Cytotoxic T cell recognition of an endogenous class I HLA peptide presented by a class II HLA molecule.

PubMed

Chen, B P; Madrigal, A; Parham, P

1990-09-01

Human leukocytes were stimulated in vitro with peptides corresponding in sequence to the highly variable helix of the alpha 1 domain of various HLA-B and -C molecules. A CD4+ CD8- cytotoxic T cell line, CTL-AV, that is specific for the HLA-B7 peptide presented by HLA-DR11.1 was obtained. The HLA-DR11.2 molecule, which only differs at three residues from HLA-DR11.1, did not present the HLA-B7 peptide to CTL-AV. Peptides from the alpha 1 domain helix of other HLA-A and HLA-B molecules, but not HLA-C molecules, competed with the HLA-B7 peptide for binding to HLA-DR11.1. A cell line (WT50) that coexpresses HLA-B7 and HLA-DR11.1 was killed by CTL-AV in the absence of any added HLA-B7 peptide. The processing and presentation of HLA-B7 in these cells appears to be through the endogenous, and not the exogenous, pathway of antigen presentation. Thus, Brefeldin A inhibits presentation and chloroquine does not. Furthermore, introduction of purified HLA-B7 molecules into HLA-DR11.1+, HLA-B7- cells by cytoplasmic loading via osmotic lysis of pinosomes, but not by simple incubation, rendered them susceptible to CTL-AV killing. These results provide an example of class II major histocompatibility complex (MHC) presentation of a constitutively synthesized self protein that uses the endogenous pathway of antigen presentation. They also emphasize the capacity for presentation of MHC peptides by MHC molecules.

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.

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

Ocular myasthenia gravis induced by human acetylcholine receptor ϵ subunit immunization in HLA DR3 transgenic mice.

PubMed

Wu, Xiaorong; Tuzun, Erdem; Saini, Shamsher S; Wang, Jun; Li, Jing; Aguilera-Aguirre, Leopoldo; Huda, Ruksana; Christadoss, Premkumar

2015-12-01

Extraocular muscles (EOM) are preferentially involved in myasthenia gravis (MG) and acetylcholine receptor (AChR) antibody positive MG patients may occasionally present with isolated ocular symptoms. Although experimental autoimmune myasthenia gravis (EAMG) induced by whole AChR immunization closely mimics clinical and immunopathological aspects of MG, EOM are usually not affected. We have previously developed an EAMG model, which imitates EOM symptoms of MG by immunization of human leukocyte antigen (HLA) transgenic mice with α or γ-subunits of human AChR (H-AChR). To investigate the significance of the ϵ-subunit in ocular MG, we immunized HLA-DR3 and HLA-DQ8 transgenic mice with recombinant H-AChR ϵ-subunit expressed in Escherichia coli. HLA-DR3 transgenic mice showed significantly higher clinical ocular and generalized MG severity scores and lower grip strength values than HLA-DQ8 mice. H-AChR ϵ-subunit-immunized HLA-DR3 transgenic mice had higher serum anti-AChR antibody (IgG, IgG1, IgG2b, IgG2c and IgM) levels, neuromuscular junction IgG and complement deposit percentages than ϵ-subunit-immunized HLA-DQ8 transgenic mice. Control mice immunized with E. coli extract or complete Freund adjuvant (CFA) did not show clinical and immunopathological features of ocular and generalized EAMG. Lymph node cells of ϵ-subunit-immunized HLA-DR3 mice showed significantly higher proliferative responses than those of ϵ-subunit-immunized HLA-DQ8 mice, crude E. coli extract-immunized and CFA-immunized transgenic mice. Our results indicate that the human AChR ϵ-subunit is capable of inducing myasthenic muscle weakness. Diversity of the autoimmune responses displayed by mice expressing different HLA class II molecules suggests that the interplay between HLA class II alleles and AChR subunits might have a profound impact on the clinical course of MG. Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

THE ZEEMAN EFFECT IN THE 44 GHZ CLASS I METHANOL MASER LINE TOWARD DR21(OH)

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

Momjian, E.; Sarma, A. P., E-mail: emomjian@nrao.edu, E-mail: asarma@depaul.edu

2017-01-10

We report detection of the Zeeman effect in the 44 GHz Class I methanol maser line, toward the star-forming region DR21(OH). In a 219 Jy beam{sup −1} maser centered at an LSR velocity of 0.83 km s{sup −1}, we find a 20- σ detection of zB {sub los} = 53.5 ± 2.7 Hz. If 44 GHz methanol masers are excited at n ∼ 10{sup 7–8} cm{sup −3}, then the B versus n {sup 1/2} relation would imply, from comparison with Zeeman effect detections in the CN(1 − 0) line toward DR21(OH), that magnetic fields traced by 44 GHz methanol masersmore » in DR21(OH) should be ∼10 mG. Combined with our detected zB {sub los} = 53.5 Hz, this would imply that the value of the 44 GHz methanol Zeeman splitting factor z is ∼5 Hz mG{sup −1}. Such small values of z would not be a surprise, as the methanol molecule is non-paramagnetic, like H{sub 2}O. Empirical attempts to determine z , as demonstrated, are important because there currently are no laboratory measurements or theoretically calculated values of z for the 44 GHz CH{sub 3}OH transition. Data from observations of a larger number of sources are needed to make such empirical determinations robust.« less

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.

Allelic and haplotypic diversity of HLA-A, -B, -C, -DRB1, and -DQB1 genes in the Korean population.

PubMed

Lee, K W; Oh, D H; Lee, C; Yang, S Y

2005-05-01

High-resolution human leukocyte antigen (HLA) typing exposes the unique patterns of HLA allele and haplotype frequencies in each population. In this study, HLA-A, -B, -C, -DRB1, and -DQB1 genotypes were analyzed in 485 apparently unrelated healthy Korean individuals. A total of 20 HLA-A, 43 HLA-B, 21 HLA-C, 31 HLA-DRB1, and 14 HLA-DQB1 alleles were identified. Eleven alleles (A*0201, A*1101, A*2402, A*3303, B*1501, Cw*0102, Cw*0302, Cw*0303, DQB1*0301, DQB1*0302, and DQB1*0303) were found in more than 10% of the population. In each serologic group, a maximum of three alleles were found with several exceptions (A2, B62, DR4, DR14, and DQ6). In each serologic group exhibiting multiple alleles, two major alleles were present at 62-96% (i.e. A*0201 and A*0206 comprise 85% of A2-positive alleles). Multiple-locus haplotypes estimated by the maximum likelihood method revealed 51 A-C, 43 C-B, 52 B-DRB1, 34 DRB1-DQB1, 48 A-C-B, 42 C-B-DRB1, 46 B-DRB1-DQB1, and 30 A-C-B-DRB1-DQB1 haplotypes with frequencies of more than 0.5%. In spite of their high polymorphism in B and DRB1, identification of relatively small numbers of two-locus (B-C and DRB1-DQB1) haplotypes suggested strong associations of those two loci, respectively. Five-locus haplotypes defined by high-resolution DNA typing correlated well with previously identified serology-based haplotypes in the population. The five most frequent haplotypes were: A*3303-Cw*1403-B*4403-DRB1*1302-DQB1*0604 (4.2%), A*3303-Cw*0701/6-B*4403-DRB1*0701-DQB1*0201/2 (3.0%), A*3303-Cw*0302-B*5801-DRB1*1302-DQB1*0609 (3.0%), A*2402-Cw*0702-B*0702-DRB1*0101-DQB1*0501 (2.9%), and A*3001-Cw*0602-B*1302-DRB1*0701-DQB1*0201/2 (2.7%). Several sets of allele level haplotypes that could not be discriminated by routine HLA-A, -B, and -DRB1 low-resolution typing originated from allelic diversity of A2, B61, DR4, and DR8 serologic groups. Information obtained in this study will be useful for medical and forensic applications as well as in anthropology.

Trends in Retinal Damage Thresholds from 100-Millisecond Near-Infrared Laser Radiation Exposures: A Study at 1,110, 1,130, 1,150, and 1,319 nm

DTIC Science & Technology

2009-01-01

Ste B-100 Directed Energy Bioeffects Division San Antonio, TX 78228 Optical Radiation Branch 2624 Louis Bauer Dr. Brooks City-Base, TX...S) Air Force Research Laboratory Human Effectiveness Directorate Directed Energy Bioeffects Division Optical Radiation Branch 2624 Louis Bauer Dr...Research Laboratory, 711th HPW, Optical Radiation Branch, 2624 Louis Bauer Dr., Brooks City-Base, Texas 78231 3Northrop Grumman, 4241 Woodcock Dr. Ste. B

Design Methods in Solid Rocket Motors. Revised Version 1988

DTIC Science & Technology

1988-04-01

15 France DrB.Zelier SNPE/CRB BP No.2 Le Bouchet 91710 Vert Ie Petit France CONTENTS PREFACE LIST OF AUTHORS/SPEAKERS INTRODUCTION by D.Reydellet...DISCUSSIONS BIBLIOGRAPHY "Not available at time of printing. v Page iii iv Reference 1 2 3 4A 4B" 5 6 7 8 9 10 11 RTD B 1-1 Introduction to the lecture series...the year 2000. 1-4 Introduction a la lecture serie 150 par D. REYDELLET Ingenieur en Chef de l’Armement Direction des Engins 26, boulevard Victor

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

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.

Major histocompatibility complex class I chain related gene-A microsatellite polymorphism shows secondary association with type 1 diabetes and celiac disease in North Indians.

PubMed

Kumar, N; Sharma, G; Kaur, G; Tandon, N; Bhatnagar, S; Mehra, N

2012-10-01

Microsatellite polymorphism in exon 5 of major histocompatibility complex class I chain related gene-A (MIC-A) has been implicated in the etiology of autoimmune diseases including type 1 diabetes (T1D) and celiac disease (CD). In this study on North Indian population, the MIC-A5.1 allele, carrying a premature termination codon in transmembrane region, was observed with increased frequency in T1D (29.6%, odds ratio OR = 2.1, P = 0.00017) and CD patients (40.3%, OR = 3.37, P = 1.67E-05) than in controls (16.7%). When the MIC-A5.1 association was adjusted for linkage with human leukocyte antigen (HLA)-DR3, the statistical significance of the association was abolished. This implies that the observed association of MIC-A5.1 is due to its linkage disequilibrium (D' = 0.94) with HLA-B8-DR3-DQ2 haplotype and is secondary to the overall association with DR3 positive MHC haplotypes. © 2012 John Wiley & Sons A/S.

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

Mode Competition in the Quasioptical Gyrotron

DTIC Science & Technology

1990-05-30

dvid Jd n J C nH ]d. v1 dCl v-1 J dC4 vm M Jd ;v M_ &(vl- v1 ) 6(vn - vn °) & r- vm ). (B18) It is clear from (B16)-( BI8 ) that r, G and D depend...AZ 85721 Attn: Dr. Willis E. Lamb, Jr. 1 copy Physical Sciences, Inc. 635 Slaters Lane #G101 Alexandria, VA 22314-1112 ATTN: Dr. M.E. Read 1 copy

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.

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

The Structure-Mapping Engine.

DTIC Science & Technology

1986-05-01

according to the following mapping rules: (1) Attributes of objects are dropped: e.g. RED ( b1 ) -I> RED (t ~) -4 .(2) Relations between objects in the...beaker,viai,water, pipe) B1 T2 T3 TEMPERATURE(coffee) TEMPERATURE(ice cube) ’ . B2 B3 PRESSURE(beaker) PRESSURE(vial) GREATER B4 FLOW(ice cube,coffee,heat...Wasnington, DC 20057 ERIC Facility-Acquisitions Dr Kenneth D. Forbus .5 V 4833 Rugby Avenue University of Illinois Dr. Robert Glaser Bethesda, MD 20014

Association of human leukocyte A, B, and DR antigens in Colombian patients with diagnosis of spondyloarthritis.

PubMed

Santos, Ana M; Peña, Paola; Avila, Mabel; Briceño, Ignacio; Jaramillo, Carlos; Vargas-Alarcon, Gilberto; Rueda, Juan C; Saldarriaga, Eugenia-Lucia; Angarita, Jose-Ignacio; Martinez-Rodriguez, Nancy; Londono, John

2017-04-01

There is substantial evidence that non-B27 major histocompatibility complex (MHC) genes are associated with spondyloarthritis (SpA). Studies in Mexican and Tunisian populations demonstrated the association of SpA and human leukocyte antigen (HLA) B15. The purpose of this study was to evaluate the association of HLA-A, B, and DR antigens in a group of Colombian patients with a diagnosis of SpA. A total of 189 patients and 100 healthy subjects were included in the present study. All subjects underwent a complete characterization of HLA alleles A, B, and DR. Of the 189 studied patients, 35 were reactive arthritis (ReA), 87 were ankylosing spondylitis (AS), and 67 undifferentiated SpA (uSpA). According to the Assessment of Spondyloarthritis International Society (ASAS) criteria, 167 were axial SpA (axSpA) and 171 were peripheral SpA (pSpA). 63.8% were men, with a mean age of 35.9 ± 12.7 years. 40.7% (77/189) of patients were HLA-B27 positive of which 52.9% had AS and 42.5% axSpA. 23.2% (44/189) of patients were HLA-B15 positive: 23.8% were uSpA, 12.57% were axSpA, and 11.7% were pSpA. In addition, HLA-DRB1*01 was associated with AS (58.6%) and axSpA (42.5%). Also, HLA-DRB1*04 was present in 62 patients with AS (71.2%) and in 26 with axSpA (15.5%). In this population, we found a strong association between the presence of HLA-B27 and the diagnosis of axSpA and AS, but the HLA-B15 is also significantly associated with all subtypes of the disease, predominantly with pSpA. Additionally, HLA-DR1 and DR4 were associated in a cohort of patients with SpA from Colombia.

Proceedings of the Computerized Adaptive Testing Conference (1979) Held at Wayzata, Minnesota on 27-30 June 1979,

DTIC Science & Technology

1980-09-01

34 .-..- , / ,’# o ’. I a / " / ,...,.. a1 - 0.25 and b1 - 0.00 * I,-- - a 2 . 0.50 and b2- 0.50 .. a3 0.75 and b3- 2.00 . * - a 1.00 and b - -1.50a / .a- 2.00...with the Parameters a - .25, b1 = 0.0, a2 = .50, and b 2 - 1.0 0 C)| Response Patterns 0, -. zI o I I I != , 4. U,o 1. I u_ i l o - I ]/ ... - c1.0...Facility-AcquiSitions Dr. Marty Rockway 4833 Rugby Avenue Technical Director yBethesda, 20014 AFHRL(OT) Dr. Susan Dlopmean Williams APB. AZ 58224

Nitric oxide sensitizes tumor cells to TRAIL-induced apoptosis via inhibition of the DR5 transcription repressor Yin Yang 1.

PubMed

Huerta-Yepez, Sara; Vega, Mario; Escoto-Chavez, Saul E; Murdock, Benjamin; Sakai, Toshiyuki; Baritaki, Stavroula; Bonavida, Benjamin

2009-02-01

Treatment of TRAIL-resistant tumor cells with the nitric oxide donor DETANONOate sensitizes the tumor cells to TRAIL-induced apoptosis concomitantly with DR5 upregulation. The mechanism of sensitization was examined based on the hypothesis that DETANONOate inhibits a transcription repressor Yin Yang 1 (YY1) that negatively regulates DR5 transcription. Treatment of the prostate carcinoma cell lines with DETANONOate inhibited both NF-kappaB and YY1 DNA-binding activities concomitantly with upregulation of DR5 expression. The direct role of YY1 in the regulation of TRAIL resistance was demonstrated in cells treated with YY1 siRNA resulting in TRAIL-induced apoptosis. The role of YY1 in the transcriptional regulation of DR5 was examined in cells treated with a DR5 luciferase reporter system (pDR5) and two constructs, namely, the pDR5/-605 construct with a deletion of the putative YY1 DNA-binding region (-1224 to -605) and a construct pDR5-YY1 with a mutation of the YY1 DNA-binding site. A significant (3-fold) augmentation of luciferase activity over baseline transfection with pDR5 was observed in cells transfected with the modified constructs. ChIP analysis corroborated the YY1 binding to the DR5 promoter. In vivo, tissues from nude mice bearing the PC-3 xenograft and treated with DETANONOate showed inhibition of YY1 and upregulation of DR5. The present findings demonstrate that YY1 negatively regulates DR5 transcription and expression and these correlated with resistance to TRAIL-induced apoptosis. DETANONOate inhibits both NF-kappaB and YY1 and in combination with TRAIL reverses tumor cell resistance to TRAIL apoptosis.

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

Chen, Haiwen; Li, Hongliang, E-mail: honglianglity@sina.com; Chen, Qi

Docetaxel efficiency in the therapy of prostate cancer (PCa) patients is limited due to the development of chemoresistance. Recent studies have implied a role of INPP4B in tumor chemoresistance, while the effects of INPP4B on docetaxel resistance in PCa have not been elucidated. In the present study, the docetaxel-resistant human PCa cell lines PC3-DR and DU-145-DR were established from the parental cell lines PC3 and DU-145, and the expression and role of INPP4B in docetaxel-resistant PCa cells were investigated. The results demonstrated that INPP4B expression was significantly downregulated in docetaxel-resistant cells. Overexpression of INPP4B increased the sensitivity to docetaxel andmore » promoted cell apoptosis in PC3-DR and DU-145-DR cells. In addition, INPP4B overexpression downregulated the expression of the mesenchymal markers fibronectin, N-cadherin, and vimentin, and upregulated the expression level of the epithelial maker E-cadherin. Furthermore, INPP4B overexpression markedly inhibited the PI3K/Akt pathway. We also found that IGF-1, the inhibitor of PI3K/Akt, markedly blocked the change in EMT markers induced by overexpression of INPP4B, and reversed the resistance of PC3-DR and DU-145-DR cells to docetaxel, which is sensitized by Flag-INPP4B. In summary, the presented data indicate that INPP4B is crucial for docetaxel-resistant PCa cell survival, potentially by regulating EMT through the PI3K/Akt signaling pathway. - Highlights: • INPP4B is downregulated in docetaxel-resistant PCa cells. • INPP4B inhibits cell proliferation. • INPP4B induces cell apoptosis. • INPP4B inhibits PCa cell EMT.« less

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

A high gain wide dynamic range transimpedance amplifier for optical receivers

NASA Astrophysics Data System (ADS)

Lianxi, Liu; Jiao, Zou; Yunfei, En; Shubin, Liu; Yue, Niu; Zhangming, Zhu; Yintang, Yang

2014-01-01

As the front-end preamplifiers in optical receivers, transimpedance amplifiers (TIAs) are commonly required to have a high gain and low input noise to amplify the weak and susceptible input signal. At the same time, the TIAs should possess a wide dynamic range (DR) to prevent the circuit from becoming saturated by high input currents. Based on the above, this paper presents a CMOS transimpedance amplifier with high gain and a wide DR for 2.5 Gbit/s communications. The TIA proposed consists of a three-stage cascade pull push inverter, an automatic gain control circuit, and a shunt transistor controlled by the resistive divider. The inductive-series peaking technique is used to further extend the bandwidth. The TIA proposed displays a maximum transimpedance gain of 88.3 dBΩ with the -3 dB bandwidth of 1.8 GHz, exhibits an input current dynamic range from 100 nA to 10 mA. The output voltage noise is less than 48.23 nV/√Hz within the -3 dB bandwidth. The circuit is fabricated using an SMIC 0.18 μm 1P6M RFCMOS process and dissipates a dc power of 9.4 mW with 1.8 V supply voltage.

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

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.

Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase.

PubMed

Gu, Lijun; Kawana-Tachikawa, Ai; Shiino, Teiichiro; Nakamura, Hitomi; Koga, Michiko; Kikuchi, Tadashi; Adachi, Eisuke; Koibuchi, Tomohiko; Ishida, Takaomi; Gao, George F; Matsushita, Masaki; Sugiura, Wataru; Iwamoto, Aikichi; Hosoya, Noriaki

2014-01-01

Drug resistance (DR) of HIV-1 can be examined genotypically or phenotypically. Although sequencing is the gold standard of the genotypic resistance testing (GRT), high-throughput GRT targeted to the codons responsible for DR may be more appropriate for epidemiological studies and public health research. We used a Japanese database to design and synthesize sequence-specific oligonucleotide probes (SSOP) for the detection of wild-type sequences and 6 DR mutations in the clade B HIV-1 reverse transcriptase region. We coupled SSOP to microbeads of the Luminex 100 xMAP system and developed a GRT based on the polymerase chain reaction (PCR)-SSOP-Luminex method. Sixteen oligoprobes for discriminating DR mutations from wild-type sequences at 6 loci were designed and synthesized, and their sensitivity and specificity were confirmed using isogenic plasmids. The PCR-SSOP-Luminex DR assay was then compared to direct sequencing using 74 plasma specimens from treatment-naïve patients or those on failing treatment. In the majority of specimens, the results of the PCR-SSOP-Luminex DR assay were concordant with sequencing results: 62/74 (83.8%) for M41, 43/74 (58.1%) for K65, 70/74 (94.6%) for K70, 55/73 (75.3%) for K103, 63/73 (86.3%) for M184 and 68/73 (93.2%) for T215. There were a number of specimens without any positive signals, especially for K65. The nucleotide position of A2723G, A2747G and C2750T were frequent polymorphisms for the wild-type amino acids K65, K66 and D67, respectively, and 14 specimens had the D67N mutation encoded by G2748A. We synthesized 14 additional oligoprobes for K65, and the sensitivity for K65 loci improved from 43/74 (58.1%) to 68/74 (91.9%). We developed a rapid high-throughput assay for clade B HIV-1 DR mutations, which could be customized by synthesizing oligoprobes suitable for the circulating viruses. The assay could be a useful tool especially for public health research in both resource-rich and resource-limited settings.

The Zeeman Effect in the 44 GHz Class I Methanol Maser Line toward DR21(OH)

NASA Astrophysics Data System (ADS)

Momjian, E.; Sarma, A. P.

2017-01-01

We report detection of the Zeeman effect in the 44 GHz Class I methanol maser line, toward the star-forming region DR21(OH). In a 219 Jy beam-1 maser centered at an LSR velocity of 0.83 km s-1, we find a 20-σ detection of zBlos = 53.5 ± 2.7 Hz. If 44 GHz methanol masers are excited at n ˜ 107-8 cm-3, then the B versus n1/2 relation would imply, from comparison with Zeeman effect detections in the CN(1 - 0) line toward DR21(OH), that magnetic fields traced by 44 GHz methanol masers in DR21(OH) should be ˜10 mG. Combined with our detected zBlos = 53.5 Hz, this would imply that the value of the 44 GHz methanol Zeeman splitting factor z is ˜5 Hz mG-1. Such small values of z would not be a surprise, as the methanol molecule is non-paramagnetic, like H2O. Empirical attempts to determine z, as demonstrated, are important because there currently are no laboratory measurements or theoretically calculated values of z for the 44 GHz CH3OH transition. Data from observations of a larger number of sources are needed to make such empirical determinations robust.

A Joint Meeting of the US-Korea Workshop on Nanostructured Materials and Nanomanufacturing (5th) and the US-Korea Workshop on Nanoelectronics (3rd). Held in Los Angeles, California on August 8-9, 2006

DTIC Science & Technology

2007-09-10

ADJOURN 9 August 2006 (Wednesday) NANOMATERIALS - SESSION IV: (Sunset Village (SV) Delta Terrace B-3 House Lounge) Dr. Shih -Chi Liu (National Science...45 Prof. Fu- Kuo Chang (Stanford Univ.) "Nano-Reinforced Interface of Piezoeletric Sensors for Structural Health Monitoring" 09:10 Prof. Steven...Delta Terrace B- 4 House Lounge) Dr. Misoon Mah (Asian Office of Aerospace R&D), Moderator 08:10 Housekeeping 08:20 Prof. Hyun- Jung Shin (Kookmin

Increased expression of activation antigens on CD8+ T lymphocytes in Myalgic Encephalomyelitis/chronic fatigue syndrome: inverse associations with lowered CD19+ expression and CD4+/CD8+ ratio, but no associations with (auto)immune, leaky gut, oxidative and nitrosative stress biomarkers.

PubMed

Maes, Michael; Bosmans, Eugene; Kubera, Marta

2015-01-01

There is now evidence that specific subgroups of patients with Myalgic Encephalomyelitis / chronic fatigue syndrome (ME/CFS) suffer from a neuro-psychiatric-immune disorder. This study was carried out to delineate the expression of the activation markers CD38 and human leukocyte antigen (HLA) DR on CD4+ and CD8+ peripheral blood lymphocytes in ME/CFS. Proportions and absolute numbers of peripheral lymphocytes expressing CD3+, CD19+, CD4+, CD8+, CD38+ and HLA-DR+ were measured in ME/CFS (n=139), chronic fatigue (CF, n=65) and normal controls (n=40). The proportions of CD3+, CD8+, CD8+CD38+ and CD8+HLA-DR+ were significantly higher in ME/CFS patients than controls, while CD38+, CD8+CD38+, CD8+HLA-DR+ and CD38+HLA-DR+ were significantly higher in ME/CFS than CF. The percentage of CD19+ cells and the CD4+/CD8+ ratio were significantly lower in ME/CFS and CF than in controls. There were highly significant inverse correlations between the increased expression of CD38+, especially that of CD8+CD38+, and the lowered CD4+/CD8+ ratio and CD19+ expression. There were no significant associations between the flow cytometric results and severity or duration of illness and peripheral blood biomarkers of oxidative and nitrosative stress (O&NS, i.e. IgM responses to O&N modified epitopes), leaky gut (IgM or IgA responses to LPS of gut commensal bacteria), cytokines (interleukin-1, tumor necrosis factor-α), neopterin, lysozyme and autoimmune responses to serotonin. The results support that a) increased CD38 and HLA-DR expression on CD8+ T cells are biomarkers of ME/CFS; b) increased CD38 antigen expression may contribute to suppression of the CD4+/CD8+ ratio and CD19+ expression; c) there are different immune subgroups of ME/CFS patients, e.g. increased CD8+ activation marker expression versus inflammation or O&NS processes; and d) viral infections or reactivation may play a role in a some ME/CFS patients.

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

Related transplantation with HLA-1 Ag mismatch in the GVH direction and HLA-8/8 allele-matched unrelated transplantation: a nationwide retrospective study.

PubMed

Kanda, Junya; Saji, Hiroh; Fukuda, Takahiro; Kobayashi, Takeshi; Miyamura, Koichi; Eto, Tetsuya; Kurokawa, Mineo; Kanamori, Heiwa; Mori, Takehiko; Hidaka, Michihiro; Iwato, Koji; Yoshida, Takashi; Sakamaki, Hisashi; Tanaka, Junji; Kawa, Keisei; Morishima, Yasuo; Suzuki, Ritsuro; Atsuta, Yoshiko; Kanda, Yoshinobu

2012-03-08

To clarify which is preferable, a related donor with an HLA-1 Ag mismatch at the HLA-A, HLA-B, or HLA-DR loci in the graft-versus-host (GVH) direction (RD/1AG-MM-GVH) or an HLA 8/8-allele (HLA-A, HLA-B, HLA-C, and HLA-DRB1)-matched unrelated donor (8/8-MUD), we evaluated 779 patients with acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome who received a T cell-replete graft from an RD/1AG-MM-GVH or 8/8-MUD. The use of an RD/1AG-MM-GVH donor was significantly associated with a higher overall mortality rate than the use of an 8/8-MUD in a multivariate analysis (hazard ratio, 1.49; P < .001), and this impact was statistically significant only in patients with standard-risk diseases (P = .001). Among patients with standard-risk diseases who received transplantation from an RD/1AG-MM-GVH donor, the presence of an HLA-B Ag mismatch was significantly associated with a lower overall survival rate than an HLA-DR Ag mismatch because of an increased risk of treatment-related mortality. The HLA-C Ag mismatch or multiple allelic mismatches were frequently observed in the HLA-B Ag-mismatched group, and were possibly associated with the poor outcome. In conclusion, an 8/8-MUD should be prioritized over an RD/1AG-MM-GVH donor during donor selection. In particular, an HLA-B Ag mismatch in the GVH direction has an adverse effect on overall survival and treatment-related mortality in patients with standard-risk diseases.

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.

Cytomegalovirus (CMV) Epitope-Specific CD4+ T Cells Are Inflated in HIV+ CMV+ Subjects.

PubMed

Abana, Chike O; Pilkinton, Mark A; Gaudieri, Silvana; Chopra, Abha; McDonnell, Wyatt J; Wanjalla, Celestine; Barnett, Louise; Gangula, Rama; Hager, Cindy; Jung, Dae K; Engelhardt, Brian G; Jagasia, Madan H; Klenerman, Paul; Phillips, Elizabeth J; Koelle, David M; Kalams, Spyros A; Mallal, Simon A

2017-11-01

Select CMV epitopes drive life-long CD8 + T cell memory inflation, but the extent of CD4 memory inflation is poorly studied. CD4 + T cells specific for human CMV (HCMV) are elevated in HIV + HCMV + subjects. To determine whether HCMV epitope-specific CD4 + T cell memory inflation occurs during HIV infection, we used HLA-DR7 (DRB1*07:01) tetramers loaded with the glycoprotein B DYSNTHSTRYV (DYS) epitope to characterize circulating CD4 + T cells in coinfected HLA-DR7 + long-term nonprogressor HIV subjects with undetectable HCMV plasma viremia. DYS-specific CD4 + T cells were inflated among these HIV + subjects compared with those from an HIV - HCMV + HLA-DR7 + cohort or with HLA-DR7-restricted CD4 + T cells from the HIV-coinfected cohort that were specific for epitopes of HCMV phosphoprotein-65, tetanus toxoid precursor, EBV nuclear Ag 2, or HIV gag protein. Inflated DYS-specific CD4 + T cells consisted of effector memory or effector memory-RA + subsets with restricted TCRβ usage and nearly monoclonal CDR3 containing novel conserved amino acids. Expression of this near-monoclonal TCR in a Jurkat cell-transfection system validated fine DYS specificity. Inflated cells were polyfunctional, not senescent, and displayed high ex vivo levels of granzyme B, CX 3 CR1, CD38, or HLA-DR but less often coexpressed CD38 + and HLA-DR + The inflation mechanism did not involve apoptosis suppression, increased proliferation, or HIV gag cross-reactivity. Instead, the findings suggest that intermittent or chronic expression of epitopes, such as DYS, drive inflation of activated CD4 + T cells that home to endothelial cells and have the potential to mediate cytotoxicity and vascular disease. Copyright © 2017 by The American Association of Immunologists, Inc.

Anticancer Effect of Ursodeoxycholic Acid in Human Oral Squamous Carcinoma HSC-3 Cells through the Caspases

PubMed Central

Pang, Liang; Zhao, Xin; Liu, Weiwei; Deng, Jiang; Tan, Xiaotong; Qiu, Lihua

2015-01-01

Bear bile was used as a traditional medicine or tonic in East Asia, and ursodeoxycholic acid (UDCA) is the most important compound in bear bile. Further, synthetic UDCA is also used in modern medicine and nutrition; therefore, its further functional effects warrant research, in vitro methods could be used for the fundamental research of its anticancer effects. In this study, the apoptotic effects of UDCA in human oral squamous carcinoma HSC-3 cells through the activation of caspases were observed by the experimental methods of MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay, DAPI (4’,6-diamidino-2-phenylindole) staining, flow cytometry analysis, RT-PCR (reverse transcription-polymerase chain reaction) assay and Western blot assay after HSC-3 cells were treated by different concentrations of UDCA. With 0 to 400 μg/mL UDCA treatment, UDCA had strong growth inhibitory effects in HSC-3 cells, but had almost no effect in HOK normal oral cells. At concentrations of 100, 200 and 400 μg/mL, UDCA could induce apoptosis compared to untreated control HSC-3 cells. Treatment of 400 μg/mL UDCA could induce more apoptotic cancer cells than 100 and 200 μg/mL treatment; the sub-G1 DNA content of 400 μg/mL UDCA treated cancer cells was 41.3% versus 10.6% (100 μg/mL) and 22.4% (200 μg/mL). After different concentrations of UDCA treatment, the mRNA and protein expressions of caspase-3, caspase-8, caspase-9, Bax, Fas/FasL (Fas ligand), TRAIL (TNF-related apoptosis-inducing ligand), DR4 (death receptor 4) and DR5 (death receptor 5) were increased in HSC-3 cells, and mRNA and protein expressions of Bcl-2 (B-cell lymphoma 2), Bcl-xL (B-cell lymphoma-extra large), XIAP (X-linked inhibitor of apoptosis protein), cIAP-1 (cellular inhibitor of apoptosis 1), cIAP-2 (cellular inhibitor of apoptosis 2) and survival were decreased. Meanwhile, at the highest concentration of 400 μg/mL, caspase-3, caspase-8, caspase-9, Bax, Fas/FasL, TRAIL, DR4, DR5, and IκB-α expression levels were the highest, and Bcl-2, Bcl-xL, XIAP, cIAP-1, cIAP-2, survival, and NF-κB expression levels were the lowest. These results proved that UDCA could induce apoptosis of HSC-3 cancer cells through caspase activation, and the higher concentration of UDCA had stronger effects in vitro. UDCA might be a good nutrient for oral cancer prevention. PMID:25951128

Sensitivity of Breast Cancer Stem Cells to TRA-8 Anti-DR5 Monoclonal Antibody

DTIC Science & Technology

2013-02-01

1 AD_________________ Award Number: W81XWH-11-1-0151 TITLE: Sensitivity of Breast Cancer Stem Cells to TRA-8 Anti-DR5...Annual Summary 3. DATES COVERED 15-January-2012 – 14-January-2013 4. TITLE AND SUBTITLE Sensitivity of Breast Cancer Stem Cells to TRA-8 Anti-DR5...release; distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Basal-like breast cancers (BLBCs) generally become resistant to

HLA-A, B and C and HLA-DR antigens in intrinsic and allergic asthma.

PubMed

Morris, M J; Faux, J A; Ting, A; Morris, P J; Lane, D J

1980-03-01

Some 103 patients with asthma and 100 healthy volunteers have been typed for HLA-A, B and C and HLA-DR antigens. The 103 patients consisted of thirty-three with intrinsic asthma, thirty-four with extrinsic asthma, and thirty-six known to have precipitins to Aspergillus fumigatus. No increase in frequency of any of the A, B, C, or DR antigens was found to be significant after correction for the number of comparisons was made. However certain trends comparable to findings in other immunopathic disorders were noted. For example B12 was increased in the allergic asthmatics (46 vs 29% controls) and it is suggested that B12 is associated with the ability to produce the IgE antibodies. A3/B7/DRw2 (which are in linkage disequilibrium) all show a decreased frequency in intrinsic asthma (24, 12 and 9% vs 32, 26 and 24% respectively in controls). Finally B8 and DRw3, which showed a moderate increase in frequency in all three groups of asthmatics, were found in five of seven patients with low atopy but persisting antibodies to A. fumigatus. Further detailed studies of these asthmatic subgroups is warranted.

HLA DPA1, DPB1 alleles and haplotypes contribute to the risk associated with type 1 diabetes: analysis of the type 1 diabetes genetics consortium families.

PubMed

Varney, Michael D; Valdes, Ana Maria; Carlson, Joyce A; Noble, Janelle A; Tait, Brian D; Bonella, Persia; Lavant, Eva; Fear, Anna Lisa; Louey, Anthony; Moonsamy, Priscilla; Mychaleckyj, Josyf C; Erlich, Henry

2010-08-01

To determine the relative risk associated with DPA1 and DPB1 alleles and haplotypes in type 1 diabetes. The frequency of DPA1 and DPB1 alleles and haplotypes in type 1 diabetic patients was compared to the family based control frequency in 1,771 families directly and conditional on HLA (B)-DRB1-DQA1-DQB1 linkage disequilibrium. A relative predispositional analysis (RPA) was performed in the presence or absence of the primary HLA DR-DQ associations and the contribution of DP haplotype to individual DR-DQ haplotype risks examined. Eight DPA1 and thirty-eight DPB1 alleles forming seventy-four DPA1-DPB1 haplotypes were observed; nineteen DPB1 alleles were associated with multiple DPA1 alleles. Following both analyses, type 1 diabetes susceptibility was significantly associated with DPB1*0301 (DPA1*0103-DPB1*0301) and protection with DPB1*0402 (DPA1*0103-DPB1*0402) and DPA1*0103-DPB1*0101 but not DPA1*0201-DPB1*0101. In addition, DPB1*0202 (DPA1*0103-DPB1*0202) and DPB1*0201 (DPA1*0103-DPB1*0201) were significantly associated with susceptibility in the presence of the high risk and protective DR-DQ haplotypes. Three associations (DPB1*0301, *0402, and *0202) remained statistically significant when only the extended HLA-A1-B8-DR3 haplotype was considered, suggesting that DPB1 alone may delineate the risk associated with this otherwise conserved haplotype. HLA DP allelic and haplotypic diversity contributes significantly to the risk for type 1 diabetes; DPB1*0301 (DPA1*0103-DPB1*0301) is associated with susceptibility and DPB1*0402 (DPA1*0103-DPB1*0402) and DPA1*0103-DPB1*0101 with protection. Additional evidence is presented for the susceptibility association of DPB1*0202 (DPA1*0103-DPB1*0202) and for a contributory role of individual amino acids and DPA1 or a gene in linkage disequilibrium in DR3-DPB1*0101 positive haplotypes.

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.

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).

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.

VizieR Online Data Catalog: Redshifts of galaxies in Abell 1351 field (Barrena+, 2014)

NASA Astrophysics Data System (ADS)

Barrena, R.; Girardi, M.; Boschin, W.; de Grandi, S.; Rossetti, M.

2015-03-01

Multi-object spectroscopic (MOS) observations of A1351 were carried out at the TNG on 2010 March 10. We used DOLORES/MOS with the LR-B Grism 1, yielding a dispersion of 187Å/mm. We used the 2048x2048 pixel E2V CCD, with a pixel size of 13.5um. In total, we observed four MOS masks including 143 slits. For each mask, the exposure time was 3x1800s. We had already observed A1351 field with the Wide Field Camera (WFC), mounted at the prime focus of the 2.5m INT telescope. We took exposures of 9x600s and 9x300s in B and R Harris filters in photometric conditions and 1.2-arcsec seeing. However, we used SDSS-DR7 data because a greater number of photometric bands are available, which allows an accurate colour analysis. INT and SDSS-DR7 photometric data are very similar. The completeness magnitude is r'=20.8. (1 data file).

The TL1A/DR3/DcR3 pathway in autoimmune rheumatic diseases.

PubMed

Siakavellas, Spyros I; Sfikakis, Petros P; Bamias, Giorgos

2015-08-01

TNF-like cytokine 1A (TL1A) and its receptors, death receptor 3 (DR3) and decoy receptor 3 (DcR3) are members of the TNF and TNF receptor superfamilies of proteins, respectively. They constitute a cytokine system that actively interferes with the regulation of immune responses and may participate in the pathogenesis of autoimmune diseases. This review aims to present the current knowledge on the role of the TL1A/DR3/DcR3 system in the pathophysiology of autoimmune rheumatic diseases, with a focus on rheumatoid arthritis (RA). An extensive literature search was performed in the PubMed database using the following keywords: TL1A, death receptor 3, DR3, decoy receptor 3, DcR3, TNFSF15, TNFRSF25, and TNFSF6B. Studies were assessed and selected in view of their relevance to autoimmune rheumatic diseases. The TL1A/DR3/DcR3 axis is a novel immune pathway that participates in the pathogenesis of a variety of autoimmune rheumatic diseases. These molecules may be promising therapeutic targets for inflammatory arthritis. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

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

Truong, Pauline T., E-mail: ptruong@bccancer.bc.ca; Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver Island Centre, University of British Columbia, Victoria, BC; Sadek, Betro T.

Purpose: To examine locoregional and distant recurrence (LRR and DR) in women with pT1-2N0 breast cancer according to approximated subtype and clinicopathologic characteristics. Methods and Materials: Two independent datasets were pooled and analyzed. The study participants were 1994 patients with pT1-2N0M0 breast cancer, treated with mastectomy without radiation therapy. The patients were classified into 1 of 5 subtypes: luminal A (ER+ or PR+/HER 2−/grade 1-2, n=1202); luminal B (ER+ or PR+/HER 2−/grade 3, n=294); luminal HER 2 (ER+ or PR+/HER 2+, n=221); HER 2 (ER−/PR−/HER 2+, n=105) and triple-negative breast cancer (TNBC) (ER−/PR−/HER 2−, n=172). Results: The median follow-up timemore » was 4.3 years. The 5-year Kaplan-Meier (KM) LRR were 1.8% in luminal A, 3.1% in luminal B, 1.7% in luminal HER 2, 1.9% in HER 2, and 1.9% in TNBC cohorts (P=.81). The 5-year KM DR was highest among women with TNBC: 1.8% in luminal A, 5.0% in luminal B, 2.4% in luminal HER 2, 1.1% in HER 2, and 9.6% in TNBC cohorts (P<.001). Among 172 women with TNBC, the 5-year KM LRR were 1.3% with clear margins versus 12.5% with close or positive margins (P=.04). On multivariable analysis, factors that conferred higher LRR risk were tumors >2 cm, lobular histology, and close/positive surgical margins. Conclusions: The 5-year risk of LRR in our pT1-2N0 cohort treated with mastectomy was generally low, with no significant differences observed between approximated subtypes. Among the subtypes, TNBC conferred the highest risk of DR and an elevated risk of LRR in the presence of positive or close margins. Our data suggest that although subtype alone cannot be used as the sole criterion to offer postmastectomy radiation therapy, it may reasonably be considered in conjunction with other clinicopathologic factors including tumor size, histology, and margin status. Larger cohorts and longer follow-up times are needed to define which women with node-negative disease have high postmastectomy LRR risks in contemporary practice.« less

VizieR Online Data Catalog: HIP and TGAS stars reddening and extinction (Gontcharov+ 2018)

NASA Astrophysics Data System (ADS)

Gontcharov, G. A.; Mosenkov, A. V.

2018-01-01

These are the reddening, interstellar extinction and extinction-to-reddening ratio estimates interpolated for 730,496 Gaia DR1 TGAS and Hipparcos stars within 415 pc from the Sun based on the 3D reddening map of Gontcharov (J/PAZh/43/521) and 3D extinction-to-reddening (total-to-selective extinction) ratio Rv=Av/E(B-V) map of Gontcharov (J/PAZh/38/15). For 711,237 Gaia DR1 TGAS stars the rMoMW distances from Astraatmadja and Bailer-Jones (2016ApJ...833..119A, Cat. J/ApJ/833/119) are used. For 19,259 Hipparcos stars, not in Gaia DR1 TGAS, the distances as the inversion of Hipparcos (I/311) parallaxes are used. The E(B-V) are calculated from initial E(J-Ks) as E(B-V)=E(J-Ks)*(0.047X3-0.1X2-0.09X+1.74), where X=(BT-VT) (B_T and V_T Tycho-2 bands) following the extinction law. This refined relation supersedes E(B-V)=1.655E(J-Ks) in the original 3D reddening map of Gontcharov. The Rv are interpolated from the 3D map of Rv of Gontcharov (2012AstL...38...12G, 2012PAZh...38...15G, Cat. J/PAZh/38/15). The Av are the product of E(B-V) and Rv. (2 data files).

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.

Is the detection rate of 18F-choline PET/CT influenced by androgen-deprivation therapy?

PubMed

Chondrogiannis, Sotirios; Marzola, Maria Cristina; Ferretti, Alice; Grassetto, Gaia; Maffione, Anna Margherita; Rampin, Lucia; Fanti, Stefano; Giammarile, Francesco; Rubello, Domenico

2014-07-01

To evaluate if the detection rate (DR) of (18)F-choline (18F-CH) PET/CT is influenced by androgen-deprivation therapy (ADT) in patients with prostate cancer (PC) already treated with radical intent and presenting biochemical relapse. We have retrospectively evaluated (18)F-CH PET/CT scans of 325 consecutive PC patients enrolled in the period November 2009 to December 2012 previously treated with radical intent and referred to our centre to perform (18)F-CH PET/CT for biochemical relapse. Two different groups of patients were evaluated. group A included the whole sample of 325 patients (mean age 70 years, range: 49-86) who presented trigger PSA between 0.1 and 80 ng/ml (mean 5.5 ng/ml), and group B included 187 patients (mean age 70 years, range 49-86) with medium-low levels of trigger PSA ranging between 0.5 and 5 ng/ml (mean PSA 2.1 ng/ml); group B was chosen in order to obtain a more homogeneous group of patients in terms of PSA values also excluding both very low and very high PSA levels avoiding the "a priori" higher probability of negative or positive PET scan, respectively. At the time of examination, 139 patients from group A and 72 patients from group B were under ADT: these patients were considered to be hormone-resistant PC patients because from their oncologic history (>18 months) an increase of PSA levels emerged despite the ongoing ADT. The relationship between (18)F-CH PET/CT findings and possible clinical predictors was investigated using both univariate and multivariate binary logistic regression analyses, including trigger PSA and ADT. Considering the whole population, overall DR of (18)F-CH PET was 58.2 % (189/325 patients). In the whole sample of patients (group A), both at the univariate and multivariate logistic regression analysis, trigger PSA and ADT were significantly correlated with the DR of (18)F-CH PET (p < 0.05). Moreover, the DR in patients under ADT (mean PSA 7.8 ng/ml) was higher than in patients not under ADT (mean PSA 3.9 ng/ml), (DR was 70.5 % and 48.9 %, respectively; p < 0.001), therefore, demonstrating the existence of a significant correlation between the DR of (18)F-CH PET and ADT. In group B patients only trigger PSA resulted a reliable predictor of the (18)F-CH positivity, since ADT was not correlated to the DR of (18)F-CH PET (p = 0.061). Also in group B the DR of (18)F-CH PET in patients under ADT was higher than in patients not under ADT (65.3 % and 51.3 %, respectively) but the difference was not significant without a statistically significant correlation in the Mann Whitney test (p = 0.456) therefore, suggesting the lack of correlation between DR (18)F-CH PET/CT and ADT. Similarly to previous published studies, in our series the overall DR of (18)F-CH PET/CT was 58 % and was significantly correlated to trigger PSA. The most important finding of the present study is that ADT does not negatively influence DR of (18)F-CH PET/CT in PC patients with biochemical relapse; therefore, it can be suggested that it is not necessary to withdraw ADT before performing (18)F-CH PET/CT.

Chesapeake Bay Study. Supplement A. Problem Identification. Supplement B. Public Involvement. Supplement C. The Chesapeake Bay Hydraulic Model.

DTIC Science & Technology

1984-09-01

1968-71 Dr. Francis S. L. Williamson, 1971-75 Dr. J. Kevin Sullivan, 1975-83 Dr. David L. Correll, 1983-84 B-I...BASIC RESEARCH (cont’d) SMITHSONIAN INSTITUTION Dr. I. Eugene Wallen, 1968-71 Dr. Francis S. L. Williamson, 1971-75 Dr. 3. Kevin Sullivan, 1975-83 Dr...MSX merical fishino and recrea- by increased distributions of waer sources fromsaltitru- the B E P predicted oysters tion industries and for the

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.

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.

[Simultaneous onset of steroid-sensitive nephrotic syndrome and type 1 diabetes].

PubMed

Rego Filho, Eduardo A; Mello, Solange F R; Omuro, André M; Loli, José O C

2003-01-01

We describe the case of a boy with steroid-sensitive nephrotic syndrome coexisting with type-1 diabetes mellitus. Nephrotic syndrome was diagnosed in a boy (age 3 years and 11 months) with generalized edema. Marked weight loss (23 to 16 kg), polyuria, polydipsia and weakness were observed after three weeks of treatment with prednisone 2 mg/kg/day. Diabetic ketoacidosis was confirmed by laboratory tests: hyperglycemia (glucose 657 mg/dl), glycosuria without proteinuria, acidosis and ketonuria. Therapy with insulin and prednisone was started. He was then maintained on a daily dose of NPH insulin. At age 4 years and 1 month a new episode of ketoacidosis without proteinuria occurred in association with a viral infection of the upper airways. At age 4 years and 4 months nephrotic syndrome relapsed, but the child responded well to steroid therapy. There was another relapse three months later, when prednisone treatment was interrupted. This led to the introduction of cyclophosphamide, with good results. Since then, the patient (now 5 years and 6 months old) has been taking insulin daily and nephrotic syndrome has not relapsed. Plasma levels of C3 and C4 and renal function are normal. Hematuria is occasionally present. Anti-GAD antibodies (glutamic decarboxilase) are normal and anti-islet cell antibodies are positive. HLA antigens: A2; B44; B52; DR4; DR8; DR53. The simultaneous occurrence of steroid-sensitive nephrotic syndrome and type-1 diabetes mellitus is rare.

Analysis of the Capability to Effectively Design Complementary Metal Oxide Semiconductor Integrated Circuits.

DTIC Science & Technology

1984-12-01

LISTING TEtiPEkATURE = 27.8u DEG C ,WIDTH OUT=bo IC V(4)=5 OPTEL IbrS FIIISi (VTL=I Td -i ’ O8 SU-E5L=.11 .MUbEL N 1OS PriOS (VTu-1V TOA?5NM Uu=3@i NS’uB...INF6riTIO TEMERA~TURE = 27.88 DEG C t *ttlMGFETS 8M) M2 M3 M4 M5 M16 dr1QDEL FfiOS halOS PmoS Im1s mtos PrtOS JD i. di -2. bbd -li i. dtdi -2.fld-ll -2,i8d-I1...remain high VIN3 ? 8 Dc 5v VIN45 8DC 5V Tkki8 INS 28NS XPOT TRMN V0i1) V(4) W$,5V) *Erib lat***t06/84 ***it*** SPICE 2G.1 (I5OCT5u *tt’Itt~ td :14:28*#* d

Dendrobium chrysotoxum Lindl. Alleviates Diabetic Retinopathy by Preventing Retinal Inflammation and Tight Junction Protein Decrease

PubMed Central

Yu, Zengyang; Gong, Chenyuan; Lu, Bin; Yang, Li; Sheng, Yuchen; Ji, Lili; Wang, Zhengtao

2015-01-01

Diabetic retinopathy (DR) is a serious complication of diabetes mellitus. This study aimed to observe the alleviation of the ethanol extract of Dendrobium chrysotoxum Lindl. (DC), a traditional Chinese herbal medicine, on DR and its engaged mechanism. After DC (30 or 300 mg/kg) was orally administrated, the breakdown of blood retinal barrier (BRB) in streptozotocin- (STZ-) induced diabetic rats was attenuated by DC. Decreased retinal mRNA expression of tight junction proteins (including occludin and claudin-1) in diabetic rats was also reversed by DC. Western blot analysis and retinal immunofluorescence staining results further confirmed that DC reversed the decreased expression of occludin and claudin-1 proteins in diabetic rats. DC reduced the increased retinal mRNA expressions of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor α (TNFα), interleukin- (IL-) 6, and IL-1β in diabetic rats. In addition, DC alleviated the increased 1 and phosphorylated p65, IκB, and IκB kinase (IKK) in diabetic rats. DC also reduced the increased serum levels of TNFα, interferon-γ (IFN-γ), IL-6, IL-1β, IL-8, IL-12, IL-2, IL-3, and IL-10 in diabetic rats. Therefore, DC can alleviate DR by inhibiting retinal inflammation and preventing the decrease of tight junction proteins, such as occludin and claudin-1. PMID:25685822

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.

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.

Optimal Structures for Multimedia Instruction.

DTIC Science & Technology

1985-07-01

Sw.oR s.2 D = (5.1 AND 8S2 OR (-Sw1 AND -Sw2) A = (5w1 AND 8.2 OR 5.1l Figure Ui-1: B Series Diagram ..6 44 H 1.2.1. B1 Script This is the basic case of...to that of B1 , except that the final summary is replaced by the following filler proposition: * So if you were to get this job working as the...4833 Rugby Avenue University of Wisconsin Bethesda, MD 20014 W. J. Brogden Psychology Bldg. 1202 W. Johnson Street Dr. Pat Federico Madison, WI 53706

Human leukocyte antigens in indigenous (mapuche) people in a regional renal transplantation program in chile.

PubMed

Droguett, M A; Oyarzún, M J; Alruiz, P; Jerez, V; Mezzano, S; Ardiles, L

2005-10-01

An active regional transplantation program established in the southern region of Chile has allowed the incorporation of ethnic minorities particularly Mapuche living in this geographic area in the development of a histocompatibility database. To identify possible differences in the human leukocyte (HLA) antigen distribution in Chilean Mapuche compared with non-Mapuche, we reviewed 442 HLA tissue-typing studies. Seventy-eight of 309 recipients (25%) and 18 of 133 donors (13%) were Mapuche. Among recipients, Mapuche people showed a significantly higher frequency of the HLA antigens, A28, B16, DR4, and DR8, and a lower one for A19, B15, and DR1 (P < .05) compared with non-Mapuche individuals. A particularly higher frequency of the haplotype A28, -B16, -DR4 was also evidenced in Mapuche. Besides, these recipients showed a higher frequency of the allele -DR4 when compared with Mapuche donors. A greater frequency of some histocompatibility antigens in patients with chronic renal disease might be attributed to allelic concentration due to a high index of endogamy, but a possible association with the development of progressive renal disease cannot be ignored, especially when a higher prevalence of DR4 was observed among Mapuche recipients.

1,8-Naphthalene Linked Cofacial Binuclear Phthalocyanines.

DTIC Science & Technology

1987-06-01

Chemistry University of Utah Indiana University Salt Lake City, Utah 84112 Bloomington, Indiana 47405 Dr. J. 0. Thomas Dr. Mark A. McHugh University...2.0g, 5.3mmol) in a mixed coupling reaction, in the presence of elementary nickel powder under conditions described for homocoupling reactions[8 ,9

The National Meeting of the Reticuloendothelial Society (19th), Program and Abstracts, 17-20 October 1982, St. Louis, Missouri

DTIC Science & Technology

1982-11-22

for activating macrophages with lymphokines and liposomes were considered. SYMPOSIUM B : Chaired by Dr. Philip Davies Dr. Daniel Steinberg, University...Organizing Committee: Herbert B . Herscowitz, Chair Philip Stahl, Local Host James W. Scheffel David Clark Saturday, October 16, 1982 8:30 a.m.- 5:00 p.m...Natural Cytotoxic Cells" Dr. Ronald B . Herberman, NCI, NIH, Chair. Participation in this "dry" workshop is open to all individuals interested in natural

ACOSS Eleven (Active Control of Space Structures)

DTIC Science & Technology

1985-09-01

M . J . Vill.a lba T. C. Henderson I. G. Rosen I). B. Kasle J . 1). I’rner J . P. Govignon Contractor: The Charles...Michael J . Villalba (Section 8), Dr. 1. Gary Rosen (Section 9), and Dr. James D. Turner and Mr. Hion M . Chun (Section 10). Assistance from Mr. Saul Serben...matrix Riccati-like equations are discussed in detail. 47/48 -,.-. I. 4. , J ,. M S a C. t ’S a..S." a-- a.,. I w *.* -a .4 a, . .,- -..... s .’. J

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

[Clinical application of alendronate for osteoporosis/osteopenia secondary to hyperthyroidism].

PubMed

Yang, Li-Juan; Shen, Fei-Xia; Zheng, Jing-Chen; Zhang, Hai-Ling

2012-02-01

To evaluate the efficacy and safety of alendronate for the treatment of osteoporosis/osteopenia secondary to hyperthyroidism. From April 2008 to November 2009, 27 patients with hyperthyroidism with osteoporosis/ osteopenia measured by dual energy X-ray absorptiometry (DXA) were included in this study, and then they were randomly divided into two groups (group A and group B) by simple random sampling. Group A consisted of 14 patients treated with antithyroid drug and caltrate D, the antithyroid drug change with thyroid function, and caltrate D 600 mg per day. Group B consisted of 13 patients treated with antithyroid drug, caltrate D and alendronate, antithyroid drug and caltrate D the same as group A, and alendronate 70 mg weekly. Meanwhile, 21 healthy voluntary adults were chosen as control group. And compared with the control group which was treated with nothing. Followed-up for one year, the bone mineral density (including T-score, Z-score, BMD) in lumbar spine (LS), femoral neck (FN) and distal radius (DR) and general information, were compared before and after treatment. BMD at FN and DR were significantly higher at 12 months after treatment than at the baseline in group A (P = 0.000); T-score, Z-score, and BMD at the LS, FN and DR were all significantly higher at 12 months after treatment than at the baseline in group B (P < 0.05), but these data could not arrive to normal level. In group A, the percentage increased in BMD at the LS, FN, and DR were (4.34 +/- 10.5)%, (3.21 +/- 1.38)%, (1.95 +/- 0.44)%, respectively, at 12 months after treatment. In group B, the percentage increased in BMD at the LS, FN, and DR were (6.10 +/- 8.12)%, (4.10 +/- 5.64)%, (3.10 +/- 3.23)%, respectively, at 12 months after treatment. There was significant difference in the rate of increase between two groups (P < 0.05). AKP decreased, weight, BMI increased, and thyroid function decreased, after treatment than those before in both of the two groups. (P < 0.05). Alendronate can significantly increase BMD in treating patients with hyperthyroidism and osteoporosis/osteopenia. Compared with anti-thyroid drugs alone, treatment with alendronate can obtain more clinical effect and also very safety.

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.

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.

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

Toxic shock syndrome: characterization of human immune responses to TSST-1 and evidence for sensitivity thresholds.

PubMed

Kimber, Ian; Nookala, Suba; Davis, Catherine C; Gerberick, G Frank; Tucker, Heidi; Foertsch, Leslie M; Dearman, Rebecca J; Parsonnet, Jeffrey; Goering, Richard V; Modern, Paul; Donnellen, Meghan; Morel, Jorge; Kotb, Malak

2013-07-01

Noninvasive vaginal infections by Staphylococcus aureus strains producing the superantigen TSST-1 can cause menstrual toxic shock syndrome (mTSS). With the objective of exploring the basis for differential susceptibility to mTSS, the relative responsiveness to TSST-1 of healthy women has been investigated. Peripheral blood mononuclear cells from healthy donors were incubated with purified TSST-1 or with the T-cell mitogen phytohemmaglutinin (PHA), and proliferation was measured. The concentrations of TSST-1 and PHA required to elicit a response equivalent to 15% of the maximal achievable response (EC15) were determined. Although with PHA, EC15 values were comparable between donors, subjects could be classified as being of high, medium, or low sensitivity based on responsiveness to TSST-1. Sensitivity to TSST-1-induced proliferation was associated with increased production of the cytokines interleukin-2 and interferon-γ. When the entire T lymphocyte population was considered, there were no differences between sensitivity groups with respect to the frequency of cells known to be responsive to TSST-1 (those bearing CD3(+) Vβ2(+)). However, there was an association between sensitivity to TSST-1 and certain HLA-class II haplotypes. Thus, the frequencies of DR7DQ2, DR14DQ5, DR4DQ8, and DR8DQ4 haplotypes were greater among those with high sensitivity, a finding confirmed by analysis of responses to immortalized homozygous B cell lines. Collectively, the results reveal that factors other than neutralizing antibody and the frequency of Vβ2(+) T lymphocytes determine immunological responsiveness to TSST-1. Differential responsiveness of lymphocytes to TSST-1 may form the basis of interindividual variations in susceptibility to mTSS.

Effects of short-term dietary restriction and glutamine supplementation in vitro on the modulation of inflammatory properties.

PubMed

C de Oliveira, Dalila; Santos, Ed Wilson; Nogueira-Pedro, Amanda; Xavier, José Guilherme; Borelli, Primavera; Fock, Ricardo Ambrósio

2018-04-01

Dietary restriction (DR) is a nutritional intervention that exerts profound effects on biochemical and immunologic parameters, modulating some inflammatory properties. Glutamine (GLN) is a conditionally essential amino acid that can modulate inflammatory properties. However, there is a lack of data evaluating the effects of DR and GLN supplementation, especially in relation to inflammatory cytokine production and the expression of transcription factors such as nuclear factor (NF)-κB. We subjected 3-mo-old male Balb/c mice to DR by reducing their food intake by 30%. DR animals lost weight and showed reduced levels of serum triacylglycerols, glucose, cholesterol, and calcium as well as a reduction in bone density. Additionally, blood, peritoneal, and spleen cellularity were reduced, lowering the number of peritoneal F4/80- and CD86-positive cells and the total number of splenic CD4- and CD8-positive cells. The production of interleukin (IL)-10 and the expression of NF-κB in splenic cells were not affected by DR or by GLN supplementation. However, peritoneal macrophages from DR animals showed reduced IL-12 and tumor necrosis factor-α production and increased IL-10 production with reduced phosphorylation of NF-κB expression. Additionally, GLN was able to modulate cytokine production by peritoneal cells from the control group, although no effects were observed in cells from the DR group. DR induces biochemical and immunologic changes, in particular by reducing IL-12 and tumor necrosis factor-α production by macrophages and clearly upregulating IL-10 production, whereas GLN supplementation did not modify these parameters in cells from DR animals. Copyright © 2017 Elsevier Inc. All rights reserved.

Sentinel node mapping in endometrial cancer following Hysteroscopic injection of tracers: A single center evaluation over 200 cases.

PubMed

Martinelli, Fabio; Ditto, Antonino; Signorelli, Mauro; Bogani, Giorgio; Chiappa, Valentina; Lorusso, Domenica; Scaffa, Cono; Recalcati, Dario; Perotto, Stefania; Haeusler, Edward; Raspagliesi, Francesco

2017-09-01

To analyze detection-rate(DR) and diagnostic-accuracy (A) of sentinel-nodes(SLNs) mapping following hysteroscopic-injection of tracer. To compare DR and A between tracers: ICG and Tc99m. Evaluation of endometrial-cancer patients who underwent SLNs mapping after hysteroscopic-peritumoral-injection of tracer±lymphadenectomy. Analysis of DR (overall-bilateral-aortic) and A in the entire cohort and comparison between tracers. 202 procedures were performed from January/2005 to February/2017. Mean age:60years (28-82); mean BMI: 26.8 kg/m 2 (15-47). In 133 cases (65.8%) hysterectomy and mapping procedure were performed laparoscopically. The overall-DR of the technique was 93.2% (179/192) (10 cases were excluded: 9 for technical-equipment failure; 1 for vagal reaction). Bilateral pelvic mapping was found in 59.7% of cases (107/179) and was more frequent in the ICG group (72.8% vs 53.3%; p: 0.012). In 50.8% of cases (91/179) SLNs were mapped both in pelvic and aortic nodes, and in 5 cases (2.8%) only in the aortic area. The mean number of detected SLNs was 3.7 (1-8). 22 patients (12.3%) had nodal involvement: 10-(45.5%)-macrometastases; 5-(22.7%)-micrometastases; 7-(31.8%)-ITCs. In 6 cases (27.3%) only aortic nodes were positive; in 5 cases (22.7%) both pelvic and aortic nodes and in 11 cases (50%) only pelvic nodes were involved. Three false-negative results were found, all in the Tc99m group. All had isolated aortic metastases with negative pelvic nodes. Overall-sensitivity was 86.4% (95%CI: 68.4-100) and overall-negative-predictive-value (NPV) was 96.4% (95%CI 86.7-100). No differences in terms of overall-DR, overall-sensitivity and overall-NPV were found between the two tracers. Hysteroscopic-injection of tracer for SLNs mapping in endometrial cancer is as accurate as cervical injection with a higher DR in the aortic area. ICG improves bilateral-DR. Further investigation is warranted on this topic. Copyright © 2017 Elsevier Inc. All rights reserved.

Integrated Development of Serum Molecular Markers for Early Diagnosis of Breast Cancer

DTIC Science & Technology

2006-09-01

Fas, FasL, Cyfra 21-1, TPA/TPS, IGFBP1, S100, angiostatin, SSC, ULBP1,2,3, βHCG, MICA , HE4, SMRP, mesothelin, SAA, and TTR. The procedure we used for... MICA , S-100, DR5, mesothelin, and myeloperoxidase (MPO), ULBP-1,2, S100, angiostatin. Our results have demonstrated that the expression of CA 125, EGF...4066. (8) Adam, B. L.; Qu , Y.; Davis, J. W.; Ward, M. D.; Clements, M. A.; Cazares, L. H.; Semmes, O. J.; Schellhammer, P. F.; Yasui, Y.; Feng, Z

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.

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.

Defense Systems Management Review. Volume 3, Number 3, Summer 1980. Maturing of the DoD Acquisition Process.

DTIC Science & Technology

1980-01-01

economic equity among the participants. Dr. Walter B. LaBerge , former Assistant Secretary General for Defense Sup- port, NATO, and now Deputy Under...1977. 34. Thomas A. Callaghan, President, Export-Import Technology, Inc., Washington, D.C. 35. Dr. Walter B. LaBerge , "A Concept of a Two-Way Street...one single activity-the production and acquisition : ’. 1. Steven Rosen, Testing the Theory of the Military-Industrial Complex (Lexington, Mass.: D. C

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.

Changing prevalence and resistance patterns in children with drug-resistant tuberculosis in Mumbai.

PubMed

Shah, Ira; Shah, Forum

2017-05-01

The prevalence of drug-resistant (DR) tuberculosis (TB) in children is increasing. Although, in India, multi-drug-resistant (MDR) TB rates have been relatively stable, the number of children with pre-extensively drug-resistant and extensively drug-resistant (XDR) TB is increasing. To determine whether the prevalence of DR TB in children in Mumbai is changing and to study the evolving patterns of resistance. A retrospective study was undertaken in 1311 paediatric patients referred between April 2007 and March 2013 to the Paediatric TB clinic at B. J. Wadia Hospital for Children, Mumbai. Children were defined as having DR TB on the basis of drug susceptibility testing (DST) of Mycobacterium tuberculosis grown on culture of body fluids (in the case of extra pulmonary TB) or from gastric lavage/bronchi-alveolar lavage/sputum in patients with pulmonary TB or from DST of the contacts. The prevalence of DR TB was calculated and the type of DR was evaluated yearly and in the pre-2010 and post-2010 eras. The overall prevalence of DR TB was 86 (6.6%) with an increase from 23 (5.6%) patients pre-2010 to 63 (7%) post-2010 (P = 0.40). Nine (10.4%) patients were diagnosed on the basis of contact with a parent with DR TB. Overall fluoroquinolone resistance increased from 9 (39.1%) pre-2010 to 59 (93.7%) post-2010 (P = 0.0001): moxifloxacin resistance increased from 2 (8.7%) to 29 (46%) (P = 0.0018) and ofloxacin resistance increased from 7 (30.4%) to 30 (47.6%) (P = 0.14). Ethionamide resistance also increased from 6 (26.1%) to 31 (49.2%) (P = 0.04), aminoglycoside resistance was one (4.3%) pre-2010 and 12 (19%) post-2010 (P = 0.17) and resistance remained virtually the same for both amikacin [0 pre-2010 and 6 (9.5%) after 2010] and kanamycin [one (4.3%) pre- and 6 (9.5%) post-2010]. Of the first-line drugs, resistance remained the same for isoniazid [23 (100%) to 61 (96.8%)], rifampicin [22 (95.7%) to 51 (80.9%),P = 0.17], pyrazinamide [15 (65.2%) to 35 (55.6%), P = 0.47], ethambutol [14 (60.9%) to 38 (60.3%), P = 1.00] and streptomycin [19 (82.6%) to 50 (79.4%), P = 1.00]. Resistance to PAS remained unchanged [2 (8.7%) to 5 (7.9%), P = 1.00]. There is increasing resistance to second-line anti-tuberculosis (ATT) drugs, particularly flouroquinolones and ethionamide. Hence, there is an urgent need to avoid the use of ATT drugs for non-tuberculous infection and to increase surveillance for DR TB in adults as MDR TB in children is usually through contact with an adult with infectious MDR TB.

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.

Nanojets: Electrification, Energetics, Dynamics, Stability and Breakup

DTIC Science & Technology

2006-12-31

OF: 17. LIMITATION OF 18 . NUMBER 19a. NAME OF RESPONSIBLE PERSON a. REPORT b. ABSTRACT c. THIS PAGE ABSTRACT OF Dr Uzi Landman PAGES SU 19b. TELEPHONE...F(Ei )dE,. = Fm,, (Ero, )F,,h (Er,,b)dEro, dEwbh. (8) 16 where F,.ot( Erot ), and Fvwb(Evib) are the normalized rotational and vibrational Maxwell...corresponding to the concentrated solution, while the jet 18 dimensions are associated with radii in the range between 2.3 and 3.29 nm, with the larger

Developing an Instrument for Measuring the Attitudes of Hispanics in the Navy: A Pilot Study.

DTIC Science & Technology

1980-11-01

C _ 085 UNCLASS7IF~ r EO -A NL. Uncassified 4...1945. 1 b ,13 I4 T-Y (0 ~ H .~ 4) ’A I _________________ .9’I:1 * r - V. ii ’a 𔃾- 0I EU .~ "-I I-. T-V Q) c b.0o 4s. > t!3 EU ~ 01 HI 4~) ~ C ) a, VIJ...CONTRACTORS Dr. Clayton P. Alderfer School of Organization and Management Yale University New Haven, CT 06520 Dr. R . Russell Bernard Department

Important risk factors of allograft survival in cadaveric renal transplantation. A study of 426 patients.

PubMed Central

Diethelm, A G; Blackstone, E H; Naftel, D C; Hudson, S L; Barber, W H; Deierhoi, M H; Barger, B O; Curtis, J J; Luke, R G

1988-01-01

Multiple risk factors contribute to the allograft survival of patients who have cadaveric renal transplantation. A retrospective review of 19 such factors in 426 patients identified race, DR match, B + DR match, number of transplants, and preservation time to have a significant influence. The parametric analysis confirmed the effect to be primarily in the early phase, i.e., first 6 months. All patients received cyclosporine with other methods of immunosuppression resulting in an overall 1-year graft survival rate of 66%. The overall 1-year graft survival rate in the white race was 73% and in the black race was 57% (p = 0.002). Allograft survival and DR match showed white recipients with a 1 DR match to have 75% survival at 1 year compared with 57% in the black patient (p = 0.009). If HLA B + DR match was considered, the white recipient allograft survival increased to 76%, 84%, and 88% for 1, 2, and 3 match kidneys by parametric analysis. Patients receiving first grafts had better graft survival (68%) than those undergoing retransplantation (58%) (p = 0.05). Organ preservation less than 12 hours influenced allograft survival with a 78% 1-year survival rate compared with 63% for kidneys with 12-18 hours of preservation. Despite the benefits of B + DR typing, short preservation time, and first transplants to the white recipient, the allograft survival in the black recipient remained uninfluenced by these parameters. PMID:3288138

A Sensitive Dynamic and Active Pixel Vision Sensor for Color or Neural Imaging Applications.

PubMed

Moeys, Diederik Paul; Corradi, Federico; Li, Chenghan; Bamford, Simeon A; Longinotti, Luca; Voigt, Fabian F; Berry, Stewart; Taverni, Gemma; Helmchen, Fritjof; Delbruck, Tobi

2018-02-01

Applications requiring detection of small visual contrast require high sensitivity. Event cameras can provide higher dynamic range (DR) and reduce data rate and latency, but most existing event cameras have limited sensitivity. This paper presents the results of a 180-nm Towerjazz CIS process vision sensor called SDAVIS192. It outputs temporal contrast dynamic vision sensor (DVS) events and conventional active pixel sensor frames. The SDAVIS192 improves on previous DAVIS sensors with higher sensitivity for temporal contrast. The temporal contrast thresholds can be set down to 1% for negative changes in logarithmic intensity (OFF events) and down to 3.5% for positive changes (ON events). The achievement is possible through the adoption of an in-pixel preamplification stage. This preamplifier reduces the effective intrascene DR of the sensor (70 dB for OFF and 50 dB for ON), but an automated operating region control allows up to at least 110-dB DR for OFF events. A second contribution of this paper is the development of characterization methodology for measuring DVS event detection thresholds by incorporating a measure of signal-to-noise ratio (SNR). At average SNR of 30 dB, the DVS temporal contrast threshold fixed pattern noise is measured to be 0.3%-0.8% temporal contrast. Results comparing monochrome and RGBW color filter array DVS events are presented. The higher sensitivity of SDAVIS192 make this sensor potentially useful for calcium imaging, as shown in a recording from cultured neurons expressing calcium sensitive green fluorescent protein GCaMP6f.

GOSSS-DR1: The First Data Release of the Galactic O-star Spectroscopic Survey

NASA Astrophysics Data System (ADS)

Sota, Alfredo; Maíz Apellániz, Jesús; Barbá, Rodolfo H.; Walborn, Nolan R.; Alfaro, Emilio J.; Gamen, Roberto C.; Morrell, Nidia I.; Arias, Julia I.; Gallego Calvente, A. T.

2013-06-01

Coinciding with this meeting, we are publishing the first data release of GOSSS. This release contains [a] revised spectral classifications and [b] blue-violet R~2500 spectra in FITS format for ~400 Galactic O stars, including all brighter than B=8. DR1 (and future releases) will take place through GOSC, the Galactic O-Star Catalog (http://gosc.iaa.es), which will be updated for the occasion. Since 2011 GOSC runs on a MySQL database and allows for queries based on coordinates, spectral class, photometry, and other parameters. Future data releases will include the rest of the stars observed in GOSSS (currently 1521 with ~1000 more planned in the next two years).

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.

An Engineering Method for Estimating the Induced Lift on V/STOL Aircraft Hovering in and Out of Ground Effect.

DTIC Science & Technology

1981-01-01

Mistletoe Dr. Newport News, Virginia 23606 AIRTASK NO. AO3V-320D/O1B/7F41-400-000 APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED Prepared for NAVAL...TASK S. PRPORINOAREA * WORK UNIT NUMBEis Richard E. Kuhn, V/STOL Consultant AIRTASK No. AO3V-320D/ 111 Mistletoe Dr. 0B/ 7F4l-400-O000 Newport News, Va

Hearing thresholds in patients with drug-resistant tuberculosis: baseline audiogram configurations and associations

PubMed Central

Sogebi, Olusola Ayodele; Fadeyi, Muse Olatunbosun; Adefuye, Bolanle Olufunlola; Soyinka, Festus Olukayode

2017-01-01

ABSTRACT Objective: To use baseline audiogram parameters in order to ascertain whether drug-resistant tuberculosis (DR-TB) has effects on hearing, as well as to describe the configurations of the audiograms and to determine whether there are parameters that can be associated with those configurations. Methods: This was a prospective study involving patients diagnosed with DR-TB at a tuberculosis treatment center in the state of Ogun, in Nigeria. The patients included in the study were submitted to pure tone audiometry at baseline (within two weeks after treatment initiation). For comparative analyses, data regarding demographic and clinical characteristics were collected from the medical records of the patients. Results: The final sample comprised 132 patients. The mean age of the patients was 34.5 ± 12.6 years (range, 8-82 years), and the male:female ratio was 2:1. Of the 132 patients, 103 (78.0%) resided in neighboring states, 125 (94.7%) had previously experienced antituberculosis treatment failure, and 18 (13.6%) were retroviral-positive. Normal audiograms were found in 12 patients (9.1%), whereas sensorineural hearing loss was identified in 104 (78.8%), the two most common configurations being ascending, in 54 (40.9%), and sloping, in 26 (19.7%). Pure-tone averages at low frequencies (0.25-1.0 kHz) and high frequencies (2.0-8.0 kHz) were 33.0 dB and 40.0 dB, respectively. Regarding the degree of hearing loss in the better ear, 36 patients (27.3%) were classified as having normal hearing and 67 (50.8%) were classified as having mild hearing loss (26-40 dB), whereas 29 (21.9%) showed moderate or severe hearing loss. Among the variables studied (age, gender, retroviral status, previous treatment outcome, and weight at admission), only male gender was associated with audiometric configurations. Conclusions: In this sample of patients with DR-TB, most presented with bilateral, mild, suboptimal sensorineural hearing loss, and ascending/sloping audiometric configurations were associated with male gender. PMID:28746530

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.

Newborn HLA-DR,DQ genotype screening: age- and ethnicity-specific type 1 diabetes risk estimates

PubMed Central

Emery, Lisa M; Babu, Sunanda; Bugawan, Teodorica L; Norris, Jill M; Erlich, Henry A; Eisenbarth, George S; Rewers, Marian

2005-01-01

Objective Certain human leukocyte antigen (HLA)-DR,DQ genotypes have been associated with type 1 diabetes mellitus (T1DM) risk, although it is unknown whether the association is due to alleles, haplotypes, genotypes, the formation of heterodimers, or all of the above. To characterize the role of the HLA-DR,DQ genotype and ethnicity on the onset age of T1DM, we analyzed these factors in patients with T1DM and the general population. Methods One thousand three hundred twenty-two well-characterized patients with T1DM were compared with 3339 children from the general population of Denver, Colorado, USA. Because of the extensive available data across age and ethnic groups, this study population is unique. Results The HLA-DR3/4,DQB1*0302, DRX/4,DQB1*0302 (where X = 1, 4, 8, and 9), and HLA-DR3/3 genotypes were associated with T1DM, supporting previous research. Additionally, the DR3/9 genotype showed a positive association with T1DM, which has not previously been described in Caucasian populations. The HLA-DR3/4*0302 genotype was most strongly associated with T1DM in diabetic individuals with the youngest onset age. Genotype frequencies were similar between Hispanics and non-Hispanic whites, except for the DR3/3 genotype, which was more likely to be found in non-Hispanic whites. Conclusions These results indicate that there are multiple alleles and genotypes associated with T1DM and that the risk associated with different genetic markers depends on the age of disease onset, suggesting that some markers may be involved in more rapid disease progression. PMID:16109069

Diagnostic Pathway with Multiparametric Magnetic Resonance Imaging Versus Standard Pathway: Results from a Randomized Prospective Study in Biopsy-naïve Patients with Suspected Prostate Cancer.

PubMed

Porpiglia, Francesco; Manfredi, Matteo; Mele, Fabrizio; Cossu, Marco; Bollito, Enrico; Veltri, Andrea; Cirillo, Stefano; Regge, Daniele; Faletti, Riccardo; Passera, Roberto; Fiori, Cristian; De Luca, Stefano

2017-08-01

An approach based on multiparametric magnetic resonance imaging (mpMRI) might increase the detection rate (DR) of clinically significant prostate cancer (csPCa). To compare an mpMRI-based pathway with the standard approach for the detection of prostate cancer (PCa) and csPCa. Between November 2014 and April 2016, 212 biopsy-naïve patients with suspected PCa (prostate specific antigen level ≤15 ng/ml and negative digital rectal examination results) were included in this randomized clinical trial. Patients were randomized into a prebiopsy mpMRI group (arm A, n=107) or a standard biopsy (SB) group (arm B, n=105). In arm A, patients with mpMRI evidence of lesions suspected for PCa underwent mpMRI/transrectal ultrasound fusion software-guided targeted biopsy (TB) (n=81). The remaining patients in arm A (n=26) with negative mpMRI results and patients in arm B underwent 12-core SB. The primary end point was comparison of the DR of PCa and csPCa between the two arms of the study; the secondary end point was comparison of the DR between TB and SB. The overall DRs were higher in arm A versus arm B for PCa (50.5% vs 29.5%, respectively; p=0.002) and csPCa (43.9% vs 18.1%, respectively; p<0.001). Concerning the biopsy approach, that is, TB in arm A, SB in arm A, and SB in arm B, the overall DRs were significantly different for PCa (60.5% vs 19.2% vs 29.5%, respectively; p<0.001) and for csPCa (56.8% vs 3.8% vs 18.1%, respectively; p<0.001). The reproducibility of the study could have been affected by the single-center nature. A diagnostic pathway based on mpMRI had a higher DR than the standard pathway in both PCa and csPCa. In this randomized trial, a pathway for the diagnosis of prostate cancer based on multiparametric magnetic resonance imaging (mpMRI) was compared with the standard pathway based on random biopsy. The mpMRI-based pathway had better performance than the standard pathway. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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.

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.

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.

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

Interferon gamma-dependent intestinal pathology contributes to the lethality in bacterial superantigen-induced toxic shock syndrome.

PubMed

Tilahun, Ashenafi Y; Holz, Marah; Wu, Tsung-Teh; David, Chella S; Rajagopalan, Govindarajan

2011-02-03

Toxic shock syndrome (TSS) caused by the superantigen exotoxins of Staphylococcus aureus and Streptococcus pyogenes is characterized by robust T cell activation, profound elevation in systemic levels of multiple cytokines, including interferon-γ (IFN-γ), followed by multiple organ dysfunction and often death. As IFN-γ possesses pro- as well as anti-inflammatory properties, we delineated its role in the pathogenesis of TSS. Antibody-mediated in vivo neutralization of IFN-γ or targeted disruption of IFN-γ gene conferred significant protection from lethal TSS in HLA-DR3 transgenic mice. Following systemic high dose SEB challenge, whereas the HLA-DR3.IFN-γ(+/+) mice became sick and succumbed to TSS, HLA-DR3.IFN-γ(-/-) mice appeared healthy and were significantly protected from SEB-induced lethality. SEB-induced systemic cytokine storm was significantly blunted in HLA-DR3.IFN-γ(-/-) transgenic mice. Serum concentrations of several cytokines (IL-4, IL-10, IL-12p40 and IL-17) and chemokines (KC, rantes, eotaxin and MCP-1) were significantly lower in HLA-DR3.IFN-γ(-/-) transgenic mice. However, SEB-induced T cell expansion in the spleens was unaffected and expansion of SEB-reactive TCR Vβ8(+) CD4(+) and CD8(+) T cells was even more pronounced in HLA-DR3.IFN-γ(-/-) transgenic mice when compared to HLA-DR3.IFN-γ(+/+) mice. A systematic histopathological examination of several vital organs revealed that both HLA-DR3.IFN-γ(+/+) and HLA-DR3.IFN-γ(-/-) transgenic mice displayed comparable severe inflammatory changes in lungs, and liver during TSS. Remarkably, whereas the small intestines from HLA-DR3.IFN-γ(+/+) transgenic mice displayed significant pathological changes during TSS, the architecture of small intestines in HLA-DR3.IFN-γ(-/-) transgenic mice was preserved. In concordance with these histopathological changes, the gut permeability to macromolecules was dramatically increased in HLA-DR3.IFN-γ(+/+) but not HLA-DR3.IFN-γ(-/-) mice during TSS. Overall, IFN-γ seemed to play a lethal role in the immunopathogenesis of TSS by inflicting fatal small bowel pathology. Our study thus identifies the important role for IFN-γ in TSS.

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.

Defense Small Business Innovation Research Program (SBIR). Volume 3. Air Force Abstracts of Phase 1 Awards from FY 1988 SBIR Solicitation

DTIC Science & Technology

1989-05-01

THE TARGET DOPPLER FREQUENCIES. ADAPTIVE SENSORS INC 216 PICO BLVD - STE 8 SANTA MONICA, CA 90405 CONTRACT NUMBER: JOHN S BAILEY TITLE: SPATIALLY...APPLIED RESEARCH ASSOCS INC 4300 SAN MATEO BLVD NE - STE A220 ALBUQUERQUE, NM 87110 CONTRACT NUMBER: FRANK A MAESTAS TITLE: PARAMETRIC ANALYSIS OF EXPLOSIVE...VERIFIED THROUGH SUBSCALE FABRICATION AND TEST. AV DYNAMICS INC 825 MYRTLE AVE MONROVIA, CA 91016 CONTRACT NUMBER: DR P B S LISSAMAN TITLE: LIGHT WEIGHT

Chemiluminescence from the Reaction of 2-Methylene-3-acetyloxazoline-4,5-dione with Hydrogen Peroxide.

DTIC Science & Technology

1982-08-20

D.C. 20375 1 Washington, D.C. 20375 1 G. B. Schuster Dr. William M. Jackson *Cheol Depart Department of Chemistry Universit linois Howard University Ur... Howard University California Washington, DC 20059 1 Los Angeles, California 90007 1 Dr. M. S. Wrighton Department of Chemistry Massachusetts Institute of Technology Cambridge, Hassachusetts 02139 1

A Cross-National Comparison of Suicide Attempts, Drug Use, and Depressed Mood Among Dominican Youth.

PubMed

Peña, Juan B; Masyn, Katherine E; Thorpe, Lorna E; Peña, Stephanie M; Caine, Eric D

2016-06-01

We compared suicide attempts, depressed mood, and drug use of 1,710 Dominican public high school students in New York City (NYC) and 9,573 in the Dominican Republic (DR) in 2009. Compared to DR Dominicans, NYC Dominicans were more likely to have reported lifetime marijuana use (27.6% vs. 1.5%), lifetime inhalant use (11.0% vs. 7.6%), lifetime other drug use (9.9% vs. 3.0%), depressed mood (31.3% vs. 27.2%), and suicide attempt (13.8% vs. 8.8%). The results of this study supported the hypothesis that substantial increases in illicit drug use, especially cocaine, heroin, ecstasy, and methamphetamines, among NYC Dominican youth account for their increased risk for suicide attempts compared to their DR Dominican counterparts. It also identified suicide attempts as a public health problem among NYC Dominicans, the largest NYC Latino immigrant population. © 2015 The American Association of Suicidology.

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

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.

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

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.

Apparent genetic difference between hypothyroid patients with blocking-type thyrotropin receptor antibody and those without, as shown by restriction fragement length polymorphism analyses of HLA-DP loci

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

Inoue, Daisuke; Sugawa, Hideo; Akamizu, Takashi

1993-09-01

HLA types in Japanese patients with primary hypothyroidism were analyzed to see whether those with blocking-type TSH receptor antibody (TSH-R BAb M) differed genetically from those with idiopathic myxedema (IM). HLA typings of -A, -B, -C, -DR, and -DQ (73 antigens) were performed serologically, and those of -D and -DP (29 antigens) were analyzed by the restriction fragment length polymorphism method. Thirty patients were studied with TSH-R BAb M, and 28 with IM. The data were analyzed and compared with previous results from 88 Graves' patients, 46 Hashimoto patients, and 186 control subjects. Overall, 192 patients with 4 autoimmune thyroidmore » disorders showed a decrease in -Aw19 and an increase in -DQw4 (corrected P < 0.05) and significant associations of -Aw33, -Bw46, -Cw3, -DRw8, -DR9, and -DQw3. In TSH-R BAb M patients, increases in -B35, -Bw60, and -Dw8 and decreases in -DR4 and -DPw2 were seen, whereas IM patients showed increased -DPw2, -Bw61, and -Dw23. In comparisons between TSH-R-BAb M and IM, the difference in -DPw2 was highly significant. HLA-B35 differed significantly in these 2 types of hypothyroidism. In conclusion, TSH-R BAb M patients have decreased frequency of -DPw2 and are genetically similar to Graves' disease, whereas IM patients are characterized by high frequency of -DPw2 and are genetically similar to Hashimoto's thyroiditis. 39 refs., 2 figs., 3 tabs.« less

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

Environmental Effects on the Incubation Time Characteristics in Stress-Corrosion Cracking

DTIC Science & Technology

2011-04-01

Corrosion Experimental Data for Specimen SL51 143 Table B2. Stress Corrosion Experimental Data for Specimen SL76 (3.5% NaCI, K , =6.8M/Wm) 144 Table B3...of action of the external load; - 143 - K =applied stress intensity factor; da/dt=crack growth rate. Table B2. Stress Corrosion Experimental Data for...Submitted to Dr. Asuri K . Vasudevan Scientific Officer Office of Naval Research, Code-332 875 North Randolph Street, Suite 1425, Room- 629

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.).

Sodium Octanoate Modulates the Innate Immune Response of Bovine Mammary Epithelial Cells through the TLR2/P38/JNK/ERK1/2 Pathway: Implications during Staphylococcus aureus Internalization.

PubMed

Alva-Murillo, Nayeli; Ochoa-Zarzosa, Alejandra; López-Meza, Joel E

2017-01-01

Bovine mammary epithelial cells (bMECs) contribute to mammary gland defense against invading pathogens, such as Staphylococcus aureus (intracellular facultative), which is recognized by TLR2. In a previous report, we showed that sodium octanoate [NaO, a medium chain fatty acid (C8)] induces (0.25 mM) or inhibits (1 mM) S. aureus internalization into bMECs and differentially regulates the innate immune response (IIR). However, the molecular mechanisms have not been described, which was the aim of this study. The results showed that α5β1 integrin membrane abundance (MA) was increased in 0.25 mM NaO-treated cells, but TLR2 or CD36 MA was not modified. When these receptors were blocked individually, 0.25 mM NaO-increased S. aureus internalization was notably reduced. Interestingly, in this condition, the IIR of the bMECs was impaired because MAPK (p38, JNK, and ERK1/2) phosphorylation and the activation of transcription factors related to these pathways were decreased. In addition, the 1 mM NaO treatment induced TLR2 MA, but neither the integrin nor CD36 MA was modified. The reduction in S. aureus internalization induced by 1 mM NaO was increased further when TLR2 was blocked. In addition, the phosphorylation levels of the MAPKs increased, and 13 transcriptional factors related to the IIR were slightly activated (CBF, CDP, c-Myb, AP-1, Ets-1/Pea-3, FAST-1, GAS/ISRE, AP-2, NFAT-1, OCT-1, RAR/DR-5, RXR/DR-1, and Stat-3). Moreover, the 1 mM NaO treatment up-regulated gene expression of IL-8 and RANTES and secretion of IL-1β. Notably, when 1 mM NaO-treated bMECs were challenged with S. aureus , the gene expression of IL-8 and IL-10 increased, while IL-1β secretion was reduced. In conclusion, our results showed that α5β1 integrin, TLR2 and CD36 are involved in 0.25 mM NaO-increased S. aureus internalization in bMECs. In addition, 1 mM NaO activates bMECs via the TLR2 signaling pathways (p38, JNK, and ERK1/2), which improves IIR before S. aureus invasion. Additionally, NaO (1 mM) might exert anti-inflammatory effects after bacterial internalization.

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.

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.

Fibroblast growth factor deficiencies impact anxiety-like behavior and the serotonergic system.

PubMed

Brooks, Leah R; Enix, Courtney L; Rich, Samuel C; Magno, Jinno A; Lowry, Christopher A; Tsai, Pei-San

2014-05-01

Serotonergic neurons in the dorsal raphe nucleus (DR) are organized in anatomically distinct subregions that form connections with specific brain structures to modulate diverse behaviors, including anxiety-like behavior. It is unclear if the functional heterogeneity of these neurons is coupled to their developmental heterogeneity, and if abnormal development of specific DR serotonergic subregions can permanently impact anxiety circuits and behavior. The goal of this study was to examine if deficiencies in different components of fibroblast growth factor (Fgf) signaling could preferentially impact the development of specific populations of DR serotonergic neurons to alter anxiety-like behavior in adulthood. Wild-type and heterozygous male mice globally hypomorphic for Fgf8, Fgfr1, or both (Fgfr1/Fgf8) were tested in an anxiety-related behavioral battery. Both Fgf8- and Fgfr1/Fgf8-deficient mice display increased anxiety-like behavior as measured in the elevated plus-maze and the open-field tests. Immunohistochemical staining of a serotonergic marker, tryptophan hydroxylase (Tph), revealed reductions in specific populations of serotonergic neurons in the ventral, interfascicular, and ventrolateral/ventrolateral periaqueductal gray subregions of the DR in all Fgf-deficient mice, suggesting a neuroanatomical basis for increased anxiety-like behavior. Overall, this study suggests Fgf signaling selectively modulates the development of different serotonergic neuron subpopulations. Further, it suggests anxiety-like behavior may stem from developmental disruption of these neurons, and individuals with inactivating mutations in Fgf signaling genes may be predisposed to anxiety disorders. Published by Elsevier B.V.

Naringin attenuates diabetic retinopathy by inhibiting inflammation, oxidative stress and NF-κB activation in vivo and in vitro

PubMed Central

Liu, Lihua; Zuo, Zhongfu; Lu, Sijing; Liu, Aihua; Liu, Xuezheng

2017-01-01

Objective(s): Naringin, an essential flavonoid, inhibits inflammatory response and oxidative stress in diabetes. However, whether naringin has beneficial effects on diabetic retinopathy (DR) remains unknown. Materials and Methods: Streptozotocin (STZ, 65 mg/kg) was intraperitoneally injected into male rats (8 weeks old weighting 200-250 g) to establish diabetic model, then naringin (20, 40 or 80 mg/kg/day) was intraperitoneally injected into the diabetic rats for twelve weeks. Glial fibrillary acidic protein (GFAP) level, thickness of ganglion cell layer (GCL) and ganglion cell counts were assessed in diabetic retina in vivo. Naringin (50 μM) that significantly inhibited high glucose (HG, 25 mM)-induced cell proliferation was used to treat rat Muller cell line (rMC1) in vitro. Inflammatory response, oxidative stress and activation of nuclear factor kappa B (NF-κB) p65 were evaluated in retina in vivo and in rMC1 cells in vitro. Results: Naringin alleviated DR symptoms as evidenced by the increased retinal ganglion cells and decreased GFAP level in rat retina. Naringin exhibited anti-inflammatory and antioxidative effects as confirmed by the down-regulated pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and the up-regulated antioxidants, glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in DR rats. Moreover, we found that naringin inhibited HG-induced proliferation, abnormal inflammatory response and oxidative stress in rMC1 cells. In addition, the enhanced nuclear translocation of NF-κB p65 in diabetic rat retina and HG-induced rMC1 cells was suppressed by naringin. Conclusion: Naringin attenuates inflammatory response, oxidative stress and NF-κB activation in experimental models of DR. PMID:28852447

Naringin attenuates diabetic retinopathy by inhibiting inflammation, oxidative stress and NF-κB activation in vivo and in vitro.

PubMed

Liu, Lihua; Zuo, Zhongfu; Lu, Sijing; Liu, Aihua; Liu, Xuezheng

2017-07-01

Naringin, an essential flavonoid, inhibits inflammatory response and oxidative stress in diabetes. However, whether naringin has beneficial effects on diabetic retinopathy (DR) remains unknown. Streptozotocin (STZ, 65 mg/kg) was intraperitoneally injected into male rats (8 weeks old weighting 200-250 g) to establish diabetic model, then naringin (20, 40 or 80 mg/kg/day) was intraperitoneally injected into the diabetic rats for twelve weeks. Glial fibrillary acidic protein (GFAP) level, thickness of ganglion cell layer (GCL) and ganglion cell counts were assessed in diabetic retina in vivo . Naringin (50 μM) that significantly inhibited high glucose (HG, 25 mM)-induced cell proliferation was used to treat rat Muller cell line (rMC1) in vitro . Inflammatory response, oxidative stress and activation of nuclear factor kappa B (NF-κB) p65 were evaluated in retina in vivo and in rMC1 cells in vitro . Naringin alleviated DR symptoms as evidenced by the increased retinal ganglion cells and decreased GFAP level in rat retina. Naringin exhibited anti-inflammatory and antioxidative effects as confirmed by the down-regulated pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and the up-regulated antioxidants, glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in DR rats. Moreover, we found that naringin inhibited HG-induced proliferation, abnormal inflammatory response and oxidative stress in rMC1 cells. In addition, the enhanced nuclear translocation of NF-κB p65 in diabetic rat retina and HG-induced rMC1 cells was suppressed by naringin. Naringin attenuates inflammatory response, oxidative stress and NF-κB activation in experimental models of DR.

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

Dramatic recovery in acute ischemic stroke is associated with arterial recanalization grade and speed.

PubMed

Mazighi, Mikael; Meseguer, Elena; Labreuche, Julien; Serfaty, Jean-Michel; Laissy, Jean-Pierre; Lavallée, Philippa C; Cabrejo, Lucie; Guidoux, Céline; Lapergue, Bertrand; Klein, Isabelle F; Olivot, Jean-Marc; Rouchaud, Aymeric; Desilles, Jean-Philippe; Schouman-Claeys, Elisabeth; Amarenco, Pierre

2012-11-01

Dramatic recovery (DR) is a predictor of stroke outcome among others. However, after successful recanalization, systematic favorable outcome is not the rule. We sought to analyze the impact of recanalization on DR in patients with acute ischemic stroke eligible for any revascularization strategies (either intravenous or endovascular). We analyzed data collected between April 2007 and May 2011 in our prospective clinical registry. All patients with acute ischemic stroke with National Institutes of Health Stroke Scale≥10 at admission and an identification of arterial status before treatment were included. DR was defined as National Institutes of Health Stroke Scale≤3 at 24 hours or a decrease of ≥10 points within 24 hours. DR occurred in 75 of 255 patients with acute ischemic stroke (29.4%). Patients with persistent occlusion had a low DR rate (11.1%) than those with no documented occlusion (36.5%) and those with occlusion followed by recanalization (35.3%; both P<0.001). Among patients with recanalization monitored by angiography, DR was higher among patients with complete recanalization than among those with partial recanalization (46.8% versus 14.3%; P<0.001) and increased with tertiles of time to recanalization (Ptrend=0.002). In multivariable logistic regression analysis, grade and time to recanalization appeared independently associated with DR; the adjusted ORs were 4.17 (95% CI, 1.61-10.77) for complete recanalization and 1.24 (95% CI, 1.04-1.48) for each 30-minute time decrease. Patients with versus without DR more frequently had modified Rankin Scale≤1 (67.6% versus 9.0%; P<0.001) and less frequently had hemorrhage (17.3% versus 33.9%; P=0.024). DR is strongly associated with favorable clinical outcome and is dependent on complete recanalization and time to recanalization.

HLA antigens and other genetic markers in the Mapuche Indians of Argentina.

PubMed

Haas, E J; Salzano, F M; Araujo, H A; Grossman, F; Barbetti, A; Weimer, T A; Franco, M H; Verruno, L; Nasif, O; Morales, V H

1985-01-01

A total of 107 Mapuche Indians living in western Argentina were studied with respect to 16 genetic systems. For HLA, there were a few differences in relation to previous studies; and considering the averages observed in 15 other South American tribes, Mapuche Indians showed low values for A2, A9 and C3, but high ones for A28 and B16. This is the first report of the presence (in low frequencies, 1-6%) of alleles C2, C6 and C7, as well as of DR antigens (most frequent alleles DR4 and DR2) in South American Indians. Some peculiar reactions shown by products of locus B suggest the presence of antigens that are characteristic of the Mapuche. As for the other systems, the frequencies of R1 (Rh) and PGM1(1) were lower but those for r (Rh), GLO1 and Hp1 were higher than the averages obtained considering previous studies of this ethnic group. Other salient findings were the variability observed in the PGM2 and C3 systems, and the low prevalence of Bfs.

A Celiac Diasease Associated lncRNA Named HCG14 Regulates NOD1 Expression in Intestinal Cells.

PubMed

Santin, Izortze; Jauregi-Miguel, Amaia; Velayos, Teresa; Castellanos-Rubio, Ainara; Garcia-Etxebarria, Koldo; Romero-Garmendia, Irati; Fernandez-Jimenez, Nora; Irastorza, Iñaki; Castaño, Luis; Bilbao, Jose Ramón

2018-03-29

To identify additional celiac disease associated loci in the Major Histocompatibility Complex independent from classical HLA risk alleles (HLA-DR3-DQ2) and to characterize their potential functional impact in celiac disease pathogenesis at the intestinal level. We performed a high resolution SNP genotyping of the MHC region, comparing HLA-DR3 homozygous celiac patients and non-celiac controls carrying a single copy of the B8-DR3-DQ2 conserved extended haplotype. Expression level of potential novel risk genes was determined by RT-PCR in intestinal biopsies and in intestinal and immune cells isolated from control and celiac individuals. Small interfering RNA-driven silencing of selected genes was performed in the intestinal cell line T84. MHC genotyping revealed two associated SNPs, one located in TRIM27 gene and another in the non-coding gene HCG14. After stratification analysis, only HCG14 showed significant association independent from HLA-DR-DQ loci Expression of HCG14 was slightly downregulated in epithelial cells isolated from duodenal biopsies of celiac patients, and eQTL analysis revealed that polymorphisms in HCG14 region were associated with decreased NOD1 expression in duodenal intestinal cells. We have sucessfully employed a conserved extended haplotype-matching strategy and identified a novel additional celiac disease risk variant in the lncRNA HGC14. This lncRNA seems to regulate the expression of NOD1 in an allele-specific manner. Further functional studies are needed to clarify the role of HCG14 in the regulation of gene expression and to determine the molecular mechanisms by which the risk variant in HCG14 contributes to celiac disease pathogenesis.

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.

First Data Release of the ESO-ARO Public Survey SAMPLING—SMT “All-sky” Mapping of Planck Interstellar Nebulae in the Galaxy

NASA Astrophysics Data System (ADS)

Wang, Ke; Zahorecz, Sarolta; Cunningham, Maria R.; Tóth, L. Viktor; Liu, Tie; Lu, Xing; Wang, Yuan; Cosentino, Giuliana; Sung, Ren-Shiang; Sokolov, Vlas; Wang, Shen; Wang, Yuwei; Zhang, Zhiyu; Li, Di; Kim, Kee-Tae; Tatematsu, Ken’ichi; Testi, Leonardo; Wu, Yuefang; Yang, Ji; SAMPLING Collaboration

2018-01-01

We make the first data release (DR1) of the ongoing ESO Public Survey SAMPLING (http://dx.doi.org/10.7910/DVN/0L8NHX). DR1 comprises of 124 fields distributed in $70^\\circ < l < 216^\\circ$, $-35^\\circ < b < 25^\\circ$. The 12CO and 13CO (2-1) cubes are gridded in $8"$ pixels, with an effective resolution of $36"$. The channel width is 0.33 km/s and the RMS noise is $T_{\\rm mb}<0.2$ K. Once completed, SAMPLING and complementary surveys will initiate the first major step forward to characterize molecular clouds and star formation on truly Galactic scales.

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

Developing Breast Cancer Program at Xavier; Genomic and Proteomic Analysis of Signaling Pathways Involved in Xenohormone and MEK5 Regulation of Breast Cancer

DTIC Science & Technology

2006-05-01

34039 44 42 4.25 5.7 unnamed protein product A04 12653057 17.1 16 6 3.8 Neucleoside-diphosphate kinase 1, isoform b A05 54696638 27 25 6 6.5 Heat shock...student traiing because the students is not able to generate a product. Both Dr. Wang and Wiese feel that the most effective student training...have developed the following idea for a mini- proposal: The protein p23 is up regulated in cancer cells. It is a co-chaperone of heat shock protein

Human leukocyte antigens as a risk factor for the primary diseases leading to end stage renal disease in Egyptian patients.

PubMed

El-Gezawy, Ebtesam M; Baset, Hesham A Abdel; Nasif, Khalid A; Osama, Amany; AbdelAzeem, Hanan G; Ali, Medhat; Khalil, Rasha Y

2011-01-01

The number of patients with end stage renal disease (ESRD) is increasing considerably worldwide. The incidence of ESRD is likely to be higher than that reported from the developed world, with diabetic nephropathy, hypertension and chronic glomerulonephritis being the most common causes in Egypt. The aim of the present study is to investigate the Human leukocyte antigens [HLA-A,-B and -DRB1 antigens] as a risk factor for the primary diseases leading to ESRD in Egyptian patients. Our study included a total of 457 individuals comprising 207 ESRD patients and 250 healthy controls were enrolled into the study. Class I [HLA-A and-B] typing was performed by complement-dependent cytotoxicity (CDC) method, while class II HLA-DRB1 typing was performed by low resolution polymerase chain reaction (PCR)-sequence-specific oligonucleotide probe [PCR-SSOP]. We found that the most common primary disease groups leading to ESRD classified as Diabetic nephropathy, hypertensive nephrosclerosis and chronic glomerulonephritis. HLA-A2, -B8 and DRB1*3 and HLA-DRB1*11 significantly correlated with diabetic nephropathy, respectively. B8-DR3 haplotype is susceptible to DM. In, conclusion, determination of HLA-A,-B and -DRB1 as a risk factor for primary diseases leading to ESRD might be beneficial in preventing progression to ESRD and recurrence of the primary disease post-transplantation.

Accuracy and reliability of retinal photo grading for diabetic retinopathy: Remote graders from a developing country and standard retinal photo grader in Australia.

PubMed

Islam, Fakir M Amirul

2017-01-01

To evaluate the accuracy and reliability of fundus retinal photos graded by local graders in Bangladesh with those graded by an expert at the Centre for Eye Research Australia (CERA) in the context of mass scale diabetic retinopathy (DR) screening in Bangladesh. A population-based cross-sectional study of 3,104 adults identified 213 (7.2%) eligible patients with diabetes of age ≥ 40 years in 2012-2013. Retinal photographs were collected using a non-mydriatic digital fundus retinal camera and a two-field imaging protocol. The photos were graded by two remote graders (G1 and G2) who were trained by a retinal specialist (RS) in Bangladesh, by the RS himself, and by a Centre for Eye Research Australia (CERA) grader. The local graders up skilled their grading ability by comparing 30% of the photos graded by the CERA grader with their own grades. Learning from that exercise was applied to the remaining 70% of photos, which were re-graded. Reliability and accuracy of grading amongst the graders were reported using cross tabulation, inter- and intra-grader reliability, and with sensitivity and specificity. Of 122 eyes from 61 patients, the mild (R1) DR was estimated to be 14 to 25%, pre-proliferative (R2) DR 4-8%, and proliferative (R3) DR 0.8 to 1.6%, whereas 25%, 8%, 18%, and 15% were found to be ungradable by CERA, RS, G1, and G2, respectively. Of 8 (6.6%) eyes identified as R2 by the CERA grader, 5 (63%), 3 (38%) and 3 (38%) were correctly classified as R2, whereas the rest were classified either as R1 or R3 but none were classified as no DR (R0) or ungradable by the RS, G1 and G2, respectively. After getting experience reviewing the 30% test set graded by the CERA grader, the local graders graded moderate and severe DR with 100% accuracy. After excluding ungradable photos, the sensitivity (specificity) relative to the CERA grader was 82% (88%) before and 80% (93%) after training for G1 and 56% (87%) before and 77% (90%) after training for G2. In case of maculopathy, the CERA grader reported 11.2% eyes with maculopathy, which included 100% of the 4.9% by RS, 6.6% by G1, and 7.4% by G2. Local graders in Bangladesh are able to grade retinal photos with high accuracy if the DR is at least of a moderate level. With appropriate training and experience, local graders have the ability to contribute significantly to the grading of millions of retinal photos, which required grading in resource- poor countries.

[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).

Interferon Gamma-Dependent Intestinal Pathology Contributes to the Lethality in Bacterial Superantigen-Induced Toxic Shock Syndrome

PubMed Central

Tilahun, Ashenafi Y.; Holz, Marah; Wu, Tsung-Teh; David, Chella S.; Rajagopalan, Govindarajan

2011-01-01

Toxic shock syndrome (TSS) caused by the superantigen exotoxins of Staphylococcus aureus and Streptococcus pyogenes is characterized by robust T cell activation, profound elevation in systemic levels of multiple cytokines, including interferon-γ (IFN-γ), followed by multiple organ dysfunction and often death. As IFN-γ possesses pro- as well as anti-inflammatory properties, we delineated its role in the pathogenesis of TSS. Antibody-mediated in vivo neutralization of IFN-γ or targeted disruption of IFN-γ gene conferred significant protection from lethal TSS in HLA-DR3 transgenic mice. Following systemic high dose SEB challenge, whereas the HLA-DR3.IFN-γ+/+ mice became sick and succumbed to TSS, HLA-DR3.IFN-γ−/− mice appeared healthy and were significantly protected from SEB-induced lethality. SEB-induced systemic cytokine storm was significantly blunted in HLA-DR3.IFN-γ−/− transgenic mice. Serum concentrations of several cytokines (IL-4, IL-10, IL-12p40 and IL-17) and chemokines (KC, rantes, eotaxin and MCP-1) were significantly lower in HLA-DR3.IFN-γ−/− transgenic mice. However, SEB-induced T cell expansion in the spleens was unaffected and expansion of SEB-reactive TCR Vβ8+ CD4+ and CD8+ T cells was even more pronounced in HLA-DR3.IFN-γ−/− transgenic mice when compared to HLA-DR3.IFN-γ+/+ mice. A systematic histopathological examination of several vital organs revealed that both HLA-DR3.IFN-γ+/+ and HLA-DR3.IFN-γ−/− transgenic mice displayed comparable severe inflammatory changes in lungs, and liver during TSS. Remarkably, whereas the small intestines from HLA-DR3.IFN-γ+/+ transgenic mice displayed significant pathological changes during TSS, the architecture of small intestines in HLA-DR3.IFN-γ−/− transgenic mice was preserved. In concordance with these histopathological changes, the gut permeability to macromolecules was dramatically increased in HLA-DR3.IFN-γ+/+ but not HLA-DR3.IFN-γ−/− mice during TSS. Overall, IFN-γ seemed to play a lethal role in the immunopathogenesis of TSS by inflicting fatal small bowel pathology. Our study thus identifies the important role for IFN-γ in TSS. PMID:21304813

Avenanthramide supplementation attenuates eccentric exercise-inflicted blood inflammatory markers in women.

PubMed

Koenig, Ryan T; Dickman, Jonathan R; Kang, Choung-Hun; Zhang, Tianou; Chu, Yi-Fang; Ji, Li Li

2016-01-01

Rigorous exercise is known to generate reactive oxygen species (ROS) and inflict inflammatory response. The present study investigated whether dietary supplementation of avenanthramides (AVA) in oats would increase antioxidant protection and reduce inflammation in humans after an acute bout of eccentric exercise. Young women (age 18-30 years, N = 16) were randomly divided into two groups in a double-blinded fashion, receiving two cookies made of oat flour providing 9.2 mg AVA (AVA) or 0.4 mg AVA (Control, C) each day for 8 weeks. Before and after the dietary regimen each group of subjects ran downhill (DR) on a treadmill at -9% grade for 1 h at a speed to elicit 75% of maximal heart rate. Blood samples were collected at rest, immediately and 24 h post-DR. Before dietary supplementation plasma creatine kinase activity and tumor necrosis factor (TNF)-α concentration were increased immediately after DR (P < 0.05), whereas neutrophil respiratory burst (NRB) was elevated 24 h post-DR (P < 0.05). CK and TNF-α response to DR was abolished during post-supplementation tests in both AVA and C groups, whereas NRB was blunted only in AVA but not in C. Plasma interleukin-6 level and mononuclear cell nuclear factor (NF) κB activity were not affected by DR either before or after dietary supplementation, but were lowered 24 h post-DR in AVA versus C (P < 0.05). Both groups increased plasma total antioxidant activity following 8-week dietary regimen (P < 0.05), whereas only AVA group increased resting plasma glutathione (GSH) concentration (P < 0.05), decreased glutathione disulfide response to DR, and lowered erythrocyte GSH peroxidase activity (P < 0.05). Our data of pre- and post-supplementation difference reflect an interaction between repeated measure effect of eccentric exercise and AVA in diet. Long-term AVA supplementation can attenuate blood inflammation markers, decrease ROS generation and NFkB activation, and increased antioxidant capacity during an eccentric exercise bout.

DMA and DMB are the only genes in the class II region of the human MHC needed for class II-associated antigen processing

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

Ceman, S.; Rudersdorf, R.A.; Petersen, J.M.

1995-03-15

Previous studies have shown that homozygous mutations between the LMP2 and DNA loci in the human MHC cause class II molecules to be abnormally conformed and unstable in the presence of SDS at low temperature, and impede class II-associated Ag processing and presentation. These abnormalities result from impaired ability to form intracellular class II/peptide complexes that predominate in normal cells. We show in this work that this defect results from deficient expression of either the DMA or the DMB gene. Human B-LCL.174 (DR3) cells, which have a deletion of all known expressible genes in the class II region, express transgene-encodedmore » HLA-DR3, but have the abnormalities. Transfer of cosmid HA14, which contains the DMA and DMB genes, into .174 (DR3) cells restored normal DR3 conformation, stability in 0.4% SDS at 0{degrees}, and ability to process and present tetanus toxoid, but only when both DMA and DMB mRNAs were present. The requirement for both genetic expressions in engendering normal phenotypes was confirmed by transferring the cloned genes into .174 (DR3) cells separately or together. Because normal phenotypes were fully restored in transferent cells expressing DMA plus DMB, other genes in the {approximately} 1-mb homozygous class II region deletion in .174 (DR3) cells either do not participate in or are dispensable for apparently normal production of intracellular class II/peptide complexes. The properties of DM-deficient EBV-transformed B lymphoblastoid cell lines (LCLs) suggest ways of identifying humans in whom DM deficiency contributes to congenital immunodeficiency and malignancy. 67 refs., 5 figs., 1 tab.« 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

Conjunctive and Disjunctive Item Response Functions.

DTIC Science & Technology

1984-10-01

fed set ofvaluesof a, b, AI , B1 A2 2 . 2 A3 , and 13 , the f ’. g ’a. nd h’a in (7) are fied. Equation (7) must still hold for S - e19029e3,..* . Thus...for Item I Is -- b ?(a:1 , b1 ,O) (1 + ’)(I + e4 (22 where a and pi are arbitrary constants. These constants mst be the sam for all Items In a given...NETHERLIS I E3I1 Focility-Acquisitions 4133 Rugby Avnue 1 Lee Cronbach Bethesda, NO 20014 16 Laburnue Road Atherton, CA 94205 1 Dr. Benjamin A. Fairbank

Enhancing Flower Color through Simultaneous Expression of the B-peru and mPAP1 Transcription Factors under Control of a Flower-Specific Promoter

PubMed Central

Kim, Da-Hye; Park, Sangkyu; Lee, Jong-Yeol; Ha, Sun-Hwa; Lim, Sun-Hyung

2018-01-01

Flower color is a main target for flower breeding. A transgenic approach for flower color modification requires a transgene and a flower-specific promoter. Here, we expressed the B-peru gene encoding a basic helix loop helix (bHLH) transcription factor (TF) together with the mPAP1 gene encoding an R2R3 MYB TF to enhance flower color in tobacco (Nicotiana tabacum L.), using the tobacco anthocyanidin synthase (ANS) promoter (PANS) to drive flower-specific expression. The transgenic tobacco plants grew normally and produced either dark pink (PANSBP_DP) or dark red (PANSBP_DR) flowers. Quantitative real time polymerase chain reaction (qPCR) revealed that the expression of five structural genes in the flavonoid biosynthetic pathway increased significantly in both PANSBP_DP and PANSBP_DR lines, compared with the non-transformed (NT) control. Interestingly, the expression of two regulatory genes constituting the active MYB-bHLH-WD40 repeat (WDR) (MBW) complex decreased significantly in the PANSBP_DR plants but not in the PANSBP_DP plants. Total flavonol and anthocyanin abundance correlated with flower color, with an increase of 1.6–43.2 fold in the PANSBP_DP plants and 2.0–124.2 fold in the PANSBP_DR plants. Our results indicate that combinatorial expression of B-peru and mPAP1 genes under control of the ANS promoter can be a useful strategy for intensifying flower color without growth retardation. PMID:29361688

Age at first introduction to complementary foods is associated with sociodemographic factors in children with increased genetic risk of developing type 1 diabetes.

PubMed

Andrén Aronsson, Carin; Uusitalo, Ulla; Vehik, Kendra; Yang, Jimin; Silvis, Katherine; Hummel, Sandra; Virtanen, Suvi M; Norris, Jill M

2015-10-01

Infant's age at introduction to certain complementary foods (CF) has in previous studies been associated with islet autoimmunity, which is an early marker for type 1 diabetes (T1D). Various maternal sociodemographic factors have been found to be associated with early introduction to CF. The aims of this study were to describe early infant feeding and identify sociodemographic factors associated with early introduction to CF in a multinational cohort of infants with an increased genetic risk for T1D. The Environmental Determinants of Diabetes in the Young study is a prospective longitudinal birth cohort study. Infants (N = 6404) screened for T1D high risk human leucocyte antigen-DQ genotypes (DR3/4, DR4/4, DR4/8, DR3/3, DR4/4, DR4/1, DR4/13, DR4/9 and DR3/9) were followed for 2 years at six clinical research centres: three in the United States (Colorado, Georgia/Florida, Washington) and three in Europe (Sweden, Finland, Germany). Age at first introduction to any food was reported at clinical visits every third month from the age of 3 months. Maternal sociodemographic data were self-reported through questionnaires. Age at first introduction to CF was primarily associated with country of residence. Root vegetables and fruits were usually the first CF introduced in Finland and Sweden and cereals were usually the first CF introduced in the United States. Between 15% and 20% of the infants were introduced to solid foods before the age of 4 months. Young maternal age (<25 years), low educational level (<12 years) and smoking during pregnancy were significant predictors of early introduction to CF in this cohort. Infants with a relative with T1D were more likely to be introduced to CF later. © 2013 John Wiley & Sons Ltd.

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.

Paraquat induces extrinsic pathway of apoptosis in A549 cells by induction of DR5 and repression of anti-apoptotic proteins, DDX3 and GSK3 expression.

PubMed

Hathaichoti, Sasiphen; Visitnonthachai, Daranee; Ngamsiri, Pronrumpa; Niyomchan, Apichaya; Tsogtbayar, Oyu; Wisessaowapak, Churaibhon; Watcharasit, Piyajit; Satayavivad, Jutamaad

2017-08-01

Paraquat (PQ) is a bipyridyl derivative herbicide known to cause lung toxicity partly through induction of apoptosis. Here we demonstrated that PQ caused apoptosis in A549 cells. PQ increased cleavage of caspase-8 and Bid, indicating caspase-8 activation and truncated Bid, the two key mediators of extrinsic apoptosis. Additionally, PQ treatment caused an increase in DR5 (death receptor-5) and caspase-8 interaction, indicating formation of DISC (death-inducing signaling complex). These results indicate that PQ induces apoptosis through extrinsic pathway in A549 cells. Moreover, PQ drastically increased DR5 expression and membrane localization. Furthermore, PQ caused prominent concentration dependent reductions of DDX3 (the DEAD box protein-3) and GSK3 (glycogen synthase kinase-3) which can associate with DR5 and prevent DISC formation. Additionally, PQ decreased DR5-DDX3 interaction, suggesting a reduction of DDX3/GSK3 anti-apoptotic complex. Inhibition of GSK3, which is known to promote extrinsic apoptosis by its pharmacological inhibitor, BIO accentuated PQ-induced apoptosis. Moreover, GSK3 inhibition caused a further decrease in PQ-reduced DR5-DDX3 interaction. Taken together, these results suggest that PQ may induce extrinsic pathway of apoptosis in A549 cells through upregulation of DR5 and repression of anti-apoptotic proteins, DDX3/GSK3 leading to reduction of anti-apoptotic complex. Copyright © 2017 Elsevier Ltd. All rights reserved.

Detection of Glaucoma and Its Association With Diabetic Retinopathy in a Diabetic Retinopathy Screening Program.

PubMed

Gangwani, Rita A; McGhee, Sarah M; Lai, Jimmy S M; Chan, Christina K W; Wong, David

2016-01-01

To determine the type of glaucoma in subjects with diabetes mellitus detected during a diabetic retinopathy screening program and to determine any association between diabetic retinopathy (DR) and glaucoma. This is a population-based prospective cross-sectional study, in which subjects with diabetes mellitus underwent screening for DR in a primary care outpatient clinic. Digital fundus photographs were taken and graded for presence/absence and severity of DR. During this grading, those fundus photographs showing increased cup-to-disc ratio (CDR) (≥0.6) were identified and these patients were referred to the specialist ophthalmology clinic for detailed examination. The presence of glaucoma was established based on CDR and abnormal visual field (VF) defects according to Hodapp-Parrish-Anderson's criteria. An elevation of intraocular pressure was not required for the diagnosis of glaucoma. The patients said to have definite glaucoma were those with vertical CDR>/=0.6, glaucomatous defects on VF examination, or retinal nerve fiber thinning if VF was unreliable. Of the 2182 subjects who underwent screening, 81 subjects (3.7%) had increased CDR and 40 subjects (1.8%) had confirmed glaucoma. Normal-tension variant of primary open-angle glaucoma was the most prevalent type (1.2%) We did not find any evidence that DR is a risk factor for glaucoma [odds ratio for DR vs. no DR=1.22 (95% confidence interval, 0.59-2.51)]. The overall prevalence of glaucoma in this diabetic population, based on finding increased cupping of optic disc in a teleretinal screening program was 1.8% (95% confidence interval, 1.0-3.0).

The effect size of type 2 diabetes mellitus on tuberculosis drug resistance and adverse treatment outcomes.

PubMed

Perez-Navarro, Lucia Monserrat; Restrepo, Blanca I; Fuentes-Dominguez, Francisco Javier; Duggirala, Ravindranath; Morales-Romero, Jaime; López-Alvarenga, Juan Carlos; Comas, Iñaki; Zenteno-Cuevas, Roberto

2017-03-01

To evaluate the effect size of type 2 diabetes mellitus (T2DM) on tuberculosis (TB) treatment outcomes and multi drug resistance (MDR). A cohort with 507 individuals with diagnosed TB included 183 with coexistence of T2DM and TB (TB-T2DM). Participants were identified at the time of TB diagnosis and followed during the course of TB treatment. Then we computed relative risks and adjustments by Cox proportional hazards for outcome variables (drug resistance, death, relapse, treatment failure), and the size of their effect as Cohen's-d. Patients with TB-T2DM were more likely to remain positive for acid-fast bacilli after two months of anti-TB treatment RR = [2.01 (95% CI: 1.3, 3.1)], to have drug resistant (DR) [OR 3.5 (95% CI: 1.8, 6.7)] and multi-drug resistant (MDR) TB [OR 3.5 (95% CI: 1.8, 7.1)]. The Cohen's-d for DR or MDR in T2DM was 0.69 when compared with non-DM subjects. The T2DM patients had higher odds of resistance to isoniazid (OR 3.9, 95% CI: 2.01, 7.9), rifampicin (OR 3.4, 95% CI: 1.6, 7.2) and pyrazinamide (OR 9.4, 95% CI: 2.8, 25.6), and their effect sizes were ≥0.67. Patients with TB-T2DM (versus no DM) were more likely to present with MDR TB (HR 3.1; 95% CI: 1.7, 5.8; p < 0.001), treatment failure (HR 2.04; 95% CI: 1.07, 3.8; p = 0.02) and relapse (HR 1.86; 95% CI: 1.09, 3.1; p = 0.02), with effect size ≥0.34. T2DM showed a substantial contribution to the presence of DR or MDR-TB and to adverse clinical outcomes during and after TB treatment. Our findings support the importance for routine screening of T2DM among newly-diagnosed TB patients in order to stratify them for immediate DR assessment, and highlight the need for clinical trials to evaluate variations to the standard TB treatment in TB-T2DM to prevent adverse treatment outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

The role of SIRT1 in diabetic retinopathy.

PubMed

Karbasforooshan, Hedyieh; Karimi, Gholamreza

2018-01-01

The prevalence of diabetes mellitus (DM), has been increasing worldwide. Diabetic retinopathy (DR) is the most common microvascular complication in diabetes. It is a multifactorial disease that occurs primarily through the long-term detrimental effects of hyperglycemia. The pathogenesis of DR is complex, including inflammation, oxidative stress and advanced glycation end products (AGES). SIRT1 is a nicotinamide adenosine dinucleotide (NAD+)-dependent deacetylase that removes acetyl groups from proteins which can be implicated in DR. Inhibition of miRNAs such as miR-23b- 3P and miR-34a and activation of adenosine monophosphate-activated protein kinas (AMPK) and Peroxisome proliferative-activated receptor α (PPARα), modulate inflammation by enhancing the level of SIRT1. SIRT1 activation leads to the down regulation of nuclear factor kappa-light-chain-enhancer of activated of B cells (NF-κB), and the downstream pathway including increased level of Interleukin-17 (IL-17) and other pro-inflammatory cytokines. Oxidative stress- induced apoptosis is due to activation of some transcriptional factors such as p53 and Protein arginine methyl transferase 1 (PRMIT1) which are inhibited by SIRT1. In addition to these, the increased level of some transcriptional factors such as, vascular endothelial growth factor (VEGF), hypoxia - induced factors (HIFs), transforming growth factor β1 (TGF-β1), endothelin-1 (ET-1), fork head box O 1 (FOXO1) and Notch signaling may be inhibited by activation of SIRT1 leads to attenuation of vascular dysfunction. In conclusion, SIRT1 regulates apoptosis, inflammation and oxidative stress resulting in improving DR. This review focuses on the role of SIRT1 in DR. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Polarization Processing Techniques Study

DTIC Science & Technology

1979-11-01

Scattere,’" IEEE Trans on AES, Vol 3, pp 171-178, 1967. - m ---: - .Jmm5 a mi •i• . Q AMODEL FOR THE SLVVLA TION OF THE SPECTRA L AND GEORGE A...Mr. Masaaki (Tom) Fujita FEB it so Dr. George Ioannidis Dr. i’han Levan Dr. Jeffery Bell Mr. Charles Lucas AMOED M PBM EAS. ISTRIUTKJN INUMIMiD I c.L...FinalUF STtY’ n " -- - p~ar 7S8 Var 79.L, Mr. t lber ~.i 4MJI George /7fioannz~ff1,;- WS"’’ wx.~~ ~ ~ ~ I.ler ~er30602-7F-C-01.39IF Dr. J~ni Ha-ezE Dr. Jeff

STAT3/NF-κB interactions determine the level of haptoglobin expression in male rats exposed to dietary restriction and/or acute phase stimuli.

PubMed

Uskoković, Aleksandra; Dinić, Svetlana; Mihailović, Mirjana; Grdović, Nevena; Arambašić, Jelena; Vidaković, Melita; Bogojević, Desanka; Ivanović-Matić, Svetlana; Martinović, Vesna; Petrović, Miodrag; Poznanović, Goran; Grigorov, Ilijana

2012-01-01

Haptoglobin is a constitutively expressed protein which is predominantly synthesized in the liver. During the acute-phase (AP) response haptoglobin is upregulated along with other AP proteins. Its upregulation during the AP response is mediated by cis-trans interactions between the hormone-responsive element (HRE) residing in the haptoglobin gene and inducible transcription factors STAT3 and C/EBP β. In male rats that have been subjected to chronic 50% dietary restriction (DR), the basal haptoglobin serum level is decreased. The aim of this study was to characterize the trans-acting factor(s) responsible for the reduction of haptoglobin expression in male rats subjected to 50% DR for 6 weeks. Protein-DNA interactions between C/EBP and STAT families of transcription factors and the HRE region of the haptoglobin gene were examined in livers of male rats subjected to DR, as well as during the AP response that was induced by turpentine administration. In DR rats, we observed associations between the HRE and C/EBPα/β, STAT5b and NF-κB p50, and the absence of interactions between STAT3 and NF-kB p65. Subsequent induction of the AP response in DR rats by turpentine administration elicited a normal, almost 2-fold increase in the serum haptoglobin level that was accompanied by HRE-binding of C/EBPβ, STAT3/5b and NF-kB p65/p50, and the establishment of interaction between STAT3 and NF-κB p65. These results suggest that STAT3 and NF-κB p65 crosstalk plays a central role while C/EBPβ acquires an accessory role in establishing the level of haptoglobin gene expression in male rats exposed to DR and AP stimuli.

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

[An analysis of immunophenotyping of peripheral lymphocytes in adult patients with infectious mononucleosis and chronic active Epstein-Barr virus infection].

PubMed

Xie, J; Wang, H L; Qiu, Z F; Li, T S

2016-06-01

To determine the immunophenotypic features of peripheral lymphocytes in adult patients with Epstein-Barr virus(EBV)-associated infectious mononucleosis(IM) and chronic active EBV infection (CAEBV). Eighteen IM patients, 12 CAEBV patients and 18 healthy donors were included. Lymphocyte subsets including CD3(-)CD19(+) B cells, CD3(-)CD16/56(+) NK cells, CD4(+) and CD8(+) T cells in peripheral blood were measured by flow cytometry. The expression of activation markers (HLA-DR and CD38) on CD8(+) T cells and CD28 expression on T cells were also determined. Kruskal-Wallis H and Mann-Whitney U tests were used to compare variables among groups. IM patients had dramatically increased CD8(+) T cell counts than healthy donors (5.22×10(9)/L vs 0.54×10(9)/L, P<0.001). B cell counts moderately reduced in patients with IM than in healthy donors. No difference was found in absolute CD4(+) T cell and NK cell counts between IM and healthy donors. The levels of HLA-DR and CD38 on CD8(+) T cells significantly increased in IM patients compared with those in healthy controls. The intensity of CD28 on CD8(+) T cells significantly decreased, which was not seen on CD4(+) T cells. The median cell counts of B, NK, CD4(+) T and CD8(+) T subsets in CAEBV patients were 0.02×10(9)/L, 0.06×10(9)/L, 0.26×10(9)/L and 0.21×10(9)/L respectively, which were significantly lower than those in healthy donors (0.22×10(9)/L, 0.38×10(9)/L, 0.78×10(9)/L, 0.54×10(9)/L)and IM patients (0.12×10(9)/L, 0.40×10(9)/L, 0.91×10(9)/L, 5.22×10(9)/L). The positive rates of HLA-DR and CD38 on CD8(+) T cells in CAEBV patients were higher than those in healthy controls, but lower than those in IM patients. The immunophenotypic pattern in adult patients with IM is characterized by a dramatic increase of extensively activated CD8(+) T cells, a moderate reduction of CD19(+) B cells and no significant change of CD4(+) T cells and CD16/56(+) NK cells. CAEBV is featured by an immunosuppression status as demonstrated by significantly decreased B, NK, CD4(+) T and CD8(+) T subsets.

En Face Doppler Optical Coherence Tomography Measurement of Total Retinal Blood Flow in Diabetic Retinopathy and Diabetic Macular Edema

PubMed Central

Lee, ByungKun; Novais, Eduardo A.; Waheed, Nadia K.; Adhi, Mehreen; de Carlo, Talisa E.; Cole, Emily D.; Moult, Eric M.; Choi, WooJhon; Lane, Mark; Baumal, Caroline R.; Duker, Jay S.; Fujimoto, James G.

2018-01-01

IMPORTANCE Alterations in ocular blood flow play an important role in the pathogenesis and progression of diabetic retinopathy (DR). However, the measurement of retinal blood flow in clinical studies has been challenging. En face Doppler optical coherence tomography (OCT) provides an effective method for measuring total retinal blood flow (TRBF) in the clinic. OBJECTIVE To investigate TRBF in eyes with DR of varying severity, with or without diabetic macular edema (DME), using en face Doppler OCT. DESIGN, SETTING, AND PARTICIPANTS This was a cross-sectional study conducted from May 23, 2014, to January 11, 2016, which analyzed 41 eyes with DR from 31 diabetic patients, 20 eyes without DR from 11 diabetic patients, and 16 eyes from 12 healthy age-matched controls, all at the New England Eye Center in Boston, Massachusetts. MAIN OUTCOMES AND MEASURES Participants were imaged with a high-speed, swept-source OCT prototype at 1050-nm wavelength using repeated en face Doppler OCT raster scans, comprising 600 × 80 axial scans and covering a 1.5 × 2-mm2 area centered at the optic disc. The TRBF was automatically calculated using custom Matlab software. RESULTS This study included 41 eyes with DR from 31 diabetic patients (mean [SD] age, 62.8 [13.4] years; 12 were female patients), 20 eyes without DR from 11 diabetic patients (mean [SD] age, 58.8 [10.1] years; 5 were female patients), and 16 eyes from 12 healthy age-matched controls (mean [SD] age, 57.9 [8.1] years; 8 were female participants). The mean (SD) TRBF was 28.0 (8.5) μL/min in the eyes with DME, 48.8 (13.4) μL/min in the eyes with DR but without DME, 40.1 (7.7) μL/min in the diabetic eyes without retinopathy, and 44.4 (8.3) μL/min in age-matched healthy eyes. A difference in TRBF between the eyes with DME that were treated and the eyes with DME that were not treated was not identified. The TRBF was consistently low in the eyes with DME regardless of DR severity. The eyes with moderate nonproliferative DR but without DME exhibited a wide range of TRBF from 31.1 to 75.0 μL/min, with the distribution being highly skewed. CONCLUSIONS AND RELEVANCE High-speed en face Doppler OCT can measure TRBF in healthy and diabetic eyes. Diabetic eyes with DME exhibited lower TRBF than healthy eyes (P ≤ .001). Further longitudinal studies of TRBF in eyes with DR would be helpful to determine whether reduced TRBF is a risk factor for DME. PMID:28196198

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

Phytotoxic flavonoids from roots of Stellera chamaejasme L. (Thymelaeaceae).

PubMed

Yan, Zhiqiang; Guo, Hongru; Yang, Jiayue; Liu, Quan; Jin, Hui; Xu, Rui; Cui, Haiyan; Qin, Bo

2014-10-01

Allelopathy, the negative effect on plants of chemicals released to the surroundings by a neighboring plant, is an important factor which contributes to the spread of some weeds in plant communities. In this field, Stellera chamaejasme L. (Thymelaeaceae) is one of the most toxic and ecologically-threatening weeds in some of the grasslands of north and west China. Bioassay-guided fractionation of root extracts of this plant led to the isolation of eight flavonoids 1-8, whose structures were elucidated by spectroscopic analysis. All compounds obtained, except 7-methoxylneochaejasmin A (4) and (+)-epiafzelechin (5), showed strong phytotoxic activity against Arabidopsis thaliana seedlings. Seedling growth was reduced by neochamaejasmin B (1), mesoneochamaejasmin A (2), chamaejasmenin C (3), genkwanol A (6), daphnodorin B (7) and dihydrodaphnodorin B (8) with IC50 values of 6.9, 12.1, 43.2, 74.8, 7.1 and 27.3μg/mL, respectively, and all of these compounds disrupted root development. Endogenous auxin levels at the root tips of the A. thaliana DR5::GUS transgenic line were largely reduced by compounds 1, 2 and 6-8, and were increased by compound 4. Moreover, the inhibition rate of A. thaliana auxin transport mutants pin2 and aux1-7 by compounds 1-8 were all lower than the wild type (Col-0). The influence of these compounds on endogenous auxin distribution is thus proposed as a critical factor for the phytotoxic effect. Compounds 1, 2, 4 and 8 were found in soils associated with S. chamaejasme, and these flavonoids also showed phytotoxicity to Clinelymus nutans L., an associated weed of S. chamaejasme. These results indicated that some phytotoxic compounds from roots of S. chamaejasme may be involved in the potential allelopathic behavior of this widespread weed. Copyright © 2014 Elsevier Ltd. All rights reserved.

NFκB-Associated Pathways in Progression of Chemoresistance to 5-Fluorouracil in an In Vitro Model of Colonic Carcinoma.

PubMed

Körber, Maria Isabel; Staribacher, Anna; Ratzenböck, Ina; Steger, Günther; Mader, Robert M

2016-04-01

Drug resistance to 5-fluorouracil (5-FU) is a major obstacle in colonic cancer treatment. Activation of nuclear factor-kappa B (NFκB), mitogen-activated protein kinase kinase kinase 8 (MAP3K8) and protein kinase B (AKT) is thought to protect cancer cells against therapy-induced cytotoxicity. Using cytotoxicity assays and immunoblotting, the impact of inhibitory strategies addressing NFκB, AKT and MAP3K8 in chemoresistance was evaluated in a colonic cancer model in vitro. This model consisted of the cell lines SW480 and SW620, and three subclones with increasing degrees of chemoresistance in order to mimic the development of secondary resistance. NFκB protein p65 was selectively activated in all resistant cell lines. Consequently, several inhibitors of NFκB, MAP3K8 and AKT effectively circumvented this chemoresistance. As a cellular reaction, NFκB inhibition may trigger a feedback loop resulting in activation of extracellular signal-regulated kinase. The results suggest that chemoresistance to 5-FU in this colonic carcinoma model (cell lines SW480 and SW620) is strongly dependent on NFκB activation. The efficacy of MAP3K8 inhibition in our model potentially uncovers a new mechanism to circumvent 5-FU resistance. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

miR-133b Regulation of Connective Tissue Growth Factor

PubMed Central

Gjymishka, Altin; Pi, Liya; Oh, Seh-Hoon; Jorgensen, Marda; Liu, Chen; Protopapadakis, Yianni; Patel, Ashnee; Petersen, Bryon E.

2017-01-01

miRNAs are involved in liver regeneration, and their expression is dysregulated in hepatocellular carcinoma (HCC). Connective tissue growth factor (CTGF), a direct target of miR-133b, is crucial in the ductular reaction (DR)/oval cell (OC) response for generating new hepatocyte lineages during liver injury in the context of hepatotoxin-inhibited hepatocyte proliferation. Herein, we investigate whether miR-133b regulation of CTGF influences HCC cell proliferation and migration, and DR/OC response. We analyzed miR-133b expression and found it to be down-regulated in HCC patient samples and induced in the rat DR/OC activation model of 2-acetylaminofluorene with partial hepatectomy. Furthermore, overexpression of miR-133b via adenoviral system in vitro led to decreased CTGF expression and reduced proliferation and Transwell migration of both HepG2 HCC cells and WBF-344 rat OCs. In vivo, overexpression of miR-133b in DR/OC activation models of 2-acetylaminofluorene with partial hepatectomy in rats, and 3,5-diethoxycarbonyl-1,4-dihydrocollidine in mice, led to down-regulation of CTGF expression and OC proliferation. Collectively, these results show that miR-133b regulation of CTGF is a novel mechanism critical for the proliferation and migration of HCC cells and OC response. PMID:26945106

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

VizieR Online Data Catalog: Hubble Source Catalog (V1 and V2) (Whitmore+, 2016)

NASA Astrophysics Data System (ADS)

Whitmore, B. C.; Allam, S. S.; Budavari, T.; Casertano, S.; Downes, R. A.; Donaldson, T.; Fall, S. M.; Lubow, S. H.; Quick, L.; Strolger, L.-G.; Wallace, G.; White, R. L.

2016-10-01

The HSC v1 contains members of the WFPC2, ACS/WFC, WFC3/UVIS and WFC3/IR Source Extractor source lists from HLA version DR8 (data release 8). The crossmatching process involves adjusting the relative astrometry of overlapping images so as to minimize positional offsets between closely aligned sources in different images. After correction, the astrometric residuals of crossmatched sources are significantly reduced, to typically less than 10mas. The relative astrometry is supported by using Pan-STARRS, SDSS, and 2MASS as the astrometric backbone for initial corrections. In addition, the catalog includes source nondetections. The crossmatching algorithms and the properties of the initial (Beta 0.1) catalog are described in Budavari & Lubow (2012ApJ...761..188B). The HSC v2 contains members of the WFPC2, ACS/WFC, WFC3/UVIS and WFC3/IR Source Extractor source lists from HLA version DR9.1 (data release 9.1). The crossmatching process involves adjusting the relative astrometry of overlapping images so as to minimize positional offsets between closely aligned sources in different images. After correction, the astrometric residuals of crossmatched sources are significantly reduced, to typically less than 10mas. The relative astrometry is supported by using Pan-STARRS, SDSS, and 2MASS as the astrometric backbone for initial corrections. In addition, the catalog includes source nondetections. The crossmatching algorithms and the properties of the initial (Beta 0.1) catalog are described in Budavari & Lubow (2012ApJ...761..188B). Hubble Source Catalog Acknowledgement: Based on observations made with the NASA/ESA Hubble Space Telescope, and obtained from the Hubble Legacy Archive, which is a collaboration between the Space Telescope Science Institute (STScI/NASA), the Space Telescope European Coordinating Facility (ST-ECF/ESAC/ESA) and the Canadian Astronomy Data Centre (CADC/NRC/CSA). (2 data files).

Death receptor 3 signaling enhances proliferation of human regulatory T cells.

PubMed

Bittner, Sebastian; Knoll, Gertrud; Ehrenschwender, Martin

2017-04-01

Exploiting regulatory T cells (Tregs) to control aberrant immune reactions is a promising therapeutic approach, but is hampered by their relative paucity. In mice, activation of death receptor 3 (DR3), a member of the TNF-receptor superfamily (TNFRSF), increases Treg frequency and efficiently controls exuberant immune activation. For human Tregs, neither DR3 expression nor potential functions have been described. Here, we show that human Tregs express DR3 and demonstrate DR3-mediated activation of p38, ERK, and NFκB. DR3 stimulation enhances Treg expansion ex vivo while retaining their suppressive capacity. In summary, our results establish a functional role for DR3 signaling in human Tregs and could potentially help to tailor Treg-based therapies. © 2017 Federation of European Biochemical Societies.

Inheritance of the 8.1 ancestral haplotype in recurrent pregnancy loss

PubMed Central

Kolte, Astrid M.; Nielsen, Henriette S.; Steffensen, Rudi; Crespi, Bernard; Christiansen, Ole B.

2015-01-01

Background and objectives: The 8.1 ancestral haplotype (AH) (HLA-A1, C7, B8, C4AQ0, C4B1, DR3, DQ2) is a remarkably long and conserved haplotype in the human major histocompatibility complex. It has been associated with both beneficial and detrimental effects, consistent with antagonistic pleiotropy. It has also been proposed that the survival of long, conserved haplotypes may be due to gestational drive, i.e. selective miscarriage of fetuses who have not inherited the haplotype from a heterozygous mother. Recurrent pregnancy loss (RPL) is defined as three or more consecutive pregnancy losses. The objective was to test the gestational drive theory for the 8.1AH in women with RPL and their live born children. Methodology: We investigated the inheritance of the 8.1AH from 82 heterozygous RPL women to 110 live born children. All participants were genotyped for HLA-A, -B and -DRB1 in DNA from EDTA-treated blood or buccal swaps. Inheritance was compared with a Mendelian inheritance of 50% using a two-sided exact binomial test. Results: We found that 55% of the live born children had inherited the 8.1AH, which was not significantly higher than the expected 50% (P = 0.29). Interestingly, we found a non-significant trend toward a higher inheritance of the 8.1AH in girls, 63%, P = 0.11 as opposed to boys, 50%, P = 1.00. Conclusions and implications: We did not find that the 8.1AH was significantly more often inherited by live born children of 8.1AH heterozygous RPL women. However our data suggest that there may be a sex-specific effect which would be interesting to explore further, both in RPL and in a background population. PMID:26675299

HLAs in children with minimal change disease and other types of nephrotic syndrome in the southern part of Turkey.

PubMed

Karabay-Bayazit, A; Noyan, A; Bayazit, Y; Ozel, A; Anarat, A

2001-01-01

The aim of this study was to investigate the human leukocyte antigen (HLA) profile of children with nephrotic syndrome in the southern part of Turkey. Seventy-eight children with nephrotic syndrome were studied for the frequency of class I and class II human leukocyte antigens. Forty-seven of them were steroid sensitive nephrotic syndrome (minimal change disease-MCD) and 31 were other types of nephrotic syndrome. The results were compared with 133 healthy subjects for HLA groups. HLA B13, Cw5, Cw7, DR4, DR7, DRw10, Drw15(2) and DQ2 in the MCD group and HLA A31, B8, B13, B17, Cw2, Cw6, Cw7, DRw10 and DRw12 in the non-MCD group were found significantly increased when compared to healthy controls. MCD patients with frequent relapses had higher frequencies of both Cw6 and DR1 (p < 0.005) and MCD patients with infrequent relapses had a higher frequency of Cw7 (p < 0.05). In conclusion, HLA groups may help in the early diagnosis of these variants.

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.

Dissociative recombination and mutual neutralization of heavier molecular ions: C{sub 10}H{sub 8}{sup +}, WF{sub 5}{sup +}, and C{sub n}F{sub m}{sup +}

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

Wiens, Justin P.; Shuman, Nicholas S.; Viggiano, Albert A., E-mail: afrl.rvborgmailbox@kirtland.af.mil

Dissociative recombination (DR) rate coefficients for the naphthalene cation, C{sub 10}H{sub 8}{sup +}, and WF{sub 5}{sup +}, and mutual neutralization (MN) rate coefficients for these species and five C{sub n}F{sub m}{sup +} ions, were determined at 300 K using variable electron and neutral density attachment mass spectrometry (VENDAMS). DR proceeds at 9 ± 3 × 10{sup −7} cm{sup 3} s{sup −1} for C{sub 10}H{sub 8}{sup +} and at 6.1 ± 1.4 × 10{sup −7} cm{sup 3} s{sup −1} for WF{sub 5}{sup +}. Consistent with previous results, MN for the polyatomic cations with the halide anions Cl{sup −}, Br{sup −}, andmore » I{sup −} exhibits an approximate μ{sup −1/2} reduced mass dependence of the reactant partners, demonstrating that ion collision velocities influence the rate coefficients. This work is an extension of VENDAMS to systems, where low reactant concentrations are necessary to avoid significant reaction of product ions with the neutral precursor, i.e., conditions not suitable for traditional flowing afterglow measurements, as well as to ions of masses > ∼ 100 Da, which are not amenable to the study of DR in magnetic storage rings. Our results expand the sparse literature on DR and MN of heavier ions.« less

Effect of human leukocyte antigen-C and -DQ matching on pediatric heart transplant graft survival.

PubMed

Butts, Ryan J; Savage, Andrew J; Nietert, Paul J; Kavarana, Minoo; Moussa, Omar; Burnette, Ali L; Atz, Andrew M

2014-12-01

A higher degree of human leukocyte antigen (HLA) matching at the A, B, and DR loci has been associated with improved long-term survival after pediatric heart transplantation in multiple International Society for Heart and Lung Transplantation registry reports. The aim of this study was to investigate the association of HLA matching at the C and DQ loci with pediatric graft survival. The United Network of Organ Sharing database was queried for isolated heart transplants that occurred from 1988 to 2012 with a recipient age of 17 or younger and at least 1 postoperative follow-up encounter. When HLA matching at the C or DQ loci were analyzed, only transplants with complete typing of donor and recipient at the respective loci were included. Transplants were divided into patients with at least 1 match at the C locus (C-match) vs no match (C-no), and at least 1 match at the DQ (DQ-match) locus vs no match (DQ-no). Primary outcome was graft loss. Univariate analysis was performed with the log-rank test. Cox regression analysis was performed with the following patient factors included in the model: recipient age, ischemic time; recipient on ventilator, extracorporeal membrane oxygenation, ventricular assist device, or inotropes at transplant; recipient serum bilirubin and creatinine closest to transplant, ratio of donor weight to recipient weight, underlying cardiac diagnosis, crossmatch results, transplant year, and HLA matching at the A, B, and DR loci. Complete typing at the C locus occurred in 2,429 of 4,731 transplants (51%), and complete typing at the DQ locus occurred in 3,498 of 4,731 transplants (74%). Patient factors were similar in C-match and C-no, except for year of transplant (median year, 2007 [interquartile range, 1997-2010] vs year 2005 [interquartile range, 1996-2009], respectively; p = 0.03) and the degree of HLA matching at the A, B, and DR loci (high level of HLA matching in 11.9% vs 3%, respectively; p < 0.01). Matching at the C locus was not associated with a decreased risk of graft loss (median graft survival: 13.1 years [95% confidence interval {CI}, 11.5-14.8] in C-no vs 15.1 years [95% CI, 13.5-16.6) in C-match, p = 0.44 log-rank; hazard ratio, 0.93; 95% CI, 0.76-1.15; p = 0.52). DQ-match did not differ from DQ-no in any of the analyzed patient factors, except DQ-match was more likely to have high degree of matching at the A, B, and DR loci vs DQ-no (9.8% vs 3.2%, p < 0.01). Matching at the DQ locus was not associated with decreased risk of graft loss (median graft survival: DQ-no, 13.1 years [95% CI, 11.7-14.6) vs DQ-match, 13.0 years [95% CI, 11.4-14.6], p = 0.80, log-rank; hazard ratio, 0.95; 95% CI, 0.81-1.1; p = 0.51. Complete typing at the C locus of both donor and recipient occurs less often then typing at the DQ locus. A higher degree of donor-recipient HLA matching at the C locus or the DQ locus appears not to confer any graft survival advantage. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Establishment of a Rotor Model Basis.

DTIC Science & Technology

1982-06-01

2 FC = J r2 dr = (r r3) W) rA Defining b, = 1 (r2 - N =(A3) b2= r the segment extremities are given by equations (87) as rn(+) = ( nbl + b2 )I1/2 (A...rn(_)] - FC n= 1 N 2 ((2n - 1)b I + 2b2 ][vnb + b2 - .(n - l)bj + b2 -F Cn= 1 S11N-i [(2N - l)bj + 2b2]rT - (b, + 2 b2)rA - b I / nbl + b- FC n=1...EEM = 4 [rn(+) + rn(-)]2[rn(+) - rn(-)] - FC n= 1 N 2 2 4 [rn(+) - rn(_)J[rn(+) + rn(_ )] - FC n= 1 = b (/I + b 2 + bI2+2 E nbl + b2 - FC 4 bj + b 2

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.

Equal Educational Opportunity: Hearings Before the Select Committee on Equal Educational Opportunity of the United States Senate, Nine-Second Congress, First Session on Equal Educational Opportunity. Part 19B--Equal Educational Opportunity in Michigan. Hearings Held Washington, D.C., September 29, October 1, and November 3-4, 1971.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. Senate Select Committee on Equal Educational Opportunity.

In these hearings, the following witnesses presented testimony: Dr. Edward B. Fort, superintendent, Inkster Public Schools; Dr. Norman Drachler, former school superintendent, Detroit; Raymond Sreboth, superintendent, Benton Harbor Area Schools; Richard Ziehmer, superintendent, Covert Public Schools; Edward C. McKinney, superintendent, Baldwin…

Construction of Escherichia coli strains producing L-serine from glucose.

PubMed

Li, Yu; Chen, Gu-Kui; Tong, Xin-Wei; Zhang, Hui-Tu; Liu, Xiao-Guang; Liu, Yi-Han; Lu, Fu-Ping

2012-08-01

L-Serine is usually produced from glycine. We have genetically engineered Escherichia coli to produce L-serine from glucose intracellularly. D-3-Phosphoglycerate dehydrogenase (PGDH, EC 1.1.1.95) in E. coli catalyzes the first committed step in L-serine formation but is inhibited by L-serine. To overcome this feedback inhibition, both the His(344) and Asn(346) residues of PGDH were converted to alanine and the mutated PGDH (PGDH(dr)) became insensitive to L-serine. However, overexpression of PGDH(dr) gave no significant increase of L-serine accumulation but, when L-serine deaminase genes (sdaA, sdaB and tdcG) were deleted, serine accumulated: (1) deletion of sdaA gave up to 0.03 mmol L-serine/g; (2) deletion of both sdaA and sdaB accumulated L-serine up to 0.09 mmol/g; and (3) deletion of sdaA, sdaB and tdcG gave up to 0.13 mmol L-serine/g cell dry wt.

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.

Sesquiterpenes with TRAIL-resistance overcoming activity from Xanthium strumarium.

PubMed

Karmakar, Utpal K; Ishikawa, Naoki; Toume, Kazufumi; Arai, Midori A; Sadhu, Samir K; Ahmed, Firoj; Ishibashi, Masami

2015-08-01

The ability of TRAIL to selectively induce apoptosis in cancer cells while sparing normal cells makes it an attractive target for the development of new cancer therapy. In search of bioactive natural products for overcoming TRAIL-resistance from natural resources, we previously reported a number of active compounds. In our screening program on natural resources targeting overcoming TRAIL-resistance, activity-guided fractionations of the extract of Xanthium strumarium led to the isolation of five sesquiterpene compounds (1-5). 11α,13-dihydroxanthinin (2) and 11α,13-dihydroxanthuminol (3) were first isolated from natural resources and xanthinosin (1), desacetylxanthanol (4), and lasidiol p-methoxybenzoate (5) were known compounds. All compounds (1-5) showed potent TRAIL-resistance overcoming activity at 8, 20, 20, 16, and 16 μM, respectively, in TRAIL-resistant AGS cells. Compounds 1 and 5 enhanced the levels of apoptosis inducing proteins DR4, DR5, p53, CHOP, Bax, cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9 and also decreased the levels of cell survival protein Bcl-2 in TRAIL-resistant AGS cells in a dose-dependent manner. Compound 1 also enhanced the levels of DR4 and DR5 proteins in a time-dependent manner. Thus, compounds 1 and 5 were found to induce both extrinsic and intrinsic apoptotic cell death. Compound 1 also exhibit TRAIL-resistance overcoming activity in DLD1, DU145, HeLa, and MCF7 cells but did not decrease viability in non-cancer HEK293 cells up to 8 μM. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Development of Fracture Mechanics Maps for Composite Materials. Volume 2.

DTIC Science & Technology

1985-12-01

AD-A169 663 DEP 1/3UR OIOST l uNCL~ss~~n HUCI S I B M 11 1*2 AF,:P,.-TR-?5,-4150 DEVELOPMENT OF FRACTURE MECHANICS MAPS FOR COMPOSITE MATERIALS Dr. H...coIo. Development of N/A N/A N/A N/A Fracture Mechanics Maps for Composite Materials 12. PERSONAL AUTHORISI Editor (Dr. H. W. Bergmann) 13. TYPE OF...GROUP SUB GR. Fiber Reinforced Composites , Dynamic Test, Thermal Cycling, 1I1 04 Quality Control, Static Test, Stress Concentrations 01 03 19

Increasing Prevalence of Pediatric Drug-Resistant Tuberculosis in Mumbai, India and its Outcome.

PubMed

Shah, Miti A; Shah, Ira

2018-03-24

B.J.Wadia Hospital,Mumbai OBJECTIVE:: The prevalence and type of DR-TB was evaluated pre and post-2013 and outcome was studied. Descriptive retrospective study. Children were defined as having DR-TB on the basis of GeneXpert or LPA and/or drug susceptibility testing(DST) of MTB grown on culture or from contact's DST. The prevalence of DR-TB was 110 out of 1145 cases (9.6%) which showed an increase, compared to 5.6% pre-2010 and 7% in 2010-2013(p=0.014408). Twenty-two (20%) children had pulmonary-TB(PTB) and 88(80%) had extra-pulmonary-TB(EPTB) with disseminated-TB being the most common presentation in 31 children (28.18%). Ninety-six (87.3%) children were bacteriologically confirmed TB cases and 14 (12.7%) were clinically diagnosed-TB and treated as per contact DST. Eight (7.2%) cases were monoresistant, 7 (6.3%) polyresistant, MDR-TB seen in 28 (25.45%) patients, 32 (29.09%) had pre-XDR-TB, 9 (8.18%) had XDR-TB and 12 (10.9%) were rifampicin resistant. Ethionamide resistance increased from 26.1% pre-2013 to 60.8% post-2013(p=0.014408) and ofloxacin resistance rose from 30.4% pre-2010, to 47.6% in 2010-2013 and 56.9% post-2013(p=0.080863). Moxifloxacin resistance showed an acute rise from 8.7% pre-2010, to 46% in 2010-2013 and 57% post-2013(p=0.000275). Thirty-three (30%) patients had completed their treatment, 21(19.09%) were lost to follow up and 56(50.09%) patients are still on treatment.

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.

United States Air Force Summer Research Program 1991. Summer Faculty Research Program (SFRP) Reports. Volume 4. Rome Laboratory, Arnold Engineering Development Center, F. J. Seiler Research Laboratory

DTIC Science & Technology

1992-01-09

Herschfelder, J. 0., C . F. Curtis, and R. B. Bird, "Molecular Theory of Gases and Liquids", John Willey and Sons, New York, (1954), Chs. 7 and 8. 12...AL iryLt’ AND SLOTME 5- FUIING NUERS 1991 Sumn~er FAculty Resezrzi! ?ro-rz~ (SFBZF) Volne 2SbV0d. 4 F496202-4:4#- C -CO076 MtrGary_ Soore ___________ 7...Engineering Tools for Parallel Software Development Dr. John Antonio 2 (Report Not Available at this Time) Dr. Abdul Aziz Bhatti 3 A Taxonomy for

Genetic analysis on HLA loci in Japanese patients with abdominal aortic aneurysm.

PubMed

Sugimoto, T; Sada, M; Miyamoto, T; Yao, H

2003-08-01

autoimmunity has been proposed as one of the pathogenesis of abdominal aortic aneurysm (AAA). There is also a likelihood that when aorto-iliac occlusive disease (AIOD) coexists with AAA, some other occlusive atherosclerotic diseases, such as ischemic heart disease and cerebrovascular disease, may develop, leading to a very poor long-term prognosis. Previous studies using serological HLA typing showed that HLA-DR15 was a risk factor for AAA. In this study, we performed HLA-DNA typing by PCR to clarify the relationship between AAA and HLA genotypes in Japanese patients with AAA. In addition, we analyzed whether HLA genotypes are involved in the pathogenesis of AIOD. we examined 78 HLA genotypes of class I (HLA-A and -B) and class II (HLA-DR) and found that 60.4 and 30.4% of 49 AAA patients had HLA-A2 and HLA-B61, respectively. These frequencies were significantly higher than those in control individuals (HLA-A2, p < 0.05; HLA-B61, p < 0.005). We also found that 55.6% of nine AAA patients with AIOD had both HLA-B52 and HLA-DR B1*1502. In contrast, only 10.0% each of 40 AAA patients without AIOD showed HLA-B53 or HLA-DR B1*1502. this study showed that HLA A-2 and HLA B-61, but not HLA DR-15, were important genetic risk factors for the development of AAA among the Japanese population. We also found high frequencies of HLA-B52 and HLA-DR B1*1502 in the AAA patients with AIOD than in those without, although this must be confirmed using a larger number of AAA patients with AIOD.

An Archeological Survey, Initial Site Testing and Geomorphic Study of Ditches 7, 13 and Lower Buffalo Creek in Craighead, Mississippi and Poinsett Counties, Arkansas.

DTIC Science & Technology

1988-04-01

of the Rebellion. Government Printing Office, Washington, D.C. United States Department of the Interior 1974 hLa Lak Wilderness Study Summary. Fish...2 9 2 X 13 50 B25 3 12 X 15 51 B26 3 18 5 26 52 B27 3 27 1 X 31 53 B28 5 16 9 X 30 54 B29 6 20 7 4 X 37 55 B30 9 12 X 21 56 B31 7 21 12 1 X 41 FSN LOC...20 A18 1 I 25 A23 1 1 26 A24 1 1 FSN LOC 0 DR UP H C PFLK SFLK IFLK FCR BT UNNOD TOTAL 30 84 1 1 49 B24 1 1 50 B25 2 2 51 B26 1 1 52 B27 1 1 57 B33 1

The mechanism of Jurkat cells apoptosis induced by Aggregatibacter actinomycetemcomitans cytolethal distending toxin.

PubMed

Chen, Hui-Ping; Li, Lu; Chen, Xu; Yang, Mi-Fang; Ye, Yu; Wang, Xiao-Qian; Xu, Yan

2017-06-01

Cytolethal distending toxin (CDT) which is produced by Aggregatibacter actinomycetemcomitans causes apoptosis in lymphocytes. But the specific mechanism is not clear. The aim of our research was to investigate the effect and mechanism during this process. The wild-type CdtA, CdtB, CdtC (CdtA W , CdtB W , CdtC W ) and mutant CdtB (CdtB M ) were expressed and purified respectively and the purity of each subunit was examined by BandScan software. And the type I deoxyribonuclease and PI-3,4,5-triphosphate (PI-3,4,5-P3, PIP3) phosphatase activity were detected by DNA agarose gel electrophoresis and enzyme-linked immunosorbent assay respectively. The cell apoptosis rates were analyzed by flow cytometry. The morphological changes of apoptosis cells were observed by confocal laser scanning microscopy. The protein expression of Bax and Bcl-2 was examined by western blot. Differentially expressed apoptosis-related proteins were identified based on isobaric tags for relative and absolute quantitation technology. In the present study we found that: (i) recombinant wild-type CdtA, CdtB and CdtC (CdtA W , CdtB W , CdtC W ) and mutant CdtB (CdtB M ) were correctly expressed and the purity of each protein was higher than 80%, (ii) the average apoptosis rate in wild-type CDT (CDT W ) treated groups was 50.54%, which was significantly higher than the controls (4.71%) and mutant CDT (CDT M ) treated groups (5.58%) (p < 0.05), (iii) morphological changes of apoptosis were observed in CDT W treated cells, (iv) the expression of Bax protein was significantly increased in CDT W treated cells, while Bcl-2 protein expression was significantly decreased, (v) 17 apoptosis-related proteins were expressed differentially, among which 10 proteins (SMNDC1, TNFRSF10B, UBE2I, ITM2A, CASP3, P53, EIF1, TCF3, HMGN5, CASP8) were up-regulated and 7 proteins (RRM2, TPX2, KIF11, NUCKS1, TOP2A, XRCC1, PTPLAD1, RRM2) were down-regulated, (vi) one possible apoptotic pathway [Ubc9 (UBE2I)/P53/DR5 (TNFRSF10B)/Caspase-8 (CASP8)/ Caspase-3 (CASP3)] was selected and partially proved.

Optical Coherence Tomographic Angiography in Type 2 Diabetes and Diabetic Retinopathy.

PubMed

Ting, Daniel Shu Wei; Tan, Gavin Siew Wei; Agrawal, Rupesh; Yanagi, Yasuo; Sie, Nicole Ming; Wong, Chee Wai; San Yeo, Ian Yew; Lee, Shu Yen; Cheung, Chui Ming Gemmy; Wong, Tien Yin

2017-04-01

Optical coherence tomographic angiography (OCT-A) is able to visualize retinal microvasculature without the need for injection of fluorescein contrast dye. Nevertheless, it is only able to capture a limited view of macula and does not show leakage. To evaluate the retinal microvasculature using OCT-A in patients with type 2 diabetes as well as the association of OCT-A characteristics with diabetic retinopathy (DR) and systemic risk factors. A prospective, observational study was conducted from January 1 to June 30, 2016, at medical retina clinics at the Singapore National Eye Center among 50 patients with type 2 diabetes with and without DR (n = 100 eyes). We examined the retinal microvasculature with swept-source OCT-A and a semiautomated software to measure the capillary density index (CDI) and fractal dimension (FD) at the superficial vascular plexus (SVP) and deep retinal vascular plexus (DVP). We collected data on histories of patients' glycated hemoglobin A1c, hypertension, hyperlipidemia, smoking, and renal impairment. The CDI and FD at the SVP and DVP for each severity level of DR and the association of systemic risk factors vs the CDI and FD. The mean (SD) glycated hemoglobin A1c of the 50 patients (26 men and 24 women; 35 Chinese; mean [SD] age, 59.5 [8.9] years) was 7.9% (1.7%). The mean (SD) CDI at the SVP decreased from 0.358 (0.017) in patients with no DR to 0.338 (0.012) in patients with proliferative DR (P < .001) and at the DVP decreased in patients with no DR from 0.361 (0.019) to 0.345 (0.020) in patients with proliferative DR (P = .04). The mean (SD) FD at the SVP increased from 1.53 (0.05) in patients with no DR to 1.60 (0.05) in patients with proliferative DR (P < .01) and at the DVP increased from 1.55 (0.06) in patients with no DR to 1.61 (0.05) in patients with proliferative DR (P = .02). For systemic risk factors, hyperlipidemia (odds ratio [OR], 9.82; 95% CI, 6.92-11.23; P < .001), smoking (OR, 10.90; 95% CI, 8.23-12.34; P < .001), and renal impairment (OR, 3.72; 95% CI, 1.80-4.81; P = .05) were associated with reduced CDI, while increased glycated hemoglobin A1c (≥8%) (OR, 8.77; 95% CI, 5.23-10.81; P < .01) and renal impairment (OR, 10.30; 95% CI, 8.21-11.91; P < .001) were associated with increased FD. Optical coherence tomographic angiography is a novel imaging modality to quantify the retinal capillary microvasculature in patients with diabetes. It can be potentially used in interventional trials to study the effect of systemic risk factors on the microvasculature that was previously not accessible in a noninvasive manner. The relevance of these findings relative to visual acuity, however, remains largely unknown at this time.

Paeoniflorin Suppressed High Glucose-Induced Retinal Microglia MMP-9 Expression and Inflammatory Response via Inhibition of TLR4/NF-κB Pathway Through Upregulation of SOCS3 in Diabetic Retinopathy.

PubMed

Zhu, Su-Hua; Liu, Bing-Qian; Hao, Mao-Juan; Fan, Yi-Xin; Qian, Cheng; Teng, Peng; Zhou, Xiao-Wei; Hu, Liang; Liu, Wen-Tao; Yuan, Zhi-Lan; Li, Qing-Ping

2017-10-01

Diabetic retinopathy (DR) is a serious-threatening complication of diabetes and urgently needed to be treated. Evidence has accumulated indicating that microglia inflammation within the retina plays a critical role in DR. Microglial matrix metalloproteinase 9 (MMP-9) has an important role in the destruction of the integrity of the blood-retinal barrier (BRB) associated with the development of DR. MMP-9 was also considered important for regulating inflammatory responses. Paeoniflorin, a monoterpene glucoside, has a potent immunomodulatory effect on microglia. We hypothesized that paeoniflorin could significantly suppress microglial MMP-9 activation induced by high glucose and further relieve DR. BV2 cells were used to investigate the effects and mechanism of paeoniflorin. The activation of MMP-9 was measured by gelatin zymography. Cell signaling was measured by western blot assay and immunofluorescence assay. High glucose increased the activation of MMP-9 in BV2 cells, which was abolished by HMGB1, TLR4, p38 MAPK, and NF-κB inhibition. Phosphorylation of p38 MAPK induced by high glucose was decreased by TLR4 inhibition in BV2 cells. Paeoniflorin induced suppressor of cytokine signaling 3 (SOCS3) expression and reduced MMP-9 activation in BV2 cells. The effect of paeoniflorin on SOCS3 was abolished by the TLR4 inhibitor. In streptozotocin (STZ)-induced diabetes mice, paeoniflorin induced SOCS3 expression and reduced MMP-9 activation. Paeoniflorin suppressed STZ-induced IBA-1 and IL-1β expression and decreased STZ-induced high blood glucose level. In conclusion, paeoniflorin suppressed high glucose-induced retinal microglia MMP-9 expression and inflammatory response via inhibition of the TLR4/NF-κB pathway through upregulation of SOCS3 in diabetic retinopathy.

Assessing the risk of CMV reactivation and reconstitution of antiviral immune response post bone marrow transplantation by the QuantiFERON-CMV-assay and real time PCR.

PubMed

Krawczyk, Adalbert; Ackermann, Jessica; Goitowski, Birgit; Trenschel, Rudolf; Ditschkowski, Markus; Timm, Jörg; Ottinger, Hellmut; Beelen, Dietrich W; Grüner, Nico; Fiedler, Melanie

CMV reactivation is a major cause of severe complications in allogeneic hematopoietic stem cell transplant (HSCT) recipients. The risk of CMV reactivation depends on the serostatus (+/-) of the donor (D) and recipient (R). The reconstitution of CMV-specific T-cell responses after transplantation is crucial for the control of CMV reactivation. The study aimed to determine the cellular immune status correlating with protection from high-level CMV viremia (>5000 copies/ml) and disease. We monitored CMV-specific cellular immune responses in 9 high-risk (D-/R+), 14 intermediate risk (D+/R+) and 3 low risk individuals (D+/R-), and 8 CMV negative controls (D-/R-). Interferon- γ (IFN-γ) levels as a marker for the CD8+ T-cell response were determined by the QuantiFERON-CMV-assay and compared to viral loads determined by PCR. Early CMV reactivation was detected in all high-risk and 13/14 intermediate risk individuals. High-level viremia was detected in 5/7 high and 7/14 intermediate risk patients. Reconstitution of the CMV-specific cellular immune response started from 3 months after transplantation and resulted in protection against CMV reactivation. Re-establishing of CMV-specific T-cell immune responses with IFN- γ levels >8.9 IU/ml is crucial for protection from high-level CMV viremia. Monitoring of HSCT-recipients with the QuantiFERON-CMV-assay might be of great benefit to optimize antiviral treatment. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Special Warfare: Restructuring for the Future

DTIC Science & Technology

2016-06-01

Government Printing Office, 2014), 7. https://armypubs.us.army.mil/doctrine/DR_pubs/dr_c/ pdf /fm3_05. pdf . 2 Joint Chiefs of Staff, Doctrine for the Armed...Forces of the United States (JP 1), (Washington, DC: Government Printing Office, 2013), GL-8. http://www.dtic.mil/doctrine/new_pubs/jp1. pdf . 3...and the Persian Gulf War. Santa Monica, California: RAND, 2001, 9. 126 Department of the Army, Vietnam Studies, 136. 127 Rosenau, Special Operations

A Solvable Self-Similar Model of the Sausage Instability in a Resistive Z-Pinch

DTIC Science & Technology

1989-09-20

Ithaca, NY 14853 Dr. V. Nardi Dr. John C. Riordan Stevens Institute of Technology Physics International Co. Hoboken, NJ 07803 2700 Merced Street Dr...92122 Dr. Rick B. Spielman Dr. Frank C. Young Sandia National Laboratories Naval Research Laboratory P.O. Box 5800 Code 4770.1 Albuquerque, NM 87115

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.

Cellular FLICE-inhibitory Protein (cFLIP) Isoforms Block CD95- and TRAIL Death Receptor-induced Gene Induction Irrespective of Processing of Caspase-8 or cFLIP in the Death-inducing Signaling Complex*

PubMed Central

Kavuri, Shyam M.; Geserick, Peter; Berg, Daniela; Dimitrova, Diana Panayotova; Feoktistova, Maria; Siegmund, Daniela; Gollnick, Harald; Neumann, Manfred; Wajant, Harald; Leverkus, Martin

2011-01-01

Death receptors (DRs) induce apoptosis but also stimulate proinflammatory “non-apoptotic” signaling (e.g. NF-κB and mitogen-activated protein kinase (MAPK) activation) and inhibit distinct steps of DR-activated maturation of procaspase-8. To examine whether isoforms of cellular FLIP (cFLIP) or its cleavage products differentially regulate DR signaling, we established HaCaT cells expressing cFLIPS, cFLIPL, or mutants of cFLIPL (cFLIPD376N and cFLIPp43). cFLIP variants blocked TRAIL- and CD95L-induced apoptosis, but the cleavage pattern of caspase-8 in the death inducing signaling complex was different: cFLIPL induced processing of caspase-8 to the p43/41 fragments irrespective of cFLIP cleavage. cFLIPS or cFLIPp43 blocked procaspase-8 cleavage. Analyzing non-apoptotic signaling pathways, we found that TRAIL and CD95L activate JNK and p38 within 15 min. cFLIP variants and different caspase inhibitors blocked late death ligand-induced JNK or p38 MAPK activation suggesting that these responses are secondary to cell death. cFLIP isoforms/mutants also blocked death ligand-mediated gene induction of CXCL-8 (IL-8). Knockdown of caspase-8 fully suppressed apoptotic and non-apoptotic signaling. Knockdown of cFLIP isoforms in primary human keratinocytes enhanced CD95L- and TRAIL-induced NF-κB activation, and JNK and p38 activation, underscoring the regulatory role of cFLIP for these DR-mediated signals. Whereas the presence of caspase-8 is critical for apoptotic and non-apoptotic signaling, cFLIP isoforms are potent inhibitors of TRAIL- and CD95L-induced apoptosis, NF-κB activation, and the late JNK and p38 MAPK activation. cFLIP-mediated inhibition of CD95 and TRAIL DR could be of crucial importance during keratinocyte skin carcinogenesis and for the activation of innate and/or adaptive immune responses triggered by DR activation in the skin. PMID:21454681

NLRP1 deficiency attenuates diabetic retinopathy (DR) in mice through suppressing inflammation response.

PubMed

Li, Yan; Liu, Chang; Wan, Xin-Shun; Li, Shao-Wei

2018-06-22

Diabetic retinopathy (DR) is the common cause of diabetic vascular complications. The NOD-like receptor (NLR) family, pyrin domain containing 1 (NLRP1), also known as NALP1, inflammasome is the first member of the NLR family to be discovered, playing an important role in inflammatory response. However, its effect on DR development has not been reported. In the study, the wild type (WT) and NLRP1 -/- mice were injected with streptozotocin (STZ) to induce DR. The results indicated that NLRP1 -/- significantly increased bodyweight reduction and decreased blood glucose levels induced by STZ. WT/DR mice exhibited higher levels of NLRP1 in retinas. NLRP1 -/- ameliorated retinal abnormalities in DR mice using H&E staining. In addition, attenuated avascular areas and neovascular tufts were also observed in NLRP1 -/- /DR mice. The levels of pro-inflammatory cytokines in serum and retinas were highly induced in WT/DR mice, whereas being markedly reduced by NLRP1 -/- . In addition, vascular endothelial growth factor (VEGF) and Iba1 expressions induced by STZ in serum or retinas were significantly down-regulated in NLRP1 -/- /DR mice. Consistently, NLRP1 -/- attenuated ASC and Caspase-1 expressions in retinas of DR mice. Compared to WT/DR group, NLRP1 -/- markedly decreased retina p-nuclear factor-κB (NF-κB), interleukin-1β (IL-1β) and IL-18 levels. And similar results were confirmed in vitro that suppressing NLRP1/ASC inflammasome ameliorated inflammatory response in fructose-treated retinal ganglion cells. The results above indicated that the modulation of NLRP1 inflammasome might be a promising strategy for DR therapy. Copyright © 2018. Published by Elsevier Inc.

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.

Differential effects of human interferon alpha and interferon gamma on xenografted human thyroid tissue in severe combined immunodeficient mice and nude mice.

PubMed

Kawai, K; Enomoto, T; Fornasier, V; Resetkova, E; Volpé, R

1997-03-01

We have studied the in vivo effects of human interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma) administration on human thyroid tissue xenografted into two mouse strains: severe combined immunodeficient (SCID) mice and nude mice. Human lymphocytes survive in SCID mice but are lysed in nude mice. Thyroid tissues from Graves' disease or Hashimoto's thyroiditis, or paranodular [normal, (N)] tissue was xenografted into SCID mice (0.8 g/mouse) pretreated with anti-asialo GM-1 antiserum and radiation and also into nude mice. One week after xenografting, SCID and nude mice were divided into three groups. Group A was treated with IFN-alpha intraperitoneally (2,000 units/mouse) three times weekly; group B was treated with IFN-gamma similarly; group C was treated with phosphate buffered saline (PBS) only (control). Autologous human peripheral blood mononuclear cells (PBMCs) were added to mice receiving N xenografts. Blood was taken every 2 weeks for levels of IgG and thyroid antibodies (TAb). After 6 weeks of treatment, mice were sacrificed, and xenograft thyrocyte histocompatibility leukocyte antigen (HLA-DR) and intercellular adhesion molecule (ICAM-1) expression were measured. In addition, thyrocyte cultures were stimulated in vitro with 200 units/ml of either IFN-alpha or IFN-gamma or PBS (control). SCID mice xenografted with autoimmune thyroid disease (AITD) in group A showed a significantly higher TAb production than group C, whereas in group B, TAb production was not statistically increased compared to control (group C). SCID mice xenografted with N did not produce TAb in any group, nor did nude mice xenografted with AITD. Thyrocyte HLA-DR expression was markedly increased in group A and B in SCID mice xenografted with Graves' disease, Hashimoto's thyroiditis, and N tissue compared to group C. In contrast, only group B (IFN-gamma) showed an increase in thyrocyte HLA-DR in nude mice. In the in vitro studies, only IFN-gamma (not IFN-alpha) stimulated thyrocyte HLA-DR and ICAM-1 expression in Graves' disease, Hashimoto's thyroiditis, and N tissues. We concluded that in SCID mice, IFN-alpha causes TAB production in AITD xenografts but not in N xenografts, while increasing thyrocyte HLA-DR expression in both. Also, IFN-gamma does not cause a statistically increased TAb in AITD xenografts in SCID mice, despite a sharp rise in thyrocyte HLA-DR expression. In addition, because IFN-alpha has no effect in nude mice or in vitro on thyrocyte HLA-DR expression, its effects in SCID mice must be mediated via local infiltrating lymphocytes. Finally, IFN-gamma has a direct effect on thyrocytes to increase HLA-DR expression (and, in vitro, ICAM-1 expression) but may not stimulate TAb production.

Use of eluted peptide sequence data to identify the binding characteristics of peptides to the insulin-dependent diabetes susceptibility allele HLA-DQ8 (DQ 3.2).

PubMed

Godkin, A; Friede, T; Davenport, M; Stevanovic, S; Willis, A; Jewell, D; Hill, A; Rammensee, H G

1997-06-01

HLA-DQ8 (A1*0301, B1*0302) and -DQ2 (A1*0501, B1*0201) are both associated with diseases such as insulin-dependent diabetes mellitus and coeliac disease. We used the technique of pool sequencing to look at the requirements of peptides binding to HLA-DQ8, and combined these data with naturally sequenced ligands and in vitro binding assays to describe a novel motif for HLA-DQ8. The motif, which has the same basic format as many HLA-DR molecules, consists of four or five anchor regions, in the positions from the N-terminus of the binding core of n, n + 3, n + 5/6 and n + 8, i.e. P1, P4, P6/7 and P9. P1 and P9 require negative or polar residues, with mainly aliphatic residues at P4 and P6/7. The features of the HLA-DQ8 motif were then compared to a pool sequence of peptides eluted from HLA-DQ2. A consensus motif for the binding of a common peptide which may be involved in disease pathogenesis is described. Neither of the disease-associated alleles HLA-DQ2 and -DQ8 have Asp at position 57 of the beta-chain. This Asp, if present, may form a salt bridge with an Arg at position 79 of the alpha-chain and so alter the binding specificity of P9. HLA-DQ2 and -DQ8 both appear to prefer negatively charged amino acids at P9. In contrast, HLA-DQ7 (A1*0301, B1*0301), which is not associated with diabetes, has Asp at beta 57, allowing positively charged amino acids at P9. This analysis of the sequence features of DQ-binding peptides suggests molecular characteristics which may be useful to predict epitopes involved in disease pathogenesis.

Dissociative Recombination of FeO(+) with Electrons: Implications for Plasma Layers in the Ionosphere.

PubMed

Bones, D L; Plane, J M C; Feng, W

2016-03-10

The dissociative recombination (DR) of FeO(+) ions with electrons has been studied in a flowing afterglow reactor. FeO(+) was generated by the pulsed laser ablation of a solid Fe target, and then entrained in an Ar(+) ion/electron plasma where the absolute electron density was measured using a Langmuir probe. A kinetic model describing gas-phase chemistry and diffusion to the reactor walls was fitted to the experimental data, yielding a DR rate coefficient at 298 K of k(FeO(+) + e(-)) = (5.5 ± 1.0) × 10(-7) cm(3) molecule(-1) s(-1), where the quoted uncertainty is at the 2σ level. Fe(+) ions in the lower thermosphere are oxidized by O3 to FeO(+), and this DR reaction is shown to provide a more important route for neutralizing Fe(+) below 110 km than the radiative/dielectronic recombination of Fe(+) with electrons. The experimental system was first validated by measuring two other DR reaction rate coefficients: k(O2(+) + e(-)) = (2.0 ± 0.4) × 10(-7) and k(N2O(+) + e(-)) = (3.3 ± 0.8) × 10(-7) cm(3) molecule(-1) s(-1), which are in good agreement with the recent literature.

VizieR Online Data Catalog: ALMA submm galaxies multi-wavelength data (Simpson+, 2017)

NASA Astrophysics Data System (ADS)

Simpson, J. M.; Smail, I.; Swinbank, A. M.; Ivison, R. J.; Dunlop, J. S.; Geach, J. E.; Almaini, O.; Arumugam, V.; Bremer, M. N.; Chen, C.-C.; Conselice, C.; Coppin, K. E. K.; Farrah, D.; Ibar, E.; Hartley, W. G.; Ma, C. J.; Michalowski, M. J.; Scott, D.; Spaans, M.; Thomson, A. P.; van der Werf, P. P.

2017-11-01

In previous work, we presented the source catalog, number counts, and far-infrared morphologies of the 52 SMGs that were detected in 30 ALMA maps (see Simpson+ 2015ApJ...799...81S, 2015ApJ...807..128S). The UKIDSS observations of the ~0.8deg2 UDS comprise four Wide-Field Camera (WFCAM) pointings in the J-, H-, and K-bands. In this paper, we use the images and catalogs released as part of the UKIDSS data release 8 (DR8). The DR8 release contains data taken between 2005 and 2010, and the final J-, H-, and K-band mosaics have a median 5σ depth (2" apertures) of J=24.9, H=24.2, and K=24.6, respectively. Deep observations of the UDS have also been taken in the U-band with Megacam at the Canada-France-Hawaii Telescope (CFHT) and in the B, V, R, i', and z' bands with Suprime-cam at the Subaru telescope. Furthermore, deep Spitzer data, obtained as part of the SpUDS program (PI: J. Dunlop) provides imaging reaching a 5σ depth of m3.6=24.2 and m4.5=24.0 at 3.6um and 4.5um, respectively. The UDS field was observed at 250, 350, and 500um with the Spectral and Photometric Imaging Receiver (SPIRE) onboard the Herschel Space Observatory as part of the Herschel Multi-tiered Extragalactic Survey (HerMES). The UDS field was observed by the VLA at 1.4GHz as part of the project UDS20 (V. Arumugam et al. 2017, in preparation). A total of 14 pointings were used to mosaic an area of ~1.3deg2 centered on the UDS field. (2 data files).

Diuretic renography in hydronephrosis: delayed tissue tracer transit accompanies both functional decline and tissue reorganization.

PubMed

Schlotmann, Andreas; Clorius, John H; Rohrschneider, Wiltrud K; Clorius, Sandra N; Amelung, Folker; Becker, Kristianna

2008-07-01

The significance of delayed tissue tracer transit (TTT) of (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG3) has not been systematically evaluated in hydronephrosis. We sought to demonstrate that delayed TTT accompanies both functional decline and histomorphologic restructuring. Twenty 2- to 3-mo-old piglets with surgically induced partial unilateral ureteral stenosis were examined with magnetic resonance urography (MRU) to evaluate morphology and with (99m)Tc-MAG3 diuretic renography (DR) to determine single-kidney function (SKF), evaluate the response to furosemide stimulation (RFS), and assess TTT. All animals had DR and MRU before and after surgery and a third DR after surgery. Piglets were sacrificed after the final DR for renal histology. A total histologic score (THS) was generated. Preoperative DR demonstrated nonobstructive RFS, timely TTT, and balanced SKF in all 20 kidneys. After ureteral ligature, MRU demonstrated pelvic dilatation in all piglets. The postoperative DRs revealed 12 kidneys with delayed TTT in one or both follow-ups. In these 12 kidneys, the SKF declined from 51% +/- 4% to 18% +/- 14%, and the THS was 9.0 +/- 4.0. Three kidneys always had timely TTT, balanced SKF, and a THS of 1.8 +/- 0.3. The contralateral, nonoperated kidneys had timely TTT and a THS of 1.2 +/- 0.9. Postoperative scintigrams showed that 3 of 8 kidneys (38%) with an obstructive RFS had timely TTT, which demonstrates that TTT and RFS are not equivalent. In hydronephrosis, a delayed TTT of (99m)Tc-MAG3 accompanies both functional decline and histomorphologic restructuring in obstruction. According to the literature, a delayed TTT is determined by the filtration fraction of the kidneys and appears to identify an obstruction-mediated upregulated renin-angiotensin system.

Pro- and antiangiogenic VEGF and its receptor status for the severity of diabetic retinopathy

PubMed Central

Mondal, Lakshmi K.; Borah, Prasanta K.; Bhattacharya, Chandra K.; Mahanta, Jagadish

2017-01-01

Purpose Alteration of pro- and antiangiogenic homeostasis of vascular endothelial growth factor (VEGF) isoforms in patients with hyperglycemia seems crucial but substantially unexplored at least quantitatively for diabetic retinopathy (DR). Therefore, in the present study we aimed to estimate the difference between the pro- (VEGF165a) and antiangiogenic (VEGF165b) VEGF isoforms and its soluble receptors for severity of DR. Methods The study included 123 participants (diabetic retinopathy: 81, diabetic control: 20, non-diabetic control: 22) from the Regional Institute of Ophthalmology, Kolkata. The protein levels of VEGF165a (proangiogenic), VEGF165b (antiangiogenic), VEGF receptor 1 (VEGFR1), VEGFR2, and VEGFR3 in plasma were determined with enzyme-linked immunosorbent assay (ELISA). Results An imbalance in VEGF homeostasis, a statistically significant concomitant increase (p<0.0001) in the level of VEGF165a and a decrease in the level of VEGF165b, was observed with the severity of the disease. Increased differences between VEGF165a and VEGF165b i.e. VEGF165a-b concomitantly increased statistically significantly with the severity of the disease (p<0.0001), patients with diffuse diabetic macular edema (DME) with proliferative DR (PDR) had the highest imbalance. The plasma soluble form of VEGFR2 concentration consistently increased statistically significantly with the severity of the disease (p<0.0001). Conclusions The increased difference or imbalance between the pro- (VEGF165a) and antiangiogenic (VEGF165b) homeostasis of the VEGF isoforms, seems crucial for an adverse prognosis of DR and may be a better explanatory marker compared with either VEGF isoform. PMID:28680264

MRI dynamic range and its compatibility with signal transmission media

PubMed Central

Gabr, Refaat E.; Schär, Michael; Edelstein, Arthur D.; Kraitchman, Dara L.; Bottomley, Paul A.; Edelstein, William A.

2010-01-01

As the number of MRI phased array coil elements grows, interactions among cables connecting them to the system receiver become increasingly problematic. Fiber optic or wireless links would reduce electromagnetic interference, but their dynamic range (DR) is generally less than that of coaxial cables. Raw MRI signals, however, have a large DR because of the high signal amplitude near the center of k-space. Here, we study DR in MRI in order to determine the compatibility of MRI multicoil imaging with non-coaxial cable signal transmission. Since raw signal data are routinely discarded, we have developed an improved method for estimating the DR of MRI signals from conventional magnitude images. Our results indicate that the DR of typical surface coil signals at 3 T for human subjects is less than 88 dB, even for three-dimensional acquisition protocols. Cardiac and spine coil arrays had a maximum DR of less than 75 dB and head coil arrays less than 88 dB. The DR derived from magnitude images is in good agreement with that measured from raw data. The results suggest that current analog fiber optic links, with a spurious-free DR of 60–70 dB at 500 kHz bandwidth, are not by themselves adequate for transmitting MRI data from volume or array coils with DR ~90 dB. However, combining analog links with signal compression might make non-coaxial cable signal transmission viable. PMID:19251444

MRI dynamic range and its compatibility with signal transmission media.

PubMed

Gabr, Refaat E; Schär, Michael; Edelstein, Arthur D; Kraitchman, Dara L; Bottomley, Paul A; Edelstein, William A

2009-06-01

As the number of MRI phased array coil elements grows, interactions among cables connecting them to the system receiver become increasingly problematic. Fiber optic or wireless links would reduce electromagnetic interference, but their dynamic range (DR) is generally less than that of coaxial cables. Raw MRI signals, however, have a large DR because of the high signal amplitude near the center of k-space. Here, we study DR in MRI in order to determine the compatibility of MRI multicoil imaging with non-coaxial cable signal transmission. Since raw signal data are routinely discarded, we have developed an improved method for estimating the DR of MRI signals from conventional magnitude images. Our results indicate that the DR of typical surface coil signals at 3T for human subjects is less than 88 dB, even for three-dimensional acquisition protocols. Cardiac and spine coil arrays had a maximum DR of less than 75 dB and head coil arrays less than 88 dB. The DR derived from magnitude images is in good agreement with that measured from raw data. The results suggest that current analog fiber optic links, with a spurious-free DR of 60-70 dB at 500 kHz bandwidth, are not by themselves adequate for transmitting MRI data from volume or array coils with DR approximately 90 dB. However, combining analog links with signal compression might make non-coaxial cable signal transmission viable.

TL1A/DR3 axis involvement in the inflammatory cytokine network during pulmonary sarcoidosis.

PubMed

Facco, M; Cabrelle, A; Calabrese, F; Teramo, A; Cinetto, F; Carraro, S; Martini, V; Calzetti, F; Tamassia, N; Cassatella, M A; Semenzato, G; Agostini, C

2015-01-01

TNF-like ligand 1A (TL1A), a recently recognized member of the TNF superfamily, and its death domain receptor 3 (DR3), firstly identified for their relevant role in T lymphocyte homeostasis, are now well-known mediators of several immune-inflammatory diseases, ranging from rheumatoid arthritis to inflammatory bowel diseases to psoriasis, whereas no data are available on their involvement in sarcoidosis, a multisystemic granulomatous disease where a deregulated T helper (Th)1/Th17 response takes place. In this study, by flow cytometry, real-time PCR, confocal microscopy and immunohistochemistry analyses, TL1A and DR3 were investigated in the pulmonary cells and the peripheral blood of 43 patients affected by sarcoidosis in different phases of the disease (29 patients with active sarcoidosis, 14 with the inactive form) and in 8 control subjects. Our results demonstrated a significant higher expression, both at protein and mRNA levels, of TL1A and DR3 in pulmonary T cells and alveolar macrophages of patients with active sarcoidosis as compared to patients with the inactive form of the disease and to controls. In patients with sarcoidosis TL1A was strongly more expressed in the lung than the blood, i.e., at the site of the involved organ. Additionally, zymography assays showed that TL1A is able to increase the production of matrix metalloproteinase 9 by sarcoid alveolar macrophages characterized, in patients with the active form of the disease, by reduced mRNA levels of the tissue inhibitor of metalloproteinase (TIMP)-1. These data suggest that TL1A/DR3 interactions are part of the extended and complex immune-inflammatory network that characterizes sarcoidosis during its active phase and may contribute to the pathogenesis and to the progression of the disease.

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.

IL-35-producing B cells in gastric cancer patients.

PubMed

Wang, Ke; Liu, Jianming; Li, Jiansheng

2018-05-01

A significant characteristic of advanced gastric cancer (GC) is immune suppression, which can promote the progression of GC. Interleukin 35 (IL-35) is an immune-suppressing cytokine, and it is generally recognized that this cytokine is secreted by regulatory T (Treg) cells. Recently, studies have found that IL-35 can also be produced by B cells in mice. However, scientific studies reporting that IL-35 is secreted by B cells in humans, specifically in cancer patients, are very rare.Blood samples were collected from 30 healthy controls (HCs) and 50 untreated GC patients, and IL-35-producing B cells in the peripheral blood were investigated. Moreover, Treg cells (CD4CD25CD127), myeloid-derived suppressor cells (MDSCs) (CD14HLA-DR) and other lymphocyte subsets (CD3, CD4, CD8 T cells, activated and memory CD4 T cells, activated CD8 T cells, CD14 monocytes, and IL-10-producing B cells) were also examined.IL-35-producing B cells were significantly upregulated in patients with advanced GC. Furthermore, the frequency of IL-35-producing B cells was positively correlated with the frequencies of Treg cells (CD4CD25CD127), MDSCs (CD14HLA-DR), IL-10-producing B cells, and CD14 monocytes in these GC patients.In summary, the frequency of IL-35-producing B cells is significantly elevated in advanced GC; this outcome implies that this group of B cells may participate in GC progression.

The Royan Public Umbilical Cord Blood Bank: Does It Cover All Ethnic Groups in Iran Based on HLA Diversity?

PubMed

Ebrahimkhani, Saeideh; Farjadian, Shirin; Ebrahimi, Marzieh

2014-04-01

Umbilical cord blood (UCB) stem cells allow the transplantation of partially human leukocyte antigen (HLA)-matched grafts and are a valuable resource for the treatment of hematologic malignancies and heritable hematologic, immunologic and metabolic diseases, especially when a compatible bone marrow donor is unavailable. The aim of this study was to determine how many ethnic groups in Iran are covered by the available UCB units based on HLA diversity. From 2009 until mid-2013, 4,981 (30.3%) of the 16,437 UCB samples collected met the storage criteria and were cryopreserved at a public cord blood bank (CBB) in Tehran, Iran. HLA-A, -B and -DRB1 were typed in 1,793 samples. The mean volume of the cryopreserved samples was 81.25 ± 20.3 ml. The range of total nucleated cells per unit was 51 × 10(7)-107 × 10(7). The most common HLA alleles were HLA-A*2 (17%) and HLA-A*24 (15.6%), HLA-B*35 (16.8%) and HLA-B*51 (13.9%), and HLA-DRB1*11 (20%) and HLA-DRB1*15 (14%). The predominant haplotypes were HLA-A*24-B*35-DRB1*11 (2%), HLA-A*02-B*50-DR*07 (1.8%), and HLA-A*02-B*51-DRB1*11 (1.5%). Based on the HLA-DRB1 profiles, the UCB units available at the Royan public UCB bank are a potentially adequate resource for hematopoietic stem cell transplantation for Iranian recipients belonging to particular ethnic groups. Regular educational programs to improve the public knowledge of UCB for transplantation can enhance the public CBB stocks for all Iranian ethnic groups in the future.

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.

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

Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161++TCR iVα7.2+ Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection.

PubMed

Yong, Yean K; Saeidi, Alireza; Tan, Hong Y; Rosmawati, Mohamed; Enström, Philip F; Batran, Rami Al; Vasuki, V; Chattopadhyay, Indranil; Murugesan, Amudhan; Vignesh, Ramachandran; Kamarulzaman, Adeeba; Rajarajeswaran, Jayakumar; Ansari, Abdul W; Vadivelu, Jamuna; Ussher, James E; Velu, Vijayakumar; Larsson, Marie; Shankar, Esaki M

2018-01-01

Mucosal-associated invariant T (MAIT) cells, defined as CD161 ++ TCR iVα7.2 + T cells, play an important role in the innate defense against bacterial infections, and their functionality is impaired in chronic viral infections. Here, we investigated the frequency and functional role of MAIT cells in chronic hepatitis B virus (HBV) infection. The peripheral CD3 + CD161 ++ TCR iVα7.2 + MAIT cells in chronic HBV-infected patients and healthy controls were phenotypically characterized based on CD57, PD-1, TIM-3, and CTLA-4, as well as HLA-DR and CD38 expression. The frequency of MAIT cells was significantly decreased among chronic HBV-infected individuals as compared to controls. Expression of CD57, PD-1, CTLA-4, as well as HLA-DR and CD38 on MAIT cells was significantly elevated in chronic HBV-infected individuals relative to controls. The percentage of T cell receptor (TCR) iVα7.2 + CD161 + MAIT cells did not correlate with HBV viral load but inversely with HLA-DR on CD4 + T cells and MAIT cells and with CD57 on CD8 + T cells suggesting that decrease of MAIT cells may not be attributed to direct infection by HBV but driven by HBV-induced chronic immune activation. The percentage and expression levels of PD-1 as well as CTLA-4 on MAIT cells inversely correlated with plasma HBV-DNA levels, which may suggest either a role for MAIT cells in the control of HBV infection or the effect of HBV replication in the liver on MAIT cell phenotype. We report that decrease of TCR iVα7.2 + MAIT cells in the peripheral blood and their functions were seemingly impaired in chronic HBV-infected patients likely because of the increased expression of PD-1.

ONR Far East Scientific Bulletin. Volume 8, Number 3, July-September 1983.

DTIC Science & Technology

1983-09-01

not be any bananas today." That kind of logic is hard to figure out even in English, but much more so in Japanese. Another comment which I wish to...is studying hydrogenation-dehydrogenation mechanisms of organic molecules adsorbed on surfaces of metals such as Ni and Pd by this method. Dr. B. Peel

A Simulation of High Latitude F-Layer Instabilities in the Presence of Magnetosphere-Ionosphere Coupling.

DTIC Science & Technology

1985-07-08

Equatorial spread F: recent observations and a new intepretation , J. Geophys. Res., 77, 5625, 1972. Basu, S., S. Basu, E. MacKenzie, W.R. Coley, W.B. Hanson...HOPKINS ROAD LAUREL, MD 20810 DR. R. GREENWALD DR. C. MENG UNIVERSITY OF PITTSBURGH PITTSBURGH, PA 15213 DR. N. ZABUSKY DR. M. BIONDI DR. E. OVERMAN 26 FILMED 9-85 DTIC RJa. I - rlt -6 ,I, a~l O -3

VizieR Online Data Catalog: Census of blue stars in SDSS DR8 (Scibelli+, 2014)

NASA Astrophysics Data System (ADS)

Scibelli, S.; Newberg, H. J.; Carlin, J. L.; Yanny, B.

2015-02-01

We present a census of the 12060 spectra of blue objects ((g-r)0<-0.25) in the Sloan Digital Sky Survey (SDSS) Data Release 8 (DR8). As part of the data release, all of the spectra were cross-correlated with 48 template spectra of stars, galaxies, and QSOs to determine the best match. We compared the blue spectra by eye to the templates assigned in SDSS DR8. 10856 of the objects matched their assigned template, 170 could not be classified due to low signal-to-noise ratio, and 1034 were given new classifications. We identify 7458 DA white dwarfs, 1145 DB white dwarfs, 273 rarer white dwarfs (including carbon, DZ, DQ, and magnetic), 294 subdwarf O stars, 648 subdwarf B stars, 679 blue horizontal branch stars, 1026 blue stragglers, 13 cataclysmic variables, 129 white dwarf-M dwarf binaries, 36 objects with spectra similar to DO white dwarfs, 179, quasi-stellar objects (QSOs), and 10 galaxies. We provide two tables of these objects, sample spectra that match the templates, figures showing all of the spectra that were grouped by eye, and diagnostic plots that show the positions, colors, apparent magnitudes, proper motions, etc., for each classification. (3 data files).

Dietary Restriction and Fasting Arrest B and T Cell Development and Increase Mature B and T Cell Numbers in Bone Marrow

PubMed Central

Shushimita, Shushimita; de Bruijn, Marjolein J. W.; de Bruin, Ron W. F.; IJzermans, Jan N. M.; Hendriks, Rudi W.; Dor, Frank J. M. F.

2014-01-01

Dietary restriction (DR) delays ageing and extends life span. Both long- and short-term DR, as well as short-term fasting provide robust protection against many “neuronal and surgery related damaging phenomena” such as Parkinson’s disease and ischemia-reperfusion injury. The exact mechanism behind this phenomenon has not yet been elucidated. Its anti-inflammatory actions prompted us to thoroughly investigate the consequences of DR and fasting on B and T cell compartments in primary and secondary lymphoid organs of male C57Bl/6 mice. In BM we found that DR and fasting cause a decrease in the total B cell population and arrest early B cell development, while increasing the number of recirculating mature B cells. In the fasting group, a significant reduction in peripheral B cell counts was observed in both spleen and mesenteric lymph nodes (mLN). Thymopoiesis was arrested significantly at double negative DN2 stage due to fasting, whereas DR resulted in a partial arrest of thymocyte development at the DN4 stage. Mature CD3+ T cell populations were increased in BM and decreased in both spleen and mLN. Thus, DR arrests B cell development in the BM but increases the number of recirculating mature B cells. DR also arrests maturation of T cells in thymus, resulting in depletion of mature T cells from spleen and mLN while recruiting them to the BM. The functional relevance in relation to protection against organ damage needs to be determined. PMID:24504160

Lithium AA-Size Cells for Navy Mine Applications: 2. Evaluation of Commercial Cells

DTIC Science & Technology

1994-02-24

45433-6563 CENTER4301 SUITLAND ROAD A’TTN CODE N7B3 (H HOLTER) 1WASI3NGTON DC 20390 CODE N7B3 (P WRIGIIT) INAVAL ORI)NANCE CENTER ATrN DGUERRINO I...77058 HORSHAM PA 19044 ATTN MS 433 (J GOWDEY) 1 ATTN DR ROBERT B DAVIDSON NASA LANGLEY SCIENCE APPLICATIONS HAMPTON VA 23665 INTERNATIONAL CORP 1710... SCIENCES P 0 BOX 1508 BATTERY TECHNOLOGY CENTER MASON CITY IA 50401 1601 RESEARCH BLVD ROCKVILLE MD 20850 ATTN S ARGADE TECtINOCHEM CO ATTN GARCHDALE 203A

THE INDUCTION OF ABERRANT CRYPT FOCI (ACF) IN MALE AND FEMALE F344/N RATS BY BROMOCHLOROACETIC ACID (BCA) ADMINISTERED IN THE DRINKING WATER

EPA Science Inventory

The Induction of Aberrant Crypt Foci (ACF) in Male and Female F344/N Rats by Bromochloroacetic Acid (BCA) Administered in the Drinking Water.

M.H. George1, D. Delker1, D.R. Geter1, C.Herbert2, J. Roycroft3, R. Melnick3, D.W.
Rosenberg4, and A.B. DeAngelo1. 1USEPA, Resea...

Achieving a physiological cortisol profile with once-daily dual-release hydrocortisone: a pharmacokinetic study.

PubMed

Johannsson, Gudmundur; Lennernäs, Hans; Marelli, Claudio; Rockich, Kevin; Skrtic, Stanko

2016-07-01

Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy was developed to provide a cortisol exposure-time profile that closely resembles the physiological cortisol profile. This study aimed to characterize single-dose pharmacokinetics (PK) of DR-HC 5-20mg and assess intrasubject variability. Thirty-one healthy Japanese or non-Hispanic Caucasian volunteers aged 20-55 years participated in this randomized, open-label, PK study. Single doses of DR-HC 5, 15 (3×5), and 20mg were administered orally after an overnight fast and suppression of endogenous cortisol secretion. After estimating the endogenous cortisol profile, PK of DR-HC over 24h were evaluated to assess dose proportionality and impact of ethnicity. Plasma cortisol concentrations were analyzed using liquid chromatography-tandem mass spectrometry. PK parameters were calculated from individual cortisol concentration-time profiles. DR-HC 20mg provided higher than endogenous cortisol plasma concentrations 0-4h post-dose but similar concentrations later in the profile. Cortisol concentrations and PK exposure parameters increased with increasing doses. Mean maximal serum concentration (Cmax) was 82.0 and 178.1ng/mL, while mean area under the concentration-time curve (AUC)0-∞ was 562.8 and 1180.8h×ng/mL with DR-HC 5 and 20mg respectively. Within-subject PK variability was low (<15%) for DR-HC 20mg. All exposure PK parameters were less than dose proportional (slope <1). PK differences between ethnicities were explained by body weight differences. DR-HC replacement resembles the daily normal cortisol profile. Within-subject day-to-day PK variability was low, underpinning the safety of DR-HC for replacement therapy. DR-HC PK were less than dose proportional - an important consideration when managing intercurrent illness in patients with adrenal insufficiency. © 2016 The authors.

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.

VizieR Online Data Catalog: Transit times of Kepler-448b and Kepler-693b (Masuda, 2017)

NASA Astrophysics Data System (ADS)

Masuda, K.

2017-11-01

I analyzed Transit Timing Variations (TTVs) of 23 confirmed, singly transiting warm Jupiters (WJs; Section 2.1) with an orbital period of 7days8R{Earth} in the DR24 of the KOI catalog (Coughlin et al. 2016, Cat. J/ApJS/224/12). Systems with multiple KOIs are all excluded, even though they consist of only one confirmed planet and false positives. I found clearly non-sinusoidal TTVs for Kepler-448/KOI-12b, Kepler-693/KOI-824b, and Kepler-419/KOI-1474b. The result is consistent with the TTV search by Holczer et al. 2016 (Cat. J/ApJS/225/9), who reported significant long-term TTVs for the same three KOIs in our sample. Of these planets, the TTVs of Kepler-419b have previously been analyzed by Dawson et al. (2014ApJ...791...89D). Therefore, I focus on Kepler-448b and Kepler-693b. (3 data files).

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

Relationship of In-Cylinder Gaseous and Particulate Concentration to Radiative Heat Transfer in Direct Injection-Type Diesel Combustion.

DTIC Science & Technology

1986-04-15

spectral reflectivities, a,.,, are included in the expression for the radiosity of surface 1, Bk1, as (I I l cos eI I(0)) 4 B cos e e 2 + B 2 cos 92 i...OAAG29-83-K-0042 (Scientific Program Officer, Dr. David M. Mann). NOMENCLATURE A band absorptance a constant determining species distribution 8 radiosity ...Fig. 1), the radiosity of the surface 1, 81, i.e., to compute the thermal and optical is expressed as properties of the species and to implement

Analysis of the Influence of HLA-A Matching Relative to HLA-B and -DR Matching on Heart Transplant Outcomes

PubMed Central

Ansari, David; Bućin, Dragan; Höglund, Peter; Ohlsson, Mattias; Andersson, Bodil; Nilsson, Johan

2015-01-01

Background There are conflicting reports on the effect of donor-recipient HLA matching on outcomes in heart transplantation. The objective of this study was to investigate the effects of HLA-A matching relative to HLA-B and -DR matching on long-term survival in heart transplantation. Methods A total of 25 583 patients transplanted between 1988 and 2011 were identified from the International Society for Heart and Lung Transplantation registry. Transplants were divided into 2 donor-recipient matching groups: HLA-A–compatible (no HLA-A mismatches) and HLA-A–incompatible (1-2 HLA-A mismatches). Primary outcome was all-cause mortality. Secondary outcomes were graft failure-, cardiovascular-, infection-, or malignancy-related deaths. Results The risk of all-cause mortality 15 years after transplantation was higher for HLA-A–compatible (vs HLA-A–incompatible) grafts in patients who had HLA-B–, HLA-DR–, or HLA-B,DR–incompatible grafts (P = 0.027, P = 0.007, and P = 0.002, respectively) but not in HLA-B– and/or HLA-DR–compatible grafts. This was confirmed in multivariable Cox regression analysis where HLA-A compatibility (vs HLA-A incompatibility) was associated with higher mortality in transplants incompatible for HLA-DR or HLA-B and -DR (hazard ratio [HR], 1.59; 95% confidence interval [95% CI], 1.11-2.28; P = 0.012 and HR, 1.69; 95% CI, 1.17-2.43; P = 0.005, respectively). In multivariable analysis, the largest compromise in survival for HLA-A compatibility (vs HLA-incompatibility) was for chronic rejection in HLA-B– and -DR–incompatible grafts (HR, 1.91; 95% CI, 1.22-3.01; P = 0.005). Conclusions Decreased long-term survival in heart transplantation was associated with HLA-A compatibility in HLA-B,DR–incompatible grafts. PMID:27500238

[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.

Physical Processes Governing Atmospheric Trace Constituents Measured from an Aircraft on PEM-Tropics

NASA Technical Reports Server (NTRS)

Newell, Reginald E.; Hoell, James M., Jr. (Technical Monitor)

2001-01-01

Before the mission, the PI (principal investigator) was instrumental in securing real-time use of the new 51-level ECMWF (European Centre for Medium Range Weather Forecasts) meteorological data. During the mission, he provided flight planning and execution guidance as meteorologist for the P-3B. Mr. Yong Zhu computed and plotted meteorological forecast maps using the ECMWF data and transmitted them to the field from MIT (Massachusetts Institute of Technology). Dr. John Cho was in the field for the Christmas Island portion to extract data from the on-site NOAA (National Oceanic and Atmospheric Administration) radars for local wind profiles that were used at the flight planning meetings. When the power supply for the VHF radar failed, he assisted the NOAA engineer in its repair. After the mission, Mr. Zhu produced meteorological data memos, which were made available to the PEM (Pacific Exploratory Mission)-Tropics B science team on request. An undergraduate student, Ms. Danielle Morse, wrote memos annotating the cloud conditions seen on the aircraft external monitor video tapes. Dr. Cho and the PI circulated a memo regarding the status (and associated problems) of the meteorological measurement systems on the DC-8 and P-3B to the relevant people on the science team. Several papers by members of our project were completed and accepted by JGR (Journal of Geophysical Research) for the first special section on PEM-Tropics B. These papers included coverage of the following topics: 1) examination of boundary layer data; 2) water vapor transport; 3) tropospheric trace constituent layers; 4) summarizations of the meteorological background and events during PEM-Tropics B; 5) concomitant lidar measurements of ozone, water vapor, and aerosol.

Characterization of the extrinsic apoptotic pathway in the basal chordate amphioxus.

PubMed

Yuan, Shaochun; Liu, Huiling; Gu, Ming; Xu, Liqun; Huang, Shengfeng; Ren, Zhenhua; Xu, Anlong

2010-09-14

The death receptor (DR)-mediated apoptosis pathway is thought to be unique to vertebrates. However, the presence of DR-encoding genes in the sea urchin and the basal chordate amphioxus prompted us to reconsider, especially given that amphioxus contains 14 DR proteins and hundreds of death domain (DD)-containing adaptor proteins. To understand how the extrinsic apoptotic pathway was originally established and what the differences in signaling are between invertebrates and vertebrates, we performed functional studies of several genes that encode DDs in the amphioxus Branchiostoma belcheri tsingtauense (Bbt). First, we observed that the increased abundance of Bbt Fas-associated death domain 1 (BbtFADD1) in HeLa cells resulted in the formation of death effector filamentous structures in the cytoplasm and the activation of the nuclear factor κB pathway, whereas BbtFADD2 protein was restricted to the nucleus, although its death effector domain induced apoptosis when in the cytoplasm. We further demonstrated that formation of a FADD-caspase-8 complex recruited amphioxus DR1 (BbtDR1), which bound to the adaptor proteins CRADD or TRAF6 (tumor necrosis factor receptor-associated factor 6) to convey distinct signals, ranging from apoptosis to gene activation. Thus, our study not only reveals the evolutionary origin of the extrinsic apoptotic pathway in a basal chordate but also adds to our understanding of the similarities and differences between invertebrate and vertebrate FADD signaling.

Prognostic Value of Dynamic Monitoring of Cellular Immunity and HMGB1 in Severe Sepsis: Delayed Chronic Inflammation may be the Leading Cause of Death in Late Severe Sepsis.

PubMed

Yu, Han; Qi, Zhijiang; Zhao, Lianxing; Shao, Rui; Fang, Yingying; Li, Chunsheng

2016-12-01

Sepsis is a life-threatening response to infection with a high mortality rate. In order to explore the prognostic value of dynamic monitoring of cellular immunity during late severe sepsis, we assessed levels of Tlymphocyte subsets, the human leukocyte antigen D-related (HLA-DR), and the high mobility group box-1 (HMGB1) protein. Study participants included 247 consecutive severe sepsis patients who were admitted to Beijing ChaoYang Hospital's Emergency Intensive Care Unit. Patients were divided into survivors and non-survivors based on 90-day survival rates, and clinical data were collected. T-lymphocyte subsets on days 1 and 7, HLA-DR on days 1 and 12, and HMGB1 on days 1, 3, 5, 7, and 12 were analyzed. Counts of CD3+, CD3+CD4+, and CD3+CD8+ T cells on day 1 in non-survivors were lower than those in survivors. By day 7, counts of all three types of T cells had increased in both survivors and non-survivors, but CD3+ and CD3+CD8+ T cells remained lower in non-survivors than in survivors. There was no significant difference in HLA-DR levels between survivors and non-survivors on day 1, but HLA-DR levels increased in survivors and decreased in non-survivors by day 12. In contrast, over days 1 - 12, HMGB1 levels increased in non-survivors and decreased in survivors. Patients with severe sepsis present with cellular immune dysfunction and persistent chronic inflammation, both of which may lead to death in the late phase of severe sepsis. Dynamic monitoring of indicators of cellular immunity and HMGB1 is useful for evaluating the immune status, chronic inflammation processes, and prognoses of patients with severe sepsis.

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

Sampling Variances and Covariances of Parameter Estimates in Item Response Theory.

DTIC Science & Technology

1982-08-01

substituting (15) into (16) and solving for k and K k = b b1 - o K , (17)k where b and b are means for m and r items, respectively. To find the variance...C5 , and C12 were treated as known. We find that the standard errors of B1 to B5 are increased drastically by ignorance of C 1 to C5 ; all...ERIC Facilltv-Acquisitlons Davie Hall 013A 4833 Rugby Avenue Chapel Hill, NC 27514 Bethesda, MD 20014 -7- Dr. A. J. Eschenbrenner 1 Dr. John R

Soluble TL1A is sufficient for activation of death receptor 3.

PubMed

Bittner, Sebastian; Knoll, Gertrud; Füllsack, Simone; Kurz, Maria; Wajant, Harald; Ehrenschwender, Martin

2016-01-01

Death receptor 3 (DR3) is a typical member of the tumor necrosis factor receptor family, and was initially identified as a T-cell co-stimulatory molecule. However, further studies revealed a more complex and partly dichotomous role for DR3 and its ligand TL1A under (patho)physiological conditions. TL1A and DR3 are not only a driving force in the development of autoimmune and inflammatory diseases, but also play an important role in counteracting these processes through an increase in the number of regulatory T cells. Ligands of the tumor necrosis factor family typically occur in two forms, membrane-bound and soluble, that can differ strikingly with respect to their efficacy in activating their corresponding receptor(s). Ligand-based approaches to activate the TL1A-DR3 pathway therefore require understanding of the molecular prerequisites of TL1A-based DR3 activation. To date, this has not been addressed. Here, we show that recombinant soluble trimeric TL1A is fully sufficient to strongly activate DR3-associated pro- and anti-apoptotic signaling pathways. In contrast to the TRAIL death receptors, which are much better activated by soluble TRAIL upon secondary ligand oligomerization, but similarly to the death receptor tumor necrosis factor receptor 1, DR3 is efficiently activated by soluble TL1A trimers. Additionally, we have measured the affinity of TL1A-DR3 interaction in a cell-based system, and demonstrated TL1A-induced DR3 internalization. Identification of DR3 as a tumor necrosis factor receptor that responds to soluble ligand trimers without further oligomerization provides a basis for therapeutic exploitation of the TL1A-DR3 pathway. © 2015 FEBS.

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.

The Green Bank Ammonia Survey: First Results of NH3 Mapping of the Gould Belt

NASA Astrophysics Data System (ADS)

Friesen, Rachel K.; Pineda, Jaime E.; co-PIs; Rosolowsky, Erik; Alves, Felipe; Chacón-Tanarro, Ana; How-Huan Chen, Hope; Chun-Yuan Chen, Michael; Di Francesco, James; Keown, Jared; Kirk, Helen; Punanova, Anna; Seo, Youngmin; Shirley, Yancy; Ginsburg, Adam; Hall, Christine; Offner, Stella S. R.; Singh, Ayushi; Arce, Héctor G.; Caselli, Paola; Goodman, Alyssa A.; Martin, Peter G.; Matzner, Christopher; Myers, Philip C.; Redaelli, Elena; The GAS Collaboration

2017-07-01

We present an overview of the first data release (DR1) and first-look science from the Green Bank Ammonia Survey (GAS). GAS is a Large Program at the Green Bank Telescope to map all Gould Belt star-forming regions with {A}{{V}}≳ 7 mag visible from the northern hemisphere in emission from NH3 and other key molecular tracers. This first release includes the data for four regions in the Gould Belt clouds: B18 in Taurus, NGC 1333 in Perseus, L1688 in Ophiuchus, and Orion A North in Orion. We compare the NH3 emission to dust continuum emission from Herschel and find that the two tracers correspond closely. We find that NH3 is present in over 60% of the lines of sight with {A}{{V}}≳ 7 mag in three of the four DR1 regions, in agreement with expectations from previous observations. The sole exception is B18, where NH3 is detected toward ∼40% of the lines of sight with {A}{{V}}≳ 7 mag. Moreover, we find that the NH3 emission is generally extended beyond the typical 0.1 pc length scales of dense cores. We produce maps of the gas kinematics, temperature, and NH3 column densities through forward modeling of the hyperfine structure of the NH3 (1, 1) and (2, 2) lines. We show that the NH3 velocity dispersion, {σ }v, and gas kinetic temperature, T K, vary systematically between the regions included in this release, with an increase in both the mean value and the spread of {σ }v and T K with increasing star formation activity. The data presented in this paper are publicly available (https://dataverse.harvard.edu/dataverse/GAS_DR1).

Prevalence and determinants of undiagnosed diabetic retinopathy and vision-threatening retinopathy in a multiethnic Asian cohort: the Singapore Epidemiology of Eye Diseases (SEED) study.

PubMed

Huang, Olivia S; Tay, Wan Ting; Ong, Peng Guan; Sabanayagam, Charumathi; Cheng, Ching-Yu; Tan, Gavin S; Cheung, Gemmy C M; Lamoureux, Ecosse L; Wong, Tien Y

2015-12-01

To determine the prevalence and risk factors of undiagnosed diabetic retinopathy (DR), in particular vision-threatening DR (VTDR) in a multiethnic Asian cohort. A population-based survey of 3353 Chinese, 3280 Malays and 3400 Indians (73.6% response) aged 40-80 years residing in Singapore. Diabetes mellitus (DM) was defined as random glucose ≥11.1 mmol/L, use of diabetic medication or a previous physician diagnosis. DR severity was graded from retinal photographs following the modified Airlie House classification. VTDR was defined as the presence of severe non-proliferative DR (NPDR), proliferative DR (PDR) or clinically significant macular oedema (CSMO), using the Eye Diseases Prevalence Research Group definition. Participants were deemed 'undiagnosed' if they reported no prior physician diagnosis in structured interviews, in those with the condition. Of 10 033 participants, 2376 had DM (23.7%), of which 805 (33.9%) had DR. Among 2376 with DM, 11.1% (n=263) were undiagnosed. Among 805 with DR, 671 (83.3%) were undiagnosed. Among 212 with VTDR, 59 (27.3%) were undiagnosed. In multivariate models, factors associated with undiagnosed VTDR were higher low-density lipoprotein (LDL) cholesterol (OR=1.53, 95% CI 0.99 to 2.35, p=0.05) and absence of visual impairment or blindness in any eye in terms of best-corrected vision OR=3.00, 95% CI 1.47 to 6.11, p=0.003). In this community, a quarter with VTDR is undiagnosed, and 8 in 10 with any DR are undiagnosed, compared with only 1 in 10 with DM undiagnosed. These findings suggest that screening for diabetes is successful, while screening for DR is currently inadequate in our population. Public health strategies to aid early diagnosis of DR in Singapore are urgently warranted to reduce blindness due to diabetes. 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/

HLA-typing, clinical, and immunological characterization of youth with type 2 diabetes mellitus phenotype from the German/Austrian DPV database.

PubMed

Awa, Wendy L; Boehm, Bernard O; Rosinger, Silke; Achenbach, Peter; Ziegler, Anette G; Krause, Stephanie; Meissner, Thomas; Wiegand, Susanne; Reinehr, Thomas; Kapellen, Thomas; Karges, Beate; Eiermann, Thomas; Schober, Edith; Holl, Reinhard W

2013-12-01

To characterize the clinical and immunological features of HLA-typed youth with pediatric onset of type 2 diabetes mellitus (T2DM). One hundred and seven patients with clinically diagnosed T2DM (aged ≤20 yr at diagnosis) were examined. DNA and serum, obtained after a median diabetes duration of 2.2 (Q1-Q3: 0.8-4.6) yr, were used for centralized HLA-typing and autoantibody (GADA, IA-2A, ZnT8A) measurements. 64.6% of patients were female and median age at diagnosis was 13.8 (Q1-Q3: 11.6-15.4) yr. Patients were obese [median body mass index-standard deviation score (BMI-SDS): 2.6 (2.0-3.1)], 88.0% had a family history of diabetes and 40.2% a migration background. Islet autoantibodies were detected in 16 (15.0%), among which 7 (6.5%) had multiple islet autoantibodies. Autoantibody positive patients had poorer metabolic control than autoantibody negative patients [glycosylated hemoglobin A1c (HbA1c): 8.1 (6.9-10.1) % vs. 6.6 (5.9-8.0) %; p = 0.033], while patients with HLA-DR genetic risk had higher BMI-SDS than those with HLA-DRXX [2.6 (2.4-3.7) vs. 2.4 (1.7-2.9); p = 0.007]. Metabolic syndrome (61.7%), microalbuminuria (13.4%), and retinopathy (3.9%) were diagnosed. Therapies used were lifestyle only (35.5%), oral anti-diabetics (OAD) only (43.3 %), insulin +  OAD (15.9%) and insulin only (5.6%). Patients with β-cell autoimmunity or HLA-DR genetic risk more frequently used insulin than confirmed T2DM patients (50.0 vs. 22.0%; p = 0.037) and less often had diabetic relatives (61.1 vs. 86.0%; p = 0.030). T2DM was confirmed in about 90% of patients while about 10% with β-cell autoimmunity or HLA-DR genetic risk likely had either T1.5DM or 'double diabetes' or an unknown diabetes type. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Gordon Research Conference on Computational Chemistry Held in Plymouth, New Hampshire on 4-8 July 1988

DTIC Science & Technology

1988-07-01

NUMBER(S) S. MONITORING ORGANIZATION REPORT NUMBER(S) _ R.TR- 90 - 0 4 70 6a. NAME OF PERFORMING ORGANIZATION 6b. OFFICE SYMBOL 7a. NAME OF MONITORING...University of Rhode Island Building 410 Kingston, RI 18195 Boiling AFB, DC 20332-6448 . Sa. NAME OF FUNDING / SPONSORING Sb. OFFICE SYMBOL 9, PROCUREMENT...AS RPT. 3 OTIC USERS UNCLASSIFIED 22a- NAME OF RESPONSIBLE INDIVIDUAL 22b. TELEPHONE (Include Area Code) 22c OFFICE SYMBOL Dr Anthony J. Matuszko (202

HLA-A, HLA-B and HLA-DRB1 allele and haplotype frequencies of 10 918 Koreans from bone marrow donor registry in Korea.

PubMed

Park, H; Lee, Y-J; Song, E Y; Park, M H

2016-10-01

The human leucocyte antigen (HLA) system is the most polymorphic genetic system in humans, and HLA matching is crucial in organ transplantation, especially in hematopoietic stem cell transplantation. We investigated HLA-A, HLA-B and HLA-DRB1 allele and haplotype frequencies at allelic level in 10 918 Koreans from bone marrow donor registry in Korea. Intermediate resolution HLA typing was performed using Luminex technology (Wakunaga, Japan), and additional allelic level typing was performed using PCR-single-strand conformation polymorphism method and/or sequence-based typing (Abbott Molecular, USA). Allele and haplotype frequencies were calculated by direct counting and maximum likelihood methods, respectively. A total of 39 HLA-A, 66 HLA-B and 47 HLA-DRB1 alleles were identified. High-frequency alleles found at a frequency of ≥5% were 6 HLA-A (A*02:01, *02:06, *11:01, *24:02, *31:01 and *33:03), 6 HLA-B (B*15:01, *35:01, *44:03, *51:01, 54:01 and *58:01) and 8 HLA-DRB1 (DRB1*01:01, *04:05, *04:06, *07:01, *08:03, *09:01, *13:02 and *15:01) alleles. At each locus, A*02, B*15 and DRB1*14 generic groups were most diverse at allelic level, consisting of 9, 12 and 11 different alleles, respectively. A total of 366, 197 and 21 different HLA-A-B-DRB1 haplotypes were estimated with frequencies of ≥0.05%, ≥0.1% and ≥0.5%, respectively. The five most common haplotypes with frequencies of ≥2.0% were A*33:03-B*44:03-DRB1*13:02 (4.97%), A*33:03-B*58:01-DRB1*13:02, A*33:03-B*44:03-DRB1*07:01, A*24:02-B*07:02-DRB1*01:01 and A*24:02-B*52:01-DRB1*15:02. Among 34 serologic HLA-A-B-DR haplotypes with frequencies of ≥0.5%, 17 haplotypes revealed allele-level diversity and majority of the allelic variation was arising from A2, A26, B61, B62, DR4 and DR14 specificities. Haplotype diversity obtained in this study is the most comprehensive data thus far reported in Koreans, and the information will be useful for unrelated stem cell transplantation as well as for disease association studies. © 2016 John Wiley & Sons Ltd.

Germline Variation in HSD3B1 as a Novel Biomarker in Prostate Cancer

DTIC Science & Technology

2016-10-01

this work in Lancet Oncology . Our target time frame was 14 months for the first milestone: validation of the predictive value of HSD3B1 genotype in...professor sessions, radiation oncology grand rounds, and meetings with Dr. Sharifi and collaborators. Additionally, I have had the privilege of...Lancet Oncology ; Oct;17(10): 2016; 1435-1444. Federal funding support acknowledged. Books or other non-periodical, one time publications

Impact of Erb-B Signaling on Myelin Repair in the CNS Following Virus-Induced Damage

DTIC Science & Technology

2012-03-01

Amile-Lefond, C. and B. Jubelt. 2009. Neurologic manifestations of varicella zoster 303 virus infections. Curr Neurol Neurosci Rep 9: 430-434. 304 3...Taos, New Mexico , January 1999. . Drescher, K.M. - 10 29 Pavelko KD, McGavern DB, Drescher KM, David CS Rodriguez M. HLA-DQ8 enhances...Peptide, Taos, New Mexico , January 1999. 30 Das P, Drescher KM, Bradley DS, Rodriguez M, David CS. HLA-DR is critical for the induction of EAE, while

Application of derivative and derivative ratio spectrophotometry to simultaneous trace determination of rhodamine B and rhodamine 6G after dispersive liquid-liquid microextraction.

PubMed

Xiao, Ni; Deng, Jian; Huang, Kaihui; Ju, Saiqin; Hu, Canhui; Liang, Jun

2014-07-15

Two novel methods, first derivative spectrophotometric method ((1)D) and first derivative ratio spectrophotometric method ((1)DR), have been developed for the simultaneous trace determination of rhodamine B (RhB) and rhodamine 6G (Rh6G) in food samples after dispersive liquid-liquid microextraction (DLLME). The combination of derivative spectrophotometric techniques and DLLME procedure endows the presented methods with enhanced sensitivity and selectivity. Under optimum conditions, the linear calibration curves ranged from 5 to 450 ng mL(-1), with the correlation coefficients (r) of 0.9997 for RhB and 0.9977 for Rh6G by (1)D method, and 0.9987 for RhB and 0.9958 for Rh6G by (1)DR method, respectively. The calculated limits of detection (LODs) based on the variability of the blank solutions (S/N = 3 criterion) for 11 measurements were in the range of 0.48-1.93 ng mL(-1). The recoveries ranged from 88.1% to 111.6% (with RSD less than 4.4%) and 91.5-110.5% (with RSD less than 4.7%) for (1)D and (1)DR method, respectively. The influence of interfering substances such as foreign ions and food colorants which might be present in the food samples on the signals of RhB and Rh6G was examined. The developed methods have been successfully applied to the determination of RhB and Rh6G in black tea, red wine and chilli powder samples with the characteristics of simplicity, cost-effectiveness, environmental friendliness, and could be valuable for routine analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

DR Reactor VSR channel damage

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

Kempf, F.J.; Rawlins, J.K.

1961-10-30

On July 11, 1961 the Ball 3X System at DR Reactor was inadventently tripped. All vertical safety rods dropped and all channels were filled with balls. This report has the twofold purpose of documenting borescope observations of ten vertical rod channels at DR Reactor and recording the estimated extent of graphite damage resulting from the above incident. Channel damage data are presented on appended drawings. With suitable notations, the tracings of these drawings may be revised to reflect any future graphite damage. All vertical rod channels at DR Reactor were visually examined with a closed circuit television system during ballmore » removal efforts. Typical photographs of trapped balls and ledges, as viewed on the television monitor, are shown. Photographs of typical graphite damage, obtained through the borescope are also included in this report. 3 refs., 8 figs., 1 tab.« less

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.

Tryptophol induces death receptor (DR) 5-mediated apoptosis in U937 cells.

PubMed

Inagaki, Shyuichiro; Morimura, Shigeru; Tang, Yueqin; Akutagawa, Hiroshi; Kida, Kenji

2007-08-01

Tryptophol is a natural component isolated from vinegar produced from the boiled extract of black soybean. We have reported that tryptophol induces apoptosis in U937 cells via activation of caspase-8 followed by caspase-3. Tryptophol, however, did not affect human peripheral blood lymphocytes (PBL). In this study, we found that tryptophol enhances formation of a death-inducing signaling complex including death receptor (DR) 5. Cell viability and induction of apoptosis by tryptophol was reduced by transfection with decoy receptor (DcR) 1. These results indicate that tryptophol induces apoptosis through DR5 and that the resistance of PBL to tryptophol-induced apoptosis might be due to competition from DcR1.

Environmental Compliance Assessment and Management System (ECAMP), U.S. Air Force - German Supplement

DTIC Science & Technology

1993-10-01

ECP, was Associate Investigator. Dr. Diane K. Mann, CECER-ECP, is Acting Team Leader. Dr. John T. Bandy is Acting Chief, CECER-EC, and William D. Goran...Officer. (1)(3) Officer must discharge certain responsibilities - works toward improved safety on the installation (BImSchG, Section 58b). - informs the...objects, glass or mineral fibers, or materials in the form of webs or boards, including associated drying facilities, when the following are used: a

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

Hearing thresholds in patients with drug-resistant tuberculosis: baseline audiogram configurations and associations.

PubMed

Sogebi, Olusola Ayodele; Fadeyi, Muse Olatunbosun; Adefuye, Bolanle Olufunlola; Soyinka, Festus Olukayode

2017-01-01

To use baseline audiogram parameters in order to ascertain whether drug-resistant tuberculosis (DR-TB) has effects on hearing, as well as to describe the configurations of the audiograms and to determine whether there are parameters that can be associated with those configurations. This was a prospective study involving patients diagnosed with DR-TB at a tuberculosis treatment center in the state of Ogun, in Nigeria. The patients included in the study were submitted to pure tone audiometry at baseline (within two weeks after treatment initiation). For comparative analyses, data regarding demographic and clinical characteristics were collected from the medical records of the patients. The final sample comprised 132 patients. The mean age of the patients was 34.5 ± 12.6 years (range, 8-82 years), and the male:female ratio was 2:1. Of the 132 patients, 103 (78.0%) resided in neighboring states, 125 (94.7%) had previously experienced antituberculosis treatment failure, and 18 (13.6%) were retroviral-positive. Normal audiograms were found in 12 patients (9.1%), whereas sensorineural hearing loss was identified in 104 (78.8%), the two most common configurations being ascending, in 54 (40.9%), and sloping, in 26 (19.7%). Pure-tone averages at low frequencies (0.25-1.0 kHz) and high frequencies (2.0-8.0 kHz) were 33.0 dB and 40.0 dB, respectively. Regarding the degree of hearing loss in the better ear, 36 patients (27.3%) were classified as having normal hearing and 67 (50.8%) were classified as having mild hearing loss (26-40 dB), whereas 29 (21.9%) showed moderate or severe hearing loss. Among the variables studied (age, gender, retroviral status, previous treatment outcome, and weight at admission), only male gender was associated with audiometric configurations. In this sample of patients with DR-TB, most presented with bilateral, mild, suboptimal sensorineural hearing loss, and ascending/sloping audiometric configurations were associated with male gender. Utilizar parâmetros do audiograma basal para verificar se a tuberculose resistente (TB-R) tem efeitos na audição, descrever as configurações dos audiogramas e determinar se há parâmetros que possam ser associados a essas configurações. Estudo prospectivo com pacientes diagnosticados com TB-R em um centro de tratamento de tuberculose no estado de Ogun, Nigéria. Os pacientes incluídos no estudo foram submetidos à audiometria de tons puros em até duas semanas após o início do tratamento (audiometria basal). Características demográficas e clínicas foram coletadas dos prontuários médicos dos pacientes para análises comparativas. A amostra final envolveu 132 pacientes. A média de idade dos pacientes foi de 34,5 ± 12,6 anos (variação, 8-82 anos), e a razão homem:mulher foi de 2:1. A maioria dos pacientes (n = 103; 78,0%) residia nos estados vizinhos e tinha história de falha de tratamento antituberculose (n = 125; 94.7%); 18 (13.6%) apresentavam status retroviral positivo. Doze pacientes (9,1%) apresentaram audiogramas normais, e 104 (78,8%) apresentaram perda auditiva neurossensorial, sendo as configurações mais comuns do tipo ascendente, em 54 (40,9%), e descendente, em 26 (19,7%). As médias de tons puros em frequências baixas (0,25-1,0 kHz) e altas (2,0-8,0 kHz) foram de 33,0 dB e 40,0 dB, respectivamente. Quanto ao grau de perda auditiva no melhor ouvido, 36 pacientes (27,3%) apresentaram audição normal, e 67 (50,8%) apresentaram perda auditiva leve (26-40 dB), enquanto 29 (21,9%) mostraram perda auditiva moderada ou grave. Entre as variáveis estudadas (idade, gênero, status retroviral, desfecho de tratamento anterior e peso na admissão), somente o gênero masculino foi associado às configurações audiométricas. Nesta amostra de pacientes com TB-R, a maioria apresentou perda auditiva neurossensorial leve e subótima bilateralmente, com configurações audiométricas ascendentes/descendentes associadas ao gênero masculino.

Prefrontal left--dominant hemisphere--gamma and delta oscillators in general anaesthesia with volatile anaesthetics during open thoracic surgery.

PubMed

Saniova, Beata; Drobny, Michal; Drobna, Eva; Hamzik, Julian; Bakosova, Erika; Fischer, Martin

2016-01-01

The main objective was to indicate sufficient general anaesthesia (GA) inhibition for negative experience rejection in GA. We investigated the group of patients (n = 17, mean age 63.59 years, 9 male--65.78 years, 8 female - 61.13 years) during GA in open thorax surgery and analyzed EEG signal by power spectrum (pEEG) delta (DR), and gamma rhythms (GR). EEG was performed: OPO - the day before surgery and in surgery phases OP1-OP5 during GA. Particular GA phases: OP1 = after pre- medication, OP2 = surgery onset, OP3 = surgery with one-side lung ventilation, OP4 = end of surgery, both sides ventilation, OP5 = end of GA. pEEG registering in the left frontal region Fp1-A1 montage in 17 right handed persons. Mean DR power in OP2 phase is significantly higher than in phase OP5 and mean DR power in OP3 is higher than in OP5. One-lung ventilation did not change minimal alveolar concentration and gases should not accelerate decrease in mean DR power. Higher mean value of GR power in OPO than in OP3 was statistically significant. Mean GR power in OP3 is statistically significantly lower than in OP4 correlating with the same gases concentration in OP3 and OP4. Our results showed DR power decreased since OP2 till the end of GA it means inhibition represented by power DR fluently decreasing is sufficient for GA depth. GR power decay near the working memory could reduce conscious cognition and unpleasant explicit experience in GA.

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.

Transcervical Inoculation with Chlamydia trachomatis Induces Infertility in HLA-DR4 Transgenic and Wild-Type Mice.

PubMed

Pal, Sukumar; Tifrea, Delia F; Zhong, Guangming; de la Maza, Luis M

2018-01-01

Chlamydia trachomatis is the leading cause of infection-induced infertility in women. Attempts to control this epidemic with screening programs and antibiotic therapy have failed. Currently, a vaccine to prevent C. trachomatis infections is not available. In order to develop an animal model for evaluating vaccine antigens that can be applied to humans, we used C. trachomatis serovar D (strain UW-3/Cx) to induce infertility in mice whose major histocompatibility complex class II antigen was replaced with the human leukocyte antigen DR4 (HLA-DR4). Transcervical inoculation of medroxyprogesterone-treated HLA-DR4 transgenic mice with 5 × 10 5 C. trachomatis D inclusion forming units (IFU) induced a significant reduction in fertility, with a mean number of embryos/mouse of 4.4 ± 1.3 compared to 7.8 ± 0.5 for the uninfected control mice ( P < 0.05). A similar fertility reduction was elicited in the wild-type (WT) C57BL/6 mice (4.3 ± 1.4 embryos/mouse) compared to the levels of the WT controls (9.1 ± 0.4 embryos/mouse) ( P < 0.05). Following infection, WT mice mounted more robust humoral and cellular immune responses than HLA-DR4 mice. As determined by vaginal shedding, HLA-DR4 mice were more susceptible to a transcervical C. trachomatis D infection than WT mice. To assess if HLA-DR4 transgenic and WT mice could be protected by vaccination, 10 4 IFU of C. trachomatis D was delivered intranasally, and mice were challenged transcervically 6 weeks later with 5 × 10 5 IFU of C. trachomatis D. As determined by severity and length of vaginal shedding, WT C57BL/6 and HLA-DR4 mice were significantly protected by vaccination. The advantages and limitations of the HLA-DR4 transgenic mouse model for evaluating human C. trachomatis vaccine antigens are discussed. Copyright © 2017 American Society for Microbiology.

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

Implementation and Evaluation of a Large-Scale Teleretinal Diabetic Retinopathy Screening Program in the Los Angeles County Department of Health Services

PubMed Central

Vasquez, Carolina; Martinez, Carlos; Tseng, Chi-Hong; Mangione, Carol M.

2017-01-01

Importance Diabetic retinopathy (DR) is the leading cause of blindness in adults of working age in the United States. In the Los Angeles County safety net, a nonvertically integrated system serving underinsured and uninsured patients, the prevalence of DR is approximately 50%, and owing to limited specialty care resources, the average wait times for screening for DR have been 8 months or more. Objective To determine whether a primary care–based teleretinal DR screening (TDRS) program reduces wait times for screening and improves timeliness of needed care in the Los Angeles County safety net. Design, Setting, and Participants Quasi-experimental, pretest-posttest evaluation of exposure to primary care–based TDRS at 5 of 15 Los Angeles County Department of Health Services safety net clinics from September 1, 2013, to December 31, 2015, with a subgroup analysis of random samples of 600 patients before and after the intervention (1200 total). Exposure Primary care clinic–based teleretinal screening for DR. Main Outcomes and Measures Annual rates of screening for DR before and after implementation of the TDRS program across the 5 clinics, time to screening for DR in a random sample of patients from these clinics, and a description of the larger framework of program implementation. Results Among the 21 222 patients who underwent the screening (12 790 female, 8084 male, and 348 other gender or not specified; mean [SD] age, 57.4 [9.6] years), the median time to screening for DR decreased from 158 days (interquartile range, 68-324 days) before the intervention to 17 days (interquartile range, 8-50 days) after initiation of the program (P < .001). Overall annual screening rates for DR increased from 5942 of 14 633 patients (40.6%) before implementation to 7470 of 13 133 patients (56.9%) after initiation of the program at all 15 targeted clinics (odds ratio, 1.9; 95% CI, 1.3-2.9; P = .002). Of the 21 222 patients who were screened, 14 595 (68.8%) did not require referral to an eye care professional, 4160 (19.6%) were referred for treatment or monitoring of DR, and 2461 (11.6%) were referred for other ophthalmologic conditions. Conclusions and Relevance A digital TDRS program was successfully implemented for the largest publicly operated county safety net population in the United States, resulting in the elimination of the need for more than 14 000 visits to specialty care professionals, a 16.3% increase in annual rates of screening for DR, and an 89.2% reduction in wait times for screening. Teleretinal DR screening programs have the potential to maximize access and efficiency in the safety net, where the need for such programs is most critical. PMID:28346590

Laminarin-induced apoptosis in human colon cancer LoVo cells.

PubMed

Ji, Chen-Feng; Ji, Yu-Bin

2014-05-01

A number of scientific studies have revealed that laminarin has antitumor effects. Therefore, the aim of the present study was to investigate the apoptosis of LoVo cells and the underlying mechanisms induced by laminarin. LoVo cells were treated with various concentrations of laminarin and fluorescence-inverted microscopy was used to observe the morphology of LoVo cells treated with laminarin. In addition, western blotting was performed to analyze the expression levels of death receptor (DR)4, DR5, TNF-related apoptosis-inducing ligand (TRAIL), Fas-associated protein with death domain (FADD), caspase-8, caspase-3, Bid and tBid. Flow cytometry was conducted to analyze the expressions of Bcl-2 and Bax, and spectrophotometry was performed to quantify the activity of caspases-8, -3, -6 and -7. Following the treatment of LoVo cells with laminarin for 24 h, the expression levels of DR4, DR5, TRAIL, FADD, Bid, tBid and Bax were observed to be upregulated, whereas the expression levels of pro-caspase-8, pro-caspase-3 and Bcl-2 were downregulated. In addition, the activities of casapse-8, -3, -6 and -7 were observed to increase, which was a significant difference when compared with those of the control group. Therefore, laminarin is considered to induce the apoptosis of LoVo cells, which may occur via a DR pathway, suggesting that laminarin may be a potent agent for cancer treatment.

Laminarin-induced apoptosis in human colon cancer LoVo cells

PubMed Central

JI, CHEN-FENG; JI, YU-BIN

2014-01-01

A number of scientific studies have revealed that laminarin has antitumor effects. Therefore, the aim of the present study was to investigate the apoptosis of LoVo cells and the underlying mechanisms induced by laminarin. LoVo cells were treated with various concentrations of laminarin and fluorescence-inverted microscopy was used to observe the morphology of LoVo cells treated with laminarin. In addition, western blotting was performed to analyze the expression levels of death receptor (DR)4, DR5, TNF-related apoptosis-inducing ligand (TRAIL), Fas-associated protein with death domain (FADD), caspase-8, caspase-3, Bid and tBid. Flow cytometry was conducted to analyze the expressions of Bcl-2 and Bax, and spectrophotometry was performed to quantify the activity of caspases-8, -3, -6 and -7. Following the treatment of LoVo cells with laminarin for 24 h, the expression levels of DR4, DR5, TRAIL, FADD, Bid, tBid and Bax were observed to be upregulated, whereas the expression levels of pro-caspase-8, pro-caspase-3 and Bcl-2 were downregulated. In addition, the activities of casapse-8, -3, -6 and -7 were observed to increase, which was a significant difference when compared with those of the control group. Therefore, laminarin is considered to induce the apoptosis of LoVo cells, which may occur via a DR pathway, suggesting that laminarin may be a potent agent for cancer treatment. PMID:24765209

Official Guard and Reserve Manpower Strengths and Statistics, Fiscal Year 2010 Summary

DTIC Science & Technology

2010-01-01

OU)r-r-ooinin \\DCD^(^COininWU)\\flhhCDCOaiOaɛim^ COrn <’lOhU)U1H(N|>li)’JO<J30llOiNU)OCNn<N ooocftrHinMMcno»H^MrHU)or^w^pi^or^OrHui(»\\Dr>i^r^rnoor...Olilr1NClcoal0^ort^^flln^ ooo(^l^Kl^ coB )^^^^cD^^co^colnnfO(n^^oalcoln^a)1’^mrl^^oHoolnflDlfl^ oinooocDaDr-vocrtr4coa3oocN(Nr-<Nmomf^oor^ina^fninooo-<j

Determination of the Complex Elastic Moduli of Materials Using A Free- Free Bar Technique

DTIC Science & Technology

1994-03-01

LCDR, Dr. D. L alner 1 Dept. of Physics (Code PH) Naval Postgrdumt School Monterey, CA 93943 10 . Cgimd Ofric. Naval Reserh Labrary ATI’N: Dr. N...Postgraduate School ( fAp~hicbl) Naval Postgraduate School 6c. ADDRESS MclY- $Mae, 02t c7;w 3 7b. ADDRESS (city, MUk and ii? code) Mogntere CA 93943-5=0...Monery CA 93943-5000 Sa. NAME OF FUNDDOISIONS0R]NG G. OFMiCE SYMBOL 9. FUU1ENIICMN IDTFCTONNUMBER ORGANUAT1ON j (If Appkiabie) NSWC. CRANE. NPS

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.

Delivery Ring Lattice Modifications for Transitionless Deceleration

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

Johnstone, J. A.; Syphers, M. J.

2016-10-09

A portion of the remnant Tevatron program infrastruc- ture at Fermilab is being reconfigured to be used for the generation and delivery of proton and muon beams for new high-precision particle physics experiments. With the 8 GeV Booster as its primary source, the Mu2e exper- iment will receive 8.9 GeV/c bunched beam on target, after being stored and slow spilled from the Delivery Ring (DR) -- a refurbished debuncher ring from Tevatron anti- proton production. For the Muon g-2 experiment, the DR will be tuned for 3.1 GeV/c to capture muons off of a target before sending them to thismore » experiment's Storage Ring. The apertures in the beam transport systems are optimized for the large muon beams of this lower-energy experiment. In order to provide further flexibility in the operation of the DR for future possible low-energy, high- intensity particle physics experiments (REDTOP[1], for example) and detector development, investigations are underway into the feasibility of decelerating beams from its maximum kinetic energy of 8 GeV level to lower en- ergies, down to 1-2 GeV. In this paper we look at possi- ble lattice modifications to the DR to avoid a transition crossing during the deceleration process. Hardware re- quirements and other operational implications of this scheme will also be discussed.« less

Prognostic Impact of the Combination of Recurrence Score and Quantitative Estrogen Receptor Expression (ESR1) on Predicting Late Distant Recurrence Risk in Estrogen Receptor–Positive Breast Cancer After 5 Years of Tamoxifen: Results From NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-28 and B-14

PubMed Central

Wolmark, Norman; Baehner, Frederick L.; Butler, Steven M.; Tang, Gong; Jamshidian, Farid; Sing, Amy P.; Shak, Steven; Paik, Soonmyung

2016-01-01

Purpose We determined the utility of the 21-Gene Recurrence Score (RS) in predicting late (> 5 years) distant recurrence (LDR) in stage I and II breast cancer within high and low-ESR1–expressing groups. Patients and Methods RS was assessed in chemotherapy/tamoxifen-treated, estrogen receptor (ER) –positive, node-positive National Surgical Adjuvant Breast and Bowel Project B-28 patients and tamoxifen-treated, ER-positive, node-negative B-14 patients. The association of the RS with risk of distant recurrence (DR) 0 to 5 years and those at risk > 5 years was assessed. An ESR1 expression cut point was optimized in B-28 and tested in B-14. Results Median follow-up was 11.2 years for B-28 and 13.9 years for B-14. Of 1,065 B-28 patients, 36% had low (< 18), 34% intermediate (18 to 30), and 30% high (≥ 31) RS. Of 668 B-14 patients, 51% had low, 22% intermediate, and 27% high RS. Median ESR1 expression by reverse transcriptase polymerase chain reaction was: B-28, 9.7 normalized expression cycle threshold units (CT) and B-14, 10.7 CT. In B-28, RS was associated with DR 0 to 5 years (log-rank P < .001) and > 5 to 10 years (log-rank P = .02) regardless of ESR1 expression. An ESR1 expression cut point of 9.1 CT was identified in B-28. It was validated in B-14 patients for whom the RS was associated with DR in years 5 to 15: 6.8% (95% CI, 4.4% to 10.6%) versus 11.2% (95% CI, 6.2% to 19.9%) versus 16.4% (95% CI, 10.2% to 25.7%) for RS < 18, RS 18 to 30, and RS ≥ 31, respectively (log-rank P = .01). Conclusion For LDR, RS is strongly prognostic in patients with higher quantitative ESR1. Risk of LDR is relatively low for patients with low RS. These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high RS with higher ESR1 expression at initial diagnosis. PMID:27217450

Prognostic Impact of the Combination of Recurrence Score and Quantitative Estrogen Receptor Expression (ESR1) on Predicting Late Distant Recurrence Risk in Estrogen Receptor-Positive Breast Cancer After 5 Years of Tamoxifen: Results From NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-28 and B-14.

PubMed

Wolmark, Norman; Mamounas, Eleftherios P; Baehner, Frederick L; Butler, Steven M; Tang, Gong; Jamshidian, Farid; Sing, Amy P; Shak, Steven; Paik, Soonmyung

2016-07-10

We determined the utility of the 21-Gene Recurrence Score (RS) in predicting late (> 5 years) distant recurrence (LDR) in stage I and II breast cancer within high and low-ESR1-expressing groups. RS was assessed in chemotherapy/tamoxifen-treated, estrogen receptor (ER) -positive, node-positive National Surgical Adjuvant Breast and Bowel Project B-28 patients and tamoxifen-treated, ER-positive, node-negative B-14 patients. The association of the RS with risk of distant recurrence (DR) 0 to 5 years and those at risk > 5 years was assessed. An ESR1 expression cut point was optimized in B-28 and tested in B-14. Median follow-up was 11.2 years for B-28 and 13.9 years for B-14. Of 1,065 B-28 patients, 36% had low (< 18), 34% intermediate (18 to 30), and 30% high (≥ 31) RS. Of 668 B-14 patients, 51% had low, 22% intermediate, and 27% high RS. Median ESR1 expression by reverse transcriptase polymerase chain reaction was: B-28, 9.7 normalized expression cycle threshold units (CT) and B-14, 10.7 CT. In B-28, RS was associated with DR 0 to 5 years (log-rank P < .001) and > 5 to 10 years (log-rank P = .02) regardless of ESR1 expression. An ESR1 expression cut point of 9.1 CT was identified in B-28. It was validated in B-14 patients for whom the RS was associated with DR in years 5 to 15: 6.8% (95% CI, 4.4% to 10.6%) versus 11.2% (95% CI, 6.2% to 19.9%) versus 16.4% (95% CI, 10.2% to 25.7%) for RS < 18, RS 18 to 30, and RS ≥ 31, respectively (log-rank P = .01). For LDR, RS is strongly prognostic in patients with higher quantitative ESR1. Risk of LDR is relatively low for patients with low RS. These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high RS with higher ESR1 expression at initial diagnosis. © 2016 by American Society of Clinical Oncology.

Effect of HLA-C and DQ matching on Pediatric Heart Transplant Graft Survival

PubMed Central

Butts, Ryan J.; Savage, Andrew J.; Nietert, Paul J.; Kavarana, Minoo; Moussa, Omar; Burnette, Ali L.; Atz, Andrew M.

2014-01-01

Background Higher degree of HLA matching at the A, B, and DR-loci has been associated with improved long-term survival after pediatric heart transplantation in multiple ISHLT registry reports. The aim of this study was to investigate the association of HLA matching at the C and DQ loci with pediatric graft survival. Methods The UNOS database was queried for isolated heart transplants that occurred from 1988 to 2012 with a recipient age of 17 or less and at least one postoperative follow up encounter. When analyzing HLA matching at the C or DQ loci, only those transplants with complete typing of donor and recipient at the respective loci were included. Transplants were divided into patients with at least one match at the C-locus (C-match) versus no match (C-no), and at least one match at the DQ locus versus no match (DQ-match versus DQ-no). Primary outcome was graft loss. Univariate analysis was performed with log-rank test. Cox regression analysis was performed with following patient factors included in the model: recipient age, ischemic time; recipient on ventilator, ECMO, ventricular assist device or inotropes at transplant; recipient serum bilirubin and creatinine closest to transplant, donor-recipient weight ratio, underlying cardiac diagnosis, crossmatch results, transplant year, and HLA matching at the A, B, and DR loci. Results Complete typing at the C-locus occurred in 2429/4731 (51%) transplants and 3498/4731 (74%) transplants had complete typing at the DQ locus. C-match did not differ from C-no with respect to patient factors, except for year of transplant; [C-match median year 2007 (IQR 1997–2010) vs. C-no median year 2005 (IQR 1996–2009), p=0.03] and degree of HLA matching at A, B, and DR loci (11.9% of C-match with high level of HLA matching v. 3% of C-no, p<0.01). Matching at the C-locus was not associated with decreased risk of graft loss [C-no median graft survival 13.1 yrs (95%CI 11.5–14.8) vs. C-match 15.1 yrs (95%CI 13.5–16.6) p=0.44, log-rank, hazard ratio 0.93 (95%CI 0.76–1.15, p=0.52)]. DQ-match did not differ from DQ-no in any of the above-mentioned patient factors, except DQ-match was more likely to have high degree of matching at the A, B, and DR loci versus DQ-no (9.8% v. 3.2%, p<0.01). Matching at the DQ-locus was not associated with decreased risk of graft loss [DQ-no median graft survival 13.1yrs (95%CI 11.7–14.6) vs. DQ-match 13.0 yrs (11.4–14.6) p=0.80, log rank, hazard ratio 0.95 (0.81–1.1), p=0.51]. Conclusion Complete typing at the C-locus of both donor and recipient occurs less often then typing at the DQ locus. A higher degree of donor-recipient HLA matching at the C-locus or the DQ-locus appears not to confer any graft survival advantage. PMID:25128416

Calcium dobesilate prevents the oxidative stress and inflammation induced by diabetes in the retina of db/db mice.

PubMed

Bogdanov, Patricia; Solà-Adell, Cristina; Hernández, Cristina; García-Ramírez, Marta; Sampedro, Joel; Simó-Servat, Olga; Valeri, Marta; Pasquali, Christian; Simó, Rafael

2017-10-01

Calcium dobesilate (CaD) is beneficial in early stages of diabetic retinopathy (DR), but its mechanisms of action remains to be elucidated. The aim was to investigate the effect of CaD on proinflammatory cytokines and oxidative stress. db/db mice were randomly assigned to daily oral treatment with CaD (200mg/kg/day) or vehicle for 15days. Biomarkers of oxidative stress (dihydroethidium, malondialdehyde), NF-κB, and proinflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α, MCP-1) were examined in the retina by immunohistochemical analysis. Cultures of human retinal endothelial cells (HRECs) were used for complementary experiments. CaD significantly reduced the biomarkers of oxidative stress in the retina of db/db mice. In addition, CaD prevented the increase of NF-κB, IL-6, IL-8, TNF-α and MCP-1 induced by diabetes. CaD inhibited the activation of NF-kβ induced by IL-1β by preventing IKKB-α phosphorylation in HRECs and reduced the upregulation of IL-6 and IL-18 induced by TNF-α in a dose-dependent manner. Our results suggest that antioxidant and antiinflammatory effects are crucial in accounting for the effectiveness of CaD for treating DR. Copyright © 2017 Elsevier Inc. All rights reserved.

Application of derivative and derivative ratio spectrophotometry to simultaneous trace determination of rhodamine B and rhodamine 6G after dispersive liquid-liquid microextraction

NASA Astrophysics Data System (ADS)

Xiao, Ni; Deng, Jian; Huang, Kaihui; Ju, Saiqin; Hu, Canhui; Liang, Jun

2014-07-01

Two novel methods, first derivative spectrophotometric method (1D) and first derivative ratio spectrophotometric method (1DR), have been developed for the simultaneous trace determination of rhodamine B (RhB) and rhodamine 6G (Rh6G) in food samples after dispersive liquid-liquid microextraction (DLLME). The combination of derivative spectrophotometric techniques and DLLME procedure endows the presented methods with enhanced sensitivity and selectivity. Under optimum conditions, the linear calibration curves ranged from 5 to 450 ng mL-1, with the correlation coefficients (r) of 0.9997 for RhB and 0.9977 for Rh6G by 1D method, and 0.9987 for RhB and 0.9958 for Rh6G by 1DR method, respectively. The calculated limits of detection (LODs) based on the variability of the blank solutions (S/N = 3 criterion) for 11 measurements were in the range of 0.48-1.93 ng mL-1. The recoveries ranged from 88.1% to 111.6% (with RSD less than 4.4%) and 91.5-110.5% (with RSD less than 4.7%) for 1D and 1DR method, respectively. The influence of interfering substances such as foreign ions and food colorants which might be present in the food samples on the signals of RhB and Rh6G was examined. The developed methods have been successfully applied to the determination of RhB and Rh6G in black tea, red wine and chilli powder samples with the characteristics of simplicity, cost-effectiveness, environmental friendliness, and could be valuable for routine analysis.

Potential Therapeutic Roles for Inhibition of the PI3K/Akt/mTOR Pathway in the Pathophysiology of Diabetic Retinopathy

PubMed Central

Jacot, Jorge L.; Sherris, David

2011-01-01

Novel therapeutics such as inhibitors of PI3K/Akt/mTOR pathway presents a unique opportunity for the management of diabetic retinopathy (DR). Second generation mTOR inhibitors have the prospect to be efficacious in managing various stages of disease progression in DR. During early stages, the mTOR inhibitors suppress HIF-1α, VEGF, leakage, and breakdown of the blood-retinal barrier. These mTOR inhibitors impart a pronounced inhibitory effect on inflammation, an early component with diverse ramifications influencing the progression of DR. These inhibitors suppress IKK and NF-κB along with downstream inflammatory cytokines, chemokines, and adhesion molecules. In proliferative DR, mTOR inhibitors suppress several growth factors that play pivotal roles in the induction of pathological angiogenesis. Lead mTOR inhibitors in clinical trials for ocular indications present an attractive treatment option for chronic use in DR with favorable safety profile and sustained ocular pharmacokinetics following single dose. Thereby, reducing dosing frequency and risk associated with chronic drug administration. PMID:22132311

U.S. Army Medical Research Institute of Infectious Diseases Annual Report, Fiscal Year 1986

DTIC Science & Technology

1986-10-01

determined. SUMMARY Strains of mice sensitive (A/J) and resistant (C3H/HeN) to C. burnetii were given varying doses of the phase 1, 9 Mile isolate...ASSOCIATE INVESTIGATORS: J. W. Ezzell , Ph.D. B. E. Ivins, Ph.D. As previously reported by Dr. Ezzell , a 93-kd extractable protein (EAI) is the principal...challenge. The following work has been carried out by Dr. Bruce Ivins in cooperation with Susan Welkos, Steve Little, John Ezzell , and Greg Knudson of

Dissociative recombination of HCl+, H2Cl+, DCl+, and D2Cl+ in a flowing afterglow

NASA Astrophysics Data System (ADS)

Wiens, Justin P.; Miller, Thomas M.; Shuman, Nicholas S.; Viggiano, Albert A.

2016-12-01

Dissociative recombination of electrons with HCl+, H2Cl+, DCl+, and D2Cl+ has been measured under thermal conditions at 300, 400, and 500 K using a flowing afterglow-Langmuir probe apparatus. Measurements for HCl+ and DCl+ employed the variable electron and neutral density attachment mass spectrometry (VENDAMS) method, while those for H2Cl+ and D2Cl+ employed both VENDAMS and the more traditional technique of monitoring electron density as a function of reaction time. At 300 K, HCl+ and H2Cl+ recombine with kDR = 7.7±2.14.5 × 10-8 cm3 s-1 and 2.6 ± 0.8 × 10-7 cm3 s-1, respectively, whereas D2Cl+ is roughly half as fast as H2Cl+ with kDR = 1.1 ± 0.3 × 10-7 cm3 s-1 (2 σ confidence intervals). DCl+ recombines with a rate coefficient below the approximate detection limit of the method (≲5 × 10-8 cm3 s-1) at all temperatures. Relatively slow dissociative recombination rates have been speculated to be responsible for the large HCl+ and H2Cl+ abundances in interstellar clouds compared to current astrochemical models, but our results imply that the discrepancy must originate elsewhere.

Analysis of Duck Hepatitis B Virus Reverse Transcription Indicates a Common Mechanism for the Two Template Switches during Plus-Strand DNA Synthesis

PubMed Central

Havert, Michael B.; Ji, Lin; Loeb, Daniel D.

2002-01-01

The synthesis of the hepadnavirus relaxed circular DNA genome requires two template switches, primer translocation and circularization, during plus-strand DNA synthesis. Repeated sequences serve as donor and acceptor templates for these template switches, with direct repeat 1 (DR1) and DR2 for primer translocation and 5′r and 3′r for circularization. These donor and acceptor sequences are at, or near, the ends of the minus-strand DNA. Analysis of plus-strand DNA synthesis of duck hepatitis B virus (DHBV) has indicated that there are at least three other cis-acting sequences that make contributions during the synthesis of relaxed circular DNA. These sequences, 5E, M, and 3E, are located near the 5′ end, the middle, and the 3′ end of minus-strand DNA, respectively. The mechanism by which these sequences contribute to the synthesis of plus-strand DNA was unclear. Our aim was to better understand the mechanism by which 5E and M act. We localized the DHBV 5E element to a short sequence of approximately 30 nucleotides that is 100 nucleotides 3′ of DR2 on minus-strand DNA. We found that the new 5E mutants were partially defective for primer translocation/utilization at DR2. They were also invariably defective for circularization. In addition, examination of several new DHBV M variants indicated that they too were defective for primer translocation/utilization and circularization. Thus, this analysis indicated that 5E and M play roles in both primer translocation/utilization and circularization. In conjunction with earlier findings that 3E functions in both template switches, our findings indicate that the processes of primer translocation and circularization share a common underlying mechanism. PMID:11861843

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.

Gene Copy-Number Variations (CNVs) of Complement C4 and C4A Deficiency in Genetic Risk and Pathogenesis of Juvenile Dermatomyositis

PubMed Central

Lintner, Katherine E.; Patwardhan, Anjali; Rider, Lisa G.; Abdul-Aziz, Rabheh; Wu, Yee Ling; Lundström, Emeli; Padyukov, Leonid; Zhou, Bi; Alhomosh, Alaaedin; Newsom, David; White, Peter; Jones, Karla B.; O’Hanlon, Terrance P.; Miller, Frederick W.; Spencer, Charles H.; Yu, C. Yung

2017-01-01

Objective Complement-mediated vasculopathy of muscle and skin are clinical features of juvenile dermatomyositis (JDM). We assess gene copy-number variations (CNVs) for complement C4 and its isotypes, C4A and C4B, in genetic risks and pathogenesis of JDM. Methods The study population included 105 JDM patients and 500 healthy European Americans. Gene copy-numbers (GCNs) for total C4, C4A, C4B and HLA-DRB1 genotypes were determined by Southern blots and PCRs. Processed activation product C4d bound to erythrocytes (E-C4d) was measured by flow cytometry. Global gene-expression microarrays were performed in 19 JDM and 7 controls using PAXgene-blood RNA. Differential expression levels for selected genes were validated by qPCR. Results Significantly lower GCNs and differences in distribution of GCN groups for total C4 and C4A were observed between JDM and controls. Lower GCN of C4A in JDM remained among HLA DR3-positive subjects (p=0.015). Homozygous or heterozygous C4A-deficiency was present in 40.0% of JDM compared to 18.2% of controls [odds ratio (OR)=3.00 (1.87–4.79), p=8.2x10−6]. JDM had higher levels of E-C4d than controls (p=0.004). In JDM, C4A-deficient subjects had higher levels of E-C4d (p=0.0003) and higher frequency of elevated levels of multiple serum muscle enzymes at diagnosis (p=0.004). Microarray profiling of blood RNA revealed upregulation of type I Interferon-stimulated genes and lower abundance of transcripts for T-cell and chemokine function genes in JDM, but this was less prominent among C4A-deficient or DR3-positive patients. Conclusions Complement C4A-deficiency appears to be an important factor for the genetic risk and pathogenesis of JDM, particularly in patients with a DR3-positive background. PMID:26493816

Role of Raf-1 Signaling in Breast Cancer - Progression to Estrogen Independent Growth

DTIC Science & Technology

1998-07-01

activity of the JNK/SAPK signaling pathway. Cell, 81:1137-1146, 1995. 84. Sanchez , I., Hughes, R.T., Mayer, B.J., Yee, K., Woodgett, J.R., Avruch, J...phosphorylation of Bad on Ser136 [In Process Citation]. Curr. Biol. 8: 779-782, 1998. 99. Moscatello, D.K., Holgado -Madruga, M., Emlet, D.R

Dyslipidemia and Diabetic Retinopathy

PubMed Central

Chang, Yo-Chen; Wu, Wen-Chuan

2013-01-01

Diabetic retinopathy (DR) is one of the major microvascular complications of diabetes. In developed countries, it is the most common cause of preventable blindness in diabetic adults. Dyslipidemia, a major systemic disorder, is one of the most important risk factors for cardiovascular disease. Patients with diabetes have an increased risk of suffering from dyslipidemia concurrently. The aim of this article is to review the association between diabetic retinopathy (DR) and traditional/nontraditional lipid markers, possible mechanisms involving lipid metabolism and diabetic retinopathy, and the effect of lipid-lowering therapies on diabetic retinopathy. For traditional lipid markers, evidence is available that total cholesterol and low-density lipoprotein cholesterol are associated with the presence of hard exudates in patients with DR. The study of nontraditional lipid markers is advancing only in recently years. The severity of DR is inversely associated with apolipoprotein A1 (ApoA1), whereas ApoB and the ApoB-to-ApoA1 ratio are positively associated with DR. The role of lipid-lowering medication is to work as adjunctive therapy for better control of diabetes-related complications including DR. PMID:24380088

78 FR 20319 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-04

... with provisions set forth in Section 552b(c) (4) and (6), Title 5 U.S.C., and the Determination of the...''. Contact Person for More Information: Jane Suen, Dr.P.H., M.S., M.P.H., Scientific Review Officer, CDC... Doc. 2013-07827 Filed 4-3-13; 8:45 am] BILLING CODE 4163-18-P ...

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

Comprehensive Synchronization Elimination for Java (PREPRINT)

DTIC Science & Technology

2003-01-01

e : % thread-local % reentrant % enclosed Figure...0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 ca ss ow ar y ja va c ja va cu p ja va do c jg l jle x pi zz a ar ra y in st an td b jlo go pl as m a sl ic e Figure 6...1998. [DR98] P. Diniz and M. Rinard. Lock Coarsening: Eliminating Lock Overhead in Automatically Parallelized Object-based Programs. In Journal

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

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.

Treatment outcomes of drug-resistant tuberculosis patients in Kenya.

PubMed

Mibei, D J; Kiarie, J W; Wairia, A; Kamene, M; Okumu, M E

2016-11-01

Successful treatment of drug-resistant tuberculosis (DR-TB) is crucial in preventing disease transmission and reducing related morbidity and mortality. A standardised DR-TB treatment regimen is used in Kenya. Although patients on treatment are monitored, no evaluation of factors affecting treatment outcomes has yet been performed. To analyse treatment outcomes of DR-TB patients in Kenya and factors associated with successful outcome. Retrospective analysis of secondary data from Kenya's National Tuberculosis, Leprosy and Lung disease programme. DR-TB data from the national database for January to December 2012 were reviewed. Of 205 DR-TB patients included in the analysis, 169 (82.4%) had a successful treatment outcome, 18 (9%) died and 18 (9%) were lost to follow-up. Only sex (P = 0.006) and human immunodeficiency virus (HIV) status (P = 0.008) were predictors of successful treatment. Females were more likely to attain treatment success (OR 3.86, 95%CI 1.47-10.12), and HIV-negative status increased the likelihood of successful treatment (OR 3.53, 95%CI 1.4-8.9). Treatment success rates were higher than World Health Organization targets. Targeted policies for HIV-positive patients and males will improve treatment outcomes in these groups.

Immunomodulatory effect of the topical ophthalmic Janus kinase inhibitor tofacitinib (CP-690,550) in patients with dry eye disease.

PubMed

Huang, Jing-Feng; Yafawi, Rolla; Zhang, Min; McDowell, Michael; Rittenhouse, Kay D; Sace, Frederick; Liew, Shiao Hui Melissa; Cooper, Scott R; Pickering, Eve H

2012-07-01

To evaluate the immunomodulatory effect of topical ophthalmic tofacitinib (CP-690,550) after an 8-week treatment period in patients with dry eye disease (DED). Biomarker substudy of a phase 1/2 prospective, randomized, vehicle- and comparator-controlled clinical trial (NCT00784719). A total of 82 patients with moderate to severe DED enrolled. Patients received 1 of 5 doses of tofacitinib (0.0003%, 0.001%, 0.003%, or 0.005% twice daily [BID] or 0.005% once daily [QD]), active comparator (cyclosporine ophthalmic emulsion, 0.05% [Restasis, Allergan Inc., Irvine, CA]), or vehicle control BID for 8 weeks. Conjunctival impression cytology and tear fluid samples were collected at baseline and after an 8-week treatment period. Conjunctival cells were analyzed by flow cytometry for human leukocyte antigen DR-1 (HLA-DR). Tear fluids were analyzed by microsphere-based immunoassays for tear levels of cytokines and inflammation markers. Reduction in inflammation assessed by change from baseline in conjunctival cell surface level of HLA-DR and tear level of cytokines and inflammation markers. At week 8, a decrease in conjunctival cell surface expression of HLA-DR was observed in patients treated with tofacitinib 0.005% QD and 0.003% BID: 71% and 67% of baseline, respectively, compared with 133% of baseline in patients treated with vehicle (P=0.023 and P=0.006, compared with vehicle, respectively). Matrix metalloproteinase (MMP)-3 in tears was reduced from baseline at week 8 (40% of baseline, P=0.035) in the tofacitinib 0.005% QD group, whereas the vehicle group showed 77% of baseline (P>0.20). Interleukin (IL)-1β in tears was 36% of baseline (P=0.053) in the tofacitinib 0.005% QD group and 95% of baseline (P > 0.20) in the vehicle group. Several other cytokines and inflammation markers in tears, including MMP-9, IL-15, IL-17A, and IL-12p70, were markedly reduced in the tofacitinib 0.005% QD group but not the vehicle group. There was an association between the changes in HLA-DR and the tear inflammation markers (P<0.05): HLA-DR with IL-12p70 (r=0.49) and IL-1β (r=0.46), IL-12p70 with IL-1β (r=0.90), and IL-17A with MMP-9 (r=0.82). Topical ophthalmic tofacitinib may act as an immunomodulator in patients with DED. Treatment for 8 weeks showed a promising reduction of conjunctival cell surface HLA-DR expression and tear levels of proinflammatory cytokines and inflammation markers. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Raman Spectroscopic Study of Molecular Orientation in Vitreous B2O3 Films.

DTIC Science & Technology

1981-07-10

upQ, and the squares of its elements, which are proportional to the experi- mental Razman intensities, are elements of the tensor a 2,where:Si j k 2...California 94720 Mr . Robert W. Jones Advanced Projects anager Dr. Turis W. Frank Hughes Aircraft Company De t. ,nt ’f Chemical Engineering Mail...Dr. George Sandoz Attn: Mr . Joe McCartney 536 S. Clark Street San Diego, California 92152 Chicago, Illinois 60605 1 Naval Weapons Center ONR Area

Lupus nephritis susceptibility loci in women with systemic lupus erythematosus.

PubMed

Chung, Sharon A; Brown, Elizabeth E; Williams, Adrienne H; Ramos, Paula S; Berthier, Celine C; Bhangale, Tushar; Alarcon-Riquelme, Marta E; Behrens, Timothy W; Criswell, Lindsey A; Graham, Deborah Cunninghame; Demirci, F Yesim; Edberg, Jeffrey C; Gaffney, Patrick M; Harley, John B; Jacob, Chaim O; Kamboh, M Ilyas; Kelly, Jennifer A; Manzi, Susan; Moser-Sivils, Kathy L; Russell, Laurie P; Petri, Michelle; Tsao, Betty P; Vyse, Tim J; Zidovetzki, Raphael; Kretzler, Matthias; Kimberly, Robert P; Freedman, Barry I; Graham, Robert R; Langefeld, Carl D

2014-12-01

Lupus nephritis is a manifestation of SLE resulting from glomerular immune complex deposition and inflammation. Lupus nephritis demonstrates familial aggregation and accounts for significant morbidity and mortality. We completed a meta-analysis of three genome-wide association studies of SLE to identify lupus nephritis-predisposing loci. Through genotyping and imputation, >1.6 million markers were assessed in 2000 unrelated women of European descent with SLE (588 patients with lupus nephritis and 1412 patients with lupus without nephritis). Tests of association were computed using logistic regression adjusting for population substructure. The strongest evidence for association was observed outside the MHC and included markers localized to 4q11-q13 (PDGFRA, GSX2; P=4.5×10(-7)), 16p12 (SLC5A11; P=5.1×10(-7)), 6p22 (ID4; P=7.4×10(-7)), and 8q24.12 (HAS2, SNTB1; P=1.1×10(-6)). Both HLA-DR2 and HLA-DR3, two well established lupus susceptibility loci, showed evidence of association with lupus nephritis (P=0.06 and P=3.7×10(-5), respectively). Within the class I region, rs9263871 (C6orf15-HCG22) had the strongest evidence of association with lupus nephritis independent of HLA-DR2 and HLA-DR3 (P=8.5×10(-6)). Consistent with a functional role in lupus nephritis, intra-renal mRNA levels of PDGFRA and associated pathway members showed significant enrichment in patients with lupus nephritis (n=32) compared with controls (n=15). Results from this large-scale genome-wide investigation of lupus nephritis provide evidence of multiple biologically relevant lupus nephritis susceptibility loci. Copyright © 2014 by the American Society of Nephrology.

Technical Leadership Development Program-Year 3

DTIC Science & Technology

2012-08-30

Develop an understanding of why achieving technology-based competitive advantage can be part of firm’s business strategy.  Review the Porter Model ...NUMBER H98230-08-D-0171 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) Gavito /Dr. Valentin 5d. PROJECT NUMBER RT 4-3 5e. TASK...NUMBER WHS TO009 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) Stevens Institute of Technology 8. PERFORMING ORGANIZATION

Fragmentation of the CRISPR-Cas Type I-B signature protein Cas8b.

PubMed

Richter, Hagen; Rompf, Judith; Wiegel, Julia; Rau, Kristina; Randau, Lennart

2017-11-01

CRISPR arrays are transcribed into long precursor RNA species, which are further processed into mature CRISPR RNAs (crRNAs). Cas proteins utilize these crRNAs, which contain spacer sequences that can be derived from mobile genetic elements, to mediate immunity during a reoccurring virus infection. Type I CRISPR-Cas systems are defined by the presence of different Cascade interference complexes containing large and small subunits that play major roles during target DNA selection. Here, we produce the protein and crRNA components of the Type I-B CRISPR-Cas complex of Clostridium thermocellum and Methanococcus maripaludis. The C. thermocellum Cascade complexes were reconstituted and analyzed via size-exclusion chromatography. Activity of the heterologous M. maripaludis CRISPR-Cas system was followed using phage lambda plaques assays. The reconstituted Type-I-B Cascade complex contains Cas7, Cas5, Cas6b and the large subunit Cas8b. Cas6b can be omitted from the reconstitution protocol. The large subunit Cas8b was found to be represented by two tightly associated protein fragments and a small C-terminal Cas8b segment was identified in recombinant complexes and C. thermocellum cell lysate. Production of Cas8b generates a small C-terminal fragment, which is suggested to fulfill the role of the missing small subunit. A heterologous, synthetic M. maripaludis Type I-B system is active in E. coli against phage lambda, highlighting a potential for genome editing using endogenous Type-I-B CRISPR-Cas machineries. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuroretinal alterations in the early stages of diabetic retinopathy in patients with type 2 diabetes mellitus.

PubMed

Carpineto, P; Toto, L; Aloia, R; Ciciarelli, V; Borrelli, E; Vitacolonna, E; Di Nicola, M; Di Antonio, L; Mastropasqua, R

2016-05-01

PurposeTo study neuroretinal alterations in patients affected by type 2 diabetes with no diabetic retinopathy (DR) or mild nonproliferative diabetic retinopathy (NPDR) and without any sign of diabetic macular edema.Patients and methodsIn total, 150 type 2 diabetic patients with no (131 eyes) or mild NPDR (19 eyes) and 50 healthy controls were enrolled in our study. All underwent a complete ophthalmologic examination, including Spectral-Domain optical coherence tomography (SD-OCT). Ganglion cell-inner plexiform layer (GC-IPL) and retinal nerve fiber layer (RNFL) thickness values were calculated after automated segmentation of SD-OCT scans.ResultsMean best-corrected visual acuity was 0.0±0.0 LogMAR in all the groups. Mean GC-IPL thickness was 80.6±8.1 μm in diabetic patients and 85.3±9.9 μm in healthy controls, respectively (P=0.001). Moreover, evaluating the two different diabetic groups, GC-IPL thickness was 80.7±8.1 μm and 79.7±8.8 μm in no-DR and mild-NPDR group (P=0.001 and P=0.022 compared with healthy controls, respectively). Average RNFL thickness was 86.1±10.1 μm in diabetes patients and 91.2±7.3 μm in controls, respectively (P=0.003). RNFL thickness was 86.4±10.2 μm in no-DR group and 84.1±9.4 μm in mild-NPDR group (P=0.007 and P=0.017 compared with healthy controls, respectively).ConclusionWe demonstrated a significantly reduced GC-IPL and RNFL thickness values in both no-DR and mild-NPDR groups compared with healthy controls. These data confirmed neuroretinal alterations are early in diabetes, preceding microvascular damages.

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.

Achieving a physiological cortisol profile with once-daily dual-release hydrocortisone: a pharmacokinetic study

PubMed Central

Lennernäs, Hans; Marelli, Claudio; Rockich, Kevin; Skrtic, Stanko

2016-01-01

Objective Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy was developed to provide a cortisol exposure−time profile that closely resembles the physiological cortisol profile. This study aimed to characterize single-dose pharmacokinetics (PK) of DR-HC 5–20mg and assess intrasubject variability. Methods Thirty-one healthy Japanese or non-Hispanic Caucasian volunteers aged 20−55 years participated in this randomized, open-label, PK study. Single doses of DR-HC 5, 15 (3×5), and 20mg were administered orally after an overnight fast and suppression of endogenous cortisol secretion. After estimating the endogenous cortisol profile, PK of DR-HC over 24h were evaluated to assess dose proportionality and impact of ethnicity. Plasma cortisol concentrations were analyzed using liquid chromatography−tandem mass spectrometry. PK parameters were calculated from individual cortisol concentration−time profiles. Results DR-HC 20mg provided higher than endogenous cortisol plasma concentrations 0−4h post-dose but similar concentrations later in the profile. Cortisol concentrations and PK exposure parameters increased with increasing doses. Mean maximal serum concentration (Cmax) was 82.0 and 178.1ng/mL, while mean area under the concentration−time curve (AUC)0−∞ was 562.8 and 1180.8h×ng/mL with DR-HC 5 and 20mg respectively. Within-subject PK variability was low (<15%) for DR-HC 20mg. All exposure PK parameters were less than dose proportional (slope <1). PK differences between ethnicities were explained by body weight differences. Conclusions DR-HC replacement resembles the daily normal cortisol profile. Within-subject day-to-day PK variability was low, underpinning the safety of DR-HC for replacement therapy. DR-HC PK were less than dose proportional – an important consideration when managing intercurrent illness in patients with adrenal insufficiency. PMID:27129362

Proinflammatory T Cell Status Associated with Early Life Adversity.

PubMed

Elwenspoek, Martha M C; Hengesch, Xenia; Leenen, Fleur A D; Schritz, Anna; Sias, Krystel; Schaan, Violetta K; Mériaux, Sophie B; Schmitz, Stephanie; Bonnemberger, Fanny; Schächinger, Hartmut; Vögele, Claus; Turner, Jonathan D; Muller, Claude P

2017-12-15

Early life adversity (ELA) has been associated with an increased risk for diseases in which the immune system plays a critical role. The ELA immune phenotype is characterized by inflammation, impaired cellular immunity, and immunosenescence. However, data on cell-specific immune effects are largely absent. Additionally, stress systems and health behaviors are altered in ELA, which may contribute to the generation of the ELA immune phenotype. The present investigation tested cell-specific immune differences in relationship to the ELA immune phenotype, altered stress parameters, and health behaviors in individuals with ELA ( n = 42) and those without a history of ELA (control, n = 73). Relative number and activation status (CD25, CD69, HLA-DR, CD11a, CD11b) of monocytes, NK cells, B cells, T cells, and their main subsets were assessed by flow cytometry. ELA was associated with significantly reduced numbers of CD69 + CD8 + T cells ( p = 0.022), increased numbers of HLA-DR + CD4 and HLA-DR + CD8 T cells ( p < 0.001), as well as increased numbers of CD25 + CD8 + T cells ( p = 0.036). ELA also showed a trend toward higher numbers of CCR4 + CXCR3 - CCR6 + CD4 T cells. Taken together, our data suggest an elevated state of immune activation in ELA, in which particularly T cells are affected. Although several aspects of the ELA immune phenotype were related to increased activation markers, neither stress nor health-risk behaviors explained the observed group differences. Thus, the state of immune activation in ELA does not seem to be secondary to alterations in the stress system or health-risk behaviors, but rather a primary effect of early life programming on immune cells. Copyright © 2017 by The American Association of Immunologists, Inc.

Genetic Determinants of Enterovirus Infections: Polymorphisms in Type 1 Diabetes and Innate Immune Genes in the MIDIA Study.

PubMed

Witsø, Elisabet; Cinek, Ondrej; Tapia, German; Brorsson, Caroline A; Stene, Lars C; Gjessing, Håkon K; Rasmussen, Trond; Bergholdt, Regine; Pociot, Flemming M; Rønningen, Kjersti S

2015-12-01

Enteroviruses have been suggested as triggers of type 1 diabetes (T1D). We aimed to assess whether established T1D susceptibility single nucleotide polymorphisms (SNPs) and candidate SNPs in innate immune genes were associated with the frequency of enterovirus infection in otherwise healthy children. Fifty-six established T1D SNPs and 97 other candidate immunity SNPs were typed in 419 children carrying the T1D high-risk genotype, HLA-DR4-DQ8/DR3-DQ2 genotype, and 373 children without this genotype. Enteroviral RNA was detected using real-time polymerase chain reaction, with primers detecting essentially all enterovirus serotypes, in 7,393 longitudinal stool samples collected monthly (age range 3-36 months). The most significant association was with two T1D SNPs, rs12150079 (ZPBP2/ORMDL3/GSDMB region) (enterovirus frequency: AA 7.3%, AG 8.7%, GG 9.7%, RR = 0.86, overall p = 1.87E-02) and rs229541 (C1QTNF6/SSTR3/RAC2) (enterovirus frequency: CC 7.8%, CT 9.7%, TT 9.4%, RR = 1.13, overall p = 3.6E-02), followed by TLR8 (rs2407992) (p = 3.8E-02), TLR3 (1914926) (p = 4.9E-02), and two other T1D SNPs (IFIH1 rs3747517, p = 4.9E-02 and PTPN22, rs2476601, p = 5.3E-02). However, the quantile-quantile plot of p-values with confidence intervals for all 153 SNPs did not reveal clear evidence for rejection of the complete null hypothesis. Among a number of SNPs in candidate genes, we found no evidence for strong associations with enterovirus presence in stool samples from Norwegian children.

Congruence as a measurement of extended haplotype structure across the genome

PubMed Central

2012-01-01

Background Historically, extended haplotypes have been defined using only a few data points, such as alleles for several HLA genes in the MHC. High-density SNP data, and the increasing affordability of whole genome SNP typing, creates the opportunity to define higher resolution extended haplotypes. This drives the need for new tools that support quantification and visualization of extended haplotypes as defined by as many as 2000 SNPs. Confronted with high-density SNP data across the major histocompatibility complex (MHC) for 2,300 complete families, compiled by the Type 1 Diabetes Genetics Consortium (T1DGC), we developed software for studying extended haplotypes. Methods The software, called ExHap (Extended Haplotype), uses a similarity measurement we term congruence to identify and quantify long-range allele identity. Using ExHap, we analyzed congruence in both the T1DGC data and family-phased data from the International HapMap Project. Results Congruent chromosomes from the T1DGC data have between 96.5% and 99.9% allele identity over 1,818 SNPs spanning 2.64 megabases of the MHC (HLA-DRB1 to HLA-A). Thirty-three of 132 DQ-DR-B-A defined haplotype groups have > 50% congruent chromosomes in this region. For example, 92% of chromosomes within the DR3-B8-A1 haplotype are congruent from HLA-DRB1 to HLA-A (99.8% allele identity). We also applied ExHap to all 22 autosomes for both CEU and YRI cohorts from the International HapMap Project, identifying multiple candidate extended haplotypes. Conclusions Long-range congruence is not unique to the MHC region. Patterns of allele identity on phased chromosomes provide a simple, straightforward approach to visually and quantitatively inspect complex long-range structural patterns in the genome. Such patterns aid the biologist in appreciating genetic similarities and differences across cohorts, and can lead to hypothesis generation for subsequent studies. PMID:22369243

Dual combination therapy targeting DR5 and EMMPRIN in pancreatic adenocarcinoma.

PubMed

Kim, Hyunki; Zhai, Guihua; Samuel, Sharon L; Rigell, Christopher J; Umphrey, Heidi R; Rana, Samir; Stockard, Cecil R; Fineberg, Naomi S; Zinn, Kurt R

2012-02-01

The goal of the study was to assess the efficacy of combined extracellular matrix metalloprotease inducer (EMMPRIN)- and death receptor 5 (DR5)-targeted therapy for pancreatic adenocarcinoma in orthotopic mouse models with multimodal imaging. Cytotoxicity of anti-EMMPRIN antibody and anti-DR5 antibody (TRA-8) in MIA PaCa-2 and PANC-1 cell lines was measured by ATPlite assay in vitro. The distributions of Cy5.5-labeled TRA-8 and Cy3-labeled anti-EMMPRIN antibody in the 2 cell lines were analyzed by fluorescence imaging in vitro. Groups 1 to 12 of severe combined immunodeficient mice bearing orthotopic MIA PaCa-2 (groups 1-8) or PANC-1 (groups 9-12) tumors were used for in vivo studies. Dynamic contrast-enhanced-MRI was applied in group 1 (untreated) or group 2 (anti-EMMPRIN antibody). The tumor uptake of Tc-99m-labeled TRA-8 was measured in group 3 (untreated) and group 4 (anti-EMMPRIN antibody). Positron emission tomography/computed tomography imaging with (18)F-FDG was applied in groups 5 to 12. Groups 5 to 8 (or groups 9 to 12) were untreated or treated with anti-EMMPRIN antibody, TRA-8, and combination, respectively. TRA-8 showed high killing efficacy for both MIA PaCa-2 and PANC-1 cells in vitro, but additional anti-EMMPRIN treatment did not improve the cytotoxicity. Cy5.5-TRA-8 formed cellular caps in both the cell lines, whereas the maximum signal intensity was correlated with TRA-8 cytotoxicity. Anti-EMMPRIN therapy significantly enhanced the tumor delivery of the MR contrast agent, but not Tc-99m-TRA-8. Tumor growth was significantly suppressed by the combination therapy, and the additive effect of the combination was shown in both MIA PaCa-2 and PANC-1 tumor models.

Automatic and Controlled Attention Processes in Auditory Detection.

DTIC Science & Technology

1981-02-01

DC 20380 1 Dr. Genevieve Hddad Progri Manager 1 Special Assistant for Marine Life Sciences Directorate Corps Matters AFOBR Code lOOM Bolling AFB, DC...INC. UIVERSITY PLAZA, SUM 10 1 Dr. Kenneth B. Cross O1160 0. STATE ST. Macape Sciences, Inc. OREM, Ur 84057 P.O. Drawer Ql i anta Bar ara,0 Dr. Pat

Prevention strategies differentially modulate the impact of cytomegalovirus replication on CD8(+) T-cell differentiation in high-risk solid organ transplant patients.

PubMed

Cantisán, Sara; Páez-Vega, Aurora; Pérez-Romero, Pilar; Montejo, Miguel; Cordero, Elisa; Gracia-Ahufinger, Irene; Martín-Gandul, Cecilia; Maruri, Naroa; Aguado, Rocío; Solana, Rafael; Torre-Cisneros, Julián

2016-08-01

The present study aimed to determine whether antiviral prevention strategies against cytomegalovirus (CMV) infection used in high-risk D+R- solid organ transplanted patients can modulate the impact of CMV replication on CD8(+) T-cell differentiation. The different CD8(+) T-cell subpopulations were measured at a single point when at least one year had elapsed since transplantation. A total of 68 D+R- patients were included, of which 33 underwent pre-emptive therapy and 35 received prophylaxis. Multivariate analysis showed that CMV replication was associated with the expansion of CD28־ EMRA CD8(+) T cells in patients managed pre-emptively but not in patients under prophylaxis (21.4% vs. 3.6%). This finding is likely related to the higher frequency of CMV recurrence observed in patients under pre-emptive therapy compared to those under prophylaxis (75% vs. 14.3%; p < 0.001). In fact, multivariate analysis showed that having more than one replication episode was associated with a 17.2% increase (p = 0.001) in the percentage of CD28־ EMRA CD8(+) T cells compared to "no episode" and with a 10.9% increase with respect to "single episodes" (p = 0.025). Additionally, patients with IFNγ response to CMV (QuantiFERON-CMV Reactive) had a higher percentage of late-differentiated CD8(+) T cells than patients lacking this response. In summary, recurrent CMV replication in D+R- patients under pre-emptive therapy was associated with the expansion of CD28־ EMRA CD8(+) T cells, which might have a short-term beneficial effect related to the high functionality of this T-cell subpopulation. Nevertheless, we cannot rule out that this accumulation might have a long-term detrimental effect related to immunosenescence and inflammation. Copyright © 2016 Elsevier B.V. All rights reserved.

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

A Transformation Yielding an Additive Representation of Data in a Two-Way Array.

DTIC Science & Technology

1980-08-15

Psychological Association 1200 17th Street N.W. 1 Dr. Gary Marco Washington, DC 20036 Educational Testing Service Princeton, NJ 08450 Dr. Wilson A. Judd...ADA,11 b6b PORTLAND STATE UNIV OR DEPT OF PSYCHOLOGY F/G 12/1 A TRANSFORMATION YILLDING AN ADDITIVE REPRESENTATION OF DATA IN--ETC(U) AUG bO J A PAUL...DATA IN A TWO-WAY ARRAY James A. Paulson Psychology Department Portland State University Approved for public release; distribution unlimited

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.

Development of a 2,4-Dinitrotoluene-Responsive Synthetic Riboswitch in E. coli cells

DTIC Science & Technology

2012-09-01

INTRODUCTION Riboswitches are naturally-occurring genetic regulatory elements found in the 5′ untranslated region of some mRNA. They provide a method...Industrial Genetics at the University of Stuttgart, Germany, respectively. The plasmid pSAL8.1 was kindly provided by Dr. Justin Gallivan from Emory...vol. 252: Ribozymes and siRNA Protocols, 2nd ed. Humana Press, Inc.; 2004, 145-164. (9) Suess, B., and Weigand, J.E. RNA Biology 2008, 5(1), 1-6

Dietary restriction improves repopulation but impairs lymphoid differentiation capacity of hematopoietic stem cells in early aging

PubMed Central

Tang, Duozhuang; Tao, Si; Chen, Zhiyang; Koliesnik, Ievgen Oleksandrovich; Calmes, Philip Gerald; Hoerr, Verena; Han, Bing; Gebert, Nadja; Zörnig, Martin; Löffler, Bettina

2016-01-01

Dietary restriction (DR) improves health, delays tissue aging, and elongates survival in flies and worms. However, studies on laboratory mice and nonhuman primates revealed ambiguous effects of DR on lifespan despite improvements in health parameters. In this study, we analyzed consequences of adult-onset DR (24 h to 1 yr) on hematopoietic stem cell (HSC) function. DR ameliorated HSC aging phenotypes, such as the increase in number of HSCs and the skewing toward myeloid-biased HSCs during aging. Furthermore, DR increased HSC quiescence and improved the maintenance of the repopulation capacity of HSCs during aging. In contrast to these beneficial effects, DR strongly impaired HSC differentiation into lymphoid lineages and particularly inhibited the proliferation of lymphoid progenitors, resulting in decreased production of peripheral B lymphocytes and impaired immune function. The study shows that DR-dependent suppression of growth factors and interleukins mediates these divergent effects caused by DR. Supplementation of insulin-like growth factor 1 partially reverted the DR-induced quiescence of HSCs, whereas IL-6/IL-7 substitutions rescued the impairment of B lymphopoiesis exposed to DR. Together, these findings delineate positive and negative effects of long-term DR on HSC functionality involving distinct stress and growth signaling pathways. PMID:26951333

Growth, Characterization and Properties of Ultrathin Magnetic Films and Multilayers. Materials Research Society Symposium Proceedings. Volume 151

DTIC Science & Technology

1990-05-01

Mahan , W. Raith, and B. Reihl, Phys. Rev. BI8, 2256 (1978). 6. R. Meservey, P. M. Tedrow, and J. S . Moodera, J. Mag. and Mag. Mat. 35, 1 (1983). 7. J...j L. X1PGr DATI 1. WIORT’ TYPE A10 DATES COjgITal 02QR -UMay 89-01 May 90 Dr Jan B BalanceAFOSR-89-0388 T. PjUQMiM ORGAMLAION NAME( S ) AND ADOXESS(I5J...L. FIZZ=g~ CGAIZAflON Materials Researc ’ SocietyA~ NmI 49800 14cKnight Road, Suite 327 AFOSR-TI ( 4 6 Pittsburgh Pa 15237-6005 S

[Study on correlation between HLA-A, B, DR alleles and Duchenne muscular dystrophy].

PubMed

Chen, Wei; Xiao, Lulu; Zhang, Cheng; Wu, Hong-ling

2007-10-01

To analyze the polymorphism of HLA-A, B and DR alleles of Duchenne muscular dystrophy (DMD) patients in Han nationality of South China and to discuss the role of immune and genetic factors in the pathogenesis of DMD and muscular fiber necrosis. Polymerase chain reaction-reverse sequence specific oligonucleotide (PCR-RSSO) and National Marrow Donor Program (NMDP) were used to analyze the polymorphism of HLA-A,B and DR alleles of 113 DMD patients and 406 normal controls in Han nationality of South China. The frequencies of HLA-A24, A30 alleles in DMD group were 11.25% and 5.46% respectively, indicating notable difference (P=0.001, < 0.01) from 22.16% and 0.87% of control group; the frequencies of HLA-B13, B15, B61 and B62 alleles in DMD group were 12.26%, 16.92%, 0.44% and 0.44%, indicating a notable difference (P=0.016, < 0.01, 0.001) from 6.76%, 1.49%, 4.79% and 5.05% of control group; the frequencies of HLA-DR04, DR07, DR12 alleles in DMD group were 17.45%, 6.40% and 19.62%, indicating a notable difference (P=0.018, < 0.01, 0.012) from 10.67%, 2.24% and 11.92% of control group. There are significant differences in the HLA gene frequencies between DMD patients and normal controls. These results suggest that HLA genotype relates to the muscular necrosis and the pathogenesis of DMD.

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.

Longitudinal Control of Intense Charged Particle Beams

DTIC Science & Technology

2011-01-01

Irving Haber , Dr. Massimo Cornacchia, and Dr. Karen Fiuza. I am also grateful to the past and current students of UMER, Dr. Charles Tobin, Dr...3, 124402, (2000). 138 [16] R.A. Kishek, G. Bai, S. Bernal, D. Feldman, T.F. Godlove, I. Haber , P.G. O’Shea, B. Quinn, C. Papadopoulos, M...M. Reiser, Physical Review Letters, 73, 66, (1994). [22] Y. Zou, Y. Cui, V. Yun, A. Valfells, R.A. Kishek, S. Bernal, I. Haber , M. Reiser, P. G

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

Three-year survival rates for all consecutive heart-only and lung-only transplants performed in Eurotransplant, 1997-1999.

PubMed

Smits, Jacqueline M A; Vanhaecke, Johan; Haverich, Axel; de Vries, Erwin; Smith, Mike; Rutgrink, Ellis; Ramsoebhag, Annemarie; Hop, Alinde; Persijn, Guido; Laufer, Gunther

2003-01-01

The definition of proper patient selection criteria remains a prominent item in constant need of attention. While the concept of gathering evidence in order to determine practice continues to be hopelessly ambiguous, it can never be emphasized too much that these univariate results are just a first foray into analysing predictors of survival; all following results should be regarded and interpreted in this perspective. HEART TRANSPLANT SURVIVAL: The 3-year survival rate for heart transplant recipients under age 16 was 83% versus 72% for adult recipients. Acutely retransplanted adult heart recipients had a 3-year survival rate of 36% compared with 72% for recipients of a first heart allograft. Patients suffering from DCM had the best survival rates at 3 years (74%) compared with patients suffering from CAD (70%) or from another end-stage heart disease (67%). With advancing age of the adult recipient, the mortality risk increased. Patients aged 16-40 had a 3-year survival rate of 77%, compared with 74%, 70% and 61% for transplant recipients aged 41-55, 56-65 and over age 65, respectively. The 3-year survival rates for adult recipients transplanted with an heart allograft from a donor aged under 16 or between 16-44 were 78% and 74%, compared with 66% and 63% for donors aged 45-55 and over 55, respectively. The 3-year survival rates for recipients of hearts with cold ischemic times under 2 hours, 2-3, 3-4, 4-5, 5-6 and more than 6 hours were 74%, 75%, 70%, 65%, 54% and 40%, respectively. Transplanting a female donor heart into a male recipient was associated with the worst prognosis: the 3-year survival rates were 73%, 71%, 66% and 76%, respectively, for the donor/recipient groups male/male, male/female, female/male and female/female, respectively. When the donor-to-recipient body weight ratio was below 0.8, the 3-year survival rate was 64%, compared to 72% for weight-matched pairs and 74% for patients who received a heart from an oversized donor (p=0.004). Better survival rates were obtained for better HLA-matched transplants. The 3-year survival rates were 75%, 89%, 78%, 78%, 69%, 72%, and 71% for HLA-A,-B,-DR zero, 1, 2, 3, 4, 5 and 6 mismatched groups, respectively (p=0.04). Survival was significantly associated with the CMV serologic status of the donor and recipient; the 3-year survival rates were: D+/R+, 71%; D+/R-, 69%; D- R-, 76%; and D-/R+, 76% (p=0.04). Patients in an ICU had a 3-year survival rate of 62%, compared to 72% for patients in a general ward and 74% for outpatients (p<0.0001). Patients that were on a VAD and there-upon transplanted had a 3-year survival rate of 65%, compared to 73% for patients without a VAD (p=0.004). Being on a ventilator was a major risk factor for death after transplantation; patients on ventilator support at the time of the transplant had a 3-year survival rate of 52% compared to 73% for the other patients (p<0.0001). LUNG TRANSPLANT SURVIVAL: The 3-year survival rate for children (73%) appeared to be better than the adult rate (61%; p=0.8). Adult lung transplant survival was significantly worse in the case of a repeat lung transplant; a 3-year retransplant survival rate of 42% was obtained compared with 61% for first transplants (p=0.049). With respect to the underlying end-stage lung disease, no statistically significant difference in long-term survival could be detected in this cohort. The 3-year survival rates were: 62% for COPD/Emphysema, 70% for CF, 58% for IPF, 64% for Alpha-1 ATD and 56% for PPH (p=0.2). Our data demonstrated no effect of the recipient's age on long-term lung transplant survival, except for 2 senior patients in this cohort. At 3-years the survival rates for recipients aged 16-40, 41-55 and 56-65 were 65%, 60% and 62%, respectively (p=0.05). The 3-year survival rates for transplants performed with lungs from donors aged under 16, 16-44, 45-55 and over 55 was 57%, 64%, 55% and 62%, respectively (p=0.1) No association between the duration of cold ischemic time and 3-year survival was observed; under 3 hours, 3-4, 4-5, 5-6 and over 6 hours of ischemia resulted in 3-year survival rates of 53%, 59%, 64%, 68% and 57%, respectively (p=0.2). Early posttransplant outcome tended to be better for gender-matched transplants, while transplanting a female donor lung into a male recipient was associated with the worst prognosis. The 3-year survival rates were 65% for male/male, 63% for male/female, 48% for female/male and 61% for female/female (p=0.009). No effect of donor-to-recipient weight match was observed in this Eurotransplant cohort; when the donor-to-recipient weight ratio was below 0.8, the 3-year survival rate was 57%, compared with 59% for weight-matched pairs and 64% for patients who received a lung from an oversized donor (p=0.5). Long-term survival after lung transplantation was influenced by HLA matching. The 3-year survival rates were 100%, 68%, 70%, 65%, 54% and 55% for the HLA-A,-B,-DR 1, 2, 3, 4, 5 and 6 mismatched groups, respectively (p=0.06). A donor CMV+ and recipient CMV- match was a risk factor for long-term mortality, with 3-year survival rates of 56% for D+/R+, 55% for D+/R-, 71% for D-/R- and 62% for D-/R+ transplants (p=0.046). En-bloc transplantation of both lungs yielded worse early results, but the 3-year survival rates for patients who underwent single (60%), bilateral sequential double lung (63%) and en-bloc double lung transplantation (56%) were not different (p=0.2). Ventilator dependency was associated with a significantly reduced survival at 3 years. Patients on a ventilator support at the time of the transplant had a 3-year survival rate of 48% compared with 63% for other patients (p=0.006).

FTIR spectra and properties of iron borophosphate glasses containing simulated nuclear wastes

NASA Astrophysics Data System (ADS)

Liao, Qilong; Wang, Fu; Chen, Kuiru; Pan, Sheqi; Zhu, Hanzhen; Lu, Mingwei; Qin, Jianfa

2015-07-01

30 wt.% simulated nuclear wastes were successfully immobilized by B2O3-doped iron phosphate base glasses. The structure and thermal stability of the prepared wasteforms were characterized by Fourier transform infrared spectroscopy and differential thermal analysis, respectively. The subtle structural variations attributed to different B2O3 doping modes have been discussed in detail. The results show that the thermal stability and glass forming tendency of the iron borophosphate glass wasteforms are faintly affected by different B2O3 doping modes. The main structural networks of iron borophosphate glass wasteforms are PO43-, P2O74-, [BO4] groups. Furthermore, for the wasteform prepared by using 10B2O3-36Fe2O3-54P2O5 as base glass, the distributions of Fe-O-P bonds, [BO4], PO43- and P2O74- groups are optimal. In general, the dissolution rate (DR) values of the studied iron borophosphate wasteforms are about 10-8 g cm-2 min-1. The obtained conclusions can offer some useful information for the disposal of high-level radioactive wastes using boron contained phosphate glasses.

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.

Aldehyde dehydrogenase-2 genotypes and HLA haplotypes in Japanese patients with esophageal cancer.

PubMed

Watanabe, Seishiro; Sasahara, Katsuyuki; Kinekawa, Fumihiko; Uchida, Naohito; Masaki, Tsutomu; Kurokohchi, Kazutaka; Murota, Masayuki; Touge, Tetsuo; Kawauchi, Kazuyoshi; Oda, Syuji; Kuriyama, Shigeki

2002-01-01

The aim of this study was to examine how aldehyde dehydrogenase-2 (ALDH2) genotypes and human leukocyte antigen (HLA) haplotypes contribute to the risk for esophageal cancer. We examined ALDH2 genotypes and HLA haplotypes in 29 Japanese patients with esophageal cancer. The ratio of patients who experienced current or former intense vasodilatation upon consuming alcohol (flushing type) was much higher in individuals with the inactive form of ALDH2 encoded by the ALDH2(2)/2(2) or ALDH2(1)/2(2) genotype than in those with the active form of ALDH2 encoded by the ALDH2(1)/2(1) genotype. The ratio of inactive ALDH2 was significantly higher in patients with esophageal cancer than in control normal subjects, suggesting that alcoholics with inactive ALDH2 were susceptible to esophageal cancer. HLA haplotypes A24, A26, B54, B61 and DR9 were prevalent in patients with esophageal cancer (82.8, 24.1, 34.5, 37.9 and 44.8%, respectively). HLA haplotype of A24 and inactive ALDH2 were simultaneously found in 58.6% of patients with esophageal cancer. Furthermore, we found other primary malignancies in 6 of 29 (20.7%) patients with esophageal cancer, and 4 of these 6 patients had both the inactive form of ALDH2 and the HLA A24 haplotype. The present study showed the high prevalence of the inactive form of ALDH2 and HLA haplotypes A24, A26, B54, B61 and DR9 in Japanese patients with esophageal cancer. Therefore, the examination of genotypes of ALDH2 loci and HLA haplotypes may allow the early detection of esophageal cancer in the Japanese population.

Solar-simulating irradiation of the skin of human subjects in vivo produces Langerhans cell responses distinct from irradiation ex vivo and in vitro.

PubMed

Laihia, J K; Jansen, C T

2000-08-01

It has been postulated that Langerhans cells (LC) provide tolerogenic signals in the local impairment of cutaneous immune functions and antigen-specific tolerance induced by UV radiation. Studies in vitro and ex vivo have indicated that UV radiation may down-regulate the expression of costimulatory molecules on LC, leading to reduced antigen-presenting function. In contrast, we recently observed an up-regulatory stage in the number of human epidermal LC with induced expression of B7 costimulatory molecules 12-24 h after solar-simulating UV radiation (SSR) in vivo. To examine the apparent discrepancy between the observed human LC responses in vitro, ex vivo and in vivo, we compared the three protocols in a parallel fashion. The intact skin as well as skin explants and epidermal cell suspensions from the same individuals were irradiated with a single erythematogenic dose of SSR. The expression of cell surface markers in the epidermal cells was analysed with flow cytometry 24 h later. The number of CD1a+/HLA-DR+ LC increased post-SSR in vivo by a factor of 2.8+/-0.4, whereas in irradiated skin explants ex vivo or in cell suspensions in vitro, reduced numbers were seen. HLA-DR expression intensities were found to have increased on DR+ and CD1a+/DR+ cells in vivo. Similarly, SSR induced B7-2 (CD86) expression in CD1a+ cells significantly in vivo (P=0.031) but reduced the expression ex vivo or in vitro. We conclude that the early up-regulatory stage of human LC number and membrane markers, recorded at 24 h after a single exposure to SSR, is exclusively an in vivo phenomenon.

Prevalence of drug-resistant pulmonary tuberculosis in India: systematic review and meta-analysis.

PubMed

Goyal, Vishal; Kadam, Vijay; Narang, Prashant; Singh, Vikram

2017-10-17

Drug-resistant pulmonary tuberculosis (DR-TB) is a significant public health issue that considerably deters the ongoing TB control efforts in India. The purpose of this review was to investigate the prevalence of DR-TB and understand the regional variation in resistance pattern across India from 1995 to 2015, based on a large body of published epidemiological studies. A systematic review of published studies reporting prevalence of DR-TB from biomedical databases (PubMed and IndMed) was conducted. Meta-analysis was performed using random effects model and the pooled prevalence estimate (95% confidence interval [CI]) of DR-TB, multidrug resistant (MDR-) TB, pre-extensively drug-resistant (pre-XDR) TB and XDR-TB were calculated across two study periods (decade 1: 1995 to 2005; decade 2: 2006 to 2015), countrywide and in different regions. Heterogeneity in this meta-analysis was assessed using I 2 statistic. A total of 75 of 635 screened studies that fulfilled the inclusion criteria were selected. Over 40% of 45,076 isolates suspected for resistance to any first-line anti-TB drugs tested positive. Comparative analysis revealed a worsening trend in DR-TB between the two study decades (decade 1: 37.7% [95% CI = 29.0; 46.4], n = 25 vs decade 2: 46.1% [95% CI = 39.0; 53.2], n = 36). The pooled estimate of MDR-TB resistance was higher in previously treated patients (decade 1: 29.8% [95% CI = 20.7; 39.0], n = 13; decade 2: 35.8% [95% CI = 29.2; 42.4], n = 24) as compared with the newly diagnosed cases (decade 1: 4.1% [95% CI = 2.7; 5.6], n = 13; decade 2: 5.6% [95% CI = 3.8; 7.4], n = 17). Overall, studies from Western states of India reported highest prevalence of DR-TB (57.8% [95% CI = 37.4; 78.2], n = 6) and MDR-TB (39.9% [95% CI = 21.7; 58.0], n = 6) during decade 2. Prevalence of pre-XDR TB was 7.9% (95% CI = 4.4; 11.4, n = 5) with resistance to fluoroquinolone (66.3% [95% CI = 58.2; 74.4], n = 5) being the highest. The prevalence of XDR-TB was 1.9% (95% CI = 1.2; 2.6, n = 14) over the 20-year period. The alarming increase in the trend of anti-TB drug resistance in India warrants the need for a structured nationwide surveillance to assist the National TB Control Program in strengthening treatment strategies for improved outcomes.

The impact of direct-acting antiviral agents on liver and kidney transplant costs and outcomes.

PubMed

Axelrod, D A; Schnitzler, M A; Alhamad, T; Gordon, F; Bloom, R D; Hess, G P; Xiao, H; Nazzal, M; Segev, D L; Dharnidharka, V R; Naik, A S; Lam, N N; Ouseph, R; Kasiske, B L; Durand, C M; Lentine, K L

2018-04-27

Direct-acting antiviral medications (DAAs) have revolutionized care for hepatitis C positive (HCV+) liver (LT) and kidney (KT) transplant recipients. Scientific Registry of Transplant Recipients registry data were integrated with national pharmaceutical claims (2007-2016) to identify HCV treatments before January 2014 (pre-DAA) and after (post-DAA), stratified by donor (D) and recipient (R) serostatus and payer. Pre-DAA, 18% of HCV+ LT recipients were treated within 3 years and without differences by donor serostatus or payer. Post-DAA, only 6% of D-/R+ recipients, 19.8% of D+/R+ recipients with public insurance, and 11.3% with private insurance were treated within 3 years (P < .0001). LT recipients treated for HCV pre-DAA experienced higher rates of graft loss (adjusted hazard ratio [aHR] 1.34 1.85 2.10 , P < .0001) and death (aHR 1.47 1.68 1.91 , P < .0001). Post-DAA, HCV treatment was not associated with death (aHR 0.34 0.67 1.32 , P = .25) or graft failure (aHR 0.32 0.64 1.26 , P = .20) in D+R+ LT recipients. Treatment increased in D+R+ KT recipients (5.5% pre-DAA vs 12.9% post-DAA), but did not differ by payer status. DAAs reduced the risk of death after D+/R+ KT by 57% ( 0.19 0.43 0.95 , P = .04) and graft loss by 46% ( 0.27 0.54 1.07 , P = .08). HCV treatment with DAAs appears to improve HCV+ LT and KT outcomes; however, access to these medications appears limited in both LT and KT recipients. © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.

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

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

VizieR Online Data Catalog: z>~5 AGN in Chandra Deep Field-South (Weigel+, 2015)

NASA Astrophysics Data System (ADS)

Weigel, A. K.; Schawinski, K.; Treister, E.; Urry, C. M.; Koss, M.; Trakhtenbrot, B.

2015-09-01

The Chandra 4-Ms source catalogue by Xue et al. (2011, Cat. J/ApJS/195/10) is the starting point of this work. It contains 740 sources and provides counts and observed frame fluxes in the soft (0.5-2keV), hard (2-8keV) and full (0.5-8keV) band. All object IDs used in this work refer to the source numbers listed in the Xue et al. (2011, Cat. J/ApJS/195/10) Chandra 4-Ms catalogue. We make use of Hubble Space Telescope (HST)/Advanced Camera for Surveys (ACS) data from the Great Observatories Origins Deep Survey South (GOODS-south) in the optical wavelength range. We use catalogues and images for filters F435W (B), F606W (V), F775W (i) and 850LP (z) from the second GOODS/ACS data release (v2.0; Giavalisco et al., 2004, Cat. II/261). We use Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS) Wide Field Camera 3 (WFC3)/infrared data from the first data release (DR1, v1.0) for passbands F105W (Y), F125W (J) and F160W (H) (Grogin et al., 2011ApJS..197...35G; Koekemoer et al., 2011ApJS..197...36K). To determine which objects are red, dusty, low-redshift interlopers, we also include the 3.6 and 4.5 micron Spitzer Infrared Array Camera (IRAC) channels. We use SIMPLE image data from the DR1 (van Dokkum et al., 2005, Spitzer Proposal, 2005.20708) and the first version of the extended SIMPLE catalogue by Damen et al. (2011, Cat. J/ApJ/727/1). (6 data files).

Manipulation for plasmid elimination by transforming synthetic competitors diversifies lactococcus lactis starters applicable to food products.

PubMed

Kobayashi, Miho; Nomura, Masaru; Kimoto, Hiromi

2007-11-01

This study was designed selectively to eliminate a theta-plasmid from Lactococcus lactis strains by transforming synthetic competitors. A shuttle vector for Escherichia coli and L. lactis, pDB1, was constructed by ligating a partial replicon of pDR1-1B, which is a 7.3 kb theta-plasmid in L. lactis DRC1, with an erythromycin resistance gene into pBluescript II KS(+). This versatile vector was used to construct competitors to common lactococcal theta-plasmids. pDB1 contains the 5' half of the replication origin and the 3' region of repB of pDR1-1B, but lacks the 1.1-kb region normally found between these two segments. A set of primers, Pv3 and Pv4, was designed to amplify the 1.1-kb middle parts of the general theta-replicons of lactococcal plasmids. When the PCR products were cloned into the Nru I and Xho I sites of pDB1, synthetic replicons were constructed and replication activity was restored. A number of theta-plasmids in L. lactis ssp. lactis and cremoris were eliminated selectively by transforming the synthetic competitors. These competitors were easily eliminated by subculture for a short time in the absence of selection. The resulting variants contained no exogenous DNA and are suitable for food products, since part of the phenotype was altered without altering other plasmids indispensable for fermentation.

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

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.

Calcium-Binding Proteins S100A8 and S100A9: Investigation of Their Immune Regulatory Effect in Myeloid Cells.

PubMed

Yang, Jianxin; Anholts, Jacqueline; Kolbe, Ulrike; Stegehuis-Kamp, Janine A; Claas, Frans H J; Eikmans, Michael

2018-06-21

High expression levels of the calcium-binding proteins S100A8 and S100A9 in myeloid cells in kidney transplant rejections are associated with a favorable outcome. Here we investigated the myeloid cell subset expressing these molecules, and their function in inflammatory reactions. Different monocyte subsets were sorted from buffy coats of healthy donors and investigated for S100A8 and S100A9 expression. To characterize S100A9high and S100A9low subsets within the CD14+ classical monocyte subset, intracellular S100A9 staining was combined with flow cytometry (FACS) and qPCR profiling. Furthermore, S100A8 and S100A9 were overexpressed by transfection in primary monocyte-derived macrophages and the THP-1 macrophage cell line to investigate the functional relevance. Expression of S100A8 and S100A9 was primarily found in classical monocytes and to a much lower extent in intermediate and non-classical monocytes. All S100A9+ cells expressed human leukocyte antigen—antigen D related (HLA-DR) on their surface. A small population (<3%) of CD14+ CD11b+ CD33+ HLA-DR− cells, characterized as myeloid derived suppressor cells (MDSCs), also expressed S100A9 to high extent. Overexpression of S100A8 and S00A9 in macrophages led to enhanced extracellular reactive oxygen species (ROS) production, as well as elevated mRNA expression of anti-inflammatory IL-10 . The results suggest that the calcium-binding proteins S100A8 and S100A9 in myeloid cells have an immune regulatory effect.

Hepatitis B Foundation Newsletter: B Informed

MedlinePlus

... CDC Awards Hepatitis B Foundation 5-Year Cooperative Agreement It Takes a Coalition to Fight Hepatitis B ... Dr. Baruch S. Blumberg HBF Awarded 3-Year Cooperative Agreement from CDC About "A Nobel Challenge" Cure Agenda ...

HbA1c Variability as an Independent Correlate of Nephropathy, but Not Retinopathy, in Patients With Type 2 Diabetes

PubMed Central

Penno, Giuseppe; Solini, Anna; Bonora, Enzo; Fondelli, Cecilia; Orsi, Emanuela; Zerbini, Gianpaolo; Morano, Susanna; Cavalot, Franco; Lamacchia, Olga; Laviola, Luigi; Nicolucci, Antonio; Pugliese, Giuseppe

2013-01-01

OBJECTIVE To examine the association of hemoglobin (Hb) A1c variability with microvascular complications in the large cohort of subjects with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study. RESEARCH DESIGN AND METHODS Serial (3–5) HbA1c values collected in a 2-year period before enrollment were available from 8,260 subjects from 9 centers (of 15,773 patients from 19 centers). HbA1c variability was measured as the intraindividual SD of 4.52 ± 0.76 values. Diabetic retinopathy (DR) was assessed by dilated funduscopy. Chronic kidney disease (CKD) was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate (eGFR) was calculated from serum creatinine. RESULTS Median and interquartile range of average HbA1c (HbA1c-MEAN) and HbA1c-SD were 7.57% (6.86–8.38) and 0.46% (0.29–0.74), respectively. The highest prevalence of microalbuminuria, macroalbuminuria, reduced eGFR, albuminuric CKD phenotypes, and advanced DR was observed when both HbA1c parameters were above the median and the lowest when both were below the median. Logistic regression analyses showed that HbA1c-SD adds to HbA1c-MEAN as an independent correlate of microalbuminuria and stages 1–2 CKD and is an independent predictor of macroalbuminuria, reduced eGFR, and stages 3–5 albuminuric CKD, whereas HbA1c-MEAN is not. The opposite was found for DR, whereas neither HbA1c-MEAN nor HbA1c-SD affected nonalbuminuric CKD. CONCLUSIONS In patients with type 2 diabetes, HbA1c variability affects (albuminuric) CKD more than average HbA1c, whereas only the latter parameter affects DR, thus suggesting a variable effect of these measures on microvascular complications. PMID:23491522

Remotely Piloted Aerial Systems Survivability: A Defense-in-Depth Approach

DTIC Science & Technology

2012-09-01

Robert J. Herman, Henry J. Kluepfel, Gen Richard L. Lawson, Dr. Graham K. Soper , Dr. Lowell L. Wood, Jr., Dr. Joan B. Woodard, Report of the...Kluepfel, Gen Richard L. Lawson, Dr. Graham K. Soper , Dr. Lowell L. Wood, Jr., Dr. Joan B. Woodard. Report of the Commission to Assess the Threat to

A Wideband Circularly Polarized Antenna with a Multiple-Circular-Sector Dielectric Resonator.

PubMed

Trinh-Van, Son; Yang, Youngoo; Lee, Kang-Yoon; Hwang, Keum Cheol

2016-11-03

This paper presents the design of a wideband circularly polarized antenna using a multiple-circular-sector dielectric resonator (DR). The DR is composed of twelve circular-sector DRs with identical central angles of 30 ∘ but with different radii. A genetic algorithm is utilized to optimize the radii of the twelve circular-sector DRs to realize wideband circular polarization. The proposed antenna is excited using an aperture-coupled feeding technique through a narrow rectangular slot etched onto the ground plane. An antenna prototype is experimentally verified. The measured -10 dB reflection and 3 dB axial ratio (AR) bandwidths are 31.39% (1.88-2.58 GHz) and 19.30% (2.06-2.50 GHz), respectively, covering the operating bands of the following systems: UMTS-2100 (2.145 GHz), WiMAX (2.3 GHz), and Wi-Fi (2.445 GHz). A measured peak gain of 7.65 dBic at 2.225 GHz and gain variation of less than 2.70 dBic within the measured 3 dB AR bandwidth are achieved. In addition, the radiation patterns of the proposed antenna are presented and discussed.

Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis.

PubMed

Kim, Ji H; Gupta, Subash C; Park, Byoungduck; Yadav, Vivek R; Aggarwal, Bharat B

2012-03-01

The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A novel kinase regulates dietary restriction-mediated longevity in Caenorhabditis elegans

PubMed Central

Chamoli, Manish; Singh, Anupama; Malik, Yasir; Mukhopadhyay, Arnab

2014-01-01

Although dietary restriction (DR) is known to extend lifespan across species, from yeast to mammals, the signalling events downstream of food/nutrient perception are not well understood. In Caenorhabditis elegans, DR is typically attained either by using the eat-2 mutants that have reduced pharyngeal pumping leading to lower food intake or by feeding diluted bacterial food to the worms. In this study, we show that knocking down a mammalian MEKK3-like kinase gene, mekk-3 in C. elegans, initiates a process similar to DR without compromising food intake. This DR-like state results in upregulation of beta-oxidation genes through the nuclear hormone receptor NHR-49, a HNF-4 homolog, resulting in depletion of stored fat. This metabolic shift leads to low levels of reactive oxygen species (ROS), potent oxidizing agents that damage macromolecules. Increased beta-oxidation, in turn, induces the phase I and II xenobiotic detoxification genes, through PHA-4/FOXA, NHR-8 and aryl hydrocarbon receptor AHR-1, possibly to purge lipophilic endotoxins generated during fatty acid catabolism. The coupling of a metabolic shift with endotoxin detoxification results in extreme longevity following mekk-3 knock-down. Thus, MEKK-3 may function as an important nutrient sensor and signalling component within the organism that controls metabolism. Knocking down mekk-3 may signal an imminent nutrient crisis that results in initiation of a DR-like state, even when food is plentiful. PMID:24655420

Noninvasive prenatal detection of sex chromosomal aneuploidies by sequencing circulating cell-free DNA from maternal plasma.

PubMed

Mazloom, Amin R; Džakula, Željko; Oeth, Paul; Wang, Huiquan; Jensen, Taylor; Tynan, John; McCullough, Ron; Saldivar, Juan-Sebastian; Ehrich, Mathias; van den Boom, Dirk; Bombard, Allan T; Maeder, Margo; McLennan, Graham; Meschino, Wendy; Palomaki, Glenn E; Canick, Jacob A; Deciu, Cosmin

2013-06-01

Whole-genome sequencing of circulating cell free (ccf) DNA from maternal plasma has enabled noninvasive prenatal testing for common autosomal aneuploidies. The purpose of this study was to extend the detection to include common sex chromosome aneuploidies (SCAs): [47,XXX], [45,X], [47,XXY], and [47,XYY] syndromes. Massively parallel sequencing was performed on ccf DNA isolated from the plasma of 1564 pregnant women with known fetal karyotype. A classification algorithm for SCA detection was constructed and trained on this cohort. Another study of 411 maternal samples from women with blinded-to-laboratory fetal karyotypes was then performed to determine the accuracy of the classification algorithm. In the training cohort, the new algorithm had a detection rate (DR) of 100% (95%CI: 82.3%, 100%), a false positive rate (FPR) of 0.1% (95%CI: 0%, 0.3%), and nonreportable rate of 6% (95%CI: 4.9%, 7.4%) for SCA determination. The blinded validation yielded similar results: DR of 96.2% (95%CI: 78.4%, 99.8%), FPR of 0.3% (95%CI: 0%, 1.8%), and nonreportable rate of 5% (95%CI: 3.2%, 7.7%) for SCA determination Noninvasive prenatal identification of the most common sex chromosome aneuploidies is possible using ccf DNA and massively parallel sequencing with a high DR and a low FPR. © 2013 John Wiley & Sons, Ltd.

[Determination of HLA-A, -B and -DRB1 polymorphism in brain dead organ donors representative of the Colombian general population, 2007-2014].

PubMed

Arias, Yazmin Rocío; Osorio-Arango, Karime; Bayona, Brayan; Ercilla, Guadalupe; Beltrán-Durán, Mauricio

2017-06-01

Genes encoding for human leukocyte antigens (HLA) are highly polymorphic and of great importance in organ transplantation procedures, as determining allelic frequencies in defined populations is taken into account among the scientific criteria for organ allocation. The objective of this study was to establish the antigen HLA-A, -B, and -DRB1 haplotype frequencies in organ donors representative of the Colombian population after brain death. We conducted a descriptive retrospective study involving 2,506 cadaveric organ donors including an allelic and haplotype analysis of HLA-A, -B and -DRB1; we also determined the Hardy-Weinberg equilibrium. We identified 21, 43 and 15 allelic loci for groups A*, B* and DRB1*, respectively. We detected 1,268 HLA-A, -B and -DR, 409 HLA-A-B, 383 HLA-DR-B, and 218 HLA-A-DR haplotypes. The three loci were found to be in Hardy-Weinberg equilibrium between the number of heterozygotes observed and the expected number, with p values of ;0.05. This study provides information on the allelic distribution of HLA class I and II in organ donors from the six regions in which Colombia is structurally divided to provide transplant services.

Macromolecular Calculations for the XTAL-System of Crystallographic Programs

DTIC Science & Technology

1990-05-24

C00 004 0 . . 0r004404- to 00 14fl 0. 41 4 zO 04 10-400D 000 0. 014 0 .- 4 14’-0 .41 I’D z qva to r. 1 4)0 0) 14 t .00. .. V’a00 0 R4 0 -4 H 4 14 014a0...Chemistry & Biochemistry 800 N. Quincy Street College Park, Maryland 20742 Arlington, Virginia 22217-5000 8a \\AE OF FLD,NG, 1 SPONSORING 8b OFFICE...Dr. Michael Marron 1 202-696-4760 1 ONR DO FORM 1473, P4 MAR 83 APR edition may be used until exhausted. SECURITY CLASSIFICATION OF THIS PAGE All

Damping Proceedings Held in Las Vegas, Nevada on 5-7 March 1986. Volume 1

DTIC Science & Technology

1986-05-01

Parin AE-1 -_ Design Oriented Measuring Techniques for Determining the Mechanical Properties of Rubber ;! Dr.lr. B. Devis, Dr.Ir. C. DeMeetsman, and...Prof,.Ir.., J. Peters AF-1 ’Selected Complex Modulus Data;JW C. Chesneau and B. Ouperray AG -I - On The Fractional Calculus Model of Viscoelastic...HUC Rubber i 0 composite material ci an elamtomeric astrf.x and iller partx Ccarbon b, ctk fibrea textiles, ... ). Although it *eem to ill

Upregulation of nuclear transporter, Kpnβ1, contributes to accelerated cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) in diffuse large B-cell lymphoma.

PubMed

He, Song; Miao, Xiaobing; Wu, Yaxun; Zhu, Xinghua; Miao, Xianjing; Yin, Haibing; He, Yunhua; Li, Chunsun; Liu, Yushan; Lu, Xiaoyun; Chen, Yali; Wang, Yuchan; Xu, Xiaohong

2016-03-01

The Karyopherin proteins are involved in the shuttling of cargo proteins, and certain RNAs, across the nuclear pore complex into and out of the cell nucleus. Karyopherin β1 (Kpnβ1) is a member of the Karyopherin β superfamily of nuclear transport proteins. In addition to the nuclear import function, Kpnβ1 is associated with the occurrence of tumors. This study investigated the expression and biologic function of Kpnβ1 in diffuse large B-cell lymphoma (DLBCL). The prognostic value of Kpnβ1 expression was evaluated using immunohistochemical staining. The role of Kpnβ1 on cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) was also determined. We demonstrated that Kpnβ1 mRNA and protein expression levels were significantly higher in DLBCL B-cells and DLBCL cell lines than in normal CD19 purified B-cells. Immunohistochemical analysis suggested that the expression of Kpnβ1 was correlated with Ki-67 (P < 0.001). Kaplan-Meier curve showed that high expression of Kpnβ1 was significantly associated with shorter overall survival. In addition, Kpnβ1 was associated with the proliferation of DLBCL cells. Importantly, we found that Kpnβ1 could interact with p65 and promote CAM-DR via accelerating NF-κB activation in DLBCL. Patients with tumors highly expressing Kpnβ1 have poorer overall survivals. Kpnβ1 interacts with p65 and enhances CAM-DR.

Increased Plasma Levels of Danger-Associated Molecular Patterns Are Associated With Immune Suppression and Postoperative Infections in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

PubMed

Leijte, Guus P; Custers, Hettie; Gerretsen, Jelle; Heijne, Amon; Roth, Johannes; Vogl, Thomas; Scheffer, Gert J; Pickkers, Peter; Kox, Matthijs

2018-01-01

Danger-associated molecular patterns (DAMPs) can elicit immune responses and may subsequently induce an immune-suppressed state. Previous work showed that increased plasma levels of DAMPs are associated with immune suppression and increased susceptibility toward infections in trauma patients. Like trauma, major surgical procedures, such as cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), are also thought to cause profound DAMP release. Furthermore, the incidence of postoperative infections in these patients, ranging from 10 to 36%, is very high compared to that observed in patients undergoing other major surgical procedures. We hypothesized that the double hit of surgical trauma (CRS) in combination with HIPEC causes excessive DAMP release, which in turn contributes to the development of immune suppression. To investigate this, we assessed DAMP release in patients undergoing CRS-HIPEC, and investigated its relationship with immune suppression and postoperative infections. In 20 patients undergoing CRS-HIPEC, blood was obtained at five time points: just before surgery (baseline), after CRS, after HIPEC, at ICU admission, and 1 day after surgery. Circulating levels of DAMPs [heat shock protein (HSP)70, high mobility group box (HMGB)1, S100A12, S100A8/S100A9, nuclear (n)DNA, mitochondrial (mt)DNA, lactate dehydrogenase (LDH), a marker of unscheduled cell death], and cytokines [tumor necrosis factor (TNF)α, IL-6, IL-8, IL-10, macrophage inflammatory protein (MIP)-1α, MIP-1β, and MCP-1] were measured. The extent of immune suppression was determined by measuring HLA-DR gene expression and ex vivo leukocytic cytokine production capacity. Plasma levels of DAMPs (maximum fold increases of HSP70: 2.1 [1.5-2.8], HMGB1: 5.9 [3.2-9.8], S100A8/S100A9: 3.6 [1.8-5.6], S100A12: 2.6 [1.8-4.3], nDNA 3.9 [1.0-10.8], LDH 1.7 [1.2-2.5]), and all measured cytokines increased profoundly following CRS-HIPEC. Evidence of immune suppression was already apparent during the procedure, illustrated by a decrease of HLA-DR expression compared with baseline (0.5-fold [0.3-0.9]) and diminished ex vivo pro-inflammatory cytokine production capacity. The increase in HMGB1 levels correlated with the decrease in HLA-DR expression ( r  = -0.46, p  = 0.04), and peak HMGB1 concentrations were significantly higher in the five patients who went on to develop a postoperative infection (p = 0.04). CRS-HIPEC is associated with profound DAMP release and immune suppression, and plasma HMGB1 levels are related with the occurrence of postoperative infections in these patients.

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

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

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.

Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease

PubMed Central

Hamza, Taye H; Zabetian, Cyrus P; Tenesa, Albert; Laederach, Alain; Montimurro, Jennifer; Yearout, Dora; Kay, Denise M; Doheny, Kimberly F; Paschall, Justin; Pugh, Elizabeth; Kusel, Victoria I; Collura, Randall; Roberts, John; Griffith, Alida; Samii, Ali; Scott, William K; Nutt, John; Factor, Stewart A; Payami, Haydeh

2010-01-01

Parkinson disease (PD) is a common disorder that leads to motor and cognitive disability. We performed a genome-wide association study (GWAS) with 2000 PD and 1986 control Caucasian subjects from NeuroGenetics Research Consortium.1–5 We confirmed SNCA2,6–8 and MAPT3,7–9; replicated GAK9 (PPankratz+NGRC=3.2×10−9); and detected a novel association with HLA (PNGRC=2.9×10−8) which replicated in two datasets (PMeta-analysis=1.9×10−10). We designate the new PD genes PARK17 (GAK) and PARK18 (HLA). PD-HLA association was uniform across genetic and environmental risk strata, and strong in sporadic (P=5.5×10−10) and late-onset (P=2.4×10−8) PD. The association peak was at rs3129882, a non-coding variant in HLA-DRA. Two studies suggested rs3129882 influences expression of HLA-DR and HLA-DQ.10,11 PD brains exhibit up-regulation of DR antigens and presence of DR-positive reactive microglia.12 Moreover, non-steroidal anti-inflammatory drugs (NSAID) reduce PD risk.4,13 The genetic association with HLA coalesces the evidence for involvement of the immune system and offers new targets for drug development and pharmacogenetics. PMID:20711177

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

Development Of A Vaccine Targeting Triple-Negative Breast Cancer

DTIC Science & Technology

2011-09-01

p787-801 8.5 0-47.1 6.1 0-49.3 p891-905 33.6 0-126.6 15.8 0-68.8 p906-920 24 0-118.9 20 0-94 p921-935 20.1 0-118 15.6 0-39 p1028- 1042 33 0-91.6...Piesche M, Hildebrandt Y, Zettl F, et.al. Identification of a promiscuous HLA DR-restricted T-cell epitope derived from the inhibitor of apoptosis protein

Neuroinflammation is increased in the parietal cortex of atypical Alzheimer's disease.

PubMed

Boon, Baayla D C; Hoozemans, Jeroen J M; Lopuhaä, Boaz; Eigenhuis, Kristel N; Scheltens, Philip; Kamphorst, Wouter; Rozemuller, Annemieke J M; Bouwman, Femke H

2018-05-29

While most patients with Alzheimer's disease (AD) present with memory complaints, 30% of patients with early disease onset present with non-amnestic symptoms. This atypical presentation is thought to be caused by a different spreading of neurofibrillary tangles (NFT) than originally proposed by Braak and Braak. Recent studies suggest a prominent role for neuroinflammation in the spreading of tau pathology. We aimed to explore whether an atypical spreading of pathology in AD is associated with an atypical distribution of neuroinflammation. Typical and atypical AD cases were selected based on both NFT distribution and amnestic or non-amnestic clinical presentation. Immunohistochemistry was performed on the temporal pole and superior parietal lobe of 10 typical and 9 atypical AD cases. The presence of amyloid-beta (N-terminal; IC16), pTau (AT8), reactive astrocytes (GFAP), microglia (Iba1, CD68, and HLA-DP/DQ/DR), and complement factors (C1q, C3d, C4b, and C5b-9) was quantified by image analysis. Differences in lobar distribution patterns of immunoreactivity were statistically assessed using a linear mixed model. We found a temporal dominant distribution for amyloid-beta, GFAP, and Iba1 in both typical and atypical AD. Distribution of pTau, CD68, HLA-DP/DQ/DR, C3d, and C4b differed between AD variants. Typical AD cases showed a temporal dominant distribution of these markers, whereas atypical AD cases showed a parietal dominant distribution. Interestingly, when quantifying for the number of amyloid-beta plaques instead of stained surface area, atypical AD cases differed in distribution pattern from typical AD cases. Remarkably, plaque morphology and localization of neuroinflammation within the plaques was different between the two phenotypes. Our data show a different localization of neuroinflammatory markers and amyloid-beta plaques between AD phenotypes. In addition, these markers reflect the atypical distribution of tau pathology in atypical AD, suggesting that neuroinflammation might be a crucial link between amyloid-beta deposits, tau pathology, and clinical symptoms.

Tools to Compare Diving-Animal Kinematics with Acoustic Behavior and Exposure

DTIC Science & Technology

2011-09-30

to humpback whales; under Dr. Stephen Insley, then at the University of California at Santa Cruz , to northern fur seals (Figure 3; Insley et al...Richardson (Anchorage, Alaska) and Dr. Manuel Castellote of the National Marine Mammal Laboratory to assess applicability of the Acousonde 3B to

Adaptation of Physiological and Cognitive Workload via Interactive Multi-modal Displays

DTIC Science & Technology

2014-05-28

peer-reviewed journals (N/A for none) 09/07/2013 Received Paper 8.00 James Merlo, Joseph E. Mercado , Jan B.F. Van Erp, Peter A. Hancock. Improving...08, . : , Mr. Joseph Mercado , Mr. Timothy White, Dr. Peter Hancock. Effects of Cross-Modal Sensory Cueing Automation Failurein a Target Detection Task...fields:...... ...... ...... ...... ...... PERCENT_SUPPORTEDNAME FTE Equivalent: Total Number: Discipline Joseph Mercado 0.50 Timothy White 0.50 1.00 2

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).

Multilocus sequence typing (MLST) of leptospiral strains isolated from two geographic locations of Tamil Nadu, India.

PubMed

Kanagavel, Murugesan; Princy Margreat, Alphonse Asirvatham; Arunkumar, Manivel; Prabhakaran, Shanmugarajan Gnanasekaran; Shanmughapriya, Santhanam; Natarajaseenivasan, Kalimuthusamy

2016-01-01

Here the rodent carrier status for the transmission of human leptospirosis in Tiruchirappalli, district, Tamil Nadu, India was assessed. The predominantly circulating leptospiral STs were recognized by multilocus sequence typing (MLST). A total of 113 rodents were trapped from different provinces of the Tiruchirappalli district. The most prevalent rodent was Bandicota bengalensis (37.2%), and of the total, 52.2% (n=59) rodents were found to be positive for leptospiral 16S rRNA. These results were validated with a leptospiral culture positivity of 45.8% (n=27). Three isolates from Chennai (2 rodents and 1 human) and 1 human isolate from Tiruchirappalli were included to understand the spatial variations and to track the source of human leptospirosis. The serogroup, serovar, and species level identification of all 31 isolates identified 28 to be Leptospira borgpetersenii serovar Javanica and three as Leptospira interrogans serovar Autumnalis. MLST analysis defined all isolates to the existing ST profiles (ST145 and ST27) with the exception of 6 L. borgpetersenii (ST DR) isolates that showed variations in the sucA and pfkB loci. The DR ST was locally confined to Chatram province of Tiruchirappalli suggesting an epidemiological link. The predominant STs, ST145 and ST-DR form a group, indicating the presence of original strain that subsequently diverged evolutionarily into two STs. The variations between L. borgpetersenii in sucA and pfkB loci may be an indication that evolutionary changes transpired in Tiruchirappalli. Copyright © 2015 Elsevier B.V. All rights reserved.

Plasmodium Coatneyi Ring-Infected Erythrocyte Surface Antigens

DTIC Science & Technology

1993-01-01

corresponding to the 3’ repeat sequence of P. during one or multiple infections, pooled sera falciparum RESA (a gift from Dr. Troye -Blom- from humans who had a...310: primte alaia delin hic an ntiodyre-789-792. primte alaia ode inwhic anantbod re 8.Kabilan L. Troye -Blomberg M, Patarroyo ME,sponse to RESA occurs...Diseases. Centers for Disease 9. Kabilan L. Troye -Blomberg M, Perlmann H. An- Control and Prevention, Atlanta. GA). We thank C. dersson G. Hogh B

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

Immunization-induced perturbation of human blood plasma cell pool: progressive maturation, IL-6 responsiveness, and high PRDI-BF1/BLIMP1 expression are critical distinctions between antigen-specific and nonspecific plasma cells.

PubMed

González-García, Inés; Ocaña, Esther; Jiménez-Gómez, Gema; Campos-Caro, Antonio; Brieva, José A

2006-04-01

The present study shows that reimmunization with tetanus toxoid (tet) caused a transient increase of the human blood plasma cell (PC) pool, detectable from 6th to 15th day postboost, as well as the temporal alteration of several PC features. Labeling of specific PC with FITC-tet C fragment (tetC) allowed kinetics analysis of the tetC(+) and tetC(-) PC, and revealed remarkable differences between them: 1) the kinetics of tetC(+) PC occurrence was exponential, and most of them appeared in a narrow time frame (5th to 8th day postboost), whereas the tetC(-) PC increase was lower (three to five times) and more prolonged (4th to 15th day postboost). 2) The tetC(+) PC subset contained a fraction of cycling cells, expressed high levels of DR, CD138, and CD126, and responded to IL-6 by improving their survival and Ig secretion; in contrast, the tetC(-) PC showed higher CXCR4 and lower DR and CD138, did not respond to IL-6, and contained a fraction of apoptotic cells. 3) Sequential phenotypic analysis revealed maturational changes within the tetC(+), but not tetC(-), PC subset; sequencing of tetC(+) PC IgVH genes showed clear features of Ag selection. 4) The tetC(+) PC expressed several times more positive regulatory domain I- binding factor 1/B lymphocyte-induced maturation protein 1 transcription factor than the tetC(-) PC. 5) The tetC(-) PC and bone marrow resident PC similarly expressed low DR and high CXCR4, but differed in that the latter exhibited higher levels of CD31, CD138, and positive regulatory domain I- binding factor 1/B lymphocyte-induced maturation protein 1. These findings support the view that tetC(+) PC contain bone marrow PC precursors, and tetC(-) PC probably belong to a removable compartment of aged PC.

A Componential Approach to Training Reading Skills.

DTIC Science & Technology

1983-03-17

1 syllable, mixed vowels A2 16 one-syll., 4 two-syll., mixed vowels A3 14 one-syll., 6 two-syll., mixed vowels A4 All two-syllable, mixed vowels* B1 ...06520 I ERIC Facility-Acquisitions I Dr. John S. Brown 4833 Rugby Avenue XEROX Palo Alto Research Center Bethesda, MD 20014 3333 Coyote Road Palo Alto, CA

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

Genetic Mapping of Quantitative Trait Loci for Grain Yield under Drought in Rice under Controlled Greenhouse Conditions

NASA Astrophysics Data System (ADS)

Solis, Julio; Gutierrez, Andres; Mangu, Venkata; Sanchez, Eduardo; Bedre, Renesh; Linscombe, Steve; Baisakh, Niranjan

2017-12-01

Drought stress is a constant threat to rice production worldwide. Most Mmodern rice cultivars are sensitive to drought, and the effect is severe at the reproductive stage. Conventional breeding for drought resistant (DR) rice varieties is slow and limited due to the quantitative nature of the DR traits. Identification of genes (QTLs)/markers associated with DR traits is a prerequisite for marker-assisted breeding. Grain yield is the most important trait and to this end drought yield QTLs have been identified under field conditions. The present study reports identification of drought yield QTLs under controlled conditions without confounding effects of other factors prevalent under natural conditions. A linkage map covering 1,781.5 cM with an average resolution of 9.76 cM was constructed using an F2 population from a cross between two Japonica cultivars, Cocodrie (drought sensitive) and Vandana (drought tolerant) with 213 markers distributed over 12 rice chromosomes. A subset of 59 markers (22 genic SSRs and 37 SNPs) derived from the transcriptome of the parents were also placed in the map. Single marker analysis using 187 F2:3 progeny identified 6 markers distributed on chromosomes 1, 5, and 8 to be associated with grain yield under drought (GYD). Composite interval mapping identified six genomic regions/quantitative trait loci (QTL) on chromosome 1, 5, 8, and 9 to be associated with GYD. QTLs located on chromosome 1 (qGYD1.2, qGYD1.3), chromosome 5 (qGYD5.1) and chromosome 8 (qGYD8.1) were contributed by Vandana alleles, whereas the QTLs, qGYD1.1 and qQYD9.1 were contributed by Cocodrie alelles. The additive positive phenotypic variance explained by the QTLs ranged from 30.0% to 34.0%. Candidate genes annotation within QTLs suggested the role of transcription factors and genes involved in osmotic potential regulation through catalytic/metabolic pathways in drought resistance tolerance mechanism contributing to yield.

DR3 regulation of apoptosis of naive T-lymphocytes in children with acute infectious mononucleosis.

PubMed

Filatova, Elena Nikolaevna; Anisenkova, Elena Viktorovna; Presnyakova, Nataliya Borisovna; Utkin, Oleg Vladimirovich

2016-09-01

Acute infectious mononucleosis (AIM) is a widespread viral disease that mostly affects children. Development of AIM is accompanied by a change in the ratio of immune cells. This is provided by means of different biological processes including the regulation of apoptosis of naive T-cells. One of the potential regulators of apoptosis of T-lymphocytes is a death receptor 3 (DR3). We have studied the role of DR3 in the regulation of apoptosis of naive CD4 + (nTh) and CD8 + (nCTL) T-cells in healthy children and children with AIM. In healthy children as well as in children with AIM, the activation of DR3 is accompanied by inhibition of apoptosis of nTh. In healthy children, the stimulation of DR3 resulted in the increase in apoptosis of nCTL. On the contrary, in children with AIM, the level of apoptosis of nCTL decreased after DR3 activation, which is a positive contribution to the antiviral immune response. In children with AIM, nCTL are characterized by reduced level of apoptosis as compared with healthy children. These results indicate that DR3 can be involved in the reduction of sensitivity of nCTL to apoptosis in children with AIM.

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.

Time Domain Astronomy with the Harvard Plates: from Cepheids to DASCH

NASA Astrophysics Data System (ADS)

Grindlay, Jonathan E.

2014-06-01

The ~500,000 Harvard glass plate photographic negatives are the world’s largest and most complete (full sky; 107y time span) database for Time Domain Astronomy (TDA) on days-months-decades to century timescales. With plate fields of view ranging from 3o - 30o exposed quasi-randomly full sky from 1885 - 1992, any object is observed ~1000 - 3000 times, with limiting magnitudes ranging from B =12-18. I briefly review some of the colorful history of this massive plate-taking project and a few of the pivotal discoveries (e.g. the “Leavitt Law” for the Cepheid Period-Luminosity relation) made by visual studies of the plates by the true TDA pioneers, the likely <300 different visual users of the plates. I then describe our Digital Access to a Sky Century @ Harvard (DASCH) project to fully digitize and reduce this wealth of data 1 Pb) and provide it on spinning disk to the full astronomical community and public. Using the full-sky APASS catalog giving BVR magnitudes (for V ~9-17) as well as GSC2.3.2 for both fainter and brighter stars, DASCH does spatially resolved (0.25o -0.6o bins) photometric calibrations to derive B magnitudes with rm 0.1mag over the full plate and over the (typically) ~6-8 different principal plate series (telescopes and plate scales) covering any given object, along with ~0.3-1 arcsec astrometry (depending on plate scale) for each stellar object averaged over ~1year. The high speed/precision scanner, plate processing, and analysis pipeline have now enabled the first data releases (DR1-DR3) of 12 to cover full sky and already enabled a wealth of new discoveries. I describe a few examples, such as: K2III giants with decadal variations; a new class of Symbiotic novae; ~50-100y recurrence times for black hole X-ray binary outbursts; and QPOs from 3C273. The DASCH data are increasingly available 15% now; 100% in 3.5y) for TDA on largely unexplored timescales. We are grateful to NSF for support with grants AST-0407380, AST-0909073 and AST-1313370.

Comparison of spectral-domain optical coherence tomography for intra-retinal layers thickness measurements between healthy and diabetic eyes among Chinese adults

PubMed Central

Li, Shu-ting; Wang, Xiang-ning; Du, Xin-hua; Wu, Qiang

2017-01-01

Purpose To compare intra-retinal layer thickness measurements between eyes with no or mild diabetic retinopathy (DR) and age-matched controls using Spectralis spectral-domain optical coherence tomography (SD-OCT). Methods Cross-sectional observational analysis study. High-resolution macular volume scans (30° * 25°) were obtained for 133 type 2 diabetes mellitus (T2DM) patients with no DR, 42 T2DM patients with mild DR and 115 healthy controls. The mean thickness was measured in all 9 Early Treatment Diabetic Retinopathy Study (ETDRS) sectors for 8 separate layers, inner retinal layer (IRL), outer retinal layer (ORL) and total retina (TR), after automated segmentation. The ETDRS grid consisted of three concentric circles of 1-, 3-, and 6-mm diameter. The superior, inferior, temporal, and nasal sectors of the 3- and 6-mm circles were respectively designated as S3, I3, T3, and N3 and S6, I6, T6, and N6. Linear regression analyses were conducted to evaluate the associations between the intra-retinal layer thicknesses, age, diabetes duration, fasting blood glucose and HbA1c. Results The mean age and duration of T2DM were 61.1 and 13.7 years, respectively. Although no significant differences in the average TR and ORL volumes were observed among the groups, significant differences were found in the volume and sectorial thicknesses of the inner plexiform layer (IPL), outer plexiform layer (OPL) and IRL among the groups. In particular, the thicknesses of the IPL (S3, T3, S6, I6 and T6 sectors) and the IRL (S6 sector) were decreased in the no-DR group compared with the controls (P < 0.05). The thickness of the OPL (S3, N3, S6 and N6 sectors) was thinner in the no-DR group than in mild DR (P < 0.05). The average IPL thickness was significantly negatively correlated with age and the duration of diabetes. Conclusion The assessment of the intra-retinal layer thickness showed a significant decrease in the IPL and IRL thicknesses in Chinese adults with T2DM, even in the absence of visible microvascular signs of DR. PMID:28493982

Gravitation on large scales

NASA Astrophysics Data System (ADS)

Giraud, E.

A sample of dwarf and spiral galaxies with extended rotation curves is analysed, assuming that the fraction of dark matter is small. The objective of the paper is to prepare a framework for a theory, based on fundamental principles, that would give fits of the same quality as the phenomenology of dark halos. The following results are obtained: 1) The geodesics of massive systems with low density (Class I galaxies) can be described by the metric ds^2 = b^{-1}(r)dr^2 - b(r)dt^2 + r^2 dOmega^2 where b(r) = 1 - {2 over c^2}({{GM} over r} + gamma_f M^{1/2}) In this expression Gamma_f is a new fundamental constant which has been deduced from rotation curves of galaxies with circular velocity V_c^2 >= 2 {{GM} over r} for all r 2) The above metric is deduced from the conformal invariant metric ds^2 = B^{-1}(r)dr^2 - B(r)dt^2 + r^2 dOmega^2 where B(r) = 1 - {2 over c^2}({{GM} over r} + Gamma_f M^{1/2} + {1 over 3} {Gamma_f^2 over G}r) through a linear transform, u, of the linear special group SL(2, R) 3) The term {2 over c^2}Gamma_f M^{1/2} accounts for the difference between the observed rotation velocity and the Newtonian velocity. The term {2 over {3c^2}}{Gamma_f^2 over G}r is interpreted as a scale invariance between systems of different masses and sizes. 4) The metric B is a vacuum solution around a mass M deduced from the least action principle applied to the unique action I_a = -2 a int (-g)^{1/2} [R_{mu kappa}R^{ mu kappa} - 1/3(Ralphaalpha)^2] dx^4 built with the conformal Weyl tensor 5) For galaxies such that there is a radius, r_0, at which {{GM} over r_0} = Gamma M^{1/2} (Class II), the term Gamma M^{1/2} might be confined by the Newtonian potential yielding stationary solutions. 6) The analysed rotation curves of Class II galaxies are indeed well described with metrics of the form b(r) = 1 - {2 over c^2}({{GM} over r} + (n + 1) Gamma_0 M^{1/2}) where n is an integer and Gamma_0 = {1 over the square root of 3}Gamma_f 7) The effective potential is determined and found to be E(Gamma, r) = {Gamma^2 over G}r 8) A quantized model is deduced from a Schrodinger-type equation - {{D^2} {{d^2 Psi(r)} over {dr^2}}} = {[E - {{G M} over r}] Psi(r)} where D^2 is the product of the energy Gamma M^{1/2} by the square of the radius r where {{G M} over r} = {Gamma_f M^{1/2}}. The boundary conditions are given by Psi (0) = 0 and the effective potential 9) The data are in agreement with the hypothesis of quantization, but that hypothesis is not proved because, the mass-to-light ratio being a ''free'' variable, it is always possible to shift a Gamma-curve out of its best ''energy level''. However, if one moves a Gamma-fit from an ''energy level'' to the next, the fitting of the curve becomes clearly poorer. 10) The Newtonian mass-to-light ratios of Class I galaxies range from ~7 to ~75. The mass-to-light ratios of the same objects deduced from the Gamma-dynamics are reduced to 1.1 <= Mdyn/L <= 7.4. For Class II galaxies, the range of the Newtonian mass-to-light ratios of the sample is 10 <= M_{lum+dark}^N/L <= 40. It is reduced to 1.7 <= Mdyn/L <= 4.2 when using the quantized version of the Gamma-dynamics. It is approximately 3.5 M_odot/L_odot for Sb galaxies and 2 M_odot/L_odot for Sc galaxies. 11) None of the Gamma-fits are poorer than the models with dark halos of the reference articles. The Gamma-dynamics is sensitive to the integrated mass through the term Gamma M^{1/2}, and to the mass and density through the Newtonian term {G M} over r. This kind of coupling is particularly efficient in galaxies like NGC 1560 whose rotation curve shows conspicuous structure.

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

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.

Nationwide Mobile Communication Systems. Volume 3. Appendix B - D

DTIC Science & Technology

1990-06-01

Layover pay: U100111 CDEPUTDB Total layover pay per month SI.0 Istimatd average rtetion (1) 1% Projected layover expene reduction $0.00 iverage musher of...Mail Stop 238-420 Jet Propulsion Laboratory 4800 Oak Grove Drive Pasadena, Ca 91109 38. Radm David M. Cooney, USN 1 6203 Larstan Dr. Alexandria, Va 22312

Catching the missing million: experiences in enhancing TB & DR-TB detection by providing upfront Xpert MTB/RIF testing for people living with HIV in India.

PubMed

Raizada, Neeraj; Sachdeva, Kuldeep Singh; Sreenivas, Achuthan; Kulsange, Shubhangi; Gupta, Radhey Shyam; Thakur, Rahul; Dewan, Puneet; Boehme, Catharina; Paramsivan, Chinnambedu Nainarappan

2015-01-01

A critical challenge in providing TB care to People Living with HIV (PLHIV) is establishing an accurate bacteriological diagnosis. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents results from PLHIV taking part in a large demonstration study across India wherein upfront Xpert MTB/RIF testing was offered to all presumptive PTB cases in public health facilities. The study covered a population of 8.8 million across 18 sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each TU. All HIV-infected patients suspected of TB (both TB and Drug Resistant TB (DR-TB)) accessing public health facilities in study area were prospectively enrolled and provided upfront Xpert MTB/RIF testing. 2,787 HIV-infected presumptive pulmonary TB cases were enrolled and 867 (31.1%, 95% Confidence Interval (CI) 29.4‒32.8) HIV-infected TB cases were diagnosed under the study. Overall 27.6% (CI 25.9-29.3) of HIV-infected presumptive PTB cases were positive by Xpert MTB/RIF, compared with 12.9% (CI 11.6-14.1) who had positive sputum smears. Upfront Xpert MTB/RIF testing of presumptive PTB and DR-TB cases resulted in diagnosis of 73 (9.5%, CI 7.6‒11.8) and 16 (11.2%, CI 6.7‒17.1) rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high 97.7% (CI 89.3‒99.8), with no significant difference with or without prior history of TB treatment. The study results strongly demonstrate limitations of using smear microscopy for TB diagnosis in PLHIV, leading to low TB and DR-TB detection which can potentially lead to either delayed or sub-optimal TB treatment. Our findings demonstrate the usefulness and feasibility of addressing this diagnostic gap with upfront of Xpert MTB/RIF testing, leading to overall strengthening of care and support package for PLHIV.

Catching the Missing Million: Experiences in Enhancing TB & DR-TB Detection by Providing Upfront Xpert MTB/RIF Testing for People Living with HIV in India

PubMed Central

Raizada, Neeraj; Sachdeva, Kuldeep Singh; Sreenivas, Achuthan; Kulsange, Shubhangi; Gupta, Radhey Shyam; Thakur, Rahul; Dewan, Puneet; Boehme, Catharina; Paramsivan, Chinnambedu Nainarappan

2015-01-01

Background A critical challenge in providing TB care to People Living with HIV (PLHIV) is establishing an accurate bacteriological diagnosis. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents results from PLHIV taking part in a large demonstration study across India wherein upfront Xpert MTB/RIF testing was offered to all presumptive PTB cases in public health facilities. Method The study covered a population of 8.8 million across 18 sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each TU. All HIV-infected patients suspected of TB (both TB and Drug Resistant TB (DR-TB)) accessing public health facilities in study area were prospectively enrolled and provided upfront Xpert MTB/RIF testing. Result 2,787 HIV-infected presumptive pulmonary TB cases were enrolled and 867 (31.1%, 95% Confidence Interval (CI) 29.4‒32.8) HIV-infected TB cases were diagnosed under the study. Overall 27.6% (CI 25.9–29.3) of HIV-infected presumptive PTB cases were positive by Xpert MTB/RIF, compared with 12.9% (CI 11.6–14.1) who had positive sputum smears. Upfront Xpert MTB/RIF testing of presumptive PTB and DR-TB cases resulted in diagnosis of 73 (9.5%, CI 7.6‒11.8) and 16 (11.2%, CI 6.7‒17.1) rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high 97.7% (CI 89.3‒99.8), with no significant difference with or without prior history of TB treatment. Conclusion The study results strongly demonstrate limitations of using smear microscopy for TB diagnosis in PLHIV, leading to low TB and DR-TB detection which can potentially lead to either delayed or sub-optimal TB treatment. Our findings demonstrate the usefulness and feasibility of addressing this diagnostic gap with upfront of Xpert MTB/RIF testing, leading to overall strengthening of care and support package for PLHIV. PMID:25658091

Absolute Measurements of Field Enhanced Dielectronic Recombination and Electron Impact Excitation

NASA Astrophysics Data System (ADS)

Savin, Daniel Wolf

Absolute measurements have been made of the dielectronic recombination (DR) rate coefficient for C^ {3+}, via the 2s-2p core -excitation, in an external electric field of 11.4 +/- 0.9(1sigma) V cm ^{-1}; and of the electron impact excitation (EIE) rate coefficient for C ^{3+}(2s-2p) at energies near threshold. The ion-rest-frame FWHM of the electron energy spread was 1.74 +/- 0.22(1sigma) eV. The measured DR rate, at a mean electron energy of 8.26 +/- 0.07(1sigma ) eV, was (2.76+/- 0.75)times 10^{-10} cm^{3 } s^{-1}. The uncertainty quoted for the DR rate is the total experimental uncertainty at a 1sigma<=vel. The present DR result appears to agree with an intermediate coupling calculation which uses the isolated-resonance, single-configuration approximation. In comparing with theory, a semi-classical formula was used to determine which recombined ions were field-ionized by the 4.65 kV cm^{-1} fields in the final-charge-state analyzer and not detected. A more precise treatment of field-ionization, which includes the lifetime of the high Rydberg C^{2+} ions in the external field and the time evolution and rotation of the fields experienced by the recombined ions, is needed before a definitive comparison between experiment and theory can be made. For the EIE results, at an ion-rest-frame energy of 10.10 eV, the measured rate coefficient was (7.79+/- 2.10)times 10^{ -8} cm^3 s^ {-1}. The measured cross section was (4.15+/- 1.12)times 10^{ -16} cm^2. The uncertainties quoted here represent the total experimental uncertainty at a 90 percent confidence level. Good agreement is found with other measurements. Agreement is not good with Coulomb -Born with exchange and two-state close-coupling calculations which fall outside the 90-percent-confidence uncertainty limits. Agreement is better with a nine-state close-coupling calculation which lies at the extreme of the uncertainty limits. Taking into account previous measurements in C ^{3+} and also a measurement of EIE in Be^+ which lies 19 percent below close-coupling calculations, there is a suggestion that the C^{3+}(2s-2p) EIE rate coefficient may fall slightly below presently accepted values.

The cytokine-dependent MUTZ-3 cell line as an in vitro model for the screening of contact sensitizers

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

Azam, Philippe; Peiffer, Jean-Luc; Chamousset, Delphine

2006-04-01

Langerhans cells (LC) are key mediators of contact allergenicity in the skin. However, no in vitro methods exist which are based on the activation process of LC to predict the sensitization potential of chemicals. In this study, we have evaluated the performances of MUTZ-3, a cytokine-dependent human monocytic cell line, in its response to sensitizers. First, we compared undifferentiated MUTZ-3 cells with several standard human cells such as THP-1, KG-1, HL-60, K-562, and U-937 in their response to the strong sensitizer DNCB and the irritant SDS by monitoring the expression levels of HLA-DR, CD54, and CD86 by flow cytometry. Onlymore » MUTZ-3 and THP-1 cells show a strong and specific response to sensitizer, while other cell lines showed very variable responses. Then, we tested MUTZ-3 cells against a wider panel of sensitizers and irritants on a broader spectrum of cell surface markers (HLA-DR, CD40, CD54, CD80, CD86, B7-H1, B7-H2, B7-DC). Of these markers, CD86 proved to be the most reliable since it detected all sensitizers, including benzocaine, a classical false negative in local lymph node assay (LLNA) but not irritants. We confirmed the MUTZ-3 response to DNCB by real-time PCR analysis. Taken together, our data suggest that undifferentiated MUTZ-3 cells may represent a valuable in vitro model for the screening of potential sensitizers.« less

Zerumbone, a Phytochemical of Subtropical Ginger, Protects against Hyperglycemia-Induced Retinal Damage in Experimental Diabetic Rats.

PubMed

Tzeng, Thing-Fong; Liou, Shorong-Shii; Tzeng, Yu-Cheng; Liu, I-Min

2016-07-25

Diabetic retinopathy (DR), the most ordinary and specific microvascular complication of diabetes, is a disease of the retina. Zerumbone (ZER) is a monocyclic sesquiterpene compound, and based on reports, it is the predominant bioactive compound from the rhizomes of Zingiber zerumbet. The aim of the current study is to evaluate the protective effect of zerumbone against DR in streptozotocin (STZ)-induced diabetic rats. STZ-diabetic rats were treated with ZER (40 mg/kg) once a day orally for 8 weeks. ZER administration significantly (p < 0.05) lowered the levels of plasma glucose (32.5% ± 5.7% lower) and glycosylated hemoglobin (29.2% ± 3.4% lower) in STZ-diabetic rats. Retinal histopathological observations indicated that disarrangement and reduction in thickness of retinal layers were reversed in ZER-treated diabetic rats. ZER downregulated both the elevated levels of advanced glycosylated end products (AGEs) and the higher levels of the receptors for AGEs (RAGE) in retinas of diabetic rats. What's more, ZER significantly (p < 0.05) ameliorated diabetes-induced upregulation of tumor necrosis factor-α, interleukin (IL)-1 and IL-6. ZER also attenuated overexpression of vascular endothelial growth factor and intercellular adhesion molecule-1, and suppressed activation of nuclear factor (NF)-κB and apoptosis in the retinas of STZ-diabetic rats. Our results suggest ZER possesses retinal protective effects, which might be associated with the blockade of the AGEs/RAGE/NF-κB pathway and its anti-inflammatory activity.

Excited-State Properties of Semiconductor Electrodes and Their Application to Optical Energy Conversion.

DTIC Science & Technology

1985-12-26

DC/TR-83/3 has been published: "Polarization Effects in the Luminescence of Cadmium Selenide Electrodes", H.H. Streckert, H. Van Ryswyk, R.N. Biagioni ...Radiative Recombination in a Stable Photoelectrochemical Cell", P.M. Smiley, P.N. Biagioni , and A.B. Ellis, J. Electrochem. Soc., 131, 1068 (1984...has been assigned to the 3M Co. .-’ PERSONNEL Arthur B. Ellis, P.1. Bryan Benedict * Dr. Richard Biagioni Daniel Bilich Al Burk, Jr. -Ph.D. received

HLA is not predictive of posttransplant diabetes mellitus.

PubMed

Torres-Romero, L F; Santiago-Delpín, E A; de Echegaray, Sally; Solis, D R; Rodriguez-Trinidad, A T; Gonzalez-Caraballo, Z A; Morales-Otero, L A

2006-04-01

New-onset posttransplant diabetes mellitus (PTDM) is a frequent complication of kidney transplantation. The goal of this study was to identify if the tendency to develop PTDM was associated to the HLA, as is seen in the general population. A retrospective study was made of 525 patients who underwent renal transplantation between 1997 and 2004. They were divided into three categories depending on the diabetic status before and after kidney transplantation. The HLA profile of each patient was identified for class 1 and class 2 antigens including HLA-A, HLA-B, and DR-R. Antigen frequencies were calculated and gene frequencies derived. These were compared among the three groups and with the published data for the Puerto Rico population. Other variables studied included weight, age, gender, and family history. Seventy-two of 526 (13.7%) were diabetic before transplantation; 92/453 (20.3%) developed PTDM after kidney transplantation. Pretransplant diabetics showed a higher incidence of A3 (0.1102 vs 0.0869 vs 0.0361), DR4 (0.3334 vs 0.1932 vs 0.2124), and DR-13 (0.1835 vs 0.1115 vs 0.1175) than nondiabetics and the normal Puerto Rican population. Posttransplant diabetics showed a higher A3 (0.1154) and a higher DR3 (0.0675 vs 0.0295 vs 0.0022) than nondiabetics and normal population. PTDM was not associated statistically with the HLA in this group of transplant recipients, although A3 and DR3 were higher. Patients with the phenotype that is related to diabetes in the normal population did not have a higher incidence of diabetes in this series.

Adaptive Liquid Crystal TV Based Joint Transform Correlator as Applied to Real-Time Pattern Recognition

DTIC Science & Technology

1991-05-23

rotational objects can b ec-tetd. E-Ac Ceedent 3exp-erimental demon ct r-ati ons for these tuo zethodsc hare L-en nerfor-med.A aner atohi naturve xs...dependent nature ---f the Joint rransifore f.Iter. Unlike theVa.dr %g~ii ssignal indepndent. a0. eir -las 3advata in real-tim ’-n14-a-entatio-n...a-tit reI ra-’ t --er is n -) 0 s-’ow Uha thsthoesc~-heo 8 spectral content of the target. A paper of this nature is published in the Optics and

Intelligent Data Fusion for Wide-Area Assessment of UXO Contamination

DTIC Science & Technology

2008-02-29

Development Program (SERDP). The authors thank the SERDP staff and team members for their assistance, particularly Dr. Herb Nelson and Dr. Dan Steinhurst...Fusion and Integration for Intelligent Systems, Taipei, Taiwan , R.O.C., Aug., 1999. 4. B.J. Johnson, T.G. Moore, B.J. Blejer, C.F. Lee, T.P. Opar, S...gene-expression data using Dempster-Shafer Theory of evidence to predict breast cancer tumors,” Bioinformation 1(5), 170-5, (2006) 21. Dr. Herb H. Nelson, personal communication (2007)

X-ray Variability Constraints on Compton Cloud Models of Cygnus X-1

NASA Technical Reports Server (NTRS)

Vaughan, Brian

1999-01-01

We have now completed this work, and all related publications have either appeared in print or are currently in press. A list of these publications is given below. There have been essentially three works that have arisen from this proposal. Spectral analysis of the data is presented in Dove et al. (1998a). Timing analysis is presented in Nowak et al. (1999a). Theoretical implications of the data analysis are discussed in Nowak et al. (1999b). Preliminary versions of all these works were presented at various conferences, and are reported in Nowak et al. (1997, 1998), Wilms et al. (1997), and Dove et al. (1998b). The grant was predominantly used for salary support for Dr. Michael Nowak, Dr. James Dove, and Dr. J. Wilms during the course of these projects. Grant funds were also used for Dr. Nowak to travel to Caltech to perform data analysis with Dr. Brian Vaughan, and for Dr. Wilms to visit JILA, University of Colorado, where much of this work was performed.

Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis

PubMed Central

Kim, Ji H.; Gupta, Subash C.; Park, Byoungduck; Yadav, Vivek R.; Aggarwal, Bharat B.

2012-01-01

Scope The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Methods and results Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Conclusion Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways. PMID:22147524

Retinal vascular injuries and intravitreal human embryonic stem cell-derived haemangioblasts.

PubMed

Wang, Jin-Da; An, Ying; Zhang, Jing-Shang; Wan, Xiu-Hua; Zhang, Wei; Lanza, Robert; Lu, Shi-Jiang; Jonas, Jost B; Xu, Liang

2017-09-01

To investigate whether intravitreally applied haemangioblasts (HB) derived from human embryonic stem cells (hESCs) are helpful for the repair of vascular damage caused in animals by an oxygen-induced retinopathy (OIR), by an induced diabetic retinopathy (DR) or by an induced retinal ischaemia with subsequent reperfusion. Human embryonic stem cell-derived HBs were transplanted intravitreally into C57BL/6J mice (OIR model), into male Wistar rats with an induced DR and into male Wistar rats undergoing induced retinal ischaemia with subsequent reperfusion. Control groups of animals received an intravitreal injection of endothelial cells (ECs) or phosphate-buffered saline (PBS). We examined the vasculature integrity in the mice with OIR, the blood-retina barrier in the rats with induced DR, and retinal thickness and retinal ganglion cell density in retina flat mounts of the rats with the retinal ischaemic-reperfusion retinopathy. In the OIR model, the study group versus control groups showed a significantly (p < 0.001) smaller retinal avascular area [5.1 ± 2.7%;n = 18 animals versus 12.2 ± 2.8% (PBS group; n = 10 animals) and versus 11.8 ± 3.7% (EC group; n = 8 animals)] and less retinal neovascularization [6.3 ± 2.5%;n = 18 versus 15.2 ± 6.3% (n = 10; PBS group) and versus 15.8 ± 3.3% (n = 8; EC group)]. On retinal flat mounts, hESC-HBs were integrated into damaged retinal vessels and stained positive for PECAM (CD31) as EC marker. In the DR model, the study group versus the EC control group showed a significantly (p = 0.001) better blood-retina barrier function as measured at 2 days after the intravitreal injections [study group: 20.2 ± 12.8 μl/(g × hr); n = 6; versus EC control group: 52.9 ± 9.9 μl/(g × hr; n = 6)]. In the retinal ischaemia-reperfusion model, the groups did not differ significantly in retinal thickness and retinal ganglion cell density at 2, 5 and 7 days after baseline. By integrating into damaged retinal vessels and differentiating into ECs, intravitreally administered hESC-HBs may have partially repaired a retinal vascular injury caused by OIR model and DR. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Genetic variability in the tumor necrosis factor-lymphotoxin region influences susceptibility to rheumatoid arthritis

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

Mulcahy, B.; Waldron-Lynch, F.; Adams, C.

The major histocompatibility complex class H1 tumor necrosis factor-tymphotoxin (TNF-LT) region (6p21.3) was investigated as a possible susceptibility locus for rheumatoid arthritis (RA). Inheritance of five TNF microsatellite markers was determined in 50 multiplex families. Overall, 47 different haplotypes were observed. One of these, the TNF a6, b5, c1, d3, e3 (H1) haplotype, was present in 35.3% of affected, but in only 20.5% of unaffected, individuals (P < .005). This haplotype accounted for 21.5% of the parental haplotypes transmitted to affected offspring and only 7.3 % not transmitted to affected offspring (P = .0003). The TNF a6 and TNF c1more » alleles were individually associated with RA (P = .0005 and .0008, respectively), as were the HLA-DRB1 {open_quotes}shared epitope{close_quotes} (SE) (P = .0001) and HLA-DRB1*0401 (P = .0018). Both univariate and bivariate conditional logistic regression analysis showed significant effects of TNF c1 and SE in increasing risk to RA (P < .001). Stratification by the presence of SE indicated an independent effect of the TNFc1 allele (P = .0003) and the HLA A1, BS, DR3 extended haplotype (always TNFa2, b3, c1, d1, e3) (P = .0027) in SE heterozygotes, while the H1 haplotype was associated with RA in SE homozygotes (P = .0018). The TNF-LT region appears to influence susceptibility to RA, distinct from HLA-DR. 50 refs., 1 fig., 1 tab.« less

Aluminium and titanium modified mesoporous TUD-1: A bimetal acid catalyst for Biginelli reaction

NASA Astrophysics Data System (ADS)

Pasupathi, M.; Santhi, N.; Pachamuthu, M. P.; Alamelu Mangai, G.; Ragupathi, C.

2018-05-01

Using a simple, non-surfactant template triethanolamine (TEA), bimetal (Al3+ and Ti4+ ions) incorporated mesoporous catalyst AlTiTUD-1 (Si/Al+Ti = 50) was synthesized. The catalyst was characterized by XRD (Low and High angle), N2 Sorption, FTIR, SEM, TEM, DR UV Visible, and pyridine adsorbed FT-IR techniques. The XRD and N2 sorption studies confirmed its amorphous, mesoporous nature, which possessed a BET surface area of 590 m2 g-1 and pore diameter of 4.4 nm. The Al3+ and Ti4+ co-ordination within the TUD-1 was evaluated by DR UV-Vis. Pyridine adsorbed FTIR revealed both Bronsted (B) and Lewis (L) acidity, which is responsible for the catalytic activity. The acid catalyst showed a good catalytic performance in Biginelli type multicomponent coupling reaction for the substituted aldehydes, ethyl acetoacetate and thiourea to yield about 70% in reflux condition.

Monoclonal antibody fluorescence for routine lymphocyte subpopulation analysis with the Abbott CELL-DYN Sapphire haematology analyser.

PubMed

Molero, T; Lemes, A; DE LA Iglesia, S; Scott, C S

2007-12-01

Using previously described procedures, this study quantified T-cell, T-cell subset, B-cell and NK-cell populations with the CD-Sapphire haematology analyser in a series of patients with mild to moderate lymphocytosis. Lymphocyte counts ranged from 6.0 to 14.9 x 10(9)/l, with 86/97 being <10.0 x 10(9)/l. Immunophenotyping (CD3/CD19/HLA-DR, CD4/CD8 and CD16/CD56 combinations) was performed using EDTA-anticoagulated blood, automated CD-Sapphire analysis and subsequent software processing. Of 35 samples from younger (<12 years) patients, 22 (63%) had nonspecific lymphocyte changes, 4 (11%) showed specific increases in nonreactive T-Helper or T-Suppressor cells, and five showed a reactive T-cell lymphocytosis. The remaining four were classified as 'Transient/Persistent NK-associated (NKa) Expansion' (n = 3) and specific B-cell lymphocytosis (n = 1). For older patients (n = 59), 15 (25%) had an increase (>1.5 x 10(9)/l) in B-cells, and seven investigated for surface immunoglobulin expression were all found to be clonal. The remaining samples were categorized as 'Transient/Persistent NK-associated (NKa) Expansion' (13/59), Reactive Lymphocytosis (5/59), 'Reactive Lymphocytosis or Transient/Persistent NKa Expansion' (8/59), specific T-Helper cell (n = 8) or T-Suppressor cell (n = 3) lymphocytosis, and 'Lymphocytosis of Undetermined Significance' (n = 7). This study has demonstrated the feasibility of applying limited immunophenotyping protocols to the investigation of patients with abnormal lymphocyte counts in routine haematology. By using commercially purchased liquid monoclonal reagents to determine lymphocyte subpopulation profiles, haematology laboratories can provide more definitive information of potential clinical importance.

Determination of physiological, taxonomic, and molecular characteristics of a cultivable arsenic-resistant bacterial community.

PubMed

Cordi, A; Pagnout, C; Devin, S; Poirel, J; Billard, P; Dollard, M A; Bauda, P

2015-09-01

A collection of 219 bacterial arsenic-resistant isolates was constituted from neutral arsenic mine drainage sediments. Isolates were grown aerobically or anaerobically during 21 days on solid DR2A medium using agar or gelan gum as gelling agent, with 7 mM As(III) or 20 mM As(V) as selective pressure. Interestingly, the sum of the different incubation conditions used (arsenic form, gelling agent, oxygen pressure) results in an overall increase of the isolate diversity. Isolated strains mainly belonged to Proteobacteria (63%), Actinobacteria (25%), and Bacteroidetes (10%). The most representative genera were Pseudomonas (20%), Acinetobacter (8%), and Serratia (15%) among the Proteobacteria; Rhodococcus (13%) and Microbacterium (5%) among Actinobacteria; and Flavobacterium (13%) among the Bacteroidetes. Isolates were screened for the presence of arsenic-related genes (arsB, ACR3(1), ACR3(2), aioA, arsM, and arrA). In this way, 106 ACR3(1)-, 74 arsB-, 22 aioA-, 14 ACR3(2)-, and one arsM-positive PCR products were obtained and sequenced. Analysis of isolate sensitivity toward metalloids (arsenite, arsenate, and antimonite) revealed correlations between taxonomy, sensitivity, and genotype. Antimonite sensitivity correlated with the presence of ACR3(1) mainly present in Bacteroidetes and Actinobacteria, and arsenite or antimonite resistance correlated with arsB gene presence. The presence of either aioA gene or several different arsenite carrier genes did not ensure a high level of arsenic resistance in the tested conditions.

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/).

ONRASIA Scientific Information Bulletin. Volume 17, Number 2, Apr-Jun 1992

DTIC Science & Technology

1992-06-01

the Physics Division, Research 7. K Yagi, H . Onuki , S. Sugiyama, Department. Dr. Rehn received his andT. Yamazaki,BunkyoKenkyu 40(5) B.A. in physics at...Pittsburgh in 1962. Aftercomplet- 8. T. Saito, K Katori, M. Nishi, and ing his thesis research in nuclear H . Onuki , Rev. Sci. Instru. 60, 2303...quadrupole resonance studies of para (1989); T. Saito, K Katori, and H . Onuki , dichlorobenzene and related mate- Physica Scripta 41,783 (1990). rials, Dr. Rchn

Extremophilic Acinetobacter strains from high-altitude lakes in Argentinean Puna: remarkable UV-B resistance and efficient DNA damage repair.

PubMed

Albarracín, Virginia Helena; Pathak, Gopal P; Douki, Thierry; Cadet, Jean; Borsarelli, Claudio Darío; Gärtner, Wolfgang; Farias, María Eugenia

2012-06-01

High-Altitude Andean Lakes (HAAL) of the South American Andes are almost unexplored ecosystems of shallow lakes. The HAAL are recognized by a remarkably high UV exposure, strong changes in temperature and salinity, and a high content of toxic elements, especially arsenic. Being exposed to remarkably extreme conditions, they have been classified as model systems for the study of life on other planets. Particularly, Acinetobacter strains isolated from the HAAL were studied for their survival competence under strong UV-B irradiation. Clinical isolates, Acinetobacter baumannii and Acinetobacter johnsonii, served as reference material. Whereas the reference strains rapidly lost viability under UV-B irradiation, most HAAL-derived strains readily survived this exposure and showed less change in cell number after the treatment. Controls for DNA repair activity, comparing dark repair (DR) or photo repair (PR), gave evidence for the involvement of photolyases in the DNA repair. Comparative measurements by HPLC-mass spectrometry detected the number of photoproducts: bipyrimidine dimers under both PR and DR treatments were more efficiently repaired in the HAAL strains (up to 85 % PR and 38 % DR) than in the controls (31 % PR and zero DR ability). Analysis of cosmid-cloned total genomic DNA from the most effective DNA-photorepair strain (Ver3) yielded a gene (HQ443199) encoding a protein with clear photolyase signatures belonging to class I CPD-photolyases. Despite the relatively low sequence similarity of 41 % between the enzymes from Ver3 and from E. coli (PDB 1DNPA), a model-building approach revealed a high structural homology to the CPD-photolyase of E. coli.

ACPA-Negative RA Consists of Two Genetically Distinct Subsets Based on RF Positivity in Japanese

PubMed Central

Terao, Chikashi; Ohmura, Koichiro; Ikari, Katsunori; Kochi, Yuta; Maruya, Etsuko; Katayama, Masaki; Yurugi, Kimiko; Shimada, Kota; Murasawa, Akira; Honjo, Shigeru; Takasugi, Kiyoshi; Matsuo, Keitaro; Tajima, Kazuo; Suzuki, Akari; Yamamoto, Kazuhiko; Momohara, Shigeki; Yamanaka, Hisashi; Yamada, Ryo; Saji, Hiroo; Matsuda, Fumihiko; Mimori, Tsuneyo

2012-01-01

HLA-DRB1, especially the shared epitope (SE), is strongly associated with rheumatoid arthritis (RA). However, recent studies have shown that SE is at most weakly associated with RA without anti-citrullinated peptide/protein antibody (ACPA). We have recently reported that ACPA-negative RA is associated with specific HLA-DRB1 alleles and diplotypes. Here, we attempted to detect genetically different subsets of ACPA-negative RA by classifying ACPA-negative RA patients into two groups based on their positivity for rheumatoid factor (RF). HLA-DRB1 genotyping data for totally 954 ACPA-negative RA patients and 2,008 healthy individuals in two independent sets were used. HLA-DRB1 allele and diplotype frequencies were compared among the ACPA-negative RF-positive RA patients, ACPA-negative RF-negative RA patients, and controls in each set. Combined results were also analyzed. A similar analysis was performed in 685 ACPA-positive RA patients classified according to their RF positivity. As a result, HLA-DRB1*04:05 and *09:01 showed strong associations with ACPA-negative RF-positive RA in the combined analysis (p = 8.8×10−6 and 0.0011, OR: 1.57 (1.28–1.91) and 1.37 (1.13–1.65), respectively). We also found that HLA-DR14 and the HLA-DR8 homozygote were associated with ACPA-negative RF-negative RA (p = 0.00022 and 0.00013, OR: 1.52 (1.21–1.89) and 3.08 (1.68–5.64), respectively). These association tendencies were found in each set. On the contrary, we could not detect any significant differences between ACPA-positive RA subsets. As a conclusion, ACPA-negative RA includes two genetically distinct subsets according to RF positivity in Japan, which display different associations with HLA-DRB1. ACPA-negative RF-positive RA is strongly associated with HLA-DRB1*04:05 and *09:01. ACPA-negative RF-negative RA is associated with DR14 and the HLA-DR8 homozygote. PMID:22792215

Predominance of DR3 in Somali children with type 1 diabetes in the twin cities, Minnesota.

PubMed

Sunni, Muna; Noble, Janelle A; Yu, Liping; Mahamed, Zahra; Lane, Julie A; Dhunkal, Abdirahman M; Bellin, Melena D; Nathan, Brandon; Kyllo, Jennifer; Abuzzahab, M Jennifer; Gottlieb, Peter A; Babu, Sunanda; Armstrong, Taylor; Moran, Antoinette

2017-03-01

Minnesota is home to the largest Somali population in USA, and pediatric diabetes teams are seeing increasing numbers of Somali children with diabetes. To assess the immune basis of diabetes in Somali children in the Twin Cities, Minnesota. A total of 31 Somali children ≤19 yr were treated for type 1 diabetes (T1D) at the University of Minnesota Masonic Children's Hospital and Children's Hospitals and Clinics of Minnesota underwent analysis of human leukocyte antigen (HLA) alleles (n = 30) and diabetes autoantibodies [glutamic acid decarboxylase (GAD65), islet antigen 2 (IA-2), zinc transporter 8 (ZnT8); n = 31]. HLA alleles were analyzed in 49 Somalis without diabetes (controls). Anti-transglutaminase autoantibodies (TGA) for celiac disease were also measured. In Somali children with T1D aged 13.5 ± 5 yr (35% female, disease duration 6.5 ± 3.6 yr), the most common HLA allele was DRB1*03:01 (93%, compared with 45% of Somali controls), followed by DRB1*13:02 (27%). There was a relatively low frequency of DR4 (13%). Controls showed a similar pattern. All 31 participants were positive for at least one diabetes autoantibody. Insulin antibodies were positive in 84% (all were on insulin). Excluding insulin antibodies, 23 (74%) subjects tested positive for at least one other diabetes autoantibody; 32% had 1 autoantibody, 32% had 2 autoantibodies, and 10% had 3 autoantibodies. GAD65 autoantibodies were found in 56% of subjects, IA-2 in 29%, and ZnT8 in 26%. Four (13%) were TGA positive. The autoantibody and HLA profiles of Somali children with diabetes are consistent with autoimmune diabetes. Their HLA profile is unique with an exceptionally high prevalence of DRB1*03:01 allele and relative paucity of DR4 alleles compared with African Americans with T1D. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Activation of the TXNIP/NLRP3 inflammasome pathway contributes to inflammation in diabetic retinopathy: a novel inhibitory effect of minocycline.

PubMed

Chen, Wei; Zhao, Minjie; Zhao, Shuzhi; Lu, Qianyi; Ni, Lisha; Zou, Chen; Lu, Li; Xu, Xun; Guan, Huaijin; Zheng, Zhi; Qiu, Qinghua

2017-02-01

Chronic low-grade inflammation occurs in diabetic retinopathy (DR), but the underlying mechanism(s) remains (remain) unclear. NLRP3 inflammasome activation is involved in several other inflammatory diseases. Thus, we investigated the role of the NLRP3 inflammasome signaling pathway in the pathogenesis of DR. Diabetes was induced in rats by streptozotocin treatment for 8 weeks. They were treated with NLRP3 shRNA or minocycline during the last 4 weeks. High glucose-exposed human retinal microvascular endothelial cells (HRMECs) were co-incubated with antioxidants or subjected to TXNIP or NLRP3 shRNA interference. In high glucose-exposed HRMECs and retinas of diabetic rats, mRNA and protein expression of NLRP3, ASC, and proinflammatory cytokines were induced significantly by hyperglycemia. Upregulated interleukin (IL)-1β maturation, IL-18 secretion, and caspase-1 cleavage were also observed with increased cell apoptosis and retinal vascular permeability, compared with the control group. NLRP3 silencing blocked these effects in the rat model and HRMECs, confirming that inflammasome activation contributed to inflammation in DR. TXNIP expression was increased by reactive oxygen species (ROS) overproduction in animal and cell models, whereas antioxidant addition or TXNIP silencing blocked IL-1β and IL-18 secretion in high glucose-exposed HRMECs, indicating that the ROS-TXNIP pathway mediates NLRP3 inflammasome activation. Minocycline significantly downregulated ROS generation and reduced TXNIP expression, subsequently inhibited NLRP3 activation, and further decreased inflammatory factors, which were associated with a decrease in retinal vascular permeability and cell apoptosis. Together, our data suggest that the TXNIP/NLRP3 pathway is a potential therapeutic target for the treatment of DR, and the use of minocycline specifically for such therapy may be a new avenue of investigation in inflammatory disease.

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.

Chalepin: A Compound from Ruta angustifolia L. Pers Exhibits Cell Cycle Arrest at S phase, Suppresses Nuclear Factor-Kappa B (NF-κB) Pathway, Signal Transducer and Activation of Transcription 3 (STAT3) Phosphorylation and Extrinsic Apoptotic Pathway in Non-small Cell Lung Cancer Carcinoma (A549).

PubMed

Richardson, Jaime Stella Moses; Aminudin, Norhaniza; Abd Malek, Sri Nurestri

2017-10-01

Plants have been a major source of inspiration in developing novel drug compounds in the treatment of various diseases that afflict human beings worldwide. Ruta angustifolia L. Pers known locally as Garuda has been conventionally used for various medicinal purposes such as in the treatment of cancer. A dihydrofuranocoumarin named chalepin, which was isolated from the chloroform extract of the plant, was tested on its ability to inhibit molecular pathways of human lung carcinoma (A549) cells. Cell cycle analysis and caspase 8 activation were conducted using a flow cytometer, and protein expressions in molecular pathways were determined using Western blot technique. Cell cycle analysis showed that cell cycle was arrested at the S phase. Further studies using Western blotting technique showed that cell cycle-related proteins such as cyclins, cyclin-dependent kinases (CDKs), and inhibitors of CDKs correspond to a cell cycle arrest at the S phase. Chalepin also showed inhibition in the expression of inhibitors of apoptosis proteins. Nuclear factor-kappa B (NF-κB) pathway, signal transducer and activation of transcription 3 (STAT-3), cyclooxygenase-2, and c-myc were also downregulated upon treatment with chalepin. Chalepin was found to induce extrinsic apoptotic pathway. Death receptors 4 and 5 showed a dramatic upregulation at 24 h. Analysis of activation of caspase 8 with the flow cytometer showed an increase in activity in a dose- and time-dependent manner. Activation of caspase 8 induced cleavage of BH3-interacting domain death agonist, which initiated a mitochondrial-dependent or -independent apoptosis. Chalepin causes S phase cell cycle arrest, NF-κB pathway inhibition, and STAT-3 inhibition, induces extrinsic apoptotic pathway, and could be an excellent chemotherapeutic agent. This study reports the capacity of an isolated bioactive compound known as chalepin to suppress the nuclear factor kappa-light-chain-enhancer of activated B cells pathway, signal transducer and activation of transcription 3, and extrinsic apoptotic pathway and also its ability to arrest cell cycle in S phase. This compound was from the leaves of Ruta angustifolia L. Pers. It provides new insight on the ability of this plant in suppressing certain cancers, especially the nonsmall cell lung carcinoma according to this study. Abbreviations used: °C: Degree Celsius, ANOVA: Analysis of variance, ATCC: American Type Culture Collection, BCL-2: B-Cell CLL/Lymphoma 2, Bcl-xL: B-cell lymphoma extra-large, BH3: Bcl-2 homology 3, BID: BH3-interacting domain death agonist, BIR: Baculovirus inhibitor of apoptosis protein repeat, Caspases: Cysteinyl aspartate-specific proteases, CDK: Cyclin-dependent kinase, CO 2 : Carbon dioxide, CST: Cell signaling technologies, DISC: Death-inducing signaling complex, DMSO: Dimethyl sulfoxide, DNA: Deoxyribonucleic acid, DR4: Death receptor 4, DR5: Death receptor 5, E1a: Adenovirus early region 1A, ECL: Enhanced chemiluminescence, EDTA: Ethylenediaminetetraacetic acid, ELISA: Enzyme-linked immunosorbent assay, etc.: Etcetera, FADD: Fas-associated protein with death domain, FBS: Fetal bovine serum, FITC: Fluorescein isothiocyanate, G1: Gap 1, G2: Gap 2, HPLC: High-performance liquid chromatography, HRP: Horseradish peroxidase, IAPs: Inhibitor of apoptosis proteins, IC50: Inhibitory concentration at half maximal inhibitory, IKK-α: Inhibitor of nuclear factor kappa-B kinase subunit alpha, IKK-β: Inhibitor of nuclear factor kappa-B kinase subunit beta, IKK-γ: Inhibitor of nuclear factor kappa-B kinase subunit gamma, IKK: IκB kinase, IkBα: Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha, m: Meter, M: Mitotic, mm: Millimeter, mRNA: Messenger ribonucleic acid, NaCl: Sodium chloride, NaVO4: Sodium orthovanadate, NEMO: NF-Kappa-B essential modulator, NF-κB: Nuclear factor kappa-light chain-enhancer of activated B cells, NSCLC: Nonsmall cell lung carcinoma, PBS: Phosphate buffered saline, PGE2: Prostaglandin E2, PI: Propidium iodide, PMSF: Phenylmethylsulfonyl fluoride, pRB: Phosphorylated retinoblastoma, R. angustifolia : Ruta angustifolia L. Pers, Rb: Retinoblastoma, rpm: Rotation per minute, RPMI: Roswell Park Memorial Institute, S phase: Synthesis phase, SD: Standard deviation, SDS-PAGE: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Smac: Second mitochondria-derived activator of caspase, SPSS: Statistical Package for the Social Sciences, STAT3: Signal transducer and activation of transcription 3, tBID: Truncated BID, TNF: Tumor necrosis factor, TRADD: Tumor necrosis factor receptor type-1 associated death domain, TRAIL: TNF-related apoptosis- inducing ligand, USA: United States of America, v/v: Volume over volume.

Regulation of TRAIL-Medicated Apoptosis in Prostate Cancer by Overexpression of XIAP

DTIC Science & Technology

2005-01-01

induced resistance to TRAIL apoptosis. We used the nitric oxide donor DETANONOate and the NF-?B inhibitior Bay 11-7085 to inhibit NF-?B activity, and...negatively regulates DR5 expression and regulates resistance. We have demonstrated that the NO donor, DETANONOate , inhibited YY1 DNA-binding activity and... DETANONOate : (Z)-1-[2-(2-aminoethyl)-N-(2-ammonio-ethyl)amino]diazen-l-ium-1, 2-diolate DHT: 5-? dihydrotestosterone DR: death receptor DTT: 1,4

Achieving Information Dominance: Seven Imperatives for Success

DTIC Science & Technology

2002-06-01

ACHIEVING INFORMATION DOMINANCE : SEVEN IMPERATIVES FOR SUCCESS Topical Area: C4ISR and Space Dr. Tom Kaye and Mr. George Galdorisi Dr. Tom Kaye Mr...00-00-2002 4. TITLE AND SUBTITLE Achieving Information Dominance : Seven Imperatives for Success 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM...time. 3 ACHIEVING INFORMATION DOMINANCE : SEVEN IMPERATIVES FOR SUCCESS by Dr. Tom Kaye and Mr. George Galdorisi An integrated joint and combined C4ISR

UPR/Mayaguez High Energy Physics

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

Mendez, Hector

This year the University of Puerto Rico at Mayaguez (UPRM) High Energy Physics (HEP) group continued with the ongoing research program outlined in the grant proposal. The program is centered on the Compact Muon Solenoid (CMS) experiment at the proton-proton (pp) collisions at the Large Hadron Collider (LHC) at CERN in Geneva, Switzerland. The main research focus is on data analysis and on the preparation for the High Luminosity (HL) LHC or experiment detector upgrade. The physics data analysis included Higgs Doublet Search and measurement of the (1) Λ 0 b branching fraction, (2) B meson mass, and (3) hyperonmore » θ - b lifetime. The detector upgrade included work on the preparations for the Forward Pixel (FPIX) detector Silicon Sensor Testing in a production run at Fermilab. In addition, the group has taken responsibilities on the Software Release through our former research associate Dr. Eric Brownson who acted until last December as a Level Two Offline Manager for the CMS Upgrade. In support of the CMS data analysis activities carried out locally, the UPRM group has built and maintains an excellent Tier3 analysis center in Mayaguez. This allowed us to analyze large data samples and to continue the development of algorithms for the upgrade tracking robustness we started several years ago, and we plan to resume in the near future. This project involves computer simulation of the radiation damage to be suffered at the higher luminosities of the upgraded LHC. This year we continued to serve as a source of outstanding students for the field of high energy physics. Three of our graduate students finished their MS work in May, 2014, Their theses research were on data analysis of heavy quark b-physics. All of them are currently enrolled at Ph.D. physics program across the nation. One of them (Hector Moreno) at New Mexico University (Hector Moreno), one at University of New Hampshire (Sandra Santiesteban) and one at University of Puerto Rico-Rio Piedras (Carlos Malca). The students H. Moreno and C. Malca has been directly supervised by Dr. Mendez and S. Santiesteban supervised by Dr. Ramirez. During the last 13 years, our group have graduated 23 MS students on experimental High Energy Physics data analysis and applied hardware techniques. Most of the students have been supported by DOE grants, included this grant. Since 2001, Dr. Mendez have directly supervised eleven students, Dr. Ramirez three students and the former PI (Dr. Lopez) nine students. These theses work are fully documented in the group web page (http://charma.uprm.edu). The High Energy Physics group at Mayaguez is small and presently consists of three Physics faculty members, the Senior Investigators Dr. Hector Mendez (Professor) and Dr. Juan Eduardo Ramirez (Professor), and Dr. Sudhir Malik who was just hired in July 2014. Dr. Ramirez is in charge of the UPRM Tier-3 computing and will be building the network bandwidth infrastructure for the campus, while Dr. Mendez will continues his effort in finishing the heavy quark physics data analysis and moving to work on SUSY analysis for the 2015 data. Our last grant application in 2012 was awarded only for 2013-2014. As a result our postdoc position was lost last month of March. Since then, we have hired Dr. Malik as a new faculty in order to reinforce the group and to continue our efforts with the CMS experiment. Our plan is to hire another junior faculty in the next two years to strengthen the HEP group even further. Dr. Mendez continues with QuarkNet activities involving an ever larger group of high school physics teachers from all around Puerto Rico.« less

Impact of four different recumbencies on the distribution of ventilation in conscious or anaesthetized spontaneously breathing beagle dogs: An electrical impedance tomography study

PubMed Central

Schramel, Johannes P.; Auer, Ulrike; Moens, Yves P. S.

2017-01-01

The aim was to examine the effects of recumbency and anaesthesia on distribution of ventilation in beagle dogs using Electrical Impedance Tomography (EIT). Nine healthy beagle dogs, aging 3.7±1.7 (mean±SD) years and weighing 16.3±1.6 kg, received a series of treatments in a fixed order on a single occasion. Conscious dogs were positioned in right lateral recumbency (RLR) and equipped with 32 EIT electrodes around the thorax. Following five minutes of equilibration, two minutes of EIT recordings were made in each recumbency in the following order: RLR, dorsal (DR), left (LLR) and sternal (SR). The dogs were then positioned in RLR, premedicated (medetomidine 0.01, midazolam 0.1, butorphanol 0.1 mg kg-1 iv) and pre-oxygenated. Fifteen minutes later anaesthesia was induced with 1 mg kg-1 propofol iv and maintained with propofol infusion (0.1–0.2 mg kg-1 minute-1 iv). After induction, the animals were intubated and allowed to breathe spontaneously (FIO2 = 1). Recordings of EIT were performed again in four recumbencies similarly to conscious state. Centre of ventilation (COV) and global inhomogeneity (GI) index were calculated from the functional EIT images. Repeated-measures ANOVA and Bonferroni tests were used for statistical analysis (p < 0.05). None of the variables changed in the conscious state. During anaesthesia left-to-right COV increased from 46.8±2.8% in DR to 49.8±2.9% in SR indicating a right shift, and ventral-to-dorsal COV increased from 49.8±1.7% in DR to 51.8±1.1% in LLR indicating a dorsal shift in distribution of ventilation. Recumbency affected distribution of ventilation in anaesthetized but not in conscious dogs. This can be related to loss of respiratory muscle tone (e.g. diaphragm) and changes in thoracic shape. Changing position of thoraco-abdominal organs under the EIT belt should be considered as alternative explanation of these findings. PMID:28922361

High-dose vitamin D in Addison's disease regulates T-cells and monocytes: A pilot trial.

PubMed

Penna-Martinez, Marissa; Filmann, Natalie; Bogdanou, Dimitra; Shoghi, Firouzeh; Huenecke, Sabine; Schubert, Ralf; Herrmann, Eva; Koehl, Ulrike; Husebye, Eystein S; Badenhoop, Klaus

2018-05-01

On the basis of the immunomodulatory actions of vitamin D (VD), we investigated the effects of high-dose VD therapy over a 3 mo period on the immune response in patients with Addison's disease (AD). This randomized, controlled, crossover trial included 13 patients with AD who received either cholecalciferol (4000 IU/d) for 3 mo followed by 3 mo placebo oil or the sequential alternative placebo followed by verum. Glucocorticoid replacement doses remained stable. The primary outcome measures were changes in 25-hydroxyvitamin D3 (25(OH)D 3 ) levels and immune cells including T helper cells (Th; CD3 + CD4 + ), late-activated Th cells (CD3 + CD4 + HLA-DR + ), regulatory T cells (CD3 + CD4 + CD25 bright CD127 dim/neg ), cytotoxic T cells (Tc; CD3 + CD8 + ), late-activated Tc cells (CD3 + CD8 + HLA-DR + ), and monocytes. The explorative analysis included the correlation of changes with VD-related gene polymorphisms and 21-hydroxylase antibody titers. Ten of 13 patients (77%) were VD deficient. Median 25(OH)D 3 concentrations increased significantly to 41.5 ng/ml (median changes: 19.95 ng/ml; P = 0.0005) after 3 mo of cholecalciferol treatment. Within the T-cells, only the late-activated Th (median changes: 1.6%; P = 0.02) and late-activated Tc cells (median changes: 4.05%; P = 0.03) decreased, whereas monocytes (median changes: 1.05%; P = 0.008) increased after VD therapy. T-cell changes were associated with two polymorphisms (CYP27B1-rs108770012 and VDR-rs10735810), but no changes in the 21-hydroxylase antibody titers were observed. Three months of treatment with cholecalciferol achieved sufficient 25(OH)D 3 levels and can regulate late-activated T-cells and monocytes in patients with AD. Explorative analysis revealed potential genetic contributions. This pilot trial provides novel insights about immunomodulation in AD. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterization of a new HLA-B allele (B{sup *}3702) generated by an intronic recombination event

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

Santos, S.; Vicario, J.L.; Merino, J.L.

1996-12-31

Routine serological HLA typing of s Syrian family revealed a Bw4-associated HLA-B blank antigen showing Mendelian segregation together with the haplotype A1, Cw2, DR11, DQ7 (a father and one of his children, cells NO. 5958641 and No. 1958125). A more extensive serological analysis was done by using additional polyclonal and monoclonal antibodies (mAb; One-Lambda BL-60 and LM172 plates) as well as the 12th International Workshop class I mAb plate. Both cells showed no conclusive typing reactions with sera towards HLA-B27 and HLA-B37 antigens. Two mAb, PAMELA (27,44,38) and FAY (13,27,37,47), were able to recognize this antigen. The great majority ofmore » polyclonal reagents against B37 showed negative reactions, while weak results were frequently observed with anti-B27 allosera. 8 refs., 1 fig., 1 tab.« less

Death Receptor 5—Targeted Depletion of Interleukin-23—Producing Macrophages, Th17, and Th1/17 Associated With Defective Tyrosine Phosphatase in Mice and Patients with Rheumatoid Arthritis

PubMed Central

Li, Jun; Yang, PingAr; Wu, Qi; Li, Hao; Ding, Yana; Hsu, Hui-Chen; Spalding, David M.; Mountz, John D.

2014-01-01

Objective. Bidirectional interactions between granulocyte-macrophage colony-stimulating factor–positive (GM-CSF+) T cell and interferon regulatory factor 5–positive (IRF-5+) macrophages play a major role in autoimmunity. In the absence of SH2 domain-containing phosphatase 1 (SHP-1), GM-CSF–stimulated cells are resistant to death receptor (DR)–mediated apoptosis. The objective of this study was to determine whether TRA-8, an anti-DR5 agonistic antibody, can eliminate inflammatory macrophages and CD4 T cells in the SHP-1–defective condition. Methods. Ubiquitous Cre (Ubc.Cre) human/mouse-chimeric DR5-transgenic mice were crossed with viable SHP-1–defective motheaten (mev/mev) mice. TRA-8 was administered weekly for up to 4 weeks. The clinical scores, histopathologic severity, and macrophage and CD4 T cell phenotypes were evaluated. The role of TRA-8 in depleting inflammatory macrophages and CD4 T cells was also evaluated, using synovial fluid obtained from patients with rheumatoid arthritis (RA). Results. The levels of Inflammatory macrophages (interleukine-23–positive [IL-23+] IRF5+) and CD4 T (IL-17+GM-CSF+) cells were elevated in mev/mev mice. In DR5-transgenic mev/mev mice, DR5 expression was up-regulated in these 2 cell populations. TRA-8 treatment depleted these cells and resulted in a significant reduction of inflammation and in the titers of autoantibodies. In synovial cells from patients with RA, the expression of IRF5 and DR5 was negatively correlated with the expression of PTPN6. TRA-8, but not TRAIL, suppressed RA inflammatory macrophages and Th17 cells under conditions in which the expression of SHP-1is low. Conclusion. In contrast with TRAIL, which lacks the capability to counteract the survival signal in the absence of SHP-1, TRA-8 eliminated both IRF5+ IL-23+ M1 macrophages and pathogenic GM-CSF+ IL-17+ CD4 T cells in a SHP-1-independent manner. The results of the current study suggest that TRA-8 can deplete inflammatory cell populations that result from a hyperactive GM-CSF/IRF-5 axis. PMID:23818173

Viscous Rayleigh-Taylor instability in spherical geometry

NASA Astrophysics Data System (ADS)

Mikaelian, Karnig O.

2016-02-01

We consider viscous fluids in spherical geometry, a lighter fluid supporting a heavier one. Chandrasekhar [Q. J. Mech. Appl. Math. 8, 1 (1955), 10.1093/qjmam/8.1.1] analyzed this unstable configuration providing the equations needed to find, numerically, the exact growth rates for the ensuing Rayleigh-Taylor instability. He also derived an analytic but approximate solution. We point out a weakness in his approximate dispersion relation (DR) and offer a somewhat improved one. A third DR, based on transforming a planar DR into a spherical one, suffers no unphysical predictions and compares reasonably well with the exact work of Chandrasekhar and a more recent numerical analysis of the problem [Terrones and Carrara, Phys. Fluids 27, 054105 (2015), 10.1063/1.4921648].

Toward Intelligence Systems for Testing.

DTIC Science & Technology

1987-03-01

corresponding to [3]. The question posed to the student will end up being, 𔄁s the current at Meter A higher, lower, or the same as the current at Meter B1 " The...List [Pittsburgh/Lesgold] NR 4422539 Dr. Diane Damos ERIC Facility-Acquisitions Arizona State University 4833 Rugby Avenue Department of Psychology

Interaction of older donor age and survival after weight-matched pediatric heart transplantation.

PubMed

Westbrook, Thomas C; Morales, David L S; Khan, Muhammad S; Bryant, Roosevelt; Castleberry, Chesney; Chin, Clifford; Zafar, Farhan

2017-05-01

Donors are matched for weight in pediatric heart transplantation (PHT), yet age differences are not considered in this decision. In this study we attempt to identify the effect of age differences in weight-matched patients and the effect these differences have on post-transplant survival. The United Network of Organ Sharing (UNOS) database was queried for the period from October 1987 to March 2014 for all pediatric heart transplant patients. Transplants with donor-to-recipient (D-R) weight ratios of 0.8 to 1.5 were identified (weight-matched). D-R age differences were categorized as: donors 5 years younger than recipients (DR+5). A total of 4,408 patients were identified as weight-matched transplants. Of these transplants, 681 were D>R+5, 3,596 were D=R±5 and 131 were DR+5 transplants were found to be associated with decreased post-transplant survival compared with D=R±5 (p = 0.002). Rates of acute rejection were similar among all groups but post-transplant coronary allograft vasculopathy (CAV) was more prevalent in D>R+5 than D=R±5 patients (28% and 18%, respectively; p < 0.001). Increasing age difference by each year was associated with decreasing median post-transplant survival time (p < 0.001; hazard ratio 1.018, range 1.011 to 1.025). The overall negative association with mortality was due to the adolescent cohort (11 to 17 years), specifically D>R+5 transplants, utilizing organs from donors >25 of age. In PHT, increasing D-R age difference decreases survival; however, this effect is driven by recipients 11 to 17 years old and donors >25 years old. Allocation of younger donor organs to adolescent recipients should be a priority. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Ischemic index changes in diabetic retinopathy after intravitreal dexamethasone implant using ultra-widefield fluorescein angiography: a pilot study.

PubMed

Querques, Lea; Parravano, Mariacristina; Sacconi, Riccardo; Rabiolo, Alessandro; Bandello, Francesco; Querques, Giuseppe

2017-08-01

To investigate the effect of dexamethasone intravitreal implant on peripheral ischemia in patients affected by diabetic macular edema (DME). Patients with treatment-naïve diabetic retinopathy (DR) undergoing intravitreal dexamethasone implant for DME between October 2015 and March 2017 were enrolled. Patients underwent a comprehensive ocular examination at baseline (<2 weeks before treatment) and 10 ± 2 weeks after dexamethasone implant including best-corrected visual acuity (BCVA), intraocular pressure, optical coherence tomography, ultra-widefield (UWF) retinography and UWF fluorescein angiography (UWFA). Nine eyes of seven consecutive patients (five males; mean age 66.4 ± 6.7 years) were enrolled. Mean duration of DR was 12.3 ± 8.4 years. Mean interval between UWFA acquisitions was 12.1 ± 2.1 weeks, and the mean interval between intravitreal injection and UWFA acquisition was 11.0 ± 1.6 weeks. Mean pre- and post-injection BCVA was 0.30 ± 0.20 and 0.21 ± 0.14 logMAR (p = 0.06), respectively. Mean pre- and post-injection central macular thickness was 449.8 ± 92.5 and 356.3 ± 52.4 μm (p = 0.03), respectively. Mean pre- and post-injection ischemic index was 24.0 ± 25.0 and 9.8 ± 12.1% (p = 0.0427), respectively. Intravitreal dexamethasone implant reduces peripheral retina ischemia in patients with DR.

Immune Cell Subsets Evaluation as a Predictive Tool for Hepatitis B Infection Outcome and Treatment Responsiveness.

PubMed

Kandilarova, Snezhina M; Georgieva, Atanaska I; Mihaylova, Anastasiya P; Baleva, Marta P; Atanasova, Valentina K; Petrova, Diana V; Popov, Georgi T; Naumova, Elissaveta J

2017-03-01

The patient's immune response is one of the major factors influencing HBV eradication or chronification, and it is thought to be responsible for the treatment success. Our study aimed to investigate whether cellular defense mechanisms are associated with the course of HBV infection (spontaneous recovery [SR] or chronification [CHB]) and with the therapeutic approach. A total of 139 patients (118 with CHB, 21 SR) and 29 healthy individuals (HI) were immunophenotyped by flowcytometry. Fifty-six patients were treatment-naïve, 20 were treated with interferons and 42 with nucleoside/ nucleotide analogues. Deficiency of T lymphocytes, helper-inducer (CD3+CD4+), suppressorcytotoxic (CD8+CD3+) and cytotoxic (CD8+CD11b-, CD8+CD28+) subsets, activated T cells (CD3+HLA-DR+, CD8+CD38+) and increased CD57+CD8- cells, elevated percentages of B lymphocytes and NKT cells were observed in CHB patients compared with HI. In SR patients, elevated CD8+CD11b+, NKT and activated T cells were found in comparison with controls. The higher values of T cells and their subsets in SR patients than in CHB patients reflect a recovery of cellular immunity in resolved HBV infection individuals. In both groups of treated patients, reduced T lymphocytes, CD3+CD4+ and CD8+CD38+ subsets were found in comparison with HI. Higher proportions of cytotoxic subsets were observed in treated patients compared with treatment-naïve CHB patients, more pronounced in the group with interferon therapy. Our data demonstrate that cellular immune profiles may be of prognostic value in predicting the clinical course of HBV infection, and the determination of the therapeutic response.

From Froot Loops to Fitness: My Journey as an Educator and Person With Diabetes

PubMed Central

2017-01-01

EDITOR’S NOTE: This article is adapted from the address Dr. Colberg delivered as the recipient of the American Diabetes Association’s Outstanding Educator in Diabetes Award for 2016. She delivered the address in June 2016 at the association’s 76th Annual Meeting and Scientific Sessions in New Orleans, La. A webcast of this speech is available for viewing at the ADA website (http://professional.diabetes.org/search/site?f%5B0%5D=im_field_dbp_ct%3A7&f%5B1%5D=sm_field_wcast_mname%3Anode%3A120&retain-filters=1). PMID:28270716

From Froot Loops to Fitness: My Journey as an Educator and Person With Diabetes.

PubMed

Colberg-Ochs, Sheri R

2017-02-01

EDITOR'S NOTE : This article is adapted from the address Dr. Colberg delivered as the recipient of the American Diabetes Association's Outstanding Educator in Diabetes Award for 2016. She delivered the address in June 2016 at the association's 76th Annual Meeting and Scientific Sessions in New Orleans, La. A webcast of this speech is available for viewing at the ADA website (http://professional.diabetes.org/search/site?f%5B0%5D=im_field_dbp_ct%3A7&f%5B1%5D=sm_field_wcast_mname%3Anode%3A120&retain-filters=1).

Critical conditions for particle motion in coarse bed materials of nonuniform size distribution

NASA Astrophysics Data System (ADS)

Bathurst, James C.

2013-09-01

Initiation of particle motion in a bed material of nonuniform size distribution may be quantified by (qci/qcr) = (Di/Dr)b, where qci is the critical unit discharge at which particle size Di enters motion, qcr is the critical condition for a reference size Dr unaffected by the hiding/exposure effects associated with nonuniform size distributions, i and r refer to percentiles of the distribution and b varies from 0 (equal mobility in entrainment of all particle sizes) to 1.5-2.5 (full size selective transport). Currently there is no generally accepted method for predicting the value of b. Flume and field data are therefore combined to investigate the above relationship. Thirty-seven sets of flume data quantify the relationship between critical unit discharge and particle size for bed materials with uniform size distributions (used here to approximate full size selective transport). Field data quantify the relationship for bed materials of nonuniform size distribution at 24 sites, with b ranging from 0.15 to 1.3. Intersection of the two relationships clearly demonstrates the hiding/exposure effect; in some but not all cases, Dr is close to the median size D50. The exponent has two clusters of values: b > 1 for sites subject to episodic rain-fed floods and data collected by bedload pit trap and tracers; and b < 0.7 for sites with seasonal snowmelt/glacial melt flow regimes and data collected by bedload sampler and large aperture trap. Field technique appears unlikely to cause variations in b of more than about 0.25. However, the clustering is consistent with possible variations in bed structure distinguishing: for b > 1, sites with relatively infrequent bedload transport where particle embedding and consolidation could reduce the mobility of coarser particles; and, for b < 0.7, a looser bed structure with frequent transport events allowing hiding/exposure and size selection effects to achieve their balance. As yet there is no firm evidence for such a dependency on bed structure but variations in b could potentially be caused by factors outside those determining equal mobility or size selection but appearing to affect b in the same way.

Improvement in Visual Symptomatology after Endovascular Treatment of Cavernous Carotid Aneurysms: A Multicenter Study.

PubMed

Drazin, Doniel; Choulakian, Armen; Nuño, Miriam; Gandhi, Ravi; Edgell, Randall C; Alexander, Michael J

2013-06-01

Aneurysms arising from the cavernous internal carotid artery (CCAs) pose technical challenges for surgical management and such patients are frequently referred for endovascular treatment. These aneurysms often produce a variety of neurological deficits, primarily those related to oculoparesis. Our purpose was to determine the visual and neurological outcome of patients with treated CCAs. We reviewed the medical records and angiograms for patients who underwent endovascular treatment for CCAs at three academic medical centers. The following outcomes were analyzed: angiographic assessment, visual improvement and outcome at 3 months using Glasgow Outcome Scale (GOS). Thirty-four patients (mean age 54.7 years) were treated for CCAs. The mean aneurysm size was 14.2 mm (range: 3-45 mm), and fourteen patients (41.2%) required stent assistance. Twenty-one aneurysms (61.8%) were completely occluded; nine aneurysms (26.6%) had near-complete occlusion; 4 aneurysms (11.8%) had partial occlusion. Seven patients (20.6%) required retreatment. Fifteen of the 34 patients (44.1%) presented with visual symptoms, while only eight patients had residual visual symptomatology at follow-up (44.1% vs. 23.5%; p=0.02). Patients that presented with visual symptoms (N=15) had a mean aneurysm size of 24.5 mm, while those without visual symptoms (N=19) had a size of 7.5 mm (p=0.001). Follow-up GOS was good (4-5) in 29 patients (90.6%). No thromboembolic complications were observed. One patient died (3.1%) of an unrelated cause. Most patients in this multicenter series improved or remained stable after treatment. The results of this study indicate that endovascular treatment may improve the outcome of visual symptoms in patients with large cavernous aneurysms with low periprocedural morbidity. MJA is a consultant for Stryker and Codman. AC receives a Cordis Endovascular Fellowship Training Grant and a Stryker Endovascular Neurosurgery Post-graduate Fellow Grant. Dr. Drazin: Conception and Design, Drafting the Article and Critically Revising the Article Dr. Choulakian: Analysis and Interpretation of Data and Drafting the Article Dr. Nuno: Analysis and Interpretation of Data Dr. Gandhi: Analysis and Interpretation of Data and Drafting the Article Dr. Edgell: Analysis and Interpretation of Data and Drafting the Article Dr. Alexander: Critically Revising the Article and Conception and Design.

Novel LC-ESI/MS/MSn Method for the Characterization and Quantification of 2′-Deoxyguanosine Adducts of the Dietary Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine by 2-D Linear Quadrupole Ion Trap Mass Spectrometry

PubMed Central

Goodenough, Angela K.; Schut, Herman A. J.; Turesky, Robert J.

2008-01-01

An accurate and sensitive liquid chromatography-electrospray ionization/multi-stage mass spectrometry (LC-ESI/MS/MSn) technique has been developed for the characterization and quantification of 2′-deoxyguanosine (dG) adducts of the dietary mutagen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). PhIP is an animal and potential human carcinogen that occurs in grilled meats. Following enzymatic digestion and adduct enrichment by solid-phase extraction (SPE), PhIP—DNA adducts were analyzed by MS/MS and MSn scan modes on a 2-D linear quadrupole ion trap mass spectrometer (QIT/MS). The major DNA adduct, N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (dG-C8-PhIP), was detected in calf thymus (CT) DNA modified in vitro with a bioactivated form of PhIP and in the colon and liver of rats given PhIP as part of the diet. The lower limit of detection (LOD) was 1 adduct per 108 DNA bases, and the limit of quantification (LOQ) was 3 adducts per 108 DNA bases in both MS/MS and MS3 scan modes, using 27 μg of DNA for analysis. Measurements were based on isotope dilution with the internal standard, N-(deoxyguanosin-8-yl)-2-amino-1-(trideutero)methyl-6-phenylimidazo[4,5-b]pyridine (dG-C8-[2H3C]-PhIP). The selected reaction monitoring (SRM) scan mode in MS/MS was employed to monitor the loss of deoxyribose (dR) from the protonated molecules of the adducts ([M + H - 116]+). The consecutive reaction monitoring (CRM) scan modes in MS3 and MS4 were used to measure and further characterize product ions of the aglycone ion (BH2+) (Guanyl-PhIP). The MS3 scan mode was effective in eliminating isobaric interferences observed in the MS/MS scan mode and resulted in an improved signal-to-noise (S/N) ratio. Moreover, the product ion spectra obtained by the MSn scan modes provided rich structural information about the adduct and were used to corroborate the identity of dG-C8-PhIP. In addition, an isomeric dG-PhIP adduct was detected in vivo. This LCESI/MS/MSn method is the first reported application on the use of the MS3 scan mode for the analysis of DNA adducts in vivo. PMID:17305409

Low VHF Channel Measurements and Simulations in Indoor and Outdoor Scenarios

DTIC Science & Technology

2015-05-01

Gregory, Dr Ethan Stamp, Dr John Rodgers, and Stuart H Young of the US Army Research Laboratory for their support with the robotic integration and...our tests.46 The USRP N210 provides an Ethernet interface that allows us to use software control for transmission and reception . The USRP is...dB] B E R Case 3b: LoS in Bldg 205 Measured (LoS) AWGN ( Theory ) Fig. 18 Theoretical and measured BER vs. SNR curves for LOS indoor channel

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.

2011 Presidential Early Career Awards for Scientists and Engineers: the PECASE Awards Ceremony

ScienceCinema

Poneman, Daniel

2018-05-31

The winners for 2011 of the DOE PECASE Awards were recognized in a ceremony held August 01, 2012. Dr. Bill Brinkman, Director of the Office of Science introduced the main speaker, DOE Deputy Secretary Daniel B. Poneman. Leaders from across the Department and the fields of energy research and technology presented the 2011 winners. They are: Dr. Stanley Atcitty (SNL); Dr. Jeffrey W. Banks (LLNL); Dr. Amy J. Clarke (LANL); Derek R. Gaston (INL); Dr. Christopher Hirata (California Institute of Technology); Dr. Heileen Hsu-Kim (Duke University); Dr. Thomas Francisco (Jaramillo Stanford University); Dr.Pablo Jarillo-Herrero (MIT); Dr. Peter Mueller (ANL); Dr. Daniel B. Sinars (SNL); Dr. Jesse Thaler (MIT); and Dr. Heather Whitley (LLNL).

2011 Presidential Early Career Awards for Scientists and Engineers: the PECASE Awards Ceremony

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

Poneman, Daniel

2012-08-01

The winners for 2011 of the DOE PECASE Awards were recognized in a ceremony held August 01, 2012. Dr. Bill Brinkman, Director of the Office of Science introduced the main speaker, DOE Deputy Secretary Daniel B. Poneman. Leaders from across the Department and the fields of energy research and technology presented the 2011 winners. They are: Dr. Stanley Atcitty (SNL); Dr. Jeffrey W. Banks (LLNL); Dr. Amy J. Clarke (LANL); Derek R. Gaston (INL); Dr. Christopher Hirata (California Institute of Technology); Dr. Heileen Hsu-Kim (Duke University); Dr. Thomas Francisco (Jaramillo Stanford University); Dr.Pablo Jarillo-Herrero (MIT); Dr. Peter Mueller (ANL); Dr.more » Daniel B. Sinars (SNL); Dr. Jesse Thaler (MIT); and Dr. Heather Whitley (LLNL).« less

Explorations of Individual Differences Relevant to High Level Skill.

DTIC Science & Technology

1981-12-15

discrete pairs that were responded to in a set order. Many real life tasks are ongoing and the performer must interweave them in some manner. It is... life skill that might relate to the predictors? 18. Individual Differences in the Rate of Repetitive Activity Recently we have begun to investigate...22211 Ale..a.drla. VA 22333 1 Dr. Sesceinve Maddad Prcgrm Manager 1 DR. 8.1. Si.AFKOSIY I Dr. Renter Pletcher Life Sriencea Directorate SCIEMTIPIr ADVISOR

Measuring the Price of Anarchy via Perspective Optimization of Unmanned Vehicles in ISR Operations

DTIC Science & Technology

2012-10-24

nagi@buffalo.edu Dr. Moises Sudit1,3 sudit@cubrc.org 1 CUBRC , Inc. Buffalo, NY USA 2 Raytheon, Inc. Annapolis Junction, MD USA 3 University at Buffalo...ADDRESS(ES) CUBRC , Inc. Buffalo, NY USA 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR

High Nuclear Hypoxia-Inducible Factor 1 Alpha Expression Is a Predictor of Distant Recurrence in Patients With Resected Pancreatic Adenocarcinoma

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

Colbert, Lauren E.; Winship Cancer Institute, Emory University, Atlanta, Georgia; Memorial Sloan-Kettering Cancer Center, New York, New York

Purpose: To evaluate nuclear hypoxia-inducible factor 1α (HIF-1α) expression as a prognostic factor for distant recurrence (DR) and local recurrence (LR) after pancreatic adenocarcinoma resection. Methods and Materials: Tissue specimens were collected from 98 patients with pancreatic adenocarcinoma who underwent resection without neoadjuvant therapy between January 2000 and December 2011. Local recurrence was defined as radiographic or pathologic evidence of progressive disease in the pancreas, pancreatic bed, or associated nodal regions. Distant recurrence was defined as radiographically or pathologically confirmed recurrent disease in other sites. Immunohistochemical staining was performed and scored by an independent pathologist blinded to patient outcomes. Highmore » HIF-1α overall expression score was defined as high percentage and intensity staining and thus score >1.33. Univariate analysis was performed for HIF-1α score with LR alone and with DR. Multivariate logistic regression was used to determine predictors of LR and DR. Results: Median follow-up time for all patients was 16.3 months. Eight patients (8%) demonstrated isolated LR, 26 patients (26.5%) had isolated DR, and 13 patients had both LR and DR. Fifty-three patients (54%) had high HIF-1α expression, and 45 patients (46%) had low HIF-1α expression. High HIF-1α expression was significantly associated with DR (P=.03), and low HIF-1α expression was significantly associated with isolated LR (P=.03). On multivariate logistic regression analysis, high HIF-1α was the only significant predictor of DR (odds ratio 2.46 [95% confidence interval 1.06-5.72]; P=.03). In patients with a known recurrence, an HIF-1α score ≥2.5 demonstrated a specificity of 100% for DR. Conclusions: High HIF-1α expression is a significant predictor of distant failure versus isolated local failure in patients undergoing resection of pancreatic adenocarcinoma. Expression of HIF-1α may have utility in determining candidates for adjuvant local radiation therapy and systemic chemotherapy.« less

8. View of DR 3 antenna showing lower front connector, ...

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

8. View of DR 3 antenna showing lower front connector, third from left vertical member at first level above foundation level, showing small diameter turnbuckle stays, vertical member with flange connection, and various struts and connectors with antenna assembly 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

Determination of SPEAR-1 Rocket Body Potential during High-Voltage Experiments

DTIC Science & Technology

1990-06-01

California at San Diego La Jolla, CA 92093 10 . Dr. C. E. McIlwain Center for Astrophysics and Space Science University of California at San Diego La Jolla...Postgraduate School 39 Naval Postgraduate School 6c. ADDRESS (City, S:are, and ZIP Code) 7b. ADDRESS (Ciy, State, and ZIP Code) Monterey. CA 93943-5000...Monterey. CA 93943-5000 8a. NAME OF FUNDING.SPONSORING 80. OFFICE SYMBOL 9. PROCUREMENT INSTRUMENT IDENTIFICATION NUMBER ORGANIZATION (If applicable

A Wideband Circularly Polarized Antenna with a Multiple-Circular-Sector Dielectric Resonator

PubMed Central

Trinh-Van, Son; Yang, Youngoo; Lee, Kang-Yoon; Hwang, Keum Cheol

2016-01-01

This paper presents the design of a wideband circularly polarized antenna using a multiple-circular-sector dielectric resonator (DR). The DR is composed of twelve circular-sector DRs with identical central angles of 30∘ but with different radii. A genetic algorithm is utilized to optimize the radii of the twelve circular-sector DRs to realize wideband circular polarization. The proposed antenna is excited using an aperture-coupled feeding technique through a narrow rectangular slot etched onto the ground plane. An antenna prototype is experimentally verified. The measured −10 dB reflection and 3 dB axial ratio (AR) bandwidths are 31.39% (1.88–2.58 GHz) and 19.30% (2.06–2.50 GHz), respectively, covering the operating bands of the following systems: UMTS-2100 (2.145 GHz), WiMAX (2.3 GHz), and Wi-Fi (2.445 GHz). A measured peak gain of 7.65 dBic at 2.225 GHz and gain variation of less than 2.70 dBic within the measured 3 dB AR bandwidth are achieved. In addition, the radiation patterns of the proposed antenna are presented and discussed. PMID:27827881

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.

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).

The effect of a simulation training package on skill acquisition for duplex arterial stenosis detection.

PubMed

Jaffer, Usman; Normahani, Pasha; Singh, Prashant; Aslam, Mohammed; Standfield, Nigel J

2015-01-01

In vascular surgery, duplex ultrasonography is a valuable diagnostic tool in patients with peripheral vascular disease, and there is increasing demand for vascular surgeons to be able to perform duplex scanning. This study evaluates the role of a novel simulation training package on vascular ultrasound (US) skill acquisition. A total of 19 novices measured predefined stenosis in a simulated pulsatile vessel using both peak systolic velocity ratio (PSVR) and diameter reduction (DR) methods before and after a short period of training using a simulated training package. The training package consisted of a simulated pulsatile vessel phantom, a set of instructional videos, duplex ultrasound objective structured assessment of technical skills (DUOSATS) tool, and a portable US scanner. Quantitative metrics (procedure time, percentage error using PSVR and DR methods, DUOSAT scores, and global rating scores) before and after training were compared. Subjects spent a median time of 144 mins (IQR: 60-195) training using the simulation package. Subjects exhibited statistically significant improvements when comparing pretraining and posttraining DUOSAT scores (pretraining = 17 [16-19.3] vs posttraining = 30 [27.8-31.8]; p < 0.01), global rating score (pretraining = 1 [1-2] vs posttraining = 4 [3.8-4]; p < 0.01), percentage error using both the DR (pretraining = 12.6% [9-29.6] vs posttraining = 10.3% [8.9-11.1]; p = 0.03) and PSVR (pretraining = 60% [40-60] vs posttraining = 20% [6.7-20]; p < 0.01) methods. In this study, subjects with no previous practical US experience developed the ability to both acquire and interpret arterial duplex images in a pulsatile simulated phantom following a short period of goal direct training using a simulation training package. A simulation training package may be a valuable tool for integration into a vascular training program. However, further work is needed to explore whether these newly attained skills are translated into clinical assessment. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Space Science

NASA Image and Video Library

1990-01-16

This montage consists of 8 individual STS-35 crew member portraits surrounding the mission’s insignia. Starting from top center, clockwise, are Vance D. Brand, commander; mission specialists Dr. Robert A. R. Parker, John M. (Mike) Lounge, and Dr. Jeffery A. Hoffman; Colonel Guy S. Gardner, pilot; and payload specialists Dr. Kenneth H. Nordsieck, Dr. Samual T. Durrance, and Dr. Ronald A. Parise. The crew of 8 launched aboard the Space Shuttle Orbiter Columbia on December 2, 1990 at 1:19:01am (EST). The primary objective of the mission was round the clock observation of the celestial sphere in ultrviolet 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.

Reply to Lawrence R. Solomon: Negative interaction of high folate status with biochemical and neurological response to vitamin B-12 treatment

USDA-ARS?s Scientific Manuscript database

We thank Dr. Lawrence Solomon for his observations and comments regarding our recent article on biochemical and neurological responses to vitamin B-12 treatment in asymptomatic Chilean elderly (1). Our article highlighted the most important effects of treatment; in our response to Dr. Solomon’s ques...

Antiretroviral Treatment Effect on Immune Activation Reduces Cerebrospinal Fluid HIV-1 Infection

PubMed Central

Sinclair, Elizabeth; Ronquillo, Rollie; Lollo, Nicole; Deeks, Steven G.; Hunt, Peter; Yiannoutsos, Constantin T.; Spudich, Serena; Price, Richard W.

2012-01-01

Objective To define the effect of antiretroviral therapy (ART) on activation of T cells in cerebrospinal fluid (CSF) and blood, and interactions of this activation with CSF HIV-1 RNA concentrations. Design Cross-sectional analysis of 14 HIV-negative subjects and 123 neuroasymptomatic HIV-1–infected subjects divided into 3 groups: not on ART (termed “offs”), on ART with plasma HIV-1 RNA >500 copies/mL (“failures”), and on ART with plasma HIV-1 RNA ≤500 copies/mL (“successes”). T-cell activation was measured by coexpression of CD38 and human leukocyte antigen DR (HLA-DR). Other measurements included CSF neopterin and white blood cell (WBC) counts. Results CD8 T-cell activation in CSF and blood was highly correlated across all subjects and was highest in the offs, lower in the failures, and lower still in the successes. While CD8 activation was reduced in failures compared to offs across the range of plasma HIV-1, it maintained a coincident relation to CSF HIV-1 in both viremic groups. In addition to correlation with CSF HIV-1 concentrations, CD8 activation in blood and CSF correlated with CSF WBCs and CSF neopterin. Multivariate analysis confirmed the association of blood CD8 T-cell activation, along with plasma HIV-1 RNA and CSF neopterin, with CSF HIV-1 RNA levels. Conclusions The similarity of CD8 T-cell activation in blood and CSF suggests these cells move from blood to CSF with only minor changes in CD38/HLA-DR expression. Differences in the relation of CD8 activation to HIV-1 concentrations in the blood and CSF in the 2 viremic groups suggest that changes in immune activation not only modulate CSF HIV-1 replication but also contribute to CSF treatment effects. The magnitude of systemic HIV-1 infection and intrathecal macrophage activation are also important determinants of CSF HIV-1 RNA levels. PMID:18362693

Evaluation of item candidates for a diabetic retinopathy quality of life item bank.

PubMed

Fenwick, Eva K; Pesudovs, Konrad; Khadka, Jyoti; Rees, Gwyn; Wong, Tien Y; Lamoureux, Ecosse L

2013-09-01

We are developing an item bank assessing the impact of diabetic retinopathy (DR) on quality of life (QoL) using a rigorous multi-staged process combining qualitative and quantitative methods. We describe here the first two qualitative phases: content development and item evaluation. After a comprehensive literature review, items were generated from four sources: (1) 34 previously validated patient-reported outcome measures; (2) five published qualitative articles; (3) eight focus groups and 18 semi-structured interviews with 57 DR patients; and (4) seven semi-structured interviews with diabetes or ophthalmic experts. Items were then evaluated during 3 stages, namely binning (grouping) and winnowing (reduction) based on key criteria and panel consensus; development of item stems and response options; and pre-testing of items via cognitive interviews with patients. The content development phase yielded 1,165 unique items across 7 QoL domains. After 3 sessions of binning and winnowing, items were reduced to a minimally representative set (n = 312) across 9 domains of QoL: visual symptoms; ocular surface symptoms; activity limitation; mobility; emotional; health concerns; social; convenience; and economic. After 8 cognitive interviews, 42 items were amended resulting in a final set of 314 items. We have employed a systematic approach to develop items for a DR-specific QoL item bank. The psychometric properties of the nine QoL subscales will be assessed using Rasch analysis. The resulting validated item bank will allow clinicians and researchers to better understand the QoL impact of DR and DR therapies from the patient's perspective.

Immune system cells in healthy ferrets: an immunohistochemical study.

PubMed

Vidaña, B; Majó, N; Pérez, M; Montoya, M; Martorell, J; Martínez, J

2014-07-01

The ferret has emerged as an excellent animal model to characterize several physiologic and pathologic conditions. The distribution and characterization of different types of immune system cells were studied in healthy ferret tissues. Eight primary antibodies were tested for immunohistochemistry in formalin-fixed tissues: anti-CD3, anti-CD79α, anti-CD20, anti-HLA-DR, anti-lysozyme, anti-CD163, anti-SWC3, and anti-Mac387. The anti-CD3 antibody labeled T cells mainly in interfollicular and paracortical areas of lymph nodes, cortex and thymic medulla, and periarteriolar lymphoid sheaths in the spleen. The anti-CD79α and anti-CD20 antibodies immunolabeled B cells located in lymphoid follicles at lymph nodes, spleen, and Peyer patches. The CD79α and CD20 antibodies also labeled cells with nonlymphoid morphology in atypical B-cell locations. The anti-HLA-DR antibody labeled macrophages, some populations of B and T lymphocytes, and different populations of dendritic cells in lymph nodes, Peyer patches, spleen, and thymus. The anti-lysozyme antibody immunolabeled macrophages in the liver, lymph nodes, spleen, and thymus. The Mac-387, CD163, and SWC3 antibodies did not show any positive reaction in formalin-fixed or frozen tissues. To elucidate the origin of the uncommon CD79α/CD20 positive cells, a double immunohistochemistry was carried out using the anti-HLA-DR + the anti-CD79α, the anti-HLA-DR + the anti-CD20, and the anti-lysozyme + the anti-CD79α antibodies. Double labeling was mainly observed when the anti-HLA-DR + the anti-CD79α antibodies were combined. The immunohistologic characterization and distribution of these immune system cells in healthy ferret tissues should be of value in future comparative studies of diseases in ferrets. © The Author(s) 2013.

Cosmological parameter estimation from CMB and X-ray cluster after Planck

NASA Astrophysics Data System (ADS)

Hu, Jian-Wei; Cai, Rong-Gen; Guo, Zong-Kuan; Hu, Bin

2014-05-01

We investigate constraints on cosmological parameters in three 8-parameter models with the summed neutrino mass as a free parameter, by a joint analysis of CCCP X-ray cluster data, the newly released Planck CMB data as well as some external data sets including baryon acoustic oscillation measurements from the 6dFGS, SDSS DR7 and BOSS DR9 surveys, and Hubble Space Telescope H0 measurement. We find that the combined data strongly favor a non-zero neutrino masses at more than 3σ confidence level in these non-vanilla models. Allowing the CMB lensing amplitude AL to vary, we find AL > 1 at 3σ confidence level. For dark energy with a constant equation of state w, we obtain w < -1 at 3σ confidence level. The estimate of the matter power spectrum amplitude σ8 is discrepant with the Planck value at 2σ confidence level, which reflects some tension between X-ray cluster data and Planck data in these non-vanilla models. The tension can be alleviated by adding a 9% systematic shift in the cluster mass function.

Tachykinin actions on deep dorsal horn neurons in vitro: an electrophysiological and morphological study in the immature rat.

PubMed

King, A E; Slack, J R; Lopez-Garcia, J A; Ackley, M A

1997-05-01

To assess whether functional neurokinin receptors exist in the deep dorsal horn of the rat, the actions of the selective neurokinin-1 receptor (NK1R) agonist [Sar9,Met(O2)11]substance P ([Sar9,Met(O2)11]SP), the neurokinin-2 receptor (NK2R) agonists [beta-Ala8]NKA(4-10) and GR64349 and the neurokinin-3 receptor (NK3R) agonist senktide were examined intracellularly in vitro. [Sar9,Met(O2)11]SP (1-4 microM) and senktide (1-2 microM) elicited slow depolarizations (<10 mV) associated with increased synaptic activity and cell firing. [beta-Ala8]NKA(4-10) (10-20 microM) and GR64349 (0.25-10 microM) caused small depolarizations (<2.0 mV) and no firing. Neurons were categorized as either 'tonic' or 'phasic' depending on their firing response to direct current step depolarizations. Tonic neurons, which, unlike phasic neurons, display no spike firing accommodation, generated a significantly larger depolarization to the NK1R and NK3R agonists. The putative contribution of these receptors to primary afferent-mediated synaptic transmission was assessed by testing the NK1R antagonist GR82334 (1 microM), the NK2R antagonist MEN10,376 (1 microM) and the NK3R antagonist [Trp7,beta-Ala8]NKA(4-10) (1 microM) against the dorsal root-evoked excitatory postsynaptic potential (DR-EPSP). GR82334 and [Trp7,beta-Ala8]NKA(4-10) significantly reduced (P < or = 0.05) the duration but not the amplitude of the DR-EPSP. MEN10,376 (1 microM) had no effect on DR-EPSP amplitude or duration. Morphological detail was obtained for seven biocytin-filled deep dorsal horn neurons tested with [Sar9,Met(O2)11]SP. Five neurons responded to the NK1R agonist, and two of these had dorsally directed dendrites into the substantia gelatinosa. The other three [Sar9,Met(O2)11]SP-sensitive neurons had dendrites within deeper laminae. These data support the existence of functional NK1Rs and NK3Rs in the deep dorsal horn which may be involved in mediating sensory afferent inputs from nociceptors.

Low Temperature Fluorination of Aerosol Suspensions of Hydrocarbons Utilizing Elemental Fluorine. Aerosol Direct Fluorination-Syntheses of Perfluoroketones.

DTIC Science & Technology

1983-03-01

81.16 ppm (in) 3 *CF 2 - -126.31 ppm (an) 2 *CF2 - -118.66 ppm (an) 2 (a) See Ref. 11. (b) A. L. Renne and Win. C. Francis, 3. Amr. Cbes. Sat...Knoxville’>Tennessee 37916 1 Professor R. Neilson Dr. A. Cowley Department of Chemistry Department of Chemistry Texas Christian University University

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.

Immunoparalysis: Clinical and immunological associations in SIRS and severe sepsis patients.

PubMed

Papadopoulos, Panagiotis; Pistiki, Aikaterini; Theodorakopoulou, Maria; Christodoulopoulou, Theodora; Damoraki, Georgia; Goukos, Dimitris; Briassouli, Efrossini; Dimopoulou, Ioanna; Armaganidis, Apostolos; Nanas, Serafim; Briassoulis, George; Tsiodras, Sotirios

2017-04-01

This study was designed to identify changes in the monocytic membrane marker HLA-DR and heat shock proteins (HSPs) in relation to T-regulatory cells (T-regs) and other immunological marker changes in patients with systemic inflammatory response syndrome (SIRS) or sepsis/septic shock. Healthy volunteers, intensive care unit (ICU) patients with SIRS due to head injury and ICU patients with severe sepsis/septic shock were enrolled in the current study. Determination of CD14+/HLA-DR+ cells, intracellular heat-shock proteins and other immunological parameters were performed by flow cytometry and RT-PCR techniques as appropriate. Univariate and multivariate analysis examined associations of CD14/HLA-DR, HSPs, T-regs and suppressor of cytokine signalling (SOCS) proteins with SIRS, sepsis and outcome. Fifty patients (37 with severe sepsis and 13 with SIRS) were enrolled, together with 20 healthy volunteers used as a control group. Compared to healthy individuals, patients with SIRS and severe sepsis showed progressive decline of their CD14/HLA-DR expression (0% to 7.7% to 50% within each study subpopulation, p<0.001). Mean fluorescent intensity (MFI) levels of HSP70 and HSP90 on monocytes and polymorphonuclear cells were significantly higher in SIRS patients compared to controls and fell significantly in severe sepsis/septic shock patients (p<0.05 for all comparisons). There was no statistically significant difference between subgroups for levels of T-regulatory cells or relative copies of Suppressor of Cytokine Signalling 3 (SOCS3) proteins. In univariate models percent of CD14/HLA-DR was associated with mortality (OR: 1.8 95%CI 1.02-3.2, p=0.05), while in multivariate models after adjusting for CD14/HLA-DR only younger age and lower Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were associated with increased chances of survival (beta -0.05, OR 0.9, 95% CI 0.9-0.99, p=0.038 for age and beta -0.11, OR 0.89, 95% CI 0.8-0.99, p=0.037 for APACHE II score). Significant associations with SIRS and sepsis were found for CD14/HLA-DR expression and monocyte and polymorphonuclear cell levels of HSP70 and 90. The role of these biomarkers in assessing the prognosis of sepsis needs to be further explored and validated in prospective studies. Copyright © 2017 Elsevier Ltd. 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.

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.

Identification of diverse Bartonella genotypes among small mammals from Democratic Republic of Congo and Tanzania.

PubMed

Gundi, Vijay A K B; Kosoy, Michael Y; Makundi, Rhodes H; Laudisoit, Anne

2012-08-01

Small mammals from the Democratic Republic (DR) of the Congo and Tanzania were tested to determine the prevalence and genetic diversity of Bartonella species. The presence of Bartonella DNA was assessed in spleen samples of the animals by rpoB- and gltA-polymerase chain reactions (PCRs). By rpoB-PCR, Bartonella was detected in 8 of 59 animals of DR Congo and in 16 of 39 Tanzanian animals. By gltA-PCR, Bartonella was detected in 5 and 15 animals of DR Congo and Tanzania, respectively. The gene sequences from Arvicanthis neumanni were closely related to Bartonella elizabethae. The genotypes from Lophuromys spp. and from Praomys delectorum were close to Bartonella tribocorum. Five genogroups were not genetically related to any known Bartonella species. These results suggest the need to conduct further studies to establish the zoonotic risks linked with those Bartonella species and, in particular, to verify whether these agents might be responsible for human cases of febrile illness of unknown etiology in Africa.

Optimization and validation of high-performance liquid chromatography method for analyzing 25-desacetyl rifampicin in human urine

NASA Astrophysics Data System (ADS)

Lily; Laila, L.; Prasetyo, B. E.

2018-03-01

A selective, reproducibility, effective, sensitive, simple and fast High-Performance Liquid Chromatography (HPLC) was developed, optimized and validated to analyze 25-Desacetyl Rifampicin (25-DR) in human urine which is from tuberculosis patient. The separation was performed by HPLC Agilent Technologies with column Agilent Eclipse XDB- Ci8 and amobile phase of 65:35 v/v methanol: 0.01 M sodium phosphate buffer pH 5.2, at 254 nm and flow rate of 0.8ml/min. The mean retention time was 3.016minutes. The method was linear from 2–10μg/ml 25-DR with a correlation coefficient of 0.9978. Standard deviation, relative standard deviation and coefficient variation of 2, 6, 10μg/ml 25-DR were 0-0.0829, 03.1752, 0-0.0317%, respectively. The recovery of 5, 7, 9μg/ml25-DR was 80.8661, 91.3480 and 111.1457%, respectively. Limits of detection (LoD) and quantification (LoQ) were 0.51 and 1.7μg/ml, respectively. The method has fulfilled the validity guidelines of the International Conference on Harmonization (ICH) bioanalytical method which includes parameters of specificity, linearity, precision, accuracy, LoD, and LoQ. The developed method is suitable for pharmacokinetic analysis of various concentrations of 25-DR in human urine.

Technical Objective Document for Food and Food Service Systems

DTIC Science & Technology

1990-10-01

full ntission posture for exlended duration . 3. POCGRESS AND ACCa -fPLISHMENI’S Natick is responsible for many Research, Development, Test , and...Dr. David L. Kaplan Telephone (508) 651-5525 (Biotechnology) b. Technology Program (1) FY91 Planned Programs Complete Joint Services Front End

MX Siting Investigation. MX System Siting Summary Report. Land Acquisition Application Package Map Sheets. Volume III.

DTIC Science & Technology

1982-01-18

O006 UNCLASSIFIED E-TR-58-VOL-3 NL3I~hEhE EhHEEE00000000E law 4r: 32 1 8 41 PHOTOGRAPH THIS SHEET //* LEVEL INVENTORY z ~ DOCUMENT IDENTIFICATION I I...kNPOTTN 44. 4 4F OPERATIO "MAL BASE TE48T SIT *.DeISlrNATED’%RAINING AREA I I IT R8W 0000 1 , Iv t DR V’ NG f4 12 󈧱 00 W - • , .: . .i .. . i

Ion Implantation in Polymers.

DTIC Science & Technology

1983-08-01

cases, the crystalline regions are often lamellar in struct- rg and the lamellae fre- quently occur in some form of spherulitic morphology. Since, in a...12181 Dr. D. H. Whitmore Department of Materials Science Dr. A. P. B. Lever Northwestern University Chemistry Department Evanston, Illinois 60201 1 York

Roymillerite, Pb24Mg9(Si9AlO28)(SiO4)(BO3)(CO3)10(OH)14O4, a new mineral: mineralogical characterization and crystal chemistry

NASA Astrophysics Data System (ADS)

Chukanov, Nikita V.; Jonsson, Erik; Aksenov, Sergey M.; Britvin, Sergey N.; Rastsvetaeva, Ramiza K.; Belakovskiy, Dmitriy I.; Van, Konstantin V.

2017-11-01

The new mineral roymillerite Pb24Mg9(Si9AlO28)(SiO4)(BO3)(CO3)10(OH)14O4, related to britvinite and molybdophyllite, was discovered in a Pb-rich assemblage from the Kombat Mine, Grootfontein district, Otjozondjupa region, Namibia, which includes also jacobsite, cerussite, hausmannite, sahlinite, rhodochrosite, barite, grootfonteinite, Mn-Fe oxides, and melanotekite. Roymillerite forms platy single-crystal grains up to 1.5 mm across and up to 0.3 mm thick. The new mineral is transparent, colorless to light pink, with a strong vitreous lustre. Cleavage is perfect on (001). Density calculated using the empirical formula is equal to 5.973 g/cm3. Roymillerite is optically biaxial, negative, α = 1.86(1), β ≈ γ = 1.94(1), 2 V (meas.) = 5(5)°. The IR spectrum shows the presence of britvinite-type tetrahedral sheets, {CO}3^{2 - }, {BO}3^{3 - }, and OH- groups. The chemical composition is (wt%; electron microprobe, H2O and CO2 determined by gas chromatography, the content of B2O3 derived from structural data): MgO 4.93, MnO 1.24, FeO 0.95, PbO 75.38, B2O3 0.50, Al2O3 0.74, CO2 5.83, SiO2 7.90, H2O 1.8, total 99.27. The empirical formula based on 83 O atoms pfu (i.e. Z = 1) is Pb24.12Mg8.74Mn1.25Fe0.94B1.03Al1.04C9.46Si9.39H14.27O83. The crystal structure was determined using single-crystal X-ray diffraction data. The new mineral is triclinic, space group P \\bar{1}, with a = 9.315(1), b = 9.316(1), c = 26.463(4) Å, α = 83.295(3)°, β = 83.308(3)°, γ = 60.023(2)°, V = 1971.2(6) Å3. The crystal structure of roymillerite is based built by alternating pyrophyllite-type TOT-modules Mg9(OH)8[(Si,Al)10O28] and I-blocks Pb24(OH)6O4(CO3)10(BO3,SiO4). The strongest lines of the powder X-ray diffraction pattern [ d, Å (I, %) ( hkl)] are: 25.9 (100) (001), 13.1 (11) (002), 3.480 (12) (017, 107, -115, 1-15), 3.378 (14) (126, 216), 3.282 (16) (-2-15, -1-25), 3.185 (12) (-116, 1-16), 2.684 (16) (031, 301, 030, 300, 332, -109, 0-19, 1-18), 2.382 (11) (0.0.-11). Roymillerite is named to honor Dr. Roy McG. Miller for his important contributions to the knowledge of the geology of Namibia.

Repeated social defeat and the rewarding effects of cocaine in adult and adolescent mice: dopamine transcription factors, proBDNF signaling pathways, and the TrkB receptor in the mesolimbic system.

PubMed

Montagud-Romero, Sandra; Nuñez, Cristina; Blanco-Gandia, M Carmen; Martínez-Laorden, Elena; Aguilar, María A; Navarro-Zaragoza, Javier; Almela, Pilar; Milanés, Maria-Victoria; Laorden, María-Luisa; Miñarro, José; Rodríguez-Arias, Marta

2017-07-01

Repeated social defeat (RSD) increases the rewarding effects of cocaine in adolescent and adult rodents. The aim of the present study was to compare the long-term effects of RSD on the conditioned rewarding effects of cocaine and levels of the transcription factors Pitx3 and Nurr1 in the ventral tegmental area (VTA), the dopamine transporter (DAT), the D2 dopamine receptor (D2DR) and precursor of brain-derived neurotrophic factor (proBDNF) signaling pathways, and the tropomyosin-related kinase B (TrkB) receptor in the nucleus accumbens (NAc) in adult and adolescent mice. Male adolescent and young adult OF1 mice were exposed to four episodes of social defeat and were conditioned 3 weeks later with 1 mg/kg of cocaine. In a second set of mice, the expressions of the abovementioned dopaminergic and proBDNF and TrkB receptor were measured in VTA and NAc, respectively. Adolescent mice experienced social defeats less intensely than their adult counterparts and produced lower levels of corticosterone. However, both adult and adolescent defeated mice developed conditioned place preference for the compartment associated with this low dose of cocaine. Furthermore, only adolescent defeated mice displayed diminished levels of the transcription factors Pitx3 in the VTA, without changes in the expression of DAT and D2DR in the NAc. In addition, stressed adult mice showed a decreased expression of proBDNF and the TrkB receptor, while stressed adolescent mice exhibited increased expression of latter without changes in the former. Our findings suggest that dopaminergic pathways and proBDNF signaling and TrkB receptors play different roles in social defeat-stressed mice exposed to cocaine.

Syndromes drépanocytaires majeurs et infections associées chez l ’enfant au Burkina Faso

PubMed Central

Douamba, Sonia; Nagalo, Kisito; Tamini, Laure; Traoré, Ismaël; Kam, Madibèlè; Kouéta, Fla; Yé, Diarra

2017-01-01

Introduction Le but de cette étude était d’étudier les infections chez les enfants présentant un syndrome drépanocytaire majeur. Méthodes Étude hospitalière monocentrique, rétrospective descriptive sur dix années menée à Ouagadougou, Burkina Faso. Étaient inclus tous les enfants porteurs d'un syndrome drépanocytaire majeur (homozygote SS et double hétérozygote SC, SDPunjab, Sβ thalassémique, SOArab et SE) hospitalisés pour une infection bactérienne confirmée à la microbiologie. Résultats Cent trente trois patients répondaient à nos critères d’inclusion. Le phénotype SS représentait 63,2% des cas et le SC 36,8%. La fréquence des infections était de 21,8%. Celles-ci touchaient dans 45,9% des cas les enfants âgés de 0 à 5 ans. Les signes les plus fréquents étaient les douleurs ostéoarticulaires (42,1%), la toux (25,7%), les douleurs abdominales (23,3%), la pâleur (43,6%). Les broncho-pneumopathies (31,6%), le paludisme (16,5%), les ostéomyélites (12,8%) et les septicémies (10,5%) étaient les principaux diagnostics trouvés. Les agents pathogènes isolés étaient Streptococcus pneumoniae (35,5%) et Salmonella sp (33,3%). Les céphalosporines de 3e génération étaient les antibiotiques les plus fréquemment prescrits. Le taux brut de mortalité était de 7,5%. Conclusion Les infections bactériennes et le paludisme dominent le tableau des infections chez l'enfant drépanocytaire majeur au Centre Hospitalier Universitaire Pédiatrique Charles De Gaulle. Les auteurs recommandent la mise en place d’un programme national de prise en charge de la drépanocytose, ce qui permettrait de prévenir voire réduire la survenue des infections chez les enfants drépanocytaires. PMID:28450986

Model validations for low-global warming potential refrigerants in mini-split air-conditioning units

DOE PAGES

Shen, Bo; Shrestha, Som; Abdelaziz, Omar

2016-09-02

To identify low GWP (global warming potential) refrigerants to replace R-22 and R-410A, extensive experimental evaluations were conducted for multiple candidates of refrigerant at the standard test conditions and at high-ambient conditions with outdoor temperature varying from 27.8 C to 55.0 C.. In the study, R-22 was compared to propane (R-290), DR-3, ARM-20B, N-20B and R-444B in a mini-split air conditioning unit originally designed for R-22; R-410A was compared to R-32, DR-55, ARM-71A, L41-2 (R-447A) in a mini-split unit designed for R-410A. To reveal physics behind the measured performance results, thermodynamic properties of the alternative refrigerants were analysed. In addition,more » the experimental data was used to calibrate a physics-based equipment model, i.e. ORNL Heat Pump Design Model (HPDM). The calibrated model translated the experimental results to key calculated parameters, i.e. compressor efficiencies, refrigerant side two-phase heat transfer coefficients, corresponding to each refrigerant. As a result, these calculated values provide scientific insights on the performance of the alternative refrigerants and are useful for other applications beyond mini-split air conditioning units.« less

Model validations for low-global warming potential refrigerants in mini-split air-conditioning units

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

Shen, Bo; Shrestha, Som; Abdelaziz, Omar

To identify low GWP (global warming potential) refrigerants to replace R-22 and R-410A, extensive experimental evaluations were conducted for multiple candidates of refrigerant at the standard test conditions and at high-ambient conditions with outdoor temperature varying from 27.8 C to 55.0 C.. In the study, R-22 was compared to propane (R-290), DR-3, ARM-20B, N-20B and R-444B in a mini-split air conditioning unit originally designed for R-22; R-410A was compared to R-32, DR-55, ARM-71A, L41-2 (R-447A) in a mini-split unit designed for R-410A. To reveal physics behind the measured performance results, thermodynamic properties of the alternative refrigerants were analysed. In addition,more » the experimental data was used to calibrate a physics-based equipment model, i.e. ORNL Heat Pump Design Model (HPDM). The calibrated model translated the experimental results to key calculated parameters, i.e. compressor efficiencies, refrigerant side two-phase heat transfer coefficients, corresponding to each refrigerant. As a result, these calculated values provide scientific insights on the performance of the alternative refrigerants and are useful for other applications beyond mini-split air conditioning units.« less

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

The influence of mutation gene rpoB of Mycobacterium tuberculosis cluster I (507-534) on the elimination 25-desacetyl rifampicin in urine of tuberculosis subjects

NASA Astrophysics Data System (ADS)

Lily; Sinaga, B. Y. M.; Ardinata, D.; Siregar, Y.

2018-03-01

The study aimed to evaluate the influence of mutation gene rpoB of Mycobacterium (M.) tuberculosis cluster I (507-534) on the elimination of 25-Desacetyl Rifampicin (25-DR) in the urine of tuberculosis (TB) subjects. Early morning sputum took from patient TB before treatment. Urine collected after 2 hours taken Fixed-Dose Combination (FDC) at days 7th treatment. All sputum were sequencing at Macrogen Korea Laboratory. Urine was analyzed by high-Performance Liquid Chromatography (HPLC) using the method of Lily et al. Mean (standard deviation) for mutation and non-mutation of rpoB M. tuberculosis group were 7.6147 (4.4478) and 4.5772 (1.7532) μg/ml, respectively. Shapiro-Wilk test showed normally distributed data, with significance 0.3. Independent t-test performed p-value 0.167 and confidence interval (CI) from -1.648 to 7.723. The mutation gene rpoB of M. tuberculosis cluster, I (507-534) in this study, did not affect elimination 25-DR in theurine of TB subjects statistically and clinically.

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

Expression of HLA Class II Molecules in Humanized NOD.Rag1KO.IL2RgcKO Mice Is Critical for Development and Function of Human T and B Cells

PubMed Central

Danner, Rebecca; Chaudhari, Snehal N.; Rosenberger, John; Surls, Jacqueline; Richie, Thomas L.; Brumeanu, Teodor-Doru; Casares, Sofia

2011-01-01

Background Humanized mice able to reconstitute a surrogate human immune system (HIS) can be used for studies on human immunology and may provide a predictive preclinical model for human vaccines prior to clinical trials. However, current humanized mouse models show sub-optimal human T cell reconstitution and limited ability to support immunoglobulin class switching by human B cells. This limitation has been attributed to the lack of expression of Human Leukocyte Antigens (HLA) molecules in mouse lymphoid organs. Recently, humanized mice expressing HLA class I molecules have been generated but showed little improvement in human T cell reconstitution and function of T and B cells. Methods We have generated NOD.Rag1KO.IL2RγcKO mice expressing HLA class II (HLA-DR4) molecules under the I-Ed promoter that were infused as adults with HLA-DR-matched human hematopoietic stem cells (HSC). Littermates lacking expression of HLA-DR4 molecules were used as control. Results HSC-infused HLA-DR4.NOD.Rag1KO.IL-2RγcKO mice developed a very high reconstitution rate (>90%) with long-lived and functional human T and B cells. Unlike previous humanized mouse models reported in the literature and our control mice, the HLA-DR4 expressing mice reconstituted serum levels (natural antibodies) of human IgM, IgG (all four subclasses), IgA, and IgE comparable to humans, and elicited high titers of specific human IgG antibodies upon tetanus toxoid vaccination. Conclusions Our study demonstrates the critical role of HLA class II molecules for development of functional human T cells able to support immunoglobulin class switching and efficiently respond to vaccination. PMID:21611197

Psychological stress is associated with altered levels of myeloid-derived suppressor cells in breast cancer patients.

PubMed

Mundy-Bosse, Bethany L; Thornton, Lisa M; Yang, Hae-Chung; Andersen, Barbara L; Carson, William E

2011-01-01

Our group has shown in a randomized clinical trial that psychological intervention to reduce stress in patients with stages II and III breast cancer led to enhanced immune function, fewer recurrences and improved overall survival. We hypothesized that patients with high levels of stress would have alterations in myeloid-derived suppressor cells (MDSC) compared to patients with lower stress. PBMC from 16 patients with high stress (n = 8) or with low stress (n = 8) after surgery as measured by the Impact of Event Scale (IES) questionnaire were evaluated for the presence of MDSC. Patients with higher IES scores had significantly elevated salivary cortisol levels (P = 0.013; 13 μg/dl vs. 9.74 μg/dl). Levels of IL-1Rα were also significantly elevated in the higher IES group (45.09 pg/ml vs. 97.16 pg/ml; P = 0.010). IP 10, G-CSF, and IL-6 were all higher in the high stress group although not to a significant degree. Flow cytometric analysis for CD33+/HLA-DR-neg/CD15+/CD11b+ MDSC revealed increased MDSC in patients with lower IES scores (P = 0.009). CD11b+/CD15+ cells constituted 9.4% of the CD33+/HLA DR-neg cell population in patients with high IES, vs. 27.3% in patients with low IES scores. Additional analyzes of the number of stressful events that affected the patients in addition to their cancer diagnosis revealed that this type of stress measure correlated with elevated levels of MDSC (P = 0.064). These data indicate the existence of a complex relationship between stress and immune function in breast cancer patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Psychological Stress is Associated with Altered Levels of Myeloid-Derived Suppressor cells in Breast Cancer Patients

PubMed Central

Mundy-Bosse, Bethany L.; Thornton, Lisa M.; Yang, Hae-Chung; Andersen, Barbara L.; Carson, William E.

2011-01-01

Our group has shown in a randomized clinical trial that psychological intervention to reduce stress in patients with stage II and III breast cancer led to enhanced immune function, fewer recurrences and improved overall survival. We hypothesized that patients with high levels of stress would have alterations in myeloid-derived suppressor cells (MDSC) compared to patients with lower stress. PBMC from 16 patients with high stress (n = 8) or with low stress (n = 8) after surgery as measured by the Impact of Event Scale (IES) questionnaire were evaluated for the presence of MDSC. Patients with higher IES scores had significantly elevated salivary cortisol levels (P = 0.013; 13 µg/dl vs. 9.74 µg/dl). Levels of IL-1Rα were also significantly elevated in the higher IES group (45.09 pg/mL vs. 97.16 pg/mL; P = 0.010). IP 10, G-CSF, and IL-6 were all higher in the high stress group although not to a significant degree. Flow cytometric analysis for CD33+/HLA-DR-neg/CD15+/CD11b+ MDSC revealed increased MDSC in patients with lower IES scores (P = 0.009). CD11b+/CD15+ cells constituted 9.4% of the CD33+/HLA DR-neg cell population in patients with high IES, versus 27.3% in patients with low IES scores. Additional analyses of the number of stressful events that affected the patients in addition to their cancer diagnosis revealed that this type of stress measure correlated with elevated levels of MDSC (P = .064). These data indicate the existence of a complex relationship between stress and immune function in breast cancer patients. PMID:21600570

Somatostatin protects photoreceptor cells against high glucose-induced apoptosis.

PubMed

Arroba, Ana I; Mazzeo, Aurora; Cazzoni, Daniele; Beltramo, Elena; Hernández, Cristina; Porta, Massimo; Simó, Rafael; Valverde, Ángela M

2016-01-01

Many cellular and molecular studies in experimental animals and early retinal function tests in patients with diabetic retinopathy (DR) have shown that retinal neurodegeneration is an early event in the pathogenesis of the disease. Somatostatin (SST) is one of the most important neuroprotective factors synthesized by the retina: SST levels are decreased in parallel to retinal neurodegeneration in early stages of DR. In this study, we characterized the induction of apoptosis (programmed cell death) in a 661W photoreceptor-like cell line cultured under high glucose (HG) conditions and the effect of SST. A 661W photoreceptor-like cell line and retinal explants from 10-week-old male C57BL/6 mice were cultured under HG conditions and treated with SST. Hyperglycemia significantly reduced the cellular viability by increasing the percentage of apoptotic cells, and this effect was ameliorated by SST (p˂0.05). Activation of caspase-8 by hyperglycemia was found in the 661W cells and retinal explants and decreased in the presence of SST (p˂0.05). Moreover, we detected activation of calpain-2 associated with hyperglycemia-induced cell death, as well as increased protein tyrosine phosphatase 1B (PTP1B) protein levels; both had a pattern of cleavage that was absent in the presence of SST (p˂0.05). Treatment of the 661W cells and retinal explants with SST for 24 h increased the phosphorylation of type 1 insulin-like growth factor receptor (IGF-IR; tyrosine 1165/1166) and protein kinase B (Akt; serine 473), suggesting this survival signaling is activated in the neuroretina by SST (p˂0.05). This study has provided new mechanistic insights first into the involvement of calpain-2 and PTP1B in the loss of cell survival and increased caspase-8-dependent apoptosis induced by hyperglycemia in photoreceptor cells and second, on the protective effect of SST against apoptosis by the enhancement of IGF-IR-mediated Akt phosphorylation.

Somatostatin protects photoreceptor cells against high glucose–induced apoptosis

PubMed Central

Mazzeo, Aurora; Cazzoni, Daniele; Beltramo, Elena; Hernández, Cristina; Porta, Massimo; Simó, Rafael; Valverde, Ángela M.

2016-01-01

Purpose Many cellular and molecular studies in experimental animals and early retinal function tests in patients with diabetic retinopathy (DR) have shown that retinal neurodegeneration is an early event in the pathogenesis of the disease. Somatostatin (SST) is one of the most important neuroprotective factors synthesized by the retina: SST levels are decreased in parallel to retinal neurodegeneration in early stages of DR. In this study, we characterized the induction of apoptosis (programmed cell death) in a 661W photoreceptor-like cell line cultured under high glucose (HG) conditions and the effect of SST. Methods A 661W photoreceptor-like cell line and retinal explants from 10-week-old male C57BL/6 mice were cultured under HG conditions and treated with SST. Results Hyperglycemia significantly reduced the cellular viability by increasing the percentage of apoptotic cells, and this effect was ameliorated by SST (p˂0.05). Activation of caspase-8 by hyperglycemia was found in the 661W cells and retinal explants and decreased in the presence of SST (p˂0.05). Moreover, we detected activation of calpain-2 associated with hyperglycemia-induced cell death, as well as increased protein tyrosine phosphatase 1B (PTP1B) protein levels; both had a pattern of cleavage that was absent in the presence of SST (p˂0.05). Treatment of the 661W cells and retinal explants with SST for 24 h increased the phosphorylation of type 1 insulin-like growth factor receptor (IGF-IR; tyrosine 1165/1166) and protein kinase B (Akt; serine 473), suggesting this survival signaling is activated in the neuroretina by SST (p˂0.05). Conclusions This study has provided new mechanistic insights first into the involvement of calpain-2 and PTP1B in the loss of cell survival and increased caspase-8-dependent apoptosis induced by hyperglycemia in photoreceptor cells and second, on the protective effect of SST against apoptosis by the enhancement of IGF-IR-mediated Akt phosphorylation. PMID:28050125

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.

Application of Regional Arrays in Seismic Verification Research

DTIC Science & Technology

1990-08-31

Hill, MA 02167 P.O. Box 1620 La Jolla, CA 92038-1620 Dr. Richard LaCoss Prof. William Menke MIT-Lincoln Laboratory L amront-Doherty -- dogical b ser t...LWH of Columbia University Hanscom AFB, MA 01731-5000 Palisades, NY 10964 3 Dr. Lorraine Wolf GLILWH Hanscom AFB, MA 01731-5000 Dr. William Wortman... William J. Best Prof. Robert W. Clayton 907 Westwood Drive Seismological Laboratory Vienna, VA 22180 Division of Geological & Planetary Sciences

The tissue microlocalisation and cellular expression of CD163, VEGF, HLA-DR, iNOS, and MRP 8/14 is correlated to clinical outcome in NSCLC.

PubMed

Ohri, Chandra M; Shikotra, Aarti; Green, Ruth H; Waller, David A; Bradding, Peter

2011-01-01

We have previously investigated the microlocalisation of M1 and M2 macrophages in NSCLC. This study investigated the non-macrophage (NM) expression of proteins associated with M1 and M2 macrophages in NSCLC. Using immunohistochemistry, CD68(+) macrophages and proteins associated with either a cytotoxic M1 phenotype (HLA-DR, iNOS, and MRP 8/14), or a non-cytotoxic M2 phenotype (CD163 and VEGF) were identified. NM expression of the markers was analysed in the islets and stroma of surgically resected tumours from 20 patients with extended survival (ES) (median 92.7 months) and 20 patients with poor survival (PS) (median 7.7 months). The NM expression of NM-HLA-DR (p<0.001), NM-iNOS (p = 0.02) and NM-MRP 8/14 (p = 0.02) was increased in ES compared to PS patients in the tumour islets. The tumour islet expression of NM-VEGF, was decreased in ES compared to PS patients (p<0.001). There was more NM-CD163 expression (p = 0.04) but less NM-iNOS (p = 0.002) and MRP 8/14 (p = 0.01) expression in the stroma of ES patients compared with PS patients. The 5-year survival for patients with above and below median NM expression of the markers in the islets was 74.9% versus 4.7% (NM-HLA-DR p<0.001), 65.0% versus 14.6% (NM-iNOS p = 0.003), and 54.3% versus 22.2% (NM-MRP 8/14 p = 0.04), as opposed to 34.1% versus 44.4% (NM-CD163 p = 0.41) and 19.4% versus 59.0% (NM-VEGF p = 0.001). Cell proteins associated with M1 and M2 macrophages are also expressed by other cell types in the tumour islets and stroma of patients with NSCLC. Their tissue and cellular microlocalisation is associated with important differences in clinical outcome.

Damage Thresholds for Cultures RPE Cells Exposed to Lasers at 532 nm and 458 nm

DTIC Science & Technology

2007-06-01

ADDRESS(ES) Air Force Research Laboratory H uman Effectiveness Directorate Directed Energy Bioeffects Division Optical Radiation Branch 2624 Louis Bauer Dr...Directed Energy Bioeffects Division Optical Radiation Branch 2624 Louis Bauer Dr. Brooks City-Base, TX 7 8235-5128 1 0. SPoNSOR/MON|TOR’S ACRONYM(S) AFRL...p t b m T a i b i fi d D o a T t i f e t A B r Journal of Biomedical Optics 123, 034030 May/June 2007 J amage thresholds for cultured retinal

Kidney transplantation outcomes in African-, Hispanic- and Caucasian-Americans with lupus.

PubMed

Contreras, G; Mattiazzi, A; Schultz, D R; Guerra, G; Ladino, M; Ortega, L M; Garcia-Estrada, M; Ramadugu, P; Gupta, C; Kupin, W L; Roth, D

2012-01-01

African-American recipients of kidney transplants with lupus have high allograft failure risk. We studied their risk adjusting for: (1) socio-demographic factors: donor age, gender and race-ethnicity; recipient age, gender, education and insurance; donor-recipient race-ethnicity match; (2) immunologic factors: donor type, panel reactive antibodies, HLA mismatch, ABO blood type compatibility, pre-transplant dialysis, cytomegalovirus risk and delayed graft function (DGF); (3) rejection and recurrent lupus nephritis (RLN). Two thousand four hundred and six African-, 1132 Hispanic-, and 2878 Caucasian-Americans were followed for 12 years after transplantation. African- versus Hispanic- and Caucasian-Americans received more kidneys from deceased donors (71.6%, 57.3% and 55.1%) with higher two HLA loci mismatches for HLA-A (50%, 39.6% and 32.4%), HLA-B (52%, 42.8% and 35.6%) and HLA-DR (30%, 24.5% and 21.1%). They developed more DGF (19.5%, 13.6% and 13.4%). More African- versus Hispanic- and Caucasian-Americans developed rejection (41.7%, 27.6% and 35.9%) and RLN (3.2, 1.8 and 1.8%). 852 African-, 265 Hispanic-, and 747 Caucasian-Americans had allograft failure (p < 0.0001). After adjusting for transplant era, socio-demographic-immunologic differences, rejection and RLN, the increased hazard ratio for allograft failure of African- compared with Caucasian-Americans became non-significant (1.26 [95% confidence interval 0.78-2.04]). African-Americans with lupus have high prevalence of risk factors for allograft failure that can explain poor outcomes.

Antitumour effects of single or combined monoclonal antibodies directed against membrane antigens expressed by human B cells leukaemia

PubMed Central

2011-01-01

Background The increasing availability of different monoclonal antibodies (mAbs) opens the way to more specific biologic therapy of cancer patients. However, despite the significant success of therapy in breast and ovarian carcinomas with anti-HER2 mAbs as well as in non-Hodkin B cell lymphomas with anti-CD20 mAbs, certain B cell malignancies such as B chronic lymphocytic leukaemia (B-CLL) respond poorly to anti-CD20 mAb, due to the low surface expression of this molecule. Thus, new mAbs adapted to each types of tumour will help to develop personalised mAb treatment. To this aim, we analyse the biological and therapeutic properties of three mAbs directed against the CD5, CD71 or HLA-DR molecules highly expressed on B-CLL cells. Results The three mAbs, after purification and radiolabelling demonstrated high and specific binding capacity to various human leukaemia target cells. Further in vitro analysis showed that mAb anti-CD5 induced neither growth inhibition nor apoptosis, mAb anti-CD71 induced proliferation inhibition with no early sign of cell death and mAb anti-HLA-DR induced specific cell aggregation, but without evidence of apoptosis. All three mAbs induced various degrees of ADCC by NK cells, as well as phagocytosis by macrophages. Only the anti-HLA-DR mAb induced complement mediated lysis. Coincubation of different pairs of mAbs did not significantly modify the in vitro results. In contrast with these discrete and heterogeneous in vitro effects, in vivo the three mAbs demonstrated marked anti-tumour efficacy and prolongation of mice survival in two models of SCID mice, grafted either intraperitoneally or intravenously with the CD5 transfected JOK1-5.3 cells. This cell line was derived from a human hairy cell leukaemia, a type of malignancy known to have very similar biological properties as the B-CLL, whose cells constitutively express CD5. Interestingly, the combined injection of anti-CD5 with anti-HLA-DR or with anti-CD71 led to longer mouse survival, as compared to single mAb injection, up to complete inhibition of tumour growth in 100% mice treated with both anti-HLA-DR and anti-CD5. Conclusions Altogether these data suggest that the combined use of two mAbs, such as anti-HLA-DR and anti-CD5, may significantly enhance their therapeutic potential. PMID:21504579

Automatic dynamic range adjustment for ultrasound B-mode imaging.

PubMed

Lee, Yeonhwa; Kang, Jinbum; Yoo, Yangmo

2015-02-01

In medical ultrasound imaging, dynamic range (DR) is defined as the difference between the maximum and minimum values of the displayed signal to display and it is one of the most essential parameters that determine its image quality. Typically, DR is given with a fixed value and adjusted manually by operators, which leads to low clinical productivity and high user dependency. Furthermore, in 3D ultrasound imaging, DR values are unable to be adjusted during 3D data acquisition. A histogram matching method, which equalizes the histogram of an input image based on that from a reference image, can be applied to determine the DR value. However, it could be lead to an over contrasted image. In this paper, a new Automatic Dynamic Range Adjustment (ADRA) method is presented that adaptively adjusts the DR value by manipulating input images similar to a reference image. The proposed ADRA method uses the distance ratio between the log average and each extreme value of a reference image. To evaluate the performance of the ADRA method, the similarity between the reference and input images was measured by computing a correlation coefficient (CC). In in vivo experiments, the CC values were increased by applying the ADRA method from 0.6872 to 0.9870 and from 0.9274 to 0.9939 for kidney and liver data, respectively, compared to the fixed DR case. In addition, the proposed ADRA method showed to outperform the histogram matching method with in vivo liver and kidney data. When using 3D abdominal data with 70 frames, while the CC value from the ADRA method is slightly increased (i.e., 0.6%), the proposed method showed improved image quality in the c-plane compared to its fixed counterpart, which suffered from a shadow artifact. These results indicate that the proposed method can enhance image quality in 2D and 3D ultrasound B-mode imaging by improving the similarity between the reference and input images while eliminating unnecessary manual interaction by the user. Copyright © 2014 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

Dissociative recombination and electron-impact de-excitation in CH photon emission under ITER divertor-relevant plasma conditions

NASA Astrophysics Data System (ADS)

van Swaaij, G. A.; Bystrov, K.; Borodin, D.; Kirschner, A.; van der Vegt, L. B.; van Rooij, G. J.; De Temmerman, G.; Goedheer, W. J.

2012-09-01

For understanding carbon erosion and redeposition in nuclear fusion devices, it is important to understand the transport and chemical break-up of hydrocarbon molecules in edge plasmas, often diagnosed by emission of the CH A 2Δ-X 2Π Gerö band around 430 nm. The CH A-level can be excited either by electron-impact (EI) or by dissociative recombination (DR) of hydrocarbon ions. These processes were included in the 3D Monte Carlo impurity transport code ERO. A series of methane injection experiments was performed in the high-density, low-temperature linear plasma generator Pilot-PSI, and simulated emission intensity profiles were benchmarked against these experiments. It was confirmed that excitation by DR dominates at Te < 1.5 eV. The results indicate that the fraction of DR events that lead to a CH radical in the A-level and consequent photon emission is at least 10%. Additionally, quenching of the excited CH radicals by EI de-excitation was included in the modeling. This quenching is shown to be significant: depending on the electron density, it reduces the effective CH emission by a factor of 1.4 at ne = 1.3 × 1020 m-3, to 2.8 at ne = 9.3 × 1020 m-3. Its inclusion significantly improved agreement between experiment and modeling.

The Concept Design of a Split Flow Liquid Hydrogen Turbopump

DTIC Science & Technology

2008-03-01

Oxygen Boost Pump OTP Oxygen Turbopump O/B Overboard b Passage depth inches Lp Passage loss Kp Passage loss constant Recommended value = 0.3...user or a diffusion model is selected . 2 1 2p tW W DR= ∗ (1.49) 39 There are eight methods within Pumpal® to estimate the value of the...allows the user to select a tip model secondary mass flow fraction. The mass fraction was set to 0.05. This value is within the range (0.02-0.10

Aerospace Materials for Extreme Environments

DTIC Science & Technology

2013-03-07

6.0% 8.0% 35.0 45.0 55.0 Zr [at%] Icosahedron Fraction • Chosen Method: Green - Kubo  =  t B t dstPstP Tk V 0 00 )()(lim  Zr Al Ni...1 DISTRIBUTION STATEMENT A – Unclassified, Unlimited Distribution 15 February 2013 Integrity  Service  Excellence Dr. Ali Sayir Program Officer...c) (d) (e) (f) (g) (h) Band structure EELS spectra Kinetic parameters Thermal properties Mechanical prop’s W. Windl (OSU), K. Flores

Kepler Planet Detection Metrics: Pixel-Level Transit Injection Tests of Pipeline Detection Efficiency for Data Release 25

NASA Technical Reports Server (NTRS)

Christiansen, Jessie L.

2017-01-01

This document describes the results of the fourth pixel-level transit injection experiment, which was designed to measure the detection efficiency of both the Kepler pipeline (Jenkins 2002, 2010; Jenkins et al. 2017) and the Robovetter (Coughlin 2017). Previous transit injection experiments are described in Christiansen et al. (2013, 2015a,b, 2016).In order to calculate planet occurrence rates using a given Kepler planet catalogue, produced with a given version of the Kepler pipeline, we need to know the detection efficiency of that pipeline. This can be empirically determined by injecting a suite of simulated transit signals into the Kepler data, processing the data through the pipeline, and examining the distribution of successfully recovered transits. This document describes the results for the pixel-level transit injection experiment performed to accompany the final Q1-Q17 Data Release 25 (DR25) catalogue (Thompson et al. 2017)of the Kepler Objects of Interest. The catalogue was generated using the SOC pipeline version 9.3 and the DR25 Robovetter acting on the uniformly processed Q1-Q17 DR25 light curves (Thompson et al. 2016a) and assuming the Q1-Q17 DR25 Kepler stellar properties (Mathur et al. 2017).

Research progress in muscle-derived stem cells: Literature retrieval results based on international database.

PubMed

Zhang, Li; Wang, Wei

2012-04-05

To identify global research trends of muscle-derived stem cells (MDSCs) using a bibliometric analysis of the Web of Science, Research Portfolio Online Reporting Tools of the National Institutes of Health (NIH), and the Clinical Trials registry database (ClinicalTrials.gov). We performed a bibliometric analysis of data retrievals for MDSCs from 2002 to 2011 using the Web of Science, NIH, and ClinicalTrials.gov. (1) Web of Science: (a) peer-reviewed articles on MDSCs that were published and indexed in the Web of Science. (b) Type of articles: original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material and news items. (c) Year of publication: 2002-2011. (d) Citation databases: Science Citation Index-Expanded (SCI-E), 1899-present; Conference Proceedings Citation Index-Science (CPCI-S), 1991-present; Book Citation Index-Science (BKCI-S), 2005-present. (2) NIH: (a) Projects on MDSCs supported by the NIH. (b) Fiscal year: 1988-present. (3) ClinicalTrials.gov: All clinical trials relating to MDSCs were searched in this database. (1) Web of Science: (a) Articles that required manual searching or telephone access. (b) We excluded documents that were not published in the public domain. (c) We excluded a number of corrected papers from the total number of articles. (d) We excluded articles from the following databases: Social Sciences Citation Index (SSCI), 1898-present; Arts & Humanities Citation Index (A&HCI), 1975-present; Conference Proceedings Citation Index - Social Science & Humanities (CPCI-SSH), 1991-present; Book Citation Index - Social Sciences & Humanities (BKCI-SSH), 2005-present; Current Chemical Reactions (CCR-EXPANDED), 1985-present; Index Chemicus (IC), 1993-present. (2) NIH: (a) We excluded publications related to MDSCs that were supported by the NIH. (b) We limited the keyword search to studies that included MDSCs within the title or abstract. (3) ClinicalTrials.gov: (a) We excluded clinical trials that were not in the ClinicalTrials.gov database. (b) We excluded clinical trials that dealt with stem cells other than MDSCs in the ClinicalTrials.gov database. (1) Type of literature; (2) annual publication output; (3) distribution according to journals; (4) distribution according to country; (5) distribution according to institution; (6) top cited authors over the last 10 years; (7) projects financially supported by the NIH; and (8) clinical trials registered. (1) In all, 802 studies on MDSCs appeared in the Web of Science from 2002 to 2011, almost half of which derived from American authors and institutes. The number of studies on MDSCs has gradually increased over the past 10 years. Most papers on MDSCs appeared in journals with a particular focus on cell biology research, such as Experimental Cell Research, Journal of Cell Science, and PLoS One. (2) Eight MDSC research projects have received over US$6 billion in funding from the NIH. The current project led by Dr. Johnny Huard of the University of Pittsburgh-"Muscle-Based Tissue Engineering to Improve Bone Healing"-is supported by the NIH. Dr. Huard has been the most productive and top-cited author in the field of gene therapy and adult stem cell research in the Web of Science over last 10 years. (3) On ClinicalTrials.gov, "Muscle Derived Cell Therapy for Bladder Exstrophy Epispadias Induced Incontinence" Phase 1 is registered and sponsored by Johns Hopkins University and has been led by Dr. John P. Gearhart since November 2009. From our analysis of the literature and research trends, we found that MDSCs may offer further benefits in regenerative medicine.

Air Force Project Competition

DTIC Science & Technology

2014-10-22

FA9550-11-1-0235 final report The Johns Hopkins University Dr Nathan Scott 7 Team BRX 2012-13: Will Crawford, Ben Wasser , Renata Smith, Danny Fisher...custom sock and braced with guy ropes. See Fig. 8. Fig. 8 Ben Wasser and Will Crawford testing the bridge in April 2013. FA9550-11-1-0235 final report...The Johns Hopkins University Dr Nathan Scott 8 Fig. 9 Ben Wasser carrying the folded, stowed bridge in its backpack. The pack weighed about 45lb

Air Force Project Competition

DTIC Science & Technology

2014-10-17

FA9550-11-1-0235 final report The Johns Hopkins University Dr Nathan Scott 7 Team BRX 2012-13: Will Crawford, Ben Wasser , Renata Smith, Danny Fisher...custom sock and braced with guy ropes. See Fig. 8. Fig. 8 Ben Wasser and Will Crawford testing the bridge in April 2013. FA9550-11-1-0235 final report...The Johns Hopkins University Dr Nathan Scott 8 Fig. 9 Ben Wasser carrying the folded, stowed bridge in its backpack. The pack weighed about 45lb

Multi-objective optimization for the economic production of d-psicose using simulated moving bed chromatography.

PubMed

Wagner, N; Håkansson, E; Wahler, S; Panke, S; Bechtold, M

2015-06-12

The biocatalytic production of rare carbohydrates from available sugar sources rapidly gains interest as a route to acquire industrial amounts of rare sugars for food and fine chemical applications. Here we present a multi-objective optimization procedure for a simulated moving bed (SMB) process for the production of the rare sugar d-psicose from enzymatically produced mixtures with its epimer d-fructose. First, model parameters were determined using the inverse method and experimentally validated on a 2-2-2-2 lab-scale SMB plant. The obtained experimental purities (PUs) were in excellent agreement with the simulated data derived from a transport-dispersive true-moving bed model demonstrating the feasibility of the proposed design. In the second part the performance of the separation was investigated in a multi-objective optimization study addressing the cost-contributing performance parameters productivity (PR) and desorbent requirement (DR) as a function of temperature. While rare sugar SMB operation under conditions of low desorbent consumption was found to be widely unaffected by temperature, SMB operation focusing on increased PR significantly benefited from high temperatures, with possible productivities increasing from 3.4kg(Lday)(-1) at 20°C to 5kg(Lday)(-1) at 70°C, indicating that decreased selectivity at higher temperatures could be fully compensated for by the higher mass transfer rates, as they translate into reduced switch times and hence higher PR. A DR/PR Pareto optimization suggested a similar but even more pronounced trend also under relaxed PU requirements, with the PR increasing from 4.3kg(Lday)(-1) to a maximum of 7.8kg(Lday)(-1) for SMB operation at 50°C when the PU of the non-product stream was reduced from 99.5% to 90%. Based on the in silico optimization results experimental SMB runs were performed yielding considerable PRs of 1.9 (30°C), 2.4 (50°C) and 2.6kg(Lday)(-1) (70°C) with rather low DR (27L per kg of rare sugar produced) on a lab-scale SMB installation. Copyright © 2015. Published by Elsevier B.V.

Appropriateness Measurement with Polychotomous Item Response Models and Standardized Indices.

DTIC Science & Technology

1984-04-01

Knoxville, TN � Lawrence, KS 66045 I Dr. John B. Carroll I ERIC Facility-Acquisitions -. ’ 409 Elliott Rd. 4833 Rugby Avenue Chapel Hill, NC...90007 University of Missouri Columbia, MO 65201 1 German Military Representative ATTN: Wolfgang Wildegrube 1 Dr. V. R. R. Uppuluri Streitkraefteast Union

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.

Astronaut Alan B. Shepard has his blood pressure and temperature checked

NASA Technical Reports Server (NTRS)

1961-01-01

Astronaut Alan B. Shepard has his blood pressure and temperate checked prior to his Mercury-Redstone 3 (MR-3) mission, the first American manned space flight. The attending physician is Dr. William K. Douglas.

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

The clustering of galaxies in the SDSS-III DR10 Baryon Oscillation Spectroscopic Survey: no detectable colour dependence of distance scale or growth rate measurements

NASA Astrophysics Data System (ADS)

Ross, Ashley J.; Samushia, Lado; Burden, Angela; Percival, Will J.; Tojeiro, Rita; Manera, Marc; Beutler, Florian; Brinkmann, J.; Brownstein, Joel R.; Carnero, Aurelio; da Costa, Luiz A. N.; Eisenstein, Daniel J.; Guo, Hong; Ho, Shirley; Maia, Marcio A. G.; Montesano, Francesco; Muna, Demitri; Nichol, Robert C.; Nuza, Sebastián E.; Sánchez, Ariel G.; Schneider, Donald P.; Skibba, Ramin A.; Sobreira, Flávia; Streblyanska, Alina; Swanson, Molly E. C.; Thomas, Daniel; Tinker, Jeremy L.; Wake, David A.; Zehavi, Idit; Zhao, Gong-bo

2014-01-01

We study the clustering of galaxies, as a function of their colour, from Data Release Ten (DR10) of the Sloan Digital Sky Survey III (SDSS-III) Baryon Oscillation Spectroscopic Survey. DR10 contains 540 505 galaxies with 0.43 < z < 0.7; from these we select 122 967 for a `Blue' sample and 131 969 for a `Red' sample based on k + e corrected (to z = 0.55) r - i colours and i-band magnitudes. The samples are chosen such that both contain more than 100 000 galaxies, have similar redshift distributions and maximize the difference in clustering amplitude. The Red sample has a 40 per cent larger bias than the Blue (bRed/bBlue = 1.39 ± 0.04), implying that the Red galaxies occupy dark matter haloes with an average mass that is 0.5 log10 M⊙ greater. Spherically averaged measurements of the correlation function, ξ0, and the power spectrum are used to locate the position of the baryon acoustic oscillation (BAO) feature of both samples. Using ξ0, we obtain distance scales, relative to the distance of our reference Λ cold dark matter cosmology, of 1.010 ± 0.027 for the Red sample and 1.005 ± 0.031 for the Blue. After applying reconstruction, these measurements improve to 1.013 ± 0.020 for the Red sample and 1.008 ± 0.026 for the Blue. For each sample, measurements of ξ0 and the second multipole moment, ξ2, of the anisotropic correlation function are used to determine the rate of structure growth, parametrized by fσ8. We find fσ8, Red = 0.511 ± 0.083, fσ8, Blue = 0.509 ± 0.085 and fσ8, Cross = 0.423 ± 0.061 (from the cross-correlation between the Red and Blue samples). We use the covariance between the bias and growth measurements obtained from each sample and their cross-correlation to produce an optimally combined measurement of fσ8, comb = 0.443 ± 0.055. This result compares favourably to that of the full 0.43 < z < 0.7 sample (fσ8, full = 0.422 ± 0.051) despite the fact that, in total, we use less than half of the number of galaxies analysed in the full sample measurement. In no instance do we detect significant differences in distance scale or structure growth measurements obtained from the Blue and Red samples. Our results are consistent with theoretical predictions and our tests on mock samples, which predict that any colour-dependent systematic uncertainty on the measured BAO position is less than 0.5 per cent.

Late-onset dietary restriction compensates for age-related increase in oxidative stress and alterations of HSP 70 and synapsin 1 protein levels in male Wistar rats.

PubMed

Sharma, Sandeep; Singh, Rumani; Kaur, Manpreet; Kaur, Gurcharan

2010-04-01

Numerous reports implicate increased oxidative stress in the functional and structural changes occurring in the brain and other organs as a part of the normal aging process. Dietary restriction (DR) has long been shown to be life-prolonging intervention in several species. This study was aimed to assess the potential efficacy of late-onset short term DR when initiated in 21 months old male wistar rats for 3 months on the antioxidant defense system and lipid peroxidation, cellular stress response protein HSP 70 and synaptic marker protein synapsin 1 in discrete brain regions such as cortex, hypothalamus, and hippocampus as well as liver, kidney and heart from 24 month old rats. Age-associated decline in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione, and elevated levels of lipid peroxidation was observed in brain and peripheral organ as well as increased expression of HSP 70 and reduction in synapsin 1 was observed in brain studied. Late-onset short term DR was effective in partially restoring the antioxidant status and in decreasing lipid peroxidation level as well as enhancing the expression of HSP 70 and synapsin 1 in aged rats. Late onset short term DR also prevented age-related neurodegeneration as revealed by Fluoro-Jade B staining in hippocampus and cortex regions of rat brain. Thus our current results suggest that DR initiated even in old age has the potential to improve age related decline in body functions.

Dual role of DR5 in death and survival signaling leads to TRAIL resistance in cancer cells

PubMed Central

Shlyakhtina, Yelyzaveta; Pavet, Valeria; Gronemeyer, Hinrich

2017-01-01

Besides its tumor-selective apoptotic activity, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) promotes pro-survival, proliferative or migratory signaling (NF-κB, PI3K/Akt, MAPK and JNK; referred to as 'non-apoptotic' cascades). Indeed, apoptosis and non-apoptotic signaling can be activated in clonal populations of cancer cells in response to treatment and, as a result, only a part of the initial cellular population dies while a fraction survives and develops resistance to TRAIL-induced apoptosis (referred to as 'fractional survival'). Notably, the molecular characterization of the protein platforms streaming into tumoricidal versus tumor-promoting cascades that control fractional survival remained elusive. Here we demonstrate that, in the context of DR4–DR5–DcR2 hetero-oligomeric complexes, a single death receptor (DR5) suffices to assemble composite plasma membrane-proximal pro-apoptotic/pro-survival platforms that propagate TRAIL signaling to both death and survival pathways in clonal populations of cancer cells. Moreover, we show that while all members of TRAIL-induced complexes support survival, none of them acted exclusively pro-apoptotic. Indeed, key apoptotic proteins as FADD and procaspase-8 were also involved in transducing non-apoptotic signaling in response to this cytokine. Collectively, this study reveals the Janus faces of DR5, and the contributions of other death complex components in fractional survival that foster the generation of resistance. Our data highlight a new level of complexity in TRAIL signaling and point to an improved therapeutic rationale in view of hitherto disappointing results. PMID:29048428

Neuroprotective effects of Bacopa monnieri (Brahmi) on novel object recognition and NMDAR1 immunodensity in the prefrontal cortex, striatum and hippocampus of sub-chronic phencyclidine rat model of schizophrenia.

PubMed

Piyabhan, Pritsana; Wetchateng, Thanitsara

2014-08-01

Cognitive impairment is a major problem, which eventually develops in schizophrenia. It contributes to the patients 'functional disability and cannot be attenuated by antipsychotic drugs. Bacopa monnieri (Brahmi), a neuroprotective herbal medicine in the elderly, might be a novel neuroprotective agent for prevention of cognitive deficit in schizophrenia. To study neuroprotective effects ofBrahmi on novel object recognition task and cerebral glutamate/N-methyl-D- aspartate receptor subtype 1 (NMDAR1) immunodensity in sub-chronic phencyclidine (PCP) rat model ofschizophrenia. Rats were assigned to three groups; Group-A: Control, Group-B: PCP administration and Group- C: Brahmi + PCP. Discrimination ratio (DR) representing cognitive ability was obtainedfrom novel object recognition task. NMDAR1 immunodensity was measured in prefrontal cortex, striatum, cornu ammonis fields I (CA 1) and 2/3 (CA2/3) and dentate gyrus (DG) using immunohistochemistry. DR was significantly reduced in PCP group compared with control. This occurred alongside NMDAR1 up-regulation in CA2/3 and DG but not in prefrontal cortex, striatum or CA1. Brahmi + PCP group showed an increased DR score up to normal which occurred alongside a significantly decreased NMDARI immunodensity in CA2/3 and DG compared with PCP group. Cognitive deficit observed in rats receiving PCP was mediated by NMDAR1 up-regulation in CA2/3 and DG Interestingly, receiving Brahmi before PCP administration can restore this cognitive deficit by decreasingNMDAR1 in these brain areas. Therefore, Brahmi could be a novel neuroprotective agentfor the prevention ofcognitive deficit in schizophrenia.

75 FR 79084 - Qualification of Drivers; Exemption Applications; Vision

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-17

....gpo.gov/2008/pdf/E8-785.pdf . FOR FURTHER INFORMATION CONTACT: Dr. Mary D. Gunnels, Director, Medical... are: Johnny Becerra John B. Ethridge Michael B. McClure Ross E. Burroughs Larry J. Folkerts Francis M. McMullin Lester W. Carter Paul W. Hunter Norman Mullins Christopher L. DePuy Ray P. Lenz David Triplett The...

MOTION VERIFIED RED STARS (MoVeRS): A CATALOG OF PROPER MOTION SELECTED LOW-MASS STARS FROM WISE, SDSS, AND 2MASS

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

Theissen, Christopher A.; West, Andrew A.; Dhital, Saurav, E-mail: ctheisse@bu.edu

2016-02-15

We present a photometric catalog of 8,735,004 proper motion selected low-mass stars (KML-spectral types) within the Sloan Digital Sky Survey (SDSS) footprint, from the combined SDSS Data Release 10 (DR10), Two Micron All-Sky Survey (2MASS) point-source catalog (PSC), and Wide-field Infrared Survey Explorer (WISE) AllWISE catalog. Stars were selected using r − i, i − z, r − z, z − J, and z − W1 colors, and SDSS, WISE, and 2MASS astrometry was combined to compute proper motions. The resulting 3,518,150 stars were augmented with proper motions for 5,216,854 earlier type stars from the combined SDSS and United States Naval Observatory B1.0 catalog (USNO-B). We used SDSS+USNO-B proper motionsmore » to determine the best criteria for selecting a clean sample of stars. Only stars whose proper motions were greater than their 2σ uncertainty were included. Our Motion Verified Red Stars catalog is available through SDSS CasJobs and VizieR.« less

Esters of Quinoxaline 1ˏ4-Di-N-oxide with Cytotoxic Activity on Tumor Cell Lines Based on NCI-60 Panel

PubMed Central

Rivera, Gildardo; Ahmad Shah, Syed Shoaib; Arrieta-Baez, Daniel; Palos, Isidro; Mongue, Antonio; Sánchez-Torres, Luvia Enid

2017-01-01

Quinoxalines display diverse and interesting pharmacological activities as antibacterial, antiviral, antiparasitic and anticancer agents. Particularly, their 1ˏ4-di-N-oxide derivatives have proved to be cytotoxic agents that are active under hypoxic conditions as that of solid tumours. A new series of quinoxaline 1ˏ4-di-N-oxide substitutes at 7-position with esters group were synthetized and characterized by infrared (IR), proton nuclear magnetic resonance (1H-NMR), spectroscopy, and elemental analysis. Seventeen derivatives (M1-M3, E1-E8, P1-P3 and DR1-DR3) were selected and evaluated for antitumor activities using the NCI-60 human tumor cell lines screen. Results showed that E7, P3 and E6 were the most active compounds against the cell lines tested. Substitutions at 7-position with esters group not necessarily affect the biological activity, but the nature of the esters group could exert an influence on the selectivity. Additionally, substitutions at 2-position influenced the cytotoxic activity of the compounds. PMID:29201086

Esters of Quinoxaline 1`4-Di-N-oxide with Cytotoxic Activity on Tumor Cell Lines Based on NCI-60 Panel.

PubMed

Rivera, Gildardo; Ahmad Shah, Syed Shoaib; Arrieta-Baez, Daniel; Palos, Isidro; Mongue, Antonio; Sánchez-Torres, Luvia Enid

2017-01-01

Quinoxalines display diverse and interesting pharmacological activities as antibacterial, antiviral, antiparasitic and anticancer agents. Particularly, their 1`4-di- N -oxide derivatives have proved to be cytotoxic agents that are active under hypoxic conditions as that of solid tumours. A new series of quinoxaline 1`4-di- N -oxide substitutes at 7-position with esters group were synthetized and characterized by infrared (IR), proton nuclear magnetic resonance ( 1 H-NMR), spectroscopy, and elemental analysis. Seventeen derivatives (M1-M3, E1-E8, P1-P3 and DR1-DR3) were selected and evaluated for antitumor activities using the NCI-60 human tumor cell lines screen. Results showed that E7, P3 and E6 were the most active compounds against the cell lines tested. Substitutions at 7-position with esters group not necessarily affect the biological activity, but the nature of the esters group could exert an influence on the selectivity. Additionally, substitutions at 2-position influenced the cytotoxic activity of the compounds.

Verifying reddening and extinction for Gaia DR1 TGAS giants

NASA Astrophysics Data System (ADS)

Gontcharov, George A.; Mosenkov, Aleksandr V.

2018-03-01

Gaia DR1 Tycho-Gaia Astrometric Solution parallaxes, Tycho-2 photometry, and reddening/extinction estimates from nine data sources for 38 074 giants within 415 pc from the Sun are used to compare their position in the Hertzsprung-Russell diagram with theoretical estimates, which are based on the PARSEC and MIST isochrones and the TRILEGAL model of the Galaxy with its parameters being widely varied. We conclude that (1) some systematic errors of the reddening/extinction estimates are the main uncertainty in this study; (2) any emission-based 2D reddening map cannot give reliable estimates of reddening within 415 pc due to a complex distribution of dust; (3) if a TRILEGAL's set of the parameters of the Galaxy is reliable and if the solar metallicity is Z < 0.021, then the reddening at high Galactic latitudes behind the dust layer is underestimated by all 2D reddening maps based on the dust emission observations of IRAS, COBE, and Planck and by their 3D followers (we also discuss some explanations of this underestimation); (4) the reddening/extinction estimates from recent 3D reddening map by Gontcharov, including the median reddening E(B - V) = 0.06 mag at |b| > 50°, give the best fit of the empirical and theoretical data with each other.

Randomized Comparison of Two Vaginal Self-Sampling Methods for Human Papillomavirus Detection: Dry Swab versus FTA Cartridge

PubMed Central

Catarino, Rosa; Vassilakos, Pierre; Bilancioni, Aline; Vanden Eynde, Mathieu; Meyer-Hamme, Ulrike; Menoud, Pierre-Alain; Guerry, Frédéric; Petignat, Patrick

2015-01-01

Background Human papillomavirus (HPV) self-sampling (self-HPV) is valuable in cervical cancer screening. HPV testing is usually performed on physician-collected cervical smears stored in liquid-based medium. Dry filters and swabs are an alternative. We evaluated the adequacy of self-HPV using two dry storage and transport devices, the FTA cartridge and swab. Methods A total of 130 women performed two consecutive self-HPV samples. Randomization determined which of the two tests was performed first: self-HPV using dry swabs (s-DRY) or vaginal specimen collection using a cytobrush applied to an FTA cartridge (s-FTA). After self-HPV, a physician collected a cervical sample using liquid-based medium (Dr-WET). HPV types were identified by real-time PCR. Agreement between collection methods was measured using the kappa statistic. Results HPV prevalence for high-risk types was 62.3% (95%CI: 53.7–70.2) detected by s-DRY, 56.2% (95%CI: 47.6–64.4) by Dr-WET, and 54.6% (95%CI: 46.1–62.9) by s-FTA. There was overall agreement of 70.8% between s-FTA and s-DRY samples (kappa = 0.34), and of 82.3% between self-HPV and Dr-WET samples (kappa = 0.56). Detection sensitivities for low-grade squamous intraepithelial lesion or worse (LSIL+) were: 64.0% (95%CI: 44.5–79.8) for s-FTA, 84.6% (95%CI: 66.5–93.9) for s-DRY, and 76.9% (95%CI: 58.0–89.0) for Dr-WET. The preferred self-collection method among patients was s-DRY (40.8% vs. 15.4%). Regarding costs, FTA card was five times more expensive than the swab (~5 US dollars (USD)/per card vs. ~1 USD/per swab). Conclusion Self-HPV using dry swabs is sensitive for detecting LSIL+ and less expensive than s-FTA. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 43310942 PMID:26630353

Randomized Comparison of Two Vaginal Self-Sampling Methods for Human Papillomavirus Detection: Dry Swab versus FTA Cartridge.

PubMed

Catarino, Rosa; Vassilakos, Pierre; Bilancioni, Aline; Vanden Eynde, Mathieu; Meyer-Hamme, Ulrike; Menoud, Pierre-Alain; Guerry, Frédéric; Petignat, Patrick

2015-01-01

Human papillomavirus (HPV) self-sampling (self-HPV) is valuable in cervical cancer screening. HPV testing is usually performed on physician-collected cervical smears stored in liquid-based medium. Dry filters and swabs are an alternative. We evaluated the adequacy of self-HPV using two dry storage and transport devices, the FTA cartridge and swab. A total of 130 women performed two consecutive self-HPV samples. Randomization determined which of the two tests was performed first: self-HPV using dry swabs (s-DRY) or vaginal specimen collection using a cytobrush applied to an FTA cartridge (s-FTA). After self-HPV, a physician collected a cervical sample using liquid-based medium (Dr-WET). HPV types were identified by real-time PCR. Agreement between collection methods was measured using the kappa statistic. HPV prevalence for high-risk types was 62.3% (95%CI: 53.7-70.2) detected by s-DRY, 56.2% (95%CI: 47.6-64.4) by Dr-WET, and 54.6% (95%CI: 46.1-62.9) by s-FTA. There was overall agreement of 70.8% between s-FTA and s-DRY samples (kappa = 0.34), and of 82.3% between self-HPV and Dr-WET samples (kappa = 0.56). Detection sensitivities for low-grade squamous intraepithelial lesion or worse (LSIL+) were: 64.0% (95%CI: 44.5-79.8) for s-FTA, 84.6% (95%CI: 66.5-93.9) for s-DRY, and 76.9% (95%CI: 58.0-89.0) for Dr-WET. The preferred self-collection method among patients was s-DRY (40.8% vs. 15.4%). Regarding costs, FTA card was five times more expensive than the swab (~5 US dollars (USD)/per card vs. ~1 USD/per swab). Self-HPV using dry swabs is sensitive for detecting LSIL+ and less expensive than s-FTA. International Standard Randomized Controlled Trial Number (ISRCTN): 43310942.

HLA: The Major Histocompatibility Complex of Man

DTIC Science & Technology

1991-01-01

an ancestor of the Jewish bution of HLA - B27 in patients with ankylosing spon- population on a precursor extended haplotype [ HLA - dylitis strongly...suggests dominant inheritance, even B38/35, SC21,SC31. DR4, DQw8] and diffused though most individuals who carry HLA - B27 do not through recombinants into...molecularly distinguishable forms of pressing the [ HLA -Bw55. SB45, DRw6, DQw5] ex- HLA - B27 and all of these are increased among patients, tended

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.

Transcriptional Regulation of Mouse Ribosomal RNA Synthesis by Pathways Involving Protein Kinase C, Calcium, Insulin and Serum

DTIC Science & Technology

1992-05-08

Southern California 1ha.iITRINUTIONI AVAILASILITY STATEMENT 12b. DITIUINCCD1 This document has been approved { OSRUTO for public release and sale ...and 500 gIl of CHCI3 : Isoamyl alcohol (24 : 1), and 2X with 1ml of CHCI 3 : Iso amyl alcohol (24 : 1). RNA was precipitated at -200C overnight in the...control. Plasmid constructions. Plasmids pMrA and pMrD (Kuhn and Grummt, 1987) were kind gifts of Dr. Ingrid Grummt. Plasmid p119 and p123 (Arnhiem

Etravirine and rilpivirine resistance in HIV-1 subtype CRF01_AE-infected adults failing non-nucleoside reverse transcriptase inhibitor-based regimens.

PubMed

Bunupuradah, Torsak; Ananworanich, Jintanat; Chetchotisakd, Ploenchan; Kantipong, Pacharee; Jirajariyavej, Supunnee; Sirivichayakul, Sunee; Munsakul, Warangkana; Prasithsirikul, Wisit; Sungkanuparph, Somnuek; Bowonwattanuwong, Chureeratana; Klinbuayaem, Virat; Petoumenos, Kathy; Hirschel, Bernard; Bhakeecheep, Sorakij; Ruxrungtham, Kiat

2011-01-01

We studied prevalence of etravirine (ETR) and rilpivirine (RPV) resistance in HIV-1 subtype CRF01_AE infection with first-line non-nucleoside reverse transcriptase inhibitor (NNRTI) failure. A total of 225 adults failing two nucleoside reverse transcriptase inhibitors (NRTIs) plus 1 NNRTI in Thailand with HIV RNA>1,000 copies/ml were included. Genotypic resistance results and HIV-1 subtype were interpreted by Stanford DR database. ETR resistance was calculated by the new Monogram weighted score (Monogram WS; ≥ 4 indicating high-level ETR resistance) and by DUET weighted score (DUET WS; 2.5-3.5 and ≥ 4 resulted in intermediate and reduce ETR response, respectively). RPV resistance interpretation was based on previous reports. Median (IQR) age was 38 (34-42) years, 41% were female and CDC A:B:C were 22%:21%:57%. HIV subtypes were 96% CRF01_AE and 4% B. Antiretrovirals at failure were lamivudine (100%), stavudine (93%), nevirapine (90%) and efavirenz (10%) with a median (IQR) duration of 3.4 (1.8-4.5) years. Median (IQR) CD4(+) T-cell count and HIV RNA were 194 (121-280) cells/mm³ and 4.1 (3.6-4.6) log₁₀ copies/ml, respectively. The common NNRTI mutations were Y181C (41%), G190A (22%) and K103N (19%). The proportion of patients with Monogram WS score ≥ 4 was 61.3%. By DUET WS, 49.8% and 7.5% of patients were scored 2.5-3.5 and ≥4, respectively. Only HIV RNA ≥ 4 log₁₀ copies/ml at failure was associated with both Monogram WS ≥ 4 (OR 2.3, 95% CI 1.3-3.9; P=0.003) and DUET WS ≥ 2.5 (OR 1.9, 95% CI 1.1-3.3; P=0.02). The RVP resistance-associated mutations (RAMs) detected were K101P (1.8%), Y181I (2.7%) and Y181V (3.6%). All patients with RPV mutation had ETR resistance. No E138R/E138K mutations were detected. Approximately 60% of patients had high-level ETR resistance. The role of ETR in second-line therapy is limited in late NNRTI failure settings. RVP RAMs were uncommon, but cross-resistance between ETR and RVP was high.

Different DRB1*03:01-DQB1*02:01 haplotypes confer different risk for celiac disease.

PubMed

Alshiekh, S; Zhao, L P; Lernmark, Å; Geraghty, D E; Naluai, Å T; Agardh, D

2017-08-01

Celiac disease is associated with the HLA-DR3-DQA1*05:01-DQB1*02:01 and DR4-DQA1*03:01-DQB1*03:02 haplotypes. In addition, there are currently over 40 non-HLA loci associated with celiac disease. This study extends previous analyses on different HLA haplotypes in celiac disease using next generation targeted sequencing. Included were 143 patients with celiac disease and 135 non-celiac disease controls investigated at median 9.8 years (1.4-18.3 years). PCR-based amplification of HLA and sequencing with Illumina MiSeq technology were used for extended sequencing of the HLA class II haplotypes HLA-DRB1, DRB3, DRB4, DRB5, DQA1 and DQB1, respectively. Odds ratios were computed marginally for every allele and haplotype as the ratio of allelic frequency in patients and controls as ratio of exposure rates (RR), when comparing a null reference with equal exposure rates in cases and controls. Among the extended HLA haplotypes, the strongest risk haplotype for celiac disease was shown for DRB3*01:01:02 in linkage with DQA1*05:01-DQB1*02:01 (RR = 6.34; P-value < .0001). In a subpopulation analysis, DRB3*01:01:02-DQA1*05:01-DQB1*02:01 remained the most significant in patients with Scandinavian ethnicity (RR = 4.63; P < .0001) whereas DRB1*07:01:01-DRB4*01:03:01-DQA1*02:01-DQB1*02:02:01 presented the highest risk of celiac disease among non-Scandinavians (RR = 7.94; P = .011). The data also revealed 2 distinct celiac disease risk DR3-DQA1*05:01-DQB*02:01 haplotypes distinguished by either the DRB3*01:01:02 or DRB3*02:02:01 alleles, indicating that different DRB1*03:01-DQB1*02:01 haplotypes confer different risk for celiac disease. The associated risk of celiac disease for DR3-DRB3*01:01:02-DQA1*05:01-DQB1*02:01 is predominant among patients of Scandinavian ethnicity. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Co-modified MCM-41 as an effective adsorbent for levofloxacin removal from aqueous solution: optimization of process parameters, isotherm, and thermodynamic studies.

PubMed

Jin, Ting; Yuan, Wenhua; Xue, Yujie; Wei, Hong; Zhang, Chaoying; Li, Kebin

2017-02-01

Antibiotics are emerging contaminants due to their potential risks to human health and ecosystems. Poor biodegradability makes it necessary to develop effective physical-chemical methods to eliminate these contaminants from water. The cobalt-modified MCM-41 was prepared by a one-pot hydrothermal method and characterized by SAXRD, N 2 adsorption-desorption, SEM, UV-Vis DR, and FTIR spectroscopy. The results revealed that the prepared 3% Co-MCM-41 possessed mesoporous structure with BET surface areas at around 898.5 m 2 g -1 . The adsorption performance of 3% Co-MCM-41 toward levofloxacin (LVF) was investigated by batch experiments. The adsorption of LVF on 3% Co-MCM-41 was very fast and reached equilibrium within 2 h. The adsorption kinetics followed the pseudo-second-order kinetic model with the second-order rate constants in the range of 0.00198-0.00391 g mg -1  min -1 . The adsorption isotherms could be well represented by the Langmuir, Freundlich, and Dubinin-Radushkevich (D-R) isotherm equations. Nevertheless, D-R isotherm provided the best fit based on the coefficient of determination and average relative error values. The mean free energy of adsorption (E) calculated from D-R model was about 11 kJ mol -1 , indicating that the adsorption was mainly governed by a chemisorption process. Moreover, the adsorption capacity was investigated as a function of pH, adsorbent dosage, LVF concentration, and temperature with help of respond surface methodology (RSM). A quadratic model was established, and an optimal condition was obtained as follows: pH 8.5, adsorbent dosage of 1 g L -1 , initial LVF concentration of 119.8 mg L -1 , and temperature of 31.6 °C. Under the optimal condition, the adsorption capacity of 3% Co-MCM-41 to LVF could reach about 108.1 mg g -1 . The solution pH, adsorbent dosage, LVF concentration, and a combination of adsorbent dose and LVF concentration were significant factors affecting the adsorption process. The adsorption thermodynamic functions were also determined. The negative ΔH 0 (-33.50 kJ mol -1 ) and ΔS 0 (-43.57 J mol -1  K -1 ) suggested that the adsorption was an exothermic process accompanied by decreasing disorder. This study may indicate that 3% Co-MCM-41 is a promising adsorbent for removing emerging pollutants of LVF from water.

Pattern of cytokine receptors expressed by human dendritic cells migrated from dermal explants.

PubMed Central

Larregina, A T; Morelli, A E; Kolkowski, E; Sanjuan, N; Barboza, M E; Fainboim, L

1997-01-01

Different reasons account for the lack of information about the expression of cytokine receptors on human dendritic cells (DC): (a) DC are a trace population; (b) the proteolytic treatment used to isolate DC may alter enzyme-sensitive epitopes; and (c) low numbers of receptors per cell. In the present work the expression of cytokine receptors was analysed by flow cytometry on the population of dermal DC (DDC) that spontaneously migrate from short-term culture dermal explants. DDC obtained after dermal culture were CD1alow, CD1b+, CD1c+, human leucocyte antigen (HLA)-DR+, CD11chigh, CD11b+ and CD32+. The DC lineage was confirmed by ultrastructural analysis. DDC expressed interleukin (IL)-1R type 1 (monoclonal antibody (mAb) hIL-1R1-M1; and 6B5); IL-1R type 2 (mAb hIL-1R2-M22); IL-2R alpha chain (mAb anti-Tac; and hIL-2R-M1) and IL-2R gamma chain (mAb 3B5; and AG14C). DDC did not stain for IL-2R beta chain using four mAbs recognizing two different epitopes of IL-2R beta (mAb 2R-B; Mik-beta 1; and CF1; Mik-beta 3, respectively). DDC were also positive for the cytokine binding chains (alpha chains) of IL-3R (mAb 9F5); IL-4R (mAb hIL-4R-M57; and S456C9); and IL-7R (mAb hIL-7R-M20; and R3434). DDC showed low levels of IL-6R alpha chain (mAb B-F19; B-R6; and B-E23) and its signal transducer gp130 (mAb A2; and B1). DDC strongly expressed interferon-gamma receptor (IFN-gamma R) (mAb GIR-208) and were negative for IL-8R (mAb B-G20; and B-F25). All DDC were highly positive for granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) alpha chain (mAb hGM-CSFR-M1; SC06; SC04, and 8G6) and to a lesser extent for the common beta chain of GM-CSFR, IL-3R and IL-5R (mAb 3D7). On the other hand, reactivity was not found for granulocyte colony-stimulating factor receptor (G-CSFR) (mAb hGCSFR-M1) nor macrophage colony-stimulating factor receptor (M-CSFR) (mAb 7-7A3-17) confirming the DC lineage of DDC. As previously reported for lymphoid DC, DDC expressed tumour necrosis factor receptort (TNFR) 75000 MW (mAb utr-1; hTNFR-M1; and MR2-1) but lacked TNFR 55000 MW (mAb htr-9; MR1-1; and MR1-2). In summary, DDC express receptors for a broad panel of cytokines, even receptors for cytokines whose effects on DC are still unknown (i.e. IL-2R alpha gamma; IL-6R alpha/gp 130; IL-7R alpha gamma). Images Figure 1 PMID:9227332

Physical Training, Hemodynamic Parameters and Arterial Stiffness: Friends or Foes of the Hypertensive Patient?

PubMed

Iurciuc, Stela; Avram, Claudiu; Turi, Vladiana; Militaru, Anda; Avram, Adina; Cimpean, Anca Maria; Iurciuc, Mircea

2016-01-01

To evaluate the impact of physical training on central hemodynamic parameters and elasticity of large arteries in hypertensive patients. A total of 129 hypertensive patients were divided into two groups: group A followed lifestyle changes and physical training; and group B acted as a control group; seven parameters were recorded: Pulse wave velocity (PWVao), systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), central aortic systolic blood pressure (SBPao), aortic diastolic blood pressure (DBPao), and central aortic pulse pressure (PPao). The difference between values at 4 months and baseline (Δ) were as follows: ΔPWVao was -1.02 m/s (p<0.001) versus 0.17 m/s (p=0.035), ΔSBPao was -9.6 mmHg (p=0.009) versus 1.6 mmHg (p=0.064), and ΔPPao was -6.8 mmHg (p<0.001) versus 3.2 mmHg, (p=0.029) in group A versus B, respectively. Exercise training improves SBP, PP, SBPao, PPao and may delay arterial ageing. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Summaries of Research Fiscal Year 1988

DTIC Science & Technology

1988-01-01

Periodontal Attachment Levels: Mathematical Models and Implications. Journal of Periodontology 54:257-2t8, 1988. Pederson, E. D., Lamberts, B. L. and...Technology, San Diego, California. CDR J. W. Rodden became a Diplomate, American Board of Periodontology . Dr. L. G. Simonson was installed as a member of

Validity of self-reported eye disease and treatment in a population-based study: the Los Angeles Latino Eye Study.

PubMed

Patty, Lauren; Wu, Cathy; Torres, Mina; Azen, Stanley; Varma, Rohit

2012-09-01

To examine the validity of self-reported eye disease, including cataract, age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR), and self-reported surgical treatment for cataract and DR in the Los Angeles Latino Eye Study (LALES). Population-based, cross-sectional study. A total of 6357 Latinos aged 40+ years from the LALES. Participants underwent a detailed interview, including survey questions about ocular health, diagnoses, and timing of last eye examination, and a standardized clinical examination. Self-report was compared with examination to determine sensitivity and specificity by length of time since last eye examination. Stepwise logistic regression was used to determine factors associated with inaccurate self-report. Sensitivity and specificity were calculated for 4 self-reported eye diseases (cataract, AMD, glaucoma, and DR) and for surgical treatment of cataract and DR. Odds ratios (ORs) were determined for factors associated with inaccurate self-report underestimating eye disease and treatment. For each disease, sensitivity and specificity in those who reported their last eye examination as <1 year ago were 36.8% and 92.5% for cataract, 37.7% and 96.3% for glaucoma, 5.1% and 98.9% for AMD, and 25.7% and 94.2% for DR, respectively. Self-report was less accurate with increasing time since last eye examination. Inaccurate self-report was independently associated with better visual acuity (OR, 2.4), <2 comorbidities (OR, 1.7), last eye examination/visit 1 to 5 years ago and ≥ 5 years ago (OR, 2.3 and 4.9, respectively), and less education (OR, 1.3 for 7-12 years and 1.7 for <7 years). Of 88 participants surgically treated for cataract who reported an eye examination <1 year ago, sensitivity and specificity of self-reported surgical history were 90.9% and 99.9%, respectively. Of the 31 participants treated for DR (laser/surgery) and reporting an eye examination <1 year ago, sensitivity and specificity of self-reported surgical history were 19.4% and 99.6%, respectively. Among Latinos, self-reporting of eye disease and surgical history provides a significant underestimate of the disease burden. This may lead to significant misclassification in vision research if self-report alone is used to identify persons with eye disease. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Designing Peptide-Based HIV Vaccine for Chinese

PubMed Central

Fan, Xiaojuan

2014-01-01

CD4+ T cells are central to the induction and maintenance of CD8+ T cell and antibody-producing B cell responses, and the latter are essential for the protection against disease in subjects with HIV infection. How to elicit HIV-specific CD4+ T cell responses in a given population using vaccines is one of the major areas of current HIV vaccine research. To design vaccine that targets specifically Chinese, we assembled a database that is comprised of sequences from 821 Chinese HIV isolates and 46 human leukocyte antigen (HLA) DR alleles identified in Chinese population. We then predicted 20 potential HIV epitopes using bioinformatics approaches. The combination of these 20 epitopes has a theoretical coverage of 98.1% of the population for both the prevalent HIV genotypes and also Chinese HLA-DR types. We suggest that testing this vaccine experimentally will facilitate the development of a CD4+ T cell vaccine especially catered for Chinese. PMID:25136573

Designing peptide-based HIV vaccine for Chinese.

PubMed

Shu, Jiayi; Fan, Xiaojuan; Ping, Jie; Jin, Xia; Hao, Pei

2014-01-01

CD4+ T cells are central to the induction and maintenance of CD8+ T cell and antibody-producing B cell responses, and the latter are essential for the protection against disease in subjects with HIV infection. How to elicit HIV-specific CD4+ T cell responses in a given population using vaccines is one of the major areas of current HIV vaccine research. To design vaccine that targets specifically Chinese, we assembled a database that is comprised of sequences from 821 Chinese HIV isolates and 46 human leukocyte antigen (HLA) DR alleles identified in Chinese population. We then predicted 20 potential HIV epitopes using bioinformatics approaches. The combination of these 20 epitopes has a theoretical coverage of 98.1% of the population for both the prevalent HIV genotypes and also Chinese HLA-DR types. We suggest that testing this vaccine experimentally will facilitate the development of a CD4+ T cell vaccine especially catered for Chinese.

Report of the Defense Science Board Task Force on University Responsiveness to National Security Requirements.

DTIC Science & Technology

1982-01-01

R.ugustine Chairman iv OFFICE OF THE SECRETARY OF DEFENSE WASHINGTON, D.C. 20301 27 January 1982 DEFENSE SCIENCIE BOARD Mr. Norman R. Augustine Chai rman...Institute of Technology Dr. Norman Hackerman President Rice University Dr. Richard L. Haley Assistant Deputy Science and Technology USA Material ...Biological and Medical Sciences 51.8 67.8 22% Materials 53.2 65.1 13% Chemistry 47.8 60.1 17% Math and Computer Sciences 44.2 53.6 12% Oceanography 43.2

Age-Related Eye Diseases and Visual Impairment Among U.S. Adults

PubMed Central

Chou, Chiu-Fang; Cotch, Mary Frances; Vitale, Susan; Zhang, Xinzhi; Klein, Ronald; Friedman, David S.; Klein, Barbara E.K.; Saaddine, Jinan B.

2014-01-01

Background Visual impairment is a common health-related disability in the U.S. The association between clinical measurements of age-related eye diseases and visual impairment in data from a national survey has not been reported. Purpose To examine common eye conditions and other correlates associated with visual impairment in the U.S. Methods Data from the 2005–2008 National Health and Nutrition Examination Survey of 5222 Americans aged ≥40 years were analyzed in 2012 for visual impairment (presenting distance visual acuity worse than 20/40 in the better-seeing eye), and visual impairment not due to refractive error (distance visual acuity worse than 20/40 after refraction). Diabetic retinopathy (DR) and age-related macular degeneration (AMD) were assessed from retinal fundus images; glaucoma was assessed from two successive frequency-doubling tests and a cup-to-disc ratio measurement. Results Prevalence of visual impairment and of visual impairment not due to refractive error was 7.5% (95% CI=6.9%, 8.1%) and 2.0% (1.7%, 2.3%), respectively. The prevalence of visual impairment not due to refractive error was significantly higher among people with AMD (2.2%) compared to those without AMD (0.8%), or with DR (3.5%) compared to those without DR (1.2%). Independent predictive factors of visual impairment not due to refractive error were AMD (OR=4.52, 95% CI=2.50, 8.17); increasing age (OR=1.09 per year, 95% CI=1.06, 1.13); and less than a high school education (OR=2.99, 95% CI=1.18, 7.55). Conclusions Visual impairment is a public health problem in the U.S. Visual impairment in two thirds of adults could be eliminated with refractive correction. Screening of the older population may identify adults at increased risk of visual impairment due to eye diseases. PMID:23790986

Learning Physical Domains: Toward a Theoretical Framework.

DTIC Science & Technology

1986-12-01

advanced ids o the iaime doinain in containing more information, especially perceptual " ’It. iho lI b1 rwt... tI hat. psychboigists by no means...Acquisitions Dr Kenneth D Forbus 4833 Rugby Avenue University of Illinois Dr Robert Glaser Bethesda, MD 20014 Department of Computer Science Learning

A 2,4-dichlorophenoxyacetic acid analog screened using a maize coleoptile system potentially inhibits indole-3-acetic acid influx in Arabidopsis thaliana

PubMed Central

Suzuki, Hiromi; Matano, Naoyuki; Nishimura, Takeshi; Koshiba, Tomokazu

2014-01-01

Studies using inhibitors of indole-3-acetic acid (IAA) transport, not only for efflux but influx carriers, provide many aspects of auxin physiology in plants. 1-Naphtoxyacetic acid (1-NOA), an analog of the synthetic auxin 1-N-naphtalene acetic acid (NAA), inhibits the IAA influx carrier AUX1. However, 1-NOA also shows auxin activity because of its structural similarity to NAA. In this study, we have identified another candidate inhibitor of the IAA influx carrier. The compound, “7-B3; ethyl 2-[(2-chloro-4-nitrophenyl)thio]acetate,” is a 2,4-dichlorophenoxyacetic acid (2,4-D) analog. At high concentrations (> 300 µM), 7-B3 slightly reduced IAA transport and tropic curvature of maize coleoptiles, whereas lower concentrations had almost no effect. We have analyzed the effects of 7-B3 on Arabidopsis thaliana seedlings. 7-B3 rescued the 2,4-D-inhibited root elongation, but not the NAA-inhibited root elongation. The effect of 7-B3 was weaker than that of 1-NOA. Both 1-NOA and 7-B3 inhibited DR5::GUS expression induced by IAA and 2,4-D, but not that induced by NAA. At high concentrations, 1-NOA exhibited auxin activity, but 7-B3 did not. Furthermore, 7-B3 inhibited apical hook formation in etiolated seedlings more effectively than 1-NOA did. These results indicate that 7-B3 is a potential inhibitor of IAA influx that has almost no effect on IAA efflux or auxin signaling. PMID:24800738

Validity of self reported eye disease and treatment in a population-based study: The Los Angeles Latino Eye Study

PubMed Central

Patty, Lauren; Wu, Cathy; Torres, Mina; Azen, Stanley; Varma, Rohit

2012-01-01

Purpose To examine the validity of self-reported eye disease, including cataract, age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR), and self-reported surgical treatment for cataract and DR in the Los Angeles Latino Eye Study (LALES). Design Population-based cross-sectional study Participants 6357 Latinos age 40+ years from the LALES Methods Participants underwent a detailed interview, including survey questions about ocular health, diagnoses and timing of last eye examination, and a standardized clinical examination. Self report was compared to examination to determine sensitivity and specificity by length of time since last eye examination. Stepwise logistic regression was used to determine factors associated with inaccurate self report. Main Outcome Measures Sensitivity and specificity were calculated for four self reported eye diseases (cataract, AMD, glaucoma, DR) and for surgical treatment of cataract and DR. Odds ratios (OR) were determined for factors associated with inaccurate self report underestimating eye disease and treatment. Results For each disease, sensitivity and specificity in those who reported their last eye examination as <1 year ago were: 36.8%, 92.5% for cataract; 37.7%, 96.3% for glaucoma; 5.1%, 98.9% for AMD; and 25.7%, 94.2% for DR. Self report was less accurate with increasing time since last eye examination. Inaccurate self report was independently associated with better visual acuity (OR=2.4), <2 comorbidities (OR=1.7), last eye exam/visit 1–5 years ago and ≥5 years ago (OR=2.3 and 4.9, respectively), and less education (OR=1.3 for 7–12 years and 1.7 for <7 years). Of 88 participants surgically treated for cataract who reported an eye examination <1 year ago, sensitivity and specificity of self-reported surgical history were 90.9% and 99.9%. Of the 31 participants treated for DR (laser/surgery) and reporting an eye examination <1 year ago, sensitivity and specificity of self-reported surgical history were 19.4% and 99.6%. Conclusions Among Latinos, self reporting of eye disease and surgical history provides a significant underestimate of the disease burden. This may lead to significant misclassification in vision research if self report alone is used to identify persons with eye disease. PMID:22537615

Ulcerative colitis associated with Takayasu's disease in two patients who received proctocolectomy.

PubMed

Masuda, Hideki; Ishii, Ukimoto; Aoki, Nobuhiko; Nakayama, Hisashi; Sato, Fumii; Karube, Hideaki; Suzuki, Shigeru; Kondo, Toshihiko

2002-01-01

Ulcerative colitis (UC) associated with Takayasu's disease (TD) is not common in Japan. Here, we report two patients with both diseases who received a total proctocolectomy. Patient 1, a 41-year-old woman with chronic continuous type UC, was first diagnosed with TD at the age of 10 years. Subsequently, she was diagnosed with UC and rectal cancer. HLA typing showed A2, A31(19), B52(5), and DR2(DRB1*1502). Coronary angiography showed 90% narrowing of the right coronary artery (RCA). After alleviating the RCA narrowing by percutaneous transluminal coronary angioplasty (PTCA), we performed a total proctocolectomy and ileostomy. Patient 2, a 20-year-old woman, was first diagnosed with TD at the age of 13 years. Severe symptoms, indicating fulminant UC, started 1 month prior to hospitalization. She was judged as needing surgery because the symptoms were not alleviated even with high doses of prednisolone. HLA typing showed A2, A31(19), B52, B61(40), DR2(DRB1*1502), and DR4 (DRB1*0405). Aortography showed a narrowing of the right renal artery; however, her renal function was normal. Based on these findings, we performed a three-stage operation for total proctocolectomy. Previously, we have reported that the DRB1*1502 and DRw11 genes were closely related to the intractability of UC. To date, we have not determined whether or how the DRB1*1502 gene might be related to TD. As the number of cases of UC associated with TD increases, it will be necessary to examine their DR2 subtypes.

Libraries: A Vision for the 90’s and Beyond. Proceedings of the Military Librarians Workshop (34th Annual), October 9-12, 1990

DTIC Science & Technology

1991-01-08

10Ito 9 O.rQ t~~l.Itid the timew fW r~IwF’lnut~ ൓= 101144 "’stfl da fta ~W Reifvged wA~t4.nn- j this data h.eadŘd ad npJet-,,q and .ne,..n 114 I O=IIr.O...baughman, Dr. lDrivid it. Ibeudeir, Ihatherine l3lauer, James HI. 13yrn, Lois J . Carey and Mary B. Leveriing; ~nigahc of Library Customers 1990-2000, by Dr...Philip Ad.D 8011n-dtir; Libra ries in the Nineties and beyond, by Dr. TIhomas J . cialvin; I.-eadk’rshim Ill thom 90’s, by B~rooke E~. Sheldon

Doxycycline-rifampin versus doxycycline-streptomycin in treatment of human brucellosis due to Brucella melitensis. The GECMEI Group. Grupo de Estudio de Castilla-la Mancha de Enfermedades Infecciosas.

PubMed

Solera, J; Rodríguez-Zapata, M; Geijo, P; Largo, J; Paulino, J; Sáez, L; Martínez-Alfaro, E; Sánchez, L; Sepulveda, M A; Ruiz-Ribó, M D

1995-09-01

Brucellosis is a common zoonosis in many parts of the world; the best regimen for the treatment of brucellosis has not been clearly determined. We have carried out a multicenter, open, controlled trial in five general hospitals in Spain to compare the efficacy and safety of doxycycline and rifampin (DR) versus doxycycline and streptomycin (DS) for the treatment of human brucellosis. The study included 194 ambulatory or hospitalized patients with acute brucellosis, without endocarditis or neurobrucellosis. The diagnostic criterion was isolation of Brucella species from blood or other tissues (n = 120) or a standard tube agglutination titer of 1/160 or more for anti-Brucella antibodies with compatible clinical findings (n = 74). Patients were randomly assigned to receive either 100 mg of doxycycline twice daily plus rifampin, 900 mg/day, in a single morning dose for 45 days (DR group) or the same dose of doxycycline for 45 days plus streptomycin, 1 g/day, intramuscularly for 14 days (DS group). A lack of therapeutic efficacy developed in 8 of the 100 patients in the DR group (8%) and in 2 of the 94 patients in the DS group (2%)(P = 0.10). Relapses occurred in 16 of the 100 patients in the DR group (16%) but in only 5 of the 94 patients in the DS group (5.3%) (P = 0.02). When relapse was considered in combination with initial lack of efficacy, 26 patients in the DR group (24%) and 7 patients in the DS group (7.45%) failed to respond to therapy (P = 0.0016). In general, therapy was well tolerated and only four patients (4%) in the DR group and two (2%) in the DS group had episodes of adverse effects necessitating discontinuation of treatment (P> 0.2). We conclude that a doxycycline-and-rifampin regimen is less effective than the doxycycline-and-streptomycin regimen in patients with acute brucellosis.

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.

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

Rivastigmine blocks voltage-activated K+ currents in dissociated rat hippocampal neurons

PubMed Central

Pan, Yaping; Xu, Xianghua; Wang, Xiaoliang

2003-01-01

Rivastigmine is an acetylcholinesterase inhibitor used in Alzheimer's disease therapy. In the present study, we investigated the effects of rivastigmine on the transient outward K+ current (IK(A)) and the delayed rectifier K+ current (IK(DR)) in acutely dissociated rat hippocampal pyramidal neurons using the whole-cell patch-clamp technique. Rivastigmine inhibited the amplitudes of IK(A) and IK(DR) in a reversible and concentration-dependent manner. At a concentration of 100 μM, rivastigmine inhibited IK(A) and IK(DR), recorded when the cells were depolarized from −50 to +40 mV, by 65.9 (P<0.01) and 67.3% (P<0.01), respectively. The IC50 values for IK(A) and IK(DR) were 3.8 and 1.7 μM, respectively. The decay time constant of IK(A), recorded following a test pulse to +40 mV, was prolonged reversibly by rivastigmine at concentrations of 10 and 100 μM (both P<0.05). Rivastigmine affected the voltage dependence of IK(A) and IK(DR). At a concentration of 10 μM, it shifted the steady-state inactivation curve of IK(A) towards more negative potentials by −11 mV (P<0.05), but had no effect on the steady-state activation curve or the recovery from inactivation. Regarding the kinetic properties of IK(DR), 10 μM rivastigmine shifted the steady-state activation and inactivation curves towards more negative potentials by −10 (P<0.05) and −27 mV (P<0.01), respectively. Our findings that rivastigmine inhibits IK(A) and IK(DR) in rat hippocampal pyramidal neurons suggest that this agent has other pharmacological actions besides its antiacetylcholinesterase activity. PMID:14504131

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.

Biodistribution and catabolism of (18)F-labeled neurotensin(8-13) analogs.

PubMed

Bergmann, Ralf; Scheunemann, Matthias; Heichert, Christoph; Mäding, Peter; Wittrisch, Holm; Kretzschmar, Marion; Rodig, Heike; Tourwé, Dirk; Iterbeke, Koen; Chavatte, Kris; Zips, Daniel; Reubi, Jean Claude; Johannsen, Bernd

2002-01-01

4-([(18)F]fluoro)benzoyl-neurotensin(8-13) ((18)FB-Arg(8)-Arg(9)-Pro(10)-Tyr(11)- Ile(12)-Leu(13)-OH, 1) and two analogs stabilized in one and two positions ((18)FB-Arg(8)psi(CH(2)NH)Arg(9)-Pro(10)-Tyr(11)- Ile(12)-Leu(13)-OH, 2, (18)FB-Arg(8)psi(CH(2)NH)Arg(9)-Pro(10)-Tyr(11)-Tle(12)-Leu(13)-OH, 3) were synthesized in a radiochemical yield of 25-36% and a specific activity of 5-15 GBq/mmol. The peptides were evaluated in vitro and in vivo for their potential to image tumors overexpressing neurotensin receptor 1 (NTR1) by positron emission tomography (PET). All analogs exhibited in vitro binding affinity in the low nanomolar range to NTR1-expressing human tumors, measured by quantitative receptor autoradiography, HT-29 and WiDr cells, and to sections of tumors derived from these cell lines in mice. The radiotracers were internalized in the cells in vitro, and the fluorinated peptides were able to mobilize intracellular Ca(2+) of WiDr cells. In in vivo studies in rats and in mice bearing HT-29 cell tumors, only a moderate uptake of the radioligands into the studied tumors was observed, presumed to be due to degradation in vivo and fast elimination by the kidneys. In comparison with the other analogs, the specific tumor uptake expressed as tumor-to-muscle relation was highest for the radioligand 3. The blood clearance of 3 was reduced by co-injection of peptidase inhibitors. The catabolic pathways of the radiofluorinated peptides were elucidated. The results suggest that the high binding affinity to NTR1 and the stabilization against proteolytic degradation are not yet sufficient for tumor imaging by PET.

Angular on-line tube current modulation in multidetector CT examinations of children and adults: The influence of different scanning parameters on dose reduction

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

Papadakis, Antonios E.; Perisinakis, Kostas; Damilakis, John

2007-07-15

The purpose of this study was to assess the potential of angular on-line tube current modulation on dose reduction in pediatric and adult patients undergoing multidetector computed tomography (MDCT) examinations. Five physical anthropomorphic phantoms that simulate the average individual as neonate, 1-year-old, 5-year-old, 10-year-old, and adult were employed in the current study. Phantoms were scanned with the use of on-line tube current modulation (TCM). Percent dose reduction (%DR) factors achieved by applying TCM, were determined for standard protocols used for head and neck, shoulder, thorax, thorax and abdomen, abdomen, abdomen and pelvis, pelvis, and whole body examinations. A preliminary studymore » on the application of TCM in MDCT examinations of adult patients was performed to validate the results obtained in anthropomorphic phantoms. Dose reduction was estimated as the percentage difference of the modulated milliamperes for each scan and the preset milliamperes prescribed by the scan protocol. The dose reduction in children was found to be much lower than the corresponding reduction achieved for adults. For helical scans the %DR factors, ranged between 1.6% and 7.4% for the neonate, 2.9% and 8.7% for the 1-year old, 2% and 6% for the 5-year-old, 5% and 10.9% for the 10-year-old, and 10.4% and 20.7% for the adult individual. For sequential scans the corresponding %DR factors ranged between 1.3% and 6.7%, 4.5% and 11%, 4.2% and 6.6%, 6.4% and 12.3%, and 8.9% and 23.3%, respectively. Broader beam collimations are associated with decreased %DR factors, when other scanning parameters are held constant. TCM did not impair image noise. In adult patients, the %DR values were found to be in good agreement with the corresponding results obtained in the anthropomorphic adult phantom. In conclusion, on-line TCM may be considered as a valuable tool for reducing dose in routine CT examinations of pediatric and adult patients. However, the dose reduction achieved with TCM in neonates and young children was found to be lower than that obtained for adults. Therefore, on-line TCM should work as an additional means to reduce dose and should not replace other conventional means of reducing dose, especially in neonates and young children.« less

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.

OPSATCOM Field Measurements. Volume 1

DTIC Science & Technology

1976-06-01

ADVANCED RESEARCH PROJECTS AGENCY AF SPACE & MISSILE SYSTEMS ORGANIZATION -. TECHNICAL ý IBRARY (3) SKX (DR. D. BARRY) (3) OFFICE OF THE IRECTOR OF DEFENSE...FORCE CAMBRIDGE kL.LSEARCH CENTER DEFENs r FELFC’OMMUNICATI[NS& COMMAND & tECHNICAL LIBRAHY r’ONTROL SYSTEMS NATIONAL AERONAUTICS AND SPACE...STREET T NAVAL. ELECTRONIC SYSTEMS COMMAND SANTA MONICA, CA 90496 NELEX.031031 IT. B. HUGHES) (3) UNIVERSITY OF CALIFORNIA, SAN DIEGO NEL X 3102 (M

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.

A novel technique for measurement of thermal rate constants and temperature dependences of dissociative recombination: CO{sub 2}{sup +}, CF{sub 3}{sup +}, N{sub 2}O{sup +}, C{sub 7}H{sub 8}{sup +}, C{sub 7}H{sub 7}{sup +}, C{sub 6}H{sub 6}{sup +}, C{sub 6}H{sub 5}{sup +}, C{sub 5}H{sub 6}{sup +}, C{sub 4}H{sub 4}{sup +}, and C{sub 3}H{sub 3}{sup +}

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

Fournier, Joseph A.; Shuman, Nicholas S.; Melko, Joshua J.

A novel technique using a flowing afterglow-Langmuir probe apparatus for measurement of temperature dependences of rate constants for dissociative recombination (DR) is presented. Low ({approx}10{sup 11} cm{sup -3}) concentrations of a neutral precursor are added to a noble gas/electron afterglow plasma thermalized at 300-500 K. Charge exchange yields one or many cation species, each of which may undergo DR. Relative ion concentrations are monitored at a fixed reaction time while the initial plasma density is varied between 10{sup 9} and 10{sup 10} cm{sup -3}. Modeling of the decrease in concentration of each cation relative to the non-recombining noble gas cationmore » yields the rate constant for DR. The technique is applied to several species (O{sub 2}{sup +}, CO{sub 2}{sup +}, CF{sub 3}{sup +}, N{sub 2}O{sup +}) with previously determined 300 K values, showing excellent agreement. The measurements of those species are extended to 500 K, with good agreement to literature values where they exist. Measurements are also made for a range of C{sub n}H{sub m}{sup +} (C{sub 7}H{sub 7}{sup +}, C{sub 7}H{sub 8}{sup +}, C{sub 5}H{sub 6}{sup +}, C{sub 4}H{sub 4}{sup +}, C{sub 6}H{sub 5}{sup +}, C{sub 3}H{sub 3}{sup +}, and C{sub 6}H{sub 6}{sup +}) derived from benzene and toluene neutral precursors. C{sub n}H{sub m}{sup +} DR rate constants vary from 8-12 Multiplication-Sign 10{sup -7} cm{sup 3} s{sup -1} at 300 K with temperature dependences of approximately T{sup -0.7}. Where prior measurements exist these results are in agreement, with the exception of C{sub 3}H{sub 3}{sup +} where the present results disagree with a previously reported flat temperature dependence.« less