiovascular Disease: A Systematic Review and Meta-analysis.

PubMed

Xie, Jing; Ikram, M Kamran; Cotch, Mary Frances; Klein, Barbara; Varma, Rohit; Shaw, Jonathan E; Klein, Ronald; Mitchell, Paul; Lamoureux, Ecosse L; Wong, Tien Yin

2017-06-01

Previous studies on the relationship between diabetic retinopathy (DR) and cardiovascular disease (CVD) focused on the early stages of DR. Understanding whether patients with type 2 diabetes and severe stages of DR (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]) have a higher risk of CVD will allow physicians to more effectively counsel patients. To examine the association of severe stages of DR (DME and PDR) with incident CVD in patients with type 2 diabetes. English-language publications were reviewed for articles evaluating the relationship of DR and CVD in MEDLINE, EMBASE, Current Contents, and the Cochrane Library from inception (January 1, 1950) to December 31, 2014, using the search terms diabetic retinopathy OR macular edema AND stroke OR cerebrovascular disease OR coronary artery disease OR heart failure OR myocardial infarction OR angina pectoris OR acute coronary syndrome OR coronary artery disease OR cardiomyopathy. Among 656 studies screened for eligibility, 7604 individuals were included from 8 prospective population-based studies with data on photographic-based DR grading, follow-up visits, and well-defined incident CVD end point. Two independent reviewers conducted a systematic search of the 4 databases, and a single pooled database was developed. Incidence rate ratios (IRRs) were estimated for patients with DME, PDR, and vision-threatening DR, compared with persons without these conditions, by using individual participant data followed by a standard inverse-variance meta-analysis (2-step analysis). The review and analyses were performed from January 1, 2009, to January 1, 2017. Incident CVD, including coronary heart disease, stroke, or death from cardiovascular causes. Among 7604 patients with type 2 diabetes, the prevalence of DME was 4.6% and PDR, 7.4%. After a mean follow-up of 5.9 years (range, 3.2-10.1 years), 1203 incident CVD events, including 916 coronary heart disease cases, were reported. Persons with DME or PDR were more likely to have incident CVD (IRR, 1.39; 95% CI, 1.16-1.67) and fatal CVD (IRR, 2.33; 95% CI, 1.49-3.67) compared with those without DME or PDR. Patients with type 2 diabetes and DME or PDR have an increased risk of incident CVD, which suggests that these persons should be followed up more closely to prevent CVD.

Index of Oral Histories Relating to Naval Research and Development

DTIC Science & Technology

1985-01-01

Repositories: NWC, DTNSRDC, NHC Individuals mentioned: Amlie, Dr. Thomas S. LaBerge , Dr. Walter McLean, Dr. William B. Parsons, RADM William S. Smith...future of R&D in the Navy. Repositories: NWC, DTNSRDC, NHC Individuals mentioned: Bennett, Dr. Ira Hollingsworth, Dr. Guilford L. LaBerge , Dr. Walter...DTNSRDC, NHC Individuals mentioned: Hunter, Dr. Hugh LaBerge . Dr. Walter McLean, Dr. William B. Brode, Dr. Wallace C. Sage, Dr. Bruce Wilson, Dr. Haskell

Application of Component Scoring to a Complicated Cognitive Domain

DTIC Science & Technology

1985-05-15

Command (N-5) NAS Pensacola, FL 32508 Dr. John M. Eddins S..""*University of IllinoisDr. Hans Crombag 252 Engineering Research University of Leyden ...Laboratory Education Research Center 103 South Mathews Street Boerhaavelaan 2 Urbana, IL 61801 2334 EN Leyden The NETHERLANDS V.- University of Illinois...Naval Air Station Pensacola, FL 32508 Ms. Kathleen Moreno Navy Personnel R&D Center Dr. Gary Marco Code 62 Stop 31-E San Diego, CA 92152 Educational

Acquisition Review Quarterly. Vol. 3, No. 2, Fall 1996

DTIC Science & Technology

1996-11-02

ACQUISITION Fall 1996 TABLE OF CONTENTS OPINION 79 - "CYCLE TIME" - A MILITARY IMPERATIVE Dr. Walter B. LaBerge Emphasis on "minimum cycle time" and...MILITARY IMPERATIVE AS WELL Dr. Walter B. LaBerge Dean Clubb, President of the Defense Systems of Electronics Group, Texas Instruments, Inc., makes in his...lives of resources to provide a broad range of tech- American personnel involved. Also, today Dr. LaBerge is Visiting Professor, Executive Institute at

Proceedings of Damping 󈨟, Held in San Diego, California on 13 - 15 February 1991. Volume 2

DTIC Science & Technology

1991-08-01

Efficiency CBC* Dr. L. H. Sperling , J. J. Fay, and Dr. D. A. Thomas The Thermorheologically Complex Material CBD* Lt. Col. Ronald L. Bagley SESSION CC...Andrew S. Bicos. and J. S. Fechter The Need for Passive Damping in Feedback Controlled Flexible Struc- GBB tures Dr. Andreas von Flotow and D. W. Vos...Vibration Research, Southampton, England (R.C. Drew) Lehigh University, Bethlehem, Pennsylvania (L. Sperling ) MrS Corporation, Minneapolis, Minnesota

Distributed Arrays and Signal Processing for the TechSat21 Space-Based Radar

DTIC Science & Technology

2009-04-01

lIlustrating the derivation of minimum aperture size and coherent integration time ............. 25 B 4. Global coordinate system and satellite-based...work of Dr. Robert Mailloux. Dr. Peter Franchi . and Dr. Scott Santarelli. VII Summary The TechSat2l space-based radar concept, suggested by AFRUVS...Linearization for small motions around a reference point in a global circular orbit leads to the Hill equations, derived in 1878, and alternatively named

The 2004 Fitts Lecture: Current Perspective on Combat Casualty Care

DTIC Science & Technology

2005-07-01

deliver this lecture, I actually wondered whether he had called the wrong number. Dr. Basil Pruitt described Dr. William P. Fitts in his 1992 Fitts Lecture...in our ability to care for injured casualties in a deployed setting. Dr. Basil Pruitt eloquently described the interaction between the AAST and...ation ( ABA ) verified burn centers (Fig. 3) in proximity to the USAF hubs.11 We anticipated between 500 and 2,500 burn casualties and created a

CHOROIDAL THICKNESS IN DIABETIC RETINOPATHY ASSESSED WITH SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY.

PubMed

Laíns, Inês; Talcott, Katherine E; Santos, Ana R; Marques, João H; Gil, Pedro; Gil, João; Figueira, João; Husain, Deeba; Kim, Ivana K; Miller, Joan W; Silva, Rufino; Miller, John B

2018-01-01

To compare the choroidal thickness (CT) of diabetic eyes (different stages of disease) with controls, using swept-source optical coherence tomography. A multicenter, prospective, cross-sectional study of diabetic and nondiabetic subjects using swept-source optical coherence tomography imaging. Choroidal thickness maps, according to the nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields, were obtained using automated software. Mean CT was calculated as the mean value within the ETDRS grid, and central CT as the mean in the central 1 mm. Diabetic eyes were divided into four groups: no diabetic retinopathy (No DR), nonproliferative DR (NPDR), NPDR with diabetic macular edema (NPDR + DME), and proliferative DR (PDR). Multilevel mixed linear models were performed for analyses. The authors included 50 control and 160 diabetic eyes (n = 27 No DR, n = 51 NPDR, n = 61 NPDR + DME, and n = 21 PDR). Mean CT (ß = -42.9, P = 0.022) and central CT (ß = -50.2, P = 0.013) were statistically significantly thinner in PDR eyes compared with controls, even after adjusting for confounding factors. Controlling for age, DR eyes presented a significantly decreased central CT than diabetic eyes without retinopathy (β = -36.2, P = 0.009). Swept-source optical coherence tomography demonstrates a significant reduction of CT in PDR compared with controls. In the foveal region, the choroid appears to be thinner in DR eyes than in diabetic eyes without retinopathy.

A Proteome Translocation Response to Complex Desert Stress Environments in Perennial Phragmites Sympatric Ecotypes with Contrasting Water Availability

PubMed Central

Li, Li; Chen, Xiaodan; Shi, Lu; Wang, Chuanjing; Fu, Bing; Qiu, Tianhang; Cui, Suxia

2017-01-01

After a long-term adaptation to desert environment, the perennial aquatic plant Phragmites communis has evolved a desert-dune ecotype. The desert-dune ecotype (DR) of Phragmites communis showed significant differences in water activity and protein distribution compared to its sympatric swamp ecotype (SR). Many proteins that were located in the soluble fraction of SR translocated to the insoluble fraction of DR, suggesting that membrane-associated proteins were greatly reinforced in DR. The unknown phenomenon in plant stress physiology was defined as a proteome translocation response. Quantitative 2D-DIGE technology highlighted these ‘bound’ proteins in DR. Fifty-eight kinds of proteins were identified as candidates of the translocated proteome in Phragmites. The majority were chloroplast proteins. Unexpectedly, Rubisco was the most abundant protein sequestered by DR. Rubisco activase, various chaperons and 2-cysteine peroxiredoxin were major components in the translocation response. Conformational change was assumed to be the main reason for the Rubisco translocation due to no primary sequence difference between DR and SR. The addition of reductant in extraction process partially reversed the translocation response, implying that intracellular redox status plays a role in the translocation response of the proteome. The finding emphasizes the realistic significance of the membrane-association of biomolecule for plant long-term adaptation to complex stress conditions. PMID:28450873

Frequency, severity and risk indicators of retinopathy in patients with diabetes screened by fundus photographs: a study from primary health care

PubMed Central

Memon, Saleh; Ahsan, Shahid; Riaz, Qamar; Basit, Abdul; Ali Sheikh, Sikandar; Fawwad, Asher; Shera, A Samad

2014-01-01

Objective: To determine the frequency, severity and risk indicators of diabetic retinopathy (DR) in patients with diabetes attending a primary care diabetes centre. Methods: This observational study was conducted at Diabetic Association of Pakistan - a World Health Organization collaborating center in Karachi, from March 2009 to December 2011. Registered patients with diabetes were screened by two field fundus photographs. Retina specialists graded the signs of retinopathy according to diabetic retinopathy disease severity scale. Results: Of total registered diabetic patients (n=11,158), 10,768 (96.5 %) were screened for DR. Overall DR was found in 2661 (24.7%) patients. DR was found in decreasing order of frequency in patients with type 2 (n= 2555, 23.7%) followed by patients with type 1 diabetes (n=101, 0.93% ) and patients with gestational diabetes mellitus (GDM) (n=5, 0.46%). Among patients with DR, signs of non-sight threatening retinopathy was dominant. Females and patients of working age group predominantly had retinopathy. Type 1 patients >16 years and type 2 patients < 5 years of history of diabetes had sign of retinopathy in increased frequency. Conclusion: Every forth patient with diabetes in this large cohort had signs of diabetic retinopathy. Females and patients in working age group predominantly had retinopathy. Type 2 patients with short while type 1 patients with long history of diabetes most frequently had DR. Dissemination of the present study findings may help in increasing the awareness of this serious complication of diabetes. PMID:24772145

Effects of maternal genotype and diet on offspring glucose and fatty acid-sensing ventromedial hypothalamic nucleus neurons.

PubMed

Le Foll, Christelle; Irani, Boman G; Magnan, Christophe; Dunn-Meynell, Ambrose; Levin, Barry E

2009-11-01

Maternal obesity accentuates offspring obesity in dams bred to develop diet-induced obesity (DIO) on a 31% fat, high-sucrose, high-energy (HE) diet but has no effect on offspring of diet-resistant (DR) dams. Also, only DIO dams become obese when they and DR dams are fed HE diet throughout gestation and lactation. We assessed glucose and oleic acid (OA) sensitivity of dissociated ventromedial hypothalamic nucleus (VMN) neurons from 3- to 4-wk old offspring of DIO and DR dams fed chow or HE diet using fura-2 calcium imaging to monitor intracellular calcium fluctuations as an index of neuronal activity. Offspring of DIO dams fed chow had approximately 2-fold more glucose-inhibited (GI) neurons than did DR offspring. This difference was eliminated in offspring of DIO dams fed HE diet. At 2.5 mM glucose, offspring of chow-fed DIO dams had more GI neurons that were either excited or inhibited by OA than did DR offspring. Maternal HE diet intake generally increased the percentage of neurons that were excited and decreased the percentage that were inhibited by OA in both DIO and DR offspring. However, this effect was more pronounced in DIO offspring. These data, as well as concentration-dependent differences in OA sensitivity, suggest that genotype, maternal obesity, and dietary content can all affect the sensitivity of offspring VMN neurons to glucose and long-chain fatty acids. Such altered sensitivities may underlie the propensity of DIO offspring to become obese when fed high-fat, high-sucrose diets.

Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: long-term follow-up of a 2-year randomized clinical trial.

PubMed

Wunderink, Lex; Nieboer, Roeline M; Wiersma, Durk; Sytema, Sjoerd; Nienhuis, Fokko J

2013-09-01

Short-term outcome studies of antipsychotic dose-reduction/discontinuation strategies in patients with remitted first-episode psychosis (FEP) showed higher relapse rates but no other disadvantages compared with maintenance treatment; however, long-term effects on recovery have not been studied before. To compare rates of recovery in patients with remitted FEP after 7 years of follow-up of a dose reduction/discontinuation (DR) vs maintenance treatment (MT) trial. Seven-year follow-up of a 2-year open randomized clinical trial comparing MT and DR. One hundred twenty-eight patients participating in the original trial were recruited from 257 patients with FEP referred from October 2001 to December 2002 to 7 mental health care services in a 3.2 million-population catchment area. Of these, 111 patients refused to participate and 18 patients did not experience remission. PARTICIPANTS After 7 years, 103 patients (80.5%) of 128 patients who were included in the original trial were located and consented to follow-up assessment. After 6 months of remission, patients were randomly assigned to DR strategy or MT for 18 months. After the trial, treatment was at the discretion of the clinician. Primary outcome was rate of recovery, defined as meeting the criteria of symptomatic and functional remission. Determinants of recovery were examined using logistic regression analysis; the treatment strategy (MT or DR) was controlled for baseline parameters. The DR patients experienced twice the recovery rate of the MT patients (40.4% vs 17.6%). Logistic regression showed an odds ratio of 3.49 (P = .01). Better DR recovery rates were related to higher functional remission rates in the DR group but were not related to symptomatic remission rates. Dose reduction/discontinuation of antipsychotics during the early stages of remitted FEP shows superior long-term recovery rates compared with the rates achieved with MT. To our knowledge, this is the first study showing long-term gains of an early-course DR strategy in patients with remitted FEP. Additional studies are necessary before these results are incorporated into general practice. isrctn.org Identifier: ISRCTN16228411.

Circulating matrix modulators (MMP-9 and TIMP-1) and their association with severity of diabetic retinopathy.

PubMed

Jayashree, Kuppuswami; Yasir, Md; Senthilkumar, Gandhipuram Periyasamy; Ramesh Babu, K; Mehalingam, Vadivelan; Mohanraj, Palani Selvam

2018-05-05

Diabetic Retinopathy (DR) is the leading cause of vision loss in the working age population. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1), are molecules involved in extracellular tissue matrix remodelling. They are implicated in the loss of retinal tissue integrity, a major cause of DR, that leads to retinal tissue degradation and apoptosis. This study is therefore, conducted to compare the serum levels of MMP-9 and TIMP-1 in T2DM patients without and with retinopathy, and to evaluate their association with the severity of DR. Our study comprised of 2 groups of 41 each. Group A (cases) included T2DM patients with retinopathy and Group B (controls) included T2DM patients without retinopathy. Routine parameters, mainly, fasting blood glucose, and lipid profile were measured using autoanalyzer. Serum MMP-9, TIMP-1, and insulin levels were assessed using ELISA method. Statistically significant increase in the levels of MMP-9, insulin, fasting blood glucose and lipid profile were observed in the serum of T2DM patients with retinopathy, as compared with those without retinopathy. These results help to conclude that rise in MMP-9, and associated serum markers promote disease progress in DR. These findings suggest that the elevations of our study markers in the serum of the type 2 diabetic patients with retinopathy, as compared to those without retinopathy, play important roles in aggravating tissue matrix degradation, supporting DR disease progression. Copyright © 2018. Published by Elsevier Ltd.

Highly stereoselective construction of the C2 stereocentre of α-tocopherol (vitamin E) by asymmetric addition of Grignard reagents to ketones.

PubMed

Bieszczad, Bartosz; Gilheany, Declan G

2017-08-09

Tertiary alcohol precursors of both C2 diastereoisomers of α-tocopherol were prepared in three ways by our recently reported asymmetric Grignard synthesis. The versatility of Grignard chemistry inherent in its three-way disconnection was exploited to allow the synthesis of three product grades: 77 : 23 dr (5 steps), 81 : 19 dr (5 steps) and 96 : 4 dr (7 steps, one gram scale) from readily available and abundant starting materials. The products were converted to their respective α-tocopherols in 3 steps, which allowed a definitive re-assignment of their absolute configurations.

Qualitative Student Models,

DTIC Science & Technology

1986-05-01

University of Leyden AFOSR Baltimore, MD 21204 Education Research Center Bol g Boerhaavelaan 2 asolling ADCDr. Davida Charney 2334 EN Leyden Washington, DC...Kotovsky Dr. Charles Lewis Washington, DC 20002Department of Psychology Faculteit Sociale Wetenschappen Dr. Kathleen McKeownCommunity College of

Space Science

NASA Image and Video Library

1990-12-02

STS-35 lifted off December 2, 1990, at 1:19 am EST, aboard the Space Shuttle Orbiter Columbia. Her crew of eight included: Vance D. Brand, commander; Colonel Guy S. Gardner, pilot; mission specialists Dr. Robert A. R. Parker, John M. (Mike) Lounge, and Dr. Jeffery A. Hoffman; and payload specialists Dr. Kenneth H. Nordsieck, Dr. Samual T. Durrance, and Dr. Ronald A. Parise. The primary objective of the mission was round the clock observation of the celestial sphere in ultraviolet and X-Ray astronomy with the Astro-1 Observatory which consisted of four telescopes: the Hopkins Ultraviolet Telescope (HUT); the Wisconsin Ultraviolet Photo-Polarimeter Experiment (WUPPE); the Ultraviolet Imaging Telescope (UIT); and the Broad Band X-Ray Telescope (BBXRT). Due to loss of data used for pointing and operating the ultraviolet telescopes, Marshall Space Flight Center ground teams were forced to aim the telescopes with fine tuning by the flight crew.

Predictions of stellar occultations by TNOs/Centaurs using Gaia

NASA Astrophysics Data System (ADS)

Desmars, Josselin; Camargo, Julio; Berard, Diane; Sicardy, Bruno; Leiva, Rodrigo; Vieira-Martins, Roberto; Braga-Ribas, Felipe; Assafin, Marcelo; Rossi, Gustavo; Chariklo occultations Team, Rio Group, Lucky Star Occultation Team, Granada Occultation Team

2017-10-01

Stellar occultations are the unique technique from the ground to access physical parameters of the distant solar system objects, such as the measure of the size and the shape at kilometric level, the detection of tenuous atmospheres (few nanobars), and the investigation of close vicinity (satellites, rings, jets).Predictions of stellar occultations require accurate positions of the star and the object.The Gaia DR1 catalog now allows to get stellar position to the milliarcsecond (mas) level. The main uncertainty in the prediction remains in the position of the object (tens to hundreds of mas).Now, we take advantage of the NIMA method for the orbit determination that uses the most recent observations reduced by the Gaia DR1 catalog and the astrometric positions derived from previous positive occultations.Up to now, we have detected nearly 50 positive occultations for about 20 objects that provide astrometric positions of the object at the time of the occultation. The uncertainty of these positions only depends on the uncertainty on the position of the occulted stars, which is a few mas with the Gaia DR1 catalog. The main limitation is now on the proper motion of the star which is only given for bright stars in the Tycho-Gaia Astrometric Solution. This limitation will be solved with the publicationof the Gaia DR2 expected on April 2018 giving proper motions and parallaxes for the Gaia stars. Until this date, we use hybrid stellar catalogs (UCAC5, HSOY) that provide proper motions derived from Gaia DR1 and another stellar catalog.Recently, the Gaia team presented a release of three preliminary Gaia DR2 stellar positions involved in the occultations by Chariklo (22 June and 23 July 2017) and by Triton (5 October 2017).Taking the case of Chariklo as an illustration, we will present a comparison between the proper motions of DR2 and the other catalogs and we will show how the Gaia DR2 will lead to a mas level precision in the orbit and in the prediction of stellar occultations.**Part of the research leading to these results has received funding from the European Research Council under theEuropean Community’s H2020 (2014-2020/ ERC Grant Agreement n 669416 ”LUCKY STAR”).

Technial Programme Committee

NASA Astrophysics Data System (ADS)

2014-06-01

Chairpersons Dr Dinesh Sathyamoorthy, Science & Technology Research Institute for Defence (STRIDE), Ministry of Defence, Malaysia Associate Professor Sr Dr Abdul Rashid Mohamed Shariff, Universiti Putra Malaysia (UPM), Malaysia Dr Ahmad Fikri Abdullah, Universiti Putra Malaysia (UPM), Malaysia Dr Farrah Melissa Muharram, Universiti Putra Malaysia (UPM), Malaysia Members Professor Dr Li Jing, Beijing Normal University, China Professor Dr Iyyanki Muralikrishna, Administrative Staff College of India (ASCI), India Professor Dr Alias Abdul Rahman, Universiti Teknologi Malaysia (UTM), Malaysia Professor Dr Ismat Mohamed El Hassan, King Saud University, Saudi Arabia Professor Dr George Miliaresis, Open University of Cyprus, Cyprus Professor Dr Christine Pohl, Universiti Teknologi Malaysia (UTM), Malaysia Professor Dr Mahender Kotha, Goa University, India Associate Professor Dr Paolo Gamba, University of Pavia, Italy Associate Professor Dr Behara Seshadri Daya Sagar, Indian Statistical Institute (ISI), India Associate Professor Sr Ranjit Singh, Infrastructure University Kuala Lumpur (IUKL), Malaysia Associate Professor Dr Abdul Nasir Matori, Universiti Teknologi Petronas (UTP), Malaysia Associate Dr Lucian Dragut, West University of Timişoara, Romania Associate Professor Dr Saied Pirasteh, Islamic Azad University, Iran Associate Professor Dr Peter Yuen, Cranfield University, United Kingdom Associate Professor Dr Lim Hwee San, Universiti Sains Malaysia (USM), Malaysia Associate Professor Dr Wayan Suparta, Universiti Kebangsaan Malaysia (UKM), Malaysia Associate Professor Dr Tuong Thuy Vu, The University of Nottingham Malaysia Campus, Malaysia Associate Professor Dr Maged Mahmoud Marghany, Universiti Teknologi Malaysia (UTM), Malaysia Associate Professor Dr Rami Al-Ruzouq, University of Sharjah, UAE Associate Professor Dr Biswajeet Pradhan, Universiti Putra Malaysia (UPM), Malaysia Associate Professor Dr Helmi Zulhaidi Mohd Shafri, Universiti Putra Malaysia (UPM), Malaysia Associate Professor Dr Benny Peter, Universiti Teknologi Malaysia (UTM), Malaysia Associate Professor Dr Norzailawati Mohd Nor, International Islamic University Malaysia (IIUM), Malaysia Dr Josée Lévesque, Defence Research and Development Canada (DRDC), Canada Dr Ali Ariapour, Islamic Azad University, Iran Dr Zulkiflee Abd Latif, Universiti Teknologi MARA (UiTM), Malaysia Dr Lim Tien Sze, Multimedia University (MMU), Malaysia Dr Ruzinoor Che Mat, Universiti Utara Malaysia (UUM), Malaysia Dr Eran Sadek Said Md Sadek, Universiti Teknologi MARA (UiTM), Malaysia Dr Siti Khairunniza Bejo, Universiti Putra Malaysia (UPM) Dr Ramin Nourqolipour, National Organization of Forest, Range and Watershed Manage Sr Mohktar Azizi Mohd Din, Universiti Malaya Col (Rt) Frederic Hernoust, Magelli Marzieh Mokarram, University of Isf Mohd Fadhil Abuhan, Royal Malaysian Police, Malaysia

Arf and Rho GAP adapter protein ARAP1 participates in the mobilization of TRAIL-R1/DR4 to the plasma membrane.

PubMed

Símová, Sárka; Klíma, Martin; Cermak, Lukas; Sourková, Vladimíra; Andera, Ladislav

2008-03-01

TRAIL, a ligand of the TNFalpha family, induces upon binding to its pro-death receptors TRAIL-R1/DR4 and TRAIL-R2/DR5 the apoptosis of cancer cells. Activated receptors incite the formation of the Death-Inducing Signaling Complex followed by the activation of the downstream apoptotic signaling. TRAIL-induced apoptosis is regulated at multiple levels, one of them being the presence and relative number of TRAIL pro- and anti-apoptotic receptors on the cytoplasmic membrane. In a yeast two-hybrid search for proteins that interact with the intracellular part (ICP) of DR4, we picked ARAP1, an adapter protein with ArfGAP and RhoGAP activities. In yeast, DR4(ICP) interacts with the alternatively spliced ARAP1 lacking 11 amino acids from the PH5 domain. Transfected ARAP1 co-precipitates with DR4 and co-localizes with it in the endoplasmic reticulum/Golgi, at the cytoplasmic membrane and in early endosomes of TRAIL-treated cells. ARAP1 knockdown significantly compromises the localization of DR4 at the cell surface of several tumor cell lines and slows down their TRAIL-induced death. ARAP1 overexpressed in HEL cells does not affect their TRAIL-induced apoptosis or the membrane localization of DR4, but it enhances the cell-surface presentation of phosphatidyl serine. Our data indicate that ARAP1 is likely involved in the regulation of the cell-specific trafficking of DR4 and might thus affect the efficacy of TRAIL-induced apoptosis.

Automated Diabetic Retinopathy Screening and Monitoring Using Retinal Fundus Image Analysis.

PubMed

Bhaskaranand, Malavika; Ramachandra, Chaithanya; Bhat, Sandeep; Cuadros, Jorge; Nittala, Muneeswar Gupta; Sadda, SriniVas; Solanki, Kaushal

2016-02-16

Diabetic retinopathy (DR)-a common complication of diabetes-is the leading cause of vision loss among the working-age population in the western world. DR is largely asymptomatic, but if detected at early stages the progression to vision loss can be significantly slowed. With the increasing diabetic population there is an urgent need for automated DR screening and monitoring. To address this growing need, in this article we discuss an automated DR screening tool and extend it for automated estimation of microaneurysm (MA) turnover, a potential biomarker for DR risk. The DR screening tool automatically analyzes color retinal fundus images from a patient encounter for the various DR pathologies and collates the information from all the images belonging to a patient encounter to generate a patient-level screening recommendation. The MA turnover estimation tool aligns retinal images from multiple encounters of a patient, localizes MAs, and performs MA dynamics analysis to evaluate new, persistent, and disappeared lesion maps and estimate MA turnover rates. The DR screening tool achieves 90% sensitivity at 63.2% specificity on a data set of 40 542 images from 5084 patient encounters obtained from the EyePACS telescreening system. On a subset of 7 longitudinal pairs the MA turnover estimation tool identifies new and disappeared MAs with 100% sensitivity and average false positives of 0.43 and 1.6 respectively. The presented automated tools have the potential to address the growing need for DR screening and monitoring, thereby saving vision of millions of diabetic patients worldwide. © 2016 Diabetes Technology Society.

75 FR 65502 - Minnesota; Amendment No. 2 to Notice of a Major Disaster Declaration

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-25

.... FEMA-1941-DR; Docket ID FEMA-2010-0002] Minnesota; Amendment No. 2 to Notice of a Major Disaster... notice of a major disaster declaration for the State of Minnesota (FEMA-1941-DR), dated October 13, 2010... for the State of Minnesota is hereby amended to include the following areas among those areas...

75 FR 77889 - Puerto Rico; Amendment No. 2 to Notice of a Major Disaster Declaration

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-14

...; Internal Agency Docket No. FEMA-1946-DR] Puerto Rico; Amendment No. 2 to Notice of a Major Disaster... notice of a major disaster declaration for the Commonwealth of Puerto Rico (FEMA-1946-DR), dated October... disaster declaration for the Commonwealth of Puerto Rico is hereby amended to include the following areas...

2. View of southerly DR 1 antenna looking north 25 ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. View of southerly DR 1 antenna looking north 25 degrees west and and showing radar scanner building no. 105 east face through antenna. - Clear Air Force Station, Ballistic Missile Early Warning System Site II, One mile west of mile marker 293.5 on Parks Highway, 5 miles southwest of Anderson, Anderson, Denali Borough, AK

3. View of middle DR 2 antenna looking north 30 ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. View of middle DR 2 antenna looking north 30 degrees west and showing radar scanner building no. 105 east face through antenna. - Clear Air Force Station, Ballistic Missile Early Warning System Site II, One mile west of mile marker 293.5 on Parks Highway, 5 miles southwest of Anderson, Anderson, Denali Borough, AK

18. View from DR 2 antenna looking south 45 degrees ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

18. View from DR 2 antenna looking south 45 degrees west to backside transmitter building 101 and in left foreground showing site well system building. - Clear Air Force Station, Ballistic Missile Early Warning System Site II, One mile west of mile marker 293.5 on Parks Highway, 5 miles southwest of Anderson, Anderson, Denali Borough, AK

78 FR 24197 - Product Cancellation Order for Certain Pesticide Registrations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-24

...; NY050002; OH030003). IN 46268-1054. 66330 Arysta Life Science North America, LLC, 15401 Weston Parkway... (ME090004) Bayer CropScience LP, 2 T.W. Alexander Dr., P.O. Box 12014, Research Triangle Park, NC 27709. 432 Bayer Environmental Science, 2 T.W. Alexander Dr., P.O. Box 12014, Research Triangle Park, NC 27709. 675...

75 FR 58420 - Wisconsin; Amendment No. 2 to Notice of a Major Disaster Declaration

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-24

.... FEMA-1933-DR; Docket ID FEMA-2010-0002] Wisconsin; Amendment No. 2 to Notice of a Major Disaster... notice of a major disaster declaration for the State of Wisconsin (FEMA-1933-DR), dated August 11, 2010... for the State of Wisconsin is hereby amended to include the Individual Assistance program for the...

76 FR 31352 - Wisconsin; Amendment No. 2 to Notice of a Major Disaster Declaration

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-31

.... FEMA-1966-DR; Docket ID FEMA-2011-0001] Wisconsin; Amendment No. 2 to Notice of a Major Disaster... notice of a major disaster declaration for the State of Wisconsin (FEMA-1966-DR), dated April 5, 2011... for the State of Wisconsin is hereby amended to include the following area among those areas...

75 FR 34703 - Procurement List; Additions and Deletions

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-18

... gallon drum, 1 DR NSN: 7930-00-NIB-0555--BioRenewable Glass Cleaner, 2-liter, 4/BX NSN: 7930-00-NIB-0556--BioRenewable Glass Cleaner, 55 gallon drum, 1 DR NSN: 7930-00-NIB-0557--Neutral Disinfectant Cleaner...-NIB-0559--BioRenewable Industrial Cleaner, 2 liter, 4/ BX NSN: 7930-00-NIB-0560--BioRenewable...

System Framework for a Multi-Band, Multi-Mode Software Defined Radio

DTIC Science & Technology

2014-06-01

detection, while the VITA Radio Transport ( VRT ) protocol over Gigabit Ethernet (GIGE) is implemented for the data interface. In addition to the SoC...CTRL VGA CTRL C2 GPP C2 CORE SW ARM0 RX SYN CTRL PL MEMORY MAP DR CTRL GENERIC INTERRUPT CONTROLLER DR GPP VITERBI ALGORITHM & VRT INTERFACE ARM1

Polarized near-infrared autofluorescence imaging combined with near-infrared diffuse reflectance imaging for improving colonic cancer detection.

PubMed

Shao, Xiaozhuo; Zheng, Wei; Huang, Zhiwei

2010-11-08

We evaluate the diagnostic feasibility of the integrated polarized near-infrared (NIR) autofluorescence (AF) and NIR diffuse reflectance (DR) imaging technique developed for colonic cancer detection. A total of 48 paired colonic tissue specimens (normal vs. cancer) were measured using the integrated NIR DR (850-1100 nm) and NIR AF imaging at the 785 nm laser excitation. The results showed that NIR AF intensities of cancer tissues are significantly lower than those of normal tissues (p<0.001, paired 2-sided Student's t-test, n=48). NIR AF imaging under polarization conditions gives a higher diagnostic accuracy (of ~92-94%) compared to non-polarized NIR AF imaging or NIR DR imaging. Further, the ratio imaging of NIR DR to NIR AF with polarization provides the best diagnostic accuracy (of ~96%) among the NIR AF and NIR DR imaging techniques. This work suggests that the integrated NIR AF/DR imaging under polarization condition has the potential to improve the early diagnosis and detection of malignant lesions in the colon.

Biological hydrogen production by Clostridium acetobutylicum in an unsaturated flow reactor.

PubMed

Zhang, Husen; Bruns, Mary Ann; Logan, Bruce E

2006-02-01

A mesophilic unsaturated flow (trickle bed) reactor was designed and tested for H2 production via fermentation of glucose. The reactor consisted of a column packed with glass beads and inoculated with a pure culture (Clostridium acetobutylicum ATCC 824). A defined medium containing glucose was fed at a flow rate of 1.6 mL/min (0.096 L/h) into the capped reactor, producing a hydraulic retention time of 2.1 min. Gas-phase H2 concentrations were constant, averaging 74 +/- 3% for all conditions tested. H2 production rates increased from 89 to 220 mL/hL of reactor when influent glucose concentrations were varied from 1.0 to 10.5 g/L. Specific H2 production rate ranged from 680 to 1270 mL/g glucose per liter of reactor (total volume). The H2 yield was 15-27%, based on a theoretical limit by fermentation of 4 moles of H2 from 1 mole of glucose. The major fermentation by-products in the liquid effluent were acetate and butyrate. The reactor rapidly (within 60-72 h) became clogged with biomass, requiring manual cleaning of the system. In order to make long-term operation of the reactor feasible, biofilm accumulation in the reactor will need to be controlled through some process such as backwashing. These tests using an unsaturated flow reactor demonstrate the feasibility of the process to produce high H2 gas concentrations in a trickle-bed type of reactor. A likely application of this reactor technology could be H2 gas recovery from pre-treatment of high carbohydrate-containing wastewaters.

Harnessing tumor necrosis factor receptors to enhance antitumor activities of drugs.

PubMed

Muntané, Jordi

2011-10-17

Cancer is the second-leading cause of death in the U.S. behind heart disease and over stroke. The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The inhibition of cell death pathways is one of these tumor characteristics which also include sustained proliferative signaling, evading growth suppressor signaling, replicative immortality, angiogenesis, and promotion of invasion and metastasis. Cell death is mediated through death receptor (DR) stimulation initiated by specific ligands that transmit signaling to the cell death machinery or through the participation of mitochondria. Cell death involving DR is mediated by the superfamily of tumor necrosis factor receptor (TNF-R) which includes TNF-R type I, CD95, DR3, TNF-related apoptosis-inducing ligand (TRAIL) receptor-1 (TRAIL-R1) and -2 (TRAIL-R2), DR6, ectodysplasin A (EDA) receptor (EDAR), and the nerve growth factor (NGF) receptor (NGFR). The expression of these receptors in healthy and tumor cells induces treatment side effects that limit the systemic administration of cell death-inducing therapies. The present review is focused on the different therapeutic strategies such as targeted antibodies or small molecules addressed to selective stimulated DR-mediated apoptosis or reduce cell proliferation in cancer cells.

Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency: a phase 3b, open-label, extension study

PubMed Central

Nilsson, Anna G; Bergthorsdottir, Ragnhildur; Burman, Pia; Dahlqvist, Per; Ekman, Bertil; Engström, Britt Edén; Ragnarsson, Oskar; Skrtic, Stanko; Wahlberg, Jeanette; Achenbach, Heinrich; Uddin, Sharif; Marelli, Claudio

2017-01-01

Objective To investigate the long-term safety and tolerability of a once-daily, dual-release hydrocortisone (DR-HC) tablet as oral glucocorticoid replacement therapy in patients with primary adrenal insufficiency (AI). Design Prospective, open-label, multicenter, 5-year extension study of DR-HC conducted at five university clinics in Sweden. Methods Seventy-one adult patients diagnosed with primary AI who were receiving stable glucocorticoid replacement therapy were recruited. Safety and tolerability outcomes included adverse events (AEs), intercurrent illness episodes, laboratory parameters and vital signs. Quality of life (QoL) was evaluated using generic questionnaires. Results Total DR-HC exposure was 328 patient-treatment years. Seventy patients reported 1060 AEs (323 per 100 patient-years); 85% were considered unrelated to DR-HC by the investigator. The most common AEs were nasopharyngitis (70%), fatigue (52%) and gastroenteritis (48%). Of 65 serious AEs reported by 32 patients (20 per 100 patient-years), four were considered to be possibly related to DR-HC: acute AI (n = 2), gastritis (n = 1) and syncope (n = 1). Two deaths were reported (fall from height and subarachnoid hemorrhage), both considered to be unrelated to DR-HC. From baseline to 5 years, intercurrent illness episodes remained relatively stable (mean 2.6–5.4 episodes per patient per year), fasting plasma glucose (0.7 mmol/L; P < 0.0001) and HDL cholesterol (0.2 mmol/L; P < 0.0001) increased and patient-/investigator-assessed tolerability improved. QoL total scores were unchanged but worsening physical functioning was recorded (P = 0.008). Conclusions In the first prospective study evaluating the long-term safety of glucocorticoid replacement therapy in patients with primary AI, DR-HC was well tolerated with no safety concerns observed during 5-year treatment. PMID:28292927

Oscillation of Angiogenesis with Vascular Dropout in Diabetic Retinopathy by VESsel GENeration Analysis (VESGEN)

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, Patricia; Radbakrishnan, Krisbnan; Vickerman, Mary B.; Kaiser, Peter K.

2010-01-01

PURPOSE. Vascular dropout and angiogenesis are hallmarks of the progression of diabetic retinopathy (DR). However, current evaluation of DR relies on grading of secondary vascular effects, such as microaneurysms and hemorrhages, by clinical examination instead of by evaluation of actual vascular changes. The purpose of this study was to map and quantify vascular changes during progression of DR by VESsel GENeration Analysis (VESGEN). METHODS. In this prospective cross-sectional study, 15 eyes with DR were evaluated with fluorescein angiography (FA) and color fundus photography, and were graded using modified Early Treatment Diabetic Retinopathy Study criteria. FA images were separated by semiautomatic image processing into arterial and venous trees. Vessel length density (L(sub v)), number density (N(sub v)), and diameter (D(sub v)) were analyzed in a masked fashion with VESGEN software. Each vascular tree was automatically segmented into branching generations (G(sub 1)...G(sub 8) or G(sub 9)) by vessel diameter and branching. Vascular remodeling status (VRS) for N(sub v) and L(sub v) was graded 1 to 4 for increasing severity of vascular change. RESULTS. By N(sub v) and L(sub v), VRS correlated significantly with the independent clinical diagnosis of mild to proliferative DR (13/15 eyes). N(sub v) and L(sub v) of smaller vessels (G(sub >=6) increased from VRS1 to VRS2 by 2.4 X and 1.6 X, decreased from VRS2 to VRS3 by 0.4 X and 0.6X, and increased from VRS3 to VRS4 by 1.7 X and 1.5 X (P < 0.01). Throughout DR progression, the density of larger vessels (G(sub 1-5)) remained essentially unchanged, and D(sub v1-5) increased slightly. CONCLUSIONS. Vessel density oscillated with the progression of DR. Alternating phases of angiogenesis/neovascularization and vascular dropout were dominated first by remodeling of arteries and subsequently by veins.

Study methodology and diabetes control in patients from the non-English diabetes management project (NEDMP).

PubMed

Dirani, Mohamed; Dang, Trung M; Xie, Jing; Gnanasekaran, Sivashanth; Nicolaou, Theona; Rees, Gwyneth; Fenwick, Eva; Lamoureux, Ecosse L

2017-03-01

To describe the clinical characteristics of non-English speaking patients from the Diabetes Management Project (NEDMP), and compare their diabetes management and severity of diabetic retinopathy (DR) with the English-speaking DMP sample (EDMP). A prospective study was conducted on non-English speaking adults with diabetes who attended the Royal Victorian Eye and Ear Hospital. 136 (90.1%) non-English speaking adults were assessed, with a mean age of 72.2 years (range: 50-88 years); 74 (54.4%) were male. Participants completed interviewer-administered questionnaires and underwent visual acuity, fundus photography, optical coherence tomography, biochemistry and anthropometric measurements. The EDMP assessed 609 patients in 2009 using a similar protocol. Type and duration of diabetes, diabetes control and diabetic retinopathy. A total of 127 (93.4%) and 8 (5.9%) participants reported having type 2 and type 1 diabetes, respectively, with a median (IQR) duration of 17 (14) years. The proportion of patients with poor diabetes control (HbA1c ≥ 7%) in the NEDMP was similar to the EDMP (64.0% and 68.2%, respectively; P = 0.411). A significantly higher proportion of patients with DR in the NEDMP were found to have poor diabetes control (HbA1c ≥ 7%) compared to those without DR (80.9% vs. 50.0%, P = 0.003). Almost two-thirds of NEDMP patients (74/118) had DR and 23% (27/115) had diabetic macular edema. The prevalence of DR was similar between the NEDMP and EDMP studies, ranging from 25-30% and 28-29%. The clinical characteristics, diabetes control, and DR severity of English and non-English-speaking patients were similar. The high proportion of poor diabetes management in non-English speaking patients with DR suggests educational and behavioural interventions to improve glycaemic control are warranted. © 2016 Royal Australian and New Zealand College of Ophthalmologists.

The relationship between insulin resistance/β-cell dysfunction and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus: the Desheng Diabetic Eye Study.

PubMed

Li, Yun-Yun; Yang, Xiu-Fen; Gu, Hong; Snellingen, Torkel; Liu, Xi-Pu; Liu, Ning-Pu

2018-01-01

To investigate the relationship between insulin resistance (IR)/β-cell dysfunction and diabetic retinopathy (DR) in Chinese patients with type 2 diabetes mellitus (T2DM), and to explore further whether there were differences in the relationship among diabetic patients with higher and lower body mass index (BMI). Cross-sectional study. A total of 1466 subjects with T2DM were recruited in a local Desheng Community of urban Beijing from November 2009 to June 2012 for the cohort of Beijing Desheng Diabetic Eye Study. Standardized evaluation was carried out for each participant, including questionnaire, ocular and anthropometric examinations, and laboratory tests. Seven fields 30° color fundus photographs were used for DR grading according to the Early Treatment Diabetic Retinopathy Study protocols. Homeostatis Model Assessment (HOMA) method was employed for IR and β-cell function assessment. After excluding those participants who were treated with insulin ( n =352) or had missing data of fasting insulin ( n =96), and further excluding those with poor quality of retinal photographs ( n =10), a total of 1008 subjects were included for the final analysis, 406 (40.3%) were men and 602 (59.7%) were women, age ranging from 34 to 86 (64.87±8.28)y. Any DR (levels 14 and above) was present in 278 (27.6%) subjects. After adjusting for possible covariates, the presence of any DR did not correlate with HOMA IR [odds ratio (OR) 1.51, 95% confidence interval (CI) 0.87-2.61, P =0.14] or HOMA β-cell (OR 0.71, 95%CI 0.40-1.26, P =0.25). After stratification by BMI, the presence of any DR was associated positively with HOMA IR (OR 2.46, 95%CI: 1.18-5.12, P =0.016), and negatively with HOMA β-cell (OR 0.40, 95%CI: 0.19-0.87, P =0.021) in the group of patients with higher BMI (≥25 kg/m 2 ). In the group of patients with lower BMI (<25 kg/m 2 ), the presence of any DR was not associated with HOMA IR (OR 1.00, 95%CI: 0.43-2.33, P =1.00) or HOMA β-cell (OR 1.41, 95%CI: 0.60-3.32, P =0.43). The data suggest that higher IR and lower β-cell function are associated with the presence of DR in the subgroup of diabetic patients with higher BMI. However, this association is not statistically significant in diabetic patients with lower BMI.

The Influence of Particle Properties on the Room Temperature Compaction of Polyether-Etherketone (PEEK) Powders.

DTIC Science & Technology

1988-04-01

W. C. Stevens Dr. B. Luxon Damaskos , Inc ........................................................ 2 P. 0. Box 469 Concordville, PA 19331 Attn: N... Damaskos Dr. W. J. Biter DISTRIBUTION LIST (CONTINUED) REPORT NO. NADC-88026-60 DuPont Company

On Learning Maps

DTIC Science & Technology

1975-09-01

Director, Office of Manpower Utilizatic Headquarters, Marine Corps (Code MPU ) MCB (Building 2009) Quantico, VA 22134 1 Dr. A.L. Slafkosky...National Defence HQ Ottawa, Canada K1A OK 2 1 Dr. Alma E. Lantz University of Denver Denver Research Institute Industrial Economics Division

Models for Multidimensional Tests and Hierarchically Structured Training Materials.

DTIC Science & Technology

1985-05-01

NAVOP 01B7 Washington, DC 20370 Dr. Hans Crombag University of Leyden Mr. Raymond E. Christal Education Research Center AFHRL/MOE Boerhaavelaan 2 Brooks...AFB, TX 78235 2334 EN Leyden The NETHERLANDS Dr. Norman Cliff Department of Psychology CTB/McGraw-Hill Library Univ. of So. Californ.a 2500 Garden Road...Diego, CA 92152 A[USTRALIA Ms. Kathleen Moreno Dr. William L. Maloy (02) Navy Personnel R&D Center Chief of Naval Education Code 62 and Training San Diego

Implementation of the Total Quality Leadership Process in U.S. Marine Corps Field Contracting Offices

DTIC Science & Technology

1993-06-01

8 b. Dr. Joseph M. Juran ... .......... 11 c. Dr. Kaoru Ishikawa .... .......... .. 13 2. TQM in the Department of Defense ..... ... 15 3. TQL in the...qualification, etc. [Ref. 8] 12 c. Dr. Kaoru Ishikawa Japan is often lauded as the world’s leader in the quality movement. To understand how the Japanese view the...34The Real Message of the Quality Movement: Building Learning Organizations", Journal for Quality and Participation, March 1992. 10. Ishikawa , Kaoru

Components of High-Level Vision: A Cognitive Neuroscience Analysis and Accounts of Neurological Syndromes

DTIC Science & Technology

1989-02-28

evidence that only one region of space can be attended to at a time (K. Cave and Kosslyn, in press; Downing and Pinker, 1985; LaBerge , 1983; Larsen...97131 New York NY 10027 Dr Steven Grossberg Or Howard Hock 50 Hyde Street Department of Psychology Newton Highland MA 02161 Florida Atlantic University...hU.m Unterstty University r Georgia Pittsburg* l 71213 Athens GA,- AI2-? Dr Stuart 9lapp Dr Steven W. Keele Department of Psychology Psychology

Practices and Standards in the Construction of BRL-CAD Target Descriptions

DTIC Science & Technology

1993-09-01

Spencer) 3 AIFRS (Dr. Steven Carter) AIFRT (John Kosiewicz) AIFRE (S. Eitelman) 220 Seventh Street, NE Charlottesville, VA 22901-5396 3 Director 6...Hawkins, Code 1740.2 2231 Faraday Ave Steven L. Cohen, Code 1230 Suite 103 Dennis Clark, Code 0111 Carlsbad, CA 92008 Dr. Paul C. St. Hilaire, Code...4E995 Washington, DC 20330 1 Dr. Robert B. LaBerge 910 Via Palo 1 Cincinnati Mailacron Inc. Aptos, CA 95003 ATTN: Mr. Richard C. Messinger

Corneal Protection for Burn Patients

DTIC Science & Technology

2013-07-01

Army Institute for Surgical Research (USISR) (by Dr. Johnson s group). This report covers results from Dr. Kochevar s lab and Dr. Johnson is...superluminensent diode source centered at 855 nm to provide an axial resolution of approximately 3 pm. A pair of galvanometric mirrors coupled to a Ziess...Bengal in PBS for 5 min, then exposed to 0, 5 or 50 J/cm2 532 nm light from a cw KTP laser , as reported previously. A weighed portion (—1 mg) was used

Targeting histone abnormality in triple negative breast cancer

DTIC Science & Technology

2017-08-01

ELEMENT NUMBER N/A 6. AUTHOR(S) 5d. PROJECT NUMBER N/A Yi Huang, M.D., Ph.D. 5e. TASK NUMBER N/A E -Mail:huangy2@upmc.edu 5f. WORK UNIT NUMBER...prevention. This funded Breast Cancer Breakthrough Award is initially a partnership between Dr. Yi Huang (initiating PI) and Dr. Nancy E . Davidson...partner PI). During the current funding period, Dr. Nancy E . Davidson moved to University of Washington at Seattle and transferred the Partnering PI to

Hydrostatic Response of Submarine Nickel Aluminum Bronze Valves with Corrosion Damage

DTIC Science & Technology

2008-07-01

Engineering PO Box 1000 Halifax, Nova Scotia B3J 2X4 Project Manager: Dr. T.S. Koko , 902-425-5101 Contract Number: W7707-078022/001/HAL Contract...Manager: Dr. T.S. Koko , 902-425-5101 ext 243 Contract Number: W7707-078022/001/HAL Contract Scientific Authority: Dr. Y. Wang, 902-427-3035...Hydrostatic Response of Submarine Nickel Aluminum Bronze Valves with Corrosion Damage B.K.C. Yuen; T.S. Koko ; R. Warner; DRDC Atlantic CR 2008

Great Institutions in Cardiothoracic Surgery: The University of Minnesota.

PubMed

Huddleston, Stephen J; Shumway, Sara

2016-01-01

With the loyal support of the chair of Surgery, Dr. Owen H. Wangensteen, the University of Minnesota cardiac surgery program led the way at the dawn of cardiac surgery when Dr F. John Lewis performed the first open heart surgery in the world using hypothermia while repairing an atrial septal defect on September 2, 1952. Soon after, Dr C. Walt Lillehei performed the first repair of a ventriculoseptal defect in the world using cross-circulation on March 26, 1954. Collaborating with Dr Richard DeWall in 1955, they developed the DeWall-Lillehei bubble oxygentor which was used at the University of Minnesota and many other centers worldwide for years to come, making open heart surgery safe and tractable. Dr Vincent Gott, a resident working in the laboratory of Lillehei, developed a method to treat complete heart block using ventricular pacing with a Grass physiological stimulator, and this led to a collaboration with Earl Bakken, founder of the Medtronic Corporation, to develop a temporary pacemaker. The program was fertile ground for many notable trainees, including Dr Norman Shumway, the "Father of Heart Transplant", and Dr Christiaan Barnard who performed the first heart transplant in the world. The collegial and forward thinking nature of the cardiac surgery program continues in the current training program today. Copyright © 2016 Elsevier Inc. All rights reserved.

Nobeyama 45 m Cygnus-X CO Survey. I. Photodissociation of Molecules Revealed by the Unbiased Large-scale CN and C18O Maps

NASA Astrophysics Data System (ADS)

Yamagishi, M.; Nishimura, A.; Fujita, S.; Takekoshi, T.; Matsuo, M.; Minamidani, T.; Taniguchi, K.; Tokuda, K.; Shimajiri, Y.

2018-03-01

We present an unbiased large-scale (9 deg2) CN (N = 1–0) and C18O (J = 1–0) survey of Cygnus-X conducted with the Nobeyama 45 m Cygnus-X CO survey. CN and C18O are detected in various objects toward the Cygnus-X North and South (e.g., DR17, DR18, DR21, DR22, DR23, and W75N). We find that CN/C18O integrated intensity ratios are systematically different from region to region, and are especially enhanced in DR17 and DR18, which are irradiated by the nearby OB stars. This result suggests that CN/C18O ratios are enhanced via photodissociation reactions. We investigate the relation between the CN/C18O ratio and strength of the UV radiation field. As a result, we find that CN/C18O ratios correlate with the far-UV intensities, G 0. We also find that CN/C18O ratios decrease inside molecular clouds, where the interstellar UV radiation is reduced due to the interstellar dust extinction. We conclude that the CN/C18O ratio is controlled by the UV radiation, and is a good probe of photon-dominated regions.

Comparative transcriptional profiling identifies takeout as a gene that regulates life span

PubMed Central

Bauer, Johannes; Antosh, Michael; Chang, Chengyi; Schorl, Christoph; Kolli, Santharam; Neretti, Nicola; Helfand, Stephen L.

2010-01-01

A major challenge in translating the positive effects of dietary restriction (DR) for the improvement of human health is the development of therapeutic mimics. One approach to finding DR mimics is based upon identification of the proximal effectors of DR life span extension. Whole genome profiling of DR in Drosophila shows a large number of changes in gene expression, making it difficult to establish which changes are involved in life span determination as opposed to other unrelated physiological changes. We used comparative whole genome expression profiling to discover genes whose change in expression is shared between DR and two molecular genetic life span extending interventions related to DR, increased dSir2 and decreased Dmp53 activity. We find twenty-one genes shared among the three related life span extending interventions. One of these genes, takeout, thought to be involved in circadian rhythms, feeding behavior and juvenile hormone binding is also increased in four other life span extending conditions: Rpd3, Indy, chico and methuselah. We demonstrate takeout is involved in longevity determination by specifically increasing adult takeout expression and extending life span. These studies demonstrate the power of comparative whole genome transcriptional profiling for identifying specific downstream elements of the DR life span extending pathway. PMID:20519778

Impaired reduction of nocturnal systolic blood pressure and severity of diabetic retinopathy

PubMed Central

Felício, João Soares; Pacheco, Juliana Torres; Ferreira, Sandra Roberta; Plavnik, Frida; Moisés, Valdir; Junior, Oswaldo Kohlmann; Ribeiro, Artur Beltrame; Zanella, Maria Tereza

2007-01-01

The aim of the present study was to evaluate the influence of elevated levels of nocturnal blood pressure (BP) on diabetic retinopathy (DR). A total of 88 diabetic hypertensive patients were divided according to the stage of DR. They underwent 24 h ambulatory BP monitoring and ophthalmological evaluation, and their average level of fasting blood glucose as well as their glycemic control index (percentage of fasting blood glucose higher than 11.2 mmol/L over the previous four years) were calculated. When diabetic patients with retinopathy (n=29) (group 1) were compared with patients without retinopathy (n=59) (group 2), a significant difference was observed in diabetes duration (124 months [range six to 460 months] versus 43 months [range six to 365 months], respectively; P<0.05). In addition, group 1 showed higher levels of nocturnal systolic BP (NSBP) (141 ± 22 mmHg versus 132±18 mmHg; P<0.05). However, no significant differences were found between the two groups (group 1 and group 2) when diurnal pressoric levels were compared (diurnal systolic BP, 153±19 mmHg versus 146±19 mmHg, P not significant; and diurnal diastolic BP, 91±9 mmHg versus 91±13 mmHg, P not significant). DR correlated with diabetes duration (r=0.26; P<0.05) and with glycemic control index (r=0.24; P<0.01). Multivariate regression analysis showed NSBP to be an independent predictor of DR (r2=0.12; P<0.01). Moreover, patients with severe stages of DR (preproliferative, proliferative or macular edema) showed a lower decrease of NSBP than the other patients (3.9±6.0 mmHg versus 9.2±6.0 mmHg; P<0.05). The present study suggests that the absence of 24 h normal pressoric rhythm can interfere with the prevalence and severity of DR. PMID:18650998

Acculturation and gestational weight gain in a predominantly Puerto Rican population.

PubMed

Tovar, Alison; Chasan-Taber, Lisa; Bermudez, Odilia I; Hyatt, Raymond R; Must, Aviva

2012-11-21

Identifying risk factors that affect excess weight gain during pregnancy is critical, especially among women who are at a higher risk for obesity. The goal of this study was to determine if acculturation, a possible risk factor, was associated with gestational weight gain in a predominantly Puerto Rican population. We utilized data from Proyecto Buena Salud, a prospective cohort study of Hispanic women in Western Massachusetts, United States. Height, weight and gestational age were abstracted from medical records among participants with full-term pregnancies (n=952). Gestational weight gain was calculated as the difference between delivery and prepregnancy weight. Acculturation (measured via a psychological acculturation scale, generation in the US, place of birth and spoken language preference) was assessed in early pregnancy. Adjusting for age, parity, perceived stress, gestational age, and prepregnancy weight, women who had at least one parent born in Puerto Rico/Dominican Republic (PR/DR) and both grandparents born in PR/DR had a significantly higher mean total gestational weight gain (0.9 kg for at least one parent born in PR/DR and 2.2 kg for grandparents born in PR/DR) and rate of weight gain (0.03 kg/wk for at least one parent born in PR/DR and 0.06 kg/wk for grandparents born in PR/DR) vs. women who were of PR/DR born. Similarly, women born in the US had significantly higher mean total gestational weight gain (1.0 kg) and rate of weight gain (0.03 kg/wk) vs. women who were PR/ DR born. Spoken language preference and psychological acculturation were not significantly associated with total or rate of pregnancy weight gain. We found that psychological acculturation was not associated with gestational weight gain while place of birth and higher generation in the US were significantly associated with higher gestational weight gain. We interpret these findings to suggest the potential importance of the US "obesogenic" environment in influencing unhealthy pregnancy weight gains over specific aspects of psychological acculturation.

Systems modeling accurately predicts responses to genotoxic agents and their synergism with BCL-2 inhibitors in triple negative breast cancer cells.

PubMed

Lucantoni, Federico; Lindner, Andreas U; O'Donovan, Norma; Düssmann, Heiko; Prehn, Jochen H M

2018-01-19

Triple negative breast cancer (TNBC) is an aggressive form of breast cancer which accounts for 15-20% of this disease and is currently treated with genotoxic chemotherapy. The BCL2 (B-cell lymphoma 2) family of proteins controls the process of mitochondrial outer membrane permeabilization (MOMP), which is required for the activation of the mitochondrial apoptosis pathway in response to genotoxic agents. We previously developed a deterministic systems model of BCL2 protein interactions, DR_MOMP that calculates the sensitivity of cells to undergo mitochondrial apoptosis. Here we determined whether DR_MOMP predicts responses of TNBC cells to genotoxic agents and the re-sensitization of resistant cells by BCL2 inhibitors. Using absolute protein levels of BAX, BAK, BCL2, BCL(X)L and MCL1 as input for DR_MOMP, we found a strong correlation between model predictions and responses of a panel of TNBC cells to 24 and 48 h cisplatin (R 2  = 0.96 and 0.95, respectively) and paclitaxel treatments (R 2  = 0.94 and 0.95, respectively). This outperformed single protein correlations (best performer BCL(X)L with R 2 of 0.69 and 0.50 for cisplatin and paclitaxel treatments, respectively) and BCL2 proteins ratio (R 2 of 0.50 for cisplatin and 0.49 for paclitaxel). Next we performed synergy studies using the BCL2 selective antagonist Venetoclax /ABT199, the BCL(X)L selective antagonist WEHI-539, or the MCL1 selective antagonist A-1210477 in combination with cisplatin. In silico predictions by DR_MOMP revealed substantial differences in treatment responses of BCL(X)L, BCL2 or MCL1 inhibitors combinations with cisplatin that were successfully validated in cell lines. Our findings provide evidence that DR_MOMP predicts responses of TNBC cells to genotoxic therapy, and can aid in the choice of the optimal BCL2 protein antagonist for combination treatments of resistant cells.

Immunogenetic background of patients with autoimmune fatigue syndrome.

PubMed

Itoh, Y; Igarashi, T; Tatsuma, N; Imai, T; Yoshida, J; Tsuchiya, M; Murakami, M; Fukunaga, Y

2000-10-01

We have previously reported that approximately 50% of children with chronic nonspecific complaints were positive for antinuclear antibodies (ANA), and that a novel autoantibody to a 62 kD protein (anti-Sa) was found in 40% of these ANA-positive patients. Therefore, we proposed a distinct disease entity termed autoimmune fatigue syndrome (AIFS). We hypothesized that if autoimmune mechanisms did play an important role in the pathogenesis of AIFS, it is possible that it is immunogenetically regulated as observed in other autoimmune disorders. In order to examine the immunogenetic background of AIFS patients, HLA-A, -B, -C, and -DR loci were analyzed serologically in 61 AIFS patients. AIFS was found to be positively associated with the class I antigen HLA-B61 and with the class II antigen HLA-DR9, with odds ratios of 2.77 (p = 0.015, Pcorr = 0.48) and 2.60 (p= 0.012, Pcorr = 0.17), respectively. A negative association was also found between AIFS and HLA-DR2 with odds ratio of 0.25 (p = 0.029, Pcorr = 0.041). When comparing anti-Sa positive AIFS patients with healthy controls, the odds ratios associated with HLA-B61, DR9, and DR2 were 3.42 (p = 0.021, Pcorr = 0.22), 3.96 (p = 0.0011, Pcorr = 0.015), and 0.16 (p = 0.0022, Porr = 0.031), respectively. Thus, the HLA associations observed in this study suggested that immunogenetic background might play a role in AIFS.

Antibodies to Ro/La, Cenp-B, and snRNPs antigens in autoimmune hepatitis of North America versus Asia: patterns of immunofluorescence, ELISA reactivities, and HLA association.

PubMed

Parveen, S; Morshed, S A; Arima, K; Nishioka, M; Czaja, A J; Chow, W C; Ng, H S

1998-06-01

To assess whether demography is one of the important factors determining antibody response to nuclear antigens [ANA: SSA-Ro (52K and 60K), SSB-La, snRNPs (A, 70K, B'/B), and Cenp-B], we investigated 95 and 47 sera of autoimmune hepatitis (AIH) from North America and Asia, respectively, by immunofluorescent (IF) and recombinant ELISA. Correlations among nuclear IF patterns, ELISA, and disease indices were analyzed. The frequency and titer of individual antibodies differed significantly between the groups. Patients with speckled patterns were younger in both regions and had higher aspartate aminotransferase levels only in North America. HLA-A1, B8, DQ2, and DR4 or DR3 or both in North America, and A2, B61, DQ7, and DR4 in Asia were predominant. In Asia, B61 correlated with anti-70K, and DQ7 correlated with antibodies to 52K, Cenp-B, and B'/B. In North America, A1, B8, DR3 haplotype, and DQ2 correlated with antibodies to A and 70K. Anti-B'/B and DR4 in North America, and A2 in Asia, were associated with concurrent immunologic disorder. Individual ANA clusters correlated with individual HLA in the demography, and different HLA alleles might determine disease expression as well as different ANA being produced in AIH.

Assessment of red blood cell deformability in type 2 diabetes mellitus and diabetic retinopathy by dual optical tweezers stretching technique.

PubMed

Agrawal, Rupesh; Smart, Thomas; Nobre-Cardoso, João; Richards, Christopher; Bhatnagar, Rhythm; Tufail, Adnan; Shima, David; Jones, Phil H; Pavesio, Carlos

2016-03-15

A pilot cross sectional study was conducted to investigate the role of red blood cells (RBC) deformability in type 2 diabetes mellitus (T2DM) without and with diabetic retinopathy (DR) using a dual optical tweezers stretching technique. A dual optical tweezers was made by splitting and recombining a single Nd:YAG laser beam. RBCs were trapped directly (i.e., without microbead handles) in the dual optical tweezers where they were observed to adopt a "side-on" orientation. RBC initial and final lengths after stretching were measured by digital video microscopy, and a Deformability index (DI) calculated. Blood from 8 healthy controls, 5 T2DM and 7 DR patients with respective mean age of 52.4 yrs, 51.6 yrs and 52 yrs was analysed. Initial average length of RBCs for control group was 8.45 ± 0.25 μm, 8.68 ± 0.49 μm for DM RBCs and 8.82 ± 0.32 μm for DR RBCs (p < 0.001). The DI for control group was 0.0698 ± 0.0224, and that for DM RBCs was 0.0645 ± 0.03 and 0.0635 ± 0.028 (p < 0.001) for DR group. DI was inversely related to basal length of RBCs (p =  .02). DI of RBC from DM and DR patients was significantly lower in comparison with normal healthy controls. A dual optical tweezers method can hence be reliably used to assess RBC deformability.

VizieR Online Data Catalog: SDSS-III/APOGEE. I. Be stars (Chojnowski+, 2015)

NASA Astrophysics Data System (ADS)

Chojnowski, S. D.; Whelan, D. G.; Wisniewski, J. P.; Majewski, S. R.; Hall, M.; Shetrone, M.; Beaton, R.; Burton, A.; Damke, G.; Eikenberry, S.; Hasselquist, S.; Holtzman, J. A.; Meszaros, S.; Nidever, D.; Schneider, D. P.; Wilson, J.; Zasowski, G.; Bizyaev, D.; Brewington, H.; Brinkmann, J.; Ebelke, G.; Frinchaboy, P. M.; Kinemuchi, K.; Malanushenko, E.; Malanushenko, V.; Marchante, M.; Oravetz, D.; Pan, K.; Simmons, A.

2015-01-01

The sample at hand consists of 238 B-type emission line (Be) stars that have been observed by APOGEE. The Apache Point Observatory Galactic Evolution Experiment (APOGEE) instrument is a 300 fiber, R~22500 spectrograph attached to the SDSS 2.5m telescope at Apache Point Observatory. APOGEE records a vacuum wavelength range of 15145-16955Å via an arrangement of three Teledyne H2RG 2048*2048 detectors. The detector layout consists of "blue," "green," and "red" detectors which cover 15145-15808Å, 15858-16433Å, and 16474-16955Å respectively, resulting in coverage gaps between 15808-15858Å and 16433-16474Å. The APOGEE survey uses the Two Micron All Sky Survey (2MASS; cat. II/246) as a source catalog. Both proprietary and publicly available spectra are used and displayed in this paper. The publicly available spectra were included in SDSS data release 10 (DR10: pertains to APOGEE data taken prior to MJD=56112), and the full data set will be made publicly available in SDSS data release 12 (DR12: scheduled for 2014 December). Shortly after DR12, we intend to convert the ABE star spectra to the format accepted by the Be Star Spectra Database (BeSS; Neiner et al., 2011AJ....142..149N) and deposit them there, ensuring convenient public access. More details on DR10-released APOGEE data can be found on the SDSS-III website (http://www.sdss3.org/dr10/irspec/). (2 data files).

Mitigation of nitrous oxide (N2 O) emission from swine wastewater treatment in an aerobic bioreactor packed with carbon fibers.

PubMed

Yamashita, Takahiro; Yamamoto-Ikemoto, Ryoko; Yokoyama, Hiroshi; Kawahara, Hirofumi; Ogino, Akifumi; Osada, Takashi

2015-03-01

Mitigation of nitrous oxide (N2 O) emission from swine wastewater treatment was demonstrated in an aerobic bioreactor packed with carbon fibers (CF reactor). The CF reactor had a demonstrated advantage in mitigating N2 O emission and avoiding NOx (NO3  + NO2 ) accumulation. The N2 O emission factor was 0.0003 g N2 O-N/gTN-load in the CF bioreactor compared to 0.03 gN2 O-N/gTN-load in an activated sludge reactor (AS reactor). N2 O and CH4 emissions from the CF reactor were 42 g-CO2 eq/m(3) /day, while those from the AS reactor were 725 g-CO2 eq/m(3) /day. The dissolved inorganic nitrogen (DIN) in the CF reactor removed an average of 156 mg/L of the NH4 -N, and accumulated an average of 14 mg/L of the NO3 -N. In contrast, the DIN in the AS reactor removed an average 144 mg/L of the NH4 -N and accumulated an average 183 mg/L of the NO3 -N. NO2 -N was almost undetectable in both reactors. © 2014 Japanese Society of Animal Science.

10 CFR 140.11 - Amounts of financial protection for certain reactors.

Code of Federal Regulations, 2014 CFR

2014-01-01

...,000,000 for each nuclear reactor he is authorized to operate at a thermal power level not exceeding ten kilowatts; (2) In the amount of $1,500,000 for each nuclear reactor he is authorized to operate at... amount of $2,500,000 for each nuclear reactor other than a testing reactor or a reactor licensed under...

10 CFR 140.11 - Amounts of financial protection for certain reactors.

Code of Federal Regulations, 2012 CFR

2012-01-01

...,000,000 for each nuclear reactor he is authorized to operate at a thermal power level not exceeding ten kilowatts; (2) In the amount of $1,500,000 for each nuclear reactor he is authorized to operate at... amount of $2,500,000 for each nuclear reactor other than a testing reactor or a reactor licensed under...

10 CFR 140.11 - Amounts of financial protection for certain reactors.

Code of Federal Regulations, 2013 CFR

2013-01-01

...,000,000 for each nuclear reactor he is authorized to operate at a thermal power level not exceeding ten kilowatts; (2) In the amount of $1,500,000 for each nuclear reactor he is authorized to operate at... amount of $2,500,000 for each nuclear reactor other than a testing reactor or a reactor licensed under...

Development of TRAIL Resistance by Radiation-Induced Hypermethylation of DR4 CpG Island in Recurrent Laryngeal Squamous Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Jong Cheol; Department of Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan; Lee, Won Hyeok

2014-04-01

Purpose: There are limited therapeutic options for patients with recurrent head and neck cancer after radiation therapy failure. To assess the use of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) as a salvage chemotherapeutic agent for recurrent cancer after radiation failure, we investigated the effect of clinically relevant cumulative irradiation on TRAIL-induced apoptosis. Methods and Materials: Using a previously established HN3 cell line from a laryngeal carcinoma patient, we generated a chronically irradiated HN3R isogenic cell line. Viability and apoptosis in HN3 and HN3R cells treated with TRAIL were analyzed with MTS and PI/annexin V-FITC assays. Western blotting and flow cytometry weremore » used to determine the underlying mechanism of TRAIL resistance. DR4 expression was semiquantitatively scored in a tissue microarray with 107 laryngeal cancer specimens. Methylation-specific polymerase chain reaction and bisulfite sequencing for DR4 were performed for genomic DNA isolated from each cell line. Results: HN3R cells were more resistant than HN3 cells to TRAIL-induced apoptosis because of significantly reduced levels of the DR4 receptor. The DR4 staining score in 37 salvage surgical specimens after radiation failure was lower in 70 surgical specimens without radiation treatment (3.03 ± 2.75 vs 5.46 ± 3.30, respectively; P<.001). HN3R cells had a methylated DR4 CpG island that was partially demethylated by the DNA demethylating agent 5-aza-2′-deoxycytidine. Conclusion: Epigenetic silencing of the TRAIL receptor by hypermethylation of a DR4 CpG island might be an underlying mechanism for TRAIL resistance in recurrent laryngeal carcinoma treated with radiation.« less

Feasibility of online IMPT adaptation using fast, automatic and robust dose restoration

NASA Astrophysics Data System (ADS)

Bernatowicz, Kinga; Geets, Xavier; Barragan, Ana; Janssens, Guillaume; Souris, Kevin; Sterpin, Edmond

2018-04-01

Intensity-modulated proton therapy (IMPT) offers excellent dose conformity and healthy tissue sparing, but it can be substantially compromised in the presence of anatomical changes. A major dosimetric effect is caused by density changes, which alter the planned proton range in the patient. Three different methods, which automatically restore an IMPT plan dose on a daily CT image were implemented and compared: (1) simple dose restoration (DR) using optimization objectives of the initial plan, (2) voxel-wise dose restoration (vDR), and (3) isodose volume dose restoration (iDR). Dose restorations were calculated for three different clinical cases, selected to test different capabilities of the restoration methods: large range adaptation, complex dose distributions and robust re-optimization. All dose restorations were obtained in less than 5 min, without manual adjustments of the optimization settings. The evaluation of initial plans on repeated CTs showed large dose distortions, which were substantially reduced after restoration. In general, all dose restoration methods improved DVH-based scores in propagated target volumes and OARs. Analysis of local dose differences showed that, although all dose restorations performed similarly in high dose regions, iDR restored the initial dose with higher precision and accuracy in the whole patient anatomy. Median dose errors decreased from 13.55 Gy in distorted plan to 9.75 Gy (vDR), 6.2 Gy (DR) and 4.3 Gy (iDR). High quality dose restoration is essential to minimize or eventually by-pass the physician approval of the restored plan, as long as dose stability can be assumed. Motion (as well as setup and range uncertainties) can be taken into account by including robust optimization in the dose restoration. Restoring clinically-approved dose distribution on repeated CTs does not require new ROI segmentation and is compatible with an online adaptive workflow.

Design and Validation of a Novel Generic Platform for the Production of Tetravalent IgG1-like Bispecific Antibodies.

PubMed

Golay, Josée; Choblet, Sylvie; Iwaszkiewicz, Justyna; Cérutti, Pierre; Ozil, Annick; Loisel, Séverine; Pugnière, Martine; Ubiali, Greta; Zoete, Vincent; Michielin, Olivier; Berthou, Christian; Kadouche, Jean; Mach, Jean-Pierre; Duonor-Cérutti, Martine

2016-04-01

We have designed and validated a novel generic platform for production of tetravalent IgG1-like chimeric bispecific Abs. The VH-CH1-hinge domains of mAb2 are fused through a peptidic linker to the N terminus of mAb1 H chain, and paired mutations at the CH1-CL interface mAb1 are introduced that force the correct pairing of the two different free L chains. Two different sets of these CH1-CL interface mutations, called CR3 and MUT4, were designed and tested, and prototypic bispecific Abs directed against CD5 and HLA-DR were produced (CD5xDR). Two different hinge sequences between mAb1 and mAb2 were also tested in the CD5xDR-CR3 or -MUT4 background, leading to bispecific Ab (BsAbs) with a more rigid or flexible structure. All four Abs produced bound with good specificity and affinity to CD5 and HLA-DR present either on the same target or on different cells. Indeed, the BsAbs were able to efficiently redirect killing of HLA-DR(+) leukemic cells by human CD5(+) cytokine-induced killer T cells. Finally, all BsAbs had a functional Fc, as shown by their capacity to activate human complement and NK cells and to mediate phagocytosis. CD5xDR-CR3 was chosen as the best format because it had overall the highest functional activity and was very stable in vitro in both neutral buffer and in serum. In vivo, CD5xDR-CR3 was shown to have significant therapeutic activity in a xenograft model of human leukemia. Copyright © 2016 by The American Association of Immunologists, Inc.

Educational differences in disability retirement among young employees in Helsinki, Finland.

PubMed

Sumanen, Hilla; Rahkonen, Ossi; Pietiläinen, Olli; Lahelma, Eero; Roos, Eira; Lahti, Jouni

2016-04-01

Disability retirement (DR) among young employees is an increasing problem affecting work life and public health, given the potential major loss of working time. Little is known about educational differences in the risk of DR among young employees, despite the need for such knowledge in targeting preventive measures. We examined the association between education and DR due to any cause and to mental and non-mental causes among young employees. Personnel register data of the City of Helsinki from the years 2002-2013 for 25-to-34-year-old employees (n= 41225) were linked to register data from the Finnish Centre for Pensions on DR (n= 381), and from Statistics Finland on education. Education was categorised into four hierarchical groups. The mean follow-up time was 5.7 years. Cox regression analysis was used. There were 381 DR events and of the events, over 70% were due to mental disorders and 72% were temporary. A consistent educational gradient was found. Those with a basic education were at the highest risk of DR due to any cause (HR 4.64, 95% CI 3.07, 7.02), and to mental (HR 4.79, 95% CI 2.89, 7.94) and non-mental causes (HR 4.32, 95% CI 2.10, 8.91). DR due to any cause, and to mental and non-mental causes, followed a clear educational gradient. Early intervention, treatment and rehabilitation with a view to maintaining work ability are needed among young employees, especially those with low education. Adapting working conditions to their health and work ability may also help to avoid premature exit from work. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Modelling surface hydrology with DR2-SAGA 1.0: development of a user-friendly interface for hillslope water balance assessments

NASA Astrophysics Data System (ADS)

López-Montero, Teresa; López-Vicente, Manuel; Navas, Ana

2013-04-01

Soil moisture variability and the depth of water stored in the arable layer of the soil are important topics in agricultural research and rangeland management. Additionally, runoff triggers soil detachment and sediment delivery, and thus is one of the most important factors in the soil erosion dynamic. Overland flow generation and accumulation are non-linear and scale-dependent processes and the development of prediction models helps researchers evaluate different scenarios at different temporal and spatial scales. In this study, we present the DR2-SAGA 1.0 module to the scientific community. The DR2 (Distributed Rainfall-Runoff) water balance model computes the depth of water stored within the soil profile (Waa) distinguishing five scenarios of the upslope contributing area, infiltration processes and climatic parameters, and assesses the soil moisture status (SMS) throughout the year for an average monthly rainfall event. The SAGA program is a free Geographical Information System (GIS) with support for vector and, specially, raster data. Its foundation is its Application Programming Interface (API), which provides data object models and basic definitions for the programming of scientific modules. Module libraries contain the scientific methods and are developed using C++ code. The new module was run in a medium size mountain Mediterranean catchment (246 ha; Spanish Central Pre-Pyrenees) at high spatial resolution (5 x 5 meters of cell size). The Estaña Lakes Catchment is affected by karstic processes which explain the presence of 15 endorheic sub-catchments and three fresh-water lakes. Additionally, this area is ungauged and offers the opportunity to test the performance of the new module in a non-conventional landscape. DR2-SAGA 1.0 demands 16 inputs and generates monthly and annual maps of initial and effective runoff depth, Waa and SMS. One user-friendly tab was created with SAGA 2.0.8 for each input and output file. The new module also includes a water balance routine to obtain accurate maps of effective cumulative runoff for any type of accumulation algorithm used. In order to make more readable the results and their legends, a predefined layout was created for each derived map. Further research seeks the development of an equation to add the Effective Hydrological Depth factor in order to improve the reliability of the model in shallow soils. A basic statistical analysis package will also appear in the next version of the module. The development of the DR2-SAGA 1.0 module in the open-source SAGA platform boosts the simulation capacity of the DR2 model in comparison with its application in other commercial GIS software. As a result, we present a scientific module that brings together the set of equations, mathematical calculations and GIS operations included in the DR2 model. DR2-SAGA 1.0 provides a powerful and efficient tool with an intuitive graphical user interface having a low computational cost. In general, DR2-SAGA 1.0 shows great potential for hydrological studies in small and medium size catchments and can be used by both advanced and non-expert users. The new module will be available in the web site of our research center in spring 2013.

Advanced Test Reactor National Scientific User Facility (ATR NSUF) Monthly Report November 2014

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soelberg, Renae

2014-11-01

Advanced Test Reactor National Scientific User Facility (ATR NSUF) Monthly Report November 2014 Highlights Rory Kennedy and Sarah Robertson attended the American Nuclear Society Winter Meeting and Nuclear Technology Expo in Anaheim, California, Nov. 10-13. ATR NSUF exhibited at the technology expo where hundreds of meeting participants had an opportunity to learn more about ATR NSUF. Dr. Kennedy briefed the Nuclear Engineering Department Heads Organization (NEDHO) on the workings of the ATR NSUF. • Rory Kennedy, James Cole and Dan Ogden participated in a reactor instrumentation discussion with Jean-Francois Villard and Christopher Destouches of CEA and several members of themore » INL staff. • ATR NSUF received approval from the NE-20 office to start planning the annual Users Meeting. The meeting will be held at INL, June 22-25. • Mike Worley, director of the Office of Innovative Nuclear Research (NE-42), visited INL Nov. 4-5. Milestones Completed • Recommendations for the Summer Rapid Turnaround Experiment awards were submitted to DOE-HQ Nov. 12 (Level 2 milestone due Nov. 30). Major Accomplishments/Activities • The University of California, Santa Barbara 2 experiment was unloaded from the GE-2000 at HFEF. The experiment specimen packs will be removed and shipped to ORNL for PIE. • The Terrani experiment, one of three FY 2014 new awards, was completed utilizing the Advanced Photon Source MRCAT beamline. The experiment investigated the chemical state of Ag and Pd in SiC shell of irradiated TRISO particles via X-ray Absorption Fine Structure (XAFS) spectroscopy. Upcoming Meetings/Events • The ATR NSUF program review meeting will be held Dec. 9-10 at L’Enfant Plaza. In addition to NSUF staff and users, NE-4, NE-5 and NE-7 representatives will attend the meeting. Awarded Research Projects Boise State University Rapid Turnaround Experiments (14-485 and 14-486) Nanoindentation and TEM work on the T91, HT9, HCM12A and 9Cr ODS specimens has been completed at CAES by Boise State PI Janelle Wharry and Cory Dolph. PI Corey Dolph returned in early November to complete their research by performing nanoindentation on unirradiated specimens that will be used as a baseline for their research.« less

Loss-of-Flow and Loss-of-Pressure Simulations of the BR2 Research Reactor with HEU and LEU Fuel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Licht, J.; Bergeron, A.; Dionne, B.

2016-01-01

Belgian Reactor 2 (BR2) is a research and test reactor located in Mol, Belgium and is primarily used for radioisotope production and materials testing. The Materials Management and Minimization (M3) Reactor Conversion Program of the National Nuclear Security Administration (NNSA) is supporting the conversion of the BR2 reactor from Highly Enriched Uranium (HEU) fuel to Low Enriched Uranium (LEU) fuel. The reactor core of BR2 is located inside a pressure vessel that contains 79 channels in a hyperboloid configuration. The core configuration is highly variable as each channel can contain a fuel assembly, a control or regulating rod, an experimentalmore » device, or a beryllium or aluminum plug. Because of this variability, a representative core configuration, based on current reactor use, has been defined for the fuel conversion analyses. The code RELAP5/Mod 3.3 was used to perform the transient thermal-hydraulic safety analyses of the BR2 reactor to support reactor conversion. The input model has been modernized relative to that historically used at BR2 taking into account the best modeling practices developed by Argonne National Laboratory (ANL) and BR2 engineers.« less

Building a drug ontology based on RxNorm and other sources

PubMed Central

2013-01-01

Background We built the Drug Ontology (DrOn) because we required correct and consistent drug information in a format for use in semantic web applications, and no existing resource met this requirement or could be altered to meet it. One of the obstacles we faced when creating DrOn was the difficulty in reusing drug information from existing sources. The primary external source we have used at this stage in DrOn’s development is RxNorm, a standard drug terminology curated by the National Library of Medicine (NLM). To build DrOn, we (1) mined data from historical releases of RxNorm and (2) mapped many RxNorm entities to Chemical Entities of Biological Interest (ChEBI) classes, pulling relevant information from ChEBI while doing so. Results We built DrOn in a modular fashion to facilitate simpler extension and development of the ontology and to allow reasoning and construction to scale. Classes derived from each source are serialized in separate modules. For example, the classes in DrOn that are programmatically derived from RxNorm are stored in a separate module and subsumed by classes in a manually-curated, realist, upper-level module of DrOn with terms such as 'clinical drug role’, 'tablet’, 'capsule’, etc. Conclusions DrOn is a modular, extensible ontology of drug products, their ingredients, and their biological activity that avoids many of the fundamental flaws found in other, similar artifacts and meets the requirements of our comparative-effectiveness research use-case. PMID:24345026

Building a drug ontology based on RxNorm and other sources.

PubMed

Hanna, Josh; Joseph, Eric; Brochhausen, Mathias; Hogan, William R

2013-12-18

We built the Drug Ontology (DrOn) because we required correct and consistent drug information in a format for use in semantic web applications, and no existing resource met this requirement or could be altered to meet it. One of the obstacles we faced when creating DrOn was the difficulty in reusing drug information from existing sources. The primary external source we have used at this stage in DrOn's development is RxNorm, a standard drug terminology curated by the National Library of Medicine (NLM). To build DrOn, we (1) mined data from historical releases of RxNorm and (2) mapped many RxNorm entities to Chemical Entities of Biological Interest (ChEBI) classes, pulling relevant information from ChEBI while doing so. We built DrOn in a modular fashion to facilitate simpler extension and development of the ontology and to allow reasoning and construction to scale. Classes derived from each source are serialized in separate modules. For example, the classes in DrOn that are programmatically derived from RxNorm are stored in a separate module and subsumed by classes in a manually-curated, realist, upper-level module of DrOn with terms such as 'clinical drug role', 'tablet', 'capsule', etc. DrOn is a modular, extensible ontology of drug products, their ingredients, and their biological activity that avoids many of the fundamental flaws found in other, similar artifacts and meets the requirements of our comparative-effectiveness research use-case.

EVALUATION OF MULTISPECTRAL IMAGING IN DIAGNOSING DIABETIC RETINOPATHY.

PubMed

Li, Liang; Zhang, Pu; Liu, Hong; Liu, Yu-Hua; Gao, Ling

2018-06-12

To investigate multispectral imaging (MSI) as a novel diagnostic approach for diabetic retinopathy (DR) in clinic. A total of 50 Type-2 diabetic patients (99 eyes) were enrolled in this cross-sectional study. All subjects underwent digital fundus photography (DFP), MSI, and fundus fluorescein angiography. A total exact agreement, sensitivity, specificity, positive predictive value, and negative predictive value of no DR/mild nonproliferative diabetic retinopathy (NPDR) and severe NPDR/proliferative diabetic retinopathy (PDR) grading were calculated based on DFP and MSI and were compared with fundus fluorescein angiography. Compared with fundus fluorescein angiography, the exact agreement for MSI was 0.835; for DFP, it was 0.614; the sensitivity for no DR/mild NPDR in both MSI and DFP was 100%, and for severe NPDR/PDR, it was 97.4% and 88.3%. The specificity for no DR/mild NPDR in MSI and DFP was 96.3% and 95%, and for severe NPDR/PDR, it was 100% in both. The positive predictive value for no DR/mild NPDR in MSI and DFP was 86.4% and 82.6%, and for severe NPDR/PDR, it was 100% in both; the negative predictive value for no DR/mild NPDR in MSI and DFP was 100%, and for severe NPDR/PDR, it was 91.7% and 71.0% in both. Multispectral imaging displayed an excellent agreement with fundus fluorescein angiography in DR grading, which suggested that it might serve as a new diagnostic technique and an informative tool for evaluating DR.

APASS Data Release 10

NASA Astrophysics Data System (ADS)

Henden, Arne A.; Levine, Stephen; Terrell, Dirk; Welch, Douglas L.; Munari, Ulisse; Kloppenborg, Brian K.

2018-06-01

The AAVSO Photometric All-Sky Survey (APASS) has been underway since 2010. This survey covers the entire sky from 7.5 < V < 16.5 magnitude, and in the BVugrizY bandpasses. A northern and a southern site are used, each with twin ASA 20cm astrographs and Apogee Aspen CG16m cameras, covering 2.9x2.9 square degrees with 2.6arcsec pixels. Landolt and SDSS standards are used for all-sky solutions, with typical 0.02mag calibration errors on the bright end. DR9 is currently available through VizieR. DR10 is a complete reprocessing of all 500K images taken with the system, including hundreds of nights not part of DR9. Sextractor is used for star finding and centroiding; DAOPHOT is used for aperture photometry; the astrometry.net plate-solving library is used for basic astrometry, supplanted with more precise WCS that utilizes knowledge of the optical train distortions. With these changes, DR10 includes many more stars than prior releases. We describe the survey, its remaining limitations, and prospects for the future, including a very-bright-star extension.

Demand Response Potential for California SubLAPs and Local Capacity Planning Areas: An Addendum to the 2025 California Demand Response Potential Study – Phase 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alstone, Peter; Potter, Jennifer; Piette, Mary Ann

The 2025 California Demand Response Potential Study Phase 2 Report1 was released on March 1, 2017, and described a range of pathways for Demand Response (DR) to support a clean, stable, and cost-effective electric grid for California. One of the Report’s key findings was that while there appears to be very low future value for untargeted DR Shed aimed at system-wide peak load conditions, there could be significant value for locally focused Shed resources. Although the dynamics of renewable capacity expansion have reduced the pressure to build new thermal generation in general, there are still transmission-constrained areas of the statemore » where load growth needs to be managed with the addition of new local capacity, which could include DERs and/or DR. This Addendum to the Phase 2 Report presents a breakdown of the expected future “Local Shed” DR potential at a finer geographic resolution than what is available in the original report, with results summarized by SubLAP and Local Capacity Area (LCA).« less

Neuroprotective Effect of Hydroxytyrosol in Experimental Diabetes Mellitus.

PubMed

Reyes, José Julio; Villanueva, Beatriz; López-Villodres, Juan Antonio; De La Cruz, José Pedro; Romero, Lidia; Rodríguez-Pérez, María Dolores; Rodriguez-Gutierrez, Guillermo; Fernández-Bolaños, Juan; González-Correa, José Antonio

2017-06-07

The aim of the study was to analyze the possible neuroprotective effect of hydroxytyrosol (HT) in diabetic animals in a model of hypoxia-reoxygenation. Rats (10 animals/group) were distributed in five groups: nondiabetic rats, control diabetic rats (DR), and DR rats treated for 2 months with 1, 5, or 10 mg/kg/day po HT. At the end of follow-up, an experimental model of hypoxia-reoxygenation in brain slices was tested. The DR group showed increased cell death, oxidative and nitrosative stress, and an increase in brain inflammatory mediators. These alterations were significantly greater in DR than in normoglycemic animals. HT significantly reduced oxidative (38.5-52.4% lipid peroxidation) and nitrosative stress (48.0-51.0% nitric oxide and 43.9-75.2% peroxynitrite concentration) and brain inflammatory mediators (18.6-40.6% prostaglandin E 2 and 17.0-65.0% interleukin 1β concentration). Cell death was reduced by 25.9, 37.5, and 41.0% after the administration of 1, 5, or 10 mg/kg/day. The administration of HT in rats with experimental diabetes thus had a neuroprotective effect.

Osteoinductive activity of insulin-functionalized cell culture surfaces obtained using diazonium chemistry

PubMed Central

Mikulska, Anna; Filipowska, Joanna; Osyczka, Anna M.; Nowakowska, Maria; Szczubiałka, Krzysztof

2015-01-01

Polymeric surfaces suitable for cell culture (DR/Pec) were constructed from diazoresin (DR) and pectin (Pec) in a form of ultrathin films using the layer-by-layer (LbL) technique. The surfaces were functionalized with insulin using diazonium chemistry. Such functionalized surfaces were used to culture human mesenchymal stem cells (hMSCs) to assess their suitability for bone tissue engineering and regeneration. The activity of insulin immobilized on the surfaces (DR/Pec/Ins) was compared to that of insulin dissolved in the culture medium. Human MSC grown on insulin-immobilized DR/Pec surfaces displayed increased proliferation and higher osteogenic activity. The latter was determined by means of alkaline phosphatase (ALP) activity, which increases at early stages of osteoblasts differentiation. Insulin dissolved in the culture medium did not stimulate cell proliferation and its osteogenic activity was significantly lower. Addition of recombinant human bone morphogenetic protein 2 (rhBMP-2) to the culture medium further increased ALP activity in hMSCs indicating additive osteogenic action of immobilized insulin and rhBMP-2. PMID:25629028