YieldStar based reticle 3D measurements and its application

NASA Astrophysics Data System (ADS)

Vaenkatesan, Vidya; Finders, Jo; ten Berge, Peter; Plug, Reinder; Sijben, Anko; Schellekens, Twan; Dillen, Harm; Pocobiej, Wojciech; Jorge, Vasco G.; van Dijck, Jurgen

2016-09-01

YieldStar (YS) is an established ASML-built scatterometer that is capable of measuring wafer Critical Dimension (CD), Overlay and Focus. In a recent work, the application range of YS was extended to measure 3D CD patterns on a reticle (pattern CD, height, Side Wall Angle-SWA). The primary motivation for this study came from imaging studies that indicated a need for measuring and controlling reticle 3D topography. CD scanning electron microscope (CD-SEM), Atomic force microscope (AFM), 3D multiple detector SEM (3D-SEM) are the preferred tools for reticle metrology. While these tools serve the industry well, the current research to the impact of reticle 3D involves extensive costs, logistic challenges and increased reticle lead time. YS provides an attractive alternative as it can measure pattern CD, SWA and height in a single measurement and at high throughput. This work demonstrates the capability of YS as a reticle metrology tool.

Gaps analysis for CD metrology beyond the 22nm node

NASA Astrophysics Data System (ADS)

Bunday, Benjamin; Germer, Thomas A.; Vartanian, Victor; Cordes, Aaron; Cepler, Aron; Settens, Charles

2013-04-01

This paper will examine the future for critical dimension (CD) metrology. First, we will present the extensive list of applications for which CD metrology solutions are needed, showing commonalities and differences among the various applications. We will then report on the expected technical limits of the metrology solutions currently being investigated by SEMATECH and others in the industry to address the metrology challenges of future nodes, including conventional CD scanning electron microscopy (CD-SEM) and optical critical dimension (OCD) metrology and new potential solutions such as He-ion microscopy (HeIM, sometimes elsewhere referred to as HIM), CD atomic force microscopy (CD-AFM), CD small-angle x-ray scattering (CD-SAXS), high-voltage scanning electron microscopy (HV-SEM), and other types. A technical gap analysis matrix will then be demonstrated, showing the current state of understanding of the future of the CD metrology space.

Development of critical dimension measurement scanning electron microscope for ULSI (S-8000 series)

NASA Astrophysics Data System (ADS)

Ezumi, Makoto; Otaka, Tadashi; Mori, Hiroyoshi; Todokoro, Hideo; Ose, Yoichi

1996-05-01

The semiconductor industry is moving from half-micron to quarter-micron design rules. To support this evolution, Hitachi has developed a new critical dimension measurement scanning electron microscope (CD-SEM), the model S-8800 series, for quality control of quarter- micron process lines. The new CD-SEM provides detailed examination of process conditions with 5 nm resolution and 5 nm repeatability (3 sigma) at accelerating voltage 800 V using secondary electron imaging. In addition, a newly developed load-lock system has a capability of achieving a high sample throughput of 20 wafers/hour (5 point measurements per wafer) under continuous operation. To support user friendliness, the system incorporates a graphical user interface (GUI), an automated pattern recognition system which helps locating measurement points, both manual and semi-automated operation, and user-programmable operating parameters.

Implementation and benefits of advanced process control for lithography CD and overlay

NASA Astrophysics Data System (ADS)

Zavyalova, Lena; Fu, Chong-Cheng; Seligman, Gary S.; Tapp, Perry A.; Pol, Victor

2003-05-01

Due to the rapidly reduced imaging process windows and increasingly stingent device overlay requirements, sub-130 nm lithography processes are more severely impacted than ever by systamic fault. Limits on critical dimensions (CD) and overlay capability further challenge the operational effectiveness of a mix-and-match environment using multiple lithography tools, as such mode additionally consumes the available error budgets. Therefore, a focus on advanced process control (APC) methodologies is key to gaining control in the lithographic modules for critical device levels, which in turn translates to accelerated yield learning, achieving time-to-market lead, and ultimately a higher return on investment. This paper describes the implementation and unique challenges of a closed-loop CD and overlay control solution in high voume manufacturing of leading edge devices. A particular emphasis has been placed on developing a flexible APC application capable of managing a wide range of control aspects such as process and tool drifts, single and multiple lot excursions, referential overlay control, 'special lot' handling, advanced model hierarchy, and automatic model seeding. Specific integration cases, including the multiple-reticle complementary phase shift lithography process, are discussed. A continuous improvement in the overlay and CD Cpk performance as well as the rework rate has been observed through the implementation of this system, and the results are studied.

Hybrid Metrology and 3D-AFM Enhancement for CD Metrology Dedicated to 28 nm Node and Below Requirements

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

Foucher, J.; Faurie, P.; Dourthe, L.

2011-11-10

The measurement accuracy is becoming one of the major components that have to be controlled in order to guarantee sufficient production yield. Already at the R and D level, we have to come up with the accurate measurements of sub-40 nm dense trenches and contact holes coming from 193 immersion lithography or E-Beam lithography. Current production CD (Critical Dimension) metrology techniques such as CD-SEM (CD-Scanning Electron Microscope) and OCD (Optical Critical Dimension) are limited in relative accuracy for various reasons (i.e electron proximity effect, outputs parameters correlation, stack influence, electron interaction with materials...). Therefore, time for R and D ismore » increasing, process windows degrade and finally production yield can decrease because you cannot manufactured correctly if you are unable to measure correctly. A new high volume manufacturing (HVM) CD metrology solution has to be found in order to improve the relative accuracy of production environment otherwise current CD Metrology solution will very soon get out of steam.In this paper, we will present a potential Hybrid CD metrology solution that smartly tuned 3D-AFM (3D-Atomic Force Microscope) and CD-SEM data in order to add accuracy both in R and D and production. The final goal for 'chip makers' is to improve yield and save R and D and production costs through real-time feedback loop implement on CD metrology routines. Such solution can be implemented and extended to any kind of CD metrology solution. In a 2{sup nd} part we will discuss and present results regarding a new AFM3D probes breakthrough with the introduction of full carbon tips made will E-Beam Deposition process. The goal is to overcome the current limitations of conventional flared silicon tips which are definitely not suitable for sub-32 nm nodes production.« less

Resilience linked to personality dimensions, alexithymia and affective symptoms in motor functional neurological disorders.

PubMed

Jalilianhasanpour, Rozita; Williams, Benjamin; Gilman, Isabelle; Burke, Matthew J; Glass, Sean; Fricchione, Gregory L; Keshavan, Matcheri S; LaFrance, W Curt; Perez, David L

2018-04-01

Reduced resilience, a construct associated with maladaptive stress coping and a predisposing vulnerability for Functional Neurological Disorders (FND), has been under-studied compared to other neuropsychiatric factors in FND. This prospective case-control study investigated self-reported resilience in patients with FND compared to controls and examined relationships between resilience and affective symptoms, personality traits, alexithymia, health status and adverse life event burden. 50 individuals with motor FND and 47 healthy controls participated. A univariate test followed by a logistic regression analysis investigated group-level differences in Connor-Davidson Resilience Scale (CD-RISC) scores. For within-group analyses performed separately in patients with FND and controls, univariate screening tests followed by multivariate linear regression analyses examined factors associated with self-reported resilience. Adjusting for age, gender, education status, ethnicity and lifetime adverse event burden, patients with FND reported reduced resilience compared to controls. Within-group analyses in patients with FND showed that individual-differences in mental health, extraversion, conscientiousness, and openness positively correlated with CD-RISC scores; post-traumatic stress disorder symptom severity, depression, anxiety, alexithymia and neuroticism scores negatively correlated with CD-RISC scores. Extraversion independently predicted resilience scores in patients with FND. In control subjects, univariate associations were appreciated between CD-RISC scores and gender, personality traits, anxiety, alexithymia and physical health; conscientiousness independently predicted resilience in controls. Patients with FND reported reduced resilience, and CD-RISC scores covaried with other important predisposing vulnerabilities for the development of FND. Future research should investigate if the CD-RISC is predictive of clinical outcomes in patients with FND. Copyright © 2018 Elsevier Inc. All rights reserved.

An Assessment of Critical Dimension Small Angle X-ray Scattering Metrology for Advanced Semiconductor Manufacturing

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

Settens, Charles M.

2015-01-01

Simultaneous migration of planar transistors to FinFET architectures, the introduction of a plurality of materials to ensure suitable electrical characteristics, and the establishment of reliable multiple patterning lithography schemes to pattern sub-10 nm feature sizes imposes formidable challenges to current in-line dimensional metrologies. Because the shape of a FinFET channel cross-section immediately influences the electrical characteristics, the evaluation of 3D device structures requires measurement of parameters beyond traditional critical dimension (CD), including their sidewall angles, top corner rounding and footing, roughness, recesses and undercuts at single nanometer dimensions; thus, metrologies require sub-nm and approaching atomic level measurement uncertainty. Synchrotron criticalmore » dimension small angle X-ray scattering (CD-SAXS) has unique capabilities to non-destructively monitor the cross-section shape of surface structures with single nanometer uncertainty and can perform overlay metrology to sub-nm uncertainty. In this dissertation, we perform a systematic experimental investigation using CD-SAXS metrology on a hierarchy of semiconductor 3D device architectures including, high-aspect-ratio contact holes, H2 annealed Si fins, and a series of grating type samples at multiple points along a FinFET fabrication process increasing in structural intricacy and ending with fully fabricated FinFET. Comparative studies between CD-SAXS metrology and other relevant semiconductor dimensional metrologies, particularly CDSEM, CD-AFM and TEM are used to determine physical limits of CD-SAXS approach for advanced semiconductor samples. CD-SAXS experimental tradeoffs, advice for model-dependent analysis and thoughts on the compatibility with a semiconductor manufacturing environment are discussed.« less

CHAM: weak signals detection through a new multivariate algorithm for process control

NASA Astrophysics Data System (ADS)

Bergeret, François; Soual, Carole; Le Gratiet, B.

2016-10-01

Derivatives technologies based on core CMOS processes are significantly aggressive in term of design rules and process control requirements. Process control plan is a derived from Process Assumption (PA) calculations which result in a design rule based on known process variability capabilities, taking into account enough margin to be safe not only for yield but especially for reliability. Even though process assumptions are calculated with a 4 sigma known process capability margin, efficient and competitive designs are challenging the process especially for derivatives technologies in 40 and 28nm nodes. For wafer fab process control, PA are declined in monovariate (layer1 CD, layer2 CD, layer2 to layer1 overlay, layer3 CD etc….) control charts with appropriated specifications and control limits which all together are securing the silicon. This is so far working fine but such system is not really sensitive to weak signals coming from interactions of multiple key parameters (high layer2 CD combined with high layer3 CD as an example). CHAM is a software using an advanced statistical algorithm specifically designed to detect small signals, especially when there are many parameters to control and when the parameters can interact to create yield issues. In this presentation we will first present the CHAM algorithm, then the case-study on critical dimensions, with the results, and we will conclude on future work. This partnership between Ippon and STM is part of E450LMDAP, European project dedicated to metrology and lithography development for future technology nodes, especially 10nm.

Sub-50 nm metrology on extreme ultra violet chemically amplified resist—A systematic assessment

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

Maas, D. J., E-mail: diederik.maas@tno.nl; Herfst, R.; Veldhoven, E. van

2015-10-15

With lithographic patterning dimensions decreasing well below 50 nm, it is of high importance to understand metrology at such small scales. This paper presents results obtained from dense arrays of contact holes (CHs) with various Critical Dimension (CD) between 15 and 50 nm, as patterned in a chemically amplified resist using an ASML EUV scanner and measured at ASML and TNO. To determine the differences between various (local) CD metrology techniques, we conducted an experiment using optical scatterometry, CD-Scanning Electron Microscopy (CD-SEM), Helium ion Microscopy (HIM), and Atomic Force Microscopy (AFM). CD-SEM requires advanced beam scan strategies to mitigate samplemore » charging; the other tools did not need that. We discuss the observed main similarities and differences between the various techniques. To this end, we assessed the spatial frequency content in the raw images for SEM, HIM, and AFM. HIM and AFM resolve the highest spatial frequencies, which are attributed to the more localized probe-sample interaction for these techniques. Furthermore, the SEM, HIM, and AFM waveforms are analyzed in detail. All techniques show good mutual correlation, albeit the reported CD values systematically differ significantly. HIM systematically reports a 25% higher CD uniformity number than CD-SEM for the same arrays of CHs, probably because HIM has a higher resolution than the CD-SEM used in this assessment. A significant speed boost for HIM and AFM is required before these techniques are to serve the demanding industrial metrology applications like optical critical dimension and CD-SEM do nowadays.« less

Sub-50 nm metrology on extreme ultra violet chemically amplified resist—A systematic assessment

NASA Astrophysics Data System (ADS)

Maas, D. J.; Fliervoet, T.; Herfst, R.; van Veldhoven, E.; Meessen, J.; Vaenkatesan, V.; Sadeghian, H.

2015-10-01

With lithographic patterning dimensions decreasing well below 50 nm, it is of high importance to understand metrology at such small scales. This paper presents results obtained from dense arrays of contact holes (CHs) with various Critical Dimension (CD) between 15 and 50 nm, as patterned in a chemically amplified resist using an ASML EUV scanner and measured at ASML and TNO. To determine the differences between various (local) CD metrology techniques, we conducted an experiment using optical scatterometry, CD-Scanning Electron Microscopy (CD-SEM), Helium ion Microscopy (HIM), and Atomic Force Microscopy (AFM). CD-SEM requires advanced beam scan strategies to mitigate sample charging; the other tools did not need that. We discuss the observed main similarities and differences between the various techniques. To this end, we assessed the spatial frequency content in the raw images for SEM, HIM, and AFM. HIM and AFM resolve the highest spatial frequencies, which are attributed to the more localized probe-sample interaction for these techniques. Furthermore, the SEM, HIM, and AFM waveforms are analyzed in detail. All techniques show good mutual correlation, albeit the reported CD values systematically differ significantly. HIM systematically reports a 25% higher CD uniformity number than CD-SEM for the same arrays of CHs, probably because HIM has a higher resolution than the CD-SEM used in this assessment. A significant speed boost for HIM and AFM is required before these techniques are to serve the demanding industrial metrology applications like optical critical dimension and CD-SEM do nowadays.

Decoration of wide bandgap semiconducting materials for enhancing photoelectrochemical efficiency of PEC systems.

NASA Astrophysics Data System (ADS)

Bakranov, N.; Zhabaikhanov, A.; Kudaibergenov, S.; Ibraev, N.

2018-03-01

The production of photoanodes based on wide-band gap materials such as TiO2 is economically viable because of the low cost of synthesis methods. Contrary to economic aspects, wide-band gap semiconductor materials have a significant disadvantage due to low sensitivity to photons of visible light. To increase the photoactive parameters of the material of the electrodes in the visible range, the methods for decorating nanomasses of titanium dioxide by narrow-gap semiconductors are used. One of the most suitable narrow-gap semiconductor materials are CdS and Fe2O3. Controlled deposition of such materials on wide-gap semiconductors allows to regulate both the diffusion time of charge carriers and the band structure of TiO2/Fe2O3 and TiO2/CdS composites. The dimensions of the structure of the photoelectrode material of the cell have a large influence on the characteristics of the photocatalyst created. Thus, in the hematite structures of nanometre dimension, the rate of recombination of charge carriers fades away in comparison with bulk structures. Reducing the size of CdS structures also positively affects the nature of the photocatalytic reaction.

Improved shallow trench isolation and gate process control using scatterometry based metrology

NASA Astrophysics Data System (ADS)

Rudolph, P.; Bradford, S. M.

2005-05-01

The ability to control critical dimensions of structures on semiconductor devices is essential to improving die yield and device performance. As geometries shrink, accuracy of the metrology equipment has increasingly become a contributing factor to the inability to detect shifts which result in yield loss. Scatterometry provides optical measurement that better enables process control of critical dimensions. Superior precision, accuracy, and higher throughput can be achieved more cost effectively through the use of this technology in production facilities. This paper outlines the implementation of Scatterometry based metrology in a production facility. The accuracy advantage it has over conventional Scanning Electron Microscope (SEM) measurement is presented. The Scatterometry tool used has demonstrated repeatability on the order of 3σ < 1 nm at STI-Etch-FICD for CD and Trench Depth (TD), and Side Wall Angle (SWA) measurements to within 0.1 degrees. Poly CD also shows 3σ < 1 nm, and poly thickness measurement 3σ < 2.5 Å. Scatterometry has capabilities which include measurement of CD, structure height and trench depth, Sidewall angle (SWA), and film thickness. The greater accuracy and the addition of in-situ Trench depth and sidewall angle have provided new measurement capabilities. There are inherent difficulties in implementing scatterometry in production wafer fabs. Difficulties with photo resist measurements, film characterization and stack set-up will be discussed. In addition, there are challenges due to the quantity data generated, in how to organize and store this data effectively. A comparison of the advantages and shortcomings of the method are presented.

Objectively measured muscle fatigue in Crohn's disease: correlation with self-reported fatigue and associated factors for clinical application.

PubMed

van Langenberg, D R; Della Gatta, P; Warmington, S A; Kidgell, D J; Gibson, P R; Russell, A P

2014-02-01

The association of fatigue with decreased physical performance and underlying mechanisms are poorly understood in Crohn's disease (CD). We aimed to measure and compare self-reported fatigue with skeletal muscle fatigue in CD subjects and healthy controls, and to identify associated factors that may be amenable to change. Demographic and clinical data were collected and fatigue assessed using the Fatigue Impact Scale (FIS) in 27 consecutive CD patients and 22 matched healthy controls. Circulating cytokines and growth factors were measured. The rate of quadriceps muscle fatigue was assessed using an isokinetic dynamometer as the decrement of force with 30 contractions performed over a 5-minute period. Compared with healthy controls, CD patients reported greater levels of fatigue (mean global FIS score 45.3 vs 10.5, physical dimension score 12.3 vs 2.7 respectively; each p<0.01) and muscle fatigue (-5.2 vs -1.3 Nm min(-1); p<0.05). The two indices were correlated (r = -0.52 in CD; p<0.01). Patients with CD had lower mean serum IGF-1 levels (16.1 vs 25.4 pmol/L, p<0.01) and higher oxidative stress (TBARS assay 4.3 vs 3.9 μM, p<0.05). On multivariate analysis, low serum vitamin D, IGF-1 and magnesium, and higher IL-6 levels were associated with increased muscle fatigue (all p ≤ 0.05). Subjects with CD had more muscle fatigue than matched healthy controls and this correlated well with self-reported fatigue. Of circulating factors that were independently associated with increased muscle fatigue, vitamin D, magnesium and IGF-1 could be targeted in future studies to reduce fatigue and improve physical performance. © 2013.

Nanostructured Electron-Selective Interlayer for Efficient Inverted Organic Solar Cells.

PubMed

Song, Jiyun; Lim, Jaehoon; Lee, Donggu; Thambidurai, M; Kim, Jun Young; Park, Myeongjin; Song, Hyung-Jun; Lee, Seonghoon; Char, Kookheon; Lee, Changhee

2015-08-26

We report a unique nanostructured electron-selective interlayer comprising of In-doped ZnO (ZnO:In) and vertically aligned CdSe tetrapods (TPs) for inverted polymer:fullerene bulkheterojunction (BHJ) solar cells. With dimension-controlled CdSe TPs, the direct inorganic electron transport pathway is provided, resulting in the improvement of the short circuit current and fill factor of devices. We demonstrate that the enhancement is attributed to the roles of CdSe TPs that reduce the recombination losses between the active layer and buffer layer, improve the hole-blocking as well as electron-transporting properties, and simultaneously improve charge collection characteristics. As a result, the power conversion efficiency of PTB7:PC70BM based solar cell with nanostructured CdSe TPs increases to 7.55%. We expect this approach can be extended to a general platform for improving charge extraction in organic solar cells.

Photomask linewidth comparison by PTB and NIST

NASA Astrophysics Data System (ADS)

Bergmann, D.; Bodermann, B.; Bosse, H.; Buhr, E.; Dai, G.; Dixson, R.; Häßler-Grohne, W.; Hahm, K.; Wurm, M.

2015-10-01

We report the initial results of a recent bilateral comparison of linewidth or critical dimension (CD) calibrations on photomask line features between two national metrology institutes (NMIs): the National Institute of Standards and Technology (NIST) in the United States and the Physikalisch-Technische Bundesanstalt (PTB) in Germany. For the comparison, a chrome on glass (CoG) photomask was used which has a layout of line features down to 100 nm nominal size. Different measurement methods were used at both institutes. These included: critical dimension atomic force microscopy (CD-AFM), CD scanning electron microscopy (CD-SEM) and ultraviolet (UV) transmission optical microscopy. The measurands are CD at 50 % height of the features as well as sidewall angle and line width roughness (LWR) of the features. On the isolated opaque features, we found agreement of the CD measurements at the 3 nm to 5 nm level on most features - usually within the combined expanded uncertainties of the measurements.

Two-layer critical dimensions and overlay process window characterization and improvement in full-chip computational lithography

NASA Astrophysics Data System (ADS)

Sturtevant, John L.; Liubich, Vlad; Gupta, Rachit

2016-04-01

Edge placement error (EPE) was a term initially introduced to describe the difference between predicted pattern contour edge and the design target for a single design layer. Strictly speaking, this quantity is not directly measurable in the fab. What is of vital importance is the relative edge placement errors between different design layers, and in the era of multipatterning, the different constituent mask sublayers for a single design layer. The critical dimensions (CD) and overlay between two layers can be measured in the fab, and there has always been a strong emphasis on control of overlay between design layers. The progress in this realm has been remarkable, accelerated in part at least by the proliferation of multipatterning, which reduces the available overlay budget by introducing a coupling of overlay and CD errors for the target layer. Computational lithography makes possible the full-chip assessment of two-layer edge to edge distances and two-layer contact overlap area. We will investigate examples of via-metal model-based analysis of CD and overlay errors. We will investigate both single patterning and double patterning. For single patterning, we show the advantage of contour-to-contour simulation over contour to target simulation, and how the addition of aberrations in the optical models can provide a more realistic CD-overlay process window (PW) for edge placement errors. For double patterning, the interaction of 4-layer CD and overlay errors is very complex, but we illustrate that not only can full-chip verification identify potential two-layer hotspots, the optical proximity correction engine can act to mitigate such hotspots and enlarge the joint CD-overlay PW.

Simultaneous overlay and CD measurement for double patterning: scatterometry and RCWA approach

NASA Astrophysics Data System (ADS)

Li, Jie; Liu, Zhuan; Rabello, Silvio; Dasari, Prasad; Kritsun, Oleg; Volkman, Catherine; Park, Jungchul; Singh, Lovejeet

2009-03-01

As optical lithography advances to 32 nm technology node and beyond, double patterning technology (DPT) has emerged as an attractive solution to circumvent the fundamental optical limitations. DPT poses unique demands on critical dimension (CD) uniformity and overlay control, making the tolerance decrease much faster than the rate at which critical dimension shrinks. This, in turn, makes metrology even more challenging. In the past, multi-pad diffractionbased overlay (DBO) using empirical approach has been shown to be an effective approach to measure overlay error associated with double patterning [1]. In this method, registration errors for double patterning were extracted from specially designed diffraction targets (three or four pads for each direction); CD variation is assumed negligible within each group of adjacent pads and not addressed in the measurement. In another paper, encouraging results were reported with a first attempt at simultaneously extracting overlay and CD parameters using scatterometry [2]. In this work, we apply scatterometry with a rigorous coupled wave analysis (RCWA) approach to characterize two double-patterning processes: litho-etch-litho-etch (LELE) and litho-freeze-litho-etch (LFLE). The advantage of performing rigorous modeling is to reduce the number of pads within each measurement target, thus reducing space requirement and improving throughput, and simultaneously extract CD and overlay information. This method measures overlay errors and CDs by fitting the optical signals with spectra calculated from a model of the targets. Good correlation is obtained between the results from this method and that of several reference techniques, including empirical multi-pad DBO, CD-SEM, and IBO. We also perform total measurement uncertainty (TMU) analysis to evaluate the overall performance. We demonstrate that scatterometry provides a promising solution to meet the challenging overlay metrology requirement in DPT.

Impact of Oppositional Defiant Disorder Dimensions on the Temporal Ordering of Conduct Problems and Depression across Childhood and Adolescence in Girls

ERIC Educational Resources Information Center

Hipwell, Alison E.; Stepp, Stephanie; Feng, Xin; Burke, Jeff; Battista, Deena R.; Loeber, Rolf; Keenan, Kate

2011-01-01

Background: Little is known about the role of oppositional defiant disorder (ODD) dimensions on the temporal unfolding of conduct disorder (CD) and depression in girls between childhood and adolescence. Method: The year-to-year associations between CD and depressive symptomatology were examined using nine waves of annually collected data (ages 8…

Effects produced by CDU improvement of resist pattern with PEB temperature control for wiring resistance variation reduction

NASA Astrophysics Data System (ADS)

Tadokoro, Masahide; Shinozuka, Shinichi; Ogata, Kunie; Morimoto, Tamotsu

2008-03-01

Semiconductor manufacturing technology has shifted towards finer design rules, and demands for critical dimension uniformity (CDU) of resist patterns have become greater than ever. One of the methods for improving CDU of resist pattern is to control the temperature of post-exposure bake (PEB). When ArF resist is used, there is a certain relationship between critical dimension (CD) and PEB temperature. By utilizing this relationship, Resist Pattern CDU can be improved through control of within-wafer temperature distribution in the PEB process. We have already applied this method to Resist Pattern CDU improvement and have achieved these results. In this evaluation, we aim at: 1. Clarifying the relationship between the improvement in Resist Pattern CDU through PEB temperature control and the improvement in Etching Pattern CDU. 2. Verifying whether Resist Pattern CDU improvement through PEB temperature control has any effect on the reduction in wiring resistance variation. The evaluation procedure is: 1. Preparation of wafers with base film of doped Poly-Si (D-Poly). 2. Creation of two sets of samples on the base, a set of samples with good Resist Pattern CDU and a set of samples with poor Resist Pattern CDU. 3. Etching of the two sets under the same conditions. 4. Measurements of CD and wiring resistance. We used Optical CD Measurement (OCD) for measurement of resist pattern and etching pattern for the reason that OCD is minimally affected by Line Edge Roughness (LER). As a result, we found that; 1. The improvement in Resist Pattern CDU leads to the improvement in Etching Pattern CDU . 2. The improvement in Resist Pattern CDU has an effect on the reduction in wiring resistance variation. There is a cause-and-effect relationship between wiring resistance variation and transistor characteristics. From this relationship, we expect that the improvement in Resist Pattern CDU through PEB temperature control can contribute to device performance improvement.

When things go pear shaped: contour variations of contacts

NASA Astrophysics Data System (ADS)

Utzny, Clemens

2013-04-01

Traditional control of critical dimensions (CD) on photolithographic masks considers the CD average and a measure for the CD variation such as the CD range or the standard deviation. Also systematic CD deviations from the mean such as CD signatures are subject to the control. These measures are valid for mask quality verification as long as patterns across a mask exhibit only size variations and no shape variation. The issue of shape variations becomes especially important in the context of contact holes on EUV masks. For EUV masks the CD error budget is much smaller than for standard optical masks. This means that small deviations from the contact shape can impact EUV waver prints in the sense that contact shape deformations induce asymmetric bridging phenomena. In this paper we present a detailed study of contact shape variations based on regular product data. Two data sets are analyzed: 1) contacts of varying target size and 2) a regularly spaced field of contacts. Here, the methods of statistical shape analysis are used to analyze CD SEM generated contour data. We demonstrate that contacts on photolithographic masks do not only show size variations but exhibit also pronounced nontrivial shape variations. In our data sets we find pronounced shape variations which can be interpreted as asymmetrical shape squeezing and contact rounding. Thus we demonstrate the limitations of classic CD measures for describing the feature variations on masks. Furthermore we show how the methods of statistical shape analysis can be used for quantifying the contour variations thus paving the way to a new understanding of mask linearity and its specification.

Benefit on health-related quality of life of adherence to gluten-free diet in adult patients with celiac disease.

PubMed

Casellas, Francisco; Rodrigo, Luis; Lucendo, Alfredo J; Fernández-Bañares, Fernando; Molina-Infante, Javier; Vivas, Santiago; Rosinach, Mercé; Dueñas, Carmen; López-Vivancos, Josefa

2015-04-01

Celiac disease (CD) affects health-related quality of life (HRQOL) of patients suffering it. The exclusion of gluten from the diet (GFD) improves HRQOL, but involves difficulties in following the diet that could adversely affect HRQOL. To determine the effect of adherence to the diet on HRQOL of adult CD patients. A prospective, cross-sectional, multicenter study of CD patients treated with a GFD for longer than 1 year. Adherence to the GFD was measured using the Morisky scale, and health status using the specific CD-QOL questionnaire and the generic EuroQol-5D questionnaire. 366 patients from 7 hospitals were included: 71.5% of patients reported a perfect treatment adherence, 23.5% unintentional poor adherence and 5% intentional poor adherence. Good adherence to a GFD was related to a higher mean score onthe CD-QOL (75 vs. 68, respectively, p < 0.05) and EuroQol-5D (0.9 vs. 0.8, respectively, p < 0.05). Ease of adherence to a GFD was also related to a better HRQOL (total CD-QOL score of 82 vs. 67 in patients who consider the GFD difficult to follow, p < 0.05). Good symptom control was also related to a better HRQOL (total CD-QOL score of 78 vs. 67 in asymptomatic vs. symptomatic patients, p < 0.01). The worse scored dimension of CD-QOL was related to "inadequate treatment". In CD, good adherence to a GFD and adequate symptom control result in improved HRQOL. Many patients consider that the lack of therapeutic alternatives to diet worsens their quality of life.

"I Cannot Be Worried": Living with Chagas Disease in Tropical Bolivia.

PubMed

Forsyth, Colin J

2017-01-01

Chagas disease (CD) profoundly affects the social and emotional dimensions of patients' lives, and disproportionately impacts poor, marginalized populations in Latin America. Biomedical treatment for CD fails to reach up to 99% of the people affected, and in any case seldom addresses the emotional health or socioeconomic conditions of patients. This study examines patient strategies for coping with CD in the department of Santa Cruz, Bolivia. In this ethnographic study, semistructured interviews took place from March-June 2013 with 63 patients who had previously tested positive for CD. During the fieldwork period, participant observation was conducted and patient family members, providers, community members, and public health officials were consulted. Patients often experienced emotional distress when diagnosed with CD, yet were generally unable to find biomedical treatment. Respondents stressed the need to avoid powerful emotions which would worsen the impact of CD symptoms. To manage CD, patients embraced a calm state of mind, described in Spanish as tranquilidad, which partially empowered them to return to a normal existence. In the perceived absence of biomedical treatment options, patients seek their own means of coping with CD diagnosis. Rather than fatalism or resignation, patients' emphasis on maintaining calm and not worrying about CD represents a pragmatic strategy for restoring a sense of normalcy and control to their lives. Programs focused on treatment of CD should remain mindful of the emotional and social impact of the disease on patients.

Photon-induced formation of CdS nanocrystals in selected areas of polymer matrices

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

Athanassiou, Athanassia; Cingolani, Roberto; Tsiranidou, Elsa

2007-10-08

We demonstrate light-induced formation of semiconductor quantum dots in TOPAS registered polymer matrix with very high control of their size and their spatial localization. Irradiation with UV laser pulses of polymer films embedding Cd thiolate precursors results in the formation of cadmium sulfide nanocrystals well confined in the irradiation area, through a macroscopically nondestructive procedure for the host matrix. With increasing number of laser pulses, we accomplish the formation of nanoparticles with gradually increasing dimensions, resulting in the dynamic change of the spectra emitted by the formed nanocomposite areas. The findings are supported by x-ray diffraction and transmission electron microscopymore » measurements.« less

CD and defect improvement challenges for immersion processes

NASA Astrophysics Data System (ADS)

Ehara, Keisuke; Ema, Tatsuhiko; Yamasaki, Toshinari; Nakagawa, Seiji; Ishitani, Seiji; Morita, Akihiko; Kim, Jeonghun; Kanaoka, Masashi; Yasuda, Shuichi; Asai, Masaya

2009-03-01

The intention of this study is to develop an immersion lithography process using advanced track solutions to achieve world class critical dimension (CD) and defectivity performance in a state of the art manufacturing facility. This study looks at three important topics for immersion lithography: defectivity, CD control, and wafer backside contamination. The topic of defectivity is addressed through optimization of coat, develop, and rinse processes as well as implementation of soak steps and bevel cleaning as part of a comprehensive defect solution. Develop and rinse processing techniques are especially important in the effort to achieve a zero defect solution. Improved CD control is achieved using a biased hot plate (BHP) equipped with an electrostatic chuck. This electrostatic chuck BHP (eBHP) is not only able to operate at a very uniform temperature, but it also allows the user to bias the post exposure bake (PEB) temperature profile to compensate for systematic within-wafer (WiW) CD non-uniformities. Optimized CD results, pre and post etch, are presented for production wafers. Wafer backside particles can cause focus spots on an individual wafer or migrate to the exposure tool's wafer stage and cause problems for a multitude of wafers. A basic evaluation of the cleaning efficiency of a backside scrubber unit located on the track was performed as a precursor to a future study examining the impact of wafer backside condition on scanner focus errors as well as defectivity in an immersion scanner.

Photomask etch system and process for 10nm technology node and beyond

NASA Astrophysics Data System (ADS)

Chandrachood, Madhavi; Grimbergen, Michael; Yu, Keven; Leung, Toi; Tran, Jeffrey; Chen, Jeff; Bivens, Darin; Yalamanchili, Rao; Wistrom, Richard; Faure, Tom; Bartlau, Peter; Crawford, Shaun; Sakamoto, Yoshifumi

2015-10-01

While the industry is making progress to offer EUV lithography schemes to attain ultimate critical dimensions down to 20 nm half pitch, an interim optical lithography solution to address an immediate need for resolution is offered by various integration schemes using advanced PSM (Phase Shift Mask) materials including thin e-beam resist and hard mask. Using the 193nm wavelength to produce 10nm or 7nm patterns requires a range of optimization techniques, including immersion and multiple patterning, which place a heavy demand on photomask technologies. Mask schemes with hard mask certainly help attain better selectivity and hence better resolution but pose integration challenges and defectivity issues. This paper presents a new photomask etch solution for attenuated phase shift masks that offers high selectivity (Cr:Resist > 1.5:1), tighter control on the CD uniformity with a 3sigma value approaching 1 nm and controllable CD bias (5-20 nm) with excellent CD linearity performance (<5 nm) down to the finer resolution. The new system has successfully demonstrated capability to meet the 10 nm node photomask CD requirements without the use of more complicated hard mask phase shift blanks. Significant improvement in post wet clean recovery performance was demonstrated by the use of advanced chamber materials. Examples of CD uniformity, linearity, and minimum feature size, and etch bias performance on 10 nm test site and production mask designs will be shown.

CD-SEM real time bias correction using reference metrology based modeling

NASA Astrophysics Data System (ADS)

Ukraintsev, V.; Banke, W.; Zagorodnev, G.; Archie, C.; Rana, N.; Pavlovsky, V.; Smirnov, V.; Briginas, I.; Katnani, A.; Vaid, A.

2018-03-01

Accuracy of patterning impacts yield, IC performance and technology time to market. Accuracy of patterning relies on optical proximity correction (OPC) models built using CD-SEM inputs and intra die critical dimension (CD) control based on CD-SEM. Sub-nanometer measurement uncertainty (MU) of CD-SEM is required for current technologies. Reported design and process related bias variation of CD-SEM is in the range of several nanometers. Reference metrology and numerical modeling are used to correct SEM. Both methods are slow to be used for real time bias correction. We report on real time CD-SEM bias correction using empirical models based on reference metrology (RM) data. Significant amount of currently untapped information (sidewall angle, corner rounding, etc.) is obtainable from SEM waveforms. Using additional RM information provided for specific technology (design rules, materials, processes) CD extraction algorithms can be pre-built and then used in real time for accurate CD extraction from regular CD-SEM images. The art and challenge of SEM modeling is in finding robust correlation between SEM waveform features and bias of CD-SEM as well as in minimizing RM inputs needed to create accurate (within the design and process space) model. The new approach was applied to improve CD-SEM accuracy of 45 nm GATE and 32 nm MET1 OPC 1D models. In both cases MU of the state of the art CD-SEM has been improved by 3x and reduced to a nanometer level. Similar approach can be applied to 2D (end of line, contours, etc.) and 3D (sidewall angle, corner rounding, etc.) cases.

Insights on correlation dimension from dynamics mapping of three experimental nonlinear laser systems.

PubMed

McMahon, Christopher J; Toomey, Joshua P; Kane, Deb M

2017-01-01

We have analysed large data sets consisting of tens of thousands of time series from three Type B laser systems: a semiconductor laser in a photonic integrated chip, a semiconductor laser subject to optical feedback from a long free-space-external-cavity, and a solid-state laser subject to optical injection from a master laser. The lasers can deliver either constant, periodic, pulsed, or chaotic outputs when parameters such as the injection current and the level of external perturbation are varied. The systems represent examples of experimental nonlinear systems more generally and cover a broad range of complexity including systematically varying complexity in some regions. In this work we have introduced a new procedure for semi-automatically interrogating experimental laser system output power time series to calculate the correlation dimension (CD) using the commonly adopted Grassberger-Proccacia algorithm. The new CD procedure is called the 'minimum gradient detection algorithm'. A value of minimum gradient is returned for all time series in a data set. In some cases this can be identified as a CD, with uncertainty. Applying the new 'minimum gradient detection algorithm' CD procedure, we obtained robust measurements of the correlation dimension for many of the time series measured from each laser system. By mapping the results across an extended parameter space for operation of each laser system, we were able to confidently identify regions of low CD (CD < 3) and assign these robust values for the correlation dimension. However, in all three laser systems, we were not able to measure the correlation dimension at all parts of the parameter space. Nevertheless, by mapping the staged progress of the algorithm, we were able to broadly classify the dynamical output of the lasers at all parts of their respective parameter spaces. For two of the laser systems this included displaying regions of high-complexity chaos and dynamic noise. These high-complexity regions are differentiated from regions where the time series are dominated by technical noise. This is the first time such differentiation has been achieved using a CD analysis approach. More can be known of the CD for a system when it is interrogated in a mapping context, than from calculations using isolated time series. This has been shown for three laser systems and the approach is expected to be useful in other areas of nonlinear science where large data sets are available and need to be semi-automatically analysed to provide real dimensional information about the complex dynamics. The CD/minimum gradient algorithm measure provides additional information that complements other measures of complexity and relative complexity, such as the permutation entropy; and conventional physical measurements.

Insights on correlation dimension from dynamics mapping of three experimental nonlinear laser systems

PubMed Central

McMahon, Christopher J.; Toomey, Joshua P.

2017-01-01

Background We have analysed large data sets consisting of tens of thousands of time series from three Type B laser systems: a semiconductor laser in a photonic integrated chip, a semiconductor laser subject to optical feedback from a long free-space-external-cavity, and a solid-state laser subject to optical injection from a master laser. The lasers can deliver either constant, periodic, pulsed, or chaotic outputs when parameters such as the injection current and the level of external perturbation are varied. The systems represent examples of experimental nonlinear systems more generally and cover a broad range of complexity including systematically varying complexity in some regions. Methods In this work we have introduced a new procedure for semi-automatically interrogating experimental laser system output power time series to calculate the correlation dimension (CD) using the commonly adopted Grassberger-Proccacia algorithm. The new CD procedure is called the ‘minimum gradient detection algorithm’. A value of minimum gradient is returned for all time series in a data set. In some cases this can be identified as a CD, with uncertainty. Findings Applying the new ‘minimum gradient detection algorithm’ CD procedure, we obtained robust measurements of the correlation dimension for many of the time series measured from each laser system. By mapping the results across an extended parameter space for operation of each laser system, we were able to confidently identify regions of low CD (CD < 3) and assign these robust values for the correlation dimension. However, in all three laser systems, we were not able to measure the correlation dimension at all parts of the parameter space. Nevertheless, by mapping the staged progress of the algorithm, we were able to broadly classify the dynamical output of the lasers at all parts of their respective parameter spaces. For two of the laser systems this included displaying regions of high-complexity chaos and dynamic noise. These high-complexity regions are differentiated from regions where the time series are dominated by technical noise. This is the first time such differentiation has been achieved using a CD analysis approach. Conclusions More can be known of the CD for a system when it is interrogated in a mapping context, than from calculations using isolated time series. This has been shown for three laser systems and the approach is expected to be useful in other areas of nonlinear science where large data sets are available and need to be semi-automatically analysed to provide real dimensional information about the complex dynamics. The CD/minimum gradient algorithm measure provides additional information that complements other measures of complexity and relative complexity, such as the permutation entropy; and conventional physical measurements. PMID:28837602

The LER/LWR metrology challenge for advance process control through 3D-AFM and CD-SEM

NASA Astrophysics Data System (ADS)

Faurie, P.; Foucher, J.; Foucher, A.-L.

2009-12-01

The continuous shrinkage in dimensions of microelectronic devices has reached such level, with typical gate length in advance R&D of less than 20nm combine with the introduction of new architecture (FinFET, Double gate...) and new materials (porous interconnect material, 193 immersion resist, metal gate material, high k materials...), that new process parameters have to be well understood and well monitored to guarantee sufficient production yield in a near future. Among these parameters, there are the critical dimensions (CD) associated to the sidewall angle (SWA) values, the line edge roughness (LER) and the line width roughness (LWR). Thus, a new metrology challenge has appeared recently and consists in measuring "accurately" the fabricated patterns on wafers in addition to measure the patterns on a repeatable way. Therefore, a great effort has to be done on existing techniques like CD-SEM, Scatterometry and 3D-AFM in order to develop them following the two previous criteria: Repeatability and Accuracy. In this paper, we will compare the 3D-AFM and CD-SEM techniques as a mean to measure LER and LWR on silicon and 193 resist and point out CD-SEM impact on the material during measurement. Indeed, depending on the material type, the interaction between the electron beam and the material or between the AFM tip and the material can vary a lot and subsequently can generate measurements bias. The first results tend to show that depending on CD-SEM conditions (magnification, number of acquisition frames) the final outputs can vary on a large range and therefore show that accuracy in such measurements are really not obvious to obtain. On the basis of results obtained on various materials that present standard sidewall roughness, we will show the limit of each technique and will propose different ways to improve them in order to fulfil advance roadmap requirements for the development of the next IC generation.

Full control of ligand positioning reveals spatial thresholds for T cell receptor triggering.

PubMed

Cai, Haogang; Muller, James; Depoil, David; Mayya, Viveka; Sheetz, Michael P; Dustin, Michael L; Wind, Shalom J

2018-04-30

Elucidating the rules for receptor triggering in cell-cell and cell-matrix contacts requires precise control of ligand positioning in three dimensions. Here, we use the T cell receptor (TCR) as a model and subject T cells to different geometric arrangements of ligands, using a nanofabricated single-molecule array platform. This comprises monovalent TCR ligands anchored to lithographically patterned nanoparticle clusters surrounded by mobile adhesion molecules on a supported lipid bilayer. The TCR ligand could be co-planar with the supported lipid bilayer (2D), excluding the CD45 transmembrane tyrosine phosphatase, or elevated by 10 nm on solid nanopedestals (3D), allowing closer access of CD45 to engaged TCR. The two configurations resulted in different T cell responses, depending on the lateral spacing between the ligands. These results identify the important contributions of lateral and axial components of ligand positioning and create a more complete foundation for receptor engineering for immunotherapy.

Pattern fidelity in nanoimprinted films using CD-SAXS

NASA Astrophysics Data System (ADS)

Jones, Ronald L.; Soles, Christopher L.; Lin, Eric K.; Hu, Walter; Reano, Ronald M.; Pang, Stella W.; Weigand, Steven J.; Keane, Denis T.; Quintana, John P.

2005-05-01

The primary measure of process quality in nanoimprint lithography (NIL) is the fidelity of pattern transfer, comparing the dimensions of the imprinted pattern to those of the mold. As a potential next generation lithography, NIL is capable of true nanofabrication, producing patterns of sub-10 nm dimensions. Routine production of nanoscale patterns will require new metrologies capable of non-destructive dimensional measurements of both the mold and the pattern with sub-nm precision. In this article, a rapid, non-destructive technique termed Critical Dimension Small Angle X-ray Scattering (CD-SAXS) is used to measure the cross sectional shape of both a pattern master, or mold, and the resulting imprinted films. CD-SAXS data are used to extract periodicity as well as pattern height, width, and sidewall angles. Films of varying materials are molded by thermal embossed NIL at temperatures both near and far from the bulk glass transition (TG). The polymer systems include a photoresist, representing a mixture of a polymer and small molecular components, and two pure homopolymers. Molding at low temperatures (T-TG < 40°C) produces small aspect ratio patterns that maintain periodicity to within a single nanometer, but feature large sidewall angles. While the pattern height does not reach that of the mold until very large imprinting temperatures (T-TG ~ 70°C), the pattern width of the mold is accurately transferred for T-TG > 30°C. In addition to obtaining basic dimensions, CD-SAXS data are used to assess the origin of loss in pattern fidelity.

Large Exciton Energy Shifts by Reversible Surface Exchange in 2D II-VI Nanocrystals.

PubMed

Zhou, Yang; Wang, Fudong; Buhro, William E

2015-12-09

Reaction of n-octylamine-passivated {CdSe[n-octylamine](0.53±0.06)} quantum belts with anhydrous metal carboxylates M(oleate)2 (M = Cd, Zn) results in a rapid exchange of the L-type amine passivation for Z-type M(oleate)2 passivation. The cadmium-carboxylate derivative is determined to have the composition {CdSe[Cd(oleate)2](0.19±0.02)}. The morphologies and crystal structures of the quantum belts are largely unaffected by the exchange processes. Addition of n-octylamine or oleylamine to the M(oleate)2-passivated quantum belts removes M(oleate)2 and restores the L-type amine passivation. Analogous, reversible surface exchanges are also demonstrated for CdS quantum platelets. The absorption and emission spectra of the quantum belts and platelets are reversibly shifted to lower energy by M(oleate)2 passivation vs amine passivation. The largest shift of 140 meV is observed for the Cd(oleate)2-passivated CdSe quantum belts. These shifts are attributed entirely to changes in the strain states in the Zn(oleate)2-passivated nanocrystals, whereas changes in strain states and confinement dimensions contribute roughly equally to the shifts in the Cd(oleate)2-passivated nanocrystals. Addition of Cd(oleate)2, which electronically couples to the nanocrystal lattices, increases the effective thickness of the belts and platelets by approximately a half of a monolayer, thus increasing the confinement dimension.

3-D reservoir characterization of the House Creek oil field, Powder River Basin, Wyoming

USGS Publications Warehouse

Higley, Debra K.; Pantea, Michael P.; Slatt, Roger M.

1997-01-01

This CD-ROM is intended to serve a broad audience. An important purpose is to explain geologic and geochemical factors that control petroleum production from the House Creek Field. This information may serve as an analog for other marine-ridge sandstone reservoirs. The 3-D slide and movie images are tied to explanations and 2-D geologic and geochemical images to visualize geologic structures in three dimensions, explain the geologic significance of porosity/permeability distribution across the sandstone bodies, and tie this to petroleum production characteristics in the oil field. Movies, text, images including scanning electron photomicrographs (SEM), thin-section photomicrographs, and data files can be copied from the CD-ROM for use in external mapping, statistical, and other applications.

One month of contemporary dance modulates fractal posture in aging

PubMed Central

Coubard, Olivier A.; Ferrufino, Lena; Nonaka, Tetsushi; Zelada, Oscar; Bril, Blandine; Dietrich, Gilles

2013-01-01

Understanding the human aging of postural control and how physical or motor activity improves balance and gait is challenging for both clinicians and researchers. Previous studies have evidenced that physical and sporting activity focusing on cardiovascular and strength conditioning help older adults develop their balance and gait and/or decrease their frequency of falls. Motor activity based on motor-skill learning has also been put forward as an alternative to develop balance and/or prevent falls in aging. Specifically dance has been advocated as a promising program to boost motor control. In this study, we examined the effects of contemporary dance (CD) on postural control of older adults. Upright stance posturography was performed in 38 participants aged 54–89 years before and after the intervention period, during which one half of the randomly assigned participants was trained to CD and the other half was not trained at all (no dance, ND). CD training lasted 4 weeks, 3 times a week. We performed classical statistic scores of postural signal and dynamic analyses, namely signal diffusion analysis (SDA), recurrence quantification analysis (RQA), and detrended fluctuation analysis (DFA). CD modulated postural control in older trainees, as revealed in the eyes closed condition by a decrease in fractal dimension and an increase in DFA alpha component in the mediolateral plane. The ND group showed an increase in length and mean velocity of postural signal, and the eyes open a decrease in RQA maximal diagonal line in the anteroposterior plane and an increase in DFA alpha component in the mediolateral plane. No change was found in SDA in either group. We suggest that such a massed practice of CD reduced the quantity of exchange between the subject and the environment by increasing their postural confidence. Since CD has low-physical but high-motor impact, we conclude that it may be recommended as a useful program to rehabilitate posture in aging. PMID:24611047

Gas Flows in Rocket Motors. Volume 3. Appendix D. Computer Code Listings

DTIC Science & Technology

1989-08-01

Information Service, where it will be available to the general public, including foreign nationals. Prepared for the Astronautics Laboratory (AFSC) Air Force...SYMIMETRIC TRANSONIC NOZZLE FLOW~ IN CENEPAL COORDINATE SYSTEM C+ USING TIME ITERATIVE CD/’CD SCHEME * c VIITH THIN-LAYER APPROXIMATED NAVIER-STOIKE’S...Q( 1,1, 2) ,RHOU( 1, 1)), DIMENSION ADD(4) DIMENSION PRE(4,4), PADD (4) C SAI-DIRECTION ENTRY ADDX COF:F=O.125D0*OMEGAX DO 70 J=I,,JL DO 70 I=1,IL IF

Automated aerial image based CD metrology initiated by pattern marking with photomask layout data

NASA Astrophysics Data System (ADS)

Davis, Grant; Choi, Sun Young; Jung, Eui Hee; Seyfarth, Arne; van Doornmalen, Hans; Poortinga, Eric

2007-05-01

The photomask is a critical element in the lithographic image transfer process from the drawn layout to the final structures on the wafer. The non-linearity of the imaging process and the related MEEF impose a tight control requirement on the photomask critical dimensions. Critical dimensions can be measured in aerial images with hardware emulation. This is a more recent complement to the standard scanning electron microscope measurement of wafers and photomasks. Aerial image measurement includes non-linear, 3-dimensional, and materials effects on imaging that cannot be observed directly by SEM measurement of the mask. Aerial image measurement excludes the processing effects of printing and etching on the wafer. This presents a unique contribution to the difficult process control and modeling tasks in mask making. In the past, aerial image measurements have been used mainly to characterize the printability of mask repair sites. Development of photomask CD characterization with the AIMS TM tool was motivated by the benefit of MEEF sensitivity and the shorter feedback loop compared to wafer exposures. This paper describes a new application that includes: an improved interface for the selection of meaningful locations using the photomask and design layout data with the Calibre TM Metrology Interface, an automated recipe generation process, an automated measurement process, and automated analysis and result reporting on a Carl Zeiss AIMS TM system.

Programmed LWR metrology by multi-techniques approach

NASA Astrophysics Data System (ADS)

Reche, Jérôme; Besacier, Maxime; Gergaud, Patrice; Blancquaert, Yoann; Freychet, Guillaume; Labbaye, Thibault

2018-03-01

Nowadays, roughness control presents a huge challenge for the lithography step. For advanced nodes, this morphological aspect reaches the same order of magnitude than the Critical Dimension. Hence, the control of roughness needs an adapted metrology. In this study, specific samples with designed roughness have been manufactured using e-beam lithography. These samples have been characterized with three different methodologies: CD-SEM, OCD and SAXS. The main goal of the project is to compare the capability of each of these techniques in terms of reliability, type of information obtained, time to obtain the measurements and level of maturity for the industry.

Impact of deformed extreme-ultraviolet pellicle in terms of CD uniformity

NASA Astrophysics Data System (ADS)

Kim, In-Seon; Yeung, Michael; Barouch, Eytan; Oh, Hye-Keun

2015-07-01

The usage of the extreme ultraviolet (EUV) pellicle is regarded as the solution for defect control since it can protect the mask from airborne debris. However some obstacles disrupt real-application of the pellicle such as structural weakness, thermal damage and so on. For these reasons, flawless fabrication of the pellicle is impossible. In this paper, we discuss the influence of deformed pellicle in terms of non-uniform intensity distribution and critical dimension (CD) uniformity. It was found that non-uniform intensity distribution is proportional to local tilt angle of pellicle and CD variation was linearly proportional to transmission difference. When we consider the 16 nm line and space pattern with dipole illumination (σc=0.8, σr=0.1, NA=0.33), the transmission difference (max-min) of 0.7 % causes 0.1 nm CD uniformity. Influence of gravity caused deflection to the aerial image is small enough to ignore. CD uniformity is less than 0.1 nm even for the current gap of 2 mm between mask and pellicle. However, heat caused EUV pellicle wrinkle might cause serious image distortion because a wrinkle of EUV pellicle causes a transmission loss variation as well as CD non-uniformity. In conclusion, local angle of a wrinkle, not a period or an amplitude of a wrinkle is a main factor to CD uniformity, and local angle of less than ~270 mrad is needed to achieve 0.1 nm CD uniformity with 16 nm L/S pattern.

The Structure of Self-Serving Cognitive Distortions: A Validation of the "How I Think" Questionnaire in a Sample of Italian Adolescents

ERIC Educational Resources Information Center

Bacchini, Dario; De Angelis, Grazia; Affuso, Gaetana; Brugman, Daniel

2016-01-01

This study aims to investigate the structure of self-serving cognitive distortions (CD), evaluating the psychometric properties of the How I Think Questionnaire in a sample of Italian adolescents. A confirmatory factor analysis supported the distinction between four categories of CD and the use of a single second-order dimension of CD. Reliability…

Asymmetric Semiconductor Nanorod/Oxide Nanoparticle Hybrid Materials: Model Nanomaterials for Light-Activated Formation of Fuels from Sunlight. Formal Progress Report -- Award DE-FG02-05ER15753

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

Armstrong, Neal R.

Executive Summary on Project Accomplishments: We focused our efforts for this project on the synthesis and characterization of semiconductor nanomaterials composed of semiconductor nanorods (NRs - e.g., CdSe, CdSe@CdS, CdS) with metal (Au, Pt, Co) or metal oxide (CoxOy) nanoparticle (NP) “tips.” These systems are attractive model systems where control of spatial, energetic and compositional features of both NRs and NP tips potentially enhances the efficiency of photogeneration and directional transport of charges, and photoelectrochemical conversion of sunlight to fuels. Synthetic methods to control material dimensions (20-200 nm in length), topology (one vs. two NP tips) and NR/NP tip compositionsmore » have been developed in the current project period (Pyun). We also achieved, for the first time in heterostructured nanorod materials, estimates of both valence band energies (E VB) and conduction band energies (E CB), using unique combinations of in vacuuo ultraviolet photoelectron spectroscopy (UPS, Armstrong), and waveguide spectroelectrochemistry (Saavedra), respectively. The spectroelectrochemical measurements in particular provide a unique path to estimation of E CB, and the distribution in E CB brought about by modification of NR composition. The combination of both approaches promises to be universally applicable to the characterization of energetics in nanomaterials of interest both for photovoltaic and sunlight-to-fuel photoelectrochemical assemblies.« less

Assembly of P3HT/CdSe nanowire networks in an insulating polymer host.

PubMed

Heo, Kyuyoung; Miesch, Caroline; Na, Jun-Hee; Emrick, Todd; Hayward, Ryan C

2018-06-27

Nanoparticles may act as compatibilizing agents for blending of immiscible polymers, leading to changes in blend morphology through a variety of mechanisms including interfacial adsorption, aggregation, and nucleation of polymer crystals. Herein, we report an approach to define highly structured donor/acceptor networks based on poly(3-hexylthiophene) (P3HT) and CdSe quantum dots (QDs) by demixing from an insulating polystyrene (PS) matrix. The incorporation of QDs led to laterally phase-separated co-continuous structures with sub-micrometer dimensions, and promoted crystallization of P3HT, yielding highly interconnected P3HT/QD hybrid nanowires embedded in the polymer matrix. These nanohybrid materials formed by controlling phase separation, interfacial activity, and crystallization within ternary donor/acceptor/insulator blends, offer attractive morphologies for potential use in optoelectronics.

Real-time line-width measurements: a new feature for reticle inspection systems

NASA Astrophysics Data System (ADS)

Eran, Yair; Greenberg, Gad; Joseph, Amnon; Lustig, Cornel; Mizrahi, Eyal

1997-07-01

The significance of line width control in mask production has become greater with the lessening of defect size. There are two conventional methods used for controlling line widths dimensions which employed in the manufacturing of masks for sub micron devices. These two methods are the critical dimensions (CD) measurement and the detection of edge defects. Achieving reliable and accurate control of line width errors is one of the most challenging tasks in mask production. Neither of the two methods cited above (namely CD measurement and the detection of edge defects) guarantees the detection of line width errors with good sensitivity over the whole mask area. This stems from the fact that CD measurement provides only statistical data on the mask features whereas applying edge defect detection method checks defects on each edge by itself, and does not supply information on the combined result of error detection on two adjacent edges. For example, a combination of a small edge defect together with a CD non- uniformity which are both within the allowed tolerance, may yield a significant line width error, which will not be detected using the conventional methods (see figure 1). A new approach for the detection of line width errors which overcomes this difficulty is presented. Based on this approach, a new sensitive line width error detector was developed and added to Orbot's RT-8000 die-to-database reticle inspection system. This innovative detector operates continuously during the mask inspection process and scans (inspects) the entire area of the reticle for line width errors. The detection is based on a comparison of measured line width that are taken on both the design database and the scanned image of the reticle. In section 2, the motivation for developing this new detector is presented. The section covers an analysis of various defect types, which are difficult to detect using conventional edge detection methods or, alternatively, CD measurements. In section 3, the basic concept of the new approach is introduced together with a description of the new detector and its characteristics. In section 4, the calibration process that took place in order to achieve reliable and repeatable line width measurements is presented. The description of an experiments conducted in order to evaluate the sensitivity of the new detector is given in section 5, followed by a report of the results of this evaluation. The conclusions are presented in section 6.

Gamma ray detector modules

NASA Technical Reports Server (NTRS)

Capote, M. Albert (Inventor); Lenos, Howard A. (Inventor)

2009-01-01

A radiation detector assembly has a semiconductor detector array substrate of CdZnTe or CdTe, having a plurality of detector cell pads on a first surface thereof, the pads having a contact metallization and a solder barrier metallization. An interposer card has planar dimensions no larger than planar dimensions of the semiconductor detector array substrate, a plurality of interconnect pads on a first surface thereof, at least one readout semiconductor chip and at least one connector on a second surface thereof, each having planar dimensions no larger than the planar dimensions of the interposer card. Solder columns extend from contacts on the interposer first surface to the plurality of pads on the semiconductor detector array substrate first surface, the solder columns having at least one solder having a melting point or liquidus less than 120 degrees C. An encapsulant is disposed between the interposer circuit card first surface and the semiconductor detector array substrate first surface, encapsulating the solder columns, the encapsulant curing at a temperature no greater than 120 degrees C.

Effect of lateral size and thickness on the electronic structure and optical properties of quasi two-dimensional CdSe and CdS nanoplatelets

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

Bose, Sumanta; Fan, W. J., E-mail: ewjfan@ntu.edu.sg; Zhang, D. H.

2016-04-14

The effect of lateral size and vertical thickness of CdSe and CdS nanoplatelets (NPLs) on their electronic structure and optical properties are investigated using an effective-mass envelope function theory based on the 8-band k ⋅ p model with valence force field considerations. Volumetrically larger NPLs have lower photon emission energy due to limited quantum confinement, but a greater transition matrix element (TME) due to larger electron-hole wavefunction overlap. The optical gain characteristics depend on several factors such as TME, Fermi factor, carrier density, NPL dimensions, material composition, and dephasing rate. There is a red shift in the peak position, moremore » so with an increase in thickness than lateral size. For an increasing carrier density, the gain spectrum undergoes a slight blue shift due to band filling effect. For a fixed carrier density, the Fermi factor is higher for volumetrically larger NPLs and so is the difference between the quasi-Fermi level separation and the effective bandgap. The transparency injection carrier density (and thus input current density threshold) is dimension dependent and falls for volumetrically larger NPLs, as they can attain the requisite exciton count for transparency with a relatively lower density. Between CdSe and CdS, CdSe has lower emission energy due to smaller bandgap, but a higher TME due to lower effective mass. CdS, however, has a higher so hole contribution due to a lower spin-orbit splitting energy. Both CdSe and CdS NPLs are suitable candidates for short-wavelength LEDs and lasers in the visible spectrum, but CdSe is expected to exhibit better optical performance.« less

A porous Cd(II) metal-organic framework with high adsorption selectivity for CO2 over CH4

NASA Astrophysics Data System (ADS)

Zhu, Chunlan

2017-05-01

Metal-organic frameworks (MOFs) have attracted a lot of attention in recent decades. We applied a semi-rigid four-carboxylic acid linker to assemble with Cd(II) ions to generate a novel microporous Cd(II) MOF material. Single crystal X-ray diffraction study reveals the different two dimension (2D) layers can be further packed together with an AB fashion by hydrogen bonds (O4sbnd H4⋯O7 = 1.863 Å) to construct a three dimension (3D) supermolecular architecture. The resulting sample can be synthesized under solvothermal reactions successfully, which exhibits high selectivity adsorption of CO2 over CH4 at room temperature. In addition, the obtained sample was characterized by thermal gravimetric analyses (TGA), Fourier-transform infrared spectra (FT-IR), elemental analysis (CHN) and powder X-ray diffraction (PXRD).

Full-chip level MEEF analysis using model based lithography verification

NASA Astrophysics Data System (ADS)

Kim, Juhwan; Wang, Lantian; Zhang, Daniel; Tang, Zongwu

2005-11-01

MEEF (Mask Error Enhancement Factor) has become a critical factor in CD uniformity control since optical lithography process moved to sub-resolution era. A lot of studies have been done by quantifying the impact of the mask CD (Critical Dimension) errors on the wafer CD errors1-2. However, the benefits from those studies were restricted only to small pattern areas of the full-chip data due to long simulation time. As fast turn around time can be achieved for the complicated verifications on very large data by linearly scalable distributed processing technology, model-based lithography verification becomes feasible for various types of applications such as post mask synthesis data sign off for mask tape out in production and lithography process development with full-chip data3,4,5. In this study, we introduced two useful methodologies for the full-chip level verification of mask error impact on wafer lithography patterning process. One methodology is to check MEEF distribution in addition to CD distribution through process window, which can be used for RET/OPC optimization at R&D stage. The other is to check mask error sensitivity on potential pinch and bridge hotspots through lithography process variation, where the outputs can be passed on to Mask CD metrology to add CD measurements on those hotspot locations. Two different OPC data were compared using the two methodologies in this study.

Control of the sidewall angle of an absorber stack using the Faraday cage system for the change of pattern printability in EUVL

NASA Astrophysics Data System (ADS)

Jang, Il-Yong; Huh, Sung-Min; Moon, Seong-Yong; Woo, Sang-Gyun; Lee, Jin-Kwan; Moon, Sang Heup; Cho, HanKu

2008-10-01

A patterned TaN substrate, which is candidate for a mask absorber in extreme ultra-violet lithography (EUVL), was etched to have inclined sidewalls by using a Faraday cage system under the condition of a 2-step process that allowed the high etch selectivity of TaN over the resist. The sidewall angle (SWA) of the patterned substrate, which was in the shape of a parallelogram after etching, could be controlled by changing the slope of a substrate holder that was placed in the Faraday cage. The performance of an EUV mask, which contained the TaN absorber of an oblique pattern over the molybdenum/silicon multi-layer, was simulated for different cases of SWA. The results indicated that the optical properties, such as the critical dimension (CD), an offset in the CD bias between horizontal and vertical patterns (H-V bias), and a shift in the image position on the wafer, could be controlled by changing the SWA of the absorber stack. The simulation result showed that the effect of the SWA on the optical properties became more significant at larger thicknesses of the absorber and smaller sizes of the target CD. Nevertheless, the contrast of the aerial images was not significantly decreased because the shadow effect caused by either sidewall of the patterned substrate cancelled with each other.

Meeting critical gate linewidth control needs at the 65 nm node

NASA Astrophysics Data System (ADS)

Mahorowala, Arpan; Halle, Scott; Gabor, Allen; Chu, William; Barberet, Alexandra; Samuels, Donald; Abdo, Amr; Tsou, Len; Yan, Wendy; Iseda, Seiji; Patel, Kaushal; Dirahoui, Bachir; Nomura, Asuka; Ahsan, Ishtiaq; Azam, Faisal; Berg, Gary; Brendler, Andrew; Zimmerman, Jeffrey; Faure, Tom

2006-03-01

With the nominal gate length at the 65 nm node being only 35 nm, controlling the critical dimension (CD) in polysilicon to within a few nanometers is essential to achieve a competitive power-to-performance ratio. Gate linewidths must be controlled, not only at the chip level so that the chip performs as the circuit designers and device engineers had intended, but also at the wafer level so that more chips with the optimum power-to-performance ratio are manufactured. Achieving tight across-chip linewidth variation (ACLV) and chip mean variation (CMV) is possible only if the mask-making, lithography, and etching processes are all controlled to very tight specifications. This paper identifies the various ACLV and CMV components, describes their root causes, and discusses a methodology to quantify them. For example, the site-to-site ACLV component is divided into systematic and random sub-components. The systematic component of the variation is attributed in part to pattern density variation across the field, and variation in exposure dose across the slit. The paper demonstrates our team's success in achieving the tight gate CD tolerances required for 65 nm technology. Certain key challenges faced, and methods employed to overcome them are described. For instance, the use of dose-compensation strategies to correct the small but systematic CD variations measured across the wafer, is described. Finally, the impact of immersion lithography on both ACLV and CMV is briefly discussed.

Personality risk profile for conduct disorder and substance use disorders in youth.

PubMed

Anderson, Kristen G; Tapert, Susan F; Moadab, Ida; Crowley, Thomas J; Brown, Sandra A

2007-10-01

The five factor model of personality is a useful metric to describe personality profiles associated with maladaptive functioning. Using the NEO-Five Factor Inventory (NEO-FFI), we examined a conceptually based profile of high neuroticism, low agreeableness and low conscientiousness among 243 youth (aged 13-18 years) with varying degrees of conduct disorder (CD) and substance use disorders (SUD). Comparisons of the NEO-FFI personality dimensions between CD/SUD youth and adolescent siblings (N=173), and relations between the personality dimensions and behavioral indicators of conduct disorder and substance involvement were examined. Youth with CD and SUD had greater neuroticism, lower agreeableness, and lower conscientiousness than siblings of a similar age. The NEO-FFI scales predicted aggression and substance involvement for both probands and siblings in this cross-sectional investigation. These findings support the role for personality in models of the etiology and persistence of conduct disorder and substance use disorders.

Lateral Tip Control Effects in CD-AFM Metrology: The Large Tip Limit.

PubMed

Dixson, Ronald G; Orji, Ndubuisi G; Goldband, Ryan S

2016-01-25

Sidewall sensing in critical dimension atomic force microscopes (CD-AFMs) usually involves continuous lateral dithering of the tip or the use of a control algorithm and fast response piezo actuator to position the tip in a manner that resembles touch-triggering of coordinate measuring machine (CMM) probes. All methods of tip position control, however, induce an effective tip width that may deviate from the actual geometrical tip width. Understanding the influence and dependence of the effective tip width on the dither settings and lateral stiffness of the tip can improve the measurement accuracy and uncertainty estimation for CD-AFM measurements. Since CD-AFM typically uses tips that range from 15 nm to 850 nm in geometrical width, the behavior of effective tip width throughout this range should be understood. The National Institute of Standards and Technology (NIST) has been investigating the dependence of effective tip width on the dither settings and lateral stiffness of the tip, as well as the possibility of material effects due to sample composition. For tip widths of 130 nm and lower, which also have lower lateral stiffness, the response of the effective tip width to lateral dither is greater than for larger tips. However, we have concluded that these effects will not generally result in a residual bias, provided that the tip calibration and sample measurement are performed under the same conditions. To validate that our prior conclusions about the dependence of effective tip width on lateral stiffness are valid for large CD-tips, we recently performed experiments using a very large non-CD tip with an etched plateau of approximately 2 μm width. The effective lateral stiffness of these tips is at least 20 times greater than typical CD-AFM tips, and these results supported our prior conclusions about the expected behavior for larger tips. The bottom-line importance of these latest observations is that we can now reasonably conclude that a dither slope of 3 nm/V is the baseline response due to the induced motion of the cantilever base.

Lateral Tip Control Effects in CD-AFM Metrology: The Large Tip Limit

PubMed Central

Dixson, Ronald G.; Orji, Ndubuisi G.; Goldband, Ryan S.

2016-01-01

Sidewall sensing in critical dimension atomic force microscopes (CD-AFMs) usually involves continuous lateral dithering of the tip or the use of a control algorithm and fast response piezo actuator to position the tip in a manner that resembles touch-triggering of coordinate measuring machine (CMM) probes. All methods of tip position control, however, induce an effective tip width that may deviate from the actual geometrical tip width. Understanding the influence and dependence of the effective tip width on the dither settings and lateral stiffness of the tip can improve the measurement accuracy and uncertainty estimation for CD-AFM measurements. Since CD-AFM typically uses tips that range from 15 nm to 850 nm in geometrical width, the behavior of effective tip width throughout this range should be understood. The National Institute of Standards and Technology (NIST) has been investigating the dependence of effective tip width on the dither settings and lateral stiffness of the tip, as well as the possibility of material effects due to sample composition. For tip widths of 130 nm and lower, which also have lower lateral stiffness, the response of the effective tip width to lateral dither is greater than for larger tips. However, we have concluded that these effects will not generally result in a residual bias, provided that the tip calibration and sample measurement are performed under the same conditions. To validate that our prior conclusions about the dependence of effective tip width on lateral stiffness are valid for large CD-tips, we recently performed experiments using a very large non-CD tip with an etched plateau of approximately 2 μm width. The effective lateral stiffness of these tips is at least 20 times greater than typical CD-AFM tips, and these results supported our prior conclusions about the expected behavior for larger tips. The bottom-line importance of these latest observations is that we can now reasonably conclude that a dither slope of 3 nm/V is the baseline response due to the induced motion of the cantilever base. PMID:27087883

Association Between Vascular Density and Loss of Protective RAS During Early NPDR by Fractal Dimension

NASA Technical Reports Server (NTRS)

Radhakrishnan, Krisnan; Vyas, Ruchi J.; Murray, Matthew; Predovic, Marina; Lim, Shiyin; Bryant, Douglas; Yaqian, Duan; Grant, Maria B.; Chalam, K. V.; Parsons-Wingerter, Patricia

2017-01-01

Purpose: Our hypothesis predicts that blood vessels within the retina increase in density during early-stage nonproliferative diabetic retinopathy (NPDR), based on previous results of a small retrospective study. For the current prospective study, the remodeling of arteries and veins during progression of early NPDR is assessed by a repertoire of parameters that includes the fractal dimension (D(sub f) ). In complex structures such as branching vascular trees, D(sub f) is a sensitive measure of space-filing capacity. The renin-angiotensin system (RAS) is implicated in DR pathogenesis and the function of circulating angiogenic cells (CACs), a critical bone marrow-derived population instrumental in vascular repair. Methods: Arterial and venous branching patterns were extracted from images of 6 normal controls and 3 early NPDR subjects (2 moderate, 1 mild) acquired by Heidelberg Spectralis (Registered Trademark) OCT following fluorescein angiography (FA). The vascular branching patterns were analyzed by NASAs VESsel GENeration Analysis (VESGEN) software, in which skeletonized representations were generated automatically to yield D(sub f) by the box-counting method. For binary 2D images, D(sub f) varies between limiting Euclidean dimensions of 1 and 2. Peripheral blood of diabetics and controls was collected for CD34+ CAC isolation. The gene expression of RAS in CACs was assessed by qPCR for Mas receptor to Ang-(1-7). The vasoreparative function of the CACs was measured by migration ability toward CXCL12 (SDF-1). Results: By D(sub f), venous and arterial densities were 1.370 +/- 0.006 and 1.329 +/- 0.016 for early NPDR, compared to 1.318 +/- 0.012 and 1.320 +/- 0.036 for control. The space filling capacity in early NPDR measured by D(sub f), a sensitive parameter, therefore demonstrated a pronounced increase for veins, but not for arteries. Mas receptor mRNA in CACs was increased in diabetics without DR but reduced with onset of NPDR, indicating possible loss of compensation of protective RAS during early DR. Migratory dysfunction of CD34+ cells was further associated with DR. Conclusions: As assessed by the fractal dimension in our preliminary study, the space-filling capacity of veins, but not arteries, was greater in early NPDR than in control. Larger patient populations will be examined as we complete our ongoing longitudinal study. Results further suggest the protective RAS axis within diabetic CACs is lost early in DR and is associated with increased vascular remodeling as evidenced by VESGEN analysis.

Final Report: DOE Award Number: DE-SC0006398, University of CA, San Diego

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

Cha, Jennifer

The focus of the proposed research is to direct the assembly of single or binary nanoparticles into meso- or macroscale three-dimensional crystals of any desired configuration and crystallographic orientation without using prohibitively expensive lithographic processes. The epitaxial nucleation of defect-free, surface-bound bulk single crystals will revolutionize technologies for energy to generate new types of solar cells that yield maximum conversion efficiencies. It has been proposed that having a nanostructured bulk hetero-interface will enable efficient charge-carrier separations, similar to organic based heterojunction cells but with potential improvements, including thermal and long-term stability, tunability of energy levels, large adsorption coefficients and carriermore » multiplication. However, engineering such devices requires nanoscale control and ordering in both 2- and 3-dimensions over macroscopic areas and this has yet to be achieved. In Nature, bulk organic and inorganic materials are arranged into precise and ordered programmed assemblies through the sequestration of raw materials into confined spaces and association through highly specific non-covalent interactions between biomolecules. Using similar strategies, the proposed research will focus on confining metal and semiconductor nanocrystals to pre-determined surface patterns and controlling their arrangement through tunable, orthogonal biomolecular binding. Once a perfect two-dimensional seed layer has been constructed, successive layers of single nanocrystals will be nucleated epitaxially with long-range order and tunable crystallographic orientations. The proposed research exploits the ability of biomolecules to bind specific targets in a tunable, orthogonal, multivalent, and reversible manner to the arrangements of DNA-nanoparticle conjugates on chemically defined surfaces. Through careful balance of the attractive and repulsive forces between the particles, the array, and the outside surface, it is envisioned that single or mixed nanoparticles can be packed to adopt uniform crystal orientation in two and three dimensions from simple mixing and annealing of biomolecule-nanoparticle conjugates with biomolecule-stamped surfaces. To control the crystallographic alignment of each particle with its neighbors, the nanoparticles will be assembled using a mixture of non-covalent biomolecular interactions. To create solar cells in which layers of donor and acceptor nanocrystals that are not only oriented normal to the top and bottom electrodes but are also arranged in a checkerboard pattern, multicomponent nanocrystals (e.g. CdSe, CdTe) will be conjugated with biochemical linkers such that only interactions between the CdTe and CdSe promote particle packing within the array. The proposed research will: (1) elucidate the role of single and binary cooperative particle-DNA interactions in influencing nanoparticle crystallographic orientation in two and three dimensions; (2) understand how confinement of nanoparticles on patterned arrays of biomolecules and modification of the surrounding substrate can nucleate long-range order over macroscopic areas via predefined grain boundaries; and (3) synthesize and characterize DNA conjugated semiconductor nanocrystals and assemble them into 2- and 3-D binary superlattice arrays for photovoltaics.« less

In-die mask registration measurement on 28nm-node and beyond

NASA Astrophysics Data System (ADS)

Chen, Shen Hung; Cheng, Yung Feng; Chen, Ming Jui

2013-09-01

As semiconductor go to smaller node, the critical dimension (CD) of process become more and more small. For lithography, RET (Resolution Enhancement Technology) applications can be used for wafer printing of smaller CD/pitch on 28nm node and beyond. SMO (Source Mask Optimization), DPT (Double Patterning Technology) and SADP (Self-Align Double Patterning) can provide lower k1 value for lithography. In another way, image placement error and overlay control also become more and more important for smaller chip size (advanced node). Mask registration (image placement error) and mask overlay are important factors to affect wafer overlay control/performance especially for DPT or SADP. In traditional method, the designed registration marks (cross type, square type) with larger CD were put into scribe-line of mask frame for registration and overlay measurement. However, these patterns are far way from real patterns. It does not show the registration of real pattern directly and is not a convincing method. In this study, the in-die (in-chip) registration measurement is introduced. We extract the dummy patterns that are close to main pattern from post-OPC (Optical Proximity Correction) gds by our desired rule and choose the patterns that distribute over whole mask uniformly. The convergence test shows 100 points measurement has a reliable result.

The role of the sca-1+/CD31- cardiac progenitor cell population in postinfarction left ventricular remodeling.

PubMed

Wang, Xiaohong; Hu, Qingsong; Nakamura, Yasuhiro; Lee, Joseph; Zhang, Ge; From, Arthur H L; Zhang, Jianyi

2006-07-01

Cardiac stem cell-like populations exist in adult hearts, and their roles in cardiac repair remain to be defined. Sca-1 is an important surface marker for cardiac and other somatic stem cells. We hypothesized that heart-derived Sca-1(+)/CD31(-) cells may play a role in myocardial infarction-induced cardiac repair/remodeling. Mouse heart-derived Sca-1(+)/CD31(-) cells cultured in vitro could be induced to express both endothelial cell and cardiomyocyte markers. Immunofluorescence staining and fluorescence-activated cell sorting analysis indicated that endogenous Sca-1(+)/CD31(-) cells were significantly increased in the mouse heart 7 days after myocardial infarction (MI). Western blotting confirmed elevated Sca-1 protein expression in myocardium 7 days after MI. Transplantation of Sca-1(+)/CD31(-) cells into the acutely infarcted mouse heart attenuated the functional decline and adverse structural remodeling initiated by MI as evidenced by an increased left ventricular (LV) ejection fraction, a decreased LV end-diastolic dimension, a decreased LV end-systolic dimension, a significant increase of myocardial neovascularization, and modest cardiomyocyte regeneration. Attenuation of LV remodeling was accompanied by remarkably improved myocardial bioenergetic characteristics. The beneficial effects of cell transplantation appear to primarily depend on paracrine effects of the transplanted cells on new vessel formation and native cardiomyocyte function. Sca-1(+)/CD31(-) cells may hold therapeutic possibilities with regard to the treatment of ischemic heart disease.

The effects of rearing light level and duration differences on the optic nerve, brain, and associated structures in developing zebrafish larvae: a light and transmission electron microscope study.

PubMed

Chapman, George B; Tarboush, Rania; Connaughton, Victoria P

2012-03-01

The ultrastructure of the optic nerve, brain, and some associated structures of larval zebrafish, grown under three different light regimens were studied. Fish grown under cyclic light (control), constant dark (CD), and constant light (CL) were studied for 4 and 8 days postfertilization (dpf). We also studied the control and CD fish at 15 dpf. The brains of the control and CL fish were larger at 4 dpf than at 8 dpf. In all 4 dpf fish, the brain occupied the entire expanse between the two retinas and the optic nerve extended the shortest distance between the retina and the brain. The 15 dpf zebrafish had the smallest brain size. Groups of skeletal muscle cells associated with the optic nerves became visible in all older larvae. In the 15 dpf larvae, bulges and dilations in the optic nerve occurred as it reached the brain and optic chiasms occurred proximal to the brain. Electron microscopy yielded information about myelinated and unmyelinated axons in the optic nerve, the dimensions of neurotubules, neurofilaments, and myofilaments, including a unique variation in actin myofilaments, and a confirmation of reported myosin myofilament changes (but with dimensions). We also describe the ultrastructure of a sheath-like structure that is confluent over the optic nerve and the brain, which has not been described before in zebrafish. Also presented are images of associated fibroblasts, epithelial cells lining the mouth, cartilage plates, blood vessels, nerve bundles, and skeletal muscle cells, most of which have not been previously described in the literature. Copyright © 2012 Wiley Periodicals, Inc.

Estimation of quality of life in Cypriot patients with inflammatory bowel disease.

PubMed

Tsoukka, Maria; Jelastopulu, Eleni; Lavranos, Giagkos; Charalambous, George

2017-01-07

To investigate the health-related quality of life (HRQoL) of patients suffering with idiopathic inflammatory bowel disease (IBD). The Greek validated version of the Short Inflammatory Bowel Disease Questionnaire was used for evaluating the quality of life of IBD patients. The questionnaire was distributed to 100 consecutive patients suffering from IBD and presenting for a clinic appointment at the endoscopy unit of Larnaca General Hospital during the period from October to November 2012. The criteria for participating in this study were constituted by the documented diagnosis of either ulcerative colitis (UC) or Crohn's disease (CD) after endoscopy and histologic examination at least 6 months before the study, adult patients (18 years old or older), the capability of verbal communication and the patient's written consent for attending this study. The majority of the questionnaires were completed by a nurse practitioner who specializes in IBD patient care. Regarding the physical dimension in patients with UC, males scored significantly higher than females (4.2 vs 3.4, P = 0.023). Higher scores were also observed in UC patients younger than 35 or older than 50 years (4.0 and 4.2 vs 3.2, respectively, P = 0.021). The psychological dimension revealed similar results in patients with UC, with males, and older ages scoring higher (5.0 vs 3.0, P = 0.01 and 4.7 vs 2.7, P < 0.5, respectively), whereas regarding CD higher scores were observed in married compared to unmarried (3.83 vs 2.33, P = 0.042). No statistical differences in any parameters in the social dimension were observed. Regarding the treatment of, patients with CD, overall higher scores were observed when treated with biological factors compared to standard therapy in all dimensions but with statistical significant difference in the social dimension (5.00 vs 3.25, P = 0.045). The study reveals a negative impact of IBD on HRQoL. Increased risks are age and gender in patients with UC and family status in patients with CD.

SU-8 negative photoresist for optical mask manufacturing

NASA Astrophysics Data System (ADS)

Bogdanov, Alexei L.

2000-06-01

The requirements for better control, linearity, and uniformity of critical dimension (CD) on photomasks in fabrication of 180 and 150 nm generation devices result in increasing demand for thinner, more etching durable, and more sensitive e-beam resists. Novolac based resists with chemical amplification have been a choice for their sensitivity and stability during etching. However, difficult CD control due to the acid catalyzer diffusion and quite narrow post exposure bake (PEB) process window are some of the major drawbacks of these resists. SU-8 is recently introduced to the market negative photoresist. High sensitivity, fairly good adhesion properties, and relatively simple processing of SU-8 make it a good substitution for novolac based chemically amplified negative e-beam resists in optical mask manufacturing. The replacement of traditional chemically amplified resists by SU- 8 can increase the process latitude and reduce resist costs. Among the obvious drawbacks of SU-8 are the use of solvent- based developer and demand of oxygen plasma for resist removal. In this paper the use of SU-8 for optical mask manufacturing is reported. All steps of resist film preparation, exposure and development are paid a share of attention. Possibilities to use reactive ion etching (RIE) with oxygen in order to increase resist mask contrast are discussed. Special exposure strategy (pattern outlining) was employed to further improve the edge definition. The resist PEB temperature and time were studied to estimate their weight in overall CD control performance. Specially designed test patterns with 0.25 micrometer design rule could be firmly transferred into a chromium layer both by wet etching and ion milling. Influence of exposure dose variation on the pattern CD change was studied.

Three-Dimensional Arrangement of Human Bone Marrow Microvessels Revealed by Immunohistology in Undecalcified Sections

PubMed Central

Wilhelmi, Verena; Seiler, Anja; Lampp, Katrin; Neff, Andreas; Guthe, Michael; Lobachev, Oleg

2016-01-01

The arrangement of microvessels in human bone marrow is so far unknown. We combined monoclonal antibodies against CD34 and against CD141 to visualise all microvessel endothelia in 21 serial sections of about 1 cm2 size derived from a human iliac crest. The specimen was not decalcified and embedded in Technovit® 9100. In different regions of interest, the microvasculature was reconstructed in three dimensions using automatic methods. The three-dimensional models were subject to a rigid semiautomatic and manual quality control. In iliac crest bone marrow, the adipose tissue harbours irregularly distributed haematopoietic areas. These are fed by networks of large sinuses, which are loosely connected to networks of small capillaries prevailing in areas of pure adipose tissue. Our findings are compatible with the hypothesis that capillaries and sinuses in human iliac crest bone marrow are partially arranged in parallel. PMID:27997569

Evaluation of a new photomask CD metrology tool

NASA Astrophysics Data System (ADS)

Dubuque, Leonard F.; Doe, Nicholas G.; St. Cin, Patrick

1996-12-01

In the integrated circuit (IC) photomask industry today, dense IC patterns, sub-micron critical dimensions (CD), and narrow tolerances for 64 M technologies and beyond are driving increased demands to minimize and characterize all components of photomask CD variation. This places strict requirements on photomask CD metrology in order to accurately characterize the mask CD error distribution. According to the gauge-maker's rule, measurement error must not exceed 30% of the tolerance on the product dimension measured or the gauge is not considered capable. The traditional single point repeatability tests are a poor measure of overall measurement system error in a dynamic, leading-edge technology environment. In such an environment, measurements may be taken at different points in the field- of-view due to stage in-accuracy, pattern recognition requirements, and throughput considerations. With this in mind, a set of experiments were designed to characterize thoroughly the metrology tool's repeatability and systematic error. Original experiments provided inconclusive results and had to be extended to obtain a full characterization of the system. Tests demonstrated a performance of better than 15 nm total CD error. Using this test as a tool for further development, the authors were able to determine the effects of various system components and measure the improvement with changes in optics, electronics, and software. Optimization of the optical path, electronics, and system software has yielded a new instrument with a total system error of better than 8 nm. Good collaboration between the photomask manufacturer and the equipment supplier has led to a realistic test of system performance and an improved CD measurement instrument.

[A validation of the MOS-HIV quality of life measure in HIV-infected patients in Mexico].

PubMed

Peña de León, Edilberto; Aguilar Gaytán, Sandra Socorro; Suárez Mendoza, Aldo Antonio; Reyes Terán, Gustavo

2007-05-01

To validate the Medical Outcomes Study HIV Health Survey (MOS-HIV) quality of life instrument for its application in clinical research in Mexico. The data for this study were collected between April, 2002, and February, 2004. An expert committee combined two Spanish-language translations of the MOS-HIV questionnaire. The new questionnaire's feasibility was assessed in a group of 32 HIV-infected persons by measuring how long they took to complete the questionnaire and the numbers of items they left unanswered. The questionnaire was then applied to a group of 120 HIV-positive patients and to a control group of 102 HIV-negative individuals. The following questionnaire characteristics were evaluated: (1) internal reliability (Cronbach alpha coefficient), (2) discriminant validity (the receiver operating characteristic (ROC) curves derived from the scores of the two groups), and (3) convergent validity (the Spearman correlation coefficients for the scores of the HIV-positive patients on the 11 MOS-HIV dimensions and their scores on the analog visual scale of the European Quality of Life 5-Dimensional format (EQ-5D) questionnaire, a list of symptoms, the viral load, and the CD4 cell count). The mean response time with the questionnaire was 10 minutes and 22 seconds, and the mean number of unanswered items was 0.62. With each of the 11 dimensions of the questionnaire, the Cronbach alpha coefficient was at least 0.75. The mean scores obtained by the two groups were different for 9 of the 11 dimensions, and the 95% confidence intervals of the areas under the ROC curves did not include the value of 0.5 for 8 of the dimensions. The absolute value of the Spearman correlation coefficient was less than 0.3 for the CD4 cell count and for the viral load, and it was greater than 0.3 for each dimension and the scores on the list of symptoms and on the analog visual scale of the EQ-5D questionnaire. The MOS-HIV measure is valid for use in clinical research among HIV-infected persons in Mexico.

Biometric study of the internal dimensions of subglottis and upper trachea in adult Indian population.

PubMed

Prasanna Kumar, S; Ravikumar, A

2014-01-01

The anatomy of the larynx and trachea is well described in literature, however the intraluminal dimensions and contour of the subglottis has not been well documented. Subglottis and trachea are dynamic structures and the internal dimensions and contours have been studied only on cadavers or by plain radiograph which has many technical and measurement errors. No data is available about the internal dimensions of the subglottic and trachea in Indian population. This is the first documented study to measure the dimensions of the trachea and subglottis in Indian population. The aim of this study is to measure the internal dimensions and contour of the subglottis and upper trachea of adult Indian population. We conducted cross-sectional, observational study in a university hospital in south India to measure the dimensions of the internal subglottic and upper tracheal lumen. CT scan with 3D reconstruction with multiplanar sections was used for precise measurements. Forty-eight subjects (30 male and 18 female) who had undergone CT scan of the neck and thorax for reasons other than airway compromise were included in the study. The internal coronal diameter (CD), sagittal diameter (SD), and circumference was measured at various levels from 5 to 70 mm below the level of glottis, in the subglottis and upper trachea. Measurements of the scan for each subject were done independently by a radiologist and ENT surgeon and average of the two were documented values of each subject. These measurements were then statistically analyzed using SSPS software. The mean CD of adult Indian male ranged from 13.18 to 17.68 mm. The average intraluminal circumference ranged from 48.82 mm at the subglottis 5 mm from the glottis to a maximum of 54.96 at 30 mm. The mean CD of adult Indian female ranged from 8.7 to 15.34 mm The average intraluminal circumference ranged from 36.5 at 5 mm and a maximum of 43.05 at 70 mm. The 95% CI for the coronal, sagittal and circumference of the subglottis and upper trachea for both genders have been calculated and discussed. We have observed that the average intraluminal dimensions of the subglottis and upper trachea in south Indian population is less than that reported in western literature and earlier studies.

Topographic distribution of EEG alpha attractor correlation dimension values in wake and drowsy states in humans.

PubMed

Kalauzi, Aleksandar; Vuckovic, Aleksandra; Bojić, Tijana

2015-03-01

Organization of resting state cortical networks is of fundamental importance for the phenomenon of awareness, which is altered in the first part of hypnagogic period (Hori stages 1-4). Our aim was to investigate the change in brain topography pattern of EEG alpha attractor correlation dimension (CD) in the period of transition from Hori stage 1 to 4. EEG of ten healthy adult individuals was recorded in the wake and drowsy states, using a 14 channel average reference montage, from which 91 bipolar channels were derived and filtered in the wider alpha (6-14 Hz) range. Sixty 1s long epochs of each state and individual were subjected to CD calculation according to the Grassberger-Procaccia method. For such a collection of signals, two embedding dimensions, d={5, 10}, and 22 time delays τ=2-23 samples were explored. Optimal values were d=10 and τ=18, where both saturation and second zero crossing of the autocorrelation function occurred. Bipolar channel CD underwent a significant decrease during the transition and showed a positive linear correlation with electrode distance, stronger in the wake individuals. Topographic distribution of bipolar channels with above median CD changed from longitudinal anterior-posterior pattern (awake) to a more diagonal pattern, with localization in posterior regions (drowsiness). Our data are in line with the literature reporting functional segregation of neuronal assemblies in anterior and posterior regions during this transition. Our results should contribute to understanding of complex reorganization of the cortical part of alpha generators during the wake/drowsy transition. Copyright © 2014 Elsevier B.V. All rights reserved.

Pedagogical Design Considerations in Sex Education on Interactive Multimedia Using CD-Rom: An Example of Sexual Intercourse

ERIC Educational Resources Information Center

Goldman, Juliette D. G.; Torrisi-Steele, Geraldine

2005-01-01

Human sexuality is a significant issue for educators to understand and teach about, and for young people to learn about. The development of interactive multimedia technologies has added a range of new dimensions associated with designing pedagogies for sex education on Interactive Multimedia (IMM). Here, a module on CD-Rom on Sexuality and Human…

CD-measurement technique for hole patterns on stencil mask

NASA Astrophysics Data System (ADS)

Ishikawa, Mikio; Yusa, Satoshi; Takikawa, Tadahiko; Fujita, Hiroshi; Sano, Hisatake; Hoga, Morihisa; Hayashi, Naoya

2004-12-01

EB lithography has a potential to successfully form hole patterns as small as 80 nm with a stencil mask. In a previous paper we proposed a technique using a HOLON dual-mode critical dimension (CD) SEM ESPA-75S in the transmission mode for CD measurement of line-and-space patterns on a stencil mask. In this paper we extend our effort of developing a CD measurement technique to contact hole features and determine it in comparison of measured values between features on mask and those printed on wafer. We have evaluated the width method and the area methods using designed 80-500 nm wide contact hole patterns on a large area membrane mask and their resist images on wafer printed by a LEEPL3000. We find that 1) the width method and the area methods show an excellent mask-wafer correlation for holes over 110 nm, and 2) the area methods show a better mask-wafer correlation than the width method does for holes below 110 nm. We conclude that the area calculated from the transmission SEM image is more suitable in defining the hole dimensions than the width for contact holes on a stencil mask.

Optoelectronics of inverted type-I CdS/CdSe core/crown quantum ring

NASA Astrophysics Data System (ADS)

Bose, Sumanta; Fan, Weijun; Zhang, Dao Hua

2017-10-01

Inverted type-I heterostructure core/crown quantum rings (QRs) are quantum-efficient luminophores, whose spectral characteristics are highly tunable. Here, we study the optoelectronic properties of type-I core/crown CdS/CdSe QRs in the zincblende phase—over contrasting lateral size and crown width. For this, we inspect their strain profiles, transition energies, transition matrix elements, spatial charge densities, electronic bandstructures, band-mixing probabilities, optical gain spectra, maximum optical gains, and differential optical gains. Our framework uses an effective-mass envelope function theory based on the 8-band k ṡ p method employing the valence force field model for calculating the atomic strain distributions. The gain calculations are based on the density-matrix equation and take into consideration the excitonic effects with intraband scattering. Variations in the QR lateral size and relative widths of core and crown (ergo the composition) affect their energy levels, band-mixing probabilities, optical transition matrix elements, emission wavelengths/intensities, etc. The optical gain of QRs is also strongly dimension and composition dependent with further dependency on the injection carrier density causing the band-filling effect. They also affect the maximum and differential gain at varying dimensions and compositions.

Design principles for HgTe based topological insulator devices

NASA Astrophysics Data System (ADS)

Sengupta, Parijat; Kubis, Tillmann; Tan, Yaohua; Povolotskyi, Michael; Klimeck, Gerhard

2013-07-01

The topological insulator properties of CdTe/HgTe/CdTe quantum wells are theoretically studied. The CdTe/HgTe/CdTe quantum well behaves as a topological insulator beyond a critical well width dimension. It is shown that if the barrier (CdTe) and well-region (HgTe) are altered by replacing them with the alloy CdxHg1-xTe of various stoichiometries, the critical width can be changed. The critical quantum well width is shown to depend on temperature, applied stress, growth directions, and external electric fields. Based on these results, a novel device concept is proposed that allows to switch between a normal semiconducting and topological insulator state through application of moderate external electric fields.

Carbon-nanotube probes for three-dimensional critical-dimension metrology

NASA Astrophysics Data System (ADS)

Park, B. C.; Ahn, S. J.; Choi, J.; Jung, K. Y.; Song, W. Y.

2006-03-01

We fabricate three kinds of carbon nanotube (CNT) probes to be employed in critical dimension atomic force microscope (CD-AFM). Despite unique advantages in its size and hardness, use of nanotube tip has been limited due to the lack of reproducible control of CNT orientation and its shape. We proposed that CNT alignment issues can be addressed based on the ion beam bending process, where a CNT free-standing on the apex of an AFM tip aligns itself in parallel to the FIB direction so that its free end is directed toward the ion source, with no external electric or magnetic field involved. The process allowed us to embody cylindrical probes of CNT diameters, and subsequently two additional types of CNT tips. One is ball-ended CNT tip which has, at the end of CNT tip, side-protrusions of tungsten/amorphous carbon in the horizontal dithering direction. The other is 'bent' CNT tip where the end of CNT is bent to a side direction. Using the former type of CNT tip, both sides of trench/line sidewall can be measured except for bottom corners, while the corners can be reached with the latter type, but the only one sidewall can be measured at a tip setting. The three types of tips appear to satisfy the requirements in both the size and accessibility to the re-entrant sidewall, and are awaiting actual test in CD-AFM.

Investigation of hyper-NA scanner emulation for photomask CDU performance

NASA Astrophysics Data System (ADS)

Poortinga, Eric; Scheruebl, Thomas; Conley, Will; Sundermann, Frank

2007-02-01

As the semiconductor industry moves toward immersion lithography using numerical apertures above 1.0 the quality of the photomask becomes even more crucial. Photomask specifications are driven by the critical dimension (CD) metrology within the wafer fab. Knowledge of the CD values at resist level provides a reliable mechanism for the prediction of device performance. Ultimately, tolerances of device electrical properties drive the wafer linewidth specifications of the lithography group. Staying within this budget is influenced mainly by the scanner settings, resist process, and photomask quality. Tightening of photomask specifications is one mechanism for meeting the wafer CD targets. The challenge lies in determining how photomask level metrology results influence wafer level imaging performance. Can it be inferred that photomask level CD performance is the direct contributor to wafer level CD performance? With respect to phase shift masks, criteria such as phase and transmission control are generally tightened with each technology node. Are there other photomask relevant influences that effect wafer CD performance? A comprehensive study is presented supporting the use of scanner emulation based photomask CD metrology to predict wafer level within chip CD uniformity (CDU). Using scanner emulation with the photomask can provide more accurate wafer level prediction because it inherently includes all contributors to image formation related to the 3D topography such as the physical CD, phase, transmission, sidewall angle, surface roughness, and other material properties. Emulated images from different photomask types were captured to provide CD values across chip. Emulated scanner image measurements were completed using an AIMS TM45-193i with its hyper-NA, through-pellicle data acquisition capability including the Global CDU Map TM software option for AIMS TM tools. The through-pellicle data acquisition capability is an essential prerequisite for capturing final CDU data (after final clean and pellicle mounting) before the photomask ships or for re-qualification at the wafer fab. Data was also collected on these photomasks using a conventional CD-SEM metrology system with the pellicles removed. A comparison was then made to wafer prints demonstrating the benefit of using scanner emulation based photomask CD metrology.

Tip Characterization Method using Multi-feature Characterizer for CD-AFM

PubMed Central

Orji, Ndubuisi G.; Itoh, Hiroshi; Wang, Chumei; Dixson, Ronald G.; Walecki, Peter S.; Schmidt, Sebastian W.; Irmer, Bernd

2016-01-01

In atomic force microscopy (AFM) metrology, the tip is a key source of uncertainty. Images taken with an AFM show a change in feature width and shape that depends on tip geometry. This geometric dilation is more pronounced when measuring features with high aspect ratios, and makes it difficult to obtain absolute dimensions. In order to accurately measure nanoscale features using an AFM, the tip dimensions should be known with a high degree of precision. We evaluate a new AFM tip characterizer, and apply it to critical dimension AFM (CD-AFM) tips used for high aspect ratio features. The characterizer is made up of comb-shaped lines and spaces, and includes a series of gratings that could be used as an integrated nanoscale length reference. We also demonstrate a simulation method that could be used to specify what range of tip sizes and shapes the characterizer can measure. Our experiments show that for non re-entrant features, the results obtained with this characterizer are consistent to 1 nm with the results obtained by using widely accepted but slower methods that are common practice in CD-AFM metrology. A validation of the integrated length standard using displacement interferometry indicates a uniformity of better than 0.75%, suggesting that the sample could be used as highly accurate and SI traceable lateral scale for the whole evaluation process. PMID:26720439

How to obtain accurate resist simulations in very low-k1 era?

NASA Astrophysics Data System (ADS)

Chiou, Tsann-Bim; Park, Chan-Ha; Choi, Jae-Seung; Min, Young-Hong; Hansen, Steve; Tseng, Shih-En; Chen, Alek C.; Yim, Donggyu

2006-03-01

A procedure for calibrating a resist model iteratively adjusts appropriate parameters until the simulations of the model match the experimental data. The tunable parameters may include the shape of the illuminator, the geometry and transmittance/phase of the mask, light source and scanner-related parameters that affect imaging quality, resist process control and most importantly the physical/chemical factors in the resist model. The resist model can be accurately calibrated by measuring critical dimensions (CD) of a focus-exposure matrix (FEM) and the technique has been demonstrated to be very successful in predicting lithographic performance. However, resist model calibration is more challenging in the low k1 (<0.3) regime because numerous uncertainties, such as mask and resist CD metrology errors, are becoming too large to be ignored. This study demonstrates a resist model calibration procedure for a 0.29 k1 process using a 6% halftone mask containing 2D brickwall patterns. The influence of different scanning electron microscopes (SEM) and their wafer metrology signal analysis algorithms on the accuracy of the resist model is evaluated. As an example of the metrology issue of the resist pattern, the treatment of a sidewall angle is demonstrated for the resist line ends where the contrast is relatively low. Additionally, the mask optical proximity correction (OPC) and corner rounding are considered in the calibration procedure that is based on captured SEM images. Accordingly, the average root-mean-square (RMS) error, which is the difference between simulated and experimental CDs, can be improved by considering the metrological issues. Moreover, a weighting method and a measured CD tolerance are proposed to handle the different CD variations of the various edge points of the wafer resist pattern. After the weighting method is implemented and the CD selection criteria applied, the RMS error can be further suppressed. Therefore, the resist CD and process window can be confidently evaluated using the accurately calibrated resist model. One of the examples simulates the sensitivity of the mask pattern error, which is helpful to specify the mask CD control.

Development of a new delivery system consisting in 'drug-in cyclodextrin-in PLGA nanoparticles'.

PubMed

Mura, Paola; Maestrelli, Francesca; Cecchi, Matteo; Bragagni, Marco; Almeida, Antonio

2010-01-01

A combined approach based on drug cyclodextrin (CD) complexation and loading into PLGA nanoparticles (NP) has been developed to improve oxaprozin therapeutic efficiency. This strategy exploits the solubilizing and stabilizing properties of CDs and the prolonged-release and targeting properties of PLGA NPs. Drug-loaded NPs, prepared by double-emulsion, were examined for dimensions, zeta-potential and entrapment efficiency. Solid-state studies demonstrated the absence of drug-polymer interactions and assessed the amorphous state of the drug-CD complex loaded into NPs. Drug release rate from NPs was strongly influenced by the presence and kind of CD used. The percentage released at 24 h varied from 16% (plain drug-loaded NPs) to 50% (drug-betaCD-loaded NPs) up to 100% (drug-methylbetaCD-loaded NPs). This result suggests the possibility of using CD complexation not only to promote, but also to regulate drug release rate from NPs, by selecting the proper type of CD or CD combination.

Expression of CTLA-4 (CD152) on human medullary CD4+ thymocytes.

PubMed

Castan, J; Klauenberg, U; Kalmár, P; Fleischer, B; Bröker, B M

1998-06-01

CTLA-4 (CD152) is a T cell surface receptor with sequence homology to the co-stimulatory molecule CD28. The molecule, which is essential for the inhibitory regulation of the immune response, becomes transiently expressed on mature T cells after stimulation in vitro. In situ, CTLA-4+ T cells are enriched in the light zones of the germinal centers in human peripheral lymphoid organs. In this study we have studied expression of CTLA-4 in human thymus in situ. CTLA-4 was expressed on about one third of CD4+/CD8-/CD1- medullary thymocytes. CTLA-4 was acquired by a subset of immature (CD1+) thymocytes and lost from the mature (CD1-) subpopulation within 48 h of cell culture, suggesting that the expression on medullary thymocytes is transient. The demonstration of CTLA-4 on a substantial subpopulation of mature CD4+ thymocytes adds a new dimension to the understanding of this important molecule. When contemplating application of anti-CTLA-4 for therapy its potential influence on T cell maturation has to be taken into account.

Short health scale: A valid measure of health-related quality of life in Korean-speaking patients with inflammatory bowel disease

PubMed Central

Park, Soo-Kyung; Ko, Bong Min; Goong, Hyeon Jeong; Seo, Jeong Yeon; Lee, Sang Hyuk; Baek, Hae Lim; Lee, Moon Sung; Park, Dong Il

2017-01-01

AIM To evaluate the short health scale (SHS), a new, simple, four-part visual analogue scale questionnaire that is designed to assess the impact of inflammatory bowel disease (IBD) on health-related quality of life (HRQOL), in Korean-speaking patients with IBD. METHODS The SHS was completed by 256 patients with Crohn’s disease (CD) and ulcerative colitis (UC). Individual SHS items were correlated with inflammatory bowel disease questionnaire (IBDQ) dimensions and with disease activity to assess validity. Test-retest reliability, responsiveness and patient or disease characteristics with probable association with high SHS scores were analyzed. RESULTS Of 256 patients with IBD, 139 (54.3%) had UC and 117 (45.7%) had CD. The correlation coefficients between SHS questions about “symptom burden”, “activities of daily living”, and “disease-related worry” and their corresponding dimensions in the IBDQ ranged from 0.62 to 0.71, compared with correlation coefficients ranging from -0.45 to -0.61 for their non-corresponding dimensions. There was a stepwise increase in SHS scores, with increasing disease activity in both CD and UC (all P values < 0.001). Reliability was confirmed with test-retest correlations ranging from 0.68 to 0.90 (all P values < 0.001). Responsiveness was confirmed with the patients who remained in remission. Their SHS scores remained unchanged, except for the SHS dimension “disease-related worry”. In the multivariate analysis, female sex was associated with worse “general well-being” (OR = 2.28, 95%CI: 1.02-5.08) along with worse disease activity. CONCLUSION The SHS is a valid and reliable measure of HRQOL in Korean-speaking patients with IBD. PMID:28596689

Short health scale: A valid measure of health-related quality of life in Korean-speaking patients with inflammatory bowel disease.

PubMed

Park, Soo-Kyung; Ko, Bong Min; Goong, Hyeon Jeong; Seo, Jeong Yeon; Lee, Sang Hyuk; Baek, Hae Lim; Lee, Moon Sung; Park, Dong Il

2017-05-21

To evaluate the short health scale (SHS), a new, simple, four-part visual analogue scale questionnaire that is designed to assess the impact of inflammatory bowel disease (IBD) on health-related quality of life (HRQOL), in Korean-speaking patients with IBD. The SHS was completed by 256 patients with Crohn's disease (CD) and ulcerative colitis (UC). Individual SHS items were correlated with inflammatory bowel disease questionnaire (IBDQ) dimensions and with disease activity to assess validity. Test-retest reliability, responsiveness and patient or disease characteristics with probable association with high SHS scores were analyzed. Of 256 patients with IBD, 139 (54.3%) had UC and 117 (45.7%) had CD. The correlation coefficients between SHS questions about "symptom burden", "activities of daily living", and "disease-related worry" and their corresponding dimensions in the IBDQ ranged from 0.62 to 0.71, compared with correlation coefficients ranging from -0.45 to -0.61 for their non-corresponding dimensions. There was a stepwise increase in SHS scores, with increasing disease activity in both CD and UC (all P values < 0.001). Reliability was confirmed with test-retest correlations ranging from 0.68 to 0.90 (all P values < 0.001). Responsiveness was confirmed with the patients who remained in remission. Their SHS scores remained unchanged, except for the SHS dimension "disease-related worry". In the multivariate analysis, female sex was associated with worse "general well-being" (OR = 2.28, 95%CI: 1.02-5.08) along with worse disease activity. The SHS is a valid and reliable measure of HRQOL in Korean-speaking patients with IBD.

Single-Photon-Sensitive HgCdTe Avalanche Photodiode Detector

NASA Technical Reports Server (NTRS)

Huntington, Andrew

2013-01-01

The purpose of this program was to develop single-photon-sensitive short-wavelength infrared (SWIR) and mid-wavelength infrared (MWIR) avalanche photodiode (APD) receivers based on linear-mode HgCdTe APDs, for application by NASA in light detection and ranging (lidar) sensors. Linear-mode photon-counting APDs are desired for lidar because they have a shorter pixel dead time than Geiger APDs, and can detect sequential pulse returns from multiple objects that are closely spaced in range. Linear-mode APDs can also measure photon number, which Geiger APDs cannot, adding an extra dimension to lidar scene data for multi-photon returns. High-gain APDs with low multiplication noise are required for efficient linear-mode detection of single photons because of APD gain statistics -- a low-excess-noise APD will generate detectible current pulses from single photon input at a much higher rate of occurrence than will a noisy APD operated at the same average gain. MWIR and LWIR electron-avalanche HgCdTe APDs have been shown to operate in linear mode at high average avalanche gain (M > 1000) without excess multiplication noise (F = 1), and are therefore very good candidates for linear-mode photon counting. However, detectors fashioned from these narrow-bandgap alloys require aggressive cooling to control thermal dark current. Wider-bandgap SWIR HgCdTe APDs were investigated in this program as a strategy to reduce detector cooling requirements.

Critical consciousness, racial and gender discrimination, and HIV disease markers in African American women with HIV.

PubMed

Kelso, Gwendolyn A; Cohen, Mardge H; Weber, Kathleen M; Dale, Sannisha K; Cruise, Ruth C; Brody, Leslie R

2014-07-01

Critical consciousness, the awareness of social oppression, is important to investigate as a buffer against HIV disease progression in HIV-infected African American women in the context of experiences with discrimination. Critical consciousness comprises several dimensions, including social group identification, discontent with distribution of social power, rejection of social system legitimacy, and a collective action orientation. The current study investigated self-reported critical consciousness as a moderator of perceived gender and racial discrimination on HIV viral load and CD4+ cell count in 67 African American HIV-infected women. Higher critical consciousness was found to be related to higher likelihood of having CD4+ counts over 350 and lower likelihood of detectable viral load when perceived racial discrimination was high, as revealed by multiple logistic regressions that controlled for highly active antiretroviral therapy (HAART) adherence. Multiple linear regressions showed that at higher levels of perceived gender and racial discrimination, women endorsing high critical consciousness had a larger positive difference between nadir CD4+ (lowest pre-HAART) and current CD4+ count than women endorsing low critical consciousness. These findings suggest that raising awareness of social oppression to promote joining with others to enact social change may be an important intervention strategy to improve HIV outcomes in African American HIV-infected women who report experiencing high levels of gender and racial discrimination.

Critical Consciousness, Racial and Gender Discrimination, and HIV Disease Markers in African American Women with HIV

PubMed Central

Kelso, Gwendolyn A.; Cohen, Mardge H.; Weber, Kathleen M.; Dale, Sannisha K.; Cruise, Ruth C.; Brody, Leslie R.

2014-01-01

Critical consciousness, the awareness of social oppression, is important to investigate as a buffer against HIV disease progression in HIV-infected African American women in the context of experiences with discrimination. Critical consciousness comprises several dimensions, including social group identification, discontent with distribution of social power, rejection of social system legitimacy, and a collective action orientation. The current study investigated self-reported critical consciousness as a moderator of perceived gender and racial discrimination on HIV viral load and CD4+ cell count in 67 African American HIV-infected women. Higher critical consciousness was found to be related to higher likelihood of having CD4+ counts over 350 and lower likelihood of detectable viral load when perceived racial discrimination was high, as revealed by multiple logistic regressions that controlled for highly active antiretroviral therapy (HAART) adherence. Multiple linear regressions showed that at higher levels of perceived gender and racial discrimination, women endorsing high critical consciousness had a larger positive difference between nadir CD4+ (lowest pre-HAART) and current CD4+ count than women endorsing low critical consciousness. These findings suggest that raising awareness of social oppression to promote joining with others to enact social change may be an important intervention strategy to improve HIV outcomes in African American HIV-infected women who report experiencing high levels of gender and racial discrimination. PMID:24077930

Reduction of across-wafer CDU via constrained optimization of a multichannel PEB plate controller based on in-situ measurements of thermal time constants

NASA Astrophysics Data System (ADS)

Tiffany, Jason E.; Cohen, Barney M.

2004-05-01

As line widths approach 90nm node in volume production, post exposure bake (PEB) uniformity becomes a much larger component of the across wafer critical dimension uniformity (CDU). In production, the need for PEB plate matching has led to novel solutions such as plate specific dose offsets. This type of correction does not help across wafer CDU. Due to unequal activation energies of the critical PEB processes, any thermal history difference can result in a corresponding CD variation. The rise time of the resist to the target temperature has been shown to affect CD, with the most critical time being the first 5-7 seconds. A typical PEB plate has multi-zone thermal control with one thermal sensor per zone. The current practice is to setup each plate to match the steady-state target temperature, ignoring any dynamic performance. Using an in-situ wireless RTD wafer, it is possible to characterize the dynamic performance, or time constant, of each RTD location on the sensing wafer. Constrained by the zone structure of the PEB plate, the proportional, integral and derivative (PID) settings of each controller channel could be optimized to reduce the variations in rise time across the RTD wafer, thereby reducing the PEB component of across wafer CDU.

Constructive thinking skills and impulsivity dimensions in conduct and substance use disorders: differences and relationships in an adolescents' sample.

PubMed

Urben, Sébastien; Suter, Maya; Pihet, Sandrine; Straccia, Claudio; Stéphan, Philippe

2015-06-01

Impact of conduct disorder (CD) and substance use disorder (SUD) on constructive thinking skills and impulsivity was explored. 71 offending adolescents were assessed for CD and SUD. Furthermore, the constructive thinking inventory, the immediate and delayed memory tasks and the UPPS impulsive behaviour scale were administered. Results showed that youths with CD, independently from SUD, presented higher personality impulsivity (urgency) and altered constructive thinking skills (categorical thinking and personal superstitious thinking). Furthermore, trait-impulsivity explained variation in constructive thinking skills. The implications of these results were discussed.

Compensation of flare-induced CD changes EUVL

DOEpatents

Bjorkholm, John E [Pleasanton, CA; Stearns, Daniel G [Los Altos, CA; Gullikson, Eric M [Oakland, CA; Tichenor, Daniel A [Castro Valley, CA; Hector, Scott D [Oakland, CA

2004-11-09

A method for compensating for flare-induced critical dimensions (CD) changes in photolithography. Changes in the flare level results in undesirable CD changes. The method when used in extreme ultraviolet (EUV) lithography essentially eliminates the unwanted CD changes. The method is based on the recognition that the intrinsic level of flare for an EUV camera (the flare level for an isolated sub-resolution opaque dot in a bright field mask) is essentially constant over the image field. The method involves calculating the flare and its variation over the area of a patterned mask that will be imaged and then using mask biasing to largely eliminate the CD variations that the flare and its variations would otherwise cause. This method would be difficult to apply to optical or DUV lithography since the intrinsic flare for those lithographies is not constant over the image field.

[Assessment of sulfasalazine and hydroxichloroqine hepatotoxicity in patients with rheumatic arthritis and isolated HBS-antigen positivity].

PubMed

Petrov, A V

2004-01-01

Findings were based on long-period survey (12-16 month) of 39 patients with rheumatoid arthritis (RA) and isolated persistent HBS-antigen. The patients were prescribed Hydroxichloroqine (H) and Sulfasolin (SF). Clinical data, laboratory tests, ultrasonic diagnostics to evaluate liver condition have been analyzed. HBs, Hbe-antigenes, DNA-virus B hepatitis blood test, nucleus dimensions, proliferative FGA response test and immune CD 8+, CD 14+ and CD 16+ cells to Fas-induced apoptosis were taken. SF therapy was found to be more hepatotoxic and likely to activate a latent virus B hepatitis as compared with Hydroxichloroqine and combine H and SF therapies. Triggering replication of virus B hepatitis occurs against a background of decreasing in functional activity of CD 14+ and CD 16+ cells. The immune critical level needed to activate VHB was determined.

Effects of gas flow rate on the etch characteristics of a low- k sicoh film with an amorphous carbon mask in dual-frequency CF4/C4F8/Ar capacitively-coupled plasmas

NASA Astrophysics Data System (ADS)

Kwon, Bong-Soo; Lee, Hea-Lim; Lee, Nae-Eung; Kim, Chang-Young; Choi, Chi Kyu

2013-01-01

Highly selective nanoscale etching of a low-dielectric constant (low- k) organosilicate (SiCOH) layer using a mask pattern of chemical-vapor-deposited (CVD) amorphous carbon layer (ACL) was carried out in CF4/C4F8/Ar dual-frequency superimposed capacitively-coupled plasmas. The etching characteristics of the SiCOH layers, such as the etch rate, etch selectivity, critical dimension (CD), and line edge roughness (LER) during the plasma etching, were investigated by varying the C4F8 flow rate. The C4F8 gas flow rate primarily was found to control the degree of polymerization and to cause variations in the selectivity, CD and LER of the patterned SiCOH layer. Process windows for ultra-high etch selectivity of the SiCOH layer to the CVD ACL are formed due to the disproportionate degrees of polymerization on the SiCOH and the ACL surfaces.

Bioinspired greigite magnetic nanocrystals: chemical synthesis and biomedicine applications

PubMed Central

Feng, Mei; Lu, Yang; Yang, Yuan; Zhang, Meng; Xu, Yun-Jun; Gao, Huai-Ling; Dong, Liang; Xu, Wei-Ping; Yu, Shu-Hong

2013-01-01

Large scale greigite with uniform dimensions has stimulated significant demands for applications such as hyperthermia, photovoltaics, medicine and cell separation, etc. However, the inhomogeneity and hydrophobicity for most of the as prepared greigite crystals has limited their applications in biomedicine. Herein, we report a green chemical method utilizing β-cyclodextrin (β-CD) and polyethylene glycol (PEG) to synthesize bioinspired greigite (Fe3S4) magnetic nanocrystals (GMNCs) with similar structure and magnetic property of magnetosome in a large scale. β-CD and PEG is responsible to control the crystal phase and morphology, as well as to bound onto the surface of nanocrystals and form polymer layers. The GMNCs exhibit a transverse relaxivity of 94.8 mM−1s−1 which is as high as iron oxide nanocrystals, and an entrapment efficiency of 58.7% for magnetic guided delivery of chemotherapeutic drug doxorubicin. Moreover, enhanced chemotherapeutic treatment of mice tumor was obtained via intravenous injection of doxorubicin loaded GMNCs. PMID:24141204

Deep machine learning based Image classification in hard disk drive manufacturing (Conference Presentation)

NASA Astrophysics Data System (ADS)

Rana, Narender; Chien, Chester

2018-03-01

A key sensor element in a Hard Disk Drive (HDD) is the read-write head device. The device is complex 3D shape and its fabrication requires over thousand process steps with many of them being various types of image inspection and critical dimension (CD) metrology steps. In order to have high yield of devices across a wafer, very tight inspection and metrology specifications are implemented. Many images are collected on a wafer and inspected for various types of defects and in CD metrology the quality of image impacts the CD measurements. Metrology noise need to be minimized in CD metrology to get better estimate of the process related variations for implementing robust process controls. Though there are specialized tools available for defect inspection and review allowing classification and statistics. However, due to unavailability of such advanced tools or other reasons, many times images need to be manually inspected. SEM Image inspection and CD-SEM metrology tools are different tools differing in software as well. SEM Image inspection and CD-SEM metrology tools are separate tools differing in software and purpose. There have been cases where a significant numbers of CD-SEM images are blurred or have some artefact and there is a need for image inspection along with the CD measurement. Tool may not report a practical metric highlighting the quality of image. Not filtering CD from these blurred images will add metrology noise to the CD measurement. An image classifier can be helpful here for filtering such data. This paper presents the use of artificial intelligence in classifying the SEM images. Deep machine learning is used to train a neural network which is then used to classify the new images as blurred and not blurred. Figure 1 shows the image blur artefact and contingency table of classification results from the trained deep neural network. Prediction accuracy of 94.9 % was achieved in the first model. Paper covers other such applications of the deep neural network in image classification for inspection, review and metrology.

Mid-infrared Plasmonic Circular Dichroism Generated by Graphene Nanodisk Assemblies.

PubMed

Kong, Xiang-Tian; Zhao, Runbo; Wang, Zhiming; Govorov, Alexander O

2017-08-09

It is very interesting to bring plasmonic circular dichroism spectroscopy to the mid-infrared spectral interval, and there are two reasons for this. This spectral interval is very important for thermal bioimaging, and simultaneously, this spectral range includes vibrational lines of many chiral biomolecules. Here we demonstrate that graphene plasmons indeed offer such opportunity. In particular, we show that chiral graphene assemblies consisting of a few graphene nanodisks can generate strong circular dichroism (CD) in the mid-infrared interval. The CD signal is generated due to the plasmon-plasmon coupling between adjacent nanodisks in the specially designed chiral graphene assemblies. Because of the large dimension mismatch between the thickness of a graphene layer and the incoming light's wavelength, three-dimensional configurations with a total height of a few hundred nanometers are necessary to obtain a strong CD signal in the mid-infrared range. The mid-infrared CD strength is mainly governed by the total dimensions (total height and helix scaffold radius) of the graphene nanodisk assembly and by the plasmon-plasmon interaction strength between its constitutive nanodisks. Both positive and negative CD bands can be observed in the graphene assembly array. The frequency interval of the plasmonic CD spectra overlaps with the vibrational modes of some important biomolecules, such as DNA and many different peptides, giving rise to the possibility of enhancing the vibrational optical activity of these molecular species by attaching them to the graphene assemblies. Simultaneously the spectral range of chiral mid-infrared plasmons in our structures appears near the typical wavelength of the human-body thermal radiation, and therefore, our chiral metastructures can be potentially utilized as optical components in thermal imaging devices.

Effect of cadmium-selenide quantum dots on the conductivity and photoconductivity of nanocrystalline indium oxide

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

Il’in, A. S., E-mail: as.ilin@physics.msu.ru; Fantina, N. P.; Martyshov, M. N.

The effect of cadmium-selenide quantum dots addition on the electrical and photoelectric properties of nanocrystalline indium oxide with nanocrystal dimensions in the range from 7 to 40 nm is studied. By impedance spectroscopy, it is shown that the addition of quantum dots substantially influences the resistance of interfaces between In{sub 2}O{sub 3} crystals. A change in the character of the photoconductivity spectrum of In{sub 2}O{sub 3} upon the addition of CdSe quantum dots is detected, and it is established that this change depends on the In{sub 2}O{sub 3}-nanocrystal dimensions. An energy band diagram is proposed to explain the observed changemore » in the photoconductivity spectrum of In{sub 2}O{sub 3} upon the addition of CdSe quantum dots.« less

Spasmodic torticollis: the dental connection.

PubMed

Sims, Anthony B; Stack, Brendan C; Demerjian, G Gary

2012-07-01

Spasmodic torticollis or cervical dystonia (CD) is the most common form of focal dystonia and is characterized by sustained abnormal muscle contractions in the head and neck area resulting in abnormal positioning or posturing of the head. The dystonic muscle spasms associated with spasmodic torticollis may affect any combination of neck muscles. Three cases are reported of spasmodic torticollis that were treated by a dental appliance with individual varying occlusal heights to open the maxillomandibular vertical dimension. Upon increasing the vertical dimension of occlusion, there was a slowing and/or discontinuance of the symptoms of cervical dystonia. The proposed hypothesis for this reversal is that there may be neuritis of the auriculotemporal branch of the trigeminal nerve, which has direct input into the reticular formation (RF), and it may activate the cells of the pontine region of the RF known for the control and deviation of head posture. There is growing clinical evidence that temporomandibular joint (TMJ) dysfunction may be a factor in this neurological and painful disorder when it coexists.

Multipronged CD4 T cell effector and memory responses cooperate to provide potent immunity against respiratory virus

PubMed Central

Strutt, Tara M.; McKinstry, K. Kai; Marshall, Nikki B.; Vong, Allen M.; Dutton, Richard W.; Swain, Susan L.

2014-01-01

Summary Over the last decade, the known spectrum of CD4 T cell effect or subsets has become much broader and it has become clear that there are multiple dimensions by which subsets with a particular cytokine commitment can be further defined, including their stage of differentiation, their location and most importantly, their ability to carryout discrete functions. Here we focus on our studies that highlight the synergy among discrete subsets, especially those defined by helper and cytotoxic function, in mediating viral protection and on distinctions between CD4 T cell effectors located in spleen, draining lymph node, and in tissue sites of infection. What emerges is a surprising multiplicity of CD4 T cell functions that indicate a large arsenal of mechanisms by which CD4 T cells act to combat viruses. PMID:23947353

Size, surface, and compositional tuning of the electronic and photocatalytic properties of II-VI quantum-size semiconductor nanocrystals

NASA Astrophysics Data System (ADS)

Korgel, Brian Allan

1997-11-01

Phosphatidylcholine vesicles provide reaction compartments for synthesis of size-quantized CdS nanocrystals of dimension predicted to within ±2 A based on initial encapsulated CdClsb2 concentration and vesicle diameter. Vesicle formation by detergent dialysis of phosphatidylcholine/hexylglucoside mixed micelles yields highly monodisperse lipid capsules within which monodisperse CdS nanoparticles are precipitated with sulfide. Size-quantized CdS nanocrystals, with diameters ranging from 20 to 60 A, have been produced with typical standard deviations about the mean diameter of ±8% as measured by transmission electron microscopy. By including ZnClsb2 or HgClsb2 in the dialyzate prior to vesicle formation, quantum-sized Znsb{y}Cdsb{1-y}S or Hgsb{y}Cdsb{1-y}S nanocrystal alloys with controlled stoichiometry are generated. Spectrophotometric and spectrofluorimetric measurements are consistent with highly crystalline, monodisperse particles with few core or surface defects. The alloyed nanocrystal spectra shift consistently with composition indicating a high degree of compositional control. Measured exciton energies for CdS show excellent agreement with data in the literature. The empirical pseudopotential model presented by Ramakrishna and Friesner for a cubic CdS lattice, correcting for experimentally measured lattice contractions, best fits the data. Size-quantized CdS nanocrystals serve as photocatalysts for nitrate reduction at neutral pH under conditions that mimic illumination by sunlight with overall product quantum yields of up to 4% for {˜}20 A, amine-terminated particles. Due to the effects of quantum confinement on electron and hole redox potentials, photocatalyzed nitrate reduction rates depend strongly on the particle size, and the fastest reduction rates are observed with the smallest nanocrystals. Using a Tafel plot and the empirical pseudopotential model to estimate electron redox potentials, the apparent electron transfer coefficient and the apparent standard rate constant is estimated at 0.23 and 4.0× 10sp{-12} cm/sec, respectively, for amine-terminated particles. Nitrate adsorption is important in this system and the effect on photoreduction rates is described well by a Langmuir-Hinschelwood expression. Nitrate reduction rates are reduced two-fold or more on negatively charged, carboxy-terminated nanocrystals that electrostatically repel nitrate. Reaction rates are additionally influenced by competetive chloride adsorption and surface charge modification due to solution pH.

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

CRESSWELL,M.W.; ALLEN,R.A.; GHOSHTAGORE,R.N.

This paper describes the fabrication and measurement of the linewidths of the reference segments of cross-bridge resistors patterned in (100) Bonded and Etched Back Silicon-on-Insulator (BESOI) material. The critical dimensions (CD) of the reference segments of a selection of the cross-bridge resistor test structures were measured both electrically and by Scanning-Electron Microscopy (SEM) cross-section imaging. The reference-segment features were aligned with <110> directions in the BESOI surface material and had drawn linewidths ranging from 0.35 to 3.0 {micro}m. They were defined by a silicon micro-machining process which results in their sidewalls being atomically-planar and smooth and inclined at 54.737{degree} tomore » the surface (100) plane of the substrate. This (100) implementation may usefully complement the attributes of the previously-reported vertical-sidewall one for selected reference-material applications. For example, the non-orthogonal intersection of the sidewalls and top-surface planes of the reference-segment features may alleviate difficulties encountered with atomic-force microscope measurements. In such applications it has been reported that it may be difficult to maintain probe-tip control at the sharp 90{degree} outside corner of the sidewalls and the upper surface. A second application is refining to-down image-processing algorithms and checking instrument performance. Novel aspects of the (100) SOI implementation that are reported here include the cross-bridge resistor test-structure architecture and details of its fabrication. The long-term goal is to develop a technique for the determination of the absolute dimensions of the trapezoidal cross-sections of the cross-bridge resistors' reference segments, as a prelude to developing them for dimensional reference applications. This is believed to be the first report of electrical CD measurements made on test structures of the cross-bridge resistor type that have been patterned in (100) SOI material. The electrical CD results are compared with cross-section SEM measurements made on the same features.« less

Normal T-cell activation in elite controllers with preserved CD4+ T-cell counts.

PubMed

Bansal, Anju; Sterrett, Sarah; Erdmann, Nathan; Westfall, Andrew O; Dionne-Odom, Jodie; Overton, Edgar T; Goepfert, Paul A

2015-11-01

HIV elite controllers suppress HIV viremia without antiretroviral therapy (ART), yet previous studies demonstrated that elite controllers maintain an activated T-cell phenotype. Chronic immune activation has detrimental consequences and thus ART has been advocated for all elite controllers. However, elite controllers are not a clinically homogenous group. Since CD4% is among the best predictors of AIDS-related events, in the current study, we assessed whether this marker can be used to stratify elite controllers needing ART. Sixteen elite controllers were divided into two groups based on CD4% (EC > 40% and EC ≤40%), and T-cell subsets were analyzed for markers of memory/differentiation (CD45RA, CCR7, CD28), activation (CD38/HLA-DR), immunosenescence (CD57), costimulation (CD73, CD28) and exhaustion (PD-1, CD160, Tim-3). Monocyte subsets (CD14, CD16) were also analyzed and sCD14 levels were quantified using ELISA. In the EC group, expression of activation, exhaustion, and immunosensescence markers on T cells were significantly reduced compared with the EC group and similar to the seronegative controls. The EC group expressed higher levels of costimulatory molecules CD28 and CD73 and had lower levels of monocyte activation (HLA-DR expression) with a reduced frequency of inflammatory monocyte (CD14 CD16) subset. Furthermore, the EC group maintained a stable CD4% during a median follow-up of 6 years. Elite controllers with preserved CD4T cells (EC) have normal T-cell and monocyte phenotypes and therefore may have limited benefit from ART. CD4% can be an important marker for evaluating future studies aimed at determining the need for ART in this group of individuals.

Reverse remodeling and the mechanism of mitral regurgitation improvement in patients with dilated cardiomyopathy.

PubMed

Kuperstein, Rafael; Blechman, Ido; Ben Zekry, Sagit; Klempfner, Robert; Freimark, Dov; Arad, Michael

2015-01-01

Functional mitral regurgitation (MR) is a common finding in dilated cardiomyopathy. Left ventricular (LV) reverse remodeling with LV size reduction and improvement in LV function is a well recognized phenomenon. We aimed to evaluate the impact of LV remodeling on the mechanism leading to functional MR. Among 188 patients with non-ischemic dilated cardiomyopathy, 10 patients significantly improved their LV function, reduced LV size and MR severity during follow-up (RRMR). A comparison was made between their baseline and follow-up echocardiographic examinations and to a matched-control group of patients who did not improve (no RRMR). LV and left atrium (LA) dimensions and volumes, LV mass (LVM), LV ejection fraction (LVEF) (Simpsons), sphericity index (SI), mitral valve tenting area (TA) coaptation distance (CD), effective regurgitant orifice (ERO), and regurgitant volume were calculated. Multivariable analysis was performed in order to evaluate which echocardiographic parameters related to MR improvement in reverse remodeling. LV and LA dimensions and volumes, LVM, SI, TA, CD, ERO and right ventricle, in the RRMR group significantly decreased at follow-up (p < 0.04 for all). When compared to no RRMR, despite a similar ERO (0.2 ± 0.05 vs. 0.2 ± 0.08, p = 0.13) and a larger regurgitant volume (38 ± 9 vs. 29 ± 8 mL, p = 0.05) and despite similar clinical characteristics and medical treatment we found significantly higher LVEF, smaller LV dimensions and volumes, smaller LVM and SI in the RRMR group (p < 0.05 for all). On multivariable analysis the SI was the sole predictor of RRMR (p = 0.04, OR = 0.76, CI 0.58-0.99). Reverse remodeling characterized by improvement in LV function, reduction in LV size and an associated reduction in MR severity is related to LV SI at baseline.

Flexible, High-Speed CdSe Nanocrystal Integrated Circuits.

PubMed

Stinner, F Scott; Lai, Yuming; Straus, Daniel B; Diroll, Benjamin T; Kim, David K; Murray, Christopher B; Kagan, Cherie R

2015-10-14

We report large-area, flexible, high-speed analog and digital colloidal CdSe nanocrystal integrated circuits operating at low voltages. Using photolithography and a newly developed process to fabricate vertical interconnect access holes, we scale down device dimensions, reducing parasitic capacitances and increasing the frequency of circuit operation, and scale up device fabrication over 4 in. flexible substrates. We demonstrate amplifiers with ∼7 kHz bandwidth, ring oscillators with <10 μs stage delays, and NAND and NOR logic gates.

Live-monitoring of Te inclusions laser-induced thermo-diffusion and annealing in CdZnTe crystals

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

Zappettini, A.; Zambelli, N.; Benassi, G.

2014-06-23

The presence of Te inclusions is one of the main factors limiting performances of CdZnTe crystals as X-ray detectors. We show that by means of infrared laser radiation it is possible to move and anneal tellurium inclusions exploiting a thermo-diffusion mechanism. The process is studied live during irradiation by means of an optical microscope equipment. Experimental conditions, and, in particular, energy laser fluence, for annealing inclusions of different dimensions are determined.

Three-dimensional profile extraction from CD-SEM image and top/bottom CD measurement by line-edge roughness analysis

NASA Astrophysics Data System (ADS)

Yamaguchi, Atsuko; Ohashi, Takeyoshi; Kawasaki, Takahiro; Inoue, Osamu; Kawada, Hiroki

2013-04-01

A new method for calculating critical dimension (CDs) at the top and bottom of three-dimensional (3D) pattern profiles from a critical-dimension scanning electron microscope (CD-SEM) image, called as "T-sigma method", is proposed and evaluated. Without preparing a library of database in advance, T-sigma can estimate a feature of a pattern sidewall. Furthermore, it supplies the optimum edge-definition (i.e., threshold level for determining edge position from a CDSEM signal) to detect the top and bottom of the pattern. This method consists of three steps. First, two components of line-edge roughness (LER); noise-induced bias (i.e., LER bias) and unbiased component (i.e., bias-free LER) are calculated with set threshold level. Second, these components are calculated with various threshold values, and the threshold-dependence of these two components, "T-sigma graph", is obtained. Finally, the optimum threshold value for the top and the bottom edge detection are given by the analysis of T-sigma graph. T-sigma was applied to CD-SEM images of three kinds of resist-pattern samples. In addition, reference metrology was performed with atomic force microscope (AFM) and scanning transmission electron microscope (STEM). Sensitivity of CD measured by T-sigma to the reference CD was higher than or equal to that measured by the conventional edge definition. Regarding the absolute measurement accuracy, T-sigma showed better results than the conventional definition. Furthermore, T-sigma graphs were calculated from CD-SEM images of two kinds of resist samples and compared with corresponding STEM observation results. Both bias-free LER and LER bias increased as the detected edge point moved from the bottom to the top of the pattern in the case that the pattern had a straight sidewall and a round top. On the other hand, they were almost constant in the case that the pattern had a re-entrant profile. T-sigma will be able to reveal a re-entrant feature. From these results, it is found that T-sigma method can provide rough cross-sectional pattern features and achieve quick, easy and accurate measurements of top and bottom CD.

Incremental healthcare resource utilization and costs in US patients with Cushing's disease compared with diabetes mellitus and population controls.

PubMed

Broder, Michael S; Neary, Maureen P; Chang, Eunice; Ludlam, William H

2015-12-01

Resource utilization and costs in Cushing's disease (CD) patients have not been studied extensively. We compared CD patients with diabetes mellitus (DM) patients and population-based controls to characterize differences in utilization and costs. Using 2008-2012 MarketScan® database, we identified three patient groups: (1) CD patients; (2) DM patients; and (3) population-based control patients without CD. DM and control patients were matched to CD patients by age, gender, region, and review year in a 2:1 ratio. Outcomes included annual healthcare resource utilization and costs. There were 1852 CD patients, 3704 DM patients and 3704 controls. Mean age was 42.9 years; 78.2 % were female. CD patients were hospitalized more frequently (19.3 %) than DM patients (11.0 %, p < .001) or controls (5.6 %, p < .001). CD patients visited the ED more frequently (25.4 %) than DM patients (21.1 %, p < .001) or controls (14.3 %, p < .001). CD patients had more office visits than DM patients (19.1 vs. 10.7, p < .001) or controls (7.1, p < .001). CD patients on average filled more prescriptions than DM patients (51.7 vs. 42.7, p < .001) or controls (20.5, p < .001). Mean total healthcare costs for CD patients were $26,269 versus $12,282 for DM patients (p < .001) and $5869 for controls (p < .001). CD patients had significantly higher annual rates of healthcare resource utilization compared to matched DM patients and population controls without CD. CD patient costs were double DM costs and quadruple control costs. This study puts into context the additional burdens of CD over DM, a common, chronic endocrine condition affecting multiple organ systems, and population controls.

Chirality controlled responsive self-assembled nanotubes in water† †Electronic supplementary information (ESI) available: Detailed experimental procedures and analyses, UV-vis absorption and CD spectroscopy, cryo-TEM and widefield microscopy. See DOI: 10.1039/c6sc02935c Click here for additional data file.

PubMed Central

van Dijken, D. J.; Štacko, P.; Stuart, M. C. A.; Browne, W. R.

2017-01-01

The concept of using chirality to dictate dimensions and to store chiral information in self-assembled nanotubes in a fully controlled manner is presented. We report a photoresponsive amphiphile that co-assembles with its chiral counterpart to form nanotubes and demonstrate how chirality can be used to effect the formation of either micrometer long, achiral nanotubes or shorter (∼300 nm) chiral nanotubes that are bundled. The nature of these assemblies is studied using a variety of spectroscopic and microscopic techniques and it is shown that the tubes can be disassembled with light, thereby allowing the chiral information to be erased. PMID:28451300

The use of isotypic control antibodies in the analysis of CD3+ and CD3+, CD4+ lymphocyte subsets by flow cytometry. Are they really necessary?

PubMed

Sreenan, J J; Tbakhi, A; Edinger, M G; Tubbs, R R

1997-02-01

Isotypic control reagents are defined as irrelevant antibodies of the same immunoglobulin class as the relevant reagent antibody in a flow cytometry panel. The use of the isotypic control antibody has been advocated as a necessary quality control measure in analysis of flow cytometry. The purpose of this study was to determine the necessity of an isotypic control antibody in the analysis of CD3+ and CD3+, CD4+ lymphocyte subsets. We performed a prospective study of 46 consecutive patient samples received for lymphocyte subset analysis to determine the need for the isotypic control. For each sample, a sham buffer (autocontrol) and isotypic control reagent were stained for three-color immunofluorescence, processed, and identically analyzed with Attractors software. The Attractors software allowed independent, multiparametric, simultaneous gating; was able to identically and reproducibly process each list mode file; and yielded population data in spreadsheet form. Statistical analysis (Fisher's z test) revealed no difference between the CD3+ autocontrol and CD3+ isotypic control (correlation = 1, P < .0001) or between the CD3+, CD4+ autocontrol and the CD3+, CD4+ isotypic control (correlation = 1, P < .0001). The elimination of the isotypic control reagent resulted in a total cost savings of $3.36 per test. Additionally, the subtraction of isotypic background can artifactually depress population enumeration. The use of an isotypic control antibody is not necessary to analyze flow cytometric data that result in discrete cell populations, such as CD3+ and CD3+, CD4+ lymphocyte subsets. The elimination of this unnecessary quality control measure results in substantial cost savings.

Neural abnormalities in early-onset and adolescence-onset conduct disorder.

PubMed

Passamonti, Luca; Fairchild, Graeme; Goodyer, Ian M; Hurford, Georgina; Hagan, Cindy C; Rowe, James B; Calder, Andrew J

2010-07-01

Conduct disorder (CD) is characterized by severe antisocial behavior that emerges in childhood (early-onset CD [EO-CD]) or adolescence (adolescence-onset CD [AO-CD]). Early-onset CD is proposed to have a neurodevelopmental basis, whereas AO-CD is thought to emerge owing to social mimicry of deviant peers. However, this developmental taxonomic theory is debated after reports of neuropsychological impairments in both CD subtypes. A critical, although unaddressed, issue is whether these subtypes present similar or distinct neurophysiological profiles. Hence, we investigated neurophysiological responses to emotional and neutral faces in regions associated with antisocial behavior (ie, the amygdala, ventromedial prefrontal cortex, insula, and orbitofrontal cortex) in individuals with EO-CD and AO-CD and in healthy control subjects. To investigate whether EO-CD and AO-CD subjects show neurophysiological abnormalities. Case-control study. Government research institute, university department. Seventy-five male adolescents and young adults aged 16 to 21 years, including 27 with EO-CD, 25 with AO-CD, and 23 healthy controls. Main Outcome Measure Neural activations measured by functional magnetic resonance imaging while participants viewed angry, sad, and neutral faces. Comparing angry vs neutral faces, participants with both CD subtypes displayed reduced responses in regions associated with antisocial behavior compared with controls; differences between the CD subtypes were not significant. Comparing each expression with fixation baseline revealed an abnormal (increased) amygdala response to neutral but not angry faces in both groups of CD relative to controls. For sad vs neutral faces, reduced amygdala activation was observed in EO-CD relative to AO-CD and control participants. Comparing each expression with fixation revealed hypoactive amygdala responses to sadness in individuals with EO-CD relative to AO-CD participants and controls. These findings were not accounted for by attention-deficit/hyperactivity disorder symptoms. Neurophysiological abnormalities are observed in both CD subtypes, contrary to the developmental taxonomic theory of CD. Additional amygdala hypofunction in relation to sad expressions might indicate why EO-CD is more severe and persistent than AO-CD.

The protective effect of character maturity in child aggressive antisocial behavior.

PubMed

Kerekes, Nóra; Falk, Örjan; Brändström, Sven; Anckarsäter, Henrik; Råstam, Maria; Hofvander, Björn

2017-07-01

Childhood aggressive antisocial behavior (CD) is one of the strongest predictors of mental health problems and criminal behavior in adulthood. The aims of this study were to describe personality profiles in children with CD, and to determine the strength of association between defined neurodevelopmental symptoms, dimensions of character maturity and CD. A sample of 1886 children with a close to equal distribution of age (9 or 12) and gender, enriched for neurodevelopmental and psychiatric problems were selected from the nationwide Child and Adolescent Twin Study in Sweden. Their parents rated them according to the Junior Temperament and Character Inventory following a telephone interview during which information about the children's development and mental health was assessed with the Autism-Tics, AD/HD and other Comorbidities inventory. Scores on the CD module significantly and positively correlated with scores on the Novelty Seeking temperament dimension and negatively with scores on character maturity (Self-Directedness and Cooperativeness). In the group of children with either neurodevelopmental or behavioral problems, the prevalence of low or very low character maturity was 50%, while when these two problems coexisted the prevalence of low or very low character maturity increased to 70%. Neurodevelopmental problems (such as: oppositional defiant disorder, symptoms of attention deficit/hyperactivity disorder and autism spectrum disorder) and low scores on character maturity emerged as independently significant predictors of CD; in a multivariable model, only oppositional defiant symptoms and impulsivity significantly increased the risk for coexisting CD while a mature self-agency in a child (Self-Directedness) remained a significant protective factor. These results suggest that children's willpower, the capacity to achieve personally chosen goals may be an important protective factor - even in the presence of neurodevelopmental and psychiatric problems - against progressing into persistent negative outcomes, such as aggressive antisocial behaviors. Copyright © 2017 Elsevier Inc. All rights reserved.

Optics for Processes, Products and Metrology

NASA Astrophysics Data System (ADS)

Mather, George

1999-04-01

Optical physics has a variety of applications in industry, including process inspection, coatings development, vision instrumentation, spectroscopy, and many others. Optics has been used extensively in the design of solar energy collection systems and coatings, for example. Also, with the availability of good CCD cameras and fast computers, it has become possible to develop real-time inspection and metrology devices that can accommodate the high throughputs encountered in modern production processes. More recently, developments in moiré interferometry show great promise for applications in the basic metals and electronics industries. The talk will illustrate applications of optics by discussing process inspection techniques for defect detection, part dimensioning, birefringence measurement, and the analysis of optical coatings in the automotive, glass, and optical disc industries. In particular, examples of optical techniques for the quality control of CD-R, MO, and CD-RW discs will be presented. In addition, the application of optical concepts to solar energy collector design and to metrology by moiré techniques will be discussed. Finally, some of the modern techniques and instruments used for qualitative and quantitative material analysis will be presented.

Abdominal Pain-Associated Functional Gastrointestinal Disorder Prevalence in Children and Adolescents with Celiac Disease on Gluten-Free Diet: A Multinational Study.

PubMed

Saps, Miguel; Sansotta, Naire; Bingham, Sean; Magazzu, Giuseppe; Grosso, Caterina; Romano, Simone; Pusatcioglu, Cenk; Guandalini, Stefano

2017-03-01

To test the hypothesis that children with celiac disease (CD) on gluten-free diet are at increased risk of abdominal pain (AP) associated-functional gastrointestinal disorders (FGIDs). This was a multinational cross-sectional study performed from 2014 to 2015. Patients 4-18 years of age with CD on gluten-free diet for longer than 6 months were recruited from pediatric CD clinics in US and Italy. Control groups included siblings of children with CD (with normal tissue transglutaminase levels) and unrelated controls. Subjects or parents completed the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III. Children (n = 289) were recruited (55% US, 45% Italy): 96 children with CD, 96 sibling controls, and 97 unrelated controls. Chronic AP was present in 30 (30.9%) subjects with CD, 22 (22.7%) sibling controls, and 21 (21.6%) unrelated controls (P = .26 patients with CD vs siblings; P = .18 patients with CD vs unrelated; P = .96 siblings vs unrelated). AP-FGIDs were present in 8 (8.2%) subjects with CD, 8 (8.2%) sibling controls, and 2 (2.1%) unrelated controls (P = 1.00 subjects with CD vs sibling controls; P = .06 subjects with CD vs unrelated controls; P = .06 sibling controls vs unrelated controls). This multinational study evaluated the prevalence of chronic abdominal pain and AP-FGIDs in the pediatric population with CD. We found that subjects with CD and controls have a similar prevalence of chronic AP and AP-FGIDs. This suggests that not all types of gastrointestinal inflammation result in AP-FGIDs in children. Copyright © 2016 Elsevier Inc. All rights reserved.

Morphological and physiological changes exhibited by a Cd-resistant Dictyosphaerium chlorelloides strain and its cadmium removal capacity.

PubMed

Bartolomé, M C; Cortés, A A; Sánchez-Fortún, A; Garnica-Romo, M G; Sánchez-Carrillo, S; Sánchez-Fortún, Sebastián

2016-12-01

Changes induced on freshwater microalga Dictyosphaerium chlorelloides (Dc(wt)) acclimated in the laboratory until their survival in culture media enriched with cadmium 100 µM have been studied. Cadmium removal by living cells of this Cd-resistant (Dc(CdR100)) strain was tested in cultures exposed to 100 µM Cd during 30 days. Cell dimensions were measured under light microscopy, and cell growth was studied. Photosynthetic yield (ΦPSII) was analyzed and the photosynthetic oxygen development and respiration response was obtained. Results show that Dc(CdR100) strain exhibited significant cell morphology changes in comparison to Dc(wt) cells, which affected both surface area and cell biovolume. Malthusian fitness analysis showed that Dc(CdR100) strain living in Cd-enriched culture had developed a lower capacity of nearly 50% growth, and its photosynthetic oxygen development and respiration response were significantly reduced in both light and dark photosynthetic phases. Dc(CdR100) strain showed a very high capacity to remove cadmium from the aquatic environment (over 90%), although most of the removed heavy metal (≈70%) is adhered to the cell wall. These specific characteristics of Dc(CdR100) cells suggest the possibility of using this strain in conjunction with Dc(wt) strain as bioelements into a dual-head biosensor, and in bioremediation processes on freshwater polluted with Cd.

Type of monocyte immunomagnetic separation affects the morphology of monocyte-derived dendritic cells, as investigated by scanning electron microscopy.

PubMed

Kowalewicz-Kulbat, M; Ograczyk, E; Krawczyk, K; Rudnicka, W; Fol, M

2016-12-01

Dendritic cells (DCs) are increasingly being used for multiple applications and are useful tools for many immunotherapeutic strategies. The understanding of the possible impact of the DCs-generation methods on the biological capacities of these cells is therefore essential. Although the immunomagnetic separation is regarded as a fast and accurate method yielding cells with the high purity and efficiency, still little is known about its impact on the properties of the generated DCs. The aim of this study was to compare the morphology of the monocyte derived dendritic cells (MoDCs), generated from monocytes selected with anti-CD14 mAbs (positive separation) and treated with anti-CD3, -CD7, -CD16, -CD19, -CD56, -CD123, glycophorin A (negative separation), using laser scanning microscopy. We found that the type of the immunomagnetic separation method used strongly influences the shape and cell dimension of the MoDCs. We observed that the height of both immature and LPS-matured DCs generated from monocytes isolated by negative separation was significantly higher compared to the cells obtained by positive separation. Copyright © 2016 Elsevier B.V. All rights reserved.

Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia

PubMed Central

Johnson, Susan; Eller, Michael; Teigler, Jeffrey E.; Maloveste, Sebastien M.; Schultz, Bruce T.; Soghoian, Damien Z.; Lu, Richard; Oster, Alexander F.; Chenine, Agnès-Laurence; Alter, Galit; Dittmer, Ulf; Marovich, Mary; Robb, Merlin L.; Michael, Nelson L.; Bolton, Diane

2015-01-01

ABSTRACT CD4+ T cells play a pivotal role in the control of chronic viral infections. Recently, nontraditional CD4+ T cell functions beyond helper effects have been described, and a role for cytolytic CD4+ T cells in the control of HIV infection has been suggested. We define here the transcriptional, phenotypic, and functional profiles of HIV-specific cytolytic CD4+ T cells. Fluidigm BioMark and multiparameter flow cytometric analysis of HIV-specific cytolytic CD4+ T cells revealed a distinct transcriptional signature compared to Th1 CD4+ cells but shared similar features with HIV-specific cytolytic CD8+ T cells. Furthermore, HIV-specific cytolytic CD4+ T cells showed comparable killing activity relative to HIV-specific CD8+ T cells and worked cooperatively in the elimination of virally infected cells. Interestingly, we found that cytolytic CD4+ T cells emerge early during acute HIV infection and tightly follow acute viral load trajectory. This emergence was associated to the early viral set point, suggesting an involvement in early control, in spite of CD4 T cell susceptibility to HIV infection. Our data suggest cytolytic CD4+ T cells as an independent subset distinct from Th1 cells that show combined activity with CD8+ T cells in the long-term control of HIV infection. IMPORTANCE The ability of the immune system to control chronic HIV infection is of critical interest to both vaccine design and therapeutic approaches. Much research has focused on the effect of the ability of CD8+ T cells to control the virus, while CD4+ T cells have been overlooked as effectors in HIV control due to the fact that they are preferentially infected. We show here that a subset of HIV-specific CD4+ T cells cooperate in the cytolytic control of HIV replication. Moreover, these cells represent a distinct subset of CD4+ T cells showing significant transcriptional and phenotypic differences compared to HIV-specific Th1 cells but with similarities to CD8+ T cells. These findings are important for our understanding of HIV immunopathology. PMID:25972560

Automated mask and wafer defect classification using a novel method for generalized CD variation measurements

NASA Astrophysics Data System (ADS)

Verechagin, V.; Kris, R.; Schwarzband, I.; Milstein, A.; Cohen, B.; Shkalim, A.; Levy, S.; Price, D.; Bal, E.

2018-03-01

Over the years, mask and wafers defects dispositioning has become an increasingly challenging and time consuming task. With design rules getting smaller, OPC getting complex and scanner illumination taking on free-form shapes - the probability of a user to perform accurate and repeatable classification of defects detected by mask inspection tools into pass/fail bins is reducing. The critical challenging of mask defect metrology for small nodes ( < 30 nm) was reviewed in [1]. While Critical Dimension (CD) variation measurement is still the method of choice for determining a mask defect future impact on wafer, the high complexity of OPCs combined with high variability in pattern shapes poses a challenge for any automated CD variation measurement method. In this study, a novel approach for measurement generalization is presented. CD variation assessment performance is evaluated on multiple different complex shape patterns, and is benchmarked against an existing qualified measurement methodology.

Defect printability of ArF alternative phase-shift mask: a critical comparison of simulation and experiment

NASA Astrophysics Data System (ADS)

Ozawa, Ken; Komizo, Tooru; Ohnuma, Hidetoshi

2002-07-01

An alternative phase shift mask (alt-PSM) is a promising device for extending optical lithography to finer design rules. There have been few reports, however, on the mask's ability to identify phase defects. We report here an alt-PSM of a single-trench type with undercut for ArF exposure, with programmed phase defects used to evaluate defect printability by measuring aerial images with a Zeiss MSM193 measuring system. The experimental results are simulated using the TEMPEST program. First, a critical comparison of the simulation and the experiment is conducted. The actual measured topographies of quartz defects are used in the simulation. Moreover, a general simulation study on defect printability using an alt-PSM for ArF exposure is conducted. The defect dimensions, which produce critical CD errors, are determined by simulation that takes into account the full 3-dimensional structure of phase defects as well as a simplified structure. The critical dimensions of an isolated bump defect identified by the alt-PSM of a single-trench type with undercut for ArF exposure are 300 nm in bottom dimension and 74 degrees in height (phase) for the real shape, where the depth of wet-etching is 100 nm and the CD error limit is +/- 5 percent.

Differential Impact of In Vivo CD8+ T Lymphocyte Depletion in Controller versus Progressor Simian Immunodeficiency Virus-Infected Macaques.

PubMed

Chowdhury, Ankita; Hayes, Timothy L; Bosinger, Steven E; Lawson, Benton O; Vanderford, Thomas; Schmitz, Joern E; Paiardini, Mirko; Betts, Michael; Chahroudi, Ann; Estes, Jacob D; Silvestri, Guido

2015-09-01

Numerous studies have demonstrated that CD8(+) T lymphocytes suppress virus replication during human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection. However, the mechanisms underlying this activity of T cells remain incompletely understood. Here, we conducted CD8(+) T lymphocyte depletion in 15 rhesus macaques (RMs) infected intravenously (i.v.) with SIVmac239. At day 70 postinfection, the animals (10 progressors with high viremia and 5 controllers with low viremia) were CD8 depleted by i.v. administration of the antibody M-T807R1. As expected, CD8 depletion resulted in increased virus replication, more prominently in controllers than progressors, which correlated inversely with predepletion viremia. Of note, the feature of CD8(+) T lymphocyte predepletion that correlated best with the increase in viremia postdepletion was the level of CD8(+) T-bet(+) lymphocytes. We next found that CD8 depletion resulted in a homogenous increase of SIV RNA in superficial and mesenteric lymph nodes, spleen, and the gastrointestinal tract of both controllers and progressors. Interestingly, the level of SIV DNA increased postdepletion in both CD4(+) central memory T lymphocytes (TCM) and CD4(+) effector memory T lymphocytes (TEM) in progressor RMs but decreased in the CD4(+) TCM of 4 out of 5 controllers. Finally, we found that CD8 depletion is associated with a greater increase in CD4(+) T lymphocyte activation (measured by Ki-67 expression) in controllers than in progressors. Overall, these data reveal a differential impact of CD8(+) T lymphocyte depletion between controller and progressor SIV-infected RMs, emphasizing the complexity of the in vivo antiviral role of CD8(+) T lymphocytes. In this study, we further dissect the impact of CD8(+) T lymphocytes on HIV/SIV replication during SIV infection. CD8(+) T lymphocyte depletion leads to a relatively homogenous increase in viral replication in peripheral blood and tissues. CD8(+) T lymphocyte depletion resulted in a more prominent increase in viral loads and CD4(+) T lymphocyte activation in controllers than in progressors. Interestingly, we found T-bet expression on CD8(+) T lymphocytes to be the best predictor of viral load increase following depletion. The levels of SIV DNA increase postdepletion in both CD4(+) TCM and TEM in progressor RMs but decrease in the CD4(+) TCM of controllers. The findings described in this study provide key insights into the differential functions of CD8(+) T lymphocytes in controller and progressor RMs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Differential Impact of In Vivo CD8+ T Lymphocyte Depletion in Controller versus Progressor Simian Immunodeficiency Virus-Infected Macaques

PubMed Central

Chowdhury, Ankita; Hayes, Timothy L.; Bosinger, Steven E.; Lawson, Benton O.; Vanderford, Thomas; Schmitz, Joern E.; Paiardini, Mirko; Betts, Michael; Chahroudi, Ann; Estes, Jacob D.

2015-01-01

ABSTRACT Numerous studies have demonstrated that CD8+ T lymphocytes suppress virus replication during human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection. However, the mechanisms underlying this activity of T cells remain incompletely understood. Here, we conducted CD8+ T lymphocyte depletion in 15 rhesus macaques (RMs) infected intravenously (i.v.) with SIVmac239. At day 70 postinfection, the animals (10 progressors with high viremia and 5 controllers with low viremia) were CD8 depleted by i.v. administration of the antibody M-T807R1. As expected, CD8 depletion resulted in increased virus replication, more prominently in controllers than progressors, which correlated inversely with predepletion viremia. Of note, the feature of CD8+ T lymphocyte predepletion that correlated best with the increase in viremia postdepletion was the level of CD8+ T-bet+ lymphocytes. We next found that CD8 depletion resulted in a homogenous increase of SIV RNA in superficial and mesenteric lymph nodes, spleen, and the gastrointestinal tract of both controllers and progressors. Interestingly, the level of SIV DNA increased postdepletion in both CD4+ central memory T lymphocytes (TCM) and CD4+ effector memory T lymphocytes (TEM) in progressor RMs but decreased in the CD4+ TCM of 4 out of 5 controllers. Finally, we found that CD8 depletion is associated with a greater increase in CD4+ T lymphocyte activation (measured by Ki-67 expression) in controllers than in progressors. Overall, these data reveal a differential impact of CD8+ T lymphocyte depletion between controller and progressor SIV-infected RMs, emphasizing the complexity of the in vivo antiviral role of CD8+ T lymphocytes. IMPORTANCE In this study, we further dissect the impact of CD8+ T lymphocytes on HIV/SIV replication during SIV infection. CD8+ T lymphocyte depletion leads to a relatively homogenous increase in viral replication in peripheral blood and tissues. CD8+ T lymphocyte depletion resulted in a more prominent increase in viral loads and CD4+ T lymphocyte activation in controllers than in progressors. Interestingly, we found T-bet expression on CD8+ T lymphocytes to be the best predictor of viral load increase following depletion. The levels of SIV DNA increase postdepletion in both CD4+ TCM and TEM in progressor RMs but decrease in the CD4+ TCM of controllers. The findings described in this study provide key insights into the differential functions of CD8+ T lymphocytes in controller and progressor RMs. PMID:26063417

Early-onset Conduct Problems: Predictions from daring temperament and risk taking behavior.

PubMed

Bai, Sunhye; Lee, Steve S

2017-12-01

Given its considerable public health significance, identifying predictors of early expressions of conduct problems is a priority. We examined the predictive validity of daring, a key dimension of temperament, and the Balloon Analog Risk Task (BART), a laboratory-based measure of risk taking behavior, with respect to two-year change in parent, teacher-, and youth self-reported oppositional defiant disorder (ODD), conduct disorder (CD), and antisocial behavior. At baseline, 150 ethnically diverse 6- to 10-year old (M=7.8, SD=1.1; 69.3% male) youth with ( n =82) and without ( n =68) DSM-IV ADHD completed the BART whereas parents rated youth temperament (i.e., daring); parents and teachers also independently rated youth ODD and CD symptoms. Approximately 2 years later, multi-informant ratings of youth ODD, CD, and antisocial behavior were gathered from rating scales and interviews. Whereas risk taking on the BART was unrelated to conduct problems, individual differences in daring prospectively predicted multi-informant rated conduct problems, independent of baseline risk taking, conduct problems, and ADHD diagnostic status. Early differences in the propensity to show positive socio-emotional responses to risky or novel experiences uniquely predicted escalating conduct problems in childhood, even with control of other potent clinical correlates. We consider the role of temperament in the origins and development of significant conduct problems from childhood to adolescence, including possible explanatory mechanisms underlying these predictions.

Optical critical dimension metrology for directed self-assembly assisted contact hole shrink

NASA Astrophysics Data System (ADS)

Dixit, Dhairya; Green, Avery; Hosler, Erik R.; Kamineni, Vimal; Preil, Moshe E.; Keller, Nick; Race, Joseph; Chun, Jun Sung; O'Sullivan, Michael; Khare, Prasanna; Montgomery, Warren; Diebold, Alain C.

2016-01-01

Directed self-assembly (DSA) is a potential patterning solution for future generations of integrated circuits. Its main advantages are high pattern resolution (˜10 nm), high throughput, no requirement of high-resolution mask, and compatibility with standard fab-equipment and processes. The application of Mueller matrix (MM) spectroscopic ellipsometry-based scatterometry to optically characterize DSA patterned contact hole structures fabricated with phase-separated polystyrene-b-polymethylmethacrylate (PS-b-PMMA) is described. A regression-based approach is used to calculate the guide critical dimension (CD), DSA CD, height of the PS column, thicknesses of underlying layers, and contact edge roughness of the post PMMA etch DSA contact hole sample. Scanning electron microscopy and imaging analysis is conducted as a comparative metric for scatterometry. In addition, optical model-based simulations are used to investigate MM elements' sensitivity to various DSA-based contact hole structures, predict sensitivity to dimensional changes, and its limits to characterize DSA-induced defects, such as hole placement inaccuracy, missing vias, and profile inaccuracy of the PMMA cylinder.

In ovo injection of anti-chicken CD25 monoclonal antibodies depletes CD4+CD25+ T cells in chickens.

PubMed

Shanmugasundaram, Revathi; Selvaraj, Ramesh K

2013-01-01

The CD4(+)CD25(+) cells have T regulatory cell properties in chickens. This study investigated the effect of in ovo injection of anti-chicken CD25 monoclonal antibodies (0.5 mg/egg) on CD4(+)CD25(+) cell depletion and on amounts of interleukin-2 mRNA and interferon-γ mRNA in CD4(+)CD25(-) cells posthatch. Anti-chicken CD25 or PBS (control) was injected into 16-d-old embryos. Chicks hatched from eggs injected with anti-chicken CD25 antibodies had a lower CD4(+)CD25(+) cell percentage in the blood until 25 d posthatch. The anti-chicken CD25 antibody injection nearly depleted CD4(+)CD25(+) cells in the blood until 16 d posthatch. At 30 d posthatch, the CD4(+)CD25(+) cell percentage in the anti-CD25-antibody-injected group was comparable with the percentage in the control group. At 16 d posthatch, the anti-chicken CD25 antibody injection decreased CD4(+)CD25(+) cell percentages in the thymus, spleen, and cecal tonsils. Chickens hatched from anti-CD25-antibody-injected eggs had approximately 25% of CD4(+)CD25(+) cells in the cecal tonsils and thymus compared with those in the cecal tonsils and thymus of the control group. The CD4(+)CD25(-) cells from the spleen and cecal tonsils of chicks hatched from anti-chicken-CD25-injected eggs had higher amounts of interferon-γ and interleukin-2 mRNA than CD4(+)CD25(-) cells from the control group. It could be concluded that injecting anti-chicken CD25 antibodies in ovo at 16 d of incubation nearly depleted the CD4(+)CD25(+) cells until 25 d posthatch.

Antilaminaribioside and antichitobioside antibodies in inflammatory bowel disease.

PubMed

Rejchrt, S; Drahosová, M; Kopácová, M; Cyrany, J; Douda, T; Pintér, M; Bures, J

2008-01-01

Testing antilaminaribioside (ALCA) and antichitobioside (ACCA) antibodies in 89 Crohn's disease (CD), 31 ulcerative colitis (UC) and 50 controls, mean values were 38.6 and 53.0 ELISA units for CD, 34.0 and 32.6 for UC, 34.5 and 36.4 for controls, respectively. There was no significant difference of ALCA values between CD and UC (p = 0.401), CD and control subjects (p = 0.698) or UC and controls (p = 0.898). ACCA were significantly higher in CD compared with UC (p = 0.011) but not with the controls (p = 0.095). No significant difference of ACCA values between UC and controls (p = 0.107) was found. ALCA and ACCA values significantly correlated in CD (r = 0.548, p < 10(-4)) and UC (r = 0.885, p < 10(-4)) but not in controls (r = 0.153, p = 0.287). The positive predictive value for CD was only 20 (ALCA) and 8 % (ACCA), the negative ones (to exclude CD) 25 (ALCA) and 86 % (ACCA). Small and/or large bowel involvement or disease type (i.e. stenosing, perforating or inflammatory) of CD did not differ in the two values. The idea that ALCA and ACCA may be useful either to differentiate between CD, UC and healthy subjects or to stratify CD was not confirmed.

Enabling CD SEM metrology for 5nm technology node and beyond

NASA Astrophysics Data System (ADS)

Lorusso, Gian Francesco; Ohashi, Takeyoshi; Yamaguchi, Astuko; Inoue, Osamu; Sutani, Takumichi; Horiguchi, Naoto; Bömmels, Jürgen; Wilson, Christopher J.; Briggs, Basoene; Tan, Chi Lim; Raymaekers, Tom; Delhougne, Romain; Van den Bosch, Geert; Di Piazza, Luca; Kar, Gouri Sankar; Furnémont, Arnaud; Fantini, Andrea; Donadio, Gabriele Luca; Souriau, Laurent; Crotti, Davide; Yasin, Farrukh; Appeltans, Raf; Rao, Siddharth; De Simone, Danilo; Rincon Delgadillo, Paulina; Leray, Philippe; Charley, Anne-Laure; Zhou, Daisy; Veloso, Anabela; Collaert, Nadine; Hasumi, Kazuhisa; Koshihara, Shunsuke; Ikota, Masami; Okagawa, Yutaka; Ishimoto, Toru

2017-03-01

The CD SEM (Critical Dimension Scanning Electron Microscope) is one of the main tools used to estimate Critical Dimension (CD) in semiconductor manufacturing nowadays, but, as all metrology tools, it will face considerable challenges to keep up with the requirements of the future technology nodes. The root causes of these challenges are not uniquely related to the shrinking CD values, as one might expect, but to the increase in complexity of the devices in terms of morphology and chemical composition as well. In fact, complicated threedimensional device architectures, high aspect ratio features, and wide variety of materials are some of the unavoidable characteristics of the future metrology nodes. This means that, beside an improvement in resolution, it is critical to develop a CD SEM metrology capable of satisfying the specific needs of the devices of the nodes to come, needs that sometimes will have to be addressed through dramatic changes in approach with respect to traditional CD SEM metrology. In this paper, we report on the development of advanced CD SEM metrology at imec on a variety of device platform and processes, for both logic and memories. We discuss newly developed approaches for standard, IIIV, and germanium FinFETs (Fin Field Effect Transistors), for lateral and vertical nanowires (NW), 3D NAND (three-dimensional NAND), STT-MRAM (Spin Transfer Magnetic Torque Random-Access Memory), and ReRAM (Resistive Random Access Memory). Applications for both front-end of line (FEOL) and back-end of line (BEOL) are developed. In terms of process, S/D Epi (Source Drain Epitaxy), SAQP (Self-Aligned Quadruple Patterning), DSA (Dynamic Self-Assembly), and EUVL (Extreme Ultraviolet Lithography) have been used. The work reported here has been performed on Hitachi CG5000, CG6300, and CV5000. In terms of logic, we discuss here the S/D epi defect classification, the metrology optimization for STI (Shallow Trench Isolation) Ge FinFETs, the defectivity of III-V STI FinFETs,, metrology for vertical and horizontal NWs. With respect to memory, we discuss a STT-RAM statistical CD analysis and its comparison to electrical performance, ReRAM metrology for VMCO (Vacancy-modulated conductive oxide) with comparison with electrical performance, 3D NAND ONO (Oxide Nitride Oxide) thickness measurements. In addition, we report on 3D morphological reconstruction using CD SEM in conjunction with FIB (Focused Ion Beam), on optimized BKM (Best Known Methods) development methodologies, and on CD SEM overlay. The large variety of results reported here gives a clear overview of the creative effort put in place to ensure that the critical potential of CD SEM metrology tools is fully enabled for the 5nm node and beyond.

Recurrence rate of clostridium difficile infection in hospitalized pediatric patients with inflammatory bowel disease.

PubMed

Kelsen, Judith R; Kim, Jason; Latta, Dan; Smathers, Sarah; McGowan, Karin L; Zaoutis, Theodore; Mamula, Petar; Baldassano, Robert N

2011-01-01

The incidence and associated morbidity of Clostridium difficile (CD) infection has been increasing at an alarming rate in North America. Clostridium difficile-associated diarrhea (CDAD) is the leading cause of nosocomial diarrhea in the USA. Patients with CDAD have longer average hospital admissions and additional hospital costs. Evidence has demonstrated that patients with inflammatory bowel disease (IBD) have a higher incidence of CD in comparison to the general population. The aim of this study was to compare the rate of recurrence of CD in hospitalized pediatric patients with IBD compared to hospitalized controls. The secondary aim was to evaluate whether infection with CD resulted in a more severe disease course of IBD. This was a nested case control retrospective study of hospitalized pediatric patients. Diagnosis of CD was confirmed with stool Toxin A and B analysis. The following data were obtained from the medical records: demographic information, classification of IBD including location of disease, IBD therapy, and prior surgeries. In addition, prior hospital admissions within 1 year and antibiotic exposure were recorded. The same information was recorded following CD infection. Cases were patients with IBD and CD; two control populations were also studied: patients with CD but without IBD, and patients with IBD but without CD. For aim 1, a total of 111 eligible patients with IBD and CD infection and 77 eligible control patients with CD infection were included. The rate of recurrence of CD in the IBD population was 34% compared to 7.5% in the control population (P < 0.0001). In evaluating the effect of CD infection on IBD disease severity, we compared the 111 IBD patients with CD to a second control population of 127 IBD patients without CD. 57% of IBD-CD patients were readmitted with an exacerbation of disease within 6 months of infection with CD and 67% required escalation of therapy following CD infection, compared to 30% of IBD patients without CD (P < 0.001). Of the patients with IBD and CD, 44% of the cases were new-onset IBD, 63% were on immunosuppression therapy, and 33% were on gastric acid suppression prior to infection. In comparing the IBD-CD and control CD populations, there was no significant difference in antibiotic exposure: 33% of IBD patients and 26% of control patients were on antibiotics (P < 0.2). With regard to prior hospitalization, 10% of patients with IBD were hospitalized in the 30 days prior to infection in comparison to 27% of the control CD patients (P < 0.002). CD infection in patients with IBD results in a higher rate of recurrence and is associated with higher morbidity than the general population. Patients with IBD often required hospitalization and escalation of therapy following infection with CD, suggesting that CD resulted in increased severity of IBD disease. In addition, IBD patients were more likely develop community-acquired CD, while the control patients developed nosocomial infections, indicating a higher susceptibility to CD infection in patients with IBD. Copyright © 2010 Crohn's & Crohn's & Colitis Foundation of America, Inc.

Feature-Based Change Detection Reveals Inconsistent Individual Differences in Visual Working Memory Capacity.

PubMed

Ambrose, Joseph P; Wijeakumar, Sobanawartiny; Buss, Aaron T; Spencer, John P

2016-01-01

Visual working memory (VWM) is a key cognitive system that enables people to hold visual information in mind after a stimulus has been removed and compare past and present to detect changes that have occurred. VWM is severely capacity limited to around 3-4 items, although there are robust individual differences in this limit. Importantly, these individual differences are evident in neural measures of VWM capacity. Here, we capitalized on recent work showing that capacity is lower for more complex stimulus dimension. In particular, we asked whether individual differences in capacity remain consistent if capacity is shifted by a more demanding task, and, further, whether the correspondence between behavioral and neural measures holds across a shift in VWM capacity. Participants completed a change detection (CD) task with simple colors and complex shapes in an fMRI experiment. As expected, capacity was significantly lower for the shape dimension. Moreover, there were robust individual differences in behavioral estimates of VWM capacity across dimensions. Similarly, participants with a stronger BOLD response for color also showed a strong neural response for shape within the lateral occipital cortex, intraparietal sulcus (IPS), and superior IPS. Although there were robust individual differences in the behavioral and neural measures, we found little evidence of systematic brain-behavior correlations across feature dimensions. This suggests that behavioral and neural measures of capacity provide different views onto the processes that underlie VWM and CD. Recent theoretical approaches that attempt to bridge between behavioral and neural measures are well positioned to address these findings in future work.

Algorithm development and the clinical and economic burden of Cushing's disease in a large US health plan database.

PubMed

Burton, Tanya; Le Nestour, Elisabeth; Neary, Maureen; Ludlam, William H

2016-04-01

This study aimed to develop an algorithm to identify patients with CD, and quantify the clinical and economic burden that patients with CD face compared to CD-free controls. A retrospective cohort study of CD patients was conducted in a large US commercial health plan database between 1/1/2007 and 12/31/2011. A control group with no evidence of CD during the same time was matched 1:3 based on demographics. Comorbidity rates were compared using Poisson and health care costs were compared using robust variance estimation. A case-finding algorithm identified 877 CD patients, who were matched to 2631 CD-free controls. The age and sex distribution of the selected population matched the known epidemiology of CD. CD patients were found to have comorbidity rates that were two to five times higher and health care costs that were four to seven times higher than CD-free controls. An algorithm based on eight pituitary conditions and procedures appeared to identify CD patients in a claims database without a unique diagnosis code. Young CD patients had high rates of comorbidities that are more commonly observed in an older population (e.g., diabetes, hypertension, and cardiovascular disease). Observed health care costs were also high for CD patients compared to CD-free controls, but may have been even higher if the sample had included healthier controls with no health care use as well. Earlier diagnosis, improved surgery success rates, and better treatments may all help to reduce the chronic comorbidity and high health care costs associated with CD.

Treatment and prevention of experimental autoimmune myocarditis with CD28 superagonists.

PubMed

Wang, Shu; Liu, Jing; Wang, Min; Zhang, Jinghui; Wang, Zhaohui

2010-01-01

Experimental autoimmune myocarditis (EAM), a rodent model of human dilated cardiomyopathy (DCM), is mediated by an autoimmune mechanism. We investigated whether a CD28 superagonistic antibody selectively targeting CD4+CD25+ regulatory T cells (T(regs)) provides effective therapy for EAM. Four groups of 5 rats were used. The normal control group was immunized with PBS. The EAM group was immunized with porcine myosin. The experimental group was immunized with myosin and superagonistic CD28 antibody JJ316. The final group was immunized with myosin and an unrelated rat IgG. Autoantibody and IL-10 production, CD4+CD25+ cell levels, Foxp3 expression and cardiac histology were analyzed. Anti-myosin autoantibody levels were higher in the EAM and isotype control groups than the normal control group (p < 0.05), and reduced in the CD28-JJ316 group (p < 0.05). The levels of CD25+CD4+ cells, IL-10 and splenocyte Foxp3 expression were significantly lower in the EAM and isotype control groups versus the CD28-JJ316 group (p < 0.05). Infiltration of inflammatory cells was observed in the EAM and isotype control groups, whereas CD28-JJ316 ameliorated myocarditis. CD28 superagonists could be effective in EAM treatment by up-regulating Foxp3 expression and contributing to CD4+CD25+ T(reg) activation and expansion. The enhancement in IL-10 by CD28 superagonists also ameliorated the disease.

Construction of 6-thioguanine and 6-mercaptopurine carriers based on βcyclodextrins and gold nanoparticles.

PubMed

Sierpe, R; Noyong, Michael; Simon, Ulrich; Aguayo, D; Huerta, J; Kogan, Marcelo J; Yutronic, N

2017-12-01

As a novel strategy to overcome some of the therapeutic disadvantages of 6-thioguanine (TG) and 6-mercaptopurine (MP), we propose the inclusion of these drugs in βcyclodextrin (βCD) to form the complexes βCD-TG and βCD-MP, followed by subsequent interaction with gold nanoparticles (AuNPs), generating the ternary systems: βCD-TG-AuNPs and βCD-MP-AuNPs. This modification increased their solubility and improved their stability, betting by a site-specific transport due to their nanometric dimensions, among other advantages. The formation of the complexes was confirmed using powder X-ray diffraction, thermogravimetric analysis and one and two-dimensional NMR. A theoretical study using DFT and molecular modelling was conducted to obtain the more stable tautomeric species of TG and MP in solution and confirm the proposed inclusion geometries. The deposition of AuNPs onto βCD-TG and βCD-MP via sputtering was confirmed by UV-vis spectroscopy. Subsequently, the ternary systems were characterized by TEM, FE-SEM and EDX to directly observe the deposited AuNPs and evaluate their sizes, size dispersion, and composition. Finally, the in vitro permeability of the ternary systems was studied using parallel artificial membrane permeability assay (PAMPA). Copyright © 2017 Elsevier Ltd. All rights reserved.

Advances in Serials Management. Volume 6.

ERIC Educational Resources Information Center

Hepfer, Cindy, Ed.; Gammon, Julia, Ed.; Malinowski, Teresa, Ed.

In order to further discussion and support constructive change, this volume presents the following eight papers on various dimensions of serials management: (1) "CD-ROMs, Surveys, and Sales: The OSA [Optical Society of America] Experience" (Frank E. Harris and Alan Tourtlotte); (2) "Management and Integration of Electronic Journals into the…

Nanomaterial-based Electrochemical Sensors for the Detection of Glucose and Cholesterol

NASA Astrophysics Data System (ADS)

Ahmadalinezhad, Asieh

Electrochemical detection methods are highly attractive for the monitoring of glucose, cholesterol, cancer, infectious diseases, and biological warfare agents due to their low cost, high sensitivity, functionality despite sample turbidity, easy miniaturization via microfabrication, low power requirements, and a relatively simple control infrastructure. The development of implantable biosensors is laden with great challenges, which include longevity and inherent biocompatibility, coupled with the continuous monitoring of analytes. Deficiencies in any of these areas will necessitate their surgical replacement. In addition, random signals arising from non-specific adsorption events can cause problems in diagnostic assays. Hence, a great deal of effort has been devoted to the specific control of surface structures. Nanotechnology involves the creation and design of structures with at least one dimension that is below 100 nm. The optical, magnetic, and electrical properties of nanostructures may be manipulated by altering their size, shape, and composition. These attributes may facilitate improvements in biocompatibility, sensitivity and the specific attachment of biomaterials. Thus, the central theme of this dissertation pertains to highlighting the critical roles that are played by the morphology and intrinsic properties of nanomaterials when they are applied in the development of electrochemical biosensors. For this PhD project, we initially designed and fabricated a novel amperometric glucose biosensor based on the immobilization of glucose oxidase (GOx) on a Prussian blue modified nanoporous gold surface, which exhibited a rapid response and a low detection limit of 2.5 microM glucose. The sensitivity of the biosensor was found to be very high (177 microA/mM) and the apparent Michaelis--Menten constant was calculated to be 2.1 mM. Our study has demonstrated that nanoporous gold provides an excellent matrix for enzyme immobilization. To adopt these advanced properties, we fabricated a highly sensitive and mediator-free electrochemical biosensor for the determination of total cholesterol. The developed biosensor possessed high selectivity and sensitivity (29.33 microA mM--1cm --2). The apparent Michaelis--Menten constant, KappM of this biosensor was very low (0.64 mM), which originated from both the effective immobilization process and the nanoporous structure of the substrate. The biosensor exhibited a wide linear range, up to 300 mg dL--1 , in a physiological environment (pH 7.4); making it a promising candidate for the clinical determination of cholesterol. The fabricated biosensor was tested further by utilizing actual food samples (e.g., margarine, butter and fish oil). The results indicated that it has the potential capacity to be employed as a facile cholesterol detection tool in the food industry and for supplement quality control. To enhance the stability of the biosensors in the continuous monitoring of glucose, we designed a novel platform that was based on buckypaper. The fabricated biosensor responded to glucose with a considerable functional lifetime of over 80 days and detected glucose with a dynamic linear range of over 9 mM with a detection limit of 0.01 mM. To investigate the effects of the physical dimensions of nanomaterials on electrochemical biosensing, we synthesized TiO2 nanowires with controllable dimensions via a facile thermal oxidation treatment of a Ti substrate. To improve the conductivity of the TiO2 nanowires and to facilitate the immobilization of enzymes, a thin layer of carbon was deposited onto the TiO2 nanowires via a chemical vapour deposition method. Upon the immobilization of glucose oxidase as a model protein, direct electron transfer was observed in a mediator-free biosensing environment. Our electrochemical studies have revealed that the electron transfer rate of the immobilized glucose oxidase is strongly dependent on the dimensions of the carbonized TiO 2 nanowires, and that the designed glucose biosensor exhibits a wide linear range, up to 18 mM glucose, as well as high sensitivity and selectivity. Glucose measurements of human serum using the developed biosensor showed excellent agreement with the data recorded by a commercial blood glucose monitoring assay. Finally, we fabricated an enzyme-free glucose sensor based on nanoporous palladium-cadmium (PdCd) networks. A hydrothermal method was applied in the synthesis of PdCd nanomaterials. The effect of the composition of the PdCd nanomaterials on the performance of the electrode was investigated by cyclic voltammetry (CV). Amperometric studies showed that the nanoporous PdCd electrode was responsive to the direct oxidation of glucose with high electrocatalytic activity. The sensitivity of the sensor for continuous glucose monitoring was 146.21 microAmM--1cm--2, with linearity up to 10 mM and a detection limit of 0.05 mM. In summary, the electrochemical biosensors proposed in my PhD study exhibited high sensitivity and selectivity for the continuous monitoring of analytes in the presence of common interference species. Our results have shown that the performance of the biosensors is significantly dependent on the dimensions and morphologies of nanostructured materials. The unique nanomaterials-based platforms proposed in this dissertation open the door to the design and fabrication of high-performance electrochemical biosensors for medical diagnostics.

Application of HRV-CD for estimation of life expectancy in various clinical disorders.

PubMed

Almoznino-Sarafian, Dorit; Sarafian, Gideon; Zyssman, Itzhak; Shteinshnaider, Miriam; Tzur, Irma; Kaplan, Ben-Zion; Berman, Sylvia; Cohen, Natan; Gorelik, Oleg

2009-12-01

Low heart rate variability (HRV) was found in various medical conditions including heart failure and acute myocardial infarction. Decreased HRV in these conditions predicted poor prognosis. HRV was estimated in 133 unselected inpatients with relevant clinical bedside conditions by non-linear analysis derived from chaos theory, which calculates the correlation dimension (CD) of the cardiac electrophysiologic system (HRV-CD). Mean HRV-CD in the entire group was 3.75+/-0.45. Heart failure, coronary artery disease, cardiac arrhythmia, low serum potassium, renal dysfunction, and diabetes mellitus were significantly associated with reduced HRV-CD compared to their counterparts [3.6 vs. 3.9 (P<.001), 3.65 vs. 3.87 (P=.005), 3.58 vs. 3.8 (P=.01), 3.38 vs. 3.81 (P=.02), 3.59 vs. 3.8 (P=.04), and 3.66 vs. 3.82 (P=.04), respectively]. Stepwise logistic regression showed heart failure to be the condition most significantly associated with low HRV-CD (odds ratio 4.2, 95% confidence interval 1.90-9.28, P<.001). In the entire group, decreased HRV-CD (< or =3.75 vs. >3.75) was associated with lower survival (P=.01). Mortality of diabetic patients with HRV-CD < or =3.75 exceeded the mortality in patients with HRV-CD >3.75 (P=.02). Heart failure, renal dysfunction or age over 70 combined with HRV-CD < or =3.75 also appeared to be associated with augmented mortality. Diminished HRV-CD is associated with heart failure, coronary artery disease, cardiac arrhythmia, renal dysfunction, diabetes mellitus and low serum potassium. Among the latter, heart failure is most significantly associated with decreased HRV-CD. Decreased HRV-CD values, especially in diabetics, are also associated with lower survival.

CD28 T-cell costimulatory molecule expression in pemphigus vulgaris.

PubMed

Alecu, M; Ursaciuc, C; Surcel, M; Coman, G; Ciotaru, D; Dobre, M

2009-03-01

CD28 superfamily of immune costimulatory molecules could play an important role in autotolerance control. CD28 costimulation seems to be necessary for regulatory T cell (Treg) activation and successive suppressive activities involved in autoimmunity protection. This study investigates CD28 expression, especially inducible costimulator fraction, on T lymphocytes in pemphigus vulgaris (PV) patients. CD28 expression on T lymphocytes was assessed in 16 PV patients during acute attack. All patients and 10 healthy control subjects were tested for lymphocyte populations, T-cell subpopulations (T-CD4+, T-CD8+), Treg and CD28 expression on T-cell subpopulations. T, B and natural killer cells average values in PV patients were close to the control group values. Compared with control group, PV values showed lower Treg (2.2% compared with 4.7%), slightly decreased CD4+ CD28+ T cells (91% compared with 95%), higher CD4+ CD28- T cells (9% compared with 5%), decreased CD8+ CD28+ T cells (57% and 73%, respectively) and significantly enhanced CD8+ CD28- T cells (43% compared with 27%). These data suggest that Treg-mediated suppressor T-cell effects could be diminished in PV, together with an abnormal or ineffective subsequent helper T-cell suppression. CD28 high expression on helper T cells and low expression on suppressor T cells are arguments for a potential CD28 role in PV autoimmune response mechanism.

Generation of 320 mW at 10.20 μm based on CdSe long-wave infrared crystal

NASA Astrophysics Data System (ADS)

Wang, Jian; Yuan, Ligang; Zhang, Yingwu; Chen, Guo; Cheng, Hongjuan; Gao, Yanzhao

2018-06-01

CdSe single crystal, with the sizes of ∼54 mm in diameter and ∼25 mm in length, was grown by a high pressure vertical gradient freeze (HPVGF) technique using (0 0 1)-oriented seed. The CdSe crystal was characterized with transmission spectrophotometer. The transmission spectra showed that the infrared transmission was above 68% and the mean absorption coefficient was 0.041 cm-1 in the range of 2.5-20 μm. Using fabricated CdSe crystal with the dimensions of 6 mm × 10 mm × 44 mm, we demonstrated an optical parametric oscillator (OPO) pumped by a 2.05 μm Ho:YLF laser at a pulse repetition frequency of 5 kHz. Up to 320 mW output was obtained at the idler wavelength of 10.20 μm with a pump power of 18.06 W. 320 mW at 10.20 μm, to our knowledge, was the highest power obtained with a 2.05 μm laser-pumped CdSe OPO.

Analysis of circulating CD14+/CD16+ monocyte-derived macrophages (MDMs) in the peripheral blood of patients with oral squamous cell carcinoma.

PubMed

Grimm, Martin; Feyen, Oliver; Coy, Johannes F; Hofmann, Heiko; Teriete, Peter; Reinert, Siegmar

2016-03-01

Monocytes/macrophages are regarded as the first line of defense in tumors. Therefore, analyzing monocyte subtypes in oral squamous cell carcinoma (OSCC) may be of value in disease monitoring and to explore immunotherapeutic strategies for cancer patients. Circulating peripheral blood CD14+/CD16+ monocyte-derived macrophages (MDMs) were evaluated in OSCC patients with oral squamous cell carcinoma (n = 44) compared with controls (n = 85). Moreover, epitope detection in monocytes (EDIM) technology was used to detect biomarkers Apo10 and transketolase-like-1 in CD14+/CD16+ MDMs. Compared with controls, no significant (P = .3646) difference (control group 9.8%, OSCC group 8.8%) in CD14+/CD16+ MDM were noted in OSCC. However, EDIM-Apo10 and EDIM-TKTL1 scores detected in the CD14+/CD16+ MDMs were increased in OSCC compared with controls (P < .0001). Analyzing CD14+/CD16+ MDMs represents a stable cell population for detecting biomarkers in cancer disease monitoring. Copyright © 2016 Elsevier Inc. All rights reserved.

Identification and quantification analysis of nonlinear dynamics properties of combustion instability in a diesel engine

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

Yang, Li-Ping, E-mail: yangliping302@hrbeu.edu.cn; Ding, Shun-Liang; Song, En-Zhe

The cycling combustion instabilities in a diesel engine have been analyzed based on chaos theory. The objective was to investigate the dynamical characteristics of combustion in diesel engine. In this study, experiments were performed under the entire operating range of a diesel engine (the engine speed was changed from 600 to 1400 rpm and the engine load rate was from 0% to 100%), and acquired real-time series of in-cylinder combustion pressure using a piezoelectric transducer installed on the cylinder head. Several methods were applied to identify and quantitatively analyze the combustion process complexity in the diesel engine including delay-coordinate embedding, recurrencemore » plot (RP), Recurrence Quantification Analysis, correlation dimension (CD), and the largest Lyapunov exponent (LLE) estimation. The results show that the combustion process exhibits some determinism. If LLE is positive, then the combustion system has a fractal dimension and CD is no more than 1.6 and within the diesel engine operating range. We have concluded that the combustion system of diesel engine is a low-dimensional chaotic system and the maximum values of CD and LLE occur at the lowest engine speed and load. This means that combustion system is more complex and sensitive to initial conditions and that poor combustion quality leads to the decrease of fuel economy and the increase of exhaust emissions.« less

Identification and quantification analysis of nonlinear dynamics properties of combustion instability in a diesel engine.

PubMed

Yang, Li-Ping; Ding, Shun-Liang; Litak, Grzegorz; Song, En-Zhe; Ma, Xiu-Zhen

2015-01-01

The cycling combustion instabilities in a diesel engine have been analyzed based on chaos theory. The objective was to investigate the dynamical characteristics of combustion in diesel engine. In this study, experiments were performed under the entire operating range of a diesel engine (the engine speed was changed from 600 to 1400 rpm and the engine load rate was from 0% to 100%), and acquired real-time series of in-cylinder combustion pressure using a piezoelectric transducer installed on the cylinder head. Several methods were applied to identify and quantitatively analyze the combustion process complexity in the diesel engine including delay-coordinate embedding, recurrence plot (RP), Recurrence Quantification Analysis, correlation dimension (CD), and the largest Lyapunov exponent (LLE) estimation. The results show that the combustion process exhibits some determinism. If LLE is positive, then the combustion system has a fractal dimension and CD is no more than 1.6 and within the diesel engine operating range. We have concluded that the combustion system of diesel engine is a low-dimensional chaotic system and the maximum values of CD and LLE occur at the lowest engine speed and load. This means that combustion system is more complex and sensitive to initial conditions and that poor combustion quality leads to the decrease of fuel economy and the increase of exhaust emissions.

Impaired Upregulation of the Costimulatory Molecules, CD27 and CD28, on CD4+ T Cells from HIV Patients Receiving ART Is Associated with Poor Proliferative Responses.

PubMed

Tanaskovic, Sara; Price, Patricia; French, Martyn A; Fernandez, Sonia

2017-02-01

HIV patients beginning antiretroviral therapy (ART) with advanced immunodeficiency often retain low CD4 + T cell counts despite virological control. We examined proliferative responses and upregulation of costimulatory molecules, following anti-CD3 stimulation, in HIV patients with persistent CD4 + T cell deficiency on ART. Aviremic HIV patients with nadir CD4 + T cell counts <100 cells/μL and who had received ART for a median time of 7 (range 1-11) years were categorized into those achieving low (<350 cells/μL; n = 13) or normal (>500 cells/μL; n = 20) CD4 + T cell counts. Ten healthy controls were also recruited. CD4 + T cell proliferation (Ki67) and upregulation of costimulatory molecules (CD27 and CD28) after anti-CD3 stimulation were assessed by flow cytometry. Results were related to proportions of CD4 + T cells expressing markers of T cell senescence (CD57), activation (HLA-DR), and apoptotic potential (Fas). Expression of CD27 and/or CD28 on uncultured CD4 + T cells was similar in patients with normal CD4 + T cell counts and healthy controls, but lower in patients with low CD4 + T cell counts. Proportions of CD4 + T cells expressing CD27 and/or CD28 correlated inversely with CD4 + T cell expression of CD57, HLA-DR, and Fas. After anti-CD3 stimulation, induction of CD27 hi CD28 hi expression was independent of CD4 + T cell counts, but lower in HIV patients than in healthy controls. Induction of CD27 hi CD28 hi expression correlated with induction of Ki67 expression in total, naïve, and CD31 + naïve CD4 + T cells from patients. In HIV patients responding to ART, impaired induction of CD27 and CD28 on CD4 + T cells after stimulation with anti-CD3 is associated with poor proliferative responses as well as greater CD4 + T cell activation and immunosenescence.

Effective Control of Chronic γ-Herpesvirus Infection by Unconventional MHC Class Ia–Independent CD8 T Cells

PubMed Central

Tibbetts, Scott A; McClellan, Kelly B

2006-01-01

Control of virus infection is mediated in part by major histocompatibility complex (MHC) Class Ia presentation of viral peptides to conventional CD8 T cells. Although important, the absolute requirement for MHC Class Ia–dependent CD8 T cells for control of chronic virus infection has not been formally demonstrated. We show here that mice lacking MHC Class Ia molecules (Kb−/−xDb−/− mice) effectively control chronic γ-herpesvirus 68 (γHV68) infection via a robust expansion of β2-microglobulin (β2-m)-dependent, but CD1d-independent, unconventional CD8 T cells. These unconventional CD8 T cells expressed: (1) CD8αβ and CD3, (2) cell surface molecules associated with conventional effector/memory CD8 T cells, (3) TCRαβ with a significant Vβ4, Vβ3, and Vβ10 bias, and (4) the key effector cytokine interferon-γ (IFNγ). Unconventional CD8 T cells utilized a diverse TCR repertoire, and CDR3 analysis suggests that some of that repertoire may be utilized even in the presence of conventional CD8 T cells. This is the first demonstration to our knowledge that β2-m–dependent, but Class Ia–independent, unconventional CD8 T cells can efficiently control chronic virus infection, implicating a role for β2-n–dependent non-classical MHC molecules in control of chronic viral infection. We speculate that similar unconventional CD8 T cells may be able to control of other chronic viral infections, especially when viruses evade immunity by inhibiting generation of Class Ia–restricted T cells. PMID:16733540

Increased Intraepithelial Vα24 Invariant NKT Cells in the Celiac Duodenum

PubMed Central

Montalvillo, Enrique; Bernardo, David; Martínez-Abad, Beatriz; Allegretti, Yessica; Fernández-Salazar, Luis; Calvo, Carmen; Chirdo, Fernando G.; Garrote, José A.; Arranz, Eduardo

2015-01-01

Celiac Disease (CD) is an interferon (IFN)γ-mediated duodenal hypersensitivity to wheat gluten occurring in genetically predisposed individuals. Gluten-free diet (GFD) leads to a complete remission of the disease. Vα24-restricted invariant NKT (iNKT) cells are important to maintain immune homeostasis in the gut mucosa because of their unique capacity to rapidly produce large quantities of both T-helper (Th)1 and Th2 cytokines upon stimulation. We studied the presence of these cells in the CD duodenum. Duodenal biopsies were obtained from 45 untreated-CD patients (uCD), 15 Gluten Free Diet-CD patients (GFD-CD), 44 non-inflamed non-CD controls (C-controls) and 15 inflamed non-CD controls (I-controls). Two populations from Spain and Argentina were recruited. Messenger RNA (mRNA) expression of Vα24-Jα18 (invariant TCRα chain of human iNKT cells), IFNγ and intracellular transcription factor Forkhead Box P3 (Foxp3), and flow cytometry intraepithelial lymphocyte (IEL) profile were determined. Both uCD and GFD-CD patients had higher Vα24-Jα18 mRNA levels than non-CD controls (I and C-controls). The expression of Vα24-Jα18 correlated with Marsh score for the severity of mucosal lesion and also with increased mRNA IFNγ levels. uCD and GFD-CD patients had decreased mRNA expression of FoxP3 but increased expression of Vα24-Jα18, which revealed a CD-like molecular profile. Increased numbers of iNKT cells were confirmed by flow cytometry within the intraepithelial lymphocyte compartment of uCD and GFD-CD patients and correlated with Vα24-Jα18 mRNA expression. In conclusion, we have found an increased number of iNKT cells in the duodenum from both uCD and GFD-CD patients, irrespective of the mucosal status. A CD-like molecular profile, defined by an increased mRNA expression of Vα24-Jα18 together with a decreased expression of FoxP3, may represent a pro-inflammatory signature of the CD duodenum. PMID:26529008

Increased Intraepithelial Vα24 Invariant NKT Cells in the Celiac Duodenum.

PubMed

Montalvillo, Enrique; Bernardo, David; Martínez-Abad, Beatriz; Allegretti, Yessica; Fernández-Salazar, Luis; Calvo, Carmen; Chirdo, Fernando G; Garrote, José A; Arranz, Eduardo

2015-10-30

Celiac Disease (CD) is an interferon (IFN)γ-mediated duodenal hypersensitivity to wheat gluten occurring in genetically predisposed individuals. Gluten-free diet (GFD) leads to a complete remission of the disease. Vα24-restricted invariant NKT (iNKT) cells are important to maintain immune homeostasis in the gut mucosa because of their unique capacity to rapidly produce large quantities of both T-helper (Th)1 and Th2 cytokines upon stimulation. We studied the presence of these cells in the CD duodenum. Duodenal biopsies were obtained from 45 untreated-CD patients (uCD), 15 Gluten Free Diet-CD patients (GFD-CD), 44 non-inflamed non-CD controls (C-controls) and 15 inflamed non-CD controls (I-controls). Two populations from Spain and Argentina were recruited. Messenger RNA (mRNA) expression of Vα24-Jα18 (invariant TCRα chain of human iNKT cells), IFNγ and intracellular transcription factor Forkhead Box P3 (Foxp3), and flow cytometry intraepithelial lymphocyte (IEL) profile were determined. Both uCD and GFD-CD patients had higher Vα24-Jα18 mRNA levels than non-CD controls (I and C-controls). The expression of Vα24-Jα18 correlated with Marsh score for the severity of mucosal lesion and also with increased mRNA IFNγ levels. uCD and GFD-CD patients had decreased mRNA expression of FoxP3 but increased expression of Vα24-Jα18, which revealed a CD-like molecular profile. Increased numbers of iNKT cells were confirmed by flow cytometry within the intraepithelial lymphocyte compartment of uCD and GFD-CD patients and correlated with Vα24-Jα18 mRNA expression. In conclusion, we have found an increased number of iNKT cells in the duodenum from both uCD and GFD-CD patients, irrespective of the mucosal status. A CD-like molecular profile, defined by an increased mRNA expression of Vα24-Jα18 together with a decreased expression of FoxP3, may represent a pro-inflammatory signature of the CD duodenum.

Characterization of core/shell structures based on CdTe and GaAs nanocrystalline layers deposited on SnO2 microwires

NASA Astrophysics Data System (ADS)

Ghimpu, L.; Ursaki, V. V.; Pantazi, A.; Mesterca, R.; Brâncoveanu, O.; Shree, Sindu; Adelung, R.; Tiginyanu, I. M.; Enachescu, M.

2018-04-01

We report the fabrication and characterization of SnO2/CdTe and SnO2/GaAs core/shell microstructures. CdTe or GaAs shell layers were deposited by radio-frequency (RF) magnetron sputtering on core SnO2 microwires synthesized by a flame-based thermal oxidation method. The produced structures were characterized by scanning electron microscopy (SEM), high-resolution scanning transmission electron microscope (HR-STEM), X-ray diffraction (XRD), Raman scattering and FTIR spectroscopy. It was found that the SnO2 core is of the rutile type, while the shells are composed of CdTe or GaAs nanocrystallites of zincblende structure with the dimensions of crystallites in the range of 10-20 nm. The Raman scattering investigations demonstrated that the quality of the porous nanostructured shell is improved by annealing at temperatures of 420-450 °C. The prospects of implementing these microstructures in intrinsic type fiber optic sensors are discussed.

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

Patil, B. N.; Acharya, S. A., E-mail: saha275@yahoo.com

In the present work ZnS-CdS composite was prepared by hydrothermal method. The prepared samples were characterized by X-ray diffraction (XRD) to confirm formation of nano particles, Scanning electron microscopy (SEM) images exhibit nanoscale dimensions of as synthesized individual phases. UV/VIS spectra were recorded for evaluation of photophysical properties. The composite was explored as photocatalysts to study dye degradation using methylene blue in aqueous slurry under irradiation of 663 nm wavelength and congo red under irradiation of 493 nm wavelength. Under the same conditions the photocatalytic activity of the individual phases ZnS and CdS were also examined. The ZnS-CdS composite is found inmore » enhancing the rate of photo degradation of toxic dyes as compare to ZnS and CdS individually in presence of visible light. This ZnS based metal sulphide/oxide semiconductor nanocomposites are high potential material for Photo-degradation of toxic dyes, and act as good photocatalyst in visible light.« less

Advanced in-line metrology strategy for self-aligned quadruple patterning

NASA Astrophysics Data System (ADS)

Chao, Robin; Breton, Mary; L'herron, Benoit; Mendoza, Brock; Muthinti, Raja; Nelson, Florence; De La Pena, Abraham; Le, Fee li; Miller, Eric; Sieg, Stuart; Demarest, James; Gin, Peter; Wormington, Matthew; Cepler, Aron; Bozdog, Cornel; Sendelbach, Matthew; Wolfling, Shay; Cardinal, Tom; Kanakasabapathy, Sivananda; Gaudiello, John; Felix, Nelson

2016-03-01

Self-Aligned Quadruple Patterning (SAQP) is a promising technique extending the 193-nm lithography to manufacture structures that are 20nm half pitch or smaller. This process adopts multiple sidewall spacer image transfers to split a rather relaxed design into a quarter of its original pitch. Due to the number of multiple process steps required for the pitch splitting in SAQP, the process error propagates through each deposition and etch, and accumulates at the final step into structure variations, such as pitch walk and poor critical dimension uniformity (CDU). They can further affect the downstream processes and lower the yield. The impact of this error propagation becomes significant for advanced technology nodes when the process specifications of device design CD requirements are at nanometer scale. Therefore, semiconductor manufacturing demands strict in-line process control to ensure a high process yield and improved performance, which must rely on precise measurements to enable corrective actions and quick decision making for process development. This work aims to provide a comprehensive metrology solution for SAQP. During SAQP process development, the challenges in conventional in-line metrology techniques start to surface. For instance, critical-dimension scanning electron microscopy (CDSEM) is commonly the first choice for CD and pitch variation control. However, it is found that the high aspect ratio at mandrel level processes and the trench variations after etch prevent the tool from extracting the true bottom edges of the structure in order to report the position shift. On the other hand, while the complex shape and variations can be captured with scatterometry, or optical CD (OCD), the asymmetric features, such as pitch walk, show low sensitivity with strong correlations in scatterometry. X-ray diffraction (XRD) is known to provide useful direct measurements of the pitch walk in crystalline arrays, yet the data analysis is influenced by the incoming geometry and must be used carefully. A successful implementation of SAQP process control for yield improvement requires the metrology issues to be addressed. By optimizing the measurement parameters and beam configurations, CDSEM measurements distinguish each of the spaces corresponding to the upstream mandrel processes and report their CDs separately to feed back to the process team for the next development cycle. We also utilize the unique capability in scatterometry to measure the structure details in-line and implement a "predictive" process control, which shows a good correlation between the "predictive" measurement and the cross-sections from our design of experiments (DOE). The ability to measure the pitch walk in scatterometry was also demonstrated. This work also explored the frontier of in-line XRD capability by enabling an automatic RSM fitting on tool to output pitch walk values. With these advances in metrology development, we are able to demonstrate the impacts of in-line monitoring in the SAQP process, to shorten the patterning development learning cycle to improve the yield.

Experimental Design For Photoresist Characterization

NASA Astrophysics Data System (ADS)

Luckock, Larry

1987-04-01

In processing a semiconductor product (from discrete devices up to the most complex products produced) we find more photolithographic steps in wafer fabrication than any other kind of process step. Thus, the success of a semiconductor manufacturer hinges on the optimization of their photolithographic processes. Yet, we find few companies that have taken the time to properly characterize this critical operation; they are sitting in the "passenger's seat", waiting to see what will come out, hoping that the yields will improve someday. There is no "black magic" involved in setting up a process at its optimum conditions (i.e. minimum sensitivity to all variables at the same time). This paper gives an example of a real world situation for optimizing a photolithographic process by the use of a properly designed experiment, followed by adequate multidimensional analysis of the data. Basic SPC practices like plotting control charts will not, by themselves, improve yields; the control charts are, however, among the necessary tools used in the determination of the process capability and in the formulation of the problems to be addressed. The example we shall consider is the twofold objective of shifting the process average, while tightening the variance, of polysilicon line widths. This goal was identified from a Pareto analysis of yield-limiting mechanisms, plus inspection of the control charts. A key issue in a characterization of this type of process is the number of interactions between variables; this example rules out two-level full factorial and three-level fractional factorial designs (which cannot detect all of the interactions). We arrive at an experiment with five factors at five levels each. A full factorial design for five factors at three levels would require 3125 wafers. Instead, we will use a design that allows us to run this experiment with only 25 wafers, for a significant reduction in time, materials and manufacturing interruption in order to complete the experiment. An optimum solution is then determined via response surface analysis and a series of 3-D and contour plots are shown. The offset between the mask dimensions and poly CD at the optimum operating conditions is discussed with respect to yield, profits and return-on-investment. The expert system used for process optimization covers all types of process steps, producing the best custom designed experiment based on the actual equipment used. The knowledge base contains parameter lists, by machine make and model, ranked by sensitivity and controllability. One option allows 3-D spatial characterization of equipment. For the purpose of this presentation, we will assume that we want to optimize a photo-lithographic process used for polysilicon pattern definition and that we have determined minimum and maximum line widths, based on electrical yield requirements of the product. For this MOS process, the minimum critical dimension (CD) for the poly gate was determined by punchthrough voltage, threshold voltage, etc., while the maximum CD was determined from other performance factors like access time. We will start with the product engineer's analysis.

Phase- and shape-controlled hydrothermal synthesis of CdS nanoparticles, and oriented attachment growth of its hierarchical architectures

NASA Astrophysics Data System (ADS)

Cao, Yali; Hu, Pengfei; Jia, Dianzeng

2013-01-01

Hydrothermal strategies were successfully used to control the phases and morphologies of CdS nanocrystals. In the absence of an external direction-controlling process, the hexagonal and cubic phase well-defined leaf- and flower-like CdS nanocrystals were controlled obtained via adjusting the reaction duration or the concentration of surfactant. Oriented attachment growth modes were suggested for the formation of CdS superstructures, which was clarified through the tracing of temporal evolution of CdS nanoparticles. The CdS superstructures were structured by primary building nanoparticles, and held excellent visible emission with a peak in the green regions. This strategy is very helpful for studying the phase and morphology controlled fabrication of sulfides nanocrystals.

The CD control improvement by using CDSEM 2D measurement of complex OPC patterns

NASA Astrophysics Data System (ADS)

Chou, William; Cheng, Jeffrey; Lee, Adder; Cheng, James; Tzeng, Alex C.; Lu, Colbert; Yang, Ray; Lee, Hong Jen; Bandoh, Hideaki; Santo, Izumi; Zhang, Hao; Chen, Chien Kang

2016-10-01

As the process node becomes more advanced, the accuracy and precision in OPC pattern CD are required in mask manufacturing. CD SEM is an essential tool to confirm the mask quality such as CD control, CD uniformity and CD mean to target (MTT). Unfortunately, in some cases of arbitrary enclosed patterns or aggressive OPC patterns, for instance, line with tiny jogs and curvilinear SRAF, CD variation depending on region of interest (ROI) is a very serious problem in mask CD control, even it decreases the wafer yield. For overcoming this situation, the 2-dimensional (2D) method by Holon is adopted. In this paper, we summarize the comparisons of error budget between conventional (1D) and 2D data using CD SEM and the CD performance between mask and wafer by complex OPC patterns including ILT features.

Image simulation and surface reconstruction of undercut features in atomic force microscopy

NASA Astrophysics Data System (ADS)

Qian, Xiaoping; Villarrubia, John; Tian, Fenglei; Dixson, Ronald

2007-03-01

CD-AFMs (critical dimension atomic force microscopes) are instruments with servo-control of the tip in more than one direction. With appropriately "boot-shaped" or flared tips, such instruments can image vertical or even undercut features. As with any AFM, the image is a dilation of the sample shape with the tip shape. Accurate extraction of the CD requires a correction for the tip effect. Analytical methods to correct images for the tip shape have been available for some time for the traditional (vertical feedback only) AFMs, but were until recently unavailable for instruments with multi-dimensional feedback. Dahlen et al. [J. Vac. Sci. Technol. B23, pp. 2297-2303, (2005)] recently introduced a swept-volume approach, implemented for 2-dimensional (2D) feedback. It permits image simulation and sample reconstruction, techniques previously developed for the traditional instruments, to be extended for the newer tools. We have introduced [X. Qian and J. S. Villarrubia, Ultramicroscopy, in press] an alternative dexel-based method, that does the same in either 2D or 3D. This paper describes the application of this method to sample shapes of interest in semiconductor manufacturing. When the tip shape is known (e.g., by prior measurement using a tip characterizer) a 3D sample surface may be reconstructed from its 3D image. Basing the CD measurement upon such a reconstruction is shown here to remove some measurement artifacts that are not removed (or are incompletely removed) by the existing measurement procedures.

Manufacturability: from design to SPC limits through "corner-lot" characterization

NASA Astrophysics Data System (ADS)

Hogan, Timothy J.; Baker, James C.; Wesneski, Lisa; Black, Robert S.; Rothenbury, Dave

2004-12-01

Texas Instruments" Digital Micro-mirror Device, is used in a wide variety of optical display applications ranging from fixed and portable projectors to high-definition television (HDTV) to digital cinema projection systems. A new DMD pixel architecture, called "FTP", was designed and qualified by Texas Instruments DLPTMTM Group in 2003 to meet increased performance objectives for brightness and contrast ratio. Coordination between design, test and fabrication groups was required to balance pixel performance requirements and manufacturing capability. "Corner Lot" designed experiments (DOE) were used to verify "fabrication space" available for the pixel design. The corner lot technique allows confirmation of manufacturability projections early in the design/qualification cycle. Through careful design and analysis of the corner-lot DOE, a balance of critical dimension (cd) "budgets" is possible so that specification and process control limits can be established that meet both customer and factory requirements. The application of corner-lot DOE is illustrated in a case history of the DMD "FTP" pixel. The process for balancing test parameter requirements with multiple critical dimension budgets is shown. MEMS/MOEMS device design and fabrication can use similar techniques to achieve agressive design-to-qualification goals.

Manufacturability: from design to SPC limits through "corner-lot" characterization

NASA Astrophysics Data System (ADS)

Hogan, Timothy J.; Baker, James C.; Wesneski, Lisa; Black, Robert S.; Rothenbury, Dave

2005-01-01

Texas Instruments" Digital Micro-mirror Device, is used in a wide variety of optical display applications ranging from fixed and portable projectors to high-definition television (HDTV) to digital cinema projection systems. A new DMD pixel architecture, called "FTP", was designed and qualified by Texas Instruments DLPTMTM Group in 2003 to meet increased performance objectives for brightness and contrast ratio. Coordination between design, test and fabrication groups was required to balance pixel performance requirements and manufacturing capability. "Corner Lot" designed experiments (DOE) were used to verify "fabrication space" available for the pixel design. The corner lot technique allows confirmation of manufacturability projections early in the design/qualification cycle. Through careful design and analysis of the corner-lot DOE, a balance of critical dimension (cd) "budgets" is possible so that specification and process control limits can be established that meet both customer and factory requirements. The application of corner-lot DOE is illustrated in a case history of the DMD "FTP" pixel. The process for balancing test parameter requirements with multiple critical dimension budgets is shown. MEMS/MOEMS device design and fabrication can use similar techniques to achieve agressive design-to-qualification goals.

What happens in the thymus does not stay in the thymus: how T cells recycle the CD4+-CD8+ lineage commitment transcriptional circuitry to control their function

PubMed Central

Vacchio, Melanie S.; Bosselut, Rémy

2016-01-01

MHC-restricted CD4+ and CD8+ T cell are at the core of most adaptive immune responses. Although these cells carry distinct functions, they arise from a common precursor during thymic differentiation, in a developmental sequence that matches CD4 and CD8 expression and functional potential with MHC restriction. While the transcriptional control of CD4+-CD8+ lineage choice in the thymus is now better understood, less was known about what maintains the CD4+- and CD8+-lineage integrity of mature T cells. In this review, we discuss the mechanisms that establish in the thymus, and maintain in post-thymic cells, the separation of these lineages. We focus on recent studies that address the mechanisms of epigenetic control of Cd4 expression and emphasize how maintaining a transcriptional circuitry nucleated around Thpok and Runx proteins, the key architects of CD4+-CD8+ lineage commitment in the thymus, is critical for CD4+ T cell helper functions. PMID:27260768

Increase of CD69, CD161 and CD94 on NK cells in women with recurrent spontaneous abortion and in vitro fertilization failure.

PubMed

Ghafourian, Mehri; Karami, Najmeh; Khodadadi, Ali; Nikbakht, Roshan

2014-06-01

Recurrent spontaneous abortion (RSA) and in vitro fertilization (IVF) failure with unknown causes are the controversial issues that are probably related to the immune system. To compare circulating NK cells expressing activation and inhibition surface markers between patients with RSA and IVF failure with those of healthy multiparous and successful IVF control women, respectively. In this case-control study peripheral blood samples were collected from 43 patients who included 23 women with RSA and 20 with IVF failure, plus 43 healthy control women comprising of 36 normal multiparous women and seven women with successful IVF. The expression of CD69, CD94 and CD161 surface markers on CD56+NK cells were assessed using specific monoclonal antibodies by flowcytometry. The percentage of NK cells increased significantly in patients with RSA and in women with IVF failure in comparison to healthy multiparous and successful IVF control groups (p<0.001). The overall expression of CD69, CD94, CD161 were also increased significantly on NK cells in both patient groups compared to control groups (p<0.001). Elevated expression of CD69 and CD161 on NK cells can be considered as immunological risk markers in RSA and IVF failure. However, it is not clear if high expression of CD94 on peripheral blood NK cells is related to abnormal activity of endometrial NK cells.

Enhanced expression of PD-1 and other activation markers by CD4+ T cells of young but not old patients with metastatic melanoma.

PubMed

van den Brom, Rob R H; van der Geest, Kornelis S M; Brouwer, Elisabeth; Hospers, Geke A P; Boots, Annemieke M H

2018-06-01

The biological behavior of melanoma is unfavorable in the elderly when compared to young subjects. We hypothesized that differences in T-cell responses might underlie the distinct behavior of melanoma in young and old melanoma patients. Therefore, we investigated the circulating T-cell compartment of 34 patients with metastatic melanoma and 42 controls, which were classified as either young or old. Absolute numbers of CD4+ T cells were decreased in young and old melanoma patients when compared to the age-matched control groups. Percentages of naive and memory CD4+ T cells were not different when comparing old melanoma patients to age-matched controls. Percentages of memory CD4+ T cells tended to be increased in young melanoma patients compared to young controls. Proportions of naive CD4+ T cells were lower in young patients than in age-matched controls, and actually comparable to those in old patients and controls. This was accompanied with increased percentages of memory CD4+ T cells expressing HLA-DR, Ki-67, and PD-1 in young melanoma patients in comparison to the age-matched controls, but not in old patients. Proportions of CD45RA-FOXP3 high memory regulatory T cells were increased in young and old melanoma patients when compared to their age-matched controls, whereas those of CD45RA+FOXP3 low naive regulatory T cells were similar. We observed no clear modulation of the circulating CD8+ T-cell repertoire in melanoma patients. In conclusion, we show that CD4+ T cells of young melanoma patients show signs of activation, whereas these signs are less clear in CD4+ T cells of old patients.

Nonlinear analysis of fetal heart rate dynamics in fetuses compromised by asymptomatic partial placental abruption.

PubMed

Choi, Won-Young; Hoh, Jeong-Kyu

2015-12-01

We analyzed fetal heart rate (FHR) parameters, dynamics, and outcomes in pregnancies with asymptomatic partial placental abruption (PPA) compared with those in normal pregnancies. We examined nonstress test (NST) data acquired from 2003 to 2012 at our institution. Normal pregnancies (N = 170) and PPA cases (N = 17) were matched for gestational age, fetal sex, and mean FHR. NSTs were performed at 33-42 weeks of gestation. FHR parameters obtained from the NST and perinatal outcomes were analyzed using linear methods. Nonlinear indices, including approximate entropy (ApEn), sample entropy (SampEn), short-term and long-term scaling exponents (α1 and α2), and correlation dimension (CD), were used to interpret FHR dynamics and system complexity. The area under a receiver operating characteristic curve (AUC) was used to evaluate the nonlinear indices. There were no significant differences in general characteristics and FHR parameters between the PPA and control groups. However, gestational age at delivery, birth weight, 5-min Apgar scores, ApEn, SampEn, and CD were significantly lower in the PPA group than in the control group (P < 0.05). The long-term scaling exponent (α2) and crossover index (α2/α1) of the PPA fetuses were significantly higher than those of the controls (P < 0.01). A multiple regression model showed better performance in predicting PPA (AUC, 0.92; sensitivity 82.35%; specificity, 94.12%). Nonlinear dynamic indices of FHR in asymptomatic PPA were qualitatively different from those in normal pregnancies, whereas the conventional FHR parameters were not significantly different. Copyright © 2015 Elsevier Ltd. All rights reserved.

Anomalies of the CD8+ T cell pool in haemochromatosis: HLA-A3-linked expansions of CD8+CD28- T cells.

PubMed

Arosa, F A; Oliveira, L; Porto, G; da Silva, B M; Kruijer, W; Veltman, J; de Sousa, M

1997-03-01

The present study consists of a phenotypic and functional characterization of peripheral blood T lymphocytes in a group of 21 patients with hereditary haemochromatosis (HH), an MHC class I-linked genetic disease resulting in iron overload, and a group of 30 healthy individuals, both HLA-phenotyped. The HH patients studied showed an increased percentage of CD8+ CD28- T cells with a corresponding reduction in the percentage of CD8+ CD28+ T cells in peripheral blood relative to healthy blood donors. No anomalies of CD28 expression were found in the CD4+ subset. The presence of the HLA-A3 antigen but not age accounted for these imbalances. Thus, an apparent failure of the CD8+ CD28+ T cell population 'to expand', coinciding with an 'expansion' of CD8+ CD28- T cells in peripheral blood of HLA-A3+ but not HLA-A3- HH patients was observed when compared with the respective HLA-A3-matched control group. A significantly higher percentage of HLA-DR+ but not CD45RO+ cells was also found within the peripheral CD8+ T cell subset in HH patients relative to controls. Phytohaemagglutinin (PHA) stimulation of peripheral blood mononuclear cells (PBMC) for 5 days showed: (i) that CD8+ CD28+ T cells both in controls and HH were able to expand in vitro; (ii) that CD8+ CD28- T cells decreased markedly after activation in controls but not in HH patients. Moreover, functional studies showed that CD8+ cytotoxic T lymphocytes (CTL) from HH patients exhibited a diminished cytotoxic activity (approx. two-fold) in standard 51Cr-release assays when compared with CD8+ CTL from healthy controls. The present results provide additional evidence for the existence of phenotypic and functional anomalies of the peripheral CD8+ T cell pool that may underlie the clinical heterogeneity of this iron overload disease. They are of particular relevance given the recent discovery of a novel mutated MHC class I-like gene in HH.

Anomalies of the CD8+ T cell pool in haemochromatosis: HLA-A3-linked expansions of CD8+CD28− T cells

PubMed Central

AROSA, F A; OLIVEIRA, L; PORTO, G; DA SILVA, B M; KRUIJER, W; VELTMAN, J; DE SOUSA, M

1997-01-01

The present study consists of a phenotypic and functional characterization of peripheral blood T lymphocytes in a group of 21 patients with hereditary haemochromatosis (HH), an MHC class I-linked genetic disease resulting in iron overload, and a group of 30 healthy individuals, both HLA-phenotyped. The HH patients studied showed an increased percentage of CD8+ CD28− T cells with a corresponding reduction in the percentage of CD8+ CD28+ T cells in peripheral blood relative to healthy blood donors. No anomalies of CD28 expression were found in the CD4+ subset. The presence of the HLA-A3 antigen but not age accounted for these imbalances. Thus, an apparent failure of the CD8+ CD28+ T cell population ‘to expand’, coinciding with an ‘expansion’ of CD8+ CD28− T cells in peripheral blood of HLA-A3+ but not HLA-A3− HH patients was observed when compared with the respective HLA-A3-matched control group. A significantly higher percentage of HLA-DR+ but not CD45RO+ cells was also found within the peripheral CD8+ T cell subset in HH patients relative to controls. Phytohaemagglutinin (PHA) stimulation of peripheral blood mononuclear cells (PBMC) for 5 days showed: (i) that CD8+ CD28+ T cells both in controls and HH were able to expand in vitro; (ii) that CD8+ CD28− T cells decreased markedly after activation in controls but not in HH patients. Moreover, functional studies showed that CD8+ cytotoxic T lymphocytes (CTL) from HH patients exhibited a diminished cytotoxic activity (approx. two-fold) in standard 51Cr-release assays when compared with CD8+ CTL from healthy controls. The present results provide additional evidence for the existence of phenotypic and functional anomalies of the peripheral CD8+ T cell pool that may underlie the clinical heterogeneity of this iron overload disease. They are of particular relevance given the recent discovery of a novel mutated MHC class I-like gene in HH. PMID:9067531

Enabling optical metrology on small 5×5μm2 in-cell targets to support flexible sampling and higher order overlay and CD control for advanced logic devices nodes

NASA Astrophysics Data System (ADS)

Salerno, Antonio; de la Fuente, Isabel; Hsu, Zack; Tai, Alan; Chang, Hammer; McNamara, Elliott; Cramer, Hugo; Li, Daoping

2018-03-01

In next generation Logic devices, overlay control requirements shrink to sub 2.5nm level on-product overlay. Historically on-product overlay has been defined by the overlay capability of after-develop in-scribe targets. However, due to design and dimension, the after development metrology targets are not completely representative for the final overlay of the device. In addition, they are confined to the scribe-lane area, which limits the sampling possibilities. To address these two issues, metrology on structures matching the device structure and which can be sampled with high density across the device is required. Conventional after-etch CDSEM techniques on logic devices present difficulties in discerning the layers of interest, potential destructive charging effects and finally, they are limited by the long measurement times[1] [2] [3] . All together, limit the sampling densities and making CDSEM less attractive for control applications. Optical metrology can overcome most of these limitations. Such measurement, however, does require repetitive structures. This requirement is not fulfilled by logic devices, as the features vary in pitch and CD over the exposure field. The solution is to use small targets, with a maximum pad size of 5x5um2 , which can easily be placed in the logic cell area. These targets share the process and architecture of the device features of interest, but with a modified design that replicates as close as possible the device layout, allowing for in-device metrology for both CD and Overlay. This solution enables measuring closer to the actual product feature location and, not being limited to scribe-lanes, it opens the possibility of higher-density sampling schemes across the field. In summary, these targets become the facilitator of in-device metrology (IDM), that is, enabling the measurements both in-device Overlay and the CD parameters of interest and can deliver accurate, high-throughput, dense and after-etch measurements for Logic. Overlay improvements derived from a high-densely sampled Overlay map measured with 5x5 um2 In Device Metrology (IDM) targets were investigated on a customer Logic application. In this work we present both the main design aspects of the 5x5 um2 IDM targets, as well as the results on the improved Overlay performance.

The role of CD27-CD70-mediated T cell co-stimulation in vasculogenesis, arteriogenesis and angiogenesis.

PubMed

Simons, K H; Aref, Z; Peters, H A B; Welten, S P; Nossent, A Y; Jukema, J W; Hamming, J F; Arens, R; de Vries, M R; Quax, P H A

2018-06-01

T cells have a distinctive role in neovascularization, which consists of arteriogenesis and angiogenesis under pathological conditions and vasculogenesis under physiological conditions. However, the role of co-stimulation in T cell activation in neovascularization has yet to be established. The aim of this study was to investigate the role T cell co-stimulation and inhibition in angiogenesis, arteriogenesis and vasculogenesis. Hind limb ischemia was induced by double ligation of the left femoral artery in mice and blood flow recovery was measured with Laser Doppler Perfusion Imaging in control, CD70 -/- , CD80/86 -/- , CD70/80/86 -/- and CTLA4 +/- mice. Blood flow recovery was significantly impaired in mice lacking CD70 compared to control mice, but was similar in CD80/86 -/- , CTLA4 +/- and control mice. Mice lacking CD70 showed impaired vasculogenesis, since the number of pre-existing collaterals was reduced as observed in the pia mater compared to control mice. In vitro an impaired capability of vascular smooth muscle cells (VSMC) to activate T cells was observed in VSMC lacking CD70. Furthermore, CD70 -/- , CD80/86 -/- and CD70/80/86 -/- mice showed reduced angiogenesis in the soleus muscle 10 days after ligation. Arteriogenesis was also decreased in CD70 -/- compared to control mice 10 and 28 days after surgery. The present study is the first to describe an important role for T cell activation via co-stimulation in angiogenesis, arteriogenesis and vasculogenesis, where the CD27-CD70 T cell co-stimulation pathway appears to be the most important co-stimulation pathway in pre-existing collateral formation and post-ischemic blood flow recovery, by arteriogenesis and angiogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

Immunological changes at rectal mucosa in appendectomised subjects and inhabitants of developing countries.

PubMed

Olivares, David; Gisbert, Javier P; Gamallo, Carlos; Maté-Jiménez, José

2007-02-01

It has been suggested that appendicitis protects against ulcerative colitis. We hypothesize that early poor hygiene protects against ulcerative colitis (UC) and predisposes to appendicitis. Our aim was to elucidate the immunological characteristics of rectal mucosa in two populations protected against UC development: appendectomised subjects and inhabitants of developing countries. this was an age-matched prospective case-control study. Each consecutive individual case appendectomised (group A) was compared to another control from a developing country (group B) and to a control from the general population (group C). Four biopsies from rectal mucosa were taken from all subjects, two for histological and two for histochemical study; specific antibodies were used for T lymphocytes CD3+, CD4+, CD8+ and B lymphocytes CD20+ populations. Mucosa samples of 45 non-smoker healthy subjects were studied, of which 15 were from group A, 15 from group B and 15 from group C. In appendectomised subjects, the proportion of CD8+ cells was higher than in the control group (p<0.001), but similar to that in B group. The proportion of CD3+ and CD20+ cells was significatively lower than in Ecuadorians, but similar to the control group. In Ecuadorians, the proportion of CD3+ and CD8+ cells was significatively higher than in the control group (p<0.001), and were similar to that of CD20+. There were no significant differences in the proportion of CD4+. Appendectomy and deficient environmental hygiene are associated with an increase of CD8+ T lymphocytes in the rectal mucosa. Moreover, deficient environmental hygiene is associated with an increase of CD3+ and CD8+ lymphocytes. The CD8+ increase is the only common significant alteration in the mucosa of both groups protected against the development of ulcerative colitis, suggesting that the factors causing changes in lamina propria lymphocytes of both groups are different.

Circulating Endothelial Progenitor Cells Present an Inflammatory Phenotype and Function in Patients With Alcoholic Liver Cirrhosis

PubMed Central

Kaur, Savneet; Sehgal, Rashi; Shastry, Saggere M.; McCaughan, Geoffrey; McGuire, Helen M.; Fazekas St de Groth, Barbara; Sarin, Shiv; Trehanpati, Nirupma; Seth, Devanshi

2018-01-01

Background and Aim: Endothelial progenitor cells (EPCs) have been implicated in liver injury and repair. However, the phenotype and potential of these heterogenous EPCs remain elusive. In particular, their involvement in the pathogenesis of alcoholic liver cirrhosis (ALC) remains unclear. The current study extensively characterized the phenotype and functions of EPCs to understand their role in ALC pathogenesis. Methods: Circulating EPCs were identified as CD34+CD133+CD31+ cells by flow cytometer in ALC patients (n = 7) and healthy controls (HC, n = 7). A comprehensive characterization of circulating EPCs using more than 30 phenotype markers was performed by mass cytometer time of flight (CyTOF) in an independent cohort of age and gender matched ALC patients (n = 4) and controls (n = 5). Ex vivo cultures of circulating EPCs from ALC patients (n = 20) and controls (n = 18) were also tested for their functions, including colony formation, LDL uptake, lectin binding and cytokine secretion (ELISA). Results: Three distinct populations of circulating EPCs (CD34+CD133+CD31+) were identified, classified on their CD45 expression (negative: CD45−; intermediate: CD45int; high: CD45hi). CD45int and CD45hi EPCs significantly increased in ALC patients compared to controls (p-val = 0.006). CyTOF data showed that CD45hi EPCs were distinct from CD45− and CD45int EPCs, with higher expression of T cell and myeloid markers, including CD3, CD4, HLA-DR, and chemokine receptors, CCR2, CCR5, CCR7, and CX3CR1. Similar to circulating EPCs, percentage of CD45hiCD34+CD31+ EPCs in ex-vivo cultures from patients, were significantly higher compared to controls (p < 0.05). Cultured EPCs from patients also showed increased LDL uptake, lectin binding and release of TNF-alpha, RANTES, FGF-2, and VEGF. Conclusions: We report the first extensive characterization of circulating human EPCs with distinct EPC subtypes. Increase in CD45hi EPC subtype in ALC patients with enhanced functions, inflammatory cytokines and angiogenic mediators in patients suggests an inflammatory role for these cells in ALC. PMID:29872403

Regulatory T cell subsets in children with systemic lupus erythematosus.

PubMed

Eltayeb, Azza A; Sayed, Douaa M; Afifi, Noha A; Ibrahim, Maggie A; Sheref, Tahra M

2014-08-01

The aim of this work was to quantify CD4(+)CD25(+)Foxp3(+) T cells (Tregs) in Egyptian children with SLE and to correlate these findings with their disease activity scores and drug therapy. We enrolled 37 Egyptian children with active SLE. Disease activity was assessed by measuring serum levels of anti-dsDNA antibody and by the SLEDAI scores. Twenty healthy children were also enrolled as normal controls. The CD4+CD25+, CD4+CD25(bright), and CD4+CD25(dim) cells in patients were significantly increased in comparison to controls. There was no significant difference in the Foxp3 gated on CD4+CD25(bright) and CD4+CD25(dim), but there was a significant increase when gated on CD4+CD25- and whole CD4+ cells in patients than controls. There was no significant difference among patients with different degrees of activity on different lines of treatments and their outcomes as regards all studied values. There was no significant correlation between SLEDAI score and any of the studied parameters except for a significant negative correlation with gated lymphocytes. There is increased expression of Foxp3 in CD4+ T cells mostly CD25- in Egyptian children with active SLE under corticosteroid treatment regardless of disease activity.

Capturing the true burden of dystonia on patients: the Cervical Dystonia Impact Profile (CDIP-58).

PubMed

Cano, S J; Warner, T T; Linacre, J M; Bhatia, K P; Thompson, A J; Fitzpatrick, R; Hobart, J C

2004-11-09

To develop a new rating scale for measuring the health impact of cervical dystonia (CD) that includes patients' perceptions and complements existing observer dependent clinician rating scales. Scale development was in three stages. In Stage 1, a large pool of items was generated from patient interviews (n = 25), expert opinion, and literature review. In Stage 2, these items were administered by postal survey to people with CD. The resulting data were analyzed using Rasch item analysis to construct, from the item pool, a rating scale that satisfied criteria for rigorous measurement. In Stage 3, the measurement properties of this rating scale were examined in an independent sample of people with CD. In Stage 1, 150 items concerning the health impact of CD were generated. In Stage 2, 556 people completed questionnaires (87% response rate) and a 58-item rating scale measuring the health impact of CD in eight areas was constructed (CD Impact Profile, CDIP-58). In Stage 3, CDIP-58 data from 391 people (87% response rate) were received. Analyses supported the measurement of eight unidimensional constructs (infit mean square range 0.62 to 1.50), item calibration (33.37 to 67.56), and patient separation statistics (2.59 to 3.38). Items demonstrated stable calibrations in subgroups of people with CD supporting the stability of the CDIP-58. The CDIP-58 is a reliable and valid patient-based rating scale measuring the health impact of CD in eight health dimensions.

Altered intestinal microbiota and blood T cell phenotype are shared by patients with Crohn's disease and their unaffected siblings.

PubMed

Hedin, Charlotte R; McCarthy, Neil E; Louis, Petra; Farquharson, Freda M; McCartney, Sara; Taylor, Kirstin; Prescott, Natalie J; Murrells, Trevor; Stagg, Andrew J; Whelan, Kevin; Lindsay, James O

2014-10-01

Crohn's disease (CD) is associated with intestinal dysbiosis, altered blood T cell populations, elevated faecal calprotectin (FC) and increased intestinal permeability (IP). CD-associated features present in siblings (increased risk of CD) but not in healthy controls, provide insight into early CD pathogenesis. We aimed to (1) Delineate the genetic, immune and microbiological profile of patients with CD, their siblings and controls and (2) Determine which factors discriminate between groups. Faecal microbiology was analysed by quantitative PCR targeting 16S ribosomal RNA, FC by ELISA, blood T cell phenotype by flow cytometry and IP by differential lactulose-rhamnose absorption in 22 patients with inactive CD, 21 of their healthy siblings and 25 controls. Subject's genotype relative risk was determined by Illumina Immuno BeadChip. Strikingly, siblings shared aspects of intestinal dysbiosis with patients with CD (lower concentrations of Faecalibacterium prausnitzii (p=0.048), Clostridia cluster IV (p=0.003) and Roseburia spp. (p=0.09) compared with controls). As in CD, siblings demonstrated a predominance of memory T cells (p=0.002) and elevated naïve CD4 T cell β7 integrin expression (p=0.01) compared with controls. FC was elevated (>50 μg/g) in 8/21 (38%) siblings compared with 2/25 (8%) controls (p=0.028); whereas IP did not differ between siblings and controls. Discriminant function analysis determined that combinations of these factors significantly discriminated between groups (χ(2)=80.4, df=20, p<0.001). Siblings were separated from controls by immunological and microbiological variables. Healthy siblings of patients with CD manifest immune and microbiological abnormalities associated with CD distinct from their genotype-related risk and provide an excellent model in which to investigate early CD pathogenesis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Depletion of pro-inflammatory CD161(+) double negative (CD3(+)CD4(-)CD8(-)) T cells in AIDS patients is ameliorated by expansion of the γδ T cell population.

PubMed

Singleterry, Will L; Henderson, Harold; Cruse, Julius M

2012-02-01

In this present investigation, flow cytometry was utilized to evaluate 13 healthy controls and 31 HIV-1 infected patients who had advanced to the AIDS stage of infection (CD4 count below 200 cells/mm(3)), for the expression of CD161 on CD3(+) double negative (DN) (CD3(+)CD4(-)CD8(-)) T cells, CD4(+) T cells, CD8(+) T cells and γδ T cells. The observed depletion of CD161(+) T cells from peripheral circulation was due primarily to the loss of CD4(+)CD161(+) T cells; as these cells represented 8.67±0.74% of the total healthy control peripheral T cell population, while the CD4(+)CD161(+) T cells of the AIDS group represented only 3.35±0.41% (p=<0.0001) of the total peripheral T cell population. We have also shown here that the DN T cell population was more than doubled in the AIDS group, with the DN T cell population expanding from 3.29±0.45% of the healthy control peripheral T cell population to 8.64±1.16% (p=0.0001) of the AIDS group peripheral T cell population. By evaluating the expression of CD161 on the surface of the DN T cells we showed that within the healthy control group, 47.4±4.99% of the DN T cells were positive for the expression of CD161, while only 26.4±3.54% (p=0.002) of the AIDS group's DN T cells expressed CD161. Despite CD161 expression being halved on the DN T cells of the AIDS group, when we compared the total peripheral T cell percentage of CD161(+) DN T cells between the healthy control group and the AIDS group, there was no statistical difference. Even though only 26.4% DN T cells within the AIDS group were positive for CD161(+), the overall DN T cell population had expanded to such an extent that there was no statistical difference between the groups with regard to CD161(+) DN T cells as a percentage of the total peripheral T cell population. Furthermore, we showed that within the DN T cell population, there was an approximate 2:1 ratio of γδ to αβ T cells, and this ratio was maintained in both the healthy control group and the AIDS group. While evaluating γδ T cells we also discovered that CD8(+) γδ T cells were expanded from 0.62±.09% of the healthy control peripheral T cell population to 5.01±.88% (p=<0.0001) of the peripheral T cell population of the AIDS group; and that this population of CD8(+) γδ T cells underwent the same reduction in percentage of cells expressing CD161(+), further demonstrated that the phenomenon of CD161(+) percentage reduction and compensatory increase in total cell population was affecting the entire circulating γδ T cell population. Copyright © 2011 Elsevier Inc. All rights reserved.

Duodenal intraepithelial T lymphocytes in patients with functional dyspepsia

PubMed Central

Gargala, Gilles; Lecleire, Stéphane; François, Arnaud; Jacquot, Serge; Déchelotte, Pierre; Ballet, Jean Jacques; Favennec, Loic; Ducrotté, Philippe

2007-01-01

AIM: To quantify the intraepithelial lymphocytes (IELs) and to document the membrane expression of CD4, CD8, TCRγδ and adhesion and/or activation-associated molecules (CD103, CD28, CD44, CD69, HLA-DR, CD95/Fas) in the duodenal mucosa of patients with functional dyspepsia (FD) in order to provide arguments for an immunological process in FD. METHODS: Twenty-six FD patients according to Rome II criteria (20 were H pylori negative) were studied and compared to 12 healthy adults. IELs were isolated from five duodenal biopsy samples, then quantified by microscopy and flow cytometry while the membrane phenotypes were determined by cytofluorometry. RESULTS: Duodenal histological examination was normal. In H pylori negative patients, the number of IELs was not different from that in healthy controls. Median percentage expression of CD4, CD8, or TCRγδ and CD103, CD44, CD28, CD69 on CD3+ IELs, among the adhesion/activation associated molecules tested, was not different from that in healthy controls. In contrast, the median percentage expression of CD95/Fas [22 (9-65) vs 45 (19-88), P = 0.03] and HLA-DR expressing CD3+ IELs [4 (0-30) vs 13 (4-42), P = 0.04] was significantly lower in the H pylori negative FD group than in healthy controls, respectively. The number of IELs was significantly greater in H pylori positive FD patients than in healthy controls [median ratiofor 100 enterocytes 27.5 (6.7-62.5) vs 10.8 (3-33.3), P = 0.02] due to a higher number of CD8+ CD3+ IELs. CONCLUSION: In H pylori negative FD patients, the phenotypic characterization of IELs suggests that we cannot exclude a role of IELs in FD. PMID:17511033

Markers of apoptosis and proliferation related gene products as predictors of treatment outcome in childhood acute lymphoblastic leukemia.

PubMed

Hafez, Mohammad; Al-Tonbary, Youssef; El-Bayoumi, Mohammed A; Hatem, Nadia; Hawas, Samia; Mansour, Ahmed; Marzouk, Iman; Hafez, Mona M; Yahia, Sohier; Farahat, Nahla

2007-06-01

The aim of the study is to characterize markers of apoptosis in children with acute lymphoblastic leukemia (ALL) in relation to treatment outcome of the disease. The study was performed on 34 children with ALL and 39 healthy children as a control group. Apoptosis was assessed by cell morphology; DNA fragmentation; ELISA and RT-PCR for CD95, CD95L, BcL-2 and nuclear factor-kappa B (NF-kappaB); and flow cytometry for CD95, CD40, CD49d and CD11a. Apoptosis was significantly lower in patients than controls. Apoptosis detected by CD95 ligand was significantly lower in cases with no remission after treatment than those who achieved remission. Anti-apoptotic factors: CD40, BcL-2, and NF-kappaB were all found to be higher in cases than controls and in cases with no remission than those achieved remission. CD49d was significantly lower in cases than controls, and significantly lower in cases with who did not achieve remission. CD11a levels were similar in the various groups. Delayed apoptosis of ALL cells is genetically controlled either directly or indirectly by a network of oncogenes and tumor suppressor genes. CD40 appeared to stimulate both T and B lineage and is considered the most potent influencer and predictor of resistance to therapy. Inhibitors for the activity of CD40, Bcl-2 and NF-kappaB as well as stimulants to CD95 could have a potential therapeutic benefit.

Clinical significance of Tim3-positive T cell subsets in patients with multiple sclerosis.

PubMed

Feng, Xuemei; Feng, Juan

2016-12-01

The present study evaluated associations between the percentages of T cell immunoglobulin and mucin domain 3 (Tim3)-positive T cells and related cytokines and multiple sclerosis (MS). We collected peripheral blood samples from 30 MS patients and 30 healthy controls. Flow cytometry was used to determine the proportions of CD3 + Tim3 + , CD4 + Tim3 + , and CD4 + CD25 + Tim3 + in peripheral blood mononuclear cells (PBMCs) and related cell subsets. The serum concentrations of galectin-9, IL-17, and IFN-γ also were determined using enzyme-linked immunosorbent assays (ELISA). The percentages of Tim3-positive T cells in CD4 + and CD4 + CD25 + T cell subsets were significantly lower among MS patients than among controls. This difference was particularly evident in the CD4 + CD25(high) T cell subset. The proportions of CD4 + Tim3 + and CD4 + CD25 + Tim3 + cells in PBMCs were significantly lower in the MS group than in the control group, whereas no significant differences were detected regarding the percentages of CD3 + Tim3 + in PBMCs and T cell subsets. The serum concentrations of galectin-9, IL-17, and IFN-γ all were increased in MS patients compared with healthy controls. Our results support that Tim3 and related cytokines may be involved in the onset of MS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Increased peripheral blood CD4+ T cell responses to deamidated but not to native gliadin in children with coeliac disease

PubMed Central

Lammi, A; Arikoski, P; Vaarala, O; Kinnunen, T; Ilonen, J

2012-01-01

T cell recognition of gliadin from dietary gluten is essential for the pathogenesis of coeliac disease (CD). The aim of the present study was to analyse whether gliadin-specific T cells are detectable in the circulation of children with newly diagnosed coeliac disease by using a sensitive carboxfluorescein diacetate succinimidyl ester (CFSE) dilution method. Peripheral blood CD4+ T cell responses were analysed in 20 children at diagnosis of CD and compared to those in 64 healthy control children carrying the CD-associated human leucocyte antigen (HLA)-DQ2 or -DQ8 alleles. Deamidated gliadin (gTG)-specific T cells were detectable in the peripheral blood of more than half the children with CD (11 of 20, 55%) compared to 15 of 64 (23·4%) of the control children (P = 0·008). Proliferative responses to gTG were also significantly stronger in children with CD than in controls (P = 0·01). In contrast, T cells specific to native gliadin were detectable at comparable frequencies in children with CD (two of 19, 10·5%) and controls (13 of 64, 20·3%). gTG-specific T cells had a memory phenotype more often than those specific to native gliadin in children with CD (P = 0·02), whereas controls had similar percentages of memory cells in both stimulations. Finally, gTG-specific CD4+ T cells had a higher expression of the gut-homing molecule β7 integrin than those specific to the control antigen tetanus toxoid. Collectively, our current results demonstrate that the frequency of circulating memory CD4+ T cells specific to gTG but not native gliadin is increased in children with newly diagnosed CD. PMID:22471282

Increased peripheral blood CD4+ T cell responses to deamidated but not to native gliadin in children with coeliac disease.

PubMed

Lammi, A; Arikoski, P; Vaarala, O; Kinnunen, T; Ilonen, J

2012-05-01

T cell recognition of gliadin from dietary gluten is essential for the pathogenesis of coeliac disease (CD). The aim of the present study was to analyse whether gliadin-specific T cells are detectable in the circulation of children with newly diagnosed coeliac disease by using a sensitive carboxfluorescein diacetate succinimidyl ester (CFSE) dilution method. Peripheral blood CD4(+) T cell responses were analysed in 20 children at diagnosis of CD and compared to those in 64 healthy control children carrying the CD-associated human leucocyte antigen (HLA)-DQ2 or -DQ8 alleles. Deamidated gliadin (gTG)-specific T cells were detectable in the peripheral blood of more than half the children with CD (11 of 20, 55%) compared to 15 of 64 (23.4%) of the control children (P = 0.008). Proliferative responses to gTG were also significantly stronger in children with CD than in controls (P = 0.01). In contrast, T cells specific to native gliadin were detectable at comparable frequencies in children with CD (two of 19, 10.5%) and controls (13 of 64, 20.3%). gTG-specific T cells had a memory phenotype more often than those specific to native gliadin in children with CD (P = 0.02), whereas controls had similar percentages of memory cells in both stimulations. Finally, gTG-specific CD4(+) T cells had a higher expression of the gut-homing molecule β7 integrin than those specific to the control antigen tetanus toxoid. Collectively, our current results demonstrate that the frequency of circulating memory CD4(+) T cells specific to gTG but not native gliadin is increased in children with newly diagnosed CD. © 2012 The Authors;Clinical and Experimental Immunology © 2012 British Society for Immunology.

Activated platelets are the source of elevated levels of soluble CD40 ligand in the circulation of inflammatory bowel disease patients.

PubMed

Danese, S; Katz, J A; Saibeni, S; Papa, A; Gasbarrini, A; Vecchi, M; Fiocchi, C

2003-10-01

The CD40/CD40L system, a key regulator and amplifier of immune reactivity, is activated in inflammatory bowel disease (IBD) mucosa. To determine whether plasma levels of sCD40L are elevated in Crohn's disease (CD) and ulcerative colitis (UC) patients compared with normal controls, to investigate the cellular source of sCD40L, and to explore CD40L induction mechanisms. CD, UC, and normal control subjects were studied. The concentration of sCD40L in plasma and supernatants of freshly isolated platelets and autologous peripheral blood T cells (PBT) was measured by ELISA. Surface CD40L expression level was measured by flow cytometry in resting and thrombin activated platelets, and unstimulated and CD3/CD28 stimulated PBT before and after coculture with human intestinal microvascular endothelial cells (HIMEC). Compared with normal controls, plasma sCD40L levels were significantly higher in both CD and UC patients and proportional to the extent of mucosal inflammation. Platelets from IBD patients displayed a significantly higher surface CD40L expression than those from control subjects, and released greater amounts of sCD40L than autologous PBT. Contact with IL-1beta activated HIMEC induced significant upregulation of CD40L surface expression and release by platelets. Elevated levels of sCD40L in the circulation of IBD patients reflect enhanced surface expression and release of CD40L by platelets. This phenomenon translates to an increased platelet activation state apparently induced by passage through an inflamed mucosal microvascular bed, a conclusion supported by the positive correlation of plasma sCD40L levels with the extent of anatomical involvement by IBD. These results suggest that platelet-endothelial interactions critically contribute to activation of the CD40 pathway in IBD.

Changes in serum levels of lipopolysaccharides and CD26 in patients with Crohn's disease

PubMed Central

Kotze, Paulo Gustavo; Martinez, Carlos Augusto Real; Camargo, Michel Gardere; Guadagnini, Dioze; Calixto, Antonio Ramos; Vasques, Ana Carolina Junqueira; Ayrizono, Maria de Lourdes Setsuko; Geloneze, Bruno; Pareja, José Carlos; Saad, Mario José; Coy, Claudio Saddy Rodrigues

2017-01-01

Background/Aims Lipopolysaccharide (LPS) is a molecule formed by lipids and polysaccharides and is the major cell wall component of gram-negative bacteria. High LPS levels are known to block CD26 expression by activating Toll-like receptor 4. The aim of this study was to correlate the serum levels of LPS and CD26 in Crohn's disease (CD) patients with serum levels of C-reactive protein (CRP), interleukins, CD activity index, and tumor necrosis factor-α (TNF-α). Methods Serum samples were collected from 27 individuals (10 with active CD, 10 with inactive CD, and 7 controls) and the levels of LPS, CD26, TNF-α, interleukin-1β (IL-1β), IL-6, IL-17, and CRP were determined by enzyme-linked immunosorbent assay. The levels of LPS and CD26 were then tested for correlation with TNF-α, IL-1β, IL-6, IL-17, and CRP. Results Serum levels of LPS were significantly elevated in the active CD group (P=0.003). Levels of IL-1β (P=0.002), IL-6 (P=0.003), and IL-17 (P<0.001) were lower in the CD groups. Serum TNF-α levels were increased in the active CD group. The CRP levels were elevated in the CD groups when compared to controls (P<0.001). The CD26 levels were lower in the CD groups than in the control group (P<0.001). Among the variables analyzed, there was a correlation between LPS and CRP (r=−0.53, P=0.016) in the CD groups. Conclusions Individuals with CD exhibited higher serum levels of LPS varying from a 2- to 6-fold increase depending on disease activity, when compared with healthy controls. CD26 levels were lower in the CD groups. Both LPS and CD26 correlated with disease severity and serve as potential CD biomarkers. PMID:28670232

[Proportion and significance of CD1d(hi)CD5⁺CD19⁺ regulatory B cell in peripheral blood of patients with neuromyelitis optica].

PubMed

Yang, Fen; Huang, Dehui; Cheng, Chen; Wu, Weiping

2015-03-01

To detect the proportion of CD1d(hi)CD5⁺CD19⁺ regulatory B cells (Bregs) in peripheral blood of the patients with neuromyelitis optica (NMO), and explore whether CD1d(hi)CD5⁺CD19⁺ Bregs can play a role as a biomarker in the diagnosis of NMO versus multiple sclerosis (MS). Flow cytometry was performed to detect the proportion of CD1d(hi)CD5⁺CD19⁺ Bregs in peripheral blood from 44 cases of NMO, 38 cases of MS, and 30 healthy controls. The serum level of aquaporin-4 antibody (AQP4-Ab) of patients with NMO was detected by indirect immunofluorescence assay. The proportion of CD1d(hi)CD5⁺CD19⁺ Bregs in CD19⁺ B cells and lymphocytes was significantly lower in NMO group than in MS and control groups; however, there was no significant difference between MS group and control group. The proportion of CD1d(hi)CD5⁺CD19⁺ Bregs in CD19⁺ B cells and lymphocytes was lower in AQP4-Ab-positive NMO patients than in AQP4-Ab-negative NMO patients, and the difference was statistically significant. CD1d(hi)CD5⁺CD19⁺ Bregs may be a biomarker in the differential diagnosis of NMO versus MS.

Influence of the baking process for chemically amplified resist on CD performance

NASA Astrophysics Data System (ADS)

Sasaki, Shiho; Ohfuji, Takeshi; Kurihara, Masa-aki; Inomata, Hiroyuki; Jackson, Curt A.; Murata, Yoshio; Totsukawa, Daisuke; Tsugama, Naoko; Kitano, Naoki; Hayashi, Naoya; Hwang, David H.

2002-12-01

CD uniformity and MTT (Mean to Target) control are very important in mask production for the 90nm node and beyond. Although it is well known that baking temperatures influence CD control in the CAR (chemically amplified resist) process for mask patterning, we found that 2 other process factors, which are related to acid diffusion and CA- reaction, greatly affect CD performance. We used a commercially available, negative CAR material and a 50kV exposure tool. We focused on the baking process for both PB (Pre Baking) and PEB (Post Exposure Bake). Film densification strength was evaluated from film thickness loss during PB. Plate temperature distribution was monitored with a thermocouple plate and IR camera. CA-reactions were also monitored with in-situ FTIR during PEB. CD uniformity was used to define the process influence. In conclusion, we found that airflow control and ramping temperature control in the baking process are very important factors to control CD in addition to conventional temperature control. These improvements contributed to a 30 % of reduction in CD variation.

CD20+ T cell numbers are decreased in untreated HIV-1 patients and recover after HAART.

PubMed

Förster, Friederike; Singla, Anuj; Arora, Sunil K; Schmidt, Reinhold E; Jacobs, Roland

2012-08-30

To elucidate if CD20(+) T cells are affected by HIV-1 infection and may have a prognostic value for the course of disease, numbers of CD20(+) T cells were determined in healthy controls, untreated and HAART-treated HIV-1 patients. Coexpression patterns of CD4, CD8, and CD38 were analysed on CD3(+)CD20(+) and CD3(+)CD20(-) T cells. We found a significant decrease of CD20(+) T cell numbers in untreated HIV-1 patients (1.4%) as compared to healthy controls (2.5%) which recovered under HAART (1.9%). Particularly, the CD8(+) T cell compartment was affected revealing significant differences between healthy controls (3.4%) and both treated (1.7%) and untreated (1.1%) patients. CD38 was expressed on a few CD20(+) T cells but preferentially on CD20(-) cells in all three groups. IFN-γ production was measured upon cell activation using PMA alone or in combination with ionomycin in order to assess functional capacities of the cells. PMA alone was much more effective in CD20(+) cells regardless of CD38 coexpression, indicating a supportive role of CD20 but not CD38 in T cell activation. Here we present data showing that CD3(+)CD20(+) T cells are decreased in untreated HIV-1 patients and normal numbers are restored under HAART. Expression of CD20 and CD38 is independently regulated on T cells. Contrary to CD38, CD20 can substitute ionophores for Ca(2+) flux in early T cell activation and also strongly amplify cell stimulation in the presence of Ca(2+) ionophores, indicating that CD20 contributes to T cell activation. Copyright © 2012 Elsevier B.V. All rights reserved.

Physiological Evaluation of Cooling Devices in Conjunction With Personal Protective Ensembles Recommended for Use in West Africa.

PubMed

Quinn, Tyler; Kim, Jung-Hyun; Strauch, Amanda; Wu, Tianzhou; Powell, Jeffery; Roberge, Raymond; Shaffer, Ronald; Coca, Aitor

2017-10-01

Cooling devices (CDs) worn under personal protective equipment (PPE) can alleviate some of the heat stress faced by health care workers responding to the Ebola outbreak in West Africa. Six healthy, young individuals were tested while wearing 4 different CDs or no cooling (control) under PPE in an environmental chamber (32°C/92% relative humidity) while walking (3 METs, 2.5 mph, 0% grade) on a treadmill for 60 minutes. Exercise was preceded by a 15-minute stabilization period and a 15-minute donning period. The control condition resulted in a significantly higher rectal temperature (Tre) at the end of the exercise than did all CD conditions (CD1, P=0.004; CD2, P=0.01; CD3, P=0.000; CD4, P=0.000) with CD1 and CD2 resulting in a higher Tre than CD3 and CD4 (P<0.05). The control condition resulted in a higher heart rate (HR) at the end of exercise than did the CD3 (P=0.01) and CD4 (P=0.009) conditions, whereas the HR of the CD1 and CD2 conditions was higher than that of the CD3 and CD4 conditions (P<0.05). Weight loss in the control condition was higher than in the CD3 (P=0.003) and CD4 (P=0.01) conditions. Significant differences in subjective measurements of thermal stress were found across conditions and time. Use of CDs can be advantageous in decreasing the negative physiological and subjective responses to the heat stress encountered by health care workers wearing PPE in hot and humid environments. (Disaster Med Public Health Preparedness. 2017;11:573-579).

Brief report: Factor structure of parenting behaviour in early adolescence.

PubMed

Spithoven, Annette W M; Bijttebier, Patricia; Van Leeuwen, Karla; Goossens, Luc

2016-12-01

Researchers have traditionally relied on a tripartite model of parenting behaviour, consisting of the dimensions parental support, psychological control, and behavioural control. However, some scholars have argued to distinguish two dimensions of behavioural control, namely reactive control and proactive control. In line with earlier work, the current study found empirical evidence for these distinct behavioural control dimensions. In addition, the study showed that the four parenting dimensions of parental support, psychological control, reactive control, and proactive control were differentially related to peer-related loneliness as well as parent-related loneliness. Thereby, the current study does not only provide empirical evidence for the distinction between various parenting dimensions, but also shows the utility of this differentiation. Copyright © 2016. Published by Elsevier Ltd.

Novel potato plants with enhanced cadmium resistance and antioxidative defence generated after in vitro cell line selection.

PubMed

Ashrafzadeh, Seyedardalan; Leung, David W M

2017-01-01

It is of interest to apply plant tissue culture to generate plants resistant to toxic effects of cadmium (Cd) on plant growth. Callus cultures were initiated from leaf explants of micropropagated potato plantlets (Solanum tuberosum L., cv. Iwa) for in vitro selection comprising 18 different Cd treatments varying in Cd exposure timing and duration. Plantlets regenerated from two different lines of Cd-selected calli, L9 and L11, were found to exhibit enhanced resistance to 218 μM Cd compared to control (source plantlets for leaf explants used to initiate callus cultures for Cd resistance). In response to 218 μM Cd, L11 plantlets had lower levels of lipid peroxidation and hydrogen peroxide than control and L9 plantlets. In addition, antioxidative enzyme activities in L11 were generally higher than control. L11 also had a higher level of proline than control.

Is tremor related to celiac disease?

PubMed

Ameghino, Lucia; Rossi, Malco Damian; Cerquetti, Daniel; Merello, Marcelo

2017-06-14

Neurological features in celiac disease (CD) are not rare (5%-36%), but tremor is scarcely described. Subjects with CD and healthy controls completed an online survey using WHIGET tremor rating scale. One thousand five hundred and twelve subjects completed the survey, finally 674 CD patients and 290 healthy subjects were included. A higher prevalence of tremor in CD patients was observed in comparison to controls (28% vs 14%, P < 0.001). Frequency of family history of tremor in CD patients with and without tremor was 25% and 20% ( P = 0.2), while in the control group it was 41% and 10% ( P < 0.001). Controls with tremor showed a higher frequency of family history of tremor when compared to CD patients with tremor (41.5% vs 24.6%, P = 0.03). The results suggested that tremor in CD might be more frequent and possibly related to the disease itself and not due to associated essential tremor.

Characteristics of depth-sensing coplanar grid CdZnTe detectors

NASA Astrophysics Data System (ADS)

He, Zhong; Sturm, Ben W.

2005-12-01

The latest depth-sensing coplanar grid CdZnTe detectors have been tested. Two of these have dimensions 1.5×1.5×1.0 cm 3 and one is a cylindrical detector with 1.5 cm diameter and 1.0 cm length, all of them using the third-generation coplanar anode design. Energy resolutions of 2.0% and 2.4% FWHM at 662 keV γ-ray energies were obtained. Detector performance has been observed experimentally as a function of depth of the γ-ray interaction, and as a function of radial position near the anode surface. The measured results show the improvement of the third-generation anode design. Material uniformity of CdZnTe crystals manufactured by eV Products have been directly observed and compared on two 1.5×1.5×1.0 cm 3 detectors.

Effects of Callous-Unemotional Traits on the Association Between Parenting and Child Conduct Problems.

PubMed

Crum, Kathleen I; Waschbusch, Daniel A; Bagner, Daniel M; Coxe, Stefany

2015-12-01

The current study investigated whether and how callous-unemotional traits (CU) moderated the association between specific parenting practices and child conduct problems (CP) with a special consideration of informant patterns. Associations between CU, ODD and CD symptom severity, and the parenting practices of deficient monitoring, positive involvement, and negative/ineffective discipline were examined across parent and teacher reports on 851 elementary-school students. Relative to children with low CU, in children with high CU: (1) positive parenting was associated with lower CD, but increased ODD; (2) negative/ineffective discipline was associated with increased ODD; (3) deficient monitoring was associated with increased CD. Results were not robust across informants. These findings suggest that in the context of CU, the associations between parenting and CP differ based on parenting characteristics, CP dimensions, and informant, and that families may benefit from treatment targeting specific parenting practices based on CP symptom profiles.

Understanding the Complexity of Temperature Dynamics in Xinjiang, China, from Multitemporal Scale and Spatial Perspectives

PubMed Central

Chen, Yaning; Li, Weihong; Liu, Zuhan; Wei, Chunmeng; Tang, Jie

2013-01-01

Based on the observed data from 51 meteorological stations during the period from 1958 to 2012 in Xinjiang, China, we investigated the complexity of temperature dynamics from the temporal and spatial perspectives by using a comprehensive approach including the correlation dimension (CD), classical statistics, and geostatistics. The main conclusions are as follows (1) The integer CD values indicate that the temperature dynamics are a complex and chaotic system, which is sensitive to the initial conditions. (2) The complexity of temperature dynamics decreases along with the increase of temporal scale. To describe the temperature dynamics, at least 3 independent variables are needed at daily scale, whereas at least 2 independent variables are needed at monthly, seasonal, and annual scales. (3) The spatial patterns of CD values at different temporal scales indicate that the complex temperature dynamics are derived from the complex landform. PMID:23843732

Application of focused ion beam for the fabrication of AFM probes

NASA Astrophysics Data System (ADS)

Kolomiytsev, A. S.; Lisitsyn, S. A.; Smirnov, V. A.; Fedotov, A. A.; Varzarev, Yu N.

2017-10-01

The results of an experimental study of the probe tips fabrication for critical-dimension atomic force microscopy (CD-AFM) using the focused ion beam (FIB) induced deposition are presented. Methods of the FIB-induced deposition of tungsten and carbon onto the tip of an AFM probe are studied. Based on the results obtained in the study, probes for the CD-AFM technique with a tip height about 1 μm and radius of 20 nm were created. The formation of CD-AFM probes by FIB-induced deposition allows creating a high efficiency tool for nanotechnology and nanodiagnostics. The use of modified cantilevers allows minimizing the artefacts of AFM images and increasing the accuracy of the relief measurement. The obtained results can be used for fabrication of AFM probes for express monitoring of the technological process in the manufacturing of the elements for micro- and nanoelectronics.

Thermal analysis of Bridgman-Stockbarger growth. [mercury cadmium telluride single crystals

NASA Technical Reports Server (NTRS)

Knopf, F. W.

1979-01-01

A thermal analysis of a cylindrical HgCdTe sample in a Bridgman-Stockbarger crystal growth configuration was conducted with emphasis on the thermal profile, interface shape and position, and the thermal gradients at the liquid-solid interface. Alloys of HgTe and CdTe with compositions approximating 20 percent CdTe, 80 percent HgTe were used. This composition results in a bandgap suited for the detection of 10.6 micron CO2 radiation. The sensitivity of the sample thermal characteristics to important growth parameters, such as thermal diffusivities, thermal conductivities, furnace temperature profile, ampoule dimensions, and growth velocity was assessed. Numerical techniques and associated computational models necessary to analyze the heat transfer process within the sample and the Bridgman-Stockbarger boundary conditions were developed. This thermal analysis mode was programmed in FORTRAN V, and is currently operational on the MSFC Univac 1100 system.

Lack of evidence of rotavirus-dependent molecular mimicry as a trigger of coeliac disease.

PubMed

Ziberna, F; De Lorenzo, G; Schiavon, V; Arnoldi, F; Quaglia, S; De Leo, L; Vatta, S; Martelossi, S; Burrone, O R; Ventura, A; Not, T

2016-12-01

New data suggest the involvement of rotavirus (RV) in triggering autoimmunity in coeliac disease (CD) by molecular mimicry between the human-transglutaminase protein and the dodecapeptide (260-271 aa) of the RV protein VP7 (pVP7). To assess the role of RV in the onset of CD, we measured anti-pVP7 antibodies in the sera of children with CD and of control groups. We analysed serum samples of 118 biopsy-proven CD patients and 46 patients with potential CD; 32 children with other gastrointestinal diseases; 107 no-CD children and 107 blood donors. Using enzyme-linked immunosorbent assay (ELISA) assay, we measured immunoglobulin (Ig)A-IgG antibodies against the synthetic peptides pVP7, the human transglutaminase-derived peptide (476-487 aa) which shows a homology with VP7 protein and a control peptide. The triple-layered RV particles (TLPs) containing the VP7 protein and the double-layered RV-particles (DLPs) lacking the VP7 protein were also used as antigens in ELISA assay. Antibody reactivity to the RV-TLPs was positive in 22 of 118 (18%) CD patients and in both paediatric (17 of 107, 16%) and adult (29 of 107, 27%) control groups, without showing a statistically significant difference among them (P = 0·6, P = 0·1). Biopsy-proven CD patients as well as the adult control group demonstrated a high positive antibody reactivity against both pVP7 (34 of 118, 29% CD patients; 66 of 107, 62% adult controls) and control synthetic peptides (35 of 118, 30% CD patients; 56 of 107, 52% adult controls), suggesting a non-specific response against RV pVP7. We show that children with CD do not have higher immune reactivity to RV, thus questioning the molecular mimicry mechanism as a triggering factor of CD. © 2016 British Society for Immunology.

Absence of somatization in non-coeliac gluten sensitivity.

PubMed

Brottveit, Margit; Vandvik, Per Olav; Wojniusz, Slawomir; Løvik, Astrid; Lundin, Knut Ea; Boye, Birgitte

2012-07-01

In contrast to coeliac disease (CD), the mechanism behind non-coeliac gluten sensitivity (NCGS) is unclear. The aims of the study were to measure the presence of somatization, personality traits, anxiety, depression, and health-related quality of life in NCGS individuals compared with CD patients and healthy controls, and to compare the response to gluten challenge between NCGS and CD patients. We examined 22 CD patients and 31 HLA-DQ2+ NCGS patients without CD, all on a gluten-free diet. All but five CD patients were challenged orally for 3 days with gluten; symptom registration was performed during challenge. A comparison group of 40 healthy controls was included. Patients and healthy controls completed questionnaires regarding anxiety, depression, neuroticism and lie, hostility and aggression, alexithymia and health locus of control, physical complaints, and health-related quality of life. The NCGS patients reported more abdominal (p = 0.01) and non-abdominal (p < 0.01) symptoms after gluten challenge than CD patients. There were no significant differences between CD and NCGS patients regarding personality traits, level of somatization, quality of life, anxiety, and depressive symptoms. The somatization level was low in CD and NCGS groups. Symptom increase after gluten challenge was not related to personality in NCGS patients. NCGS patients did not exhibit a tendency for general somatization. Personality and quality of life did not differ between NCGS and CD patients, and were mostly at the same level as in healthy controls. NCGS patients reported more symptoms than CD patients after gluten challenge.

Decision making and executive function in male adolescents with early-onset or adolescence-onset conduct disorder and control subjects.

PubMed

Fairchild, Graeme; van Goozen, Stephanie H M; Stollery, Sarah J; Aitken, Michael R F; Savage, Justin; Moore, Simon C; Goodyer, Ian M

2009-07-15

Although conduct disorder (CD) is associated with an increased susceptibility to substance use disorders, little is known about decision-making processes or reward mechanisms in CD. This study investigated decision making under varying motivational conditions in CD. Performances on the Risky Choice Task (RCT) and the Wisconsin Card Sorting Test (WCST) were assessed in 156 adolescents (84 control subjects, 34 with adolescence-onset CD, and 38 with early-onset CD). The RCT was performed twice, once under normal motivational conditions and once under conditions of increased motivation and psychosocial stress. Increased motivation and stress led to more cautious decision making and changes in framing effects on the RCT in all groups, although such effects were least pronounced in the early-onset CD group. Participants from both CD subgroups selected the risky choice more frequently than control subjects. Under normal motivational conditions, early-onset CD participants chose the risky choice more frequently in trials occurring after small gains, relative to control subjects and adolescence-onset CD participants. Following adjustment for IQ differences, the groups did not differ significantly in terms of WCST performance. Differences in decision making between control subjects and individuals with CD suggest that the balance between sensitivity to reward and punishment is shifted in this disorder, particularly the early-onset form. Our data on modulation of decision making according to previous outcomes suggest altered reward mechanisms in early-onset CD. The WCST data suggest that impairments in global executive function do not underlie altered decision making in CD.

Characterization of circulating CD4+ CD8+ double positive and CD4- CD8- double negative T-lymphocyte in children with β-thalassemia major.

PubMed

Zahran, Asmaa M; Saad, Khaled; Elsayh, Khalid I; Alblihed, Mohamd A

2017-03-01

Infectious complications represent the second most common cause of mortality and a major cause of morbidity in β-thalassemia major (BTM), with a prevalence of 12-13%. The data on unconventional T-lymphocyte subsets in BTM children are limited. The aim of the present study was to investigate and evaluate phenotypic alterations in CD4 + CD8 + double positive (DP), CD4 - CD8 - double negative (DN), and natural killer T-lymphocytes (NKT) in BTM children in comparison to healthy controls. Our case control study included 80 children with BTM and 40 healthy children as controls. Assessment of unconventional T-lymphocyte populations was done using sensitive four-color flow cytometry (FACSCalibur). Our analysis of the data showed a significantly higher frequency CD4 + CD8 + (double-positive) T cells, CD4 - CD8 - (double negative) T cells, and natural killer T cells in the peripheral blood of both BTM groups (splenectomized and non-splenectomized) as compared to healthy controls, suggesting that these cells may play a role in the clinical course of BTM. The relationship of the unconventional T-lymphocytes to immune disorders in BTM children remains to be determined. Further longitudinal study with a larger sample size is warranted to elucidate the role these cells in BTM. TRIAL NUMBER: UMIN000018950.

Role of FAT/CD36 in fatty acid sensing, energy, and glucose homeostasis regulation in DIO and DR rats.

PubMed

Le Foll, Christelle; Dunn-Meynell, Ambrose A; Levin, Barry E

2015-02-01

Hypothalamic fatty acid (FA) sensing neurons alter their activity utilizing the FA translocator/receptor, FAT/CD36. Depletion of ventromedial hypothalamus (VMH) CD36 with adeno-associated viral vector expressing CD36 shRNA (AAV CD36 shRNA) leads to redistribution of adipose stores and insulin resistance in outbred rats. This study assessed the requirement of VMH CD36-mediated FA sensing for the regulation of energy and glucose homeostasis in postnatal day 5 (P5) and P21 selectively bred diet-induced obese (DIO) and diet-resistant (DR) rats using VMH AAV CD36 shRNA injections. P5 CD36 depletion altered VMH neuronal FA sensing predominantly in DIO rats. After 10 wk on a 45% fat diet, DIO rats injected with VMH AAV CD36 shRNA at P21 ate more and gained more weight than DIO AAV controls, while DR AAV CD36 shRNA-injected rats gained less weight than DR AAV controls. VMH CD36 depletion increased inguinal fat pad weights and leptin levels in DIO and DR rats. Although DR AAV CD36 shRNA-injected rats became as obese as DIO AAV controls, only DIO control and CD36 depleted rats became insulin-resistant on a 45% fat diet. VMH CD36 depletion stunted linear growth in DIO and DR rats. DIO rats injected with AAV CD36 shRNA at P5 had increased fat mass, mostly due to a 45% increase in subcutaneous fat. They were also insulin-resistant with an associated 71% increase of liver triglycerides. These results demonstrate that VMH CD36-mediated FA sensing is a critical factor in the regulation of energy and glucose homeostasis and fat deposition in DIO and DR rats.

Quantifying CD4 receptor protein in two human CD4+ lymphocyte preparations for quantitative flow cytometry.

PubMed

Wang, Meiyao; Misakian, Martin; He, Hua-Jun; Bajcsy, Peter; Abbasi, Fatima; Davis, Jeffrey M; Cole, Kenneth D; Turko, Illarion V; Wang, Lili

2014-01-01

In our previous study that characterized different human CD4+ lymphocyte preparations, it was found that both commercially available cryopreserved peripheral blood mononuclear cells (PBMC) and a commercially available lyophilized PBMC (Cyto-Trol™) preparation fulfilled a set of criteria for serving as biological calibrators for quantitative flow cytometry. However, the biomarker CD4 protein expression level measured for T helper cells from Cyto-Trol was about 16% lower than those for cryopreserved PBMC and fresh whole blood using flow cytometry and mass cytometry. A primary reason was hypothesized to be due to steric interference in anti- CD4 antibody binding to the smaller sized lyophilized control cells. Targeted multiple reaction monitoring (MRM) mass spectrometry (MS) is used to quantify the copy number of CD4 receptor protein per CD4+ lymphocyte. Scanning electron microscopy (SEM) is utilized to assist searching the underlying reasons for the observed difference in CD4 receptor copy number per cell determined by MRM MS and CD4 expression measured previously by flow cytometry. The copy number of CD4 receptor proteins on the surface of the CD4+ lymphocyte in cryopreserved PBMCs and in lyophilized control cells is determined to be (1.45 ± 0.09) × 10(5) and (0.85 ± 0.11) × 10(5), respectively, averaged over four signature peptides using MRM MS. In comparison with cryopreserved PBMCs, there are more variations in the CD4 copy number in lyophilized control cells determined based on each signature peptide. SEM images of CD4+ lymphocytes from lyophilized control cells are very different when compared to the CD4+ T cells from whole blood and cryopreserved PBMC. Because of the lyophilization process applied to Cyto-Trol control cells, a lower CD4 density value, defined as the copy number of CD4 receptors per CD4+ lymphocyte, averaged over three different production lots is most likely explained by the loss of the CD4 receptors on damaged and/or broken microvilli where CD4 receptors reside. Steric hindrance of antibody binding and the association of CD4 receptors with other biomolecules likely contribute significantly to the nearly 50% lower CD4 receptor density value for cryopreserved PBMC determined from flow cytometry compared to the value obtained from MRM MS.

Effects of Mulching Tolerant Plant Straw on Soil Surface on Growth and Cadmium Accumulation of Galinsoga parviflora

PubMed Central

Lin, Lijin; Liao, Ming’an; Ren, Yajun; Luo, Li; Zhang, Xiao; Yang, Daiyu; He, Jing

2014-01-01

Pot and field experiments were conducted to study the effects of mulching with straw of cadmium (Cd) tolerant plants (Ranunculus sieboldii, Mazus japonicus, Clinopodium confine and Plantago asiatica) on growth and Cd accumulation of Galinsoga parviflora in Cd-contaminated soil. In the pot experiment, mulching with M. japonicus straw increased the root biomass, stem biomass, leaf biomass, shoot biomass, plant height and activities of antioxidant enzymes (superoxide dismutase, peroxidase and catalase) of G. parviflora compared with the control, whereas mulching with straws of R. sieboldii, C. confine and P. asiatica decreased these parameters. Straws of the four Cd-tolerant plants increased the Cd content in roots of G. parviflora compared with the control. However, only straws of M. japonicus and P. asiatica increased the Cd content in shoots of G. parviflora, reduced the soil pH, and increased the soil exchangeable Cd concentration. Straw of M. japonicus increased the amount of Cd extraction in stems, leaves and shoots of G. parviflora by 21.11%, 29.43% and 24.22%, respectively, compared with the control, whereas straws of the other three Cd-tolerant plants decreased these parameters. In the field experiment, the M. japonicus straw also increased shoot biomass, Cd content in shoots, and amount of Cd extraction in shoots of G. parviflora compared with the control. Therefore, straw of M. japonicus can be used to improve the Cd extraction ability of G. parviflora from Cd-contaminated soil. PMID:25490210

Human Immunodeficiency Virus Type-1 Elite Controllers Maintain Low Co-Expression of Inhibitory Receptors on CD4+ T Cells.

PubMed

Noyan, Kajsa; Nguyen, Son; Betts, Michael R; Sönnerborg, Anders; Buggert, Marcus

2018-01-01

Human immunodeficiency virus type-1 (HIV-1) elite controllers (ELCs) represent a unique population that control viral replication in the absence of antiretroviral therapy (cART). It is well established that expression of multiple inhibitory receptors on CD8+ T cells is associated with HIV-1 disease progression. However, whether reduced co-expression of inhibitory receptors on CD4+ T cells is linked to natural viral control and slow HIV-1 disease progression remains undefined. Here, we report on the expression pattern of numerous measurable inhibitory receptors, associated with T cell exhaustion (programmed cell death-1, CTLA-4, and TIGIT), on different CD4+ T cell memory populations in ELCs and HIV-infected subjects with or without long-term cART. We found that the co-expression pattern of inhibitory receptors was significantly reduced in ELCs compared with HIV-1 cART-treated and viremic subjects, and similar to healthy controls. Markers associated with T cell exhaustion varied among different memory CD4+ T cell subsets and highest levels were found mainly on transitional memory T cells. CD4+ T cells co-expressing all inhibitory markers were positively correlated to T cell activation (CD38+ HLA-DR+) as well as the transcription factors Helios and FoxP3. Finally, clinical parameters such as CD4 count, HIV-1 viral load, and the CD4/CD8 ratio all showed significant associations with CD4+ T cell exhaustion. We demonstrate that ELCs are able to maintain lower levels of CD4+ T cell exhaustion despite years of ongoing viral replication compared with successfully cART-treated subjects. Our findings suggest that ELCs harbor a "healthy" state of inhibitory receptor expression on CD4+ T cells that might play part in maintenance of their control status.

Down-regulation of CD73 on B cells of patients with viremic HIV correlates with B cell activation and disease progression.

PubMed

Kim, Eun-Seong; Ackermann, Christin; Tóth, Ilona; Dierks, Patrick; Eberhard, Johanna M; Wroblewski, Raluca; Scherg, Felix; Geyer, Matthias; Schmidt, Reinhold E; Beisel, Claudia; Bockhorn, Maximilian; Haag, Friedrich; van Lunzen, Jan; Schulze Zur Wiesch, Julian

2017-05-01

Recently, alterations of the T cell expression of the ectonucleotidases, CD39 and CD73, during HIV infection have been described. Here, peripheral ( n = 70) and lymph nodal B cells ( n = 10) of patients with HIV at different stages of disease as well as uninfected individuals were analyzed via multicolor flow cytometry with regard to expression of CD39 and CD73 and differentiation, proliferation, and exhaustion status. Patients with chronic, untreated HIV showed a significantly decreased frequency of CD73-expressing B cells ( P < 0.001) compared with healthy controls. Decreased frequencies of CD39 + CD73 + B cells in patients with HIV correlated with low CD4 + counts ( P < 0.0256) as well as increased proliferation and exhaustion status as determined by Ki-67 and programmed death-1 expression. Down-regulation of CD73 was observed in naive and memory B cells as determined by CD27 and CD21. Neither HIV elite controller patients nor antiretroviral therapy-treated patients had significantly lower CD39 and CD73 expression on B cells compared with healthy controls. Of importance, low CD73 + expression on B cells was associated with modulated in vitro B cell function. Further in vivo studies are warranted to evaluate the in vivo role of phenotypic loss of CD73 in B cell dysregulation in HIV. © Society for Leukocyte Biology.

Nutritional status, growth and disease management in children with single and dual diagnosis of type 1 diabetes mellitus and coeliac disease.

PubMed

Mackinder, Mary; Allison, Gavin; Svolos, Vaios; Buchanan, Elaine; Johnston, Alison; Cardigan, Tracey; Laird, Nicola; Duncan, Hazel; Fraser, Karen; Edwards, Christine A; Craigie, Ian; McGrogan, Paraic; Gerasimidis, Konstantinos

2014-05-28

The consequences of subclinical coeliac disease (CD) in Type 1 diabetes mellitus (T1DM) remain unclear. We looked at growth, anthropometry and disease management in children with dual diagnosis (T1DM + CD) before and after CD diagnosis. Anthropometry, glycated haemoglobin (HbA1c) and IgA tissue transglutaminase (tTg) were collected prior to, and following CD diagnosis in 23 children with T1DM + CD. This group was matched for demographics, T1DM duration, age at CD diagnosis and at T1DM onset with 23 CD and 44 T1DM controls. No differences in growth or anthropometry were found between children with T1DM + CD and controls at any time point. Children with T1DM + CD, had higher BMI z-score two years prior to, than at CD diagnosis (p < 0.001). BMI z-score change one year prior to CD diagnosis was lower in the T1DM + CD than the T1DM group (p = 0.009). At two years, height velocity and change in BMI z-scores were similar in all groups. No differences were observed in HbA1c between the T1DM + CD and T1DM groups before or after CD diagnosis. More children with T1DM + CD had raised tTg levels one year after CD diagnosis than CD controls (CDx to CDx + 1 yr; T1DM + CD: 100% to 71%, p = 0.180 and CD: 100% to 45%, p < 0.001); by two years there was no difference. No major nutrition or growth deficits were observed in children with T1DM + CD. CD diagnosis does not impact on T1DM glycaemic control. CD specific serology was comparable to children with single CD, but those with dual diagnosis may need more time to adjust to gluten free diet.

Sex- and age-dependent effects of celiac disease on growth and weight gain in children with type 1 diabetes: Analysis of the type 1 diabetes Exchange Clinic Registry.

PubMed

Simmons, Jill H; Foster, Nicole C; Riddlesworth, Tonya D; DuBose, Stephanie N; Redondo, Maria J; Liu, Edwin; Freemark, Michael

2018-06-01

Celiac disease (CD) is common in patients with type 1 diabetes (T1D) and effects of CD on growth in children with T1D remain unclear. We analyzed heights, weights, and body mass index (BMI) in 215 matched pediatric CD/control pairs in the T1D Exchange Clinic Registry. CD was defined by a clinic-reported diagnosis and positive celiac serology (n = 80) and/or positive small bowel biopsy (n = 135). Cases and controls were matched by age (mean: 14 years), diabetes duration (median: 7 years), sex (57% female), and clinic site. There were 5569 height/weight measurements. Gluten was restricted for varying periods of time in 61% of females and 51% of males with CD. Females with CD were shorter than female controls at all ages (P = 0.01). Weight z-scores were initially lower in preschool females with CD but similar to controls by middle childhood. Males with CD were initially shorter but adult heights were similar. Height in both sexes and weight in males were lower in CD participants diagnosed at younger age. Growth in T1D children with biopsy-proven CD, 76% of them were gluten-restricted, was comparable to that of T1D controls. Concurrent CD impairs linear growth in T1D females at all stages of development and in young T1D males. Young females with CD have lower weights, but both sexes have similar weights by middle childhood. Children younger at CD onset remain shorter throughout childhood; males younger at CD onset have persistently lower weights. Long-term gluten restriction may restore weight gain and linear growth in children with CD and T1D. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Synthesis and electronic properties of nanophase semiconductor materials

NASA Astrophysics Data System (ADS)

Sailor, Michael J.

1993-05-01

The objective of the research effort is to understand and learn to control the morphologic and electronic properties of electrodeposited nanophase semiconductors. The initial work has focused on electrodeposition of nanophase CdSe, using a sequential monolayer deposition technique that we are developing. We are currently extending the synthesis phase of this project into silicon, silicon carbide, and phosphor materials. This work also encompasses studying semiconductor electrodeposition into materials with restricted dimensions, such as microporous alumina and porous silicon membranes. By growing films with very small grain sizes, we hope to produce and study materials that display unusual electronic or luminescent effects. We are primarily interested in the electronic properties of the II-VI and group IV materials, for potential applications in nanoscale electronics and optical detector technologies. The phosphors are being studied for their potential as efficient high-resolution display materials.

Autologous CD133+ bone marrow cells and bypass grafting for regeneration of ischaemic myocardium: the Cardio133 trial.

PubMed

Nasseri, Boris A; Ebell, Wolfram; Dandel, Michael; Kukucka, Marian; Gebker, Rolf; Doltra, Adelina; Knosalla, Christoph; Choi, Yeong-Hoon; Hetzer, Roland; Stamm, Christof

2014-05-14

Intra-myocardial transplantation of CD133(+) bone marrow stem cells (BMC) yielded promising results in clinical pilot trials. We now performed the double-blinded, randomized, placebo-controlled CARDIO133 trial to determine its impact on left ventricular (LV) function and clinical symptoms. Sixty patients with chronic ischaemic heart disease and impaired LV function (left ventricular ejection fraction, LVEF <35%) were randomized to undergo either coronary artery bypass grafting (CABG) and injection of CD133(+) BMC in the non-transmural, hypokinetic infarct border zone (CD133), or CABG and placebo injection (placebo). Pre-operative LVEF was 27 ± 6% in CD133 patients and 26 ± 6% in placebo patients. Outcome was assessed after 6 months, and the primary endpoint was LVEF measured by cardiac magnetic resonance imaging (MRI) at rest. The incidence of adverse events was similar in both groups. There was no difference in 6-min walking distance, Minnesota Living with Heart Failure score, or Canadian Cardiovascular Society (CCS) class between groups at follow-up, and New York Heart Association class improved more in the placebo group (P = 0.004). By cardiac MRI, LVEF at 6 months was 33 ± 8% in the placebo group and 31 ± 7% in verum patients (P = 0.3), with an average inter-group difference of -2.1% (95% CI -6.3 to 2.1). Systolic or diastolic LV dimensions at 6 months were not different, either. In the CD133 group, myocardial perfusion at rest recovered in more LV segments than in the placebo group (9 vs. 2%, P < 0.001). Scar mass decreased by 2.2 ± 5 g in CD133(+) patients (P = 0.05), but was unchanged in the placebo group (0.3 ± 4 g, P = 0.7; inter-group difference in change = 2 g (95% CI -1.1 to 5)). By speckle-tracking echocardiography, cell-treated patients showed a better recovery of regional wall motion when the target area was posterior. Although there may be some improvements in scar size and regional perfusion, intra-myocardial injection of CD133(+) BMC has no effect on global LV function and clinical symptoms. Improvements in regional myocardial function are only detectable in patients with posterior infarction, probably because the interventricular septum after anterior infarction is not accessible by trans-epicardial injection. This trial was registered at http://www.clinicaltrials.gov under NCT00462774. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Modulation of B cell regulatory molecules CD22 and CD72 in myasthenia gravis and multiple sclerosis.

PubMed

Lu, Jiayin; Li, Jing; Zhu, Tai-qing; Zhang, Longbo; Wang, Yuzhong; Tian, Fa-fa; Yang, Huan

2013-06-01

B cell activation mediated by cluster of differentiation (CD) molecules plays an important role in B cell-related autoimmune diseases. CD22 and CD72 have been demonstrated to act as B cell inhibitory receptors in many autoimmune diseases. Activated B cells are involved in the pathogenesis of myasthenia gravis (MG) by secretion of anti-acetylcholine receptor (AchR) antibodies. However, the roles of CD22 and CD72 on B cells of MG are unknown. In this study, we detected the expression of CD22 and CD72 on B cells of MG, compared to multiple sclerosis (MS) patient controls and healthy controls by flow cytometry and quantitative real-time polymerase transcription chain reaction. Our data demonstrated that aberrant expression of CD72 exists on B cells of MG and MS patients and expression level of CD72 molecule has a significantly negative correlation with anti-AchR antibody levels in MG, which suggests that CD72 may be involved in the pathogenesis of MG and MS. There were no significant differences between study patients (MG, ocular MG, generalized MG, and MS) and healthy controls.

Donor states in a semimagnetic Cd1 -xinMnxin Te /Cd1 -xoutMnxout Te Double Quantum Well

NASA Astrophysics Data System (ADS)

Kalpana, Panneer Selvam; Nithiananthi, Perumal; Jayakumar, Kalyanasundaram

2017-02-01

The theoretical investigation has been carried out on the binding energy of donor associated with the electrons confined in a Cd1 -xinMnxin Te /Cd1 -xoutMnxout Te Double Quantum Well (DQW) as a function of central barrier width for various well dimensions and impurity locations in the barrier and the well. The magnetic field can act as a tool to continuously change the interwell coupling inside this DQW systems and its effect on donor binding has also been studied. Moreover, the polaronic corrections, which is due to the strong exchange interaction between the magnetic moment of Mn2+ ion and the spin of the confined carrier, to the binding energy of the hydrogenic donor impurity has also been estimated with and without the application of magnetic field. The binding energy of the donor impurity is determined by solving the Schrodinger equation variationally in the effective mass approximation and the effect due to Bound Magnetic Polaron (BMP) is included using mean field theory with the modified Brillouin function. The results are reported and discussed.

Increased loss of CCR5+ CD45RA- CD4+ T cells in CD8+ lymphocyte-depleted Simian immunodeficiency virus-infected rhesus monkeys.

PubMed

Veazey, Ronald S; Acierno, Paula M; McEvers, Kimberly J; Baumeister, Susanne H C; Foster, Gabriel J; Rett, Melisa D; Newberg, Michael H; Kuroda, Marcelo J; Williams, Kenneth; Kim, Eun-Young; Wolinsky, Steven M; Rieber, E Peter; Piatak, Michael; Lifson, Jeffrey D; Montefiori, David C; Brown, Charles R; Hirsch, Vanessa M; Schmitz, Jörn E

2008-06-01

Previously we have shown that CD8(+) T cells are critical for containment of simian immunodeficiency virus (SIV) viremia and that rapid and profound depletion of CD4(+) T cells occurs in the intestinal tract of acutely infected macaques. To determine the impact of SIV-specific CD8(+) T-cell responses on the magnitude of the CD4(+) T-cell depletion, we investigated the effect of CD8(+) lymphocyte depletion during primary SIV infection on CD4(+) T-cell subsets and function in peripheral blood, lymph nodes, and intestinal tissues. In peripheral blood, CD8(+) lymphocyte-depletion changed the dynamics of CD4(+) T-cell loss, resulting in a more pronounced loss 2 weeks after infection, followed by a temporal rebound approximately 2 months after infection, when absolute numbers of CD4(+) T cells were restored to baseline levels. These CD4(+) T cells showed a markedly skewed phenotype, however, as there were decreased levels of memory cells in CD8(+) lymphocyte-depleted macaques compared to controls. In intestinal tissues and lymph nodes, we observed a significantly higher loss of CCR5(+) CD45RA(-) CD4(+) T cells in CD8(+) lymphocyte-depleted macaques than in controls, suggesting that these SIV-targeted CD4(+) T cells were eliminated more efficiently in CD8(+) lymphocyte-depleted animals. Also, CD8(+) lymphocyte depletion significantly affected the ability to generate SIV Gag-specific CD4(+) T-cell responses and neutralizing antibodies. These results reemphasize that SIV-specific CD8(+) T-cell responses are absolutely critical to initiate at least partial control of SIV infection.

Selective CD28 blockade attenuates CTLA-4–dependent CD8+ memory T cell effector function and prolongs graft survival

PubMed Central

Liu, Danya; Badell, I. Raul; Ford, Mandy L.

2018-01-01

Memory T cells pose a significant problem to successful therapeutic control of unwanted immune responses during autoimmunity and transplantation, as they are differentially controlled by cosignaling receptors such as CD28 and CTLA-4. Treatment with abatacept and belatacept impede CD28 signaling by binding to CD80 and CD86, but they also have the unintended consequence of blocking the ligands for CTLA-4, a process that may inadvertently boost effector responses. Here, we show that a potentially novel anti-CD28 domain antibody (dAb) that selectively blocks CD28 but preserves CTLA-4 coinhibition confers improved allograft survival in sensitized recipients as compared with CTLA-4 Ig. However, both CTLA-4 Ig and anti-CD28 dAb similarly and significantly reduced the accumulation of donor-reactive CD8+ memory T cells, demonstrating that regulation of the expansion of CD8+ memory T cell populations is controlled in part by CD28 signals and is not significantly impacted by CTLA-4. In contrast, selective CD28 blockade was superior to CTLA-4 Ig in inhibiting IFN-γ, TNF, and IL-2 production by CD8+ memory T cells, which in turn resulted in reduced recruitment of innate CD11b+ monocytes into allografts. Importantly, this superiority was CTLA-4 dependent, demonstrating that effector function of CD8+ memory T cells is regulated by the balance of CD28 and CTLA-4 signaling. PMID:29321374

Does haemochromatosis predispose to coeliac disease? A study of 29,096 coeliac disease patients

PubMed Central

Ludvigsson, Jonas F; Murray, Joseph A; Adams, Paul C; Elmberg, Maria

2013-01-01

Background and aim Case reports suggest an association between hereditary haemochromatosis (HH) and coeliac disease (CD), but estimates of association are lacking. We estimated the association between HH and CD in a population-based study. Materials and methods Case-control study. We identified 29,096 individuals with biopsy-verified CD (equal to villous atrophy, Marsh stage III) through biopsy reports from all 28 pathology departments in Sweden. We then investigated the risk of a clinical diagnosis of HH in CD and in 144,522 controls matched for age, sex, county and calendar year. Conditional logistic regression was used to calculate odds ratios (ORs) for CD in patients with HH. Results HH was seen in 30 patients with CD and in 60 matched controls. HH was hence associated with an increased risk of CD (OR=2.30; 95%CI=1.53–3.25). Restricting HH to individuals with at least 2 records of HH, the OR for CD was 2.54 (95%CI=1.57–4.11), with a similar risk estimate when we only looked at HH diagnosed before CD (and matched date in controls) (OR=2.64; 95%CI=1.24–5.60). Conclusion HH seems to be associated with an increased risk of CD. PMID:23256862

Electrochemical control over photoinduced electron transfer and trapping in CdSe-CdTe quantum-dot solids.

PubMed

Boehme, Simon C; Walvis, T Ardaan; Infante, Ivan; Grozema, Ferdinand C; Vanmaekelbergh, Daniël; Siebbeles, Laurens D A; Houtepen, Arjan J

2014-07-22

Understanding and controlling charge transfer between different kinds of colloidal quantum dots (QDs) is important for devices such as light-emitting diodes and solar cells and for thermoelectric applications. Here we study photoinduced electron transfer between CdTe and CdSe QDs in a QD film. We find that very efficient electron trapping in CdTe QDs obstructs electron transfer to CdSe QDs under most conditions. Only the use of thiol ligands results in somewhat slower electron trapping; in this case the competition between trapping and electron transfer results in a small fraction of electrons being transferred to CdSe. However, we demonstrate that electron trapping can be controlled and even avoided altogether by using the unique combination of electrochemistry and transient absorption spectroscopy. When the Fermi level is raised electrochemically, traps are filled with electrons and electron transfer from CdTe to CdSe QDs occurs with unity efficiency. These results show the great importance of knowing and controlling the Fermi level in QD films and open up the possibility of studying the density of trap states in QD films as well as the systematic investigation of the intrinsic electron transfer rates in donor-acceptor films.

Line-edge roughness performance targets for EUV lithography

NASA Astrophysics Data System (ADS)

Brunner, Timothy A.; Chen, Xuemei; Gabor, Allen; Higgins, Craig; Sun, Lei; Mack, Chris A.

2017-03-01

Our paper will use stochastic simulations to explore how EUV pattern roughness can cause device failure through rare events, so-called "black swans". We examine the impact of stochastic noise on the yield of simple wiring patterns with 36nm pitch, corresponding to 7nm node logic, using a local Critical Dimension (CD)-based fail criteria Contact hole failures are examined in a similar way. For our nominal EUV process, local CD uniformity variation and local Pattern Placement Error variation was observed, but no pattern failures were seen in the modest (few thousand) number of features simulated. We degraded the image quality by incorporating Moving Standard Deviation (MSD) blurring to degrade the Image Log-Slope (ILS), and were able to find conditions where pattern failures were observed. We determined the Line Width Roughness (LWR) value as a function of the ILS. By use of an artificial "step function" image degraded by various MSD blur, we were able to extend the LWR vs ILS curve into regimes that might be available for future EUV imagery. As we decreased the image quality, we observed LWR grow and also began to see pattern failures. For high image quality, we saw CD distributions that were symmetrical and close to Gaussian in shape. Lower image quality caused CD distributions that were asymmetric, with "fat tails" on the low CD side (under-exposed) which were associated with pattern failures. Similar non-Gaussian CD distributions were associated with image conditions that caused missing contact holes, i.e. CD=0.

Designing Selectivity in Metal-Semiconductor Nanocrystals: Synthesis, Characterization, and Self-Assembly

NASA Astrophysics Data System (ADS)

Pavlopoulos, Nicholas George

This dissertation contains six chapters detailing recent advances that have been made in the synthesis and characterization of metal-semiconductor hybrid nanocrystals (HNCs), and the applications of these materials. Primarily focused on the synthesis of well-defined II-VI semiconductor nanorod (NR) and tetrapod (TP) based constructs of interest for photocatalytic and solar energy applications, the research described herein discusses progress towards the realization of key design rules for the synthesis of functional semiconductor nanocrystals (NCs). As such, a blend of novel synthesis, advanced characterization, and direct application of heterostructured nanoparticles are presented. The first chapter is a review summarizing the design, synthesis, properties, and applications of multicomponent nanomaterials composed of disparate semiconductor and metal domains. By coupling two compositionally distinct materials onto a single nanocrystal, synergistic properties can arise that are not present in the isolated components, ranging from self-assembly to photocatalysis. For semiconductor nanomaterials, this was first realized in the ability to tune nanomaterial dimensions from 0-D quantum dot (QD) structures to cylindrical (NR) and branched (TP) structures by exploitation of advanced colloidal synthesis techniques and understandings of NC facet reactivities. The second chapter is focused on the synthesis and characterization of well-defined CdSe-seeded-CdS (CdSe CdS) NR systems synthesized by overcoating of wurtzite (W) CdSe quantum dots with W-CdS shells. 1-dimensional NRs have been interesting constructs for applications such as solar concentrators, optical gains, and photocatalysis. Through synthetic control over CdSe CdS NR systems, materials with small and large CdSe seeds were prepared, and for each seed size, multiple NR lengths were prepared. Through transient absorption studies, it was found that band alignment did not affect the efficiency of charge localization in the CdSe core, whereas NR length had a profound effect. This work indicated that longer NRs resulted in poor exciton localization efficiencies owing to ultrafast trapping of photoexcited excitons generated in the CdS NR. The third chapter describes the synthesis of Au-tipped CdSe NRs and studies of the effects of selective metal nanoparticle deposition on the band edge energetics of these model photocatalytic systems. Previous studies had demonstrated ultrafast localization of photoexcited electrons in Au nanoparticles (AuNP) (and PtNP) deposited at the termini of CdSe and CdSe CdS NR constructs. Also, for similar systems, the hydrogen evolution reaction (HER) had been studied, for which it was found that noble metal nanoparticle tips were necessary to extract photoexcited electrons from the NR constructs and drive catalytic reactions. However, in these studies, energetic trap states, generally ascribed to surface defects on the NC surface, are often cited as contributing to loss of catalytic efficiency. Through a combination of ultraviolet photoelectron spectroscopy and waveguide based spectroelectrochemistry on films of 40 nm long CdSe NRs before and after AuNP functionalization, we found that metal deposition resulted in the formation of mid-gap energy states, which were assigned as metal-semiconductor interface states. The fourth chapter transitions from NR constructs to highly absorbing CdSe CdS TP materials, for which a single zincblende (ZB) CdSe NC is used to seed the growth of four identical CdS arms. These arms act as highly efficient light absorbers, resulting in absorption cross sections an order of magnitude greater than for comparable NR systems. In the past, many studies have been published on the striking properties of TP nanocrystals, such as dual wavelength fluorescence, multiple exciton generation, and inherent self-assembly owing to their unique geometry. Nonetheless, these materials have not been exploited for photocatalysis, primarily owing to challenges in preparing TP from ultrasmall ZB-CdSe seed size, thus preventing access to quasi-type II structures necessary for efficient photocatalysis. In this study, we successfully break through the type I/quasi-type II barrier for TP NCs, reclaiming lost ground in this field and demonstrating for the first time quasi-type II behavior in CdSe CdS TPs through transient absorption measurements. The fifth chapter continues with the study of CdSe CdS TPs, and elaborates on a new method for the selective functionalization of the highly symmetrical TP construct. TP materials have been notoriously difficult to selectively functionalize, owing to their symmetric nature. Using a novel photoinduced electrochemical Ostwald ripening process, we found that initially randomly deposited AuNPs could be ripened to a single, large AuNP tip at the end of one arm of a type I CdSe CdS TP with 40 nm arms. The sixth chapter elaborates further on the preparation of colloidal polymers, further extending the analogy between molecular and colloidal levels of synthetic control. One challenge in the field of colloidal science is the realization of new modes of self-assemble for compositionally distinct nanoparticles. In this work, it was found that Au Co nanoparticle dipole strength could be systematically varied by tuning of AuNP size on CdSe CdS nanorods/tetrapods. (Abstract shortened by ProQuest.).

Cadmium alteration of root physiology and potassium ion fluxes.

PubMed

Keck, R W

1978-07-01

Segments of oat (Avena sativa L.) roots which had been exposed to 1 millimolar CdSO(4) in quarter-strength Hoagland No. 1 solution exhibited decreased respiratory rates, ATP levels, membrane-bound ATPase activity, and reduced K(+) fluxes. Respiration and ATP levels were decreased after a 2-hour treatment with 1 millimolar CdSO(4) to 65 and 75%, respectively, of control rates. A membrane-bound, Mg(2+)-dependent, K(+)-stimulated acid ATPase was rapidly inhibited to 12% of control activity in the presence of 1 millimolar CdSO(4). Potassium uptake into root segments was inhibited to 80% of control values after 30 minutes in the presence of CdSO(4). A 2-hour pretreatment of root segments with CdSO(4) inhibited K(+) uptake to 15% of control values. Cytoplasmic K(+) efflux was inhibited with 1 millimolar CdSO(4).The rates and the degree of Cd(2+) inhibition of the parameters listed above suggest that one of the first sites of Cd(2+) action is the plasmalemma K(+) carrier (ATPase) in oat roots.

Optical field dissipation in heterostructures for nanophotovoltaic devices

NASA Astrophysics Data System (ADS)

Villa-Angulo, Carlos; Sauceda-Carvajal, Daniel; Villa-Angulo, José R.; Villa-Angulo, Rafael

2016-10-01

In heterostructures for nanophotovoltaic (NPV) devices, a number of layers are concatenated in a multilayer configuration. In the analysis of a multilayer configuration, it is commonly assumed that the intensity of the optical field has an exponential decrease along the direction of propagation inside the structure. Effects such as reflections and interference are neglected. These neglected effects become especially important ones once the layer dimension reaches several nanometers. At this width regimen, quantum effects are present since layers are thin compared with the penetration depth and the wavelength of the incident light. Quantum effects influence photon absorption and affect the optical field dissipation that controls electron-hole pairs generation. Hence, dissipation of the optical field inside an NPV device is an important aspect to consider in studying and determining performance properties. We employed the one-dimensional optical transfer matrix theory and the quantum well theory to analyze the optical field dissipation in the active layer of heterostructures for NPV devices. Illumination of 100 mW·cm-2 air mass 1.5 global (AM 1.5G) standard was considered for the analysis. The study was extended to low-dimensional heterostructures of the binary compound CdS/CdSe/CdS, the ternary compound Ga0.9Al0.1As/GaAs/Ga0.9Al0.1As, and the quaternary compound In0.85Ga0.15As0.30P0.70/In0.7Ga0.3As0.6P0.4/In0.85Ga0.15As0.30P0.70.

The effects of the bottom anti-reflective coating with different baked temperatures and thicknesses on nanoscale patterns

NASA Astrophysics Data System (ADS)

Zheng, Jie; Li, Ling; Chen, Weidong

2015-12-01

The bottom anti-reflective coating (BARC) material can enhance the resolution of the nanopatterns structures in laser interference lithography process. In this study, WIDE-B ARC material was investigated to confirm the reduction of the vertical standing wave which leads to defect of nanopatterns. And the critical dimension (CD) of 100 nm L/S patterns with and without the application of BARC material was fabricated by laser interference lithography technology. The compared results showed that BARC can effectively reduce CD swing and obtain more uniform nanopatterns. Meanwhile, we also verified the influence of cured temperature and film thickness of BARC on the uniformity of nanopatterns.

Post-Spaceflight (STS-135) Mouse Splenocytes Demonstrate Altered Activation Properties and Surface Molecule Expression

PubMed Central

Crucian, Brian; Sams, Clarence

2015-01-01

Alterations in immune function have been documented during or post-spaceflight and in ground based models of microgravity. Identification of immune parameters that are dysregulated during spaceflight is an important step in mitigating crew health risks during deep space missions. The in vitro analysis of leukocyte activity post-spaceflight in both human and animal species is primarily focused on lymphocytic function. This report completes a broader spectrum analysis of mouse lymphocyte and monocyte changes post 13 days orbital flight (mission STS-135). Analysis includes an examination in surface markers for cell activation, and antigen presentation and co-stimulatory molecules. Cytokine production was measured after stimulation with T-cell mitogen or TLR-2, TLR-4, or TLR-5 agonists. Splenocyte surface marker analysis immediate post-spaceflight and after in vitro culture demonstrated unique changes in phenotypic populations between the flight mice and matched treatment ground controls. Post-spaceflight splenocytes (flight splenocytes) had lower expression intensity of CD4+CD25+ and CD8+CD25+ cells, lower percentage of CD11c+MHC II+ cells, and higher percentage of CD11c+MHC I+ populations compared to ground controls. The flight splenocytes demonstrated an increase in phagocytic activity. Stimulation with ConA led to decrease in CD4+ population but increased CD4+CD25+ cells compared to ground controls. Culturing with TLR agonists led to a decrease in CD11c+ population in splenocytes isolated from flight mice compared to ground controls. Consequently, flight splenocytes with or without TLR-agonist stimulation showed a decrease in CD11c+MHC I+, CD11c+MHC II+, and CD11c+CD86+ cells compared to ground controls. Production of IFN-γ was decreased and IL-2 was increased from ConA stimulated flight splenocytes. This study demonstrated that expression of surface molecules can be affected by conditions of spaceflight and impaired responsiveness persists under culture conditions in vitro. PMID:25970640

Low testosterone in non-responsive coeliac disease: A case series, case-control study with comparisons to the National Health and Nutrition Examination Survey.

PubMed

Kurada, Satya; Veeraraghavan, Gopal; Kaswala, Dharmesh; Hansen, Josh; Cohen, David; Kelly, Ciaran; Leffler, Daniel

2016-10-01

Adults with coeliac disease (CD) often report persistent fatigue, even when CD appears well controlled for unknown reasons. To evaluate common indications for testosterone panel (TP) testing and prevalence of low testosterone (T) in CD. In our case series, we determined common indications for checking TP in CD. Next, we conducted a case-control study to compare TP in CD vs. healthy controls (HC). We compared mean total T (TT), free T (FT) based on serologic, histologic disease activity. Finally, we assessed TT in tissue transglutaminase (tTG)+ vs. tTG- subjects and CD vs. HC obtained from the National Health and Nutrition Examination Survey (NHANES). 53 coeliac males had TP tested. Common indications included osteoporosis and fatigue. Low FT was observed in 7/13 men with osteoporosis and 5/6 with fatigue. In our case-control study (n=26 each), there was no difference in mean TT or FT between CD vs. HC, tTG+ vs tTG- or Marsh 0 vs. Marsh 3 groups. NHANES data showed no difference in mean TT between tTG+ vs tTG- (n=16 each) or CD vs. HC subjects (n=5 each). Low T occurs in CD patients at a similar rate as the general population. Common presentations of low T may mimic non-responsive CD symptoms. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Endoglin (CD105) expression in sinonasal polyposis.

PubMed

Ottaviano, Giancarlo; Cappellesso, Rocco; Mylonakis, Ioannis; Lionello, Marco; Favaretto, Niccolò; Giacomelli, Luciano; Spoladore, Cristiano; Marchese-Ragona, Rosario; Marino, Filippo; Staffieri, Alberto; Martini, Alessandro; Marioni, Gino

2015-11-01

Despite appropriate surgical therapy, 5-10 % of patients with chronic rhinosinusitis (CRS) and nasal polyps (NP) experience disease recurrences. It has been suggested that angiogenesis may relate to the pathogenesis and prognosis of CRS with NP. Endoglin (CD105) is a component of the receptor complex of transforming growth factor-beta, a pleiotropic cytokine that modulates angiogenesis. A series of patients treated surgically for CRS with NP was analyzed to assess the relationship between CD105 expression, main clinicopathological features, and recurrence rate. The immunohistochemical expression of CD105 was assessed in 70 patients consecutively operated for CRS with NP. In the univariate setting, the presence of CD105 (1/0) showed a trend towards a significant association with increasing NP dimensions (p = 0.054). Intensity of CD105 reaction was also significantly associated with NP size (0.04) and with an eosinophilic histology (p = 0.048). In our multivariate setting, only asthma (p = 0.016), hypereosinophilia (p = 0.022), and preoperative polyposis score (p = 0.046) retained their independent prognostic significance in relation to NP recurrence. Further efforts are needed to elucidate the biological, angiogenic and proliferative mechanisms behind recurrent NP. Our preliminary results support the clinical utility of extra postoperative care, in terms of closer follow-ups and medication with oral anti-histamines, topical and/or oral steroids, and antileukotrienes in patients with asthma, advanced nasal polyposis at presentation, and serum hypereosinophilia.

EuroQol (EQ-5D) measure of quality of life predicts mortality, emergency department utilization, and hospital discharge rates in HIV-infected adults under care.

PubMed

Mathews, William C; May, Susanne

2007-01-25

Health-related quality of life (HR-QOL) is a relevant and quantifiable outcome of care. We implemented HR-QOL assessment at all primary care visits at UCSD Owen Clinic using EQ-5D. The study aim was to estimate the prognostic value of EQ-5D for survival, hospitalization, and emergency department (ED) utilization after controlling for CD4 and HIV plasma viral load (pVL). We conducted a retrospective analysis of HIV clinic based cohort (1996-2000). The EQ-5D includes single item measures of: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each item is coded using 3-levels (1 = no problems; 2 = some problems; 3 = severe problems). The instrument includes a global rating of current health using a visual analog scale (VAS) ranging from 0 (worst imaginable) to 100 (best imaginable). An additional single item measure of health change (better, much the same, worse) was included. A predicted VAS (pVAS) was estimated by regressing the 5 EQ-5D health states on VAS using reference cell coding of health states and random effects linear models. Survival models were fit using Cox modelling. Hospitalization and ED rate models were estimated using population-averaged Poisson models. 965 patients met eligibility criteria. 12% were female; 42% were non-white. Median time-at-risk was 1.2 years. Median CD4 was 233. Median log10(pVL) was 4.6. 47 deaths occurred. In two Cox models controlling for CD4 and pVL, the adjusted hazard ratios (aHR) for VAS and pVAS as time-varying covariates were 0.73 (95% CI: 0.63-0.83) and 0.66 (95% CI: 0.56-0.77) respectively, for every 10 point increase in (p)VAS rating. In Poisson regression models predicting ED visit rates and hospital discharge rates controlling for current CD4 and pVL, each of the EQ-5D health dimensions, VAS, and health change items were significantly (p < 0.05) associated with the outcomes. For ED visit rates, the adjusted incidence rate ratios (aIRR) were 0.86 (0.83-0.89) and 0.79 (0.75-0.82) for VAS and pVAS, respectively. For hospital discharge rates, the aIRR's were 0.85 (0.82-0.88) and 0.79 (0.75-0.82) for VAS and pVAS, respectively. EQ-5D is a brief and prognostically useful predictor of mortality, hospitalization, and ED utilization among adults under care for HIV infection, even after adjusting for CD4 and HIV plasma viral load.

Resting and Activated Natural Tregs Decrease in the Peripheral Blood of Patients with Atherosclerosis.

PubMed

Yazdani, Mohammadreza; Khosropanah, Shahdad; Hosseini, Ahmad; Doroudchi, Mehrnoosh

2016-12-01

Atherosclerosis is a chronic inflammatory disease affecting large and medium arteries. CD4+ T cells are known to play a role in the progression of the disease. CD4+CD25+Foxp3+ natural Treg (nTreg) cells seem to have a protective role in the disease and their reduction in acute coronary syndrome is recently shown. To investigate the frequency of nTreg subsets in the peripheral blood of patients with atherosclerosis. Confirmation of atherosclerosis was done by angiography and 15 ml heparinized blood was obtained from each of the 13 non-diabetic patients and 13 non-diabetic, non-smoker individuals with normal/insignificant coronary artery disease confirmed by angiography. Lipid profiles of the patients and controls were measured at the time of sampling. Mononuclear cells were used for both RNA extraction and immunophenotyping by real-time PCR and flowcytometry techniques, respectively. In natural Treg subsets, the frequency of CD4+CD45RO-CD25+Foxp3lo T-cells (resting nTregs) was greater in controls than patients (p=0.02). The frequency of CD4+CD45RO+CD25hiFoxp3hi T-cells (activated nTregs) was significantly higher in controls compared with patients (p=0.02). However, the frequency of CD4+CD25+CD45RO+Foxp3- T-cells (effector/memory T-cell) increased in patients compared with controls (p=0.01). Both the MFI and gene expression of Foxp3 were higher in control group than in patients (p=0.015 and p=0.017, respectively). Moreover, the TGF-β gene expression showed a decrease in the peripheral blood mononuclear cells of patients compared with controls (p=0.03). Decrease in both subsets of resting and activated nTregs along with a decrease in the expression of Foxp3 and TGF-β genes in patients with atherosclerosis suggests phenotypic changes in these subsets, which may as well be correlated with a more inflammatory profile in their lymphocytes.

A new critical dimension metrology for chrome-on-glass substrates based on s-parameter measurements extracted from coplanar waveguide test structures

NASA Astrophysics Data System (ADS)

Nwokoye, Chidubem A.; Zaghloul, Mona; Cresswell, Michael W.; Allen, Richard A.; Murabito, Christine E.

2006-10-01

The technical objective of the work reported here is to assess whether radio-frequency (RF) measurements made on coplanar waveguide (CPW) test structures, which are replicated in conducting material on insulating substrates, could be employed to extract the critical dimension (CD) of the signal line using its center-to-center separation from the groundlines as a reference. The specific near-term objective is to assess whether this CPW-based CD-metrology has sensitivity and repeatability competitive with the other metrology techniques that are now used for chrome-on-glass (COG) photomasks. An affirmative answer is encouraging because advancing to a non-contact and non-vacuum implementation would then seem possible for this application. Our modeling of specific cases shows that, when the pitch of the replicated lines of the CPW is maintained constant, the sensitivity of its characteristic impedance to the CDs of the signal and ground lines is approximately 60 Ω/μm. This is a potentially useful result. For the same implementation, the quantity ∂C/∂w has a value of approximately 45 (pF/m)/μm, which appears to be large enough to provide acceptable accuracy.

Measurement of soluble CD59 in CSF in demyelinating disease: Evidence for an intrathecal source of soluble CD59.

PubMed

Zelek, Wioleta M; Watkins, Lewis M; Howell, Owain W; Evans, Rhian; Loveless, Sam; Robertson, Neil P; Beenes, Marijke; Willems, Loek; Brandwijk, Ricardo; Morgan, B Paul

2018-02-01

CD59, a broadly expressed glycosylphosphatidylinositol-anchored protein, is the principal cell inhibitor of complement membrane attack on cells. In the demyelinating disorders, multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), elevated complement protein levels, including soluble CD59 (sCD59), were reported in cerebrospinal fluid (CSF). We compared sCD59 levels in CSF and matched plasma in controls and patients with MS, NMOSD and clinically isolated syndrome (CIS) and investigated the source of CSF sCD59 and whether it was microparticle associated. sCD59 was quantified using enzyme-linked immunosorbent assay (ELISA; Hycult; HK374-02). Patient and control CSF was subjected to western blotting to characterise anti-CD59-reactive materials. CD59 was localised by immunostaining and in situ hybridisation. CSF sCD59 levels were double those in plasma (CSF, 30.2 ng/mL; plasma, 16.3 ng/mL). Plasma but not CSF sCD59 levels differentiated MS from NMOSD, MS from CIS and NMOSD/CIS from controls. Elimination of microparticles confirmed that CSF sCD59 was not membrane anchored. CSF levels of sCD59 are not a biomarker of demyelinating diseases. High levels of sCD59 in CSF relative to plasma suggest an intrathecal source; CD59 expression in brain parenchyma was low, but expression was strong on choroid plexus (CP) epithelium, immediately adjacent the CSF, suggesting that this is the likely source.

Renin-angiotensin system (RAS) blockade attenuates growth and metastatic potential of renal cell carcinoma in mice.

PubMed

Araújo, Wedson F; Naves, Marcelo A; Ravanini, Juliana N; Schor, Nestor; Teixeira, Vicente P C

2015-09-01

Renal cell carcinoma (RCC) is the most frequent type of cancer among renal neoplasms in adults and responds poorly to radiotherapy and chemotherapy. There is evidence that blockade of the renin-angiotensin system (RAS) might have antineoplastic effects. The aim of this study was to investigate the effects of RAS blockade on RCC in a murine model. Murine renal cancer cells (Renca) were injected (1 × 10(5)) into the subcapsular space of the left kidney of BALB/c mice (8 wk of age). The animals were divided into 4 groups: a control group (no treatment), angiotensin-receptor blockers group (losartan 100mg/kg/d), angiotensin-converting enzyme inhibitor group (captopril 10mg/kg/d), and angiotensin-receptor blockers +angiotensin-converting enzyme inhibitor group (losartan 100mg/kg/d +captopril 10mg/kg/d). The animals received the drugs by gavage for 21 days after inoculation, beginning 2 days before tumor induction, and were then euthanized. After killing the animals, the kidneys and lungs were removed, weighed, and processed for histopathological and immunohistochemical analyses. Angiogenesis and vascular microvessels were assessed with the antibodies anti-vascular endothelial growth factor and anti-CD34. Angiotensin II-inoculated animals developed renal tumors. Treated animals presented smaller tumors, regardless of the therapeutic regimen, and far fewer lung metastases in both quantity and dimension compared with the controls. The expression of vascular endothelial growth factor and CD34 were significantly decreased in renal tumors of treated animals compared with the controls. Our findings suggest that blockade of RAS decreases tumor proliferation and metastatic capacity of RCC in this experimental model. Copyright © 2015 Elsevier Inc. All rights reserved.

Increased Numbers of CD4+CD25+ and CD8+CD25+ T-Cells in Peripheral Blood of Patients with Rheumatoid Arthritis with Parvovirus B19 Infection.

PubMed

Naciute, Milda; Maciunaite, Gabriele; Mieliauskaite, Diana; Rugiene, Rita; Zinkeviciene, Aukse; Mauricas, Mykolas; Murovska, Modra; Girkontaite, Irute

2017-01-01

To investigate T-cell subpopulations in peripheral blood of human parvovirus B19 DNA-positive (B19 + ) and -negative (B19 - ) patients with rheumatoid arthritis (RA) and healthy persons. Blood samples were collected from 115 patients with RA and 47 healthy volunteers; 27 patients with RA and nine controls were B19 + Cluster of differentiation (CD) 4, 8, 25 and 45RA were analyzed on blood cells. CD25 expression on CD4 + CD45RA + , CD4 + CD45RA - , CD8 + CD45RA + , CD8 + CD45RA - subsets were analyzed by flow cytometry. The percentage of CD25 low and CD25 hi cells was increased on CD4 + CD45RA + , CD4 + CD45RA - T-cells and the percentage of CD25 + cells was increased on CD8 + CD45RA + , CD8 + CD45RA - T-cells of B19 + patients with RA in comparison with B19 - patients and controls. Raised levels of CD4 and CD8 regulatory T-cells in B19 + RA patients could cause down-regulation of antiviral clearance mechanisms and lead to activation of persistent human parvovirus B19 infection in patients with RA. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Increased Numbers of CD4+CD25+ and CD8+CD25+ T-Cells in Peripheral Blood of Patients with Rheumatoid Arthritis with Parvovirus B19 Infection

PubMed Central

NACIUTE, MILDA; MACIUNAITE, GABRIELE; MIELIAUSKAITE, DIANA; RUGIENE, RITA; ZINKEVICIENE, AUKSE; MAURICAS, MYKOLAS; MUROVSKA, MODRA; GIRKONTAITE, IRUTE

2017-01-01

Aim: To investigate T-cell subpopulations in peripheral blood of human parvovirus B19 DNA-positive (B19+) and -negative (B19−) patients with rheumatoid arthritis (RA) and healthy persons. Patients and Methods: Blood samples were collected from 115 patients with RA and 47 healthy volunteers; 27 patients with RA and nine controls were B19+. Cluster of differentiation (CD) 4, 8, 25 and 45RA were analyzed on blood cells. CD25 expression on CD4+CD45RA+, CD4+CD45RA−, CD8+CD45RA+, CD8+CD45RA− subsets were analyzed by flow cytometry. Results: The percentage of CD25low and CD25hi cells was increased on CD4+CD45RA+, CD4+CD45RA− T-cells and the percentage of CD25+ cells was increased on CD8+CD45RA+, CD8+CD45RA− T-cells of B19+ patients with RA in comparison with B19− patients and controls. Conclusion: Raised levels of CD4 and CD8 regulatory T-cells in B19+ RA patients could cause down-regulation of antiviral clearance mechanisms and lead to activation of persistent human parvovirus B19 infection in patients with RA PMID:28358698

Siblings of patients with Crohn's disease exhibit a biologically relevant dysbiosis in mucosal microbial metacommunities.

PubMed

Hedin, Charlotte; van der Gast, Christopher J; Rogers, Geraint B; Cuthbertson, Leah; McCartney, Sara; Stagg, Andrew J; Lindsay, James O; Whelan, Kevin

2016-06-01

To determine the existence of mucosal dysbiosis in siblings of patients with Crohn's disease (CD) using 454 pyrosequencing and to comprehensively characterise and determine the influence of genotypical and phenotypical factors, on that dysbiosis. Siblings of patients with CD have elevated risk of developing CD and display aspects of disease phenotype, including faecal dysbiosis. Whether the mucosal microbiota is disrupted in these at-risk individuals is unknown. Rectal biopsy DNA was extracted from 21 patients with quiescent CD, 17 of their healthy siblings and 19 unrelated healthy controls. Mucosal microbiota was analysed by 16S rRNA gene pyrosequencing and were classified into core and rare species. Genotypical risk was determined using Illumina Immuno BeadChip, faecal calprotectin by ELISA and blood T-cell phenotype by flow cytometry. Core microbiota of both patients with CD and healthy siblings was significantly less diverse than controls. Metacommunity profiling (Bray-Curtis (SBC) index) showed the sibling core microbial composition to be more similar to CD (SBC=0.70) than to healthy controls, whereas the sibling rare microbiota was more similar to healthy controls (SBC=0.42). Faecalibacterium prausnitzii contributed most to core metacommunity dissimilarity both between siblings and controls, and between patients and controls. Phenotype/genotype markers of CD risk significantly influenced microbiota variation between and within groups, of which genotype had the largest effect. Individuals with elevated CD-risk display mucosal dysbiosis characterised by reduced diversity of core microbiota and lower abundance of F. prausnitzii. This dysbiosis in healthy people at risk of CD implicates microbiological processes in CD pathogenesis. 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/

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.

CD81 Controls Sustained T Cell Activation Signaling and Defines the Maturation Stages of Cognate Immunological Synapses

PubMed Central

Rocha-Perugini, V.; Zamai, M.; González-Granado, J. M.; Barreiro, O.; Tejera, E.; Yañez-Mó, M.; Caiolfa, V. R.

2013-01-01

In this study, we investigated the dynamics of the molecular interactions of tetraspanin CD81 in T lymphocytes, and we show that CD81 controls the organization of the immune synapse (IS) and T cell activation. Using quantitative microscopy, including fluorescence recovery after photobleaching (FRAP), phasor fluorescence lifetime imaging microscopy-Föster resonance energy transfer (phasorFLIM-FRET), and total internal reflection fluorescence microscopy (TIRFM), we demonstrate that CD81 interacts with ICAM-1 and CD3 during conjugation between T cells and antigen-presenting cells (APCs). CD81 and ICAM-1 exhibit distinct mobilities in central and peripheral areas of early and late T cell-APC contacts. Moreover, CD81–ICAM-1 and CD81-CD3 dynamic interactions increase over the time course of IS formation, as these molecules redistribute throughout the contact area. Therefore, CD81 associations unexpectedly define novel sequential steps of IS maturation. Our results indicate that CD81 controls the temporal progression of the IS and the permanence of CD3 in the membrane contact area, contributing to sustained T cell receptor (TCR)-CD3-mediated signaling. Accordingly, we find that CD81 is required for proper T cell activation, regulating CD3ζ, ZAP-70, LAT, and extracellular signal-regulated kinase (ERK) phosphorylation; CD69 surface expression; and interleukin-2 (IL-2) secretion. Our data demonstrate the important role of CD81 in the molecular organization and dynamics of the IS architecture that sets the signaling threshold in T cell activation. PMID:23858057

Immunological alterations in individuals exposed to metal(loid)s in the Panasqueira mining area, Central Portugal.

PubMed

Coelho, Patrícia; García-Lestón, Julia; Costa, Solange; Costa, Carla; Silva, Susana; Fuchs, Dietmar; Geisler, Simon; Dall'Armi, Valentina; Zoffoli, Roberto; Bonassi, Stefano; Pásaro, Eduardo; Laffon, Blanca; Teixeira, João Paulo

2014-03-15

Environmental studies performed in Panasqueira mine area (central Portugal) identified high concentrations of several metal(loid)s in environmental media, and individuals environmentally and occupationally exposed showed higher levels of As, Cr, Mg, Mn, Mo, Pb and Zn in blood, urine, hair and nails when compared to unexposed controls. To evaluate the presence of immunological alterations attributable to environmental contamination, we quantified neopterin, kynurenine, tryptophan, and nitrite concentrations in plasma, and analysed the percentage of several lymphocytes subsets, namely CD3(+), CD4(+) and CD8(+) T-cells, CD19(+) B-cells, and CD16(+)56(+) natural killer (NK) cells in a group of individuals previously tested for metal(loid) levels in different biological matrices. The environmentally exposed group had significantly lower levels of %CD8(+) and higher CD4(+)/CD8(+) ratios, whereas the occupationally exposed individuals showed significant decreases in %CD3(+) and %CD4(+), and significant increases in %CD16(+)56(+), when compared to controls. Analysed biomarkers were found to be influenced by age, particularly neopterin, kynurenine and kynurenine to tryptophan ratio (Kyn/Trp) with significantly higher levels in older individuals, and %CD3(+), %CD8(+) and %CD19(+) with significantly lower values in older individuals. Males environmentally exposed showed significantly lower values of %CD19(+) when compared to control females. The concentration of Pb in toenails was associated to the level of neopterin, kynurenine and Kyn/Trp ratio (all direct), and the concentration of Mn in blood to the level of %CD8(+), %CD19(+) (both inverse) and CD4(+)/CD8(+) ratio (direct). Overall our results show that the metal(loid) contamination in Panasqueira mine area induced immunotoxic effects in exposed populations, possibly increasing susceptibility to diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

T-lymphocyte Subsets as a Prognostic Factor in a Clinical Course of Chickenpox

PubMed Central

Baljic, Rusmir; Konjo, Hadzan; Hrustemovic, Dzenana; Gazibera, Belma; Katica, Amela; Hukic, Mirsada

2017-01-01

Objective: To investigate possible prognostic values of CD4+, CD8+ T-lymphocytes, CD4/CD8 ratio to clinical course of chickenpox in immunocompetent hosts. Materials and methods: We performed a prospective study which included 69 immunocompetent patients with chickenpox who were addmited to Clinic for infectious disease, Clinical Center University of Sarajevo, in a 18 month period. All patients were divided into two groups depending on clinical presentation on admission. Patients with mild clinical form were dedicated to „outpatient” group, and patients with moderate, severe or life-threatening clinical forms were dedicated to „hospitalized” group. Also 30 healthy volunteers are included in study as a control group. We analyzed values of CD4+, CD8+ percentage, CD4/CD8 ratio with comparison to clinical course of chickenpox. All specimens were taken in acute phase of illness. Results: Values of CD4+ percentage were significantly declined in a group of hospitalized patients, compared to group of outpatients and control group. Values of CD8+ percentage were higher in a group of hospitalized patients, while CD4/CD8 values were lower in comparison to a group of outpatients and control group. Conclusion: We found significant correlation between these parameters and clinical course of chickenpox. PMID:28484347

Interfacial scanning tunneling spectroscopy (STS) of chalcogenide/metal hybrid nanostructure

NASA Astrophysics Data System (ADS)

Saad, Mahmoud M.; Abdallah, Tamer; Easawi, Khalid; Negm, Sohair; Talaat, Hassan

2015-05-01

The electronic structure at the interface of chalcogenide/metal hybrid nanostructure (CdSe-Au tipped) had been studied by UHV scanning tunneling spectroscopy (STS) technique at room temperature. This nanostructure was synthesized by a phase transfer chemical method. The optical absorption of this hybrid nanostructure was recorded, and the application of the effective mass approximation (EMA) model gave dimensions that were confirmed by the direct measurements using the scanning tunneling microscopy (STM) as well as the high-resolution transmission electron microscope (HRTEM). The energy band gap obtained by STS agrees with the values obtained from the optical absorption. Moreover, the STS at the interface of CdSe-Au tipped hybrid nanostructure between CdSe of size about 4.1 ± 0.19 nm and Au tip of size about 3.5 ± 0.29 nm shows a band bending about 0.18 ± 0.03 eV in CdSe down in the direction of the interface. Such a result gives a direct observation of the electron accumulation at the interface of CdSe-Au tipped hybrid nanostructure, consistent with its energy band diagram. The presence of the electron accumulation at the interface of chalcogenides with metals has an important implication for hybrid nanoelectronic devices and the newly developed plasmon/chalcogenide photovoltaic solar energy conversion.

Effect of black cumin (Nigella sativa) on cadmium-induced oxidative stress in the blood of rats.

PubMed

Kanter, Mehmet; Coskun, Omer; Gurel, Ahmet

2005-12-01

The protective effect of black cumin (Nigella sativa = NS) on cadmium-induced oxidative stress was studied in rats. The rats were randomly divided into three experimental groups: A (conrol), B (Cd treated), and C (Cd + NS treated), each containing 10 animals. The Cd-treated and Cd + NS-treated groups were injected subcutaneously daily with CdCl2 dissolved in isotonic NaCl in the amount of 2 mL/kg for 30 d, resulting in a dosage of 0.49 mg Cd/kg/d. The control group was injected with only isotonic NaCl (2 mL/kg/d) throughout the experiment (for 30 d). Three days prior to induction of CdCl2, the Cd + NS-treated group received a daily intraperitoneal injection of 0.2 mL/kg NS until the end of the study. Cd treatment increased significantly the malondialdehyde levels in plasma and erythrocyte (p<0.01 and p<0.05, respectively) and also increased significantly the antioxidant levels (superoxide dismutase, glutathione peroxidase, and catalase) (p<0.05) compared to the control group. Cd + NS treatment decreased significantly the elevated malondialdehyde levels in plasma and erythrocyte (p<0.01 and p<0.05, respectively) and also reduced significantly the enhanced antioxidant levels (p<0.05). Cd treatment increased significantly the activity of iron levels (p<0.05) in the plasma compared to the control group. Cd + NS treatment decreased the activity of iron levels (p<0.05) in the plasma compared to the Cd-treated group. In the control group with no treatment, histology of erythrocytes was normal. In the Cd-treated group, there were remarkable membrane destruction and hemolytic changes in erythrocytes. In the Cd + NS-treated group, these changes were less than in the Cd-treated group. Our results show that N. sativa exerts a protective effect against cadmium toxicity.

Increased numbers of CD4+ and CD8+ T cells in lesional skin of cats with allergic dermatitis.

PubMed

Roosje, P J; van Kooten, P J; Thepen, T; Bihari, I C; Rutten, V P; Koeman, J P; Willemse, T

1998-07-01

The aim of this study was to characterize T cells in the skin of cats with an allergic dermatitis histologically compatible with atopic dermatitis, since T cells play an important role in the pathogenesis of atopic dermatitis in humans. We observed a significantly greater number of T cells in lesional skin of domestic short-haired cats with allergic dermatitis (n = 10; median age 5.8 years) than in the skin of healthy control animals (n = 10; median age 5.0 years). In the skin of the healthy control animals, one or two CD4+ cells and no CD8+ cells were found. A predominant increase of CD4+ T cells and a CD4+/CD8+ ratio (mean +/- SD: 3.9 +/- 2.0) was found in the lesional skin of 10 cats with allergic dermatitis. The CD4+/CD8+ cell ratio in the skin of healthy control animals could not be determined because of the absence of CD8+ cells. The CD4+/CD8+ cell ratio in the peripheral blood of 10 cats with allergic dermatitis (mean +/- SD: 1.9 +/- 0.4) did not differ significantly from that in 10 healthy control animals (2.2 +/- 0.4). The CD4+/CD8+ cell ratio and predominance of CD4+ T cells in the lesional skin of cats with allergic dermatitis is comparable to that found in atopic dermatitis in humans. In addition, the observed increase of CD4+ T cells in the nonlesional skin of cats with allergic dermatitis compared to the skin of healthy cats is similar to what is seen in humans. Cytokines produced by T cells and antigen-specific T cells are important mediators in the inflammatory cascade resulting in atopic dermatitis in humans. This study is a first step to investigate their role in feline allergic dermatitis.

Human CD34+ Progenitor Cells Freshly Isolated from Umbilical Cord Blood Attenuate Inflammatory Lung Injury following LPS Challenge

PubMed Central

Huang, Xiaojia; Sun, Kai; Zhao, Yidan D.; Vogel, Stephen M.; Song, Yuanling; Mahmud, Nadim; Zhao, You-Yang

2014-01-01

Adult stem cell-based therapy is a promising novel approach for treatment of acute lung injury. Here we investigated the therapeutic potential of freshly isolated human umbilical cord blood CD34+ progenitor cells (fCB-CD34+ cells) in a mouse model of acute lung injury. At 3 h post-lipopolysaccharide (LPS) challenge, fCB-CD34+ cells were transplanted i.v. to mice while CD34− cells or PBS were administered as controls in separate cohorts of mice. We observed that fCB-CD34+ cell treatment inhibited lung vascular injury evident by decreased lung vascular permeability. In contrast, CD34− cells had no effects on lung vascular injury. Lung inflammation determined by myeloperoxidase activity, neutrophil sequestration and expression of pro-inflammatory mediators was attenuated in fCB-CD34+ cell-treated mice at 26 h post-LPS challenge compared to PBS or CD34− cell-treated controls. Importantly, lung inflammation in fCB-CD34+ cell-treated mice was returned to normal levels as seen in basal mice at 52 h post-LPS challenge whereas PBS or CD34− cell-treated control mice exhibited persistent lung inflammation. Accordingly, fCB-CD34+ cell-treated mice exhibited a marked increase of survival rate. Employing in vivo 5-bromo-2′-deoxyuridine incorporation assay, we found a drastic induction of lung endothelial proliferation in fCB-CD34+ cell-treated mice at 52 h post-LPS compared to PBS or CD34− cell-treated controls, which contributed to restoration of vascular integrity and thereby inhibition of lung inflammation. Taken together, these data have demonstrated the protective effects of fCB-CD34+ cell on acute lung injury induced by LPS challenge, suggesting fCB-CD34+ cells are an important source of stem cells for the treatment of acute lung injury. PMID:24558433

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.

Immunologic and psychosocial status in chronic fatigue syndrome.

PubMed

Nas, K; Cevik, R; Batum, S; Sarac, A J; Acar, S; Kalkanli, S

2011-01-01

The aim of the study was to investigate the immunologic functions and psychosocial status in patients with chronic fatigue syndrome (CFS). Twenty-five patients with CFS diagnosed by the international CFS definition criteria and 20 age- and gender-matched healthy controls were recruited. Depression was assessed by Beck Depression Inventory (BDI) and health status was assessed by Nottingham Health Profile (NHP). Monoclonal antibodies (MAbs) were measured to identify the following NK cell subsets: CD3, CD4, CD8 and CD56 and cytokine measurements were performed for IL2r, IL6 and IL8 in both patients and control subjects. The BDI and NHP scores of CFS group were found to be significantly higher than in the control group. The absolute numbers of CD56 cell were also significantly decreased in the patients with CFS compared with the healthy controls. There were no other significant differences of NK cell activity (CD3, CD4 and CD8) and there were significant differences in IL6 and IL2r levels between patients and controls. There were significant correlations between serum IL-6 level and sleep, social isolation and physical ability NHP subscores, and betweenCD56 NK cell activity and emotional reaction NHP sub score in CFS patients. Significantly higher ratios of psychological and physical disturbances were found in patients with CFS. Decreased CD56 NK cell activity and increased IL2r levels seem to be important immunopathologic changes in CFS. IL-6 and CD 56 NK cell activity may play an important role in sleep, physical, social, and physicological manifestations of CFS (Tab. 3, Fig. 1, Ref. 36). Full Text in free PDF www.bmj.sk.

Mobilization Characteristics and Strategies to Improve Hematopoietic Progenitor Cell Mobilization and Collection in Patients with Chronic Granulomatous Disease and Severe Combined Immunodeficiency

PubMed Central

Panch, Sandhya R.; Yau, Yu Ying; Kang, Elizabeth M.; De Ravin, Suk See; Malech, Harry L.; Leitman, Susan F.

2014-01-01

Background G-CSF mobilized autologous hematopoietic progenitor cells (HPC) may be collected by apheresis of patients with chronic granulomatous disease (CGD) and severe combined immunodeficiency (SCID) for use in gene therapy trials. CD34+ cell mobilization has not been well characterized in such patients. Study Design and Methods We retrospectively evaluated CD34+ cell mobilization and collection in 73 consecutive CGD and SCID patients and in 99 age, weight and G-CSF dose-matched healthy allogeneic controls. Results In subjects aged ≤20 years, day 5 pre-apheresis circulating CD34+ counts were significantly lower in CGD and SCID than in controls; mean peak CD34+ cells 58, 64, and 87/uL, respectively, p=0.01. The SCIDs had lower CD34+ collection efficiency than CGDs and controls; mean efficiency 40%, 63% and 57%, respectively, p=0.003. In subjects >20 years, the CGDs had significantly lower CD34+ cell mobilization than controls; mean peak CD34+ cells 41 and 113/uL, respectively, p<0.0001. In a multivariate analysis, lower sedimentation rate (ESR) at mobilization was significantly correlated with better CD34+ cell mobilization, p=0.007. In SCIDs, CD34 collection efficiency was positively correlated with higher red cell indices (MCV: R2=0.77; MCH: R2=0.94; MCHC: R2=0.7, p<0.007) but not hemoglobin. Conclusions CGD and SCID populations are characterized by significantly less robust CD34+ HPC mobilization than healthy controls. The presence of active inflammation/infection as suggested by an elevated ESR may negatively impact mobilization. Among SCIDs, markedly reduced CD34 collection efficiencies were related to iron deficiency, wherein decreased red cell size and density may impair apheresis cell separation mechanics. PMID:25143186

Neuropathology of Cervical Dystonia

PubMed Central

Prudente, C.N.; Pardo, C.A.; Xiao, J.; Hanfelt, J.; Hess, E.J.; LeDoux, M.S.; Jinnah, H.A.

2012-01-01

The aim of this study was to search for neuropathological changes in postmortem brain tissue of individuals with cervical dystonia (CD). Multiple regions of formalin-preserved brains were collected from patients with CD and controls and examined with an extensive battery of histopathological stains in a two-stage study design. In stage one, 4 CD brains underwent a broad screening neuropathological examination. In stage two, these 4 CD brains were combined with 2 additional CD brains, and the subjective findings were quantified and compared to 16 age-matched controls. The initial subjective neuropathological assessment revealed only two regions with relatively consistent changes. The substantia nigra had frequent ubiquitin-positive intranuclear inclusions known as Marinesco bodies. Additionally, the cerebellum showed patchy loss of Purkinje cells, areas of focal gliosis and torpedo bodies. Other brain regions showed minor or inconsistent changes. In the second stage of the analysis, quantitative studies failed to reveal significant differences in the numbers of Marinesco bodies in CD versus controls, but confirmed a significantly lower Purkinje cell density in CD. Molecular investigations revealed 4 of the CD cases and 2 controls to harbor sequence variants in non-coding regions of THAP1, and these cases had lower Purkinje cell densities regardless of whether they had CD. The findings suggest that subtle neuropathological changes such as lower Purkinje cell density may be found in primary CD when relevant brain regions are investigated with appropriate methods. PMID:23195594

Peripheral natural killer cytotoxicity and CD56(pos)CD16(pos) cells increase during early pregnancy in women with a history of recurrent spontaneous abortion.

PubMed

Emmer, P M; Nelen, W L; Steegers, E A; Hendriks, J C; Veerhoek, M; Joosten, I

2000-05-01

For diagnostic purposes we assessed peripheral natural killer (NK) cell cytotoxicity and NK and T cell numbers to assess their putative predictive value in recurrent spontaneous abortion (RSA). A total of 43 women with subsequent pregnancy, 37 healthy controls and 39 women successfully partaking in an in-vitro fertilization (IVF) procedure, were included in the study. We show that before pregnancy, levels of NK cytotoxicity and numbers of both single CD56(pos) and double CD56(pos)CD16(pos) cells were similar between RSA women and controls. But notably, within the RSA group, NK cell numbers of <12% were strongly associated with a subsequent pregnancy carried to term. Supplementation of folic acid led to an increase of single CD56(pos) cells, but cytotoxic function appeared unaffected. The expression pattern of killer inhibitory receptors on CD56(pos) cells was not different between patients and controls. A longitudinal study revealed that, compared with controls, in RSA women higher numbers of double CD56(pos)CD16(pos) cells were present during early pregnancy, paralleled by an increase in cytotoxic NK cell reactivity. The single CD56(pos) population decreased in number. In conclusion, the analysis of peripheral NK cell characteristics appears a suitable diagnostic tool in RSA. Immunomodulation aimed at NK cell function appears a promising therapeutic measure.

[Effect of cellular immune supportive treatment on immunity of esophageal carcinoma patients after modern two-field lymph node dissection].

PubMed

Wang, Jun-Ye; Ma, Guo-Wei; Dai, Shu-Qin; Rong, Tie-Hua; Wang, Xin; Lin, Peng; Ye, Wen-Feng; Zhang, Lan-Jun; Li, Xiao-Dong; Zhang, Xu; Yao, Guang-Yu

2007-07-01

Cellular immunity suppression is marked in patients with esophageal carcinoma, which may be resulted temporarily from surgical injury. This study was to evaluate the effect of cellular immune supportive treatment on cellular immunity of patients with esophageal carcinoma. A total of 60 patients with thoracic esophageal carcinoma, received two-field dissection, were randomized into control group and trial (immune supportive treatment) group. The patients in trial group were injected with Shenqi injection after operation; the patients in control group received no immune supportive treatment. Peripheral blood samples were obtained before operation, and 3 and 9 days after operation. AgNOR (argyrophilic nucleolar organizer regions) activity in peripheral blood T lymphocytes was measured by tumor immune microphotometry. T cell subsets were measured by flow cytometry. The proportions of CD3+CD4+ and CD4+/CD8+ cells were significantly higher in trial group than in control group at 3 days after operation (P < 0.05). The amount of AgNOR and proportions of CD3+, CD3+CD4+, CD4+/CD8+, and CD4+CD25+ cells were significantly higher in trial group than in control group at 9 days after operation (P < 0.05). There was no significant difference in 1-year survival rate between the 2 groups (P > 0.05). Shenqi injection could obviously improve cellular immunity of the esophageal carcinoma patients after modern two-field dissection.

Integrated approach to improving local CD uniformity in EUV patterning

NASA Astrophysics Data System (ADS)

Liang, Andrew; Hermans, Jan; Tran, Timothy; Viatkina, Katja; Liang, Chen-Wei; Ward, Brandon; Chuang, Steven; Yu, Jengyi; Harm, Greg; Vandereyken, Jelle; Rio, David; Kubis, Michael; Tan, Samantha; Dusa, Mircea; Singhal, Akhil; van Schravendijk, Bart; Dixit, Girish; Shamma, Nader

2017-03-01

Extreme ultraviolet (EUV) lithography is crucial to enabling technology scaling in pitch and critical dimension (CD). Currently, one of the key challenges of introducing EUV lithography to high volume manufacturing (HVM) is throughput, which requires high source power and high sensitivity chemically amplified photoresists. Important limiters of high sensitivity chemically amplified resists (CAR) are the effects of photon shot noise and resist blur on the number of photons received and of photoacids generated per feature, especially at the pitches required for 7 nm and 5 nm advanced technology nodes. These stochastic effects are reflected in via structures as hole-to-hole CD variation or local CD uniformity (LCDU). Here, we demonstrate a synergy of film stack deposition, EUV lithography, and plasma etch techniques to improve LCDU, which allows the use of high sensitivity resists required for the introduction of EUV HVM. Thus, to improve LCDU to a level required by 5 nm node and beyond, film stack deposition, EUV lithography, and plasma etch processes were combined and co-optimized to enhance LCDU reduction from synergies. Test wafers were created by depositing a pattern transfer stack on a substrate representative of a 5 nm node target layer. The pattern transfer stack consisted of an atomically smooth adhesion layer and two hardmasks and was deposited using the Lam VECTOR PECVD product family. These layers were designed to mitigate hole roughness, absorb out-of-band radiation, and provide additional outlets for etch to improve LCDU and control hole CD. These wafers were then exposed through an ASML NXE3350B EUV scanner using a variety of advanced positive tone EUV CAR. They were finally etched to the target substrate using Lam Flex dielectric etch and Kiyo conductor etch systems. Metrology methodologies to assess dimensional metrics as well as chip performance and defectivity were investigated to enable repeatable patterning process development. Illumination conditions in EUV lithography were optimized to improve normalized image log slope (NILS), which is expected to reduce shot noise related effects. It can be seen that the EUV imaging contrast improvement can further reduce post-develop LCDU from 4.1 nm to 3.9 nm and from 2.8 nm to 2.6 nm. In parallel, etch processes were developed to further reduce LCDU, to control CD, and to transfer these improvements into the final target substrate. We also demonstrate that increasing post-develop CD through dose adjustment can enhance the LCDU reduction from etch. Similar trends were also observed in different pitches down to 40 nm. The solutions demonstrated here are critical to the introduction of EUV lithography in high volume manufacturing. It can be seen that through a synergistic deposition, lithography, and etch optimization, LCDU at a 40 nm pitch can be improved to 1.6 nm (3-sigma) in a target oxide layer and to 1.4 nm (3-sigma) at the photoresist layer.

Within-wafer CD variation induced by wafer shape

NASA Astrophysics Data System (ADS)

Huang, Chi-hao; Yang, Mars; Yang, Elvis; Yang, T. H.; Chen, K. C.

2016-03-01

In order to meet the increasing storage capacity demand and reduce bit cost of NAND flash memories, 3D stacked vertical flash cell array has been proposed. In constructing 3D NAND flash memories, the bit number per unit area is increased as increasing the number of stacked layers. However, the increased number of stacked layers has made the film stress control extremely important for maintaining good process quality. The residual film stress alters the wafer shape accordingly several process impacts have been readily observed across wafer, such as film deposition non-uniformity, etch rate non-uniformity, wafer chucking error on scanner, materials coating/baking defects, overlay degradation and critical dimension (CD) non-uniformity. The residual tensile and compressive stresses on wafers will result in concave and convex wafer shapes, respectively. This study investigates within-wafer CD uniformity (CDU) associated with wafer shape change induced by the 3D NAND flash memory processes. Within-wafer CDU was correlated with several critical parameters including different wafer bow heights of concave and convex wafer shapes, photo resists with different post exposure baking (PEB) temperature sensitivities, and DoseMapper compensation. The results indicated the trend of within-wafer CDU maintains flat for convex wafer shapes with bow height up to +230um and concave wafer shapes with bow height ranging from 0 ~ -70um, while the within-wafer CDU trends up from -70um to -246um wafer bow heights. To minimize the within-wafer CD distribution induced by wafer warpage, carefully tailoring the film stack and thermal budget in the process flow for maintaining the wafer shape at CDU friendly range is indispensable and using photo-resist materials with lower PEB temperature sensitivity is also suggested. In addition, DoseMapper compensation is also an alternative to greatly suppress the within-wafer CD non-uniformity but the photo-resist profile variation induced by across-wafer PEB temperature non-uniformity attributed to wafer warpage is uncorrectable, and the photo-resist profile variation is believed to affect across-wafer etch bias uniformity to some degree.

Absorption and emission spectroscopy of individual semiconductor nanostructures

NASA Astrophysics Data System (ADS)

McDonald, Matthew P.

The advent of controllable synthetic methods for the production of semiconductor nanostructures has led to their use in a host of applications, including light-emitting diodes, field effect transistors, sensors, and even television displays. This is, in part, due to the size, shape, and morphologically dependent optical and electrical properties that make this class of materials extremely customizable; wire-, rod- and sphere-shaped nanocrystals are readily synthesized through common wet chemical methods. Most notably, confining the physical dimension of the nanostructure to a size below its Bohr radius (aB) results in quantum confinement effects that increase its optical energy gap. Not only the size, but the shape of a particle can be exploited to tailor its optical and electrical properties. For example, confined CdSe quantum dots (QDs) and nanowires (NWs) of equivalent diameter possess significantly different optical gaps. This phenomenon has been ascribed to electrostatic contributions arising from dielectric screening effects that are more pronounced in an elongated (wire-like) morphology. Semiconducting nanostructures have thus received significant attention over the past two decades. However, surprisingly little work has been done to elucidate their basic photophysics on a single particle basis. What has been done has generally been accomplished through emission-based measurements, and thus does not fully capture the full breadth of these intriguing systems. What is therefore needed then are absorption-based studies that probe the size and shape dependent evolution of nanostructure photophysics. This thesis summarizes the single particle absorption spectroscopy that we have carried out to fill this knowledge gap. Specifically, the diameter-dependent progression of one-dimensional (1D) excitonic states in CdSe NWs has been revealed. This is followed by a study that focuses on the polarization selection rules of 1D excitons within single CdSe NWs. Finally, shape effects are explored by probing the absorption spectra of CdSe nanowires and nanorods of varying length. All experimental studies are complemented by theoretical predictions from an effective mass model that takes electrostatic interactions into account. Thus, this thesis seeks to show the delicate interplay between quantum confinement and dielectric screening effects in single CdSe nanostructures.

Malignant and Tuberculous Pleural Effusions: Immunophenotypic Cellular Characterization

PubMed Central

de Aguiar, Lucia Maria Zanatta; Antonangelo, Leila; Vargas, Francisco S.; Zerbini, Maria Cláudia Nogueira; Sales, Maria Mirtes; Uip, David E.; Saldiva, Paulo Hilário Nascimento

2008-01-01

INTRODUCTION AND OBJECTIVES Tuberculosis and cancer are the main causes of pleural effusion. Pleural involvement is associated with migration of immune cells to the pleural cavity. We sought to characterize the immunophenotype of leukocytes in the pleural effusion and peripheral blood of patients with tuberculosis or malignancy. METHODS Thirty patients with tuberculosis (14) or malignancy (16) were studied. A control group included 20 healthy blood donors. RESULTS Malignant phycoerythrin pleural effusions showed higher percentages of CD3, CD4, CD3CD45RO, and CD20CD25 lymphocytes and lower percentages of CD3CD25 and CD20HLA-DR when compared to PB lymphocytes. Compared to PB, tuberculous effusions had a higher percentage of lymphocytes that co-expressed CD3, CD4, CD3CD45RO, CD3TCRαβ, CD3CD28, and CD20 and a lower percentage of CD14, CD8 and CD3TCRγδ-positive lymphocytes. Malignant effusions presented higher expression of CD14 whereas tuberculous effusions had higher expression of CD3 and CD3CD95L. Peripheral blood cells from tuberculosis patients showed higher expression of CD14, CD20CD25 and CD3CD95L. Compared with the control cells, tuberculosis and cancer peripheral blood cells presented a lower percentage of CD3CD4 and CD3CD28-positive cells as well as a higher percentage of CD3CD8, CD3CD25 and CD3CD80-positive cells. CONCLUSIONS Tuberculous and malignant peripheral blood is enriched with lymphocytes with a helper/inducer T cell phenotype, which are mainly of memory cells. CD14-positive cells were more frequently found in malignant effusions, while CD3-positive cells expressing Fas ligand were more frequently found in tuberculous effusions. PMID:18925324

Evaluation of proteome alterations induced by cadmium stress in sunflower (Helianthus annuus L.) cultures.

PubMed

Lopes Júnior, Cícero Alves; Barbosa, Herbert de Sousa; Moretto Galazzi, Rodrigo; Ferreira Koolen, Hector Henrique; Gozzo, Fábio Cesar; Arruda, Marco Aurélio Zezzi

2015-09-01

The present study evaluates, at a proteomic level, changes in protein abundance in sunflower leaves in the absence or presence (at 50 or 700mg) of cadmium (as CdCl2). At the end of the cultivation period (45 days), proteins are extracted from leaves with phenol, separated by two-dimensional difference gel electrophoresis (2-D DIGE), and excised from the gels. The differential protein abundances (for proteins differing by more than 1.8 fold, which corresponds to 90% variation) are characterized using nESI-LC-MS/MS. The protein content decreases by approximately 41% in plants treated with 700mg Cd compared with control plants. By comparing all groups of plants evaluated in this study (Control vs. Cd-lower, Control vs. Cd-higher and Cd-lower vs. Cd-higher), 39 proteins are found differential and 18 accurately identified; the control vs. Cd-higher treatment is that presenting the most differential proteins. From identified proteins, those involved in energy and disease/defense (including stress), are the ribulose bisphosphate carboxylase large chain, transketolase, and heat shock proteins are the most differential abundant proteins. Thus, at the present study, photosynthesis is the main process affected by Cd in sunflowers, although these plants are highly tolerant to Cd. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of hard mask etch on final topography of advanced phase shift masks

NASA Astrophysics Data System (ADS)

Hortenbach, Olga; Rolff, Haiko; Lajn, Alexander; Baessler, Martin

2017-07-01

Continuous shrinking of the semiconductor device dimensions demands steady improvements of the lithographic resolution on wafer level. These requirements challenge the photomask industry to further improve the mask quality in all relevant printing characteristics. In this paper topography of the Phase Shift Masks (PSM) was investigated. Effects of hard mask etch on phase shift uniformity and mask absorber profile were studied. Design of experiments method (DoE) was used for the process optimization, whereas gas composition, bias power of the hard mask main etch and bias power of the over-etch were varied. In addition, influence of the over-etch time was examined at the end of the experiment. Absorber depth uniformity, sidewall angle (SWA), reactive ion etch lag (RIE lag) and through pitch (TP) dependence were analyzed. Measurements were performed by means of Atomic-force microscopy (AFM) using critical dimension (CD) mode with a boot-shaped tip. Scanning electron microscope (SEM) cross-section images were prepared to verify the profile quality. Finally CD analysis was performed to confirm the optimal etch conditions. Significant dependence of the absorber SWA on hard mask (HM) etch conditions was observed revealing an improvement potential for the mask absorber profile. It was found that hard mask etch can leave a depth footprint in the absorber layer. Thus, the etch depth uniformity of hard mask etch is crucial for achieving a uniform phase shift over the active mask area. The optimized hard mask etch process results in significantly improved mask topography without deterioration of tight CD specifications.

Study of modification methods of probes for critical-dimension atomic-force microscopy by the deposition of carbon nanotubes

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

Ageev, O. A., E-mail: ageev@sfedu.ru; Bykov, Al. V.; Kolomiitsev, A. S.

2015-12-15

The results of an experimental study of the modification of probes for critical-dimension atomicforce microscopy (CD-AFM) by the deposition of carbon nanotubes (CNTs) to improve the accuracy with which the surface roughness of vertical walls is determined in submicrometer structures are presented. Methods of the deposition of an individual CNT onto the tip of an AFM probe via mechanical and electrostatic interaction between the probe and an array of vertically aligned carbon nanotubes (VACNTs) are studied. It is shown that, when the distance between the AFM tip and a VACNT array is 1 nm and the applied voltage is withinmore » the range 20–30 V, an individual carbon nanotube is deposited onto the tip. On the basis of the results obtained in the study, a probe with a carbon nanotube on its tip (CNT probe) with a radius of 7 nm and an aspect ratio of 1:15 is formed. Analysis of the CNT probe demonstrates that its use improves the resolution and accuracy of AFM measurements, compared with the commercial probe, and also makes it possible to determine the roughness of the vertical walls of high-aspect structures by CD-AFM. The results obtained can be used to develop technological processes for the fabrication and reconditioning of special AFM probes, including those for CD-AFM, and procedures for the interoperational express monitoring of technological process parameters in the manufacturing of elements for micro- and nanoelectronics and micro- and nanosystem engineering.« less

Distributed force probe bending model of critical dimension atomic force microscopy bias

NASA Astrophysics Data System (ADS)

Ukraintsev, Vladimir A.; Orji, Ndubuisi G.; Vorburger, Theodore V.; Dixson, Ronald G.; Fu, Joseph; Silver, Rick M.

2013-04-01

Critical dimension atomic force microscopy (CD-AFM) is a widely used reference metrology technique. To characterize modern semiconductor devices, small and flexible probes, often 15 to 20 nm in diameter, are used. Recent studies have reported uncontrolled and significant probe-to-probe bias variation during linewidth and sidewall angle measurements. To understand the source of these variations, tip-sample interactions between high aspect ratio features and small flexible probes, and their influence on measurement bias, should be carefully studied. Using theoretical and experimental procedures, one-dimensional (1-D) and two-dimensional (2-D) models of cylindrical probe bending relevant to carbon nanotube (CNT) AFM probes were developed and tested. An earlier 1-D bending model was refined, and a new 2-D distributed force (DF) model was developed. Contributions from several factors were considered, including: probe misalignment, CNT tip apex diameter variation, probe bending before snapping, and distributed van der Waals-London force. A method for extracting Hamaker probe-surface interaction energy from experimental probe-bending data was developed. Comparison of the new 2-D model with 1-D single point force (SPF) model revealed a difference of about 28% in probe bending. A simple linear relation between biases predicted by the 1-D SPF and 2-D DF models was found. The results suggest that probe bending can be on the order of several nanometers and can partially explain the observed CD-AFM probe-to-probe variation. New 2-D and three-dimensional CD-AFM data analysis software is needed to take full advantage of the new bias correction modeling capabilities.

HIV Controllers Exhibit Enhanced Frequencies of Major Histocompatibility Complex Class II Tetramer+ Gag-Specific CD4+ T Cells in Chronic Clade C HIV-1 Infection

PubMed Central

Laher, Faatima; Ranasinghe, Srinika; Porichis, Filippos; Mewalal, Nikoshia; Pretorius, Karyn; Ismail, Nasreen; Buus, Søren; Stryhn, Anette; Carrington, Mary; Walker, Bruce D.; Ndung'u, Thumbi

2017-01-01

ABSTRACT Immune control of viral infections is heavily dependent on helper CD4+ T cell function. However, the understanding of the contribution of HIV-specific CD4+ T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibility complex (MHC) class II tetramers have emerged as a powerful tool for interrogating antigen-specific CD4+ T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4+ T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to the viral load of HIV-specific CD4+ T cell responses in a cohort of untreated HIV clade C-infected persons. We observed significantly higher frequencies of MHC class II tetramer-positive CD4+ T cells in HIV controllers than progressors (P = 0.0001), and these expanded Gag-specific CD4+ T cells in HIV controllers showed higher levels of expression of the cytolytic proteins granzymes A and B. Importantly, targeting of the immunodominant Gag41 peptide in the context of HLA class II DRB1*1101 was associated with HIV control (r = −0.5, P = 0.02). These data identify an association between HIV-specific CD4+ T cell targeting of immunodominant Gag epitopes and immune control, particularly the contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infection. Furthermore, these results highlight the advantage of the use of class II tetramers in evaluating HIV-specific CD4+ T cell responses in natural infections. IMPORTANCE Increasing evidence suggests that virus-specific CD4+ T cells contribute to the immune-mediated control of clade B HIV-1 infection, yet there remains a relative paucity of data regarding the role of HIV-specific CD4+ T cells in shaping adaptive immune responses in individuals infected with clade C, which is responsible for the majority of HIV infections worldwide. Understanding the contribution of HIV-specific CD4+ T cell responses in clade C infection is particularly important for developing vaccines that would be efficacious in sub-Saharan Africa, where clade C infection is dominant. Here, we employed MHC class II tetramers designed to immunodominant Gag epitopes and used them to characterize CD4+ T cell responses in HIV-1 clade C infection. Our results demonstrate an association between the frequency of HIV-specific CD4+ T cell responses targeting an immunodominant DRB1*11-Gag41 complex and HIV control, highlighting the important contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infections. PMID:28077659

Polymorphisms in CD14 Gene May Modify Soluble CD14 Levels and Represent Risk Factors for Multiple Sclerosis.

PubMed

Farrokhi, Mehrdad; Moeini, Pedram; Fazilati, Mohammad; Nazem, Habibollah; Faraji, Shahla; Saadatpour, Zahra; Fadaei, Elyas; Saadatpour, Leila; Rezaei, Ali; Ansaripour, Sadra; Amani-Beni, Ali

2016-11-07

Besides the central role of the adaptive immune system, a disturbance of innate immune system is also suggested to be involved in the pathogenesis of multiple sclerosis (MS). CD14, a receptor upregulated in activated microglia, is known to be an essential mediator of inflammation in innate immune responses. Therefore, in this study we aimed to assess possible roles of CD14-159 and -260 gene polymorphisms in MS susceptibility and the effects of those polymorphisms to its protein producing capacity in Iranian population. In this case control study, CD14-159 and -260 polymorphisms were genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in 200 MS patients and 200 healthy controls matched in age and gender. Serum levels of soluble CD14 (sCD14) was determined by enzyme-linked immunosorbent assay (ELISA). There were significant differences in genotype distribution of CD14-159 and -260 polymorphisms between patients and controls (P = 0.01, for-both). Mean serum level of sCD14 was significantly higher in MS patients than in control subjects (3340.30 ± 612.50 ng/ml vs 2353.73 ± 539.07 ng/ml; P < 0.01). In summary, we conclude that CD14-159 and -260 polymorphisms are associated with the risk of MS in Iranian population and affects CD14 promoter activity, thereby regulating CD14 expression. Furthermore, our study provides preliminary evidence for the activation of innate immunity in the pathogenesis of MS. In addition, the findings of the present study suggest serum level of sCD14 as candidate biomarker of MS severity.

Psychological disorders and oral lichen planus: matched case-control study and literature review.

PubMed

Pippi, R; Romeo, U; Santoro, M; Del Vecchio, A; Scully, C; Petti, S

2016-04-01

Oral lichen planus (OLP) may be linked to psychological disorders. This study investigated psychological factors associated with OLP. A case-control study with incident OLP case patients and age-gender-socio-economic status-matched controls, recruited from among relatives, accompanying persons, and departmental staff, investigated psychological traits using the Psychological General Well-Being Index-Short form. Common factor analysis was used to generate a set of psychological dimensions. The association between these dimensions and OLP adjusted for confounders (education, number of lifetime sexual partners, drinking-smoking) and interactions was assessed through conditional logistic regression and odds ratios (OR) were estimated. A total of 67 case-control pairs were recruited. Psychological dimensions generated were: dimension-1 (anxiety, low vitality), dimension-2 (negative well-being, low vitality), dimension-3 (depressed mood, low self-control). The ORs for OLP were, dimension-1, 1.0 (95% confidence interval -95CI, 0.3-2.6); dimension-2, 0.5 (95CI, 0.2-1.2); dimension-3, 4.8 (95CI, 1.8-12.9). Dimension-3 was highly associated with mild, but not associated with severe, OLP. Literature searching provided 21 studies, with anxiety and depression principally associated with OLP. Depressed mood and low self-control were highly associated with OLP, particularly the reticular-papular forms. These traits could have a causative role in OLP development-progression, but further investigations are necessary. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Use of clay to remediate cadmium contaminated soil under different water management regimes.

PubMed

Li, Jianrui; Xu, Yingming

2017-07-01

We examined in situ remediation of sepiolite on cadmium-polluted soils with diverse water regimes, and several variables including brown rice Cd, exchangeable Cd, pH, and available Fe/P. pH, available Fe/P in soils increased gradually during continuous flooding, which contributed to Cd absorption on colloids. In control group (untreated soils), compared to conventional irrigation, brown rice Cd in continuous flooding reduced by 37.9%, and that in wetting irrigation increased by 31.0% (p<0.05). In contrast to corresponding controls, brown rice Cd in sepiolite treated soils reduced by 44.4%, 34.5% and 36.8% under continuous flooding, conventional irrigation and wetting irrigation (p<0.05), and exchangeable Cd in amended soils reduced by 27.5-49.0%, 14.3-40.5%, and 24.9-32.8% under three water management regimes (p<0.05). Compared to corresponding controls, decreasing amplitudes of exchangeable Cd and brown rice Cd in sepiolite treated soils were higher in continuous flooding than in conventional irrigation and wetting irrigation. Continuous flooding management promoted soil Cd immobilization by sepiolite. Copyright © 2017. Published by Elsevier Inc.

Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura

PubMed Central

Yu, Jin; Heck, Susanne; Patel, Vivek; Levan, Jared; Yu, Yu; Bussel, James B.

2008-01-01

Immune thrombocytopenic purpura (ITP) is characterized by the presence of antiplatelet autoantibodies as a result of loss of tolerance. CD4+CD25+ regulatory T cells (Tregs) are important for maintenance of peripheral tolerance. Decreased levels of peripheral Tregs in patients with ITP have been reported. To test whether inefficient production or reduced immunosuppressive activity of Tregs contributes to loss of tolerance in patients with chronic ITP, we investigated the frequency and function of their circulating CD4+CD25hi Tregs. We found a com-parable frequency of circulating CD4+CD25hiFoxp3+ Tregs in patients and controls (n = 16, P > .05). However, sorted CD4+CD25hi cells from patients with chronic ITP (n = 13) had a 2-fold reduction of in vitro immunosuppressive activity compared with controls (n = 10, P < .05). The impaired suppression was specific to Tregs as shown by cross-mixing experiments with T cells from controls. These data suggest that functional defects in Tregs contribute to breakdown of self-tolerance in patients with chronic ITP. PMID:18420827

Regulatory T Cells in Patients with Idiopathic Thrombocytopenic Purpura.

PubMed

Akyol Erikçi, Alev; Karagöz, Bülent; Bilgi, Oğuz

2016-06-05

Immune thrombocytopenic purpura (ITP) is an immune-mediated bleeding disorder in which platelets are opsonized by autoantibodies and destroyed by an Fc receptor-mediated phagocytosis by the reticuloendothelial system within the spleen. Autoimmune processes are also considered in the pathogenesis of this disorder. CD4+CD25+FoxP3+ regulatory T (Treg) cells and CD8+CD28- Treg cells have roles in autoimmune diseases. We investigated these regulatory cells in ITP patients. We included 22 ITP patients and 16 age-matched healthy subjects. CD4+CD25+FoxP3+ Treg cells and CD8+CD28- cells were investigated by three-color flow cytometry. The ratios of these cell populations to total lymphocytes were calculated. Statistical analysis was carried out with the Mann-Whitney U test. CD4+CD25+ Treg cells were 9.69±3.70% and 12.99±5.58% in patients with ITP and controls, respectively. CD4+CD25highFoxP3+ cells were 27.72±19.74% and 27.55±23.98% in ITP patients and controls, respectively. The percentages of both of these cell types were not statistically significant when compared to the control group. We did not find any differences in ratios of CD4+CD25+FoxP3+ Treg cells or CD8+CD28- T cells in lymphocytes between patients and healthy subjects. We conclude that these circulatory cells are not different in ITP, but further studies are needed to explore the putative roles of these regulatory cells.

[Increased expressions of peripheral PD-1+ lymphocytes and CD4+CD25+FOXP3+ T cells in gastric adenocarcinoma patients].

PubMed

Li, Hao; Li, Songyan; Hu, Shidong; Zou, Guijun; Hu, Zilong; Wei, Huahua; Wang, Yufeng; Du, Xiaohui

2017-01-01

Objective To detect the frequencies of peripheral programmed death-1 + (PD-1 + ) lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells in patients with gastric adenocarcinoma. Methods The study enrolled 29 patients with gastric adenocarcinoma and 29 age- and sex-matched healthy controls. Frequencies of PD-1 + lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells were detected using flow cytometry. Results The number of PD-1 + lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells in peripheral blood was higher in patients with gastric adenocarcinoma than that in the control group. Moreover, linear correlation analysis indicated a positive correlation between PD-1 expression and frequency of CD4 + CD25 + FOXP3 + regulatory T cells in peripheral blood of the patients. Conclusion Gastric adenocarcinoma patients present with increased PD-1 + lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells in the peripheral blood.

Increased IFN-gamma production by NK and CD3+/CD56+ cells in sexually HIV-1-exposed but uninfected individuals.

PubMed

Montoya, Carlos Julio; Velilla, Paula Andrea; Chougnet, Claire; Landay, Alan L; Rugeles, Maria Teresa

2006-08-01

The mechanisms involved in controlling the establishment of HIV-1 infection are not fully understood. In particular, the role of innate immunity in natural resistance exhibited by individuals who are continuously exposed to HIV-1 but remain seronegative (ESN) has not been thoroughly evaluated. We determined the frequency and function of peripheral blood innate immune cells (plasmacytoid and myeloid dendritic cells, monocytes, NK cells, CD3+/CD56+ cells and invariant NKT cells) in ESN, chronically HIV-1-infected and low-risk HIV-1 seronegative individuals. ESN demonstrated a similar frequency of innate immune cells in comparison to controls and a higher frequency of dendritic cells, NK and invariant NKT cells compared to HIV-1-infected subjects. Incubation of mononuclear cells with stimulatory CpG ODN induced CD86 and CD69 up-regulation to a similar degree on innate cells from the three study groups. CpG ODN-stimulated secretion of cytokines was also similar between ESN and controls, while secretion of IFN-alpha was significantly decreased in HIV-1+ individuals. Importantly, expression of IFN-gamma by PMA/Ionomycin-activated CD56(bright) NK cells and CD3+/CD56+ cells was significantly higher in ESN when compared with controls. The anti-viral effects of IFN-gamma are well established, and so our results suggest that IFN-gamma production by innate immune cells might be one of the multiple factors involved in controlling the establishment of sexually transmitted HIV-1 infection.

Selective CD28 Antagonist Blunts Memory Immune Responses and Promotes Long-Term Control of Skin Inflammation in Nonhuman Primates.

PubMed

Poirier, Nicolas; Chevalier, Melanie; Mary, Caroline; Hervouet, Jeremy; Minault, David; Baker, Paul; Ville, Simon; Le Bas-Bernardet, Stephanie; Dilek, Nahzli; Belarif, Lyssia; Cassagnau, Elisabeth; Scobie, Linda; Blancho, Gilles; Vanhove, Bernard

2016-01-01

Novel therapies that specifically target activation and expansion of pathogenic immune cell subsets responsible for autoimmune attacks are needed to confer long-term remission. Pathogenic cells in autoimmunity include memory T lymphocytes that are long-lived and present rapid recall effector functions with reduced activation requirements. Whereas the CD28 costimulation pathway predominantly controls priming of naive T cells and hence generation of adaptive memory cells, the roles of CD28 costimulation on established memory T lymphocytes and the recall of memory responses remain controversial. In contrast to CD80/86 antagonists (CTLA4-Ig), selective CD28 antagonists blunt T cell costimulation while sparing CTLA-4 and PD-L1-dependent coinhibitory signals. Using a new selective CD28 antagonist, we showed that Ag-specific reactivation of human memory T lymphocytes was prevented. Selective CD28 blockade controlled both cellular and humoral memory recall in nonhuman primates and induced long-term Ag-specific unresponsiveness in a memory T cell-mediated inflammatory skin model. No modification of memory T lymphocytes subsets or numbers was observed in the periphery, and importantly no significant reactivation of quiescent viruses was noticed. These findings indicate that pathogenic memory T cell responses are controlled by both CD28 and CTLA-4/PD-L1 cosignals in vivo and that selectively targeting CD28 would help to promote remission of autoimmune diseases and control chronic inflammation. Copyright © 2015 by The American Association of Immunologists, Inc.

Altered CD19/CD22 balance in Egyptian children and adolescents with systemic lupus erythematosus.

PubMed

El-Sayed, Zeinab A; Ragab, Seham M; Khalifa, Khaled A; El Ashmawy, Ramy A

2009-01-01

B cells from systemic lupus erythematosus (SLE) patients display signalling defects that may underlie disease pathogenesis activity.CD19 and CD22 play a major role as regulators of B-cell response. The aim of this study was to clarify the relationship between B cell surface markers namely CD19, CD20 and CD22 expression and clinical and laboratory indices of SLE activity. The study included 33 SLE patients and 20 healthy children and adolescents as controls. Flowcytometric assay of dual markers, CD19/CD20, and CD20/CD22 was done. SLE disease activity was assessed by SLEDAI score. CD22% was significantly higher while CD20% was significantly lower in the study compared to the control group. No significant difference was observed in both groups with respect to CD19% or CD19/CD22% ratio. The level of CD22 expression was significantly lower in high and very high active cases than in mild and moderate cases and negatively correlated with SLDEAI score and ESR. Results obtained showed that, B cell surface receptors CD20 and CD22 are significantly affected in patients with SLE, pointing to their possible involvement in the aetiopathogenesis of the disease and in the regulatory mechanisms in response to the immune disturbance.

Formation and Characterization of Gold Nanoparticles

DTIC Science & Technology

2013-09-01

nanowires are useful because they can be grown almost dislocation free, due to their nano dimension. The quality of crystalline materials is diminished by...real substrate temperature was obtained from the calibration based on the melting points of indium (In), selenium (Se), cadmium (Cd), and zinc (Zn...hydrogen fluoride In indium MBE molecular beam epitaxy NH3OH ammonium hydroxide RHEED reflection high-energy electron diffraction Se selenium SEM

Automated CD-SEM recipe creation technology for mass production using CAD data

NASA Astrophysics Data System (ADS)

Kawahara, Toshikazu; Yoshida, Masamichi; Tanaka, Masashi; Ido, Sanyu; Nakano, Hiroyuki; Adachi, Naokaka; Abe, Yuichi; Nagatomo, Wataru

2011-03-01

Critical Dimension Scanning Electron Microscope (CD-SEM) recipe creation needs sample preparation necessary for matching pattern registration, and recipe creation on CD-SEM using the sample, which hinders the reduction in test production cost and time in semiconductor manufacturing factories. From the perspective of cost reduction and improvement of the test production efficiency, automated CD-SEM recipe creation without the sample preparation and the manual operation has been important in the production lines. For the automated CD-SEM recipe creation, we have introduced RecipeDirector (RD) that enables the recipe creation by using Computer-Aided Design (CAD) data and text data that includes measurement information. We have developed a system that automatically creates the CAD data and the text data necessary for the recipe creation on RD; and, for the elimination of the manual operation, we have enhanced RD so that all measurement information can be specified in the text data. As a result, we have established an automated CD-SEM recipe creation system without the sample preparation and the manual operation. For the introduction of the CD-SEM recipe creation system using RD to the production lines, the accuracy of the pattern matching was an issue. The shape of design templates for the matching created from the CAD data was different from that of SEM images in vision. Thus, a development of robust pattern matching algorithm that considers the shape difference was needed. The addition of image processing of the templates for the matching and shape processing of the CAD patterns in the lower layer has enabled the robust pattern matching. This paper describes the automated CD-SEM recipe creation technology for the production lines without the sample preparation and the manual operation using RD applied in Sony Semiconductor Kyusyu Corporation Kumamoto Technology Center (SCK Corporation Kumamoto TEC).

How much is enough? An analysis of CD measurement amount for mask characterization

NASA Astrophysics Data System (ADS)

Ullrich, Albrecht; Richter, Jan

2009-10-01

The demands on CD (critical dimension) metrology amount in terms of both reproducibility and measurement uncertainty steadily increase from node to node. Different mask characterization requirements have to be addressed like very small features, unevenly distributed features, contacts, semi-dense structures to name only a few. Usually this enhanced need is met by an increasing number of CD measurements, where the new CD requirements are added to the well established CD characterization recipe. This leads straight forwardly to prolonged cycle times and highly complex evaluation routines. At the same time mask processes are continuously improved to become more stable. The enhanced stability offers potential to actually reduce the number of measurements. Thus, in this work we will start to address the fundamental question of how many CD measurements are needed for mask characterization for a given confidence level. We used analysis of variances (ANOVA) to distinguish various contributors like mask making process, measurement tool stability and measurement methodology. These contributions have been investigated for classical photomask CD specifications e.g. mean to target, CD uniformity, target offset tolerance and x-y bias. We found depending on specification that the importance of the contributors interchanges. Interestingly, not only short and long-term metrology contributions are dominant. Also the number of measurements and their spatial distribution on the mask layout (sampling methodology) can be the most important part of the variance. The knowledge of contributions can be used to optimize the sampling plan. As a major finding, we conclude that there is potential to reduce a significant amount of measurements without loosing confidence at all. Here, full sampling in x and y as well as full sampling for different features can be shortened substantially almost up to 50%.

The clinical usefulness of the new LPE specifier for subtyping adolescents with conduct disorder in the DSM 5.

PubMed

Jambroes, Tijs; Jansen, Lucres M C; Vermeiren, Robert R J M; Doreleijers, Theo A H; Colins, Olivier F; Popma, Arne

2016-08-01

In DSM 5, conduct disorder (CD) has been expanded with a new specifier 'with Limited Prosocial Emotions' (LPE) in addition to the age-of-onset (AoO) subtyping, and is thought to identify a severe antisocial subgroup of CD. However, research in clinical practice has been scarce. Therefore, the current study will examine differences in clinical symptoms between subtypes of CD, based on both subtyping schemes. Subsequently, it will investigate whether the LPE specifier explains unique variance in aggression, added to the AoO subtyping. A sample of 145 adolescents with CD (51 % male, mean age 15.0) from a closed treatment institution participated in this study. CD diagnoses and AoO subtype were assessed using a structured diagnostic interview. The LPE specifier was assessed using the callous-unemotional dimension of the Youth Psychopathy Traits Inventory (YPI). Self-reported proactive and reactive aggression, rule-breaking behavior and internalizing problems within the subtypes were compared. Youth with childhood-onset CD and LPE showed significantly more aggression than adolescent-onset CD without LPE (proactive aggression: F = 3.1, p < 0.05, reactive aggression: F = 3.7, p < 0.05). Hierarchical regression revealed that the LPE specifier uniquely explained 7 % of the variance in reactive aggression, additionally to the AoO subtyping. For proactive aggression, the interaction between AoO and the LPE added 4.5 % to the explained variance. Although the LPE specifier may help to identify a more aggressive subtype of CD in adolescents, the incremental utility seems to be limited. Therefore, clinical relevance of the LPE specifier in high-risk adolescent samples still needs to be investigated thoroughly.

Sensorineural hearing loss and celiac disease: A coincidental finding

PubMed Central

Volta, Umberto; Ferri, Gian Gaetano; De Giorgio, Roberto; Fabbri, Angela; Parisi, Claudia; Sciajno, Laura; Castellari, Alessandra; Fiorini, Erica; Piscaglia, Maria; Barbara, Giovanni; Granito, Alessandro; Pirodda, Antonio

2009-01-01

BACKGROUND Celiac disease (CD) can be associated with a variety of extraintestinal manifestations, including neurological diseases. A new neurological correlation has been found between CD and sensorineural hearing loss (SNHL). OBJECTIVE To verify the association between SNHL and CD, and to establish whether the neurological hearing impairment in CD is related to nonorgan-specific and antineuronal antibodies, as well as the presence of autoimmune disorders. METHODS A sample of 59 consecutive biopsy- and serologically proven CD patients were studied. Among CD patients, 11 were newly diagnosed and 48 were on a gluten-free diet. Hearing function was assessed by audiometric analysis in all CD patients as well as in 59 age- and sex-matched controls. Patients were tested for a panel of immune markers including nonorgan-specific autoantibodies and antineuronal antibodies. RESULTS SNHL was detected in five CD patients (8.5%) and in two controls (3.4%). In one patient, the SNHL was bilateral, whereas the remaining four had a monolateral impairment. The prevalence of SNHL was not significantly different between CD patients and controls. At least one of the antibodies tested for was positive in two of the five CD patients with SNHL and in 12 of the 54 CD patients without SNHL. Antineuronal antibodies to central nervous system antigens were consistently negative in the five CD patients with SNHL. Only one of the five CD patients with SNHL had Hashimoto thyroiditis. CONCLUSIONS SNHL and CD occur coincidentally. Hearing function should be assessed only in CD patients with clinical signs of hearing deficiency. PMID:19668795

Whole body BMC in pediatric Crohn disease: independent effects of altered growth, maturation, and body composition.

PubMed

Burnham, Jon M; Shults, Justine; Semeao, Edisio; Foster, Bethany; Zemel, Babette S; Stallings, Virginia A; Leonard, Mary B

2004-12-01

Whole body BMC was assessed in 104 children and young adults with CD and 233 healthy controls. CD was associated with significant deficits in BMC and lean mass, relative to height. Adjustment for lean mass eliminated the bone deficit in CD. Steroid exposure was associated with short stature but not bone deficits relative to height. Children with Crohn disease (CD) have multiple risk factors for impaired bone accrual. The confounding effects of poor growth and delayed maturation limit the interpretation of prior studies of bone health in CD. The objective of this study was to assess BMC relative to growth, body composition, and maturation in CD compared with controls. Whole body BMC and lean mass were assessed by DXA in 104 CD subjects and 233 healthy controls, 4-26 years of age. Multivariable linear regression models were developed to sequentially adjust for differences in skeletal size, pubertal maturation, and muscle mass. BMC-for-height z scores were derived to determine CD-specific covariates associated with bone deficits. Subjects with CD had significantly lower height z score, body mass index z score, and lean mass relative to height compared with controls (all p < 0.0001). After adjustment for group differences in age, height, and race, the ratio of BMC in CD relative to controls was significantly reduced in males (0.86; 95% CI, 0.83, 0.94) and females (0.91; 95% CI, 0.85, 0.98) with CD. Adjustment for pubertal maturation did not alter the estimate; however, addition of lean mass to the model eliminated the bone deficit. Steroid exposure was associated with short stature but not bone deficits. This study shows the importance of considering differences in body size and composition when interpreting DXA data in children with chronic inflammatory conditions and shows an association between deficits in muscle mass and bone in pediatric CD.

The influence of monetary punishment on cognitive control in abstinent cocaine-users*

PubMed Central

Hester, Robert; Bell, Ryan P.; Foxe, John J.; Garavan, Hugh

2013-01-01

Background Dependent drug users show a diminished neural response to punishment, in both limbic and cortical regions, though it remains unclear how such changes influence cognitive processes critical to addiction. To assess this relationship, we examined the influence of monetary punishment on inhibitory control and adaptive post-error behaviour in abstinent cocaine dependent (CD) participants. Methods 15 abstinent CD and 15 matched control participants performed a Go/No-go response inhibition task, which administered monetary fines for failed response inhibition, during collection of fMRI data. Results CD participants showed reduced inhibitory control and significantly less adaptive post-error slowing in response to punishment, when compared to controls. The diminished behavioural punishment sensitivity shown by CD participants was associated with significant hypoactive error-related BOLD responses in the dorsal anterior cingulate cortex (ACC), right insula and right prefrontal regions. Specifically, CD participants’ error-related response in these regions was not modulated by the presence of punishment, whereas control participants’ response showed a significant BOLD increase during punished errors. Conclusions CD participants showed a blunted response to failed control (errors) that was not modulated by punishment. Consistent with previous findings of reduced sensitivity to monetary loss in cocaine users, we further demonstrate that such insensitivity is associated with an inability to increase cognitive control in the face of negative consequences, a core symptom of addiction. The pattern of deficits in the CD group may have implications for interventions that attempt to improve cognitive control in drug dependent groups via positive/negative incentives. PMID:23791040

The influence of monetary punishment on cognitive control in abstinent cocaine-users.

PubMed

Hester, Robert; Bell, Ryan P; Foxe, John J; Garavan, Hugh

2013-11-01

Dependent drug users show a diminished neural response to punishment, in both limbic and cortical regions, though it remains unclear how such changes influence cognitive processes critical to addiction. To assess this relationship, we examined the influence of monetary punishment on inhibitory control and adaptive post-error behavior in abstinent cocaine dependent (CD) participants. 15 abstinent CD and 15 matched control participants performed a Go/No-go response inhibition task, which administered monetary fines for failed response inhibition, during collection of fMRI data. CD participants showed reduced inhibitory control and significantly less adaptive post-error slowing in response to punishment, when compared to controls. The diminished behavioral punishment sensitivity shown by CD participants was associated with significant hypoactive error-related BOLD responses in the dorsal anterior cingulate cortex (ACC), right insula and right prefrontal regions. Specifically, CD participants' error-related response in these regions was not modulated by the presence of punishment, whereas control participants' response showed a significant BOLD increase during punished errors. CD participants showed a blunted response to failed control (errors) that was not modulated by punishment. Consistent with previous findings of reduced sensitivity to monetary loss in cocaine users, we further demonstrate that such insensitivity is associated with an inability to increase cognitive control in the face of negative consequences, a core symptom of addiction. The pattern of deficits in the CD group may have implications for interventions that attempt to improve cognitive control in drug dependent groups via positive/negative incentives. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

Immune Status 'in Children with Beta Thalassemia' in Correlation 'with Iron Overload': Single Center Egyptian Study.

PubMed

Hagag, Adel A; Elgamsy, Mohamed A; El-Asy, Hassan M; Gamal, Rasha M; Elshahaby, Walid N; Abd Elbar, Enaam S

2016-01-01

'Beta thalassemia is inherited hemoglobin disorder resulting in chronic hemolytic anemia that requires lifelong transfusion therapy'. 'Repeated blood transfusions and RBCs hemolysis are the main causes of iron overload', which in addition to immune abnormalities, are common predisposing factors to infections in patients with thalassemia. The Aim of this Work: The aim of this work was to study immune status including T lymphocyte subsets and serum immunoglobulin levels 'in children with beta- thalassemia in correlation with iron overload'. The present 'study was conducted on 40 children with beta thalassemia major under follow up at Hematology Unit, Pediatric Department, Tanta University' 'including 24 males and 16 females with mean' age value of 9. 22 ± 3.9 years and 20 'healthy children of matched age and sex as a control group'. All children included in the study were subjected to; 'complete blood count, Hb electrophoresis, serum iron status', T cell subsets including CD3, CD4 and CD8 and serum immunoglobulin levels including IgM, IgA and IgG. 'Pallor and jaundice were the most common presenting' clinical manifestations. Infective episodes 'were significantly higher in patients' compared with controls. There were significantly lower Hb, MCV and MCH levels and significantly higher WBCs and platelets counts, reticulocytes and lymphocytes percentage in patients than controls and no significant differences in MCHC between patients and controls. Serum ferritin and iron were 'significantly higher but TIBC was significantly lower in' patients than controls. CD3, CD4 and IgM were significantly lower but CD8, IgG, and IgA 'were significantly higher in patients than controls' with negative correlation between CD3, CD4, IgM and ferritin and positive correlation between CD8, IgG, IgA and ferritin. Iron overload can affect humeral and cell mediated immunity in patients with beta thalassemia with reduction of IgM, CD3 and CD4 and elevation of CD8, IgG, and IgA. Regular follow up of patients with beta thalassemia for detection of iron overload as it affects humeral and cell mediated immunity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Fluorescent carbon dot-gated multifunctional mesoporous silica nanocarriers for redox/enzyme dual-responsive targeted and controlled drug delivery and real-time bioimaging.

PubMed

Wang, Ying; Cui, Yu; Zhao, Yating; He, Bing; Shi, Xiaoli; Di, Donghua; Zhang, Qiang; Wang, Siling

2017-08-01

A distinctive and personalized nanocarrier is described here for controlled and targeted antitumor drug delivery and real-time bioimaging by combining a redox/enzyme dual-responsive disulfide-conjugated carbon dot with mesoporous silica nanoparticles (MSN-SS-CD HA ). The carbon dot with controlling and targeting abilities was prepared through a polymerizing reaction by applying citric acid and HA as starting materials (named CD HA ). The as-prepared MSN-SS-CD HA exhibited not only superior photostability and excellent biocompatibility, but also the ability to target A549 cells with overexpression of CD44 receptors. Upon loading the antitumor drug, doxorubicin (DOX), into the mesoporous channels of MSN nanoparticles, CD HA with a diameter size of 3nm completely blocked the pore entrance of DOX-encapsulated MSN nanoparticles with a pore size of about 3nm, thus preventing the premature leakage of DOX and increasing the antitumor activity until being triggered by specific stimuli in the tumor environment. The results of the cell imaging and cytotoxicity studies demonstrated that the redox/enzyme dual-responsive DOX-encapsulated MSN-SS-CD HA nanoparticles can selectively deliver and control the release of DOX into tumor cells. Ex vivo fluorescence images showed a much stronger fluorescence of MSN-SS-CD HA -DOX in the tumor site than in normal tissues, greatly facilitating the accumulation of DOX in the target tissue. However, its counterpart, MSN-SH-DOX exhibited no or much lower tumor cytotoxicity and drug accumulation in tumor tissue. In addition, MSN-SS-CD was also used as a control to investigate the ability of MSN-SS-CD HA to target A549 cells. The results obtained indicated that MSN-SS-CD HA possessed a higher cellular uptake through the CD44 receptor-mediated endocytosis compared with MSN-SS-CD in the A549 cells. Such specific redox/enzyme dual-responsive targeted nanocarriers are a useful strategy achieving selective controlled and targeted delivery of therapeutic reagents with real-time bioimaging, and may also facilitate the development of drug delivery systems for a number of clinical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Peripheral CD24hi CD27+ CD19+ B cells subset as a potential biomarker in naïve systemic lupus erythematosus.

PubMed

Jin, Lin; Weiqian, Chen; Lihuan, Yue

2013-12-01

B cells are likely to play critical roles in the pathogenesis of systemic lupus erythematosus (SLE). Our aim was to investigate the role of peripheral CD24(hi) CD27(+) CD19(+) B cells in Chinese patients with new-onset SLE. Peripheral CD24(hi) CD27(+) CD19(+) B cells were analyzed in 55 new-onset lupus and 36 healthy controls by flow cytometry. All SLE cases were treated with prednisolone and hydroxychloroquine during a 1-year follow-up. Thirteen cases were added with cyclophosphamide or mycophenolate mofetil. The CD24(hi) CD27(+) CD19(+) B cells were analyzed at days 0, 7, 14 and months 1, 3, 6, 9 and 12. Interleukin-10 (IL-10)-producing B cell was detected in eight naïve lupus and 10 healthy controls. Compared to healthy controls, the frequency and number of primary circulating CD24(hi) CD27(+) CD19(+) B cells was significantly reduced in SLE cases (8.22 ± 3.48% vs. 31.67 ± 5.53%, P < 0.0001; 4.04 ± 2.85 vs. 38.66 ± 10.22 10(3) cells/mL, P = 0.0001) before treatment; IL-10(+) CD19(+) B cells and IL-10(+) CD24(hi) CD27(+) CD19(+) B cells also decreased in SLE. Interestingly, primary CD24(hi) CD27(+) CD19(+) B cells inversely correlated with SLE disease activity index (SLEDAI) score. Patients with arthritis and hematologic disorders had a lower primary CD24(hi) CD27(+) CD19(+) B cells. In 48 SLE cases who finished the 1-year follow-up, the frequency and number of CD24(hi) CD27(+) CD19(+) B cells increased from 8.26 ± 3.61% to 25.51 ± 4.56%; 3.99 ± 2.86 to 28.64 ± 11.81 10(3) cells/mm(3) (P < 0.0001), accompanied by a significantly decreased SLEDAI score. Of note, CD24(hi) CD27(+) CD19(+) B cells decreased in some flare cases with an elevated SLEDAI score. These results demonstrate that a lower primary CD24(hi) CD27(+) CD19(+) B cells may be an immunologic aspect of new-onset SLE. CD24(hi) CD27(+) CD19(+) B cells may be a useful tool to evaluate lupus activity and monitor the response to therapy. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

G-CSF-primed autologous and allogeneic bone marrow for transplantation in clinical oncology. Cell content and immunological characteristics

NASA Astrophysics Data System (ADS)

Grivtsova, L. Yu; Melkova, K. N.; Kupryshkina, N. A.; Vorotnikov, I. K.; Grigoryeva, T. A.; Selchuk, V. Yu; Grebennikova, O. P.; Titova, G. V.; Tupitsyn, N. N.

2018-01-01

60 samples of G-CSF-primed bone marrow (39 cancer patients and 21 healthy donors) to be used for transplantation to cancer patients were analyzed and compared by main characteristics with historical control and 13 bone marrow samples from control patient with mastopathy. Basing on morphological and multicolor flow cytometry findings certain characteristics of G-CSF-primed bone marrow were discovered, such as a significant increase in blast count in cancer patients as compared to donors and control patients (p<0.037), a higher neutrophil maturation index (p<0.001) and a lower percentage of mature lymphocytes (p<0.008) as compared to the control group. Among lymphocyte populations G-CSF-priming was associated with a significant increase in the total of mature CD3+ T-cells and CD8+ T-killers (p<0.0001) and a decrease in CD56+CD3- and/or CD16+CD3- NK-cells (p<0.006) both in cancer patients and healthy donors in comparison with the controls.

Internet-orientated Assessment of QOL and Actual Treatment Status in Japanese Patients with Inflammatory Bowel Disease: The 3I survey.

PubMed

Matsumoto, Takayuki; Yanai, Shunichi; Toya, Yosuke; Ueno, Masato; Nakamura, Shotaro

2015-06-01

This survey aimed to compare actual lifestyle factors and QOL between Japanese IBD patients and healthy Japanese controls, by questionnaire using an internet-web system. Through the internet-web system, we asked 464 patients with Crohn's disease [CD], 360 patients with ulcerative colitis [UC], and 4100 healthy controls to answer a questionnaire including an eight-item short-form health survey [SF-8]. The survey was conducted until data had been accumulated from the predetermined numbers of patients [120 patients each with CD and UC] and healthy controls [240 subjects]. QOL assessment by SF-8 revealed scores for six of the eight subscale items and the summary score for the mental component to be significantly lower in the CD and UC groups than in controls. There was a significant negative correlation between each SF-8 score and the degree of CD and UC symptoms. The marriage rate in adult patients was significantly lower in the CD than in the UC group or the controls. The mean annual income and the employment rate were significantly lower in the CD than in the UC group or the controls. CD patients receiving biologicals were more frequently satisfied with the efficacy of treatment than UC patients were with their treatment regimens [56% vs 29%]. Actual lifestyle factors and QOL appear to be impaired in Japanese patients with IBD, especially those with CD. The subjective efficacy of biologicals might be greater in CD than in UC. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Expansions of CD8+CD28- and CD8+TcRVbeta5.2+ T cells in peripheral blood of heavy alcohol drinkers.

PubMed

Arosa, F A; Porto, G; Cabeda, J M; Lacerda, R; Resende, D; Cruz, E; Cardoso, C; Fonseca, M; Simões, C; Rodrigues, P; Bravo, F; Oliveira, J C; Alves, H; Fraga, J; Justiça, B; de Sousa, M

2000-04-01

Despite heavy alcohol consumption, only a low percentage of heavy drinkers develop liver disease. Imbalances in T-cell subsets and iron metabolism parameters are common findings in heavy drinkers, yet the possible role played by discrete T-lymphocyte subsets under heavy alcohol consumption remains unclear. To gain new insights into the possible role played by T lymphocytes during alcohol consumption, characterization of CD28 expression and TcR repertoire in peripheral blood CD4+ and CD8+ T cells by two and three-color flow cytometry was performed. A group of heavy alcohol drinkers (AHD, n = 71) and a group of age-matched controls (n = 81), both HLA-phenotyped and HFE-genotyped, constituted the groups under study. Marked expansions of CD28- T cells within the CD8+ but not the CD4+ T-cell pool were observed in AHD compared with controls. These CD8+CD28- expansions were paralleled by expansions of CD8+ T cells bearing specific TcR Valpha/beta chains, namely VP5.2. Moreover, AHD, but not controls, carrying the H63D mutation in the HFE gene showed significantly higher percentages of CD28- T cells within the CD8+ T-cell pool than AHD carrying the normal HFE gene. Finally, high numbers of CD8+CD28- T cells in AHD were associated with lower levels of the liver-related enzymes ALT and GGT. This study showed that under active ethanol consumption, expansions of discrete CD8+ T-cell subsets occur within the CD8+ T-cell pool, that molecules of the MHC-class I locus seem to influence the extent of the expansions, and that high numbers of CD8+CD28- T cells are associated with low levels of liver enzymes in AHD.

Influence of farmyard manure on some morphological and biochemical parameters of cowpea (Vigna unguiculata) seedling grown in cadmium-treated soil.

PubMed

Asagba, Samuel Ogheneovo; Ezedom, Theresa; Kadiri, Helen

2017-10-01

The present study aims to assess the effects of the two kinds of farmyard manure (poultry and pig manures) as amendments for soil on cadmium (Cd) toxicity in plants using cowpea seedlings as plant model. Cd toxicity was evaluated by assessing the effect of the metal on the growth rate and antioxidant status as well as the ability of the plant to metabolise xenobiotic. There was a significantly (p < 0.05) increased concentration of Cd in the root, stem and leaves of cowpea seedlings grown in all the treated soils relative to control. Addition of poultry manure to the soil significantly (p < 0.05) decreased the level of Cd in these component parts of the seedlings and their corresponding bioaccumulation factor in a dose-dependent manner as compared with treatments with Cd pollution without manure addition and Cd pollution with pig manure addition. There was restoration of Cd-induced effect on growth rate parameters to levels comparable to controls in cowpea seedlings grown in Cd-treated soil augmented with poultry manure but not in cowpea seedlings in cadmium-treated soil with pig manure amendments. Similarly, augmentation of Cd-treated soil with pig manure did not alter the Cd-induced effect on the levels of superoxide dismutase (SOD) and lipid peroxidation (LPO) in leaf, stem and roots, as SOD remained significantly (p < 0.05) decreased and LPO increased relative to control. On the other hand, the levels of SOD and LPO in these parts of cowpea seedlings grown in Cd-treated soils amended with poultry manure were restored to a level not significantly (p > 0.05) different from control. Like in the case of SOD, the Cd-induced inhibition of the activity of xenobiotic metabolising enzymes, aldehyde oxidase and sulphite oxidase remained significantly (p < 0.05) decreased in the organs of seedling grown in Cd-treated soil amended with pig manure. Conversely, the Cd-induced effect on the activities of these enzymes was reversed in the organs of seedlings exposed to Cd and poultry manure as it was not significantly (p > 0.05) different from control. In conclusion, the findings of the study revealed that supplementation of Cd-treated soils with pig and poultry manures reversed effects of Cd on cowpea seedlings. However, poultry manure was more effective than pig manure in ameliorating the effects of Cd.

Early Short-Term Antiretroviral Therapy Is Associated with a Reduced Prevalence of CD8+FoxP3+ T Cells in Simian Immunodeficiency Virus-Infected Controller Rhesus Macaques

PubMed Central

George, Jeffy; Cofano, Egidio Brocca; Lybarger, Elizabeth; Louder, Mark; Lafont, Bernard A.P.; Mascola, John R.; Robert-Guroff, Marjorie

2011-01-01

Abstract Regulatory T cells contain a mix of CD4 and CD8 T cell subsets that can suppress immune activation and at the same time suppress immune responses, thereby contributing to disease progression. Recent studies have shown that an increased prevalence of CD8+FoxP3+ T regulatory cells was associated with immune suppression and diminished viral control in simian immunodeficiency virus (SIV)-infected rhesus macaques. Preventing an increase in the prevalence of CD8 T regulatory subsets is likely to lead to a better long-term outcome. Here we show that short-term antiretroviral therapy initiated within 1 week after SIV infection was associated with lower viral set point and immune activation after withdrawal of therapy as compared to untreated animals. Early short-term treated controller animals were found to have better SIV-specific immune responses and a significantly lower prevalence of immunosuppressive CD8+FoxP3+ T cells. Lower levels of CD8+FoxP3+ T cells coincided with preservation of CD4+FoxP3+ T cells at homeostatic levels, and significantly correlated with lower immune activation, suggesting a role for viral infection-driven immune activation in the expansion of CD8+FoxP3+ T cells. Interestingly, initiation of continuous therapy later in infection did not reduce the increased prevalence of CD8+FoxP3+ T cells to homeostatic levels. Taken together, our results suggest that early antiretroviral therapy preserves the integrity of the immune system leading to a lower viral set point in controller animals, and prevents alterations in the homeostatic balance between CD4+ and CD8+ T regulatory cells that could aid in better long-term outcome. PMID:21142402

CD4+ CD25+ CD127low Regulatory T Cells as Indicator of Rheumatoid Arthritis Disease Activity.

PubMed

Khattab, Sahar S; El-Saied, Amany M; Mohammed, Rehab A; Mohamed, Eman E

2016-06-01

Rheumatoid arthritis (RA) is an autoimmune disease characterized by disturbed immune regulation, inducing a progressive cartilage and bone destruction. Despite enrichment of T regulatory cell (T-regs) in synovial fluid, conflicting results are reported concerning T-regs in peripheral blood (PB) of RA patients. To determine possible correlation between the frequency of PB CD4+ CD25+CD127low (T-regs) with RA disease activity. Forty females with RA, classified according to the Disease Activity Score 28 (DAS-28), as highly active, mild-moderate or low disease activity; and 20 age and sex matched healthy controls, were enrolled to study CD4+ CD25+ CD127low T- regs in PB by flow cytometry. Active RA patients had lower frequency of the CD4+ CD25+ CD127low T- regs compared to those with mild-moderate or low disease activity (P <0.001). The frequencies of the T- regs showed negative correlation with the DAS-28 (P<0.01). In conclusion, CD4+ CD25+ CD127low T-regs is significantly lower in highly active RA patients compared to patients with lower activity or controls. Copyright© by the Egyptian Association of Immunologists.

Lamina propria macrophage phenotypes in relation to Escherichia coli in Crohn's disease.

PubMed

Elliott, Timothy R; Rayment, Neil B; Hudspith, Barry N; Hands, Rebecca E; Taylor, Kirstin; Parkes, Gareth C; Prescott, Natalie J; Petrovska, Liljana; Hermon-Taylor, John; Brostoff, Jonathan; Boussioutas, Alex; Mathew, Christopher G; Bustin, Stephen A; Sanderson, Jeremy D

2015-07-03

Abnormal handling of E. coli by lamina propria (LP) macrophages may contribute to Crohn's disease (CD) pathogenesis. We aimed to determine LP macrophage phenotypes in CD, ulcerative colitis (UC) and healthy controls (HC), and in CD, to compare macrophage phenotypes according to E. coli carriage. Mucosal biopsies were taken from 35 patients with CD, 9 with UC and 18 HCs. Laser capture microdissection was used to isolate E. coli-laden and unladen LP macrophages from ileal or colonic biopsies. From these macrophages, mRNA was extracted and cytokine and activation marker expression measured using RT-qPCR. E. coli-laden LP macrophages were identified commonly in mucosal biopsies from CD patients (25/35, 71 %), rarely in UC (1/9, 11 %) and not at all in healthy controls (0/18). LP macrophage cytokine mRNA expression was greater in CD and UC than healthy controls. In CD, E. coli-laden macrophages expressed high IL-10 & CD163 and lower TNFα, IL-23 & iNOS irrespective of macroscopic inflammation. In inflamed tissue, E. coli-unladen macrophages expressed high TNFα, IL-23 & iNOS and lower IL-10 & CD163. In uninflamed tissue, unladen macrophages had low cytokine mRNA expression, closer to that of healthy controls. In CD, intra-macrophage E. coli are commonly found and LP macrophages express characteristic cytokine mRNA profiles according to E. coli carriage. Persistence of E. coli within LP macrophages may provide a stimulus for chronic inflammation.

Decoupling activation and exhaustion of B cells in spontaneous controllers of HIV infection

PubMed Central

Sciaranghella, Gaia; Tong, Neath; Mahan, Alison E.; Suscovich, Todd J.; Alter, Galit

2013-01-01

Objective To define the impact of chronic viremia and associated immune activation on B-cell exhaustion in HIV infection. Design Progressive HIV infection is marked by B-cell anergy and exhaustion coupled with dramatic hypergammaglobulinemia. Although both upregulation of CD95 and loss of CD21 have been used as markers of infection-associated B-cell dysfunction, little is known regarding the specific profiles of dysfunctional B cells and whether persistent viral replication and its associated immune activation play a central role in driving B-cell dysfunction. Methods Multiparameter flow cytometry was used to define the profile of dysfunctional B cells. The changes in the expression of CD21 and CD95 were tracked on B-cell subpopulations in patients with differential control of viral replication. Results Although the emergence of exhausted, CD21low tissue-like memory B cells followed similar patterns in both progressors and controllers, the frequency of CD21low activated memory B cells was lower in spontaneous controllers. Conclusion Our results suggest that the loss of CD21 and the upregulation of CD95 occur as separate events during the development of B-cell dysfunction. The loss of CD21 is a marker of B-cell exhaustion induced in the absence of appreciable viral replication, whereas the upregulation of CD95 is tightly linked to persistent viral replication and its associated immune activation. Thus, these dysfunctional profiles potentially represent two functionally distinct states within the B-cell compartment. PMID:23135171

A four-dimensional virtual hand brain-machine interface using active dimension selection.

PubMed

Rouse, Adam G

2016-06-01

Brain-machine interfaces (BMI) traditionally rely on a fixed, linear transformation from neural signals to an output state-space. In this study, the assumption that a BMI must control a fixed, orthogonal basis set was challenged and a novel active dimension selection (ADS) decoder was explored. ADS utilizes a two stage decoder by using neural signals to both (i) select an active dimension being controlled and (ii) control the velocity along the selected dimension. ADS decoding was tested in a monkey using 16 single units from premotor and primary motor cortex to successfully control a virtual hand avatar to move to eight different postures. Following training with the ADS decoder to control 2, 3, and then 4 dimensions, each emulating a grasp shape of the hand, performance reached 93% correct with a bit rate of 2.4 bits s(-1) for eight targets. Selection of eight targets using ADS control was more efficient, as measured by bit rate, than either full four-dimensional control or computer assisted one-dimensional control. ADS decoding allows a user to quickly and efficiently select different hand postures. This novel decoding scheme represents a potential method to reduce the complexity of high-dimension BMI control of the hand.

Subcellular distribution and chemical forms of cadmium in the edible seaweed, Porphyra yezoensis.

PubMed

Zhao, Yanfang; Wu, Jifa; Shang, Derong; Ning, Jinsong; Zhai, Yuxiu; Sheng, Xiaofeng; Ding, Haiyan

2015-02-01

The subcellular distribution and chemical forms of Cd were investigated in the edible seaweed, Porphyra yezoensis. The seaweed was exposed to different Cd concentrations (0.01, 0.05, 0.1, 0.5, 1.0 and 5.0mgl(-1)) for up to 96h. In both the controls (no Cd added) and treatment groups, 41.2-79.2% of Cd was localised in the cell wall, and the proportion of Cd in the cell wall increased with increasing concentrations of Cd and exposure time. In the control groups, 74.8% of Cd was extracted by 1M NaCl, followed by 2% acetic acid, HAC (18.9%). In the treatment groups, most Cd was extracted by 2% HAC. The proportion of Cd extracted by 2% HAC increased with exposure to increasing concentrations of Cd and over time. Cell wall deposition and forming of precipitates with phosphate may be a key strategy to reduce Cd toxicity in P. yezoensis. Copyright © 2014 Elsevier Ltd. All rights reserved.

CD8 T-Cell Expansion and Inflammation Linked to CMV Coinfection in ART-treated HIV Infection

PubMed Central

Freeman, Michael L.; Mudd, Joseph C.; Shive, Carey L.; Younes, Souheil-Antoine; Panigrahi, Soumya; Sieg, Scott F.; Lee, Sulggi A.; Hunt, Peter W.; Calabrese, Leonard H.; Gianella, Sara; Rodriguez, Benigno; Lederman, Michael M.

2016-01-01

Background. Persistent CD8 T-cell expansion, low CD4/CD8 T-cell ratios, and heightened inflammation persist in antiretroviral therapy (ART)-treated human immunodeficiency virus (HIV) infection and are associated with increased risk of morbid outcomes. We explored the role of cytomegalovirus (CMV) infection in CD8 lymphocytosis and inflammation in ART-treated HIV infection. Methods. Absolute CD4 and CD8 T-cell counts were abstracted from clinical records and compared among 32 HIV-infected CMV-seronegative subjects, 126 age, CD4 and gender-matched HIV-infected CMV-seropositive subjects, and among 21 HIV-uninfected controls (9 CMV-negative, 12 CMV-positive). Plasma inflammatory indices were measured in a subset by ELISA. Results. Median CD8 counts/µL were higher in HIV-positive/CMV-positive patients (795) than in HIV-positive/CMV-negative subjects (522, P = .006) or in healthy controls (451, P = .0007), whereas CD8 T-cell counts were similar to controls' levels in HIV-positive/CMV-negative subjects. Higher plasma levels of IP-10 (P = .0011), TNF-RII (P = .0002), and D-dimer (P = .0444) were also found in coinfected patients than in HIV-positive/CMV-negative subjects. Conclusions. CMV infection is associated with higher CD8 T-cell counts, resultant lower CD4/CD8 ratios, and increased systemic inflammation in ART-treated HIV infection. CMV infection may contribute to risk for morbid outcomes in treated HIV infection. PMID:26400999

Hybridomas using athymic nude mouse injected with Crohn's disease (CD) tissue filtrate. Immunoreactivity of the hybridomas with CD sera.

PubMed Central

Das, K. M.; Vecchi, M.; Novikoff, A.; Mazumdar, S.; Novikoff, P. M.

1990-01-01

Injections of Crohn's disease (CD) tissue filtrates produce lymphoma and hyperplastic lymph nodes from plasma cell hyperplasia (PCH) in athymic nude (nu/nu) mice; these lymphoid tissue contain an antigen(s) recognized by CD serum/gamma G immunoglobulin (IgG). To immortalize the "CD-reactive antigen(s)," the authors fused the lymphoid cells from a CD tissue filtrate primed nu/nu mouse with nonsecretory mouse myeloma cells. Hybrids were screened and selected based on their reactivity with CD serum IgG, but not with control serum IgG in an indirect immunofluorescence assay (IF). Two CD-positive hybridomas were examined by IF with sera from 47 CD, 38 ulcerative colitis (UC), 13 controls with other gastrointestinal diseases, 19 with autoimmune diseases, and 21 normal subjects. Sera from 16 CD patients (34%) reacted with the two hybridomas, but only one of 38 UC sera and none of the 53 other disease or normal control sera reacted. The immunoreactivity of CD sera was significantly higher than UC sera (P less than 0.01) and each of the other groups (P less than 0.007). Using immunoperoxidase techniques at light and electron microscopic levels, the authors localized CD-associated antigen(s) in the plasma membrane of the two hybridomas. Further characterization of these hybridomas and the immunoreactive protein(s) may provide an important probe(s) for the diagnosis and the understanding of the pathogenesis of CD. Images Figure 2 Figure 3 PMID:2192559

Platelets Toll-like receptor-4 in Crohns disease.

PubMed

Schmid, Werner; Novacek, Gottfried; Vogelsang, Harald; Papay, Pavol; Primas, Christian; Eser, Alexander; Panzer, Simon

2017-02-01

Platelets are activated in Crohn's disease (CD) and interplay with leukocytes. Engagement of Toll-like receptor-4 (TLR-4), which is expressed in human platelets, may be involved in crosstalks between platelets and leukocytes leading to their mutual activation for host defense. Human neutrophil peptides (HNPs), lipoprotein binding peptides, and sCD14 were determined by enzyme-linked immunosorbent assays in 42 patients with active CD, in 43 patients with CD in remission, and in 30 healthy individuals. Neutrophil-platelet aggregates and binding of the TLR-4 monoclonal antibody to platelets were determined by flow cytometry. Levels of HNPs were higher in patients with CD than in controls (P = 0.0003 vs. active CD and P = 0.01 vs. CD in remission). Likewise, neutrophils with adhering platelets were higher in patients with active CD than in controls (P = 0.004). Binding of the TLR-4 antibody in patients with active CD was similar to that in controls, while patients in remission had significantly higher binding capacities (P = 0.59 and P = 0.003). Incubation of plasma from patients with active disease or patients in remission with platelets from healthy controls confirmed lower binding of the TLR-4 antibody in the presence of plasma from active diseased patients compared to controls (P = 0.039), possibly due to high levels of lipopolysaccharides, as suggested by high levels of sCD14 and lipoprotein binding protein. Our study indicates involvement of platelet TLR-4 in enhancing the secretion of antimicrobial peptides from neutrophils. While platelet aggregation can be due to a variety of mechanisms in inflammatory disease, the mutual activation of platelets and neutrophils may augment host defense. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

The brown seaweed Sargassum cymosum: changes in metabolism and cellular organization after long-term exposure to cadmium.

PubMed

Costa, Giulia B; Simioni, Carmen; Pereira, Débora T; Ramlov, Fernanda; Maraschin, Marcelo; Chow, Fungyi; Horta, Paulo A; Bouzon, Zenilda L; Schmidt, Éder C

2017-03-01

Sargassum cymosum was exposed to cadmium (Cd) to determine any physiological and ultrastructural effects. To accomplish this, S. cymosum samples were cultivated under photosynthetic active radiation (PAR) and Cd (0, 0.1, 0.2, 0.4 and 0.8 mg L -1 ) during 7 and 14 days in laboratory-controlled conditions (0 mg L -1 Cd at both exposure times as control). Seaweeds had high retention capacity (over 90 %) for both exposure times. Growth rates showed significant increases by 14 days, especially for 0.1 and 0.4 mg L -1 Cd. Photosynthetic parameters were unaffected by Cd treatments. Chlorophyll contents were present in higher concentrations for all Cd treatments compared to respective control. Carotenoid profile showed significant differences in total composition and proportion of fucoxanthin and β-carotene, and no lutein was detected at 14 days. Phenolic and flavonoid compounds showed major accumulation at 14 days. Transmission electron microscopy (TEM) analyses presented major alterations in Cd-treated samples, when compared with respective control, in particular disorganization of cell wall fibrils. When compared to respective control samples, multivariate analyses showed disparate and complex interactions among metabolites in Cd-exposed seaweeds, giving evidence of physiological defence response. Thus, it can be concluded that Cd is a stressor for S. cymosum, resulting in physiological and structural alterations related to defence mechanisms against oxidative stress and toxicological effects resulting from long-term metal exposure. However, in the present paper, some observed changes also appear to result from acclimation mechanisms under lower concentration of Cd relative to the tolerance of S. cymosum to experimental conditions.

Expression of CD154 by a Simian Immunodeficiency Virus Vector Induces Only Transitory Changes in Rhesus Macaques

PubMed Central

Hodara, Vida L.; Velasquillo, M. Cristina; Parodi, Laura M.; Giavedoni, Luis D.

2005-01-01

Human immunodeficiency virus infection is characterized by dysregulation of antigen-presenting cell function and defects in cell-mediated immunity. Recent evidence suggests that impaired ability of CD4+ T cells to upregulate the costimulatory molecule CD154 is at the core of this dysregulation. To test the hypothesis that increased expression of CD154 on infected CD4+ T cells could modulate immune function, we constructed a replication-competent simian immunodeficiency virus (SIV) vector that expressed CD154. We found that this recombinant vector directed the expression of CD154 on the surface of infected CD4+ T cells and that expression of CD154 resulted in activation of B cells present in the same cultures. Experimental infection of rhesus macaques resulted in very low viral loads for the CD154-expressing virus and the control virus, indicating that expression of CD154 did not result in increased viral replication. Analyses of the anti-SIV immune responses and the phenotype of lymphocytes in blood and lymphoid tissues showed changes that occurred during the acute phase of infection only in animals infected with the CD154-expressing SIV, but that became indistinguishable from those seen in animals infected with the control virus at later time points. We conclude that the level of expression of CD154 in itself is not responsible for affecting the immune response to an attenuated virus. Considering that the CD154-expressing SIV vector and the virus control did not carry an active nef gene, our results suggest that, in CD4+ T cells infected with wild-type virus, Nef is the viral factor that interferes with the immune mechanisms that regulate expression of CD154. PMID:15795254

Elevated Plasma Soluble CD14 and Skewed CD16+ Monocyte Distribution Persist despite Normalisation of Soluble CD163 and CXCL10 by Effective HIV Therapy: A Changing Paradigm for Routine HIV Laboratory Monitoring?

PubMed Central

Castley, Alison; Berry, Cassandra; French, Martyn; Fernandez, Sonia; Krueger, Romano; Nolan, David

2014-01-01

Objective We investigated plasma and flow cytometric biomarkers of monocyte status that have been associated with prognostic utility in HIV infection and other chronic inflammatory diseases, comparing 81 HIV+ individuals with a range of treatment outcomes to a group of 21 healthy control blood donors. Our aim is to develop and optimise monocyte assays that combine biological relevance, clinical utility, and ease of adoption into routine HIV laboratory practice. Design Cross-sectional evaluation of concurrent plasma and whole blood samples. Methods A flow cytometry protocol was developed comprising single-tube CD45, CD14, CD16, CD64, CD163, CD143 analysis with appropriately matched isotype controls. Plasma levels of soluble CD14 (sCD14), soluble CD163 (sCD163) and CXCL10 were measured by ELISA. Results HIV status was associated with significantly increased expression of CD64, CD143 and CD163 on CD16+ monocytes, irrespective of the virological response to HIV therapy. Plasma levels of sCD14, sCD163 and CXCL10 were also significantly elevated in association with viremic HIV infection. Plasma sCD163 and CXCL10 levels were restored to healthy control levels by effective antiretroviral therapy while sCD14 levels remained elevated despite virological suppression (p<0.001). Conclusions Flow cytometric and plasma biomarkers of monocyte activation indicate an ongoing systemic inflammatory response to HIV infection, characterised by persistent alterations of CD16+ monocyte expression profiles and elevated sCD14 levels, that are not corrected by antiretroviral therapy and likely to be prognostically significant. In contrast, sCD163 and CXCL10 levels declined on antiretroviral therapy, suggesting multiple activation pathways revealed by these biomarkers. Incorporation of these assays into routine clinical care is feasible and warrants further consideration, particularly in light of emerging therapeutic strategies that specifically target innate immune activation in HIV infection. PMID:25544986

Alleviation of Cd toxicity by composted sewage sludge in Cd-treated Schmidt birch (Betula schmidtii) seedlings.

PubMed

Han, Sim-Hee; Lee, Jae-Cheon; Oh, Chang-Young; Kim, Pan-Gi

2006-10-01

We investigated alleviation of Cd toxicity and changes in the physiological characteristics of Betula schmidtii seedlings following application of composted sewage sludge to Cd-treated plants. Plants were grown under four test conditions: control, Cd treatment, sludge amendment, and Cd treatment with sludge amendment. B. schmidtii treated with Cd only accumulated the greatest amount of Cd in the leaves, but absorbed Cd was also highly concentrated in the roots. In contrast, Cd concentrations in the Cd and sludge amendment treated seedlings were the lowest in the roots. Since sludge amendment increased the growth of seedlings, it may have alleviated toxicity by dilution of Cd. Additionally, the absorbed Cd was more widely distributed since it was transported from the roots and accumulated in the stems and leaves of Cd and sludge treated plants. Cd treatment inhibited the growth and physiological functions of B. schmidtii seedlings, but sludge amendment compensated for these effects and improved growth and physiological functions in both Cd-treated and control plants. SOD activity in the leaves of seedlings was increased in the Cd-treated plants, but not in the Cd and sludge amendment treated seedlings. In conclusion, alleviation of Cd toxicity in response to sludge amendment may be related to a dilution effect, in which the Cd concentration in the tissues was effectively lowered by the improved growth performance of the seedlings.

Serum soluble CD30 in early arthritis: a sign of inflammation but not a predictor of outcome.

PubMed

Savolainen, E; Matinlauri, I; Kautiainen, H; Luosujärvi, R; Kaipiainen-Seppänen, O

2008-01-01

To evaluate serum soluble CD30 levels (sCD30) in an early arthritis series and assess their ability to predict the outcome in patients with rheumatoid arthritis (RA) and undifferentiated arthritis (UA) at one year follow-up. Serum sCD30 levels were measured by ELISA from 92 adult patients with RA and UA at baseline and from 60 adult controls. The patients were followed up for one year in the Kuopio 2000 Arthritis Survey. Receiver operating characteristic (ROC) curves were constructed to determine cut off points of sCD30 in RA and UA that select the inflammatory disease from controls. Sensitivity, specificity and positive likelihood ratio, and their 95 % CIs were calculated for sCD30 levels in RA and UA. Median serum sCD30 levels were higher in RA 25.1 (IQ range 16.3-38.6) IU/ml (p<0.001) and in UA 23.4 (15.4-35.6) IU/ml (p<0.001) than in controls 15.1 (10.7-20.8) IU/ml. No differences were recorded between RA and UA (p=0.840). Serum sCD30 levels at baseline did not predict remission at one year follow-up. Serum sCD30 levels were higher in RA and UA than in controls at baseline but they did not predict remission at one year follow-up in this series.

Experimental investigation on discharge coefficient for a combined broad crested weir-box culvert structure

NASA Astrophysics Data System (ADS)

Guven, A.; Hassan, M.; Sabir, Shahin

2013-09-01

This study investigates the hydraulic characteristics of simultaneous flow over broad crested weir and through box (square) culverts experimentally. The variation of discharge coefficient (Cd) of the combined structure with various affective parameters such as upstream head, length of culvert, culvert inlet shape, culvert internal dimension, weir crest height, weir side slope angle, and weir width was analyzed. For this purpose 12 glass models of combined broad crested weirs and box culverts were manufactured and tested in a laboratory flume of 12 m. Discharge coefficient predicting equations were developed as a function of the dimensionless terms. The overall results showed that Cd increases as the ratio of the total head of water above the weir crest to the height of the weir crest H/P increases for all the models and for each flow state (weir and combined). Cd values increased as the head increased for all the models tested as culvert flow only, and also with decreasing of the angle between crest of the weir with the sides.

Design and development of hyaluronan-functionalized polybenzofulvene nanoparticles as CD44 receptor mediated drug delivery system

NASA Astrophysics Data System (ADS)

Licciardi, Mariano; Scialabba, Cinzia; Giammona, Gaetano; Paolino, Marco; Razzano, Vincenzo; Grisci, Giorgio; Giuliani, Germano; Makovec, Francesco; Cappelli, Andrea

2017-06-01

A tri-component polymer brush (TCPB ), composed of a polybenzofulvene copolymer bearing low molecular weight hyaluronic acid (HA) on the surface of its cylindrical brush-like backbone and oligo-PEG fractions, was employed in the preparation of 350 nm nanostructured drug delivery systems capable of delivering the anticancer drug doxorubicin. The obtained drug delivery systems were characterized on the basis of drug loading and release, dimensions and zeta potential, morphology and in vitro cell activity, and uptake on three different human cell lines, namely the bronchial epithelial 16HBE, the breast adenocarcinoma MCF-7, and the colon cancer HCT116 cells. Finally, the ability of doxorubicin-loaded TCPB nanoparticles (DOXO-TCPB) to be internalized into cancer cells by CD44 receptor mediated uptake was assessed by means of uptake studies in HCT cells. These data were supported by anti-CD44-FITC staining assay. The proposed TCPB nanostructured drug delivery systems have many potential applications in nanomedicine, including cancer targeted drug delivery.

Characterization of 193-nm resists for optical mask manufacturing

NASA Astrophysics Data System (ADS)

Fosshaug, Hans; Paulsson, Adisa; Berzinsh, Uldis; Magnusson, Helena

2004-12-01

The push for smaller linewidths and tighter critical dimension (CD) budgets forced manufacturers of optical pattern generators to move from traditional i-line to deep ultraviolet (DUV) resist processing. Entering the DUV area was not without pain. The process conditions, especially exposure times of a few hours, put very tough demands on the resist material itself. However, today 248nm laser writers are fully operating using a resist process that exhibits the requested resolution, CD uniformity and environmental stability. The continuous demands of CD performance made Micronic to investigate suitable resist candidate materials for the next generation optical writer using 193nm excimer laser exposure. This paper reports on resist benchmarking of one commercial as well as several newly developed resists. The resists were investigated using a wafer scanner. The data obtained illustrate the current performance of 193nm photoresists, and further demonstrate that despite good progress in resist formulation optimization, the status is still a bit from the required lithographic performance.

Synthesis of modified cyclic and acyclic dextrins and comparison of their complexation ability

PubMed Central

Jicsinszky, László; Sohajda, Tamás; Puskás, István; Fenyvesi, Éva

2014-01-01

Summary We compared the complex forming ability of α-, β- and γ-cyclodextrins (α-CD, β-CD and γ-CD) with their open ring analogs. In addition to the native cyclodextrins also modified cyclodextrins and the corresponding maltooligomers, functionalized with neutral 2-hydroxypropyl moieties, were synthesized. A new synthetic route was worked out via bromination, benzylation, deacetylation and debenzylation to obtain the 2-hydroxypropyl maltooligomer counterparts. The complexation properties of non-modified and modified cyclic and acyclic dextrins were studied and compared by photon correlation spectroscopy (PCS) and capillary electrophoresis (CE) using model guest compounds. In some cases cyclodextrins and their open-ring analogs (acyclodextrins) show similar complexation abilities, while with other guests considerably different behavior was observed depending on the molecular dimensions and chemical characteristics of the guests. This was explained by the enhanced flexibility of the non-closed rings. Even the signs of enantiorecognition were observed for the chloropheniramine/hydroxypropyl maltohexaose system. Further studies are planned to help the deeper understanding of the interactions. PMID:25550750

Cd (II) and holodirected lead (II) 3D-supramolecular coordination polymers based on nicotinic acid: Structure, fluorescence property and photocatalytic activity

NASA Astrophysics Data System (ADS)

Etaiw, Safaa El-din H.; Abd El-Aziz, Dina M.; Marie, Hassan; Ali, Elham

2018-05-01

Two new supramolecular coordination polymers namely {[Cd(NA)2(H2O)]}, SCP 1 and {[Pb(NA)2]}, SCP 2, (NA = nicotinate ligand) were synthesized by self-assembly method and structurally characterized by different analytical and spectroscopic methods. Single-crystal X-ray diffraction showed that SCP 1 extend in three dimensions containing bore structure where the 3D- network is constructed via interweaving zigzag chains. The Cd atom coordinates to (O4N2) atoms forming distorted-octahedral configuration. The structure of SCP 2 extend down the projection of the b-axis creating parallel zigzag 1D-chains connected by μ2-O2 atoms and H-bonds forming a holodirected lead (II) hexagonal bi-pyramid configuration. SCP 2 extend to 3D-network via coordinate and hydrogen bonds. The thermal stability, photoluminescence properties, photocatalytic activity for the degradation of methylene blue dye (MB) under UV-irradiation and sunlight irradiation were also studied.

Relationship between sensitizer concentration and resist performance of chemically amplified extreme ultraviolet resists in sub-10 nm half-pitch resolution region

NASA Astrophysics Data System (ADS)

Kozawa, Takahiro; Santillan, Julius Joseph; Itani, Toshiro

2017-01-01

The development of lithography processes with sub-10 nm resolution is challenging. Stochastic phenomena such as line width roughness (LWR) are significant problems. In this study, the feasibility of sub-10 nm fabrication using chemically amplified extreme ultraviolet resists with photodecomposable quenchers was investigated from the viewpoint of the suppression of LWR. The relationship between sensitizer concentration (the sum of acid generator and photodecomposable quencher concentrations) and resist performance was clarified, using the simulation based on the sensitization and reaction mechanisms of chemically amplified resists. For the total sensitizer concentration of 0.5 nm-3 and the effective reaction radius for the deprotection of 0.1 nm, the reachable half-pitch while maintaining 10% critical dimension (CD) LWR was 11 nm. The reachable half-pitch was 7 nm for 20% CD LWR. The increase in the effective reaction radius is required to realize the sub-10 nm fabrication with 10% CD LWR.

The link between callous-unemotional traits and neural mechanisms of reward processing: An fMRI study.

PubMed

Veroude, Kim; von Rhein, Daniel; Chauvin, Roselyne J M; van Dongen, Eelco V; Mennes, Maarten J J; Franke, Barbara; Heslenfeld, Dirk J; Oosterlaan, Jaap; Hartman, Catharina A; Hoekstra, Pieter J; Glennon, Jeffrey C; Buitelaar, Jan K

2016-09-30

Callous-unemotional (CU) traits, i.e., unconcernedness and lack of prosocial feelings, may manifest in Conduct Disorder (CD), but also in Oppositional Defiant Disorder (ODD) and Attention Deficit Hyperactivity Disorder (ADHD). These disorders have been associated with aberrant reward processing, while the influence of CU traits is unclear. Using functional Magnetic Resonance Imaging (fMRI), we examined whether CU traits affect the neural circuit for reward. A Monetary Incentive Delay (MID) task was administered to 328 adolescents and young adults with varying levels of CU traits: 40 participants with ODD/CD plus ADHD, 101 participants with ADHD only, 84 siblings of probands with ADHD and 103 typically developing (TD) individuals. During reward anticipation, CU traits related negatively to medial prefrontal cortex (mPFC) activity, independent of ADHD symptoms and ODD/CD diagnosis. Our results indicate that CU traits are a valuable dimension for assessing the neural basis of reward processing. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The dimensions of food insecurity and malnutrition among people living with HIV in Senegal, West Africa.

PubMed

Benzekri, Noelle A; Sambou, Jacques F; Diaw, Binetou; Sall, El Hadji Ibrahima; Sall, Fatima; Niang, Alassane; Ba, Selly; Guèye, Ndèye Fatou Ngom; Diallo, Mouhamadou Baïla; Hawes, Stephen E; Seydi, Moussa; Gottlieb, Geoffrey S

2017-12-01

An understanding of the factors contributing to food insecurity and malnutrition among people living with HIV (PLHIV) in Senegal is urgently needed in order to develop effective interventions. The goals of this study were to identify differences in the dimensions of food security among PLHIV in Dakar versus Ziguinchor, Senegal, to determine which of these dimensions are most predictive of severe food insecurity, and to identify factors associated with malnutrition. We conducted a cross-sectional study at outpatient clinics in Dakar and Ziguinchor, Senegal. Data were collected using participant interviews, anthropometry, the Household Food Insecurity Access Scale, the Individual Dietary Diversity Scale, and chart review. Interviews were conducted with ninety-five food insecure, HIV-infected subjects. Daily household income and daily food expenditure per household member were the strongest predictors of severe food insecurity. The practice of agriculture, livestock ownership, nutritional status, and HIV outcomes were not predictive of severe food insecurity. CD4 count <350/mm 3 was the strongest predictor of malnutrition. Severe food insecurity, daily household income, daily food expenditure per household member, dietary diversity score, skipping meals, the practice of agriculture, livestock ownership, ART status, and adherence were not predictive of malnutrition. This is the first study to analyze the dimensions of food security among PLHIV in Senegal. We discovered important differences in food access, availability, stability, and utilization in Dakar versus Ziguinchor. We found that economic access was the strongest predictor of severe food insecurity and poorly controlled HIV was the strongest predictor of malnutrition. Our findings suggest that the interventions needed to address food insecurity differ from those necessary to target malnutrition, and that effective interventions may differ in Dakar versus Ziguinchor. Furthermore, this study highlights a need for a greater understanding of the relationship between HIV and malnutrition among individuals receiving ART in resource-limited settings.

Roughness and uniformity improvements on self-aligned quadruple patterning technique for 10nm node and beyond by wafer stress engineering

NASA Astrophysics Data System (ADS)

Liu, Eric; Ko, Akiteru; O'Meara, David; Mohanty, Nihar; Franke, Elliott; Pillai, Karthik; Biolsi, Peter

2017-05-01

Dimension shrinkage has been a major driving force in the development of integrated circuit processing over a number of decades. The Self-Aligned Quadruple Patterning (SAQP) technique is widely adapted for sub-10nm node in order to achieve the desired feature dimensions. This technique provides theoretical feasibility of multiple pitch-halving from 193nm immersion lithography by using various pattern transferring steps. The major concept of this approach is to a create spacer defined self-aligned pattern by using single lithography print. By repeating the process steps, double, quadruple, or octuple are possible to be achieved theoretically. In these small architectures, line roughness control becomes extremely important since it may contribute to a significant portion of process and device performance variations. In addition, the complexity of SAQP in terms of processing flow makes the roughness improvement indirective and ineffective. It is necessary to discover a new approach in order to improve the roughness in the current SAQP technique. In this presentation, we demonstrate a novel method to improve line roughness performances on 30nm pitch SAQP flow. We discover that the line roughness performance is strongly related to stress management. By selecting different stress level of film to be deposited onto the substrate, we can manipulate the roughness performance in line and space patterns. In addition, the impact of curvature change by applied film stress to SAQP line roughness performance is also studied. No significant correlation is found between wafer curvature and line roughness performance. We will discuss in details the step-by-step physical performances for each processing step in terms of critical dimension (CD)/ critical dimension uniformity (CDU)/line width roughness (LWR)/line edge roughness (LER). Finally, we summarize the process needed to reach the full wafer performance targets of LWR/LER in 1.07nm/1.13nm on 30nm pitch line and space pattern.

[Effect of different organic fertilizers on bioavailability of soil Cd and Zn].

PubMed

Xie, Yun-he; Ji, Xiong-hui; Wu, Jia-mei; Huang, Juan; Guan, Di; Zhu, Jian

2015-03-01

The active effect of soil Cd and Zn and their interaction was studied in typical paddy field in south China by monitoring the contents of Cd and Zn in soil and rice in rice fields applied with pig manure, chicken manure or rice straw for 4 years continuously. The results showed that applying pig manure, chicken manure or rice straw had no significant impact on the soil total Cd content, soil available Cd content and soil Cd activity, but tended to increase the soil total Cd content and increased the soil total Zn content, soil available Zn content and Zn activity significantly. Applications of pig manure, chicken manure and rice straw all reduced the Cd content of brown rice, in order of pig manure > chicken manure > rice straw. The Cd contents of brown rice, stem and leaf in the treatment applied with pig manure were lower than in the control by 37.5%, 44.0% and 36.4%, respectively; the Cd contents of brown rice, stem and leaf in the treatment applied with chicken manure were lower than in the control by 22.5%, 33.8%, and 22.7%, respectively; the Cd content of brown rice in the treatment applied with rice straw was lower than in the control by 7.5% but its contents in stem and leaf increased by 8.2% and 22.7% , respectively. The reduction in the brown rice Cd content was mainly due to the reduction of Cd enrichment from soil to brown rice after application of pig or chicken manure, but mainly due to the reduction of Cd transportation from stem to brown rice after straw application. Applications of pig manure, chicken manure and rice straw increased Zn contents in rice stem by 53.4%, 53.4% and 13.9%, respectively, but all had no significant effect on brown rice and leaf' s Zn contents. Zn and Cd had the significant antagonistic effects in the soil and rice stem. The increase of Zn content in soil and rice stem inhibited the adsorption and accumulation of Cd in the brown rice, stem and leaf significantly, and with the increase of the proportion of Zn/Cd, the competitive absorption between Cd and Zn by rice was the main control factor affecting the Cd absorption by rice than their competitive adsorption by soil.

Current matching using CdSe quantum dots to enhance the power conversion efficiency of InGaP/GaAs/Ge tandem solar cells.

PubMed

Lee, Ya-Ju; Yao, Yung-Chi; Tsai, Meng-Tsan; Liu, An-Fan; Yang, Min-De; Lai, Jiun-Tsuen

2013-11-04

A III-V multi-junction tandem solar cell is the most efficient photovoltaic structure that offers an extremely high power conversion efficiency. Current mismatching between each subcell of the device, however, is a significant challenge that causes the experimental value of the power conversion efficiency to deviate from the theoretical value. In this work, we explore a promising strategy using CdSe quantum dots (QDs) to enhance the photocurrent of the limited subcell to match with those of the other subcells and to enhance the power conversion efficiency of InGaP/GaAs/Ge tandem solar cells. The underlying mechanism of the enhancement can be attributed to the QD's unique capacity for photon conversion that tailors the incident spectrum of solar light; the enhanced efficiency of the device is therefore strongly dependent on the QD's dimensions. As a result, by appropriately selecting and spreading 7 mg/mL of CdSe QDs with diameters of 4.2 nm upon the InGaP/GaAs/Ge solar cell, the power conversion efficiency shows an enhancement of 10.39% compared to the cell's counterpart without integrating CdSe QDs.

HIV Controllers Exhibit Enhanced Frequencies of Major Histocompatibility Complex Class II Tetramer+ Gag-Specific CD4+ T Cells in Chronic Clade C HIV-1 Infection.

PubMed

Laher, Faatima; Ranasinghe, Srinika; Porichis, Filippos; Mewalal, Nikoshia; Pretorius, Karyn; Ismail, Nasreen; Buus, Søren; Stryhn, Anette; Carrington, Mary; Walker, Bruce D; Ndung'u, Thumbi; Ndhlovu, Zaza M

2017-04-01

Immune control of viral infections is heavily dependent on helper CD4 + T cell function. However, the understanding of the contribution of HIV-specific CD4 + T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibility complex (MHC) class II tetramers have emerged as a powerful tool for interrogating antigen-specific CD4 + T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4 + T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to the viral load of HIV-specific CD4 + T cell responses in a cohort of untreated HIV clade C-infected persons. We observed significantly higher frequencies of MHC class II tetramer-positive CD4 + T cells in HIV controllers than progressors ( P = 0.0001), and these expanded Gag-specific CD4 + T cells in HIV controllers showed higher levels of expression of the cytolytic proteins granzymes A and B. Importantly, targeting of the immunodominant Gag41 peptide in the context of HLA class II DRB1*1101 was associated with HIV control ( r = -0.5, P = 0.02). These data identify an association between HIV-specific CD4 + T cell targeting of immunodominant Gag epitopes and immune control, particularly the contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infection. Furthermore, these results highlight the advantage of the use of class II tetramers in evaluating HIV-specific CD4 + T cell responses in natural infections. IMPORTANCE Increasing evidence suggests that virus-specific CD4 + T cells contribute to the immune-mediated control of clade B HIV-1 infection, yet there remains a relative paucity of data regarding the role of HIV-specific CD4 + T cells in shaping adaptive immune responses in individuals infected with clade C, which is responsible for the majority of HIV infections worldwide. Understanding the contribution of HIV-specific CD4 + T cell responses in clade C infection is particularly important for developing vaccines that would be efficacious in sub-Saharan Africa, where clade C infection is dominant. Here, we employed MHC class II tetramers designed to immunodominant Gag epitopes and used them to characterize CD4 + T cell responses in HIV-1 clade C infection. Our results demonstrate an association between the frequency of HIV-specific CD4 + T cell responses targeting an immunodominant DRB1*11-Gag41 complex and HIV control, highlighting the important contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infections. Copyright © 2017 American Society for Microbiology.

Assessment of metabolic and mitochondrial dynamics in CD4+ and CD8+ T cells in virologically suppressed HIV-positive individuals on combination antiretroviral therapy.

PubMed

Masson, Jesse J R; Murphy, Andrew J; Lee, Man K S; Ostrowski, Matias; Crowe, Suzanne M; Palmer, Clovis S

2017-01-01

Metabolism plays a fundamental role in supporting the growth, proliferation and effector functions of T cells. We investigated the impact of HIV infection on key processes that regulate glucose uptake and mitochondrial biogenesis in subpopulations of CD4+ and CD8+ T cells from 18 virologically-suppressed HIV-positive individuals on combination antiretroviral therapy (cART; median CD4+ cell count: 728 cells/μl) and 13 HIV seronegative controls. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production were also analysed in total CD4+ and CD8+ T cells. Among HIV+/cART individuals, expression of glucose transporter (Glut1) and mitochondrial density were highest within central memory and naïve CD4+ T cells, and lowest among effector memory and transitional memory T cells, with similar trends in HIV-negative controls. Compared to HIV-negative controls, there was a trend towards higher percentage of circulating CD4+Glut1+ T cells in HIV+/cART participants. There were no significant differences in mitochondrial dynamics between subject groups. Glut1 expression was positively correlated with mitochondrial density and MMP in total CD4+ T cells, while MMP was also positively correlated with ROS production in both CD4+ and CD8+ T cells. Our study characterizes specific metabolic features of CD4+ and CD8+ T cells in HIV-negative and HIV+/cART individuals and will invite future studies to explore the immunometabolic consequences of HIV infection.

A Co-Receptor Independent Transgenic Human TCR Mediates Anti-Tumor and Anti-Self Immunity in Mice

PubMed Central

Mehrotra, Shikhar; Al-Khami, Amir A.; Klarquist, Jared; Husain, Shahid; Naga, Osama; Eby, Jonathan M.; Murali, Anuradha K.; Lyons, Gretchen E.; Li, Mingli; Spivey, Natali D.; Norell, Håkan; Martins da Palma, Telma; Onicescu, Georgiana; Diaz-Montero, C. Marcela; Garrett-Mayer, Elizabeth; Cole, David J.; Le Poole, I. Caroline; Nishimura, Michael I.

2013-01-01

Recent advancements in T cell immunotherapy suggest that T cells engineered with high affinity T cell receptors (TCR) can offer better tumor regression. However, whether a high affinity TCR alone is sufficient to control tumor growth, or the T cell subset bearing the TCR is also important remains unclear. Using the human tyrosinase epitope reactive, CD8 independent, high affinity TCR isolated from MHC class-I restricted CD4+ T cells obtained from tumor infiltrating lymphocytes of a metastatic melanoma patient, we developed a novel TCR transgenic mouse with a C57BL/6 background. This HLA-A2 restricted TCR was positively selected on both CD4+ and CD8+ single-positive (SP) cells. However, when the TCR transgenic mouse was developed with an HLA-A2 background, the transgenic TCR was primarily expressed by CD3+CD4-CD8- double-negative (DN) T cells. TIL 1383I TCR transgenic CD4+, CD8+ and CD4-CD8- T cells were functional and retained the ability to control tumor growth without the need for vaccination or cytokine support in vivo. Furthermore, the HLA-A2+/human tyrosinase TCR double transgenic mice developed spontaneous hair depigmentation and had visual defects that progressed with age. Our data show that the expression of the high affinity TIL 1383I TCR alone in CD3+ T cells is sufficient to control the growth of murine and human melanoma and the presence or absence of CD4 and CD8 co-receptors had little effect on its functional capacity. PMID:22798675

Celiac Disease and Epilepsy: The Effect of Gluten-Free Diet on Seizure Control.

PubMed

Bashiri, Homayoon; Afshari, Darioush; Babaei, Nosrat; Ghadami, Mohammad R

2016-01-01

Determining the true prevalence of celiac disease (CD) is difficult because of many atypical symptoms. Although CD primarily affects the gastrointestinal tract, patients may be asymptomatic or have extra intestinal symptoms. In this study, we assessed the prevalence of CD in patients with epilepsy and the effect of a gluten-free diet on seizure control in these patients. Patients with epilepsy in Imam Reza and Farabi Hospitals, Kermanshah, Iran, were studied. At first, the patients were screened by means of measuring the immunoglobulin A antiendomysial (IgA) antibodies. In the patients testing positive for IgA antibodies, 2-3 endoscopic small bowel biopsies were taken from the distal duodenum to confirm CD changes. People with CD received a gluten-free diet for 5 months and their seizure activity was recorded. During the study period, we studied 113 patients with epilepsy. Seven patients (6%) were diagnosed with CD. After 5 months of instituting a gluten-free diet, in 6 patients seizures were completely under control and antiepileptic drugs were discontinued. In one case, anticonvulsant drugs were reduced by half and seizures were controlled. Our results showed that about 6% of epileptic patients were positive for CD. Institution of a glutenfree diet is useful for seizure control in these patients.

CD39 is upregulated during activation of mouse and human T cells and attenuates the immune response to Listeria monocytogenes.

PubMed

Raczkowski, Friederike; Rissiek, Anne; Ricklefs, Isabell; Heiss, Kirsten; Schumacher, Valéa; Wundenberg, Kira; Haag, Friedrich; Koch-Nolte, Friedrich; Tolosa, Eva; Mittrücker, Hans-Willi

2018-01-01

The ectoenzymes CD39 and CD73 degrade extracellular ATP to adenosine. ATP is released by stressed or damaged cells and provides pro-inflammatory signals to immune cells through P2 receptors. Adenosine, on the other hand, suppresses immune cells by stimulating P1 receptors. Thus, CD39 and CD73 can shape the quality of immune responses. Here we demonstrate that upregulation of CD39 is a consistent feature of activated conventional CD4+ and CD8+ T cells. Following stimulation in vitro, CD4+ and CD8+ T cells from human blood gained surface expression of CD39 but displayed only low levels of CD73. Activated human T cells from inflamed joints largely presented with a CD39+CD73- phenotype. In line, in spleens of mice with acute Listeria monocytogenes, listeria-specific CD4+ and CD8+ T cells acquired a CD39+CD73- phenotype. To test the function of CD39 in control of bacterial infection, CD39-deficient (CD39-/-) mice were infected with L. monocytogenes. CD39-/- mice showed better initial control of L. monocytogenes, which was associated with enhanced production of inflammatory cytokines. In the late stage of infection, CD39-/- mice accumulated more listeria-specific CD8+ T cells in the spleen than wildtype animals suggesting that CD39 attenuates the CD8+ T-cell response to infection. In conclusion, our results demonstrate that CD39 is upregulated on conventional CD4+ and CD8+ T cells at sites of acute infection and inflammation, and that CD39 dampens responses to bacterial infection.

Impact of benznidazole treatment on the functional response of Trypanosoma cruzi antigen-specific CD4+CD8+ T cells in chronic Chagas disease patients.

PubMed

Pérez-Antón, Elena; Egui, Adriana; Thomas, M Carmen; Puerta, Concepción J; González, John Mario; Cuéllar, Adriana; Segovia, Manuel; López, Manuel Carlos

2018-05-11

Chagas disease is caused by Trypanosoma cruzi. The persistence of the parasite is associated with the disease chronicity and the impairment of the cellular immune response. It has been reported that the CD4+CD8+ T cell population expands in chronic Chagas disease patients. Few studies have focused on this subset of cells, and very little is known about the impact of antiparasitic treatment on this population. Thirty-eight chronic Chagas disease patients (20 asymptomatic and 18 symptomatic) and twelve healthy controls were enrolled in this study. Peripheral blood mononuclear cells were stimulated with soluble T. cruzi antigens to analyze the production of cytokines and cytotoxic molecules by CD4+CD8+ T cells before and after benznidazole treatment. Additionally, expression and co-expression of five inhibitory receptors in these patients after treatment were studied using a multiparameter flow cytometry technique. The frequency of CD4+CD8+ T cells was higher in chronic Chagas disease patients compared with healthy donors. Furthermore, a higher ratio of CD4+CD8low/CD4+CD8high subpopulations was observed in chronic Chagas disease patients than in healthy donors. Additionally, CD4+CD8+ T cells from these patients expressed and co-expressed higher levels of inhibitory receptors in direct proportion to the severity of the pathology. Benznidazole treatment reduced the frequency of CD4+CD8+ T cells and decreased the ratio of CD4+CD8low/CD4+CD8high subpopulations. The co-expression level of the inhibitory receptor was reduced after treatment simultaneously with the enhancement of the multifunctional capacity of CD4+CD8+ T cells. After treatment, an increase in the frequency of T. cruzi antigen-specific CD4+CD8+ T cells expressing IL-2 and TNF-α was also observed. CD4+CD8+ T cells could play an important role in the control of T. cruzi infection since they were able to produce effector molecules for parasite control. Benznidazole treatment partially reversed the exhaustion process caused by T. cruzi infection in these cells with an improvement in the functional response of the T. cruzi antigen-specific CD4+CD8+ T cells.

Impact of benznidazole treatment on the functional response of Trypanosoma cruzi antigen-specific CD4+CD8+ T cells in chronic Chagas disease patients

PubMed Central

Pérez-Antón, Elena; Egui, Adriana; Thomas, M. Carmen; Puerta, Concepción J.; González, John Mario; Cuéllar, Adriana; Segovia, Manuel

2018-01-01

Background Chagas disease is caused by Trypanosoma cruzi. The persistence of the parasite is associated with the disease chronicity and the impairment of the cellular immune response. It has been reported that the CD4+CD8+ T cell population expands in chronic Chagas disease patients. Few studies have focused on this subset of cells, and very little is known about the impact of antiparasitic treatment on this population. Methodology Thirty-eight chronic Chagas disease patients (20 asymptomatic and 18 symptomatic) and twelve healthy controls were enrolled in this study. Peripheral blood mononuclear cells were stimulated with soluble T. cruzi antigens to analyze the production of cytokines and cytotoxic molecules by CD4+CD8+ T cells before and after benznidazole treatment. Additionally, expression and co-expression of five inhibitory receptors in these patients after treatment were studied using a multiparameter flow cytometry technique. Principal findings The frequency of CD4+CD8+ T cells was higher in chronic Chagas disease patients compared with healthy donors. Furthermore, a higher ratio of CD4+CD8low/CD4+CD8high subpopulations was observed in chronic Chagas disease patients than in healthy donors. Additionally, CD4+CD8+ T cells from these patients expressed and co-expressed higher levels of inhibitory receptors in direct proportion to the severity of the pathology. Benznidazole treatment reduced the frequency of CD4+CD8+ T cells and decreased the ratio of CD4+CD8low/CD4+CD8high subpopulations. The co-expression level of the inhibitory receptor was reduced after treatment simultaneously with the enhancement of the multifunctional capacity of CD4+CD8+ T cells. After treatment, an increase in the frequency of T. cruzi antigen-specific CD4+CD8+ T cells expressing IL-2 and TNF-α was also observed. Conclusions CD4+CD8+ T cells could play an important role in the control of T. cruzi infection since they were able to produce effector molecules for parasite control. Benznidazole treatment partially reversed the exhaustion process caused by T. cruzi infection in these cells with an improvement in the functional response of the T. cruzi antigen-specific CD4+CD8+ T cells. PMID:29750791

Cutaneous CD30+ cells in children with atopic dermatitis.

PubMed

Cavagni, G; Caffarelli, C; Facchetti, F; Brugnoni, D; Notarangelo, L D; Tosoni, C; Altobelli, R

2000-03-01

CD30 expression can be considered a marker of Th2 cells. We investigated the presence of CD30+ cells in the lesional skin of children with atopic dermatitis (AD). We also analyzed the possible relationship between CD30+ cells and serum soluble CD 30 (sCD30) levels, and IgE, soluble interleukin-2 (IL-2) receptor (sIL-2R) or soluble CD23 (sCD23) levels in the blood, and clinical score. Ten eczematous children (4 males, 6 females; median age: 4 years and 5 months; range: 11 months to 14 years), 9 sex- and age-matched control children and an adult control group were studied. A clinical score (SCORAD index), was given to eczematous lesions. Blood was taken for the determination of IgE, sCD30, sIL-2R and sCD23 levels. Punch biopsies of lesional skin were stained with hematoxylin and eosin or incubated with anti-CD30 monoclonal antibodies. Skin prick tests (SPTs) were also performed. In the biopsy specimens, CD30 expression was observed in high proportions of infiltrating cells. In children with AD, total serum IgE, sCD30, sIL-2R, sCD23 and eosinophils were significantly elevated compared to controls. CD30+ cells were not associated with serum IgE, sCD30, sIL-2R, sCD23, or SPT results, score of inflammatory cells in lesional skin or clinical score. Children with AD who had high total IgE and specific IgE antibodies did not differ from those with normal total IgE and negative specific IgE in respect of age, clinical score, number of CD30+ cells, sCD30, sIL-2R and sCD23 levels, score of inflammatory cells in skin or clinical score. Our results showed remarkable numbers of CD30+ cells in the lesional skin and high sCD30 in the serum of children with AD. CD30+ cells did not correlate with systemic markers of IgE reaction. Copyright 2000 S. Karger AG, Basel

Nutritional status of children with coeliac disease.

PubMed

Aurangzeb, B; Leach, S T; Lemberg, D A; Day, A S

2010-07-01

The main aim of this study was to assess the nutritional status of children with newly diagnosed Coeliac disease (CD)with comparison to matched controls. A further aim was to assess relationships between presentation patterns and nutrition in childhood CD. The nutritional status of newly diagnosed CD was assessed by anthropometry, Bioelectrical Impedance and serum leptin levels, and contrasted to age and gender matched controls. Twenty-five children with CD (mean age of 8.2 +/- 4.5 years) and 25 control children (mean age 8.1 +/- 4.4.) were enrolled. Thirteen (52%) children with CD had gastrointestinal symptoms with 14 having a family history of CD. At presentation 8.7% were wasted, 4.2% were stunted and 20.8% overweight, although none were obese. Mean height and weight for age, other nutritional parameters and serum leptin did not differ between the groups. Serum leptin correlated with BMI in both groups. Children with CD more commonly present with atypical symptoms than with classical features. Variations in nutrition (under to overnutrition) may be seen at diagnosis, without relationship to the presence of symptoms. Leptin levels were not altered specifically in the setting of CD. Nutritional assessment remains important in the assessment and management of CD in children.

Preparation of Cd/Pb Chalcogenide Heterostructured Janus Particles via Controllable Cation Exchange

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

Zhang, Jianbing; Chernomordik, Boris D.; Crisp, Ryan W.

2015-07-28

We developed a strategy for producing quasi-spherical nanocrystals of anisotropic heterostructures of Cd/Pb chalcogenides. The nanostructures are fabricated via a controlled cation exchange reaction where the Cd2+ cation is exchanged for the Pb2+ cation. The cation exchange reaction is thermally activated and can be controlled by adjusting the reaction temperature or time. We characterized the particles using TEM, XPS, PL, and absorption spectroscopy. With complete exchange, high quality Pb-chalcogenide quantum dots are produced. In addition to Cd2+, we also find suitable conditions for the exchange of Zn2+ cations for Pb2+ cations. The cation exchange is anisotropic starting at one edgemore » of the nanocrystals and proceeds along the <111> direction producing a sharp interface at a (111) crystallographic plane. Instead of spherical core/shell structures, we produced and studied quasi-spherical CdS/PbS and CdSe/PbSe Janus-type heterostructures. Nontrivial PL behavior was observed from the CdS(e)/PbS(e) heterostructures as the Pb:Cd ratio is increased.« less

CD8+ lymphocytes are required to maintain virus suppression in SIV-infected macaques treated with short-term antiretroviral therapy

PubMed Central

Cartwright, Emily K.; Spicer, Lori; Smith, S. Abigail; Lee, David; Fast, Randy; Paganini, Sara; Lawson, Benton O.; Nega, Melon; Easley, Kirk; Schmitz, Joern E.; Bosinger, Steven E.; Paiardini, Mirko; Chahroudi, Ann; Vanderford, Thomas H.; Estes, Jacob D.; Lifson, Jeffrey D.; Derdeyn, Cynthia A.; Silvestri, Guido

2016-01-01

Infection with HIV persists despite suppressive antiretroviral therapy (ART) and treatment interruption results in rapid viral rebound. Antibody-mediated CD8+ lymphocyte depletion in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) shows these cells contribute to virus control in untreated animals. However, the contribution of CD8+ lymphocytes to maintaining virus suppression under ART remains unknown. We showed that in SIV-infected RMs treated with short-term ART (i.e., 8-32 weeks), depletion of CD8+ lymphocytes resulted in increased plasma viremia in all animals, and that repopulation of CD8+ T cells was associated with prompt reestablishment of virus control. Although the number of SIV-DNA-positive cells remained unchanged after CD8 depletion and reconstitution, the frequency of SIV-infected CD4+ T cells pre-depletion positively correlated with both peak and area-under-the-curve of viremia post-depletion. These results suggest a role for CD8+ T cells in controlling virus production during ART, thus providing rationale to explore immunotherapeutic approaches in ART-treated HIV-infected individuals. PMID:27653601

Preparation of Cd/Pb Chalcogenide Heterostructured Janus Particles via Controllable Cation Exchange.

PubMed

Zhang, Jianbing; Chernomordik, Boris D; Crisp, Ryan W; Kroupa, Daniel M; Luther, Joseph M; Miller, Elisa M; Gao, Jianbo; Beard, Matthew C

2015-07-28

We developed a strategy for producing quasi-spherical nanocrystals of anisotropic heterostructures of Cd/Pb chalcogenides. The nanostructures are fabricated via a controlled cation exchange reaction where the Cd(2+) cation is exchanged for the Pb(2+) cation. The cation exchange reaction is thermally activated and can be controlled by adjusting the reaction temperature or time. We characterized the particles using TEM, XPS, PL, and absorption spectroscopy. With complete exchange, high quality Pb-chalcogenide quantum dots are produced. In addition to Cd(2+), we also find suitable conditions for the exchange of Zn(2+) cations for Pb(2+) cations. The cation exchange is anisotropic starting at one edge of the nanocrystals and proceeds along the ⟨111⟩ direction producing a sharp interface at a (111) crystallographic plane. Instead of spherical core/shell structures, we produced and studied quasi-spherical CdS/PbS and CdSe/PbSe Janus-type heterostructures. Nontrivial PL behavior was observed from the CdS(e)/PbS(e) heterostructures as the Pb:Cd ratio is increased.

Studies on the protective effect of the artichoke (Cynara scolymus) leaf extract against cadmium toxicity-induced oxidative stress, hepatorenal damage, and immunosuppressive and hematological disorders in rats.

PubMed

El-Boshy, Mohamed; Ashshi, Ahmad; Gaith, Mazen; Qusty, Naeem; Bokhary, Thalat; AlTaweel, Nagwa; Abdelhady, Mohamed

2017-05-01

Our objective was to explore the protective effect of artichoke leaf extract (ALE) against cadmium (Cd) toxicity-induced oxidative organ damage in rats. Male albino Wistar rats were divided into four equal groups of eight animals each. The first group was assigned as a control. Groups 2-4 were orally administered with ALE (300 mg/kg bw), Cd (CdCl 2 , 100 mg/L drinking water), and ALE plus Cd, respectively, daily for 4 weeks. After treatment with Cd, the liver and kidney malondialdehyde (MDA) increased significantly compared with the control rats. The sera interleukin (IL)-1β, tumor necrosis factor (TNF-α), and IL-10, liver transaminase, urea, creatinine, and peripheral neutrophil count were significantly increased in Cd-exposed rats compared to the control group. The reduced glutathione (GSH), glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) decreased in the liver and kidney in Cd-exposed group. In combination treatment, Cd and ALE significantly improved immune response, an antioxidant system, and hepatorenal function with a significant decline in MDA. In conclusion, ALE ameliorates the immunosuppressive and hepatorenal oxidative injury stimulated by Cd in rats. These results suggest that artichoke has shown promising effects against adverse effects of Cd toxicity.

Past and future cadmium emissions from municipal solid-waste incinerators in Japan for the assessment of cadmium control policy.

PubMed

Ono, Kyoko

2013-11-15

Cadmium (Cd) is a harmful pollutant emitted from municipal solid-waste incinerators (MSWIs). Cd stack emissions from MSWIs have been estimated between 1970 and 2030 in Japan. The aims of this study are to quantify emitted Cd by category and to analyze Cd control policies to reduce emissions. Emissions were estimated using a dynamic substance flow analysis (SFA) that took into account representative waste treatment flows and historical changes in emission factors. This work revealed that the emissions peaked in 1973 (11.1t) and were ten times those in 2010 (1.2 t). Emission from MSWIs was two-thirds of that from non-ferrous smelting in 2010. The main Cd emission source was pigment use in the 1970s, but after 2000 it had shifted to nickel-cadmium (Ni-Cd) batteries. Future emissions were estimated for 2030. Compared to the business-as-usual scenario, an intensive collection of used Ni-Cd batteries and a ban on any future use of Ni-Cd batteries will reduce emissions by 0.09 and 0.3 1t, respectively, in 2030. This approach enables us to identify the major Cd emission source from MSWIs, and to prioritize the possible Cd control policies. Copyright © 2013 Elsevier B.V. All rights reserved.

Analysis of endoscopic brush samples identified mucosa-associated dysbiosis in inflammatory bowel disease.

PubMed

Nishino, Kyohei; Nishida, Atsushi; Inoue, Ryo; Kawada, Yuki; Ohno, Masashi; Sakai, Shigeki; Inatomi, Osamu; Bamba, Shigeki; Sugimoto, Mitsushige; Kawahara, Masahiro; Naito, Yuji; Andoh, Akira

2018-01-01

The mucosa-associated gut microbiota directly modulates epithelial and mucosal function. In this study, we investigated the mucosa-associated microbial community in patients with inflammatory bowel disease (IBD), using endoscopic brush samples. A total of 174 mucus samples from 43 patients with ulcerative colitis (UC), 26 with Crohn's disease (CD) and 14 non-IBD controls were obtained by gentle brushing of mucosal surfaces using endoscopic cytology brushes. The gut microbiome was analyzed using 16S rRNA gene sequencing. There were no significant differences in microbial structure among different anatomical sites (the ileum, cecum and sigmoid colon) within individuals. There was, however, a significant difference in microbial structure between CD, UC and non-IBD controls. The difference between CD and non-IBD controls was more marked than that between UC patients and non-IBD controls. α-Diversity was significantly lower in UC and CD patients than non-IBD controls. When comparing CD patients with non-IBD controls, the phylum Proteobacteria was significantly increased and the phyla Firmicutes and Bacteroidetes were significantly reduced. These included a significant increase in the genera Escherichia, Ruminococcus (R. gnavus), Cetobacterium, Actinobacillus and Enterococcus, and a significant decrease in the genera Faecalibacterium, Coprococcus, Prevotella and Roseburia. Comparisons between CD and UC patients revealed a greater abundance of the genera Escherichia, Ruminococcus (R. gnavus), Clostridium, Cetobacterium, Peptostreptococcus in CD patients, and the genera Faecalibacterium, Blautia, Bifidobacterium, Roseburia and Citrobacter in UC patients. Mucosa-associated dysbiosis was identified in IBD patients. CD and UC may be distinguishable from the mucosa-associated microbial community structure.

Improving OCD time to solution using Signal Response Metrology

NASA Astrophysics Data System (ADS)

Fang, Fang; Zhang, Xiaoxiao; Vaid, Alok; Pandev, Stilian; Sanko, Dimitry; Ramanathan, Vidya; Venkataraman, Kartik; Haupt, Ronny

2016-03-01

In recent technology nodes, advanced process and novel integration scheme have challenged the precision limits of conventional metrology; with critical dimensions (CD) of device reduce to sub-nanometer region. Optical metrology has proved its capability to precisely detect intricate details on the complex structures, however, conventional RCWA-based (rigorous coupled wave analysis) scatterometry has the limitations of long time-to-results and lack of flexibility to adapt to wide process variations. Signal Response Metrology (SRM) is a new metrology technique targeted to alleviate the consumption of engineering and computation resources by eliminating geometric/dispersion modeling and spectral simulation from the workflow. This is achieved by directly correlating the spectra acquired from a set of wafers with known process variations encoded. In SPIE 2015, we presented the results of SRM application in lithography metrology and control [1], accomplished the mission of setting up a new measurement recipe of focus/dose monitoring in hours. This work will demonstrate our recent field exploration of SRM implementation in 20nm technology and beyond, including focus metrology for scanner control; post etch geometric profile measurement, and actual device profile metrology.

T-cell help permits memory CD8(+) T-cell inflation during cytomegalovirus latency.

PubMed

Walton, Senta M; Torti, Nicole; Mandaric, Sanja; Oxenius, Annette

2011-08-01

CD4(+) T cells are implied to sustain CD8(+) T-cell responses during persistent infections. As CD4(+) T cells are often themselves antiviral effectors, they might shape CD8(+) T-cell responses via help or via controlling antigen load. We used persistent murine CMV (MCMV) infection to dissect the impact of CD4(+) T cells on virus-specific CD8(+) T cells, distinguishing between increased viral load in the absence of CD4(+) T cells and CD4(+) T-cell-mediated helper mechanisms. Absence of T-helper cells was associated with sustained lytic MCMV replication and led to a slow and gradual reduction of the size and function of the MCMV-specific CD8(+) T-cell pool. However, when virus replication was controlled in the absence of CD4(+) T cells, CD8(+) T-cell function was comparably impaired, but in addition CD8(+) T-cell inflation, a hallmark of CMV infection, was completely abolished. Thus, CD8(+) T-cell inflation during latent CMV infection is strongly dependent on CD4(+) T-cell helper functions, which can partially be compensated by ongoing lytic viral replication in the absence of CD4(+) T cells. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Aging of immune system: Immune signature from peripheral blood lymphocyte subsets in 1068 healthy adults.

PubMed

Qin, Ling; Jing, Xie; Qiu, Zhifeng; Cao, Wei; Jiao, Yang; Routy, Jean-Pierre; Li, Taisheng

2016-05-01

Aging is a major risk factor for several conditions including neurodegenerative, cardiovascular diseases and cancer. Functional impairments in cellular pathways controlling genomic stability, and immune control have been identified. Biomarker of immune senescence is needed to improve vaccine response and to develop therapy to improve immune control. To identify phenotypic signature of circulating immune cells with aging, we enrolled 1068 Chinese healthy volunteers ranging from 18 to 80 years old. The decreased naïve CD4+ and CD8+ T cells, increased memory CD4+ or CD8+ T cells, loss of CD28 expression on T cells and reverse trend of CD38 and HLA-DR, were significant for aging of immune system. Conversely, the absolute counts and percentage of NK cells and CD19+B cells maintained stable in aging individuals. The Chinese reference ranges of absolute counts and percentage of peripheral lymphocyte in this study might be useful for future clinical evaluation.

Empathic Accuracy in Male Adolescents with Conduct Disorder and Higher versus Lower Levels of Callous-Unemotional Traits.

PubMed

Martin-Key, N; Brown, T; Fairchild, G

2017-10-01

Adolescents with disruptive behavior disorders are reported to show deficits in empathy and emotion recognition. However, prior studies have mainly used questionnaires to measure empathy or experimental paradigms that are lacking in ecological validity. We used an empathic accuracy (EA) task to study EA, emotion recognition, and affective empathy in 77 male adolescents aged 13-18 years: 37 with Conduct Disorder (CD) and 40 typically-developing controls. The CD sample was divided into higher callous-emotional traits (CD/CU+) and lower callous-unemotional traits (CD/CU-) subgroups using a median split. Participants watched films of actors recalling happy, sad, surprised, angry, disgusted or fearful autobiographical experiences and provided continuous ratings of emotional intensity (assessing EA), as well as naming the emotion (recognition) and reporting the emotion they experienced themselves (affective empathy). The CD and typically-developing groups did not significantly differ in EA and there were also no differences between the CD/CU+ and CD/CU- subgroups. Participants with CD were significantly less accurate than controls in recognizing sadness, fear, and disgust, all ps < 0.050, rs ≥ 0.30, whilst the CD/CU- and CD/CU+ subgroups did not differ in emotion recognition. Participants with CD also showed affective empathy deficits for sadness, fear, and disgust relative to controls, all ps < 0.010, rs ≥ 0.33, whereas the CD/CU+ and CD/CU- subgroups did not differ in affective empathy. These results extend prior research by demonstrating affective empathy and emotion recognition deficits in adolescents with CD using a more ecologically-valid task, and challenge the view that affective empathy deficits are specific to CD/CU+.

Evidence of functional cell-mediated immune responses to nontypeable Haemophilus influenzae in otitis-prone children

PubMed Central

Seppanen, Elke; Tan, Dino; Corscadden, Karli J.; Currie, Andrew J.; Richmond, Peter C.; Thornton, Ruth B.

2018-01-01

Otitis media (OM) remains a common paediatric disease, despite advances in vaccinology. Susceptibility to recurrent acute OM (rAOM) has been postulated to involve defective cell-mediated immune responses to common otopathogenic bacteria. We compared the composition of peripheral blood mononuclear cells (PBMC) from 20 children with a history of rAOM (otitis-prone) and 20 healthy non-otitis-prone controls, and assessed innate and cell-mediated immune responses to the major otopathogen nontypeable Haemophilus influenzae (NTHi). NTHi was a potent stimulator of inflammatory cytokine secretion from PBMC within 4 hours, with no difference in cytokine levels produced between PBMC from cases or controls. In the absence of antigen stimulation, otitis-prone children had more circulating Natural Killer (NK) cells (p<0.01), particularly NKdim (CD56lo) cells (p<0.01), but fewer CD4+ T cells (p<0.01) than healthy controls. NTHi challenge significantly increased the proportion of activated (CD107a+) NK cells in otitis-prone and non-otitis-prone children (p<0.01), suggesting that NK cells from otitis-prone children are functional and respond to NTHi. CD8+ T cells and NK cells from both cases and controls produced IFNγ in response to polyclonal stimulus (Staphylococcal enterotoxin B; SEB), with more IFNγ+ CD8+ T cells present in cases than controls (p<0.05) but similar proportions of IFNγ+ NK cells. Otitis-prone children had more circulating IFNγ-producing NK cells (p<0.05) and more IFNγ-producing CD4+ (p<0.01) or CD8+ T-cells (p<0.05) than healthy controls. In response to SEB, more CD107a-expressing CD8+ T cells were present in cases than controls (p<0.01). Despite differences in PBMC composition, PBMC from otitis-prone children mounted innate and T cell-mediated responses to NTHi challenge that were comparable to healthy children. These data provide evidence that otitis-prone children do not have impaired functional cell mediated immunity. PMID:29621281

Knowledge and experiences of Chagas disease in Bolivian women living in Spain: a qualitative study.

PubMed

Blasco-Hernández, Teresa; García-San Miguel, Lucía; Navaza, Bárbara; Navarro, Miriam; Benito, Agustín

2016-01-01

In Europe, Spain has the highest number of people with Chagas disease (CD). Bolivian migrants account for 81% of the reported cases. One of the priorities in controlling the disease is prevention of mother-to-child transmission. Despite under-diagnosis in Spain being estimated at 90%, there are currently few studies that explore the social and cultural dimensions of this disease. The aim of this study was to explore the knowledge and experiences of Bolivian women with CD, in order to generate a useful understanding for the design and implementation of public health initiatives. Qualitative study based on semi-structured interviews, triangular groups, and field notes. Fourteen Bolivian women with CD living in Madrid. The participants were aware that the disease was transmitted through the vector, that it could be asymptomatic, and that it could also be associated with sudden death by heart failure. They opined that the treatment as such could not cure the disease but only slow it down. There was a sense of indifference along with a lack of understanding of the risk of contracting the disease. Participants who presented with symptoms, or those with relatives suffering from the disease, were concerned about fatalities, cardiac problems, and possible vertical transmission. There was also a fear of being rejected by others. The disease was described as something that affected a large number of people but only showed up in a few cases and that too after many years. There was a widespread assumption that it was better not to know because doing so, allows the disease to take hold. Disease risk perception was very low in Bolivian women living in Madrid. This factor, together with the fear of being screened, may be contributing to the current rate of under-diagnosis.

Reverse Non-Equilibrium Molecular Dynamics Demonstrate That Surface Passivation Controls Thermal Transport at Semiconductor-Solvent Interfaces.

PubMed

Hannah, Daniel C; Gezelter, J Daniel; Schaller, Richard D; Schatz, George C

2015-06-23

We examine the role played by surface structure and passivation in thermal transport at semiconductor/organic interfaces. Such interfaces dominate thermal transport in semiconductor nanomaterials owing to material dimensions much smaller than the bulk phonon mean free path. Utilizing reverse nonequilibrium molecular dynamics simulations, we calculate the interfacial thermal conductance (G) between a hexane solvent and chemically passivated wurtzite CdSe surfaces. In particular, we examine the dependence of G on the CdSe slab thickness, the particular exposed crystal facet, and the extent of surface passivation. Our results indicate a nonmonotonic dependence of G on ligand-grafting density, with interfaces generally exhibiting higher thermal conductance for increasing surface coverage up to ∼0.08 ligands/Å(2) (75-100% of a monolayer, depending on the particular exposed facet) and decreasing for still higher coverages. By analyzing orientational ordering and solvent penetration into the ligand layer, we show that a balance of competing effects is responsible for this nonmonotonic dependence. Although the various unpassivated CdSe surfaces exhibit similar G values, the crystal structure of an exposed facet nevertheless plays an important role in determining the interfacial thermal conductance of passivated surfaces, as the density of binding sites on a surface determines the ligand-grafting densities that may ultimately be achieved. We demonstrate that surface passivation can increase G relative to a bare surface by roughly 1 order of magnitude and that, for a given extent of passivation, thermal conductance can vary by up to a factor of ∼2 between different surfaces, suggesting that appropriately tailored nanostructures may direct heat flow in an anisotropic fashion for interface-limited thermal transport.

The prevalence of abnormal celiac antibodies and celiac disease in patients with suspected irritable bowel syndrome: a prospective multi-center US study

PubMed Central

Cash, Brooks D.; Rubenstein, Joel H.; Young, Patrick E.; Gentry, Andrew; Nojkov, Borko; Lee, Dong; Andrews, A. Hirsohi; Dobhan, Richard; Chey, William D.

2011-01-01

Background & Aims Guidelines recommend that patients with symptoms of non-constipated inflammatory bowel syndrome (NC-IBS) undergo testing for celiac disease (CD). We evaluated the prevalence of CD antibodies and biopsy confirmed CD among patients with NC-IBS in a large US population. Methods In a study conducted at 4 sites, from 2003 to 2008, we compared data from 492 patients with symptoms of NC-IBS to 458 asymptomatic individuals who underwent colonoscopy examinations for cancer screening or polyp surveillance (controls). All participants provided blood samples for specific and non-specific CD-associated antibodies. Additionally, patients with IBS were analyzed for complete blood cell counts, metabolic factors, erythrocyte sedimentation rates, and levels of C-reactive protein and thyroid-stimulating hormone. Any subjects found to have CD-associated antibodies were offered esophagogastroduodenoscopy and duodenal biopsy analysis. Results Of patients with NC-IBS, 7.3% had abnormal results in tests for CD-associated antibodies, compared to 4.8% of controls (adjusted odds ratio=1.49; 95% confidence interval, 0.76–2.90. P=.25). Within the NC-IBS group, 6.51% had antibodies against gliadin, 1.22% against tissue transglutaminase, and 0.61% against endomysium (P>.05 vs controls for all antibodies tested). CD was confirmed in 0.41% of patients in the NC-IBS group and 0.44% of controls (P>0.99). Conclusions Although CD-associated antibodies are relatively common, the prevalence of CD among patients with NC-IBS is similar to that among controls in a large US population. These findings challenge recommendations to routinely screen patients with NC-IBS for CD. More than 7% of patients with NC-IBS had CD-associated antibodies, indicating that gluten sensitivity might mediate IBS symptoms; further studies are needed. PMID:21762658

Functional significance of CD105-positive cells in papillary renal cell carcinoma.

PubMed

Matak, Damian; Brodaczewska, Klaudia K; Szczylik, Cezary; Koch, Irena; Myszczyszyn, Adam; Lipiec, Monika; Lewicki, Slawomir; Szymanski, Lukasz; Zdanowski, Robert; Czarnecka, Anna M

2017-01-05

CD105 was postulated as a renal cell carcinoma (RCC) stem cell marker, and CD133 as a putative RCC progenitor. Hypoxia, a natural microenvironment that prevails in tumors, was also incorporated into the study, especially in terms of the promotion of hypothetical stem-like cell properties. Within this study, we verify the existence of CD105+ and CD133+ populations in selected papillary subtype RCC (pRCC) cell lines. Both populations were analyzed for correlation with stem-like cell properties, such as stemness gene expression, and sphere and colony formation. For the preliminary analysis, several RCC cell lines were chosen (786-O, SMKT-R2, Caki-2, 796-P, ACHN, RCC6) and the control was human kidney cancer stem cells (HKCSC) and renal cells of embryonic origin (ASE-5063). Four cell lines were chosen for further investigation: Caki-2 (one of the highest numbers of CD105+ cells; primary origin), ACHN (a low number of CD105+ cells; metastatic origin), HKCSC (putative positive control), and ASE-5063 (additional control). In 769-P and RCC6, we could not detect a CD105+ population. Hypoxia variously affects pRCC cell growth, and mainly diminishes the stem-like properties of cells. Furthermore, we could not observe the correlation of CD105 and/or CD133 expression with the enhancement of stem-like properties. Based on this analysis, CD105/CD133 cannot be validated as cancer stem cell markers of pRCC cell lines.

Immune-Regulatory Molecule CD69 Controls Peritoneal Fibrosis

PubMed Central

Liappas, Georgios; González-Mateo, Guadalupe Tirma; Sánchez-Díaz, Raquel; Lazcano, Juan José; Lasarte, Sandra; Matesanz-Marín, Adela; Zur, Rafal; Ferrantelli, Evelina; Ramírez, Laura García; Aguilera, Abelardo; Fernández-Ruiz, Elena; Beelen, Robert H.J.; Selgas, Rafael; Sánchez-Madrid, Francisco

2016-01-01

Patients with ESRD undergoing peritoneal dialysis develop progressive peritoneal fibrosis, which may lead to technique failure. Recent data point to Th17-mediated inflammation as a key contributor in peritoneal damage. The leukocyte antigen CD69 modulates the setting and progression of autoimmune and inflammatory diseases by controlling the balance between Th17 and regulatory T cells (Tregs). However, the relevance of CD69 in tissue fibrosis remains largely unknown. Thus, we explored the role of CD69 in fibroproliferative responses using a mouse model of peritoneal fibrosis induced by dialysis fluid exposure under either normal or uremic status. We found that cd69−/− mice compared with wild-type (WT) mice showed enhanced fibrosis, mesothelial to mesenchymal transition, IL-17 production, and Th17 cell infiltration in response to dialysis fluid treatment. Uremia contributed partially to peritoneal inflammatory and fibrotic responses. Additionally, antibody–mediated CD69 blockade in WT mice mimicked the fibrotic response of cd69−/− mice. Finally, IL-17 blockade in cd69−/− mice decreased peritoneal fibrosis to the WT levels, and mixed bone marrow from cd69−/− and Rag2−/−γc−/− mice transplanted into WT mice reproduced the severity of the response to dialysis fluid observed in cd69−/− mice, showing that CD69 exerts its regulatory function within the lymphocyte compartment. Overall, our results indicate that CD69 controls tissue fibrosis by regulating Th17-mediated inflammation. PMID:27151919

Increased duodenal expression of miR-146a and -155 in pediatric Crohn’s disease

PubMed Central

Szűcs, Dániel; Béres, Nóra Judit; Rokonay, Réka; Boros, Kriszta; Borka, Katalin; Kiss, Zoltán; Arató, András; Szabó, Attila J; Vannay, Ádám; Sziksz, Erna; Bereczki, Csaba; Veres, Gábor

2016-01-01

AIM: To evaluate the role of microRNA (miR)-146a, -155 and -122 in the duodenal mucosa of pediatric patients with Crohn’s disease (CD) and the effect of transforming growth factor-β (TGF-β) on these miRs in duodenal epithelial and fibroblast cells. METHODS: Formalin-fixed, paraffin-embedded biopsies derived from the macroscopically inflamed (CD inflamed: n = 10) and intact (CD intact: n = 10) duodenal mucosa of pediatric CD patients and control children (C: n = 10) were examined. Expression of miR-146a, -155 and -122 was determined by real-time polymerase-chain reaction (PCR). The expression of the above miRs was investigated in recombinant human TGF-β (1 nmol/L, 24 h) or vehicle treated small intestinal epithelial cells (CCL-241) and primary duodenal fibroblast cells derived from healthy children as well. RESULTS: Expression of miR-146a was significantly higher in the inflamed duodenal mucosa compared to the intact duodenal mucosa of children with CD (CD inflamed: 3.21 ± 0.50 vs CD intact: 0.62 ± 0.26, P ≤ 0.01) and to the control group (CD inflamed: 3.21 ± 0.50 vs C: 1.00 ± 0.33, P ≤ 0.05). The expression of miR-155 was significantly increased in the inflamed region of the duodenum compared to the control group (CD inflamed: 4.87 ± 1.02 vs Control: 1.00 ± 0.40, P ≤ 0.001). The expression of miR-122 was unchanged in the inflamed or intact mucosa of CD patients compared to controls. TGF-β treatment significantly decreased the expression of miR-155 in small intestinal epithelial cells (TGF-β: 0.7 ± 0.083 vs Control: 1 ± 0.09, P ≤ 0.05) and also the expression of miR-146a (TGF-β: 0.67 ± 0.04 vs Control: 1 ± 0.15, P ≤ 0.01) and miR-155 (TGF-β: 0.72 ± 0.09 vs Control: 1 ± 0.06, P ≤ 0.05) in primary duodenal fibroblasts compared to corresponding vehicle treated controls. TGF-β treatment did not influence the expression of miR-122. CONCLUSION: The elevated expression of miR-146a and -155 in the inflamed duodenal mucosa of CD patients suggests the role of these miRs in the pathomechanism of inflammatory bowel disease. Anti-inflammatory TGF-β plays an important role in the regulation of the expression of these miRs. PMID:27468194

Emotion-motion interactions in conversion disorder: an FMRI study.

PubMed

Aybek, Selma; Nicholson, Timothy R; O'Daly, Owen; Zelaya, Fernando; Kanaan, Richard A; David, Anthony S

2015-01-01

To evaluate the neural correlates of implicit processing of negative emotions in motor conversion disorder (CD) patients. An event related fMRI task was completed by 12 motor CD patients and 14 matched healthy controls using standardised stimuli of faces with fearful and sad emotional expressions in comparison to faces with neutral expressions. Temporal changes in the sensitivity to stimuli were also modelled and tested in the two groups. We found increased amygdala activation to negative emotions in CD compared to healthy controls in region of interest analyses, which persisted over time consistent with previous findings using emotional paradigms. Furthermore during whole brain analyses we found significantly increased activation in CD patients in areas involved in the 'freeze response' to fear (periaqueductal grey matter), and areas involved in self-awareness and motor control (cingulate gyrus and supplementary motor area). In contrast to healthy controls, CD patients exhibited increased response amplitude to fearful stimuli over time, suggesting abnormal emotional regulation (failure of habituation / sensitization). Patients with CD also activated midbrain and frontal structures that could reflect an abnormal behavioral-motor response to negative including threatening stimuli. This suggests a mechanism linking emotions to motor dysfunction in CD.

Percentage and function of CD4+CD25+ regulatory T cells in patients with hyperthyroidism

PubMed Central

Jiang, Ting-Jun; Cao, Xue-Liang; Luan, Sha; Cui, Wan-Hui; Qiu, Si-Huang; Wang, Yi-Chao; Zhao, Chang-Jiu; Fu, Peng

2018-01-01

The current study observed the percentage of peripheral blood (PB) CD4+CD25+ regulatory T cells (Tregs) and the influence of CD4+CD25+ Tregs on the proliferation of naïve CD4 T cells in patients with hyperthyroidism. Furthermore, preliminary discussions are presented on the action mechanism of CD4+CD25+ Tregs on hyperthyroidism attacks. The present study identified that compared with the percentage of PB CD4+CD25+ Tregs in healthy control subjects, no significant changes were observed in the percentage of PB CD4+CD25+ Tregs in patients with hyperthyroidism (P>0.05). For patients with hyperthyroidism, CD4+CD25+ Tregs exhibited significantly reduced inhibition of the proliferation of naïve CD4 T cells and decreased secretion capacity on the cytokines of CD4 T cells, compared with those of healthy control subjects (P<0.05). In addition, it was demonstrated that thyroid function of patients with hyperthyroidism was significantly improved (P<0.05) subsequent to receiving medication. Compared with the percentage of PB CD4+CD25+ Tregs in patients with hyperthyroidism before treatment, no significant changes were observed in the percentage of PB CD4+CD25+ Tregs in hyperthyroidism patients following treatment (P>0.05). In the patients with hyperthyroidism, following treatment, CD4+CD25+ Tregs exhibited significantly increased inhibition of the proliferation of naïve CD4 T cells and increased secretion capacity of CD4 T cell cytokines, compared with those of the patients with hyperthyroidism prior to treatment (P<0.05). PB CD4+CD25+ Tregs function was decreased in patients with hyperthyroidism, and its non-proportional decrease may be closely associated with the occurrence and progression of hyperthyroidism. PMID:29207121

Presymptomatic Diagnosis of Celiac Disease in Predisposed Children: The Role of Gene Expression Profile.

PubMed

Galatola, Martina; Cielo, Donatella; Panico, Camilla; Stellato, Pio; Malamisura, Basilio; Carbone, Lorenzo; Gianfrani, Carmen; Troncone, Riccardo; Greco, Luigi; Auricchio, Renata

2017-09-01

The prevalence of celiac disease (CD) has increased significantly in recent years, and risk prediction and early diagnosis have become imperative especially in at-risk families. In a previous study, we identified individuals with CD based on the expression profile of a set of candidate genes in peripheral blood monocytes. Here we evaluated the expression of a panel of CD candidate genes in peripheral blood mononuclear cells from at-risk infants long time before any symptom or production of antibodies. We analyzed the gene expression of a set of 9 candidate genes, associated with CD, in 22 human leukocyte antigen predisposed children from at-risk families for CD, studied from birth to 6 years of age. Nine of them developed CD (patients) and 13 did not (controls). We analyzed gene expression at 3 different time points (age matched in the 2 groups): 4-19 months before diagnosis, at the time of CD diagnosis, and after at least 1 year of a gluten-free diet. At similar age points, controls were also evaluated. Three genes (KIAA, TAGAP [T-cell Activation GTPase Activating Protein], and SH2B3 [SH2B Adaptor Protein 3]) were overexpressed in patients, compared with controls, at least 9 months before CD diagnosis. At a stepwise discriminant analysis, 4 genes (RGS1 [Regulator of G-protein signaling 1], TAGAP, TNFSF14 [Tumor Necrosis Factor (Ligand) Superfamily member 14], and SH2B3) differentiate patients from controls before serum antibodies production and clinical symptoms. Multivariate equation correctly classified CD from non-CD children in 95.5% of patients. The expression of a small set of candidate genes in peripheral blood mononuclear cells can predict CD at least 9 months before the appearance of any clinical and serological signs of the disease.

The impact of moderate-to-severe Crohn's Disease on employees' salary growth.

PubMed

Loftus, Edward V; Skup, Martha; Ozbay, Ahmet Burak; Wu, Eric; Guérin, Annie; Chao, Jingdong; Mulani, Parvez

2014-10-01

Moderate-to-severe Crohn's Disease (CD) has been shown to reduce daily activities; however, little is known of the impact on employees' salary growth. Employment and health care benefit data were extracted from the OptumHealth Reporting and Insights database, aggregating data from 23 self-insured U.S. companies with approximately 2.5 million covered beneficiaries. Employees diagnosed with moderate-to-severe CD (i.e., ≥1 prescription fill for systemic corticosteroids, immunosuppressive drugs, methotrexate or cyclosporine, or biologic agents within 6 months after the first observed CD diagnosis) between January 1999 and December 2006 were retrospectively matched with controls without CD based on year of birth, sex, industry, and geographic region. Employees' salaries and salary growth rates were estimated and compared between cohorts. Both descriptive comparison and multivariate regression analyses controlling for baseline characteristics and differences in comorbidities were performed. A total of 918 employees with moderate-to-severe CD were matched to 2154 CD-free controls. The 2 cohorts did not differ in their annual salary in the first year of observation. However, regression analyses revealed that the 2 groups had significantly different adjusted annualized salary growth rates (0.69% versus 1.01%, P < 0.001), and employees with CD had a 31% lower salary increase rate than controls. A total income loss of $3195 per person was estimated for employees with CD compared with their CD-free peers over a cumulative 5 years after the first calendar year. In the United States, employees with moderate-to-severe CD had a substantially lower salary growth rate than their peers without CD, suggesting an impaired career progression.

Role of beta-cell autoantibodies as a predictor marker in diabetic patients and their relationship to glycemic control.

PubMed

Ali, Naglaa A; Swelam, Enas; AI Banna, Ehab A; Showkry, Amira

2012-01-01

To evaluate glutamic acid decarboxylase autoantibodies (GAD65), islet cell autoantibodies (ICA) and insulin autoantibodies (IAA) as disease markers and their relationship to certain residual beta-cell function as well as glycemic control among patients with diabetes mellitus. Also, to evaluate of the level of CD4+CD25+(Treg) out of CD4 cells among patients with immune mediated diabetes mellitus (DM). The study included 80 individuals divided into: 40 diabetic patients (group A) and 20 risk siblings (group B) of diabetic father or mother or both. 20 healthy individuals enrolled as control group (group C) all were with no family history of DM. GAD, ICA, IAA autoantibodies and C-peptide were determined by ELISA. HbA1 by ion exchange chromatography and measurement of the expression of CD4+CD25+ (T reg) by flowcytometry. The most frequently encountered antibody in adult and children groups was GAD65, followed by ICA. But in risk group the most frequently antibody was ICA, followed by GAD. In the risk group, there was no statistical difference in the level of CD4+CD25+ in comparison with control group. There was significant decrease in the percentage of CD4+CD25+ in adult and children patients groups with positive autoantibodies than those with negative autoantibodies. In conclusions, at the time of diagnosis the majority of patients with type I diabetes have autoantibodies that are reactive to islet antigens. GAD, ICA, IAA are of value for predicting IDDM in sibling of diabetic parents type I. CD4+CD25+ Treg cells may actively suppress activation of the immune system and prevent pathological self-reactivity.

Correlations between Transmembrane 4 L6 Family Member 5 (TM4SF5), CD151, and CD63 in Liver Fibrotic Phenotypes and Hepatic Migration and Invasive Capacities

PubMed Central

Kang, Minkyung; Ryu, Jihye; Lee, Doohyung; Lee, Mi-Sook; Kim, Hye-Jin; Nam, Seo Hee; Song, Haeng Eun; Choi, Jungeun; Lee, Gyu-Ho; Kim, Tai Young; Lee, Hansoo; Kim, Sang Jick; Ye, Sang-Kyu; Kim, Semi; Lee, Jung Weon

2014-01-01

Transmembrane 4 L6 family member 5 (TM4SF5) is overexpressed during CCl4-mediated murine liver fibrosis and in human hepatocellular carcinomas. The tetraspanins form tetraspanin-enriched microdomains (TEMs) consisting of large membrane protein complexes on the cell surface. Thus, TM4SF5 may be involved in the signal coordination that controls liver malignancy. We investigated the relationship between TM4SF5-positive TEMs with liver fibrosis and tumorigenesis, using normal Chang hepatocytes that lack TM4SF5 expression and chronically TGFβ1-treated Chang cells that express TM4SF5. TM4SF5 expression is positively correlated with tumorigenic CD151 expression, but is negatively correlated with tumor-suppressive CD63 expression in mouse fibrotic and human hepatic carcinoma tissues, indicating cooperative roles of the tetraspanins in liver malignancies. Although CD151 did not control the expression of TM4SF5, TM4SF5 appeared to control the expression levels of CD151 and CD63. TM4SF5 interacted with CD151, and caused the internalization of CD63 from the cell surface into late lysosomal membranes, presumably leading to terminating the tumor-suppressive functions of CD63. TM4SF5 could overcome the tumorigenic effects of CD151, especially cell migration and extracellular matrix (ECM)-degradation. Taken together, TM4SF5 appears to play a role in liver malignancy by controlling the levels of tetraspanins on the cell surface, and could provide a promising therapeutic target for the treatment of liver malignancies. PMID:25033048

Plasma Soluble CD30 as a Possible Marker of Adult T-cell Leukemia in HTLV-1 Carriers: a Nested Case-Control Study.

PubMed

Takemoto, Shigeki; Iwanaga, Masako; Sagara, Yasuko; Watanabe, Toshiki

2015-01-01

Elevated levels of soluble CD30 (sCD30) are linked with various T-cell neoplasms. However, the relationship between sCD30 levels and the development of adult T-cell leukemia (ATL) in human T-cell leukemia virus type 1 (HTLV-1) carriers remains to be clarified. We here investigated whether plasma sCD30 is associated with risk of ATL in a nested case-control study within a cohort of HTLV-1 carriers. We compared sCD30 levels between 11 cases (i.e., HTLV-1 carriers who later progressed to ATL) and 22 age-, sex- and institution-matched control HTLV-1 carriers (i.e., those with no progression). The sCD30 concentration at baseline was significantly higher in cases than in controls (median 65.8, range 27.2-134.5 U/mL vs. median 22.2, range 8.4-63.1 U/mL, P=0.001). In the univariate logistic regression analysis, a higher sCD30 (≥30.2 U/mL) was significantly associated with ATL development (odds ratio 7.88 and the 95% confidence intervals 1.35-45.8, P = 0.02). Among cases, sCD30 concentration tended to increase at the time of diagnosis of aggressive-type ATL, but the concentration was stable in those developing the smoldering-type. This suggests that sCD30 may serve as a predictive marker for the onset of aggressive-type ATL in HTLV-1 carriers.

Defect printability of alternating phase-shift mask: a critical comparison of simulation and experiment

NASA Astrophysics Data System (ADS)

Ozawa, Ken; Komizo, Tooru; Kikuchi, Koji; Ohnuma, Hidetoshi; Kawahira, Hiroichi

2002-07-01

An alternative phase shift mask (alt-PSM) is a promising device for extending optical lithography to finer design rules. There have been few reports, however, on the mask's ability to identify phase defects. We report here an alt-PSM of a dual-trench type for KrF exposure, with programmed quartz defects used to evaluate defect printability by measuring aerial images with a Zeiss MSM100 measuring system. The experimental results are simulated using the TEMPEST program. First, a critical comparison of the simulation and the experiment is conducted. The actual measured topography of quartz defects are used in the simulation. Moreover, a general simulation study on defect printability using an alt-PSM for ArF exposure is conducted. The defect dimensions, which produce critical CD errors are determined by simulation that takes into account the full 3-dimensional structure of phase defects as well as a simplified structure. The critical dimensions of an isolated defect identified by the alt-PSM of a single-trench type for ArF exposure are 240 nm in bottom diameter and 50 degrees in height (phase) for the cylindrical shape and 240 nm in bottom diameter and 90 degrees in height (phase) for the rotating trapezoidal shape, where the CD error limit is +/- 5%.

Line-width roughness of advanced semiconductor features by using FIB and planar-TEM as reference metrology

NASA Astrophysics Data System (ADS)

Takamasu, Kiyoshi; Takahashi, Satoru; Kawada, Hiroki; Ikota, Masami

2018-03-01

LER (Line Edge Roughness) and LWR (Line Width Roughness) of the semiconductor device are an important evaluation scale of the performance of the device. Conventionally, LER and LWR is evaluated from CD-SEM (Critical Dimension Scanning Electron Microscope) images. However, CD-SEM measurement has a problem that high frequency random noise is large, and resolution is not sufficiently high. For random noise of CD-SEM measurement, some techniques are proposed. In these methods, it is necessary to set parameters for model and processing, and it is necessary to verify the correctness of these parameters using reference metrology. We have already proposed a novel reference metrology using FIB (Focused Ion Beam) process and planar-TEM (Transmission Electron Microscope) method. In this study, we applied the proposed method to three new samples such as SAQP (Self-Aligned Quadruple Patterning) FinFET device, EUV (Extreme Ultraviolet Lithography) conventional resist, and EUV new material resist. LWR and PSD (Power Spectral Density) of LWR are calculated from the edge positions on planar-TEM images. We confirmed that LWR and PSD of LWR can be measured with high accuracy and evaluated the difference by the proposed method. Furthermore, from comparisons with PSD of the same sample by CD-SEM, the validity of measurement of PSD and LWR by CD-SEM can be verified.

A four-dimensional virtual hand brain-machine interface using active dimension selection

NASA Astrophysics Data System (ADS)

Rouse, Adam G.

2016-06-01

Objective. Brain-machine interfaces (BMI) traditionally rely on a fixed, linear transformation from neural signals to an output state-space. In this study, the assumption that a BMI must control a fixed, orthogonal basis set was challenged and a novel active dimension selection (ADS) decoder was explored. Approach. ADS utilizes a two stage decoder by using neural signals to both (i) select an active dimension being controlled and (ii) control the velocity along the selected dimension. ADS decoding was tested in a monkey using 16 single units from premotor and primary motor cortex to successfully control a virtual hand avatar to move to eight different postures. Main results. Following training with the ADS decoder to control 2, 3, and then 4 dimensions, each emulating a grasp shape of the hand, performance reached 93% correct with a bit rate of 2.4 bits s-1 for eight targets. Selection of eight targets using ADS control was more efficient, as measured by bit rate, than either full four-dimensional control or computer assisted one-dimensional control. Significance. ADS decoding allows a user to quickly and efficiently select different hand postures. This novel decoding scheme represents a potential method to reduce the complexity of high-dimension BMI control of the hand.

A four-dimensional virtual hand brain-machine interface using active dimension selection

PubMed Central

Rouse, Adam G.

2018-01-01

Objective Brain-machine interfaces (BMI) traditionally rely on a fixed, linear transformation from neural signals to an output state-space. In this study, the assumption that a BMI must control a fixed, orthogonal basis set was challenged and a novel active dimension selection (ADS) decoder was explored. Approach ADS utilizes a two stage decoder by using neural signals to both i) select an active dimension being controlled and ii) control the velocity along the selected dimension. ADS decoding was tested in a monkey using 16 single units from premotor and primary motor cortex to successfully control a virtual hand avatar to move to eight different postures. Main Results Following training with the ADS decoder to control 2, 3, and then 4 dimensions, each emulating a grasp shape of the hand, performance reached 93% correct with a bit rate of 2.4 bits/s for eight targets. Selection of eight targets using ADS control was more efficient, as measured by bit rate, than either full four-dimensional control or computer assisted one-dimensional control. Significance ADS decoding allows a user to quickly and efficiently select different hand postures. This novel decoding scheme represents a potential method to reduce the complexity of high-dimension BMI control of the hand. PMID:27171896

Blimp-1–mediated CD4 T cell exhaustion causes CD8 T cell dysfunction during chronic toxoplasmosis

PubMed Central

Cobb, Dustin A.; Bhadra, Rajarshi

2016-01-01

CD8, but not CD4, T cells are considered critical for control of chronic toxoplasmosis. Although CD8 exhaustion has been previously reported in Toxoplasma encephalitis (TE)–susceptible model, our current work demonstrates that CD4 not only become exhausted during chronic toxoplasmosis but this dysfunction is more pronounced than CD8 T cells. Exhausted CD4 population expressed elevated levels of multiple inhibitory receptors concomitant with the reduced functionality and up-regulation of Blimp-1, a transcription factor. Our data demonstrates for the first time that Blimp-1 is a critical regulator for CD4 T cell exhaustion especially in the CD4 central memory cell subset. Using a tamoxifen-dependent conditional Blimp-1 knockout mixed bone marrow chimera as well as an adoptive transfer approach, we show that CD4 T cell–intrinsic deletion of Blimp-1 reversed CD8 T cell dysfunction and resulted in improved pathogen control. To the best of our knowledge, this is a novel finding, which demonstrates the role of Blimp-1 as a critical regulator of CD4 dysfunction and links it to the CD8 T cell dysfunctionality observed in infected mice. The critical role of CD4-intrinsic Blimp-1 expression in mediating CD4 and CD8 T cell exhaustion may provide a rational basis for designing novel therapeutic approaches. PMID:27481131

The CD14+CD16+ Inflammatory Monocyte Subset Displays Increased Mitochondrial Activity and Effector Function During Acute Plasmodium vivax Malaria

PubMed Central

Antonelli, Lis R. V.; Leoratti, Fabiana M. S.; Costa, Pedro A. C.; Rocha, Bruno C.; Diniz, Suelen Q.; Tada, Mauro S.; Pereira, Dhelio B.; Teixeira-Carvalho, Andrea; Golenbock, Douglas T.; Gonçalves, Ricardo; Gazzinelli, Ricardo T.

2014-01-01

Infection with Plasmodium vivax results in strong activation of monocytes, which are important components of both the systemic inflammatory response and parasite control. The overall goal of this study was to define the role of monocytes during P. vivax malaria. Here, we demonstrate that P. vivax–infected patients display significant increase in circulating monocytes, which were defined as CD14+CD16− (classical), CD14+CD16+ (inflammatory), and CD14loCD16+ (patrolling) cells. While the classical and inflammatory monocytes were found to be the primary source of pro-inflammatory cytokines, the CD16+ cells, in particular the CD14+CD16+ monocytes, expressed the highest levels of activation markers, which included chemokine receptors and adhesion molecules. Morphologically, CD14+ were distinguished from CD14lo monocytes by displaying larger and more active mitochondria. CD14+CD16+ monocytes were more efficient in phagocytizing P. vivax-infected reticulocytes, which induced them to produce high levels of intracellular TNF-α and reactive oxygen species. Importantly, antibodies specific for ICAM-1, PECAM-1 or LFA-1 efficiently blocked the phagocytosis of infected reticulocytes by monocytes. Hence, our results provide key information on the mechanism by which CD14+CD16+ cells control parasite burden, supporting the hypothesis that they play a role in resistance to P. vivax infection. PMID:25233271

Fecal calprotectin in coeliac disease.

PubMed

Capone, Pietro; Rispo, Antonio; Imperatore, Nicola; Caporaso, Nicola; Tortora, Raffaella

2014-01-14

We would like to share with the readers the results of our experience in 50 celiac disease (CD) patients, enrolled between September 2012 and April 2013, who were referred to our third-level CD Unit. The fecal calprotectin (FC) concentration of 50 adults with newly diagnosed CD was compared to that of a control group of 50 healthy subjects. FC level was determined by enzyme linked immunosorbent assay with diagnostic cut-off of 75 μg/g. In addition, we tried to correlate the FC level with symptoms, histological severity of CD (Marsh grade) and level of tissue transglutaminase antibodies (aTg) in CD patients. Finally, FC level was increased in five CD patients and in four controls (10% vs 8%, P = NS); mean FC concentration of patients and controls were 57.7 (SD ± 29.1) and 45.1 (SD ± 38.4) respectively. Furthermore, no significant correlation was seen between FC levels and symptoms/Marsh grade/aTg. The five CD patients did not show inflammatory lesions (e.g., ulcers, erosions) at upper endoscopy. The four healthy controls with positive FC were followed-up for further six months; in this observational period they did not show clinical signs of any underlying disease. On these bases, we think that FC is not able to investigate the subclinical inflammatory changes of active CD and FC should be considered a useless tool in the diagnostic work-up of uncomplicated CD but it should be accompanied by aTg when ruling out organic disease in patients with irritable bowel syndrome.

Top-down control analysis of the cadmium effects on molluscan mitochondria and the mechanisms of cadmium-induced mitochondrial dysfunction.

PubMed

Kurochkin, Ilya O; Etzkorn, Markus; Buchwalter, David; Leamy, Larry; Sokolova, Inna M

2011-01-01

Cadmium (Cd) is a toxic metal and an important environmental pollutant that can strongly affect mitochondrial function and bioenergetics in animals. We investigated the mechanisms of Cd action on mitochondrial function of a marine mollusk (the eastern oyster Crassostrea virginica) by performing a top-down control analysis of the three major mitochondrial subsystems (substrate oxidation, proton leak, and phosphorylation). Our results showed that the substrate oxidation and proton leak subsystems are the main targets for Cd toxicity in oyster mitochondria. Exposure to 12.5 μM Cd strongly inhibited the substrate oxidation subsystem and stimulated the proton conductance across the inner mitochondrial membrane. Proton conductance was also elevated and substrate oxidation inhibited by Cd in the presence of a mitochondrially targeted antioxidant, MitoVitE, indicating that Cd effects on these subsystems were to a large extent ROS independent. Cd did not affect the kinetics of the phosphorylation system, indicating that it has negligible effects on F₁, F(O) ATP synthase and/or the adenine nucleotide transporter in oyster mitochondria. Cd exposure altered the patterns of control over mitochondrial respiration, increasing the degree of control conferred by the substrate oxidation subsystem, especially in resting (state 4) mitochondria. Taken together, these data suggest that Cd-induced decrease of mitochondrial efficiency and ATP production are predominantly driven by the high sensitivity of substrate oxidation and proton leak subsystems to this metal.

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing.

PubMed

Neltner, Janna H; Abner, Erin L; Baker, Steven; Schmitt, Frederick A; Kryscio, Richard J; Jicha, Gregory A; Smith, Charles D; Hammack, Eleanor; Kukull, Walter A; Brenowitz, Willa D; Van Eldik, Linda J; Nelson, Peter T

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer's Disease Centre, Nun Study, and National Alzheimer's Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case-control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0.03), and larger vessel areas (P < 0.03) than controls. Unlike the arterioles, CD34-immunoreactive capillaries had dimensions that were unchanged in cases with hippocampal sclerosis of ageing versus controls. Arteriolosclerosis appears specific to hippocampal sclerosis of ageing brains, because brains with Alzheimer's disease pathology did not show the same morphological alterations. We conclude that there may be a pathogenetic change in aged human brain arterioles that impacts multiple brain areas and contributes to hippocampal sclerosis of ageing.

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing

PubMed Central

Neltner, Janna H.; Abner, Erin L.; Baker, Steven; Schmitt, Frederick A.; Kryscio, Richard J.; Jicha, Gregory A.; Smith, Charles D.; Hammack, Eleanor; Kukull, Walter A.; Brenowitz, Willa D.; Van Eldik, Linda J.

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer’s Disease Centre, Nun Study, and National Alzheimer’s Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case–control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0.03), and larger vessel areas (P < 0.03) than controls. Unlike the arterioles, CD34-immunoreactive capillaries had dimensions that were unchanged in cases with hippocampal sclerosis of ageing versus controls. Arteriolosclerosis appears specific to hippocampal sclerosis of ageing brains, because brains with Alzheimer’s disease pathology did not show the same morphological alterations. We conclude that there may be a pathogenetic change in aged human brain arterioles that impacts multiple brain areas and contributes to hippocampal sclerosis of ageing. PMID:24271328

Adaptation of feedforward movement control is abnormal in patients with cervical dystonia and tremor.

PubMed

Avanzino, Laura; Ravaschio, Andrea; Lagravinese, Giovanna; Bonassi, Gaia; Abbruzzese, Giovanni; Pelosin, Elisa

2018-01-01

It is under debate whether the cerebellum plays a role in dystonia pathophysiology and in the expression of clinical phenotypes. We investigated a typical cerebellar function (anticipatory movement control) in patients with cervical dystonia (CD) with and without tremor. Twenty patients with CD, with and without tremor, and 17 healthy controls were required to catch balls of different load: 15 trials with a light ball, 25 trials with a heavy ball (adaptation) and 15 trials with a light ball (post-adaptation). Arm movements were recorded using a motion capture system. We evaluated: (i) the anticipatory adjustment (just before the impact); (ii) the extent and rate of the adaptation (at the impact) and (iii) the aftereffect in the post-adaptation phase. The anticipatory adjustment was reduced during adaptation in CD patients with tremor respect to CD patients without tremor and controls. The extent and rate of adaptation and the aftereffect in the post-adaptation phase were smaller in CD with tremor than in controls and CD without tremor. Patients with cervical dystonia and tremor display an abnormal predictive movement control. Our findings point to a possible role of cerebellum in the expression of a clinical phenotype in dystonia. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Early elevation of soluble CD14 may help identify trauma patients at high risk for infection.

PubMed

Carrillo, E H; Gordon, L; Goode, E; Davis, E; Polk, H C

2001-05-01

Elevated levels of soluble CD14 (sCD14) have been implicated in both gram-positive and gram-negative sepsis, and it has been associated with high mortality in trauma patients who become infected. Eleven healthy volunteers and 25 adult trauma patients with multiple injuries and a mean Injury Severity Score of 32 participated. Whole blood was obtained at intervals. Immunohistochemistry was used to quantify membrane CD14 (mCD14), by flow cytometry and plasma levels of sCD14 by enzyme-linked immunosorbent assay. Analysis of variance and Student's T test with Mann-Whitney posttest were used to determine significance at p < 0.05. On posttrauma day 1, sCD14 was significantly different in the plasma of infected patients compared with normal controls (7.16 +/- 1.87 microg/mL vs. 4.4 +/- 0.92 microg/mL, p < 0.01), but not significantly different from noninfected patients. The percentage of monocytes expressing mCD14 in trauma patients did not differentiate them from normal controls; however, mCD14 receptor density did demonstrate significance in septic trauma patients (n = 15) versus normal controls on posttrauma day 3 (p = 0.0065). On the basis of our data, mCD14 did not differentiate infected and noninfected trauma patients, although trauma in general reduced mCD14 and elevated sCD14. Interestingly, 100% of patients who exceeded plasma levels of 8 microg/mL of sCD14 on day 1 after injury developed infections. Therefore, early high expressers of sCD14 may be at higher risk for infectious complications after trauma.

Inline detection of Chrome degradation on binary 193nm photomasks

NASA Astrophysics Data System (ADS)

Dufaye, Félix; Sippel, Astrid; Wylie, Mark; García-Berríos, Edgardo; Crawford, Charles; Hess, Carl; Sartelli, Luca; Pogliani, Carlo; Miyashita, Hiroyuki; Gough, Stuart; Sundermann, Frank; Brochard, Christophe

2013-09-01

193nm binary photomasks are still used in the semiconductor industry for the lithography of some critical layers for the nodes 90nm and 65nm, with high volumes and over long periods. However, these 193nm binary photomasks can be impacted by a phenomenon of chrome oxidation leading to critical dimensions uniformity (CDU) degradation with a pronounced radial signature. If not detected early enough, this CDU degradation may cause defectivity issues and lower yield on wafers. Fortunately, a standard cleaning and repellicle service at the mask shop has been demonstrated as efficient to remove the grown materials and get the photomask CD back on target.Some detection methods have been already described in literature, such as wafer CD intrafield monitoring (ACLV), giving reliable results but also consuming additional SEM time with less precision than direct photomask measurement. In this paper, we propose another approach, by monitoring the CDU directly on the photomask, concurrently with defect inspection for regular requalification to production for wafer fabs. For this study, we focused on a Metal layer in a 90nm technology node. Wafers have been exposed with production conditions and then measured by SEM-CD. Afterwards, this photomask has been measured with a SEM-CD in mask shop and also inspected on a KLA-Tencor X5.2 inspection system, with pixels 125 and 90nm, to evaluate the Intensity based Critical Dimension Uniformity (iCDU) option. iCDU was firstly developed to provide feed-forward CDU maps for scanner intrafield corrections, from arrayed dense structures on memory photomasks. Due to layout complexity and differing feature types, CDU monitoring on logic photomasks used to pose unique challenges.The selection of suitable feature types for CDU monitoring on logic photomasks is no longer an issue, since the transmitted intensity map gives all the needed information, as shown in this paper. In this study, the photomask was heavily degraded after more than 18,000 300mm wafers exposed and the cleaning brought it back almost to its original state after manufacture. Wafer CD, photomask CD and iCDU results can be compared, before and after a standard mask shop cleaning. Measurement points have be chosen in logic areas and SRAM areas, so that their respective behaviours can be studied separately. Transmitted maps before and after cleaning were analysed in terms of CD shift and CDU degradation. The delta map shows a nice correlation with photomask CD shift. iCDU demonstrated the capability to detect a reliable CD range degradation of 5nm on photomask by a comparison between a reference inspection and the current inspection. Die to die inspection mode provides also valuable data, highlighting the degraded chrome sidewalls, more in the photomask centre than on the edges. Ultimately, these results would enable to trigger the preventive cleanings rather than on predefined thresholds. The expected gains for wafer fabs are cost savings (adapted cleanings frequency), increased photomask availability for production, longer photomask lifetime, no additional SEM time neither for photomask nor on wafer.

Local connected fractal dimension analysis in gill of fish experimentally exposed to toxicants.

PubMed

Manera, Maurizio; Giari, Luisa; De Pasquale, Joseph A; Sayyaf Dezfuli, Bahram

2016-06-01

An operator-neutral method was implemented to objectively assess European seabass, Dicentrarchus labrax (Linnaeus, 1758) gill pathology after experimental exposure to cadmium (Cd) and terbuthylazine (TBA) for 24 and 48h. An algorithm-derived local connected fractal dimension (LCFD) frequency measure was used in this comparative analysis. Canonical variates (CVA) and linear discriminant analysis (LDA) were used to evaluate the discrimination power of the method among exposure classes (unexposed, Cd exposed, TBA exposed). Misclassification, sensitivity and specificity, both with original and cross-validated cases, were determined. LCFDs frequencies enhanced the differences among classes which were visually selected after their means, respective variances and the differences between Cd and TBA exposed means, with respect to unexposed mean, were analyzed by scatter plots. Selected frequencies were then scanned by means of LDA, stepwise analysis, and Mahalanobis distance to detect the most discriminative frequencies out of ten originally selected. Discrimination resulted in 91.7% of cross-validated cases correctly classified (22 out of 24 total cases), with sensitivity and specificity, respectively, of 95.5% (1 false negative with respect to 21 really positive cases) and 75% (1 false positive with respect to 3 really negative cases). CVA with convex hull polygons ensured prompt, visually intuitive discrimination among exposure classes and graphically supported the false positive case. The combined use of semithin sections, which enhanced the visual evaluation of the overall lamellar structure; of LCFD analysis, which objectively detected local variation in complexity, without the possible bias connected to human personnel; and of CVA/LDA, could be an objective, sensitive and specific approach to study fish gill lamellar pathology. Furthermore this approach enabled discrimination with sufficient confidence between exposure classes or pathological states and avoided misdiagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Citrus Epicarp-Derived Biochar Reduced Cd Uptake and Ameliorates Oxidative Stress in Young Abelmoschus esculentus (L.) Moench (okra) Under Low Cd Stress.

PubMed

Ogunkunle, Clement O; Varun, Mayank; Ogundele, Iyanuoluwa G; Olorunmaiye, Kehinde S; Paul, Manoj S

2018-06-01

Due to the important role of biochar (BC) in reducing metal-toxicity in plants, this study was aimed at assessing the potential of citrus epicarp-derived BC in ameliorating Cd toxicity in young Abelmoschus esculentus (okra) under low Cd toxicity. Okra was grown in soil amended with BC at four treatment levels for 49 days as follows: control (A), sole 1.4 mg Cd/kg-spiked soil (B), 1.4 mg Cd/kg-spiked soil + 1% BC (C) and 1.4 mg Cd/kg-spiked soil + 3% BC (D). The results showed a dose-dependent reduction in shoot accumulation of Cd due to the BC application. In addition, compared to control and sole Cd-amended soil, BC treatments (both at 1% and 3% w/w) decreased the oxidative stress, and enhanced activities of enzymatic and non-enzymatic antioxidants in the young okra. Generally, the application of BC to the soil was effective in ameliorating the Cd-induced oxidative stress in okra with limited shoot bioaccumulation of Cd.

Biochar and Glomus caledonium Influence Cd Accumulation of Upland Kangkong (Ipomoea aquatica Forsk.) Intercropped with Alfred Stonecrop (Sedum alfredii Hance)

NASA Astrophysics Data System (ADS)

Hu, Junli; Wu, Fuyong; Wu, Shengchun; Lam, Cheung Lung; Lin, Xiangui; Wong, Ming Hung

2014-04-01

Both biochar application and mycorrhizal inoculation have been proposed to improve plant growth and alter bioaccumulation of toxic metals. A greenhouse pot trial was conducted to investigate growth and Cd accumulation of upland kangkong (Ipomoea aquatica Forsk.) intercropped with Alfred stonecrop (Sedum alfredii Hance) in a Cd-contaminated soil inoculated with Glomus caledonium and/or applied with biochar. Compared with the monocultural control, intercropping with stonecrop (IS) decreased kangkong Cd acquisition via rhizosphere competition, and also decreased kangkong yield. Gc inoculation (+M) accelerated growth and Cd acquisition of stonecrop, and hence resulted in further decreases in kangkong Cd acquisition. Regardless of IS and +M, biochar addition (+B) increased kangkong yield via elevating soil available P, and decreased soil Cd phytoavailability and kangkong Cd concentration via increasing soil pH. Compared with the control, the treatment of IS + M + B had a substantially higher kangkong yield (+25.5%) with a lower Cd concentration (-62.7%). Gc generated additive effects on soil alkalinization and Cd stabilization to biochar, causing lower DTPA-extractable (phytoavailable) Cd concentrations and post-harvest transfer risks.

[Anti-mouse CD122 antibody promotes the hematopoietic repopulating capacity of cord blood CD34⁺ cells in NOD/SCID mice].

PubMed

Sheng, Men-Yao; Shi, Hui; Xing, Wen; Wang, Wen-Jun; Si, Xiao-Hui; Bai, Jie; Yuan, Wei-Ping; Zhou, Yuan; Yang, Feng-Chun

2014-12-01

The study was aimed to investigate the effect of anti-mouse CD122 antibody on the hematopoietic repopulating capacity of cord blood CD34⁺ cells in a humanized murine model-non obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. After sublethal irradiation with γ-ray, NOD/SCID mice were intraperitoneally injected with 200 µg mouse isotype control antibody or anti-mouse CD122 antibody. Human cord blood CD34⁺ cells or phosphate-buffered saline (PBS) were injected via the tail vein at 6-8 hours later. Cohort of the mice injected with anti-mice CD122 antibody or control antibody alone were sacrificed at different time point (at week 2, 3, and 4 weeks) after the injection, and the percentage of NK cells in the peripheral blood was analyzed by flow cytometry. To evaluate the effect of anti-mouse CD122 antibody on the repopulating capacity of cord blood CD34⁺ cells in the recipient mice, phenotype analysis was performed in the bone marrow at 6 and 8 weeks after the transplantation. The results showed that the proportion of NK cells in the peripheral blood were (4.6 ± 0.6)% and (5.7 ± 1.7)% at week 2 and 3 after anti-CD122 antibody injection respectively,which decreased by 60%, compared with the mice injected with isotype control antibody. After 6 and 8 weeks of cord blood CD34⁺ cell transplantation,the percentage of human CD45⁺ in the bone marrow of the recipient mice treated with anti-mice CD122 antibody was (63.0 ± 12.2)% and (53.2 ± 16.3)%,respectively,which were dramatically higher than that in the mice treated with isotype control antibody (7.7 ± 3.6)% and (6.1 ± 2.4)%. Moreover,at 8 weeks after transplantation,human CD34⁺ cells appeared significantly in the recipients treated with anti-CD122 antibody. It is concluded that the anti-mouse CD122 antibody enhances the hematopoietic repopulating capacity of cord blood CD34⁺ cells in the NOD/SCID mice through decreasing the proportion of NK cells.

Long noncoding RNA derived from CD244 signaling epigenetically controls CD8+ T-cell immune responses in tuberculosis infection

PubMed Central

Wang, Yang; Zhong, Huiling; Xie, Xiaodan; Chen, Crystal Y.; Huang, Dan; Shen, Ling; Zhang, Hui; Chen, Zheng W.; Zeng, Gucheng

2015-01-01

Molecular mechanisms for T-cell immune responses modulated by T cell-inhibitory molecules during tuberculosis (TB) infection remain unclear. Here, we show that active human TB infection up-regulates CD244 and CD244 signaling-associated molecules in CD8+ T cells and that blockade of CD244 signaling enhances production of IFN-γ and TNF-α. CD244 expression/signaling in TB correlates with high levels of a long noncoding RNA (lncRNA)-BC050410 [named as lncRNA-AS-GSTT1(1-72) or lncRNA-CD244] in the CD244+CD8+ T-cell subpopulation. CD244 signaling drives lncRNA-CD244 expression via sustaining a permissive chromatin state in the lncRNA-CD244 locus. By recruiting polycomb protein enhancer of zeste homolog 2 (EZH2) to infg/tnfa promoters, lncRNA-CD244 mediates H3K27 trimethylation at infg/tnfa loci toward repressive chromatin states and inhibits IFN-γ/TNF-α expression in CD8+ T cells. Such inhibition can be reversed by knock down of lncRNA-CD244. Interestingly, adoptive transfer of lncRNA-CD244–depressed CD8+ T cells to Mycobacterium tuberculosis (MTB)-infected mice reduced MTB infection and TB pathology compared with lncRNA-CD244–expressed controls. Thus, this work uncovers previously unidentified mechanisms in which T cell-inhibitory signaling and lncRNAs regulate T-cell responses and host defense against TB infection. PMID:26150504

Life events and escape in conversion disorder.

PubMed

Nicholson, T R; Aybek, S; Craig, T; Harris, T; Wojcik, W; David, A S; Kanaan, R A

2016-09-01

Psychological models of conversion disorder (CD) traditionally assume that psychosocial stressors are identifiable around symptom onset. In the face of limited supportive evidence such models are being challenged. Forty-three motor CD patients, 28 depression patients and 28 healthy controls were assessed using the Life Events and Difficulties Schedule in the year before symptom onset. A novel 'escape' rating for events was developed to test the Freudian theory that physical symptoms of CD could provide escape from stressors, a form of 'secondary gain'. CD patients had significantly more severe life events and 'escape' events than controls. In the month before symptom onset at least one severe event was identified in 56% of CD patients - significantly more than 21% of depression patients [odds ratio (OR) 4.63, 95% confidence interval (CI) 1.56-13.70] and healthy controls (OR 5.81, 95% CI 1.86-18.2). In the same time period 53% of CD patients had at least one 'high escape' event - again significantly higher than 14% in depression patients (OR 6.90, 95% CI 2.05-23.6) and 0% in healthy controls. Previous sexual abuse was more commonly reported in CD than controls, and in one third of female patients was contextually relevant to life events at symptom onset. The majority (88%) of life events of potential aetiological relevance were not identified by routine clinical assessments. Nine per cent of CD patients had no identifiable severe life events. Evidence was found supporting the psychological model of CD, the Freudian notion of escape and the potential aetiological relevance of childhood traumas in some patients. Uncovering stressors of potential aetiological relevance requires thorough psychosocial evaluation.

64nm pitch metal1 double patterning metrology: CD and OVL control by SEMCD, image based overlay and diffraction based overlay

NASA Astrophysics Data System (ADS)

Ducoté, Julien; Dettoni, Florent; Bouyssou, Régis; Le-Gratiet, Bertrand; Carau, Damien; Dezauzier, Christophe

2015-03-01

Patterning process control of advanced nodes has required major changes over the last few years. Process control needs of critical patterning levels since 28nm technology node is extremely aggressive showing that metrology accuracy/sensitivity must be finely tuned. The introduction of pitch splitting (Litho-Etch-Litho-Etch) at 14FDSOInm node requires the development of specific metrologies to adopt advanced process control (for CD, overlay and focus corrections). The pitch splitting process leads to final line CD uniformities that are a combination of the CD uniformities of the two exposures, while the space CD uniformities are depending on both CD and OVL variability. In this paper, investigations of CD and OVL process control of 64nm minimum pitch at Metal1 level of 14FDSOI technology, within the double patterning process flow (Litho, hard mask etch, line etch) are presented. Various measurements with SEMCD tools (Hitachi), and overlay tools (KT for Image Based Overlay - IBO, and ASML for Diffraction Based Overlay - DBO) are compared. Metrology targets are embedded within a block instanced several times within the field to perform intra-field process variations characterizations. Specific SEMCD targets were designed for independent measurement of both line CD (A and B) and space CD (A to B and B to A) for each exposure within a single measurement during the DP flow. Based on those measurements correlation between overlay determined with SEMCD and with standard overlay tools can be evaluated. Such correlation at different steps through the DP flow is investigated regarding the metrology type. Process correction models are evaluated with respect to the measurement type and the intra-field sampling.

Changes in Vitamin D and PTH Metabolism in Incident Pediatric Crohn Disease

PubMed Central

Prosnitz, Aaron R.; Leonard, Mary B.; Shults, Justine; Zemel, Babette S.; Hollis, Bruce W.; Denson, Lee A.; Baldassano, Robert N.; Cohen, Aaron B.; Thayu, Meena

2015-01-01

Background and Aims Prior studies of vitamin D metabolism in Crohn disease (CD) did not include controls or examine changes following diagnosis. This study examined associations among 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D] and parathyroid hormone (PTH) levels in incident pediatric CD, compared with controls, and following diagnosis. Methods Serum vitamin D and PTH were measured at diagnosis (n = 78), 6, 12, and a median of 43 months (n = 52) later in CD participants, and once in 221 controls. Multivariate regression was used to examine baseline associations, and quasi-least squares regression to assess subsequent changes. Results At diagnosis, 42% of CD participants were 25(OH)D deficient (<20 ng/mL). The odds ratio for deficiency was 2.1 (95% CI 1.1, 3.9; p<0.05) vs. controls, adjusted for age, race, and season. 1,25(OH)2D was lower in CD vs. controls (p<0.05), adjusted for 25(OH)D, tumor necrosis factor–α (TNF-α) and PTH. TNF-α was associated with lower 1,25(OH)2D (p<0.05), and the positive association between PTH and 1,25(OH)2D in controls was absent in CD (interaction p=0.02). Among participants with 25(OH)D <30 ng/mL, CD was associated with lower PTH (p<0.05) vs. controls. Following diagnosis, 25(OH)D and 1,25(OH)2D improved (p<0.001). At the final visit, 3% were 25(OH)D deficient, PTH was no longer low relative to 25(OH)D, and 1,25(OH)2D was significantly elevated (p<0.001), compared with controls. Conclusions Incident CD was associated with 25(OH)D and 1,25(OH)2D deficiency and a relative hypoparathyroidism that resolved following diagnosis. Inflammatory cytokine suppression of PTH and renal 1-α-hyroxylase may contribute to these alterations. PMID:22488969

Distribution of intrahepatic T, NK and CD3(+)CD56(+)NKT cells alters after liver transplantation: Shift from innate to adaptive immunity?

PubMed

Werner, Jens M; Lang, Corinna; Scherer, Marcus N; Farkas, Stefan A; Geissler, Edward K; Schlitt, Hans J; Hornung, Matthias

2011-07-01

The liver is an immunological organ containing a large number of T, NK and NKT cells, but little is known about intrahepatic immunity after LTx. Here, we investigated whether the distribution of T, NK and CD3(+)CD56(+)NKT cells is altered in transplanted livers under different circumstances. Core biopsies of transplanted livers were stained with antibodies against CD3 and CD56. Several cell populations including T (CD3(+)CD56(-)), NK (CD3(-)CD56(+)) and NKT cells (CD3(+)CD56(+)) were studied by fluorescence microscopy. Cell numbers were analyzed in relation to the time interval after LTx, immunosuppressive therapy and stage of acute graft rejection (measured with the rejection activity index: RAI) compared to tumor free liver tissue from patients after liver resection due to metastatic disease as control. Recruitment of CD3(+)CD56(+)NKT cells revealed a significant decrease during high RAI scores in comparison to low and middle RAI scores (RAI 7-9: 0.03±0.01/HPF vs. RAI 4-6: 0.1±0.005/HPF). CD3(+)CD56(+)NKT cells were also lower during immunosuppressive therapy with tacrolimus (0.03±0.01/HPF) than with cyclosporine (0.1±0.003/HPF), cyclosporine/MMF (0.1±0.003/HPF) or sirolimus (0.1±0.01/HPF) treatment. Intrahepatic T cell numbers increased significantly 50days after LTx compared to control liver tissue (4.5±0.2/HPF vs. 1.9±0.1/HPF). In contrast, NK cells (0.3±0.004/HPF) were significantly fewer in all biopsies after LTx compared to the control (0.7±0.04/HPF). These data indicate significant alterations in the hepatic recruitment of T, NK and CD3(+)CD56(+)NKT cells after LTx. The increase in T cells and the decrease in NK and CD3(+)CD56(+)NKT cells suggest a shift from innate to adaptive hepatic immunity in the liver graft. Copyright © 2011 Elsevier B.V. All rights reserved.

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

Wohlgemuth, J.; Bokria, J.; Gu, X.

Polymeric encapsulation materials may a change size when processed at typical module lamination temperatures. The relief of residual strain, trapped during the manufacture of encapsulation sheet, can affect module performance and reliability. For example, displaced cells and interconnects threaten: cell fracture; broken interconnects (open circuits and ground faults); delamination at interfaces; and void formation. A standardized test for the characterization of change in linear dimensions of encapsulation sheet has been developed and verified. The IEC 62788-1-5 standard quantifies the maximum change in linear dimensions that may occur to allow for process control of size change. Developments incorporated into the Committeemore » Draft (CD) of the standard as well as the assessment of the repeatability and reproducibility of the test method are described here. No pass/fail criteria are given in the standard, rather a repeatable protocol to quantify the change in dimension is provided to aid those working with encapsulation. The round-robin experiment described here identified that the repeatability and reproducibility of measurements is on the order of 1%. Recent refinements to the test procedure to improve repeatability and reproducibility include: the use of a convection oven to improve the thermal equilibration time constant and its uniformity; well-defined measurement locations reduce the effects of sampling size -and location- relative to the specimen edges; a standardized sand substrate may be readily obtained to reduce friction that would otherwise complicate the results; specimen sampling is defined, so that material is examined at known sites across the width and length of rolls; and encapsulation should be examined at the manufacturer’s recommended processing temperature, except when a cross-linking reaction may limit the size change. EVA, for example, should be examined 100 °C, between its melt transition (occurring up to 80 °C) and the onset of cross-linking (often at 100 °C).« less

No association between gluten sensitivity and amyotrophic lateral sclerosis.

PubMed

Visser, Anne E; Pazoki, Raha; Pulit, Sara L; van Rheenen, Wouter; Raaphorst, Joost; van der Kooi, Anneke J; Ricaño-Ponce, Isis; Wijmenga, Cisca; Otten, Henny G; Veldink, Jan H; van den Berg, Leonard H

2017-04-01

To examine evidence for a role of gluten sensitivity (GS) or celiac disease (CD) in ALS etiology, we included participants from a population-based case-control study in The Netherlands between January 2006 and December 2015. We compared levels and seroprevalence of IgA antibodies to tissue transglutaminase 6 (TG6) in 359 ALS patients and 359 controls, and to transglutaminase 2 (TG2) and endomysium (EMA) in 199 ALS patients and 199 controls. Questionnaire data on 1829 ALS patients and 3920 controls were examined for CD or gluten-free diets (GFD). Genetic correlation and HLA allele frequencies were analyzed using two genome-wide association studies: one on ALS (12,577 cases, 23,475 controls), and one on CD (4533 cases, 10,750 controls). We found one patient with TG6, TG2 and EMA antibodies who had typical ALS and no symptoms of GS. TG6 antibody concentrations and positivity, CD prevalence and adherence to a GFD were similar in patients and controls (p > 0.66) and in these patients disease progression was compatible with typical ALS. CD and ALS were not found to be genetically correlated (p > 0.37). CD-associated HLA allele frequencies were similar in patients and controls (p > 0.28). In conclusion, we found no serological evidence for involvement of gluten-related antibodies in ALS etiology nor did we observe an association between CD and ALS in medical history or genetic data, indicating that there is no evidence in our data for an association between the two diseases. Hence, a role for a GFD in the ALS treatment seems unlikely.

CD8 T cells and Mycobacterium tuberculosis infection

PubMed Central

Lin, Philana Ling; Flynn, JoAnne L.

2015-01-01

Tuberculosis is primarily a respiratory disease that is caused by Mycobacterium tuberculosis. M. tuberculosis can persist and replicate in macrophages in vivo, usually in organized cellular structures called granulomas. There is substantial evidence for the importance of CD4 T cells in control of tuberculosis, but the evidence for a requirement for CD8 T cells in this infection has not been proven in humans. However, animal model data support a non-redundant role for CD8 T cells in control of M. tuberculosis infection, and in humans, infection with this pathogen leads to generation of specific CD8 T cell responses. These responses include classical (MHC Class I restricted) and non-classical CD8 T cells. Here, we discuss the potential roles of CD8 T cells in defense against tuberculosis, and our current understanding of the wide range of CD8 T cell types seen in M. tuberculosis infection. PMID:25917388

Understanding the biology of ex vivo-expanded CD8 T cells for adoptive cell therapy: role of CD62L.

PubMed

Díaz-Montero, C Marcela; Zidan, Abdel-Aziz; Pallin, Maria F; Anagnostopoulos, Vasileios; Salem, Mohamed L; Wieder, Eric; Komanduri, Krishna; Montero, Alberto J; Lichtenheld, Mathias G

2013-12-01

CD62L governs the circulation of CD8(+) T cells between lymph nodes and peripheral tissues, whereby the expression of CD62L by CD8(+) T cells promotes their recirculation through lymph nodes. As such, CD62L participates in the fate of adoptively transferred CD8(+) T cells and may control their effectiveness for cancer immunotherapy, including settings in which host preconditioning results in the acute lymphopenia-induced proliferation of the transferred cells. Indeed, previous studies correlated CD62L expression by donor CD8(+) cells with the success rate of adoptive cell therapy (ACT). Here, we analyzed the functions and fate of ex vivo-activated, tumor-specific CD62L(-/-) CD8(+) T cells in a mouse melanoma model for ACT. Unexpectedly, we observed that CD62L(-/-) CD8(+) T cells were functionally indistinguishable from CD62L(+/+) CD8(+) T cells, i.e., both greatly expanded in cyclophosphamide preconditioned animals, controlled subcutaneously and hematogenously spreading tumors, and generated anti-tumor-specific CD8(+) T cell memory. Moreover, even in hosts with rudimentary secondary lymphoid organs (LT(-/-) animals), CD8(+) T cells with and without CD62L expanded equivalently to those adoptively transferred into wild-type animals. These results put into question the utility of CD62L as a predictive biomarker for the efficacy of ex vivo-expanded T cells after ACT in lymphopenic conditions and also offer new insights into the homing, engraftment, and memory generation of adoptively transferred ex vivo-activated CD8(+) T cells.

Long-term protection against SHIV89.6P replication in HIV-1 Tat vaccinated cynomolgus monkeys.

PubMed

Maggiorella, Maria Teresa; Baroncelli, Silvia; Michelini, Zuleika; Fanales-Belasio, Emanuele; Moretti, Sonia; Sernicola, Leonardo; Cara, Andrea; Negri, Donatella R M; Buttò, Stefano; Fiorelli, Valeria; Tripiciano, Antonella; Scoglio, Arianna; Caputo, Antonella; Borsetti, Alessandra; Ridolfi, Barbara; Bona, Roberta; ten Haaft, Peter; Macchia, Iole; Leone, Pasqualina; Pavone-Cossut, Maria Rosaria; Nappi, Filomena; Ciccozzi, Massimo; Heeney, Jonathan; Titti, Fausto; Cafaro, Aurelio; Ensoli, Barbara

2004-09-03

Vaccination with a biologically active Tat protein or tat DNA contained infection with the highly pathogenic SHIV89.6P virus, preventing CD4 T-cell decline and disease onset. Here we show that protection was prolonged, since neither CD4 T-cell decline nor active virus replication was observed in all vaccinated animals that controlled virus replication up to week 104 after the challenge. In contrast, virus persisted and replicated in peripheral blood mononuclear cells and lymph nodes of infected animals, two of which died. Tat-specific antibody, CD4 and CD8 T-cell responses were high and stable only in the animals controlling the infection. In contrast, Gag-specific antibody production and CD4 and CD8 T-cell responses were consistently and persistently positive only in the monkeys that did not control primary virus replication. These results indicate that vaccination with Tat protein or DNA induced long-term memory Tat-specific immune responses and controlled primary infection at its early stages allowing a long-term containment of virus replication and spread in blood and tissues.

Toxicity evaluation of hydrophilic CdTe quantum dots and CdTe@SiO2 nanoparticles in mice.

PubMed

Sadaf, Asma; Zeshan, Basit; Wang, Zhuyuan; Zhang, Ruohu; Xu, Shuhong; Wang, Chunlei; Cui, Yiping

2012-11-01

Quantum dots have drawn tremendous attention in the field of in vitro and small animal in vivo fluorescence imaging in the last decade. However, concerns over the cytotoxicity of their heavy metal constituents have limited their use in clinical applications. Here, we report our comparative studies on the toxicities of quantum dots (QDs) and silica coated CdTe nanoparticles (NPs) to mice after intravenous injection. The blood cells analysis showed significant increased level of white blood cells (WBCs) in groups treated with CdTe QDs as compared to the control while red blood cells (RBCs) and platelet counts were normal in treated as well as control groups. The concentration of biochemical markers of hepatic damage, alanine amino transferase (ALT) and aspartate aminotransferase (AST) were in the normal range in all the groups. However, renal function analyses of mice showed significantly increased in the concentration of blood urea nitrogen (BUN) and creatinine (CREA) in mice treated with CdTe QDs while remained within normal ranges in both the CdTe@SiO2 NPs and control group. The results of histopathology showed that the CdTe QDs caused mild nephrotoxicity while other organs were normal and no abnormalities were detected in control and CdTe@SiO2 treated group. These findings suggest that the nephrotoxicity could be minimized by silica coating which would be useful for many biomedical applications.

Foxp3+ T cells inhibit antitumor immune memory modulated by mTOR inhibition.

PubMed

Wang, Yanping; Sparwasser, Tim; Figlin, Robert; Kim, Hyung L

2014-04-15

Inhibition of mTOR signaling enhances antitumor memory lymphocytes. However, pharmacologic mTOR inhibition also enhances regulatory T-cell (Treg) activity. To counter this effect, Treg control was added to mTOR inhibition in preclinical models. Tregs were controlled with CD4-depleting antibodies because CD4 depletion has high translational potential and already has a well-established safety profile in patients. The antitumor activity of the combination therapy was CD8 dependent and controlled growth of syngeneic tumors even when an adoptive immunotherapy was not used. Lymphocytes resulting from the combination therapy could be transferred into naïve mice to inhibit aggressive growth of lung metastases. The combination therapy enhanced CD8 memory formation as determined by memory markers and functional studies of immune recall. Removal of FoxP3-expressing T lymphocytes was the mechanism underlying immunologic memory formation following CD4 depletion. This was confirmed using transgenic DEREG (depletion of regulatory T cells) mice to specifically remove Foxp3(+) T cells. It was further confirmed with reciprocal studies where stimulation of immunologic memory because of CD4 depletion was completely neutralized by adoptively transferring tumor-specific Foxp3(+) T cells. Also contributing to tumor control, Tregs that eventually recovered following CD4 depletion were less immunosuppressive. These results provide a rationale for further study of mTOR inhibition and CD4 depletion in patients. ©2014 AACR.

Elevated numbers of CD163+ macrophages in hearts of simian immunodeficiency virus-infected monkeys correlate with cardiac pathology and fibrosis.

PubMed

Walker, Joshua A; Sulciner, Megan L; Nowicki, Katherine D; Miller, Andrew D; Burdo, Tricia H; Williams, Kenneth C

2014-07-01

The role of macrophage activation, traffic, and accumulation on cardiac pathology was examined in 23 animals. Seventeen animals were simian immunodeficiency virus (SIV) infected, 12 were CD8 lymphocyte depleted, and the remaining six were uninfected controls (two CD8 lymphocyte depleted, four nondepleted). None of the uninfected controls had cardiac pathology. One of five (20%) SIV-infected, non-CD8 lymphocyte-depleted animals had minor cardiac pathology with increased numbers of macrophages in ventricular tissue compared to controls. Seven of the 12 (58%) SIV-infected, CD8 lymphocyte-depleted animals had cardiac pathology in ventricular tissues, including macrophage infiltration and myocardial degeneration. The extent of fibrosis (measured as the percentage of collagen per tissue area) was increased 41% in SIV-infected, CD8 lymphocyte-depleted animals with cardiac pathology compared to animals without pathological abnormalities. The number of CD163+ macrophages increased significantly in SIV-infected, CD8 lymphocyte-depleted animals with cardiac pathology compared to ones without pathology (1.66-fold) and controls (5.42-fold). The percent of collagen (percentage of collagen per total tissue area) positively correlated with macrophage numbers in ventricular tissue in SIV-infected animals. There was an increase of BrdU+ monocytes in the heart during late SIV infection, regardless of pathology. These data implicate monocyte/macrophage activation and accumulation in the development of cardiac pathology with SIV infection.

Circulating promyelocytes and low levels of CD16 expression on polymorphonuclear leukocytes accompany early-onset periodontitis.

PubMed Central

Nemoto, E; Nakamura, M; Shoji, S; Horiuchi, H

1997-01-01

Early-onset periodontitis (EOP) is characterized by rapidly progressive alveolar bone loss, chemotactic defects of neutrophils, and significant familial aggregation. We found immature myeloid lineage cells, defined as promyelocytes, in the peripheral blood in patients with EOP. A hematological examination of peripheral blood cells showed normal reference values regarding cell proportions. Flow cytometry revealed significantly lower expression of CD16, a glycosylphosphatidylinositol (GPI)-anchored protein, on peripheral neutrophils in patients compared with those in age- and sex-matched healthy controls, whereas the levels of CD11a and CD11b expression were similar. The chemotactic response of neutrophils was lower toward not only formyl-methionyl-leucyl-phenylalanine but also complement fragment C5a than that of healthy controls. The expression of another GPI-anchored protein, CD14, was equally expressed by controls and patients. Therefore, the low level of CD16 expression was not due to the incomplete synthesis of the GPI anchor. GPI anchors of CD16 on neutrophils from controls and patients were both partially resistant to phosphatidylinositol-specific phospholipase C. The presence of promyelocytes in peripheral blood, low expression of CD16, and low chemotactic response of neutrophils suggest that patients with EOP have an abnormal maturation system in myeloid lineage cells in the bone marrow, which may be associated with the onset and course of EOP. PMID:9284170

Can liming reduce cadmium (Cd) accumulation in rice (Oryza sativa) in slightly acidic soils? A contradictory dynamic equilibrium between Cd uptake capacity of roots and Cd immobilisation in soils.

PubMed

Yang, Yongjie; Chen, Jiangmin; Huang, Qina; Tang, Shaoqing; Wang, Jianlong; Hu, Peisong; Shao, Guosheng

2018-02-01

Cadmium (Cd) accumulation in rice is strongly controlled by liming, but information on the use of liming to control Cd accumulation in rice grown in slightly acidic soils is inconsistent. Here, pot experiments were carried out to investigate the mechanisms of liming on Cd accumulation in two rice varieties focusing on two aspects: available/exchangeable Cd content in soils that were highly responsive to liming, and Cd uptake and transport capacity in the roots of rice in terms of Cd accumulation-relative gene expression. The results showed that soil availability and exchangeable iron, manganese, zinc and Cd contents decreased with increased liming, and that genes related to Cd uptake (OsNramp5 and OsIRT1) were sharply up-regulated in the roots of the two rice varieties. Thus, iron, manganese, zinc and Cd contents in rice plants increased under low liming applications but decreased in response to high liming applications. However, yield and rice quantities were only slightly affected. These results indicated that Cd accumulation in rice grown in slightly acidic soils presents a contradictory dynamic equilibrium between Cd uptake capacity by roots and soil Cd immobilisation in response to liming. The enhanced Cd uptake capacity under low liming dosages increases risks to human health. Copyright © 2017 Elsevier Ltd. All rights reserved.

DNA tetrahedral scaffolds-based platform for the construction of electrochemiluminescence biosensor.

PubMed

Feng, Qiu-Mei; Zhou, Zhen; Li, Mei-Xing; Zhao, Wei; Xu, Jing-Juan; Chen, Hong-Yuan

2017-04-15

Proximal metallic nanoparticles (NPs) could quench the electrochemiluminescence (ECL) emission of semiconductor quantum dots (QDs) due to Förster energy transfer (FRET), but at a certain distance, the coupling of light-emission with surface plasmon resonance (SPR) result in enhanced ECL. Thus, the modification strategies and distances control between QDs and metallic NPs are critical for the ECL intensity of QDs. In this strategy, a SPR enhanced ECL sensor based on DNA tetrahedral scaffolds modified platform was reported for the detection of telomerase activity. Due to the rigid three-dimensional structure, DNA tetrahedral scaffolds grafting on the electrode surface could accurately modulate the distance between CdS QDs and luminol labelled gold nanoparticles (L-Au NPs), meanwhile provide an enhanced spatial dimension and accessibility for the assembly of multiple L-Au NPs. The ECL intensities of both CdS QDs (-1.25V vs. SCE) and luminol (+0.33V vs. SCE) gradually increased along with the formation of multiple L-Au NPs at the vertex of DNA tetrahedral scaffolds induced by telomerase, bringing in a dual-potential ECL analysis. The proposed method showed high sensitivity for the identification of telomerase and was successfully applied for the differentiation of cancer cells from normal cells. This work suggests that DNA tetrahedral scaffolds could serve as an excellent choice for the construction of SPR-ECL system. Copyright © 2016 Elsevier B.V. All rights reserved.

Growth Associated Protein 43 (GAP-43) as a Novel Target for the Diagnosis, Treatment and Prevention of Epileptogenesis.

PubMed

Nemes, Ashley D; Ayasoufi, Katayoun; Ying, Zhong; Zhou, Qi-Gang; Suh, Hoonkyo; Najm, Imad M

2017-12-18

We previously showed increased growth associated protein 43 (GAP-43) expression in brain samples resected from patients with cortical dysplasia (CD), which was correlated with duration of epilepsy. Here, we used a rat model of CD to examine the regulation of GAP-43 in the brain and serum over the course of epileptogenesis. Baseline GAP-43 expression was higher in CD animals compared to control non-CD rats. An acute seizure increased GAP-43 expression in both CD and control rats. However, GAP-43 expression decreased by day 15 post-seizure in control rats, which did not develop spontaneous seizures. In contrast, GAP-43 remained up-regulated in CD rats, and over 50% developed chronic epilepsy with increased GAP-43 levels in their serum. GAP-43 protein was primarily located in excitatory neurons, suggesting its functional significance in epileptogenesis. Inhibition of GAP-43 expression by shRNA significantly reduced seizure duration and severity in CD rats after acute seizures with subsequent reduction in interictal spiking. Serum GAP-43 levels were significantly higher in CD rats that developed spontaneous seizures. Together, these results suggest GAP-43 as a key factor promoting epileptogenesis, a possible therapeutic target for treatment of progressive epilepsy and a potential biomarker for epilepsy progression in CD.

Changes of regulatory T and B cells in patients with papillary thyroid carcinoma after 131I radioablation: a preliminary study.

PubMed

Jiang, Lei; Zhan, Yanxia; Gu, Yusen; Ye, Yi; Cheng, Yunfeng; Shi, Hongcheng

2013-01-01

Introduction. Lymphocytic infiltration and specific lymphocytes subsets may play important roles in papillary thyroid carcinoma (PTC) progression and prognosis. In this study, we try to understand the influence of (131)I radioablation on the important lymphocytes subtypes of regulatory T and B cells (Tregs and Bregs). Methods. Peripheral blood mononuclear cells from 30 PTC patients before and after (131)I therapy, and 20 healthy donors were collected. The expression of Tregs (CD4(+)CD25(+)CD127(-/low)) and B cell (CD5(+)CD19(+)) and production and secretion of interleukin 10 (IL-10) were analyzed by FACS and ELISA assay, respectively. Results. For Tregs percentage in peripheral blood lymphocytes, there was no difference between pretreatment and control and between posttreatment and control. Compared with pretherapy, increased Tregs infiltration was noted in posttherapy (P < 0.05). Although no difference was between pretreatment and control, compared with these two groups, decreased CD19(+) and CD5(+)CD19(+) B cell percentage in posttreatment was observed (P < 0.05). Among these groups, no significant difference was displayed in intracellular IL-10 production and extracellular IL-10 secretion. Conclusions. (131)I Radioablation increased Tregs and decreased CD19(+) and CD5(+)CD19(+) B cells percentage after treatment. However, it has no effect on IL-10 and lymphocytes in peripheral blood. Therefore, longer follow-up of Tregs and Bregs should be further investigated.

Cd immobilization and reduced tissue Cd accumulation of rice (Oryza sativa wuyun-23) in the presence of heavy metal-resistant bacteria.

PubMed

Li, Ya; Pang, Hai-Dong; He, Lin-Yan; Wang, Qi; Sheng, Xia-Fang

2017-04-01

Two metal-resistant Bacillus megaterium H3 and Neorhizobium huautlense T1-17 were investigated for their immobilization of Cd in solution and tissue Cd accumulation of rice (Oryza sativa wuyun-23) in the Cd-contaminated soil. Strains H3 and T1-17 decreased 79-96% of water-soluble Cd in solution and increased grain biomass in the high Cd-contaminated soil. Inoculation with H3 and T1-17 significantly decreased the root (ranging from 25% to 58%), above-ground tissue (ranging from 13% to 34%), and polished rice (ranging from 45% to 72%) Cd contents as well as Cd bioconcentration factor of the rice compared to the controls. Furthermore, H3 and T1-17 significantly reduced the exchangeable Cd content of the rhizosphere soils compared with the controls. Notably, strain T1-17 had significantly higher ability to reduce Cd bioconcentration factor and polished rice Cd uptake than strain H3. The results demonstrated that H3 and T1-17 decreased the tissue (especially polished rice) Cd uptake by decreasing Cd availability in soil and Cd bioconcentration factor and the effect on the reduced polished rice Cd uptake was dependent on the strains. The results may provide an effective synergistic bioremediation of Cd-contaminated soils in the bacteria and rice plants and bacterial-assisted safe production of rice in Cd-contaminated soils. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Soluble CD30 serum levels before and after treatment with alpha-interferon in patients with chronic hepatitis C.

PubMed

Di Cesare, Enrico; Spadaro, Aldo; Ajello, Antonino; Ferraù, Oscar; Alessi, Nunziata; Luigiano, Carmelo; Melluso, Rossana; Freni, Maria A

2005-01-01

It has been suggested that soluble CD30 (sCD30) serum levels in chronic hepatitis C are correlated with the activity of the disease and with the outcome of interferon (IFN) treatment. In this study, sCD30 serum levels in 25 patients with chronic hepatitis C, before and after treatment with IFN-2alpha, were measured. A total of 20 healthy subjects were used as controls. High sCD30 levels in serum were found in 36% of patients and in 5% of controls. In patients with sCD30 levels above or within the normal range, no significant differences in age, gender, serum transaminases and histology activity index were found. In relation to IFN treatment, only responder patients had serum sCD30 higher than controls, although the difference between responders and non-responders was not significant. No changes from baseline values were observed after treatment. Although high, sCD30 serum levels in chronic hepatitis C are not correlated with the disease activity, are not affected by IFN treatment and are not predictors of response to IFN treatment.

Ameliorants to immobilize Cd in rice paddy soils contaminated by abandoned metal mines in Korea.

PubMed

Ok, Yong Sik; Kim, Sung-Chul; Kim, Dong-Kuk; Skousen, Jeffrey G; Lee, Jin-Soo; Cheong, Young-Wook; Kim, Su-Jung; Yang, Jae E

2011-01-01

The cadmium (Cd) content of rice grain grown in metal-contaminated paddy soils near abandoned metal mines in South Korea was found to exceed safety guidelines (0.2 mg Cd kg⁻¹) set by the Korea Food and Drug Administration (KFDA). However, current remediation technologies for heavy metal-contaminated soils have limited application with respect to rice paddy soils. Laboratory and greenhouse experiments were conducted to assess the effects of amending contaminated rice paddy soils with zerovalent iron (ZVI), lime, humus, compost, and combinations of these compounds to immobilize Cd and inhibit Cd translocation to rice grain. Sequential extraction analysis revealed that treatment with the ameliorants induced a 50-90% decrease in the bioavailable Cd fractions when compared to the untreated control soil. When compared to the control, Cd uptake by rice was decreased in response to treatment with ZVI + humus (69%), lime (65%), ZVI + compost (61%), compost (46%), ZVI (42%), and humus (14%). In addition, ameliorants did not influence rice yield when compared to that of the control. Overall, the results of this study indicated that remediation technologies using ameliorants effectively reduce Cd bioavailability and uptake in contaminated rice paddy soils.

Expression of an Arabidopsis Ca2+/H+ antiporter CAX1 variant in petunia enhances cadmium tolerance and accumulation.

PubMed

Wu, Qingyu; Shigaki, Toshiro; Williams, Kimberly A; Han, Jeung-Sul; Kim, Chang Kil; Hirschi, Kendal D; Park, Sunghun

2011-01-15

Phytoremediation is a cost-effective and minimally invasive technology to cleanse soils contaminated with heavy metals. However, few plant species are suitable for phytoremediation of metals such as cadmium (Cd). Genetic engineering offers a powerful tool to generate plants that can hyperaccumulate Cd. An Arabidopsis CAX1 mutant (CAXcd), which confers enhanced Cd transport in yeast, was ectopically expressed in petunia to evaluate whether the CAXcd expression would enhance Cd tolerance and accumulation in planta. The CAXcd-expressing petunia plants showed significantly greater Cd tolerance and accumulation than the controls. After being treated with either 50 or 100μM CdCl(2) for 6 weeks, the CAXcd-expressing plants showed more vigorous growth compared with controls, and the transgenic plants accumulated significantly more Cd (up to 2.5-fold) than controls. Moreover, the accumulation of Cd did not affect the development and morphology of the CAXcd-expressing petunia plants until the flowering and ultimately the maturing of seeds. Therefore, petunia has the potential to serve as a model species for developing herbaceous, ornamental plants for phytoremediation. Copyright © 2010 Elsevier GmbH. All rights reserved.

Influence of Cadmium on Water Relations, Stomatal Resistance, and Abscisic Acid Content in Expanding Bean Leaves 1

PubMed Central

Poschenrieder, Charlotte; Gunsé, Benet; Barceló, Juan

1989-01-01

Ten day old bush bean plants (Phaseolus vulgaris L. cv Contender) were used to analyze the effects of 3 micromolar Cd on the time courses of expansion growth, dry weight, leaf water relations, stomatal resistance, and abscisic acid (ABA) levels in roots and leaves. Control and Cd-treated plants were grown for 144 hours in nutrient solution. Samples were taken at 24 hour intervals. At the 96 and 144 hour harvests, additional measurements were made on excised leaves which were allowed to dry for 2 hours. From the 48 hour harvest, Cd-treated plants showed lower leaf relative water contents and higher stomatal resistances than controls. At the same time, root and leaf expansion growth, but not dry weight, was significantly reduced. The turgor potentials of leaves from Cd-treated plants were nonsignificantly higher than those of control leaves. A significant increase (almost 400%) of the leaf ABA concentration was detected after 120 hours exposure to Cd. But Cd was found to inhibit ABA accumulation during drying of excised leaves. It is concluded that Cd-induced decrease of expansion growth is not due to turgor decrease. The possible mechanisms of Cd-induced stomatal closure are discussed. PMID:16666937

CD8+ lymphocytes control viral replication in SIVmac239-infected rhesus macaques without decreasing the lifespan of productively infected cells.

PubMed

Klatt, Nichole R; Shudo, Emi; Ortiz, Alex M; Engram, Jessica C; Paiardini, Mirko; Lawson, Benton; Miller, Michael D; Else, James; Pandrea, Ivona; Estes, Jacob D; Apetrei, Cristian; Schmitz, Joern E; Ribeiro, Ruy M; Perelson, Alan S; Silvestri, Guido

2010-01-29

While CD8+ T cells are clearly important in controlling virus replication during HIV and SIV infections, the mechanisms underlying this antiviral effect remain poorly understood. In this study, we assessed the in vivo effect of CD8+ lymphocyte depletion on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques. We treated two groups of animals that were either CD8+ lymphocyte-depleted or controls with antiretroviral therapy, and used mathematical modeling to assess the lifespan of infected cells either in the presence or absence of CD8+ lymphocytes. We found that, in both early (day 57 post-SIV) and late (day 177 post-SIV) chronic SIV infection, depletion of CD8+ lymphocytes did not result in a measurable increase in the lifespan of either short- or long-lived productively infected cells in vivo. This result indicates that the presence of CD8+ lymphocytes does not result in a noticeably shorter lifespan of productively SIV-infected cells, and thus that direct cell killing is unlikely to be the main mechanism underlying the antiviral effect of CD8+ T cells in SIV-infected macaques with high virus replication.

CD8+ Lymphocytes Control Viral Replication in SIVmac239-Infected Rhesus Macaques without Decreasing the Lifespan of Productively Infected Cells

PubMed Central

Klatt, Nichole R.; Shudo, Emi; Ortiz, Alex M.; Engram, Jessica C.; Paiardini, Mirko; Lawson, Benton; Miller, Michael D.; Else, James; Pandrea, Ivona; Estes, Jacob D.; Apetrei, Cristian; Schmitz, Joern E.; Ribeiro, Ruy M.; Perelson, Alan S.; Silvestri, Guido

2010-01-01

While CD8+ T cells are clearly important in controlling virus replication during HIV and SIV infections, the mechanisms underlying this antiviral effect remain poorly understood. In this study, we assessed the in vivo effect of CD8+ lymphocyte depletion on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques. We treated two groups of animals that were either CD8+ lymphocyte-depleted or controls with antiretroviral therapy, and used mathematical modeling to assess the lifespan of infected cells either in the presence or absence of CD8+ lymphocytes. We found that, in both early (day 57 post-SIV) and late (day 177 post-SIV) chronic SIV infection, depletion of CD8+ lymphocytes did not result in a measurable increase in the lifespan of either short- or long-lived productively infected cells in vivo. This result indicates that the presence of CD8+ lymphocytes does not result in a noticeably shorter lifespan of productively SIV-infected cells, and thus that direct cell killing is unlikely to be the main mechanism underlying the antiviral effect of CD8+ T cells in SIV-infected macaques with high virus replication. PMID:20126441

CD(+)(4)CD(+)(25) Treg cells in thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus patients.

PubMed

Huang, Hongdong; Sun, Weiming; Liang, Yumei; Long, Xi-Dai; Peng, Youming; Liu, Zhihua; Wen, Xiaojun; Jia, Meng

2014-09-01

CD(+)(4)CD(+)(25) Treg cells are of critical importance for maintenance of tolerance. The purpose of the this study was to observe the number of CD(+)(4)CD(+)(25) Treg cells in the patients with thrombotic thrombocytopenic purpura (TTP) associated with systemic lupus erythematosus (SLE), and to study pathogenesis of TTP with SLE. Seven patients with TTP associated with SLE and seven healthy volunteers were studied. The CD(+)(4)CD(+)(25) Treg cells were examined by flow cytometry. Clinical and laboratory data, such as urinary protein, serum creatinine, endothelial markers and immunologic serologics, were obtained from each patient and healthy volunteer. Glomerular injury was assessed by histopathology. Serum IL-2, IL-4, IL-6 and anti-endothelial cell antibody were analyzed by ELISA and anti-ADAMTS13 antibody were detected by Western blotting. CD(+)(4)CD(+)(25) Treg cells significantly decreased in TTP with SLE patients compared with controls (p < 0.05). CD(+)(4)CD(+)(25) Treg cells are negatively correlated with blood urea nitrogen, serum uric acid, supernatant IL-4, and proteinuria, and positively with estimated glomerular filtration rate (eGFR) in TTP with SLE patients. [Formula: see text] Treg cells gradually decreased as the severity of renal histology increased. Serum IL-2, IL-6, supernatant IL-4, anti-endothelial cell antibody, and anti-ADAMTS13 antibody significantly increased in TTP with SLE patients compared to those of the control groups (all p < 0.05). In contrast, serum levels of C3 were significantly decreased in TTP with SLE patients compared to those of the control groups (p < 0.05). CD(+)(4)CD(+)(25) Treg cells are not only lower in TTP with SLE patients, but also are correlated with disease severity in TTP with SLE patients.CD(+)(4)CD(+)(25)Treg cells may play an important role in the pathogenesis of TTP with SLE.

Regulation of adaptive NK cells and CD8 T cells by HLA-C correlates with allogeneic hematopoietic cell transplantation and with CMV reactivation1

PubMed Central

Horowitz, Amir; Guethlein, Lisbeth A.; Nemat-Gorgani, Neda; Norman, Paul J.; Cooley, Sarah; Miller, Jeffrey S.; Parham, Peter

2015-01-01

Mass cytometry was used to investigate the effect of CMV reactivation on lymphocyte reconstitution in hematopoietic cell transplant patients. For eight transplant recipients, four CMV negative and four CMV positive, we studied peripheral blood mononuclear cells (PBMC) obtained six months after unrelated donor hematopoietic cell transplantation (HCT). Forty cell-surface markers, distinguishing all major leukocyte populations in PBMC, were analyzed by mass cytometry. These included 34 NK cell markers. Compared to healthy controls, transplant recipients had higher HLA-C expression on CD56−CD16+ NK cells, B cells, CD33bright myeloid cells and CD4CD8 T cells. The increase in HLA-C expression was greater for CMV-positive HCT recipients than CMV negative recipients. Present in CMV-positive HCT recipients, but not in CMV-negative HCT recipients or controls, is a population of KIR-expressing CD8 T cells not previously described. These CD8 T cells co-express CD56, CD57 and NKG2C. The HCT recipients also have a population of CD57+NKG2A+ NK cells that preferentially express KIR2DL1. An inverse correlation was observed between the frequencies of CD57+NKG2C+ NK cells and CD57+NKG2A+ NK cells. Although CD57+NKG2A+ NK cells are less abundant in CMV-positive recipients, their phenotype is of a more activated cell than the CD57+NKG2A+ NK cells of controls and CMV-negative HCT recipients. These data demonstrate that HCT and CMV reactivation are associated with an increased expression of HLA-C. This could influence NK cell education during lymphocyte reconstitution. The increased inhibitory KIR expression by proliferating CMV-specific CD8 T cells suggests regulatory interactions between HLA-C and KIR might promote GVL effects following transplantation. PMID:26416275

Central memory CD4 T cells are associated with incomplete restoration of the CD4 T cell pool after treatment-induced long-term undetectable HIV viraemia.

PubMed

Rallón, Norma; Sempere-Ortells, José M; Soriano, Vincent; Benito, José M

2013-11-01

It is unclear to what extent T cell reconstitution may be possible in HIV-1-infected individuals on continuous successful highly active antiretroviral therapy (HAART). Herein, we analysed distinct phenotypic markers of immune recovery in patients with undetectable viraemia for 8 years, taking as reference untreated patients and healthy controls. Seventy-two subjects were examined: 28 HIV-1+ patients on successful long-term HAART, 24 HIV-1+ untreated viraemic patients and 20 age-matched healthy controls. Analysis of naive and memory CD4 and CD8 T cells was combined with measurements of activation status (expression of CD38) and with thymic function (expression of CD31). Statistical significance was determined by non-parametric tests. After long-term HAART, the majority of parameters were normalized compared with age-matched control values, including T cell activation and thymic function. However, absolute counts of naive and central memory CD4 T cells remained below normal levels. The only parameters significantly associated with CD4 counts at the end of follow-up were the pre-HAART CD4 count ( β ± SD = 0.54 ± 0.16, P = 0.003) and the level of CD4 central memory cells at the end of follow-up (β ± SD = 1.18 ± 0.23, P < 0.0001). Only patients starting HAART with CD4 counts >350 cells/mm(3) reached a complete normalization of CD4 counts. Even after long-term successful HAART, complete CD4 restoration may be attainable only in patients starting therapy with moderately high CD4 counts, prompting early initiation of antiretroviral therapy. Incomplete CD4 restoration may be associated with a defective restoration of central memory CD4 T cells, a cell subset with a pivotal role in T cell homeostasis.

Alterations in the Immune Cell Composition in Premalignant Breast Tissue that Precede Breast Cancer Development.

PubMed

Degnim, Amy C; Hoskin, Tanya L; Arshad, Muhammad; Frost, Marlene H; Winham, Stacey J; Brahmbhatt, Rushin A; Pena, Alvaro; Carter, Jodi M; Stallings-Mann, Melody L; Murphy, Linda M; Miller, Erin E; Denison, Lori A; Vachon, Celine M; Knutson, Keith L; Radisky, Derek C; Visscher, Daniel W

2017-07-15

Purpose: Little is known about the role of the immune system in the earliest stages of breast carcinogenesis. We studied quantitative differences in immune cell types between breast tissues from normal donors and those from women with benign breast disease (BBD). Experimental Design: A breast tissue matched case-control study was created from donors to the Susan G. Komen for the Cure Tissue Bank (KTB) and from women diagnosed with BBD at Mayo Clinic (Rochester, MN) who either subsequently developed cancer (BBD cases) or remained cancer-free (BBD controls). Serial tissue sections underwent immunostaining and digital quantification of cell number per mm 2 for CD4 + T cells, CD8 + T cells, CD20 + B cells, and CD68 + macrophages and quantification of positive pixel measure for CD11c (dendritic cells). Results: In 94 age-matched triplets, BBD lobules showed greater densities of CD8 + T cells, CD11c + dendritic cells, CD20 + B cells, and CD68 + macrophages compared with KTB normals. Relative to BBD controls, BBD cases had lower CD20 + cell density ( P = 0.04). Nearly 42% of BBD cases had no CD20 + B cells in evaluated lobules compared with 28% of BBD controls ( P = 0.02). The absence of CD20 + cells versus the presence in all lobules showed an adjusted OR of 5.7 (95% confidence interval, 1.4-23.1) for subsequent breast cancer risk. Conclusions: Elevated infiltration of both innate and adaptive immune effectors in BBD tissues suggests an immunogenic microenvironment. The reduced B-cell infiltration in women with later breast cancer suggests a role for B cells in preventing disease progression and as a possible biomarker for breast cancer risk. Clin Cancer Res; 23(14); 3945-52. ©2017 AACR . ©2017 American Association for Cancer Research.

Use of internal control T-cell populations in the flow cytometric evaluation for T-cell neoplasms.

PubMed

Hunt, Alicia M; Shallenberger, Wendy; Ten Eyck, Stephen P; Craig, Fiona E

2016-09-01

Flow cytometry is an important tool for identification of neoplastic T-cells, but immunophenotypic abnormalities are often subtle and must be distinguished from nonneoplastic subsets. Use of internal control (IC) T-cells in the evaluation for T-cell neoplasms was explored, both as a quality measure and as a reference for evaluating abnormal antigen expression. All peripheral blood specimens (3-month period), or those containing abnormal T-cells (29-month period), stained with CD45 V500, CD2 V450, CD3 PE-Cy7, CD7 PE, CD4 Per-CP-Cy5.5, CD8 APC-H7, CD56 APC, CD16&57 FITC, were evaluated. IC T-cells were identified (DIVA, BD Biosciences) and median fluorescence intensity (MFI) recorded. Selected files were merged and reference templates generated (Infinicyt, Cytognos). IC T-cells were present in all specimens, including those with abnormal T-cells, but subsets were less well-represented. IC T-cell CD3 MFI differed between instruments (p = 0.0007) and subsets (p < 0.001), but not specimen categories, and served as a longitudinal process control. Merged files highlighted small unusual IC-T subsets: CD2+(dim) (0.25% total), CD2- (0.03% total). An IC reference template highlighted neoplastic T-cells, but was limited by staining variability (IC CD3 MFI reference samples different from test (p = 0.003)). IC T-cells present in the majority of specimens can serve as positive and longitudinal process controls. Use of IC T-cells as an internal reference is limited by variable representation of subsets. Analysis of merged IC T-cells from previously analyzed patient samples can alert the interpreter to less-well-recognized non-neoplastic subsets. However, application of a merged file IC reference template was limited by staining variability. © 2016 Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

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.

Evaluation of blood T-lymphocyte subpopulations involved in host cellular immunity in dogs with mammary cancer.

PubMed

Karayannopoulou, Maria; Anagnostou, Tilemachos; Margariti, Apostolia; Kostakis, Charalampos; Kritsepi-Konstantinou, Maria; Psalla, Dimitra; Savvas, Ioannis

2017-04-01

Cancer-bearing patients are often immunosuppressed. In dogs with mammary or other cancers, various alterations in blood cell populations involved in host cellular immunity have been reported; among these cell populations some T-lymphocyte subsets play an important role against cancer. The purpose of the present study was to investigate any alterations in circulating T-lymphocyte subpopulations involved in cellular immunity in bitches with mammary cancer, in comparison to age-matched healthy intact bitches. Twenty eight dogs with mammary cancer and 14 control dogs were included in this study. Twelve out of the 28 bitches had mammary cancer of clinical stage II and 16/28 of stage III. Histological examination revealed that 23/28 animals had carcinomas, 3/28 sarcomas and 2/28 carcinosarcomas. White blood cell, neutrophil and lymphocyte absolute numbers were measured by complete blood count. Furthermore, blood T-lymphocyte population (CD3 + ) and the subpopulations CD4 + , CD8 + and CD5 low+ were assessed by flow cytometry. White blood cell and neutrophil but not lymphocyte absolute numbers were higher (P=0.003 and P=0.001, respectively) in cancer patients than controls. Flow cytometric analysis revealed that the relative percentage of T-lymphocytes (CD3 + ) and of CD4 + , CD8 + subpopulations was lower (the CD4 + /CD8 + ratio was higher), whereas the percentage of CD5 low+ T-cells was higher, in dogs with cancer compared to controls; however, a statistically significant difference was found only in the case of CD8 + T-cells (P=0.014), whereas in the case of the CD4 + /CD8 + ratio the difference almost reached statistical significance (P=0.059). Based on these findings, it can be suggested that, although the absolute number of blood lymphocytes is unchanged, the relative percentages of T-lymphocyte subpopulations involved in host cell-mediated immunity are altered, but only cytotoxic CD8 + T-cells are significantly suppressed, in dogs with mammary cancer of clinical stage II or III compared to age-matched healthy controls. Copyright © 2017 Elsevier B.V. All rights reserved.

Differential Expression of Metallothionein Isoforms in Terrestrial Snail Embryos Reflects Early Life Stage Adaptation to Metal Stress

PubMed Central

Baurand, Pierre-Emmanuel; Pedrini-Martha, Veronika; de Vaufleury, Annette; Niederwanger, Michael; Capelli, Nicolas; Scheifler, Renaud; Dallinger, Reinhard

2015-01-01

The aim of this study was to analyze the expression of three metallothionein (MT) isoform genes (CdMT, CuMT and Cd/CuMT), already known from adults, in the Early Life Stage (ELS) of Cantareus aspersus. This was accomplished by detection of the MT isoform-specific transcription adopting Polymerase Chain Reaction (PCR) amplification and quantitative Real Time (qRT)-PCR of the three MT genes. Freshly laid eggs were kept for 24 hours under control conditions or exposed to three cadmium (Cd) solutions of increasing concentration (5, 10, and 15 mg Cd/L). The transcription of the three MT isoform genes was detected via PCR in 1, 6 and 12-day-old control or Cd-exposed embryos. Moreover, the transcription of this isoform genes during development was followed by qRT-PCR in 6 and 12-day-old embryos. Our results showed that the CdMT and Cd/CuMT genes, but not the CuMT gene, are expressed in embryos at the first day of development. The transcription of the 3 MT genes in control embryos increased with development time, suggesting that the capacities of metal regulation and detoxification may have gradually increased throughout embryogenesis. However in control embryos, the most highly expressed MT gene was that of the Cd/CuMT isoform, whose transcription levels greatly exceeded those of the other two MT genes. This contrasts with the minor significance of this gene in adult snails and suggests that in embryos, this isoform may play a comparatively more important role in metal physiology compared to adult individuals. This function in adult snails appears not to be related to Cd detoxification. Instead, snail embryos responded to Cd exposure by over-expression of the CdMT gene in a concentration-dependent manner, whereas the expression of the Cd/CuMT gene remained unaffected. Moreover, our study demonstrates the ability of snail embryos to respond very early to Cd exposure by up-regulation of the CdMT gene. PMID:25706953

Prevalence of transfusion-transmitted Chagas Disease among multitransfused patients in Brazil.

PubMed

De Paula, Erich V; Goncales, Neiva S L; Xueref, Serge; Addas-Carvalho, Marcelo; Gilli, Simone C O; Angerami, Rodrigo N; Goncales, Fernando L

2008-01-16

Blood transfusion has always been an important route for Chagas Disease (CD) transmission. The high prevalence of CD in Latin America and its lifelong asymptomatic clinical picture pose a threat for the safety of the blood supply. The outcome of measures designed to improve transfusion safety can be assessed by evaluating the prevalence of CD among multitransfused patients In order to assess the impact of CD control measures on the safety of the blood supply, an observational cross-sectional study was designed to determine the prevalence of CD in 351 highly transfused patients, in which vectorial transmission was excluded. This study compared patients that received transfusion products before (n = 230) and after (n = 121) 1997, when measures to control transfusion-transmitted CD were fully implemented in Brazil. The study group consisted of 351 patients exposed to high numbers of blood products during their lifetime (median number of units transfused = 51, range 10-2086). A higher prevalence of transfusion-transmitted CD (1.30%) was observed among multitransfused patients that received their first transfusion before 1997, compared with no cases of transfusion-transmitted CD among multitransfused patients transfused after that year. The magnitude of the exposure to blood products was similar among both groups (mean number of units transfused per year of exposure = 25.00 +/- 26.46 and 23.99 +/- 30.58 respectively; P = 0.75, Mann-Whitney test). Multiple initiatives aimed to control vector and parental transmission of CD can significantly decrease transfusion-transmitted CD in Brazil. Our data suggest that mandatory donor screening for CD represents the most important measure to interrupt transmission of CD by blood transfusions.

The Association of Peripheral Blood Regulatory T-Cell Concentrations With Epithelial Ovarian Cancer: A Brief Report.

PubMed

Cannioto, Rikki A; Sucheston-Campbell, Lara E; Hampras, Shalaka; Goode, Ellen L; Knutson, Keith; Ness, Roberta; Modugno, Francesmary; Wallace, Paul; Szender, J Brian; Mayor, Paul; Hong, Chi-Chen; Joseph, Janine M; Friel, Grace; Davis, Warren; Nesline, Mary; Eng, Kevin H; Edwards, Robert P; Kruszka, Bridget; Schmitt, Kristina; Odunsi, Kunle; Moysich, Kirsten B

2017-01-01

There is a mounting body of evidence demonstrating higher percentages of regulatory T (Treg) cells in the peripheral blood of patients with cancer in comparison to healthy controls, but there is a paucity of epidemiological literature characterizing circulating Treg cells among patients with epithelial ovarian cancer (EOC). To investigate the role of peripheral Treg cells in ovarian neoplasms, we conducted a case-control study to characterize circulating concentrations of Treg cells among patients with EOC, women with benign ovarian conditions, and healthy controls without a history of cancer. Participants were identified for inclusion due to their participation in the Data Bank and BioRepository program at Roswell Park Cancer Institute in Buffalo, NY. Patients included 71 women with a primary diagnosis of EOC and 195 women with a diagnosis of benign ovarian conditions. Controls included 101 age- and race-matched women without a history of cancer. Nonfasting, pretreatment peripheral blood levels of CD3+CD4+CD25+FOXP3+ Treg cells were measured using flow cytometric analyses and expressed as a percentage of total CD3+ cells and as a percentage of total CD3+CD4+ cells. Compared to healthy controls and women with benign ovarian conditions, patients with EOC had significantly higher frequency of Treg cells (P < 0.04). In multivariable logistic regression analyses using Treg frequency expressed as a percentage of CD+3 cells, we observed a significant positive association between Treg cell percentage and EOC risk, with each 1% increase associated with a 37% increased risk of EOC (odds ratio, 1.37; 95% confidence interval, 1.04-1.80). We observed a similar trend when Treg frequency was expressed as a percentage of CD3+CD+4 cells (odds ratio, 1.22; 95% confidence interval, 0.99-1.49). The current study provides support that peripheral Treg cell frequency is elevated in patients with EOC in comparison to women with benign ovarian conditions and healthy controls.

The association of peripheral blood regulatory T-cell concentrations with epithelial ovarian cancer: A brief report

PubMed Central

Hampras, Shalaka; Goode, Ellen L.; Knutson, Keith; Ness, Roberta; Modugno, Francesmary; Wallace, Paul; Szender, J. Brian; Mayor, Paul; Hong, Chi-Chen; Joseph, Janine M.; Friel, Grace; Davis, Warren; Nesline, Mary; Eng, Kevin H.; Edwards, Robert P.; Kruszka, Bridget; Schmitt, Kristina; Odunsi, Kunle; Moysich, Kirsten B.

2016-01-01

Objective There is a mounting body of evidence demonstrating higher percentages of regulatory T (Treg) cells in the peripheral blood of cancer patients in comparison to healthy controls, but there is a paucity of epidemiological literature characterizing circulating Treg cells among epithelial ovarian cancer (EOC) patients. To investigate the role of peripheral Treg cells in ovarian neoplasms, we conducted a case-control study to characterize circulating concentrations of Treg cells among EOC patients, women with benign ovarian conditions, and healthy controls without a history of cancer. Materials and Methods Participants were identified for inclusion due to their participation in the Data Bank and BioRepository program at Roswell Park Cancer Institute in Buffalo, NY. Patients included 71 women with a primary diagnosis of EOC and 195 women with a diagnosis of benign ovarian conditions. Controls included 101 age- and race-matched women without a history of cancer. Non-fasting, pre-treatment peripheral blood levels of CD3+CD4+CD25+FOXP3+ Treg cells were measured using flow cytometric analyses and expressed as a percentage of total CD3+ cells and as a percentage of total CD3+CD4+ cells. Results Compared to healthy controls and women with benign ovarian conditions, EOC patients had significantly higher frequency of Treg cells (p<0.04). In multivariable logistic regression analyses utilizing Treg frequency expressed as a percentage of CD+3 cells, we observed a significant positive association between Treg cell percentage and EOC risk, with each one percent increase associated with a 37% increased risk of EOC (OR=1.37, 95% CI: 1.04-1.80). We observed a similar trend when Treg frequency was expressed as a percentage of CD3+CD+4 cells (OR=1.22, 95% CI: 0.99-1.49). Conclusions The current study provides support that peripheral Treg cell frequency is elevated in EOC patients in comparison to women with benign ovarian conditions and healthy controls. PMID:27759594

Increased CD56(bright) NK cells in HIV-HCV co-infection and HCV mono-infection are associated with distinctive alterations of their phenotype.

PubMed

Bhardwaj, Suvercha; Ahmad, Fareed; Wedemeyer, Heiner; Cornberg, Marcus; Schulze Zur Wiesch, Julian; van Lunzen, Jan; Sarin, Shiv K; Schmidt, Reinhold E; Meyer-Olson, Dirk

2016-04-18

HIV-HCV co-infection is associated with accelerated progression to hepatic fibrosis, cirrhosis and hepatocellular carcinoma than HCV mono-infection. The contribution of innate immunity during HIV-HCV co-infection has been a relatively under-investigated area. Natural killer (NK) cells are pivotal sentinels of innate immunity against viruses and tumour cells. In this study we evaluated the effect of HIV-HCV co-infection on peripheral blood NK cell subsets with emphasis on the phenotype of CD56(bright) NK cells. Sixty patients were included in the study; HIV mono-infected (n = 12), HCV mono-infected (n = 15), HCV-HIV co-infected (n = 21) and healthy controls (n = 16). PBMCs were isolated and immunophenotyping of NK cells was performed by flowcytometry. We observed an expansion of CD56(bright) NK cell subset in HIV-HCV co-infection as compared to healthy controls and HIV mono-infected group. All the infected groups had an upregulated expression of the activating receptor NKG2D on CD56(bright) NK cells in comparison to healthy controls while not differing amongst themselves. The expression of NKp46 in HIV-HCV co-infected group was significantly upregulated as compared to both HIV as well as HCV mono-infections while NKp30 expression in the HIV-HCV co-infected group significantly differed as compared to HIV mono-infection. The CD56(bright) NK cell subset was activated in HIV-HCV co-infection as assessed by the expression of CD69 as compared to healthy controls but was significantly downregulated in comparison to HIV mono-infection. CD95 expression on CD56(bright) NK cells followed the same pattern where there was an increased expression of CD95 in HIV mono-infection and HIV-HCV co-infection as compared to healthy controls. In contrast to CD69 expression, CD95 expression in HCV mono-infection was decreased when compared to HIV mono-infection and HIV-HCV co-infection. Finally, expression of CXCR3 on CD56(bright) NK cells was increased in HIV-HCV co-infection in comparison to HIV mono-infection while remaining similar to HCV mono-infection. Thus, HIV-HCV co-infection is able to modulate the phenotype of CD56(bright) NK cell subset in a unique way such that NKp46 and CXCR3 expressions are distinct for co-infection while both mono-infections have an additive effect on CD56(bright), CD69 with CD95 expressions. HCV mono-infection has a dominant effect on NKp30 expression while NKG2D and CD127 expressions remained same in all the groups.

[CD22 signal abnormalities in the pathogenesis of immune related pancytopenia].

PubMed

Wu, Xiaojing; Shao, Zonghong; Ruan, Erbao; Fu, Rong; Wang, Guojin; Liu, Hong; Wu, Yuhong; Song, Jia; Xing, Limin; Qu, Wen; Cuan, Jing; Li, Lijuan; Wang, Xiaoming; Liu, Hui; Wang, Yihao; Wang, Huaquan

2015-07-14

To investigate the expression of CD22 and its downstream signal molecule spleen tyrosine kinase (SYK) and their phosphorylation of B lymphocytes in patients with immune related pancytopenia(IRP), and to explore the role of CD22 in pathogenesis of IRP. The expression of CD22, SYK and their phosphorylation, along with the expression of IgG and IgM, which obtained from B lymphocytes in peripheral blood of 46 patients with IRP(22 new diagnosed and 24 remitted patients returned to normal after treatment), 22 healthy controls and 12 chronic lymphocytic leukemia(CLL) patients from February to December 2014 were analyzed by flow cytometry. And the mRNA expression of CD22 in peripheral blood mononuclear cell was determined by real-time quantitative PCR. The ratios of CD22+ cells and phosphorylated CD22(pCD22)+ cells of B lymphocytes in new diagnosed group (60. 03% ± 20. 94% 71. 32% ± 11. 16%) were significantly higher than those in remission group (46. 92% ± 20. 04%, 55. 82% ± 14. 42%), normal control group (46. 86% ± 17. 78%, 53. 28% ± 14. 76%) and CLL group (39. 74% ± 18. 96%, 59. 07% ± 17.09%) (all P <0.05). The ratios of phosphorylated SYK( pSYK) + cells in the four groups had the same trend (all P <0. 05). The ratio of pCD22+ cells/pSYK+ cells in new diagnosed group was significantly lower than that in normal control group and CLL group (27. 39 (5. 06 - 102. 70) vs 55. 95 (15. 25 - 298. 53), 56. 92(5. 60 - 228. 96), both P <0. 05), and pCD22+ cells positively correlated to pSYK+ cells ( r = 0. 341, P < 0. 05). The expression of IgG in new diagnosed group and remission group was significantly higher than that in normal control group, and the expression of IgM in new diagnosed group was significantly higher than that in normal control group and CLL group (all P <0. 05). The expression levels of CD22 mRNA in new diagnosed group was significantly higher than that in remission group, normal control group and CLL group (all P <0. 05). The BCR signal pathway of B lymphocyte in IRP patients is enhanced, and the quantity and function of CD22 are increased, while which are still insufficient to inhibit B cell proliferation, and these may have some relationships with the pathogenesis of IRP. [Key words] Pancytopenia; Antigens, CD22; Immune related pancytopenia; Spleen tyrosine kinase; Phosphorylation

CD4+ memory T cells retain surface expression of CD31 independently of thymic function in patients with lymphoproliferative disorders following autologous hematopoietic stem-cell transplantation.

PubMed

Batorov, Egor V; Tikhonova, Marina A; Kryuchkova, Irina V; Sergeevicheva, Vera V; Sizikova, Svetlana A; Ushakova, Galina Y; Batorova, Dariya S; Gilevich, Andrey V; Ostanin, Alexander A; Shevela, Ekaterina Y; Chernykh, Elena R

2017-07-01

High-dose chemotherapy with autologous hematopoietic stem-cell transplantation (AHSCT) causes severe and long-lasting immunodeficiency in patients with lymphoproliferative disorders. The thymus begins to restore the T-cell repertoire approximately from the sixth month post-transplant. We assessed the dynamics of post-transplant recovery of CD4 + CD45RA + CD31 + T cells, "recent thymic emigrants" (RTEs), and a poorly described subtype of CD4 + CD45RA - CD31 + T cells in 90 patients with lymphoproliferative disorders following high-dose chemotherapy with AHSCT. Relative and absolute counts of CD4 + CD31 + naïve and memory T cells were evaluated before AHSCT, at the day of engraftment, and 6- and 12-month post-transplant. The pre-transplant count of CD4 + CD45RA + CD31 + T cells was lower than in healthy controls, and did not reach donors' values during the 12-month period. The pre-transplant number of CD4 + CD45RA - CD31 + T cells was higher than in healthy controls and was restored rapidly following AHSCT. Post-transplant mediastinal radiotherapy reduced counts of RTEs and elongated recovery period. Non-thymic tissue irradiation did not reduce this subset. The obtained data indicate that homeostatic proliferation may decrease the significance of CD31 expression on CD4 + CD45RA + T cells as a marker of RTEs, and suggest that evaluation of RTEs recovery by flow cytometry requires an accurate gating strategy to exclude CD31 + memory T cells.

[Influence of Leukodeplated Blood Transfusion on Cellular Immunity of Acute Leukemia Patients].

PubMed

Lu, Ya-Lan; Zhang, Xin; Wang, Yu-Fang; Ke, Shan-Dong; Ke, Jin-Yong; Liu, Geng-Fu; Chen, Shi-Ming

2016-08-01

To study the influence of leukodeplated blood transfusion on cellular immunity of patients with acute leuemia, so as to provide support for application of leuko-deplated blood transfusion in clinic. A total of 100 AL patients from January 2012 to December 2015 were chosen, and were divided into 2 groups: leukodeplated blood transfusion group(50 cases) and routine blood transfusion group(RBT) as control (50 cases). The effective rate, side effects, peripheral blood T cells and expression level of TLR2 and TLR4 were compared between 2 groups. The expression levels CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+) of TLR2 and TLR4 in control group were (52.18±2.14)%, （27.28±1.19）%,（24.21±1.65）%,1.22±0.18,0.62±0.04 and 0.57±0.05, respectively, after treatment; while these indicators in LdBT group were （52.18±2.14）%,（30.97±2.01）%,（27.08±1.55）%,1.39±0.24,0.91±0.06 and 0.87±0.07, respectively, and above-mentioned indicators in LdBT group were significantly higher than those in control group（P<0.05）. Compared with these indicators before treatment, CD3(+), CD4(+), CD8(+) and CD4(+)/CD8(+) in the patients increased significantly（P<0.05）. The efficiency was 92.00% (46/50) in LdBT group, and 84.00% (42/50) in control group, without statistically significant difference（P>0.05）. The rate of side effects in study group was 6% (3/50), 18% (9/50) in control group, with statistically significance difference （P<0.05）. Leukodeplated blood transfusion can improve the cellular immunity of AL patients, and reduce the rate of side effects.

Variation and significance of secretory immunoglobulin A, interleukin 6 and dendritic cells in oral cancer.

PubMed

Zhang, Suxin; Zhang, Xin; Yin, Ke; Li, Tianke; Bao, Yang; Chen, Zhong

2017-04-01

The present study aimed to determine changes in the concentration of secretory immunoglobulin A (SIgA) and interleukin 6 (IL-6) in the saliva of patients with oral cancer, to evaluate the abnormal expression of cluster of differentiation (CD) 1a, CD83, CD80 and CD86 on dendritic cells (DCs) of oral cancer tissues and to discuss the interaction between SIgA, IL-6 and DCs in oral cancer. A total of 40 patients between 27 and 70 years of age, median age 52 years, with primary oral cancer were enrolled in the present study, and a group of 20 healthy male and female volunteers was used as the control group. The concentration of SIgA and IL-6 in the saliva of the preoperative patients was determined by ELISA. The expression levels of CD1a, CD83, CD80 and CD86 were detected by immunohistochemistry and flow cytometry, which was performed on histopathological sections from paraffin-embedded tumor and corresponding adjacent control tissues. The specimens were assessed using the semi-quantitative immunoreactive score (IRS). The concentration of SIgA in the saliva from patients with oral cancer decreased, whereas the IL-6 level significantly increased compared with the control subjects (P<0.05). In addition, the decrease of SIgA level and increase of IL-6 level exhibited a negative correlation (r=-0.543, P<0.05). According to the IRS score, the expression levels of CD1a, CD83, CD80 and CD86 in the cancer tissue were lower than the expression levels of the control group (P<0.05). Furthermore, the expression of CD80 and CD86 exhibited no correlation with histological grade or pathological type (P>0.05), but exhibited a negative correlation with clinical stage and lymph node metastasis (P<0.05). The concentration of SIgA and IL-6 in saliva may be used as an auxiliary diagnostic indicator for oral cancer. The detection of CD80 and CD86 expressed on DCs in oral cancer tissue may be useful for the diagnosis and evaluation of the prognosis of tumors. The present study hypothesized that the use of SIgA vaccines or IL-6 inhibitors may be useful for reversing the immune deficiency associated with DCs in oral cancer.

Low expression of CD39 on regulatory T cells as a biomarker for resistance to methotrexate therapy in rheumatoid arthritis

PubMed Central

Peres, Raphael Sanches; Liew, Foo Y.; Talbot, Jhimmy; Carregaro, Vanessa; Oliveira, Rene D.; Almeida, Sergio L.; França, Rafael F. O.; Donate, Paula B.; Pinto, Larissa G.; Ferreira, Flavia I. S.; Costa, Diego L.; Demarque, Daniel P.; Gouvea, Dayana Rubio; Lopes, Norberto P.; Queiroz, Regina Helena C.; Silva, Joao Santana; Figueiredo, Florencio; Alves-Filho, Jose Carlos; Cunha, Thiago M.; Ferreira, Sérgio H.; Louzada-Junior, Paulo; Cunha, Fernando Q.

2015-01-01

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by joint destruction and severe morbidity. Methotrexate (MTX) is the standard first-line therapy of RA. However, about 40% of RA patients are unresponsive to MTX treatment. Regulatory T cells (Tregs, CD4+CD25+FoxP3+) are thought to play an important role in attenuating RA. To investigate the role of Tregs in MTX resistance, we recruited 122 RA patients (53 responsive, R-MTX; 69 unresponsive, UR-MTX) and 33 healthy controls. Three months after MTX treatment, R-MTX but not UR-MTX showed higher frequency of peripheral blood CD39+CD4+CD25+FoxP3+ Tregs than the healthy controls. Tregs produce adenosine (ADO) through ATP degradation by sequential actions of two cell surface ectonucleotidases: CD39 and CD73. Tregs from UR-MTX expressed a lower density of CD39, produced less ADO, and had reduced suppressive activity than Tregs from R-MTX. In a prospective study, before MTX treatment, UR-MTX expressed a lower density of CD39 on Tregs than those of R-MTX or control (P < 0.01). In a murine model of arthritis, CD39 blockade reversed the antiarthritic effects of MTX treatment. Our results demonstrate that MTX unresponsiveness in RA is associated with low expression of CD39 on Tregs and the decreased suppressive activity of these cells through reduced ADO production. Our findings thus provide hitherto unrecognized mechanism of immune regulation in RA and on mode of action of MTX. Furthermore, our data suggest that low expression of CD39 on Tregs could be a noninvasive biomarker for identifying MTX-resistant RA patients. PMID:25675517

Low expression of CD39 on regulatory T cells as a biomarker for resistance to methotrexate therapy in rheumatoid arthritis.

PubMed

Peres, Raphael Sanches; Liew, Foo Y; Talbot, Jhimmy; Carregaro, Vanessa; Oliveira, Rene D; Almeida, Sergio L; França, Rafael F O; Donate, Paula B; Pinto, Larissa G; Ferreira, Flavia I S; Costa, Diego L; Demarque, Daniel P; Gouvea, Dayana Rubio; Lopes, Norberto P; Queiroz, Regina Helena C; Silva, Joao Santana; Figueiredo, Florencio; Alves-Filho, Jose Carlos; Cunha, Thiago M; Ferreira, Sérgio H; Louzada-Junior, Paulo; Cunha, Fernando Q

2015-02-24

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by joint destruction and severe morbidity. Methotrexate (MTX) is the standard first-line therapy of RA. However, about 40% of RA patients are unresponsive to MTX treatment. Regulatory T cells (Tregs, CD4(+)CD25(+)FoxP3(+)) are thought to play an important role in attenuating RA. To investigate the role of Tregs in MTX resistance, we recruited 122 RA patients (53 responsive, R-MTX; 69 unresponsive, UR-MTX) and 33 healthy controls. Three months after MTX treatment, R-MTX but not UR-MTX showed higher frequency of peripheral blood CD39(+)CD4(+)CD25(+)FoxP3(+) Tregs than the healthy controls. Tregs produce adenosine (ADO) through ATP degradation by sequential actions of two cell surface ectonucleotidases: CD39 and CD73. Tregs from UR-MTX expressed a lower density of CD39, produced less ADO, and had reduced suppressive activity than Tregs from R-MTX. In a prospective study, before MTX treatment, UR-MTX expressed a lower density of CD39 on Tregs than those of R-MTX or control (P < 0.01). In a murine model of arthritis, CD39 blockade reversed the antiarthritic effects of MTX treatment. Our results demonstrate that MTX unresponsiveness in RA is associated with low expression of CD39 on Tregs and the decreased suppressive activity of these cells through reduced ADO production. Our findings thus provide hitherto unrecognized mechanism of immune regulation in RA and on mode of action of MTX. Furthermore, our data suggest that low expression of CD39 on Tregs could be a noninvasive biomarker for identifying MTX-resistant RA patients.

Interfacial Engineering and Charge Carrier Dynamics in Extremely Thin Absorber Solar Cells

NASA Astrophysics Data System (ADS)

Edley, Michael

Photovoltaic energy is a clean and renewable source of electricity; however, it faces resistance to widespread use due to cost. Nanostructuring decouples constraints related to light absorption and charge separation, potentially reducing cost by allowing a wider variety of processing techniques and materials to be used. However, the large interfacial areas also cause an increased dark current which negatively affects cell efficiency. This work focuses on extremely thin absorber (ETA) solar cells that used a ZnO nanowire array as a scaffold for an extremely thin CdSe absorber layer. Photoexcited electrons generated in the CdSe absorber are transferred to the ZnO layer, while photogenerated holes are transferred to the liquid electrolyte. The transfer of photoexcited carriers to their transport layer competes with bulk recombination in the absorber layer. After charge separation, transport of charge carriers to their respective contacts must occur faster than interfacial recombination for efficient collection. Charge separation and collection depend sensitively on the dimensions of the materials as well as their interfaces. We demonstrated that an optimal absorber thickness can balance light absorption and charge separation. By treating the ZnO/CdSe interface with a CdS buffer layer, we were able to improve the Voc and fill factor, increasing the ETA cell's efficiency from 0.53% to 1.34%, which is higher than that achievable using planar films of the same material. We have gained additional insight into designing ETA cells through the use of dynamic measurements. Ultrafast transient absorption spectroscopy revealed that characteristic times for electron injection from CdSe to ZnO are less than 1 ps. Electron injection is rapid compared to the 2 ns bulk lifetime in CdSe. Optoelectronic measurements such as transient photocurrent/photovoltage and electrochemical impedance spectroscopy were applied to study the processes of charge transport and interfacial recombination. With these techniques, the extension of the depletion layer from CdSe into ZnO was determined to be vital to suppression of interfacial recombination. However, depletion of the ZnO also restricted the effective diffusion core for electrons and slowed their transport. Thus, materials and geometries should be chosen to allow for a depletion layer that suppresses interfacial recombination without impeding electron transport to the point that it is detrimental to cell performance. Thin film solar cells are another promising technology that can reduce costs by relaxing material processing requirements. CuInxGa (1-x)Se (CIGS) is a well studied thin film solar cell material that has achieved good efficiencies of 22.6%. However, use of rare elements raise concerns over the use of CIGS for global power production. CuSbS2 shares chemistry with CuInSe2 and also presents desirable properties for thin film absorbers such as optimal band gap (1.5 eV), high absorption coefficient, and Earth-abundant and non-toxic elements. Despite the promise of CuSbS2, direct characterization of the material for solar cell application is scarce in the literature. CuSbS2 nanoplates were synthesized by a colloidal hot-injection method at 220 °C in oleylamine. The CuSbS2 platelets synthesized for 30 minutes had dimensions of 300 nm by 400 nm with a thickness of 50 nm and were capped with the insulating oleylamine synthesis ligand. The oleylamine synthesis ligand provides control over nanocrystal growth but is detrimental to intercrystal charge transport that is necessary for optoelectronic device applications. Solid-state and solution phase ligand exchange of oleylamine with S2- were used to fabricate mesoporous films of CuSbS2 nanoplates for application in solar cells. Exchange of the synthesis ligand with S2- resulted in a two order of magnitude increase in 4-point probe conductivity. Photoexcited carrier lifetimes of 1.4 ns were measured by time-resolved terahertz spectroscopy, indicating potential for CuSbS2 as a solar cell absorber material.

[Oxidative damage effects induced by CdTe quantum dots in mice].

PubMed

Xie, G Y; Chen, W; Wang, Q K; Cheng, X R; Xu, J N; Huang, P L

2017-07-20

Objective: To investigate Oxidative damage effects induced by CdTe Quantum Dots (QDs) in mice. Methods: 40 ICR mice were randomly divided into 5 groups: one control group (normal saline) ; four CdTe QDs (exposed by intravenous injection of 0.2 ml of CdTe QDs at the concentration of 0、0.5、5.0、50.0 and 500.0 nmol/ml respectively) . After 24 h, the mice were decapitated and the blood was collected for serum biochemically indexes、hematology indexes, the activities of SOD、GSH-Px and the concentration of MDA were all detected. Results: The results showed in the four CdTe QDs exposure groups, the level of CRE、PLT and the concentration of MDA were all significantly lower than those of the control group ( P <0.05 or P <0.01) ; the activities GSH - Px in 50.0 and 500.0 nmol/ml CdTe QDs group were significantly higher than those of control group ( P <0.01) . Conclusion: It was suggested that CdTe QDs at 0.5 nmol/ml could induce Oxidative damage effects in mice.

Preparation and Characterization of Ternary Antimicrobial Films of β-Cyclodextrin/Allyl Isothiocyanate/Polylactic Acid for the Enhancement of Long-Term Controlled Release

PubMed Central

Wang, Jinpeng; Qiu, Chao; Narsimhan, Ganesan; Jin, Zhengyu

2017-01-01

Allyl isothiocyanate (AITC) are natural essential oil components that have outstanding antimicrobial activities. However, low water solubility, high volatility, and easy degradation by heat, restricting their application in food packing industry. Development of the inclusion complex of β-cyclodextrin/AITC (β-CD/AITC) is a promising solution. Furthermore, the incorporation of β-CD/AITC complex into polylactic acid (PLA) films would be an attractive method to develop food antimicrobial materials. The aim of this study was to evaluate the enhancement in physicochemical properties, antimicrobial activities, and controlled release of β-CD/AITC from such films. The addition of β-CD/AITC significantly increased the flexibility and thermal stability of films. The Fourier transform infrared (FTIR) results revealed that the interactions between β-CD/AITC and PLA films occurred. The controlled release of AITC encapsulated in β-CD was significantly affected by relative humidity and temperature. The PLA films containing β-CD/AITC can be applied as an effective antimicrobial packing material for food and non-food applications. PMID:29053573

Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover

PubMed Central

Almeida, Jorge R.; Price, David A.; Papagno, Laura; Arkoub, Zaïna Aït; Sauce, Delphine; Bornstein, Ethan; Asher, Tedi E.; Samri, Assia; Schnuriger, Aurélie; Theodorou, Ioannis; Costagliola, Dominique; Rouzioux, Christine; Agut, Henri; Marcelin, Anne-Geneviève; Douek, Daniel; Autran, Brigitte; Appay, Victor

2007-01-01

The key attributes of CD8+ T cell protective immunity in human immunodeficiency virus (HIV) infection remain unclear. We report that CD8+ T cell responses specific for Gag and, in particular, the immunodominant p24 epitope KK10 correlate with control of HIV-1 replication in human histocompatibility leukocyte antigen (HLA)–B27 patients. To understand further the nature of CD8+ T cell–mediated antiviral efficacy, we performed a comprehensive study of CD8+ T cells specific for the HLA-B27–restricted epitope KK10 in chronic HIV-1 infection based on the use of multiparametric flow cytometry together with molecular clonotypic analysis and viral sequencing. We show that B27-KK10–specific CD8+ T cells are characterized by polyfunctional capabilities, increased clonal turnover, and superior functional avidity. Such attributes are interlinked and constitute the basis for effective control of HIV-1 replication. These data on the features of effective CD8+ T cells in HIV infection may aid in the development of successful T cell vaccines. PMID:17893201

CD56-enriched donor cell infusion after post-transplantation cyclophosphamide for haploidentical transplantation of advanced myeloid malignancies is associated with prompt reconstitution of mature natural killer cells and regulatory T cells with reduced incidence of acute graft versus host disease: A pilot study.

PubMed

Jaiswal, Sarita Rani; Zaman, Shamsur; Nedunchezhian, Murugaiyan; Chakrabarti, Aditi; Bhakuni, Prakash; Ahmed, Margoob; Sharma, Kanika; Rawat, Sheh; O'donnell, Paul; Chakrabarti, Suparno

2017-04-01

We conducted a pilot study on the feasibility of CD56-enriched donor cell infusion after post-transplantation cyclophosphamide (PTCy) for 10 patients with advanced myeloid malignancies undergoing haploidentical peripheral blood stem cell transplantation with cyclosporine alone as graft-versus-host disease (GVHD) prophylaxis and compared the outcome and immune reconstitution with a control group of 20 patients undergoing the same without CD56-enriched donor cell infusion. An early and rapid surge of mature NK cells as well as CD4 + T cells and regulatory T cells (Tregs) was noted compared with the control group. KIR of donor phenotype reconstituted as early as day 30 with expression of CD56 dim CD16 + NKG2A - KIR + phenotype. None experienced viral or fungal infections, and non-relapse mortality was 10% only. The incidence of grade 2-4 acute GVHD was 50% in the control group with none in the CD56 group (P = 0.01). Only two had de novo chronic GVHD in each group. Relapse occurred in five patients in CD56 group with a median follow-up of 12 months, similar to the control group. Our preliminary data show that CD56 + donor cell infusion after PTCy and short-course cyclosporine is feasible with prompt engraftment, rapid reconstitution of CD4 + T cells, Tregs and NK cells and reduced incidence of acute GVHD. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Budesonide increases TLR4 and TLR2 expression in Treg lymphocytes of allergic asthmatics.

PubMed

Pace, Elisabetta; Di Sano, Caterina; Ferraro, Maria; Bruno, Andreina; Caputo, Valentina; Gallina, Salvatore; Gjomarkaj, Mark

2015-06-01

Reduced innate immunity responses as well as reduced T regulatory activities characterise bronchial asthma. In this study the effect of budesonide on the expression of TLR4 and TLR2 in T regulatory lymphocyte sub-population was assessed. TLR4 and TLR2 expression in total peripheral blood mononuclear cells (PBMC), in CD4+/CD25+ and in CD4+/CD25- was evaluated, by flow cytometric analysis, in mild intermittent asthmatics (n = 14) and in controls (n = 11). The in vitro effects of budesonide in modulating: TLR4 and TLR2 expression in controls and in asthmatics; IL-10 expression and cytokine release (IL-6 and TNF-α selected by a multiplex assay) in asthmatics were also explored. TLR4 and TLR2 were reduced in total PBMC from asthmatics in comparison to PBMC from controls. CD4+CD25+ cells expressed at higher extent TLR2 and TLR4 in comparison to CD4+CD25- cells. Budesonide was able to increase the expression of TLR4, TLR2 and IL-10 in CD4+/CD25 highly+ cells from asthmatics. TLR4 ligand, LPS induced Foxp3 expression. Budesonide was also able to reduce the release of IL-6 and TNF-α by PBMC of asthmatics. Budesonide potentiates the activity of Treg by increasing TLR4, TLR2 and IL-10 expression. This event is associated to the decreased release of IL-6 and TNF-α in PBMC treated with budesonide. These findings shed light on new mechanisms by which corticosteroids, drugs widely used for the clinical management of bronchial asthma, control T lymphocyte activation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Flow cytometric analyses of CD34+ cells with inclusion of internal positive controls.

PubMed

Gutensohn, Kai; Jessen, Maria; Ketels, Andrea; Gramatzki, Martin; Humpe, Andreas

2012-02-01

Flow cytometric measurement of CD34+ events is used to ensure the quality of human progenitor cell grafts. This study was conducted to evaluate whether the spiking of routine samples from peripheral blood and apheresis products with CD34+ positive controls is feasible. A total of 42 samples from 32 patients and one healthy donor were stained in duplicate for CD34+ cells. Before flow cytometric analysis, one tube was spiked with stabilized CD34+ cells at a defined concentration. Median numbers of viable CD34+ cells/µL did not differ between unspiked and spiked tubes (median 37, range 0-714; and median 34, range 0-719, respectively). The 95% confidence interval (CI) of the mean showed a broad overlap between these samples (41.9-119.1 and 41.4-119.3, respectively). In addition, the 95% CI of the mean for CD45+ cells/µL overlapped broadly and median numbers did not differ. Median viability of all CD45+ cells was significantly lower in the spiked tubes (96.75, range 64-98.8 vs. 99.25, range 97.5-99.8) with no overlap of the 95% CI of the mean viability. The results of this study show that spiking of routine samples with internal positive controls does not affect CD34+ cell analyses, but does support the reliability of important clinical data. The inclusion of positive controls is expedient for laboratories that perform analyses with low CD34+ numbers and laboratories that use different flow cytometric analyzers and may also become a requirement to meet statutory regulations. © 2012 American Association of Blood Banks.

Soluble CD30 is more relevant to disease activity of atopic dermatitis than soluble CD26

PubMed Central

Katoh, N; Hirano, S; Suehiro, M; Ikenaga, K; Yamashita, T; Sugawara, N; Yasuno, H

2000-01-01

It is suggested that CD30 and CD26 are surface molecules expressed on activated Th2 and Th1 cells, respectively. We examined plasma levels of soluble CD26 (sCD26) and sCD30 in patients with atopic dermatitis (AD) when their eruptions were aggravated and in non-atopic healthy controls, and then analysed the possible correlation between these values and the levels of several clinical markers. The plasma levels of both sCD30 and sCD26 were significantly higher in AD patients than in controls, both in exacerbation status and after conventional treatment. Multiple regression analyses showed that plasma sCD30 was a much better predictor of the levels of serum IgE, serum LDH and plasma sCD25, and the area and the score of AD eruption than sCD26, although elevated levels of both sCD30 and sCD26 are associated with these clinical predictors of AD. Importantly, sCD30 plasma levels decreased significantly in AD patients after conventional treatment, while no significant transition was noted in the concentration of sCD26. Moreover, a significant reduction of sCD30 levels was observed in the group of patients whose eruption score was reduced > 50%, whereas it was not in those < 50%. These findings provide evidence that the successful treatment of AD is associated with down-activation of Th2. PMID:10931130

Circulating follicular helper T cells in Crohn's disease (CD) and CD-associated colorectal cancer.

PubMed

Wang, Zhenlong; Wang, Zhiming; Diao, Yanqing; Qian, Xiaoli; Zhu, Nan; Dong, Wen

2014-09-01

Follicular helper T cells (Tfh) represent a distinct subset of CD4+ T cells specialized in providing help to B lymphocytes. Studies have indicated that Tfh in circulating blood can act as a prognostic marker for diseases. In the current study, we investigated the percentages of circulating Tfh (CTfh) in Crohn's disease (CD) and CD-associated colorectal cancer (CRC). CTfh and it subtypes were determined by measuring CD3, CD4, CXCR5, CXCR3, and CCR6 using flow cytometry in 32 healthy controls and 78 CD patients, which included 16 CD-associated CRC. Data showed that proportion of CTfh in CD4+ T cells was significantly increased in CD patients (9.8 %) than in controls (5.1 %) (p < 0.01). Further analysis revealed that the upregulation of CTfh was contributed by CTfh-Th1 subtype and CTfh-Th17 subtype. Investigating the behavior of the patients demonstrated that prevalence of CTfh was significantly elevated in penetrating CD (20.9 %) than inflammatory CD (8.2 %) or stricturing CD (7.5 %). In addition, we analyzed CTfh in CD-associated CRC, and identified that patients with CRC had 1.59-fold higher percentage of CTfh than patients without CRC (p < 0.01). Furthermore, the distribution of CTfh subsets was significantly altered in patients with the cancer. This study suggests the involvement of CTfh in CD and CD-associated CRC, in which the effect of CTfh is partially different between these two diseases.

Size-controlled synthesis of nanocrystalline CdSe thin films by inert gas condensation

NASA Astrophysics Data System (ADS)

Sharma, Jeewan; Singh, Randhir; Kumar, Akshay; Singh, Tejbir; Agrawal, Paras; Thakur, Anup

2018-02-01

Size, shape and structure are considered to have significant influence on various properties of semiconducting nanomaterials. Different properties of these materials can be tailored by controlling the size. Size-controlled CdSe crystallites ranging from ˜ 04 to 95 nm were deposited by inert gas-condensation technique (IGC). In IGC method, by controlling the inert gas pressure in the condensation chamber and the substrate temperature or both, it was possible to produce nanoparticles with desired size. Structure and crystallite size of CdSe thin films were determined from Hall-Williamson method using X-ray diffraction data. The composition of CdSe samples was estimated by X-ray microanalysis. It was confirmed that CdSe thin film with different nanometer range crystallite sizes were synthesized with this technique, depending upon the synthesis conditions. The phase of deposited CdSe thin films also depend upon deposition conditions and cubic to hexagonal phase transition was observed with increase in substrate temperature. The effect of crystallite size on optical and electrical properties of these films was also studied. The crystallite size affects the optical band gap, electrical conductivity and mobility activation of nanocrystalline CdSe thin films. Mobility activation study suggested that there is a quasi-continuous linear distribution of three different trap levels below the conduction band.

Spatial-temporal migration laws of Cd in Jiaozhou Bay

NASA Astrophysics Data System (ADS)

Yang, Dongfang; Li, Haixia; Zhang, Xiaolong; Wang, Qi; Miao, Zhenqing

2018-02-01

Many marine bays have been polluted by various pollutants, and understanding the migration laws is essential to scientific research and pollution control. This paper analyzed the spatial and temporal migration laws of Cd in waters in Jiaozhou Bay during 1979—1983. Results showed that there were twenty spatial-temporal migration law for the migration processes of Cd. These laws were helpful for better understanding the migration of Cd in marine bay, providing basis for scientific research and pollution control.

Differential Impact of Acute High-Intensity Exercise on Circulating Endothelial Microparticles and Insulin Resistance between Overweight/Obese Males and Females

PubMed Central

Durrer, Cody; Robinson, Emily; Wan, Zhongxiao; Martinez, Nic; Hummel, Michelle L.; Jenkins, Nathan T.; Kilpatrick, Marcus W.; Little, Jonathan P.

2015-01-01

Background An acute bout of exercise can improve endothelial function and insulin sensitivity when measured on the day following exercise. Our aim was to compare acute high-intensity continuous exercise (HICE) to high-intensity interval exercise (HIIE) on circulating endothelial microparticles (EMPs) and insulin sensitivity in overweight/obese men and women. Methods Inactive males (BMI = 30 ± 3, 25 ± 6 yr, n = 6) and females (BMI = 28 ± 2, 21 ± 3 yr, n = 7) participated in three experimental trials in a randomized counterbalanced crossover design: 1) No exercise control (Control); 2) HICE (20 min cycling @ just above ventilatory threshold); 3) HIIE (10 X 1-min @ ∼90% peak aerobic power). Exercise conditions were matched for external work and diet was controlled post-exercise. Fasting blood samples were obtained ∼18 hr after each condition. CD62E+ and CD31+/CD42b- EMPs were assessed by flow cytometry and insulin resistance (IR) was estimated by homeostasis model assessment (HOMA-IR). Results There was a significant sex X exercise interaction for CD62E+ EMPs, CD31+/CD42b- EMPs, and HOMA-IR (all P<0.05). In males, both HICE and HIIE reduced EMPs compared to Control (P≤0.05). In females, HICE increased CD62E+ EMPs (P<0.05 vs. Control) whereas CD31+/CD42b- EMPs were unaltered by either exercise type. There was a significant increase in HOMA-IR in males but a decrease in females following HIIE compared to Control (P<0.05). Conclusions Overweight/obese males and females appear to respond differently to acute bouts of high-intensity exercise. A single session of HICE and HIIE reduced circulating EMPs measured on the morning following exercise in males but in females CD62E+ EMPs were increased following HICE. Next day HOMA-IR paradoxically increased in males but was reduced in females following HIIE. Future research is needed to investigate mechanisms responsible for potential differential responses between males and females. PMID:25710559

Effects of cadmium-spiked sediment on cadmium accumulation and bioturbation by nymphs of the burrowing mayfly Hexagenia bilineata

USGS Publications Warehouse

Bartsch, Michelle; Cope, W. Gregory; Rada, Ronald G.

1999-01-01

We assessed accumulation of cadmium (Cd) and bioturbation by nymphs of the burrowing mayfly Hexagenia bilineata as indicators of exposure to Cd-spiked sediment in a 21-d test. Surficial sediments (top 5 cm) from Pool 7 of the Upper Mississippi River were spiked with Cd to concentrations of 3, 7, and 15 µg Cd g-1 dry weight. The experimental design was completely randomized, with three Cd-spiked sediment treatments plus an unspiked sediment control (1 µg Cd g-1 dry weight), and 10 nymphs in each of six replicates per treatment. Nymphs accumulated Cd during the 21-d exposure; mean concentrations varied from 0.22 to 6.24 µg g-1 dry weight, and tissue concentrations were correlated with Cd concentration in unfiltered test water (r = 0.93, P -1 treatment (our greatest exposure concentration) did not differ significantly from the control. Concentrations of Cd in unfiltered, overlying test water increased significantly within treatments during the test, indicating that nymphs mobilized sediment-associated Cd into the overlying water, presumably through burrowing and respiratory activities.

The CD4/CD8 ratio is associated with coronary artery disease (CAD) in elderly Chinese patients.

PubMed

Gao, Pan; Rong, Hong-Hui; Lu, Ting; Tang, Gang; Si, Liang-Yi; Lederer, James A; Xiong, Wei

2017-01-01

The aim of this study was to investigate the relationship between number of circulating T cells and coronary artery disease (CAD) in an elderly Chinese population. A total of 295 elderly inpatients (age≥60) were included in this cross-sectional study. Their clinical and biochemical characteristics were recorded. Patients were divided to two groups: control patients and CAD patients. The risk factors of CAD were explored by binary logistic regression analysis. Compared with control patients, the ratio of CD4 to CD8 T cells was significantly increased in CAD patients. There was no difference in the number of CD3, CD4, and CD8 T cells between the two groups. Multiple logistic regression analysis showed that CAD was independently associated with age, gender, body mass index (BMI), systolic blood pressure (SBP), chronic heart failure (CHF) and the CD4/CD8 ratio. In addition, after adjusting for different clinical parameters (including gender, age, CHF, hypertension, arrhythmia, SBP, and BMI), the risk of CAD was significantly increased in patients with a CD4/CD8 ratio>1.5. There was a strong and independent association between the ratio of CD4/CD8 and CAD in elderly Chinese population. Copyright © 2016. Published by Elsevier B.V.

Impaired circulating CD4+ LAP+ regulatory T cells in patients with acute coronary syndrome and its mechanistic study.

PubMed

Zhu, Zheng-Feng; Meng, Kai; Zhong, Yu-Cheng; Qi, Liang; Mao, Xiao-Bo; Yu, Kun-Wu; Zhang, Wei; Zhu, Peng-Fei; Ren, Ze-Peng; Wu, Bang-Wei; Ji, Qin-Wei; Wang, Xiang; Zeng, Qiu-Tang

2014-01-01

CD4(+) latency-associated peptide (LAP)(+) regulatory T cells (Tregs) are a newly discovered T cell subset in humans and the role of these cells in patients with acute coronary syndrome (ACS) has not been explored. We designed to investigate whether circulating frequency and function of CD4(+)LAP(+) Tregs are defective in ACS. One hundred eleven ACS patients (acute myocardial infarction and unstable angina) and 117 control patients were enrolled in the study. The control patients consisted of chronic stable angina (CSA) and chest pain syndrome (CPS). The frequencies of circulating CD4(+)LAP(+) Tregs and the expression of the transmembrane protein glycoprotein-A repetitions predominant (GARP) on CD4(+) T cells were determined by flow cytometry. The function of CD4(+)LAP(+) Tregs was detected using thymidine uptake. Serum interleukin-10 (IL-10) and transforming growth factor-β protein (TGF-β) levels were detected using ELISA and expression of GARP mRNA in peripheral blood mononuclear cells (PBMCs) was measured by real time-polymerase chain reaction. We found ACS patients had a significantly lower frequency of circulating CD4(+)LAP(+) Tregs, and the function of these cells was reduced compared to controls. The expression of GARP in CD4(+) T cells and the serum levels of TGF-β in ACS patients were lower than those of control patients. The serum levels of IL-10 were similar between the two cohorts. A novel regulatory T cell subset, defined as CD4(+)LAP(+) T cells is defective in ACS patients.

Gender-stratified analysis of DLG5 R30Q in 4707 patients with Crohn disease and 4973 controls from 12 Caucasian cohorts.

PubMed

Browning, B L; Annese, V; Barclay, M L; Bingham, S A; Brand, S; Büning, C; Castro, M; Cucchiara, S; Dallapiccola, B; Drummond, H; Ferguson, L R; Ferraris, A; Fisher, S A; Gearry, R B; Glas, J; Henckaerts, L; Huebner, C; Knafelz, D; Lakatos, L; Lakatos, P L; Latiano, A; Liu, X; Mathew, C; Müller-Myhsok, B; Newman, W G; Nimmo, E R; Noble, C L; Palmieri, O; Parkes, M; Petermann, I; Rutgeerts, P; Satsangi, J; Shelling, A N; Siminovitch, K A; Török, H-P; Tremelling, M; Vermeire, S; Valvano, M R; Witt, H

2008-01-01

DLG5 p.R30Q has been reported to be associated with Crohn disease (CD), but this association has not been replicated in most studies. A recent analysis of gender-stratified data from two case-control studies and two population cohorts found an association of DLG5 30Q with increased risk of CD in men but not in women and found differences between 30Q population frequencies for males and females. Male-female differences in population allele frequencies and male-specific risk could explain the difficulty in replicating the association with CD. DLG5 R30Q genotype data were collected for patients with CD and controls from 11 studies that did not include gender-stratified allele counts in their published reports and tested for male-female frequency differences in controls and for case-control frequency differences in men and in women. The data showed no male-female allele frequency differences in controls. An exact conditional test gave marginal evidence that 30Q is associated with decreased risk of CD in women (p = 0.049, OR = 0.87, 95% CI 0.77 to 1.00). There was also a trend towards reduced 30Q frequencies in male patients with CD compared with male controls, but this was not significant at the 0.05 level (p = 0.058, OR = 0.87, 95% CI 0.74 to 1.01). When data from this study were combined with previously published, gender-stratified data, the 30Q allele was found to be associated with decreased risk of CD in women (p = 0.010, OR = 0.86, 95% CI 0.76 to 0.97), but not in men. DLG5 30Q is associated with a small reduction in risk of CD in women.

Epidermal growth factor receptor inhibition by anti-CD147 therapy in cutaneous squamous cell carcinoma.

PubMed

Frederick, John W; Sweeny, Larissa; Hartman, Yolanda; Zhou, Tong; Rosenthal, Eben L

2016-02-01

Advanced cutaneous squamous cell carcinoma (SCC) is an uncommon and aggressive malignancy. As a result, there is limited understanding of its biology and pathogenesis. CD147 and epidermal growth factor receptor (EGFR) have been identified as oncologically important targets, but their relationship remains undefined in cutaneous SCC. Multiple cutaneous SCC cell lines (Colo-16, SRB-1, and SRB-12), were treated in vitro with a range of chimeric anti-CD147 monoclonal antibody (mAb) (0, 50, 100, and 200 µg/mL) or transfected with a small interfering RNA against CD147 (SiCD147). Cell proliferation, migration (scratch wound healing assay), and protein expression was then assessed. In vivo, Colo-16 flank xenografts were treated anti-CD147 mAb (150 µg i.p. triweekly). After treatment with anti-CD147 (200 µg/mL), there was a significant decrease in proliferation for all cell lines relative to controls (p < .005). In addition, treatment with anti-CD147 (200 µg/mL) resulted in decreased cell migration for all cell lines, with an average of 43% reduction in closure compared to controls (p < .001). Colo-16 SiCD147 expression demonstrated similar reduction in proliferation and wound closure. Anti-CD147 antibody therapy and siRNA mediated reduction in CD147 expression were both found to decrease protein expression of EGFR, which correlated with a reduction in downstream total and phosphorylated protein kinase B (pAKT). Tumor growth in vivo was reduced for both the anti-CD147 treatment group and the SiCD147 group relative to controls. Inhibition and downregulation of CD147 in cutaneous SCC resulted in suppression of the malignant phenotype in vitro and in vivo, which may be mediated in part by an alteration in EGFR expression. As a result, CD147 may serve as a potential therapeutic target for advanced cutaneous SCC. © 2014 Wiley Periodicals, Inc.

A correlate of HIV-1 control consisting of both innate and adaptive immune parameters best predicts viral load by multivariable analysis in HIV-1 infected viremic controllers and chronically-infected non-controllers.

PubMed

Tomescu, Costin; Liu, Qin; Ross, Brian N; Yin, Xiangfan; Lynn, Kenneth; Mounzer, Karam C; Kostman, Jay R; Montaner, Luis J

2014-01-01

HIV-1 infected viremic controllers maintain durable viral suppression below 2000 copies viral RNA/ml without anti-retroviral therapy (ART), and the immunological factor(s) associated with host control in presence of low but detectable viral replication are of considerable interest. Here, we utilized a multivariable analysis to identify which innate and adaptive immune parameters best correlated with viral control utilizing a cohort of viremic controllers (median 704 viral RNA/ml) and non-controllers (median 21,932 viral RNA/ml) that were matched for similar CD4+ T cell counts in the absence of ART. We observed that HIV-1 Gag-specific CD8+ T cell responses were preferentially targeted over Pol-specific responses in viremic controllers (p = 0.0137), while Pol-specific responses were positively associated with viral load (rho = 0.7753, p = 0.0001, n = 23). Viremic controllers exhibited significantly higher NK and plasmacytoid dendritic cells (pDC) frequency as well as retained expression of the NK CD16 receptor and strong target cell-induced NK cell IFN-gamma production compared to non-controllers (p<0.05). Despite differences in innate and adaptive immune function however, both viremic controllers (p<0.05) and non-controller subjects (p<0.001) exhibited significantly increased CD8+ T cell activation and spontaneous NK cell degranulation compared to uninfected donors. Overall, we identified that a combination of innate (pDC frequency) and adaptive (Pol-specific CD8+ T cell responses) immune parameters best predicted viral load (R2 = 0.5864, p = 0.0021, n = 17) by a multivariable analysis. Together, this data indicates that preferential Gag-specific over Pol-specific CD8+ T cell responses along with a retention of functional innate subsets best predict host control over viral replication in HIV-1 infected viremic controllers compared to chronically-infected non-controllers.

Distinct kinetics in the frequency of peripheral CD4+ T cells in patients with ulcerative colitis experiencing a flare during treatment with mesalazine or with a herbal preparation of myrrh, chamomile, and coffee charcoal.

PubMed

Langhorst, Jost; Frede, Annika; Knott, Markus; Pastille, Eva; Buer, Jan; Dobos, Gustav J; Westendorf, Astrid M

2014-01-01

We found the first evidence of the efficacy of a herbal treatment with myrrh, dry extract of chamomile flowers, and coffee charcoal for ulcerative colitis (UC). However, the impact of the herbal treatment on the CD4+ T-cell compartment, which is essential for both the induction of UC and the maintenance of tolerance in the gut, is not well understood. To analyze the frequency and functional phenotype of CD4+ T cells and of immune-suppressive CD4+CD25high regulatory T cells (Tregs) in healthy control subjects, patients with UC in remission, and patients with clinical flare of UC. Patients in clinical remission were treated with either mesalazine or the herbal preparation for 12 months. The frequencies of whole CD4+ T cells, CD4+CD25med effector T cells, and Tregs and the expression of Foxp3 within the CD4+CD25hig Tregs were determined by flow cytometry at 6 time points. We determined the suppressive capability of Tregs from healthy control subjects and from patients in remission or clinical flare. A total of 79 patients (42 women, 37 men; mean age, 48.5 years; 38 with clinical flare) and 5 healthy control subjects were included in the study. At baseline the frequencies of whole CD4+ T cells, CD4+CD25med effector cells, and Tregs did not differ between the two treatment groups and the healthy control subjects. In addition, patients with UC in sustained clinical remission showed no alteration from baseline after 1, 3, 6, 9, or 12 months of either treatment. In contrast, CD4+ T cells, CD4+CD25med effector T cells, and Tregs demonstrated distinctly different patterns at time points pre-flare and flare. The mesalazine group showed a continuous but not statistically significant increase from baseline to pre-flare and flare (p = ns). In the herbal treatment group, however, the percentage of the CD4+ T cells was lower at pre-flare than at baseline. This decrease was completely reversed after flare, when a significant increase was seen (CD4+CD25med pre-flare/flare p = 0.0461; CD4+CD25high baseline/flare p = 0.0269 and pre-flare/flare p = 0.0032). In contrast, no changes in the expression of Foxp3 cells were detected within the subsets of CD4+CD25high regulatory T cells. Of note, no alterations were detected in the suppressive capability of CD4+CD25high regulatory T cells isolated from the peripheral blood of healthy donors, from patients in remission, or from patients with clinical flare. In patients with UC experiencing acute flare, the CD4+ T compartment demonstrates a distinctly different pattern during treatment with myrrh, chamomile extract, and coffee charcoal than during treatment with mesalazine. These findings suggest an active repopulation of regulatory T cells during active disease. EU Clinical Trials Register 2007-007928-18/DE.

Distinct Kinetics in the Frequency of Peripheral CD4+ T Cells in Patients with Ulcerative Colitis Experiencing a Flare during Treatment with Mesalazine or with a Herbal Preparation of Myrrh, Chamomile, and Coffee Charcoal

PubMed Central

Langhorst, Jost; Frede, Annika; Knott, Markus; Pastille, Eva; Buer, Jan; Dobos, Gustav J.; Westendorf, Astrid M.

2014-01-01

Background We found the first evidence of the efficacy of a herbal treatment with myrrh, dry extract of chamomile flowers, and coffee charcoal for ulcerative colitis (UC). However, the impact of the herbal treatment on the CD4+ T-cell compartment, which is essential for both the induction of UC and the maintenance of tolerance in the gut, is not well understood. Aim To analyze the frequency and functional phenotype of CD4+ T cells and of immune-suppressive CD4+CD25high regulatory T cells (Tregs) in healthy control subjects, patients with UC in remission, and patients with clinical flare of UC. Methods Patients in clinical remission were treated with either mesalazine or the herbal preparation for 12 months. The frequencies of whole CD4+ T cells, CD4+CD25med effector T cells, and Tregs and the expression of Foxp3 within the CD4+CD25hig Tregs were determined by flow cytometry at 6 time points. We determined the suppressive capability of Tregs from healthy control subjects and from patients in remission or clinical flare. Results A total of 79 patients (42 women, 37 men; mean age, 48.5 years; 38 with clinical flare) and 5 healthy control subjects were included in the study. At baseline the frequencies of whole CD4+ T cells, CD4+CD25med effector cells, and Tregs did not differ between the two treatment groups and the healthy control subjects. In addition, patients with UC in sustained clinical remission showed no alteration from baseline after 1, 3, 6, 9, or 12 months of either treatment. In contrast, CD4+ T cells, CD4+CD25medeffector T cells, and Tregs demonstrated distinctly different patterns at time points pre-flare and flare. The mesalazine group showed a continuous but not statistically significant increase from baseline to pre-flare and flare (p = ns). In the herbal treatment group, however, the percentage of the CD4+ T cells was lower at pre-flare than at baseline. This decrease was completely reversed after flare, when a significant increase was seen (CD4+CD25med pre-flare/flare p = 0.0461; CD4+CD25high baseline/flare p = 0.0269 and pre-flare/flare p = 0.0032). In contrast, no changes in the expression of Foxp3 cells were detected within the subsets of CD4+CD25high regulatory T cells. Of note, no alterations were detected in the suppressive capability of CD4+CD25high regulatory T cells isolated from the peripheral blood of healthy donors, from patients in remission, or from patients with clinical flare. Conclusions In patients with UC experiencing acute flare, the CD4+ T compartment demonstrates a distinctly different pattern during treatment with myrrh, chamomile extract, and coffee charcoal than during treatment with mesalazine. These findings suggest an active repopulation of regulatory T cells during active disease. Trial Registration EU Clinical Trials Register 2007-007928-18/DE PMID:25144293

Ricinus communis L. A Value Added Crop for Remediation of Cadmium Contaminated Soil.

PubMed

Bauddh, Kuldeep; Singh, Kripal; Singh, Rana P

2016-02-01

Heavy metal pollution of soil is a global environmental problem and therefore its remediation is of paramount importance. Cadmium (Cd) is a potential toxicant to living organisms and even at very low concentrations. This study was aimed to assess the effectiveness of Ricinus communis for remediation of Cd contaminated soils. For this, growth and biomass of R. communis and Cd accumulation, translocation and partitioning in different plant parts were investigated after 8 months of plant growth in Cd contaminated soil (17.50 mg Cd kg−1 soil). Eight months old plants stabilized 51 % Cd in its roots and rest of the metal was transferred to the stem and leaves. There were no significant differences in growth, biomass and yield between control and Cd treated plants, except fresh weight of shoots. The seed yield per plant was reduced only by 5 % of Cd contaminated plants than control. The amount of Cd translocated to the castor seeds was nominal i.e. 0.007 µg Cd g−1 seeds. The bioconcentration factor reduced significantly in shoots and seeds in comparison to roots. The data indicates that R. communis is highly tolerant to Cd contamination and can be used for remediation of heavy metal polluted sites.

Biochar and Glomus caledonium Influence Cd Accumulation of Upland Kangkong (Ipomoea aquatica Forsk.) Intercropped with Alfred Stonecrop (Sedum alfredii Hance)

PubMed Central

Hu, Junli; Wu, Fuyong; Wu, Shengchun; Lam, Cheung Lung; Lin, Xiangui; Wong, Ming Hung

2014-01-01

Both biochar application and mycorrhizal inoculation have been proposed to improve plant growth and alter bioaccumulation of toxic metals. A greenhouse pot trial was conducted to investigate growth and Cd accumulation of upland kangkong (Ipomoea aquatica Forsk.) intercropped with Alfred stonecrop (Sedum alfredii Hance) in a Cd-contaminated soil inoculated with Glomus caledonium and/or applied with biochar. Compared with the monocultural control, intercropping with stonecrop (IS) decreased kangkong Cd acquisition via rhizosphere competition, and also decreased kangkong yield. Gc inoculation (+M) accelerated growth and Cd acquisition of stonecrop, and hence resulted in further decreases in kangkong Cd acquisition. Regardless of IS and +M, biochar addition (+B) increased kangkong yield via elevating soil available P, and decreased soil Cd phytoavailability and kangkong Cd concentration via increasing soil pH. Compared with the control, the treatment of IS + M + B had a substantially higher kangkong yield (+25.5%) with a lower Cd concentration (−62.7%). Gc generated additive effects on soil alkalinization and Cd stabilization to biochar, causing lower DTPA-extractable (phytoavailable) Cd concentrations and post-harvest transfer risks. PMID:24728157

Colloidal Random Terpolymers: Controlling Reactivity Ratios of Colloidal Comonomers via Metal Tipping

DOE PAGES

Pavlopoulos, Nicholas G.; Dubose, Jeffrey T.; Hartnett, Erin D.; ...

2016-07-26

We report on a versatile synthetic m-shell nanoparticles (NPs) in the backbone, along with semiconductor CdSe@CdS nanorod (NR), or tetrapod (TP) side chain groups. A seven-step colloidal total synthesis enabled the synthesis of well-defined colloidal comonomers composed of a dipolar Au@CoNP attached to a single CdSe@CdS NR, or TP, where magnetic dipolar associations between Au@CoNP units promoted the formation of colloidal co- or terpolymers. The key step in this synthesis was the ability to photodeposit a single AuNP tip onto CdSe@CdS NR or TP that enables selective seeding of a dipolar CoNP onto the AuNP seed. In conclusion, we showmore » that the variation of the AuNP size directly controlled the size and dipolar character of the CoNP tip, where the size modulation of the Au and Au@CoNP tips is analogous to control of comonomer reactivity ratios in classical copolymerization processes.« less

Modeling of axial vibrational control technique for CdTe VGF crystal growth under controlled cadmium partial pressure

NASA Astrophysics Data System (ADS)

Avetissov, I.; Kostikov, V.; Meshkov, V.; Sukhanova, E.; Grishechkin, M.; Belov, S.; Sadovskiy, A.

2014-01-01

A VGF growth setup assisted by axial vibrations of baffle submerged into CdTe melt with controlled Cd partial pressure was designed. An influence of baffle shape on flow velocity map, temperature distribution in CdTe melt and interface shape of growing crystal was analyzed by numerical simulation and physical modeling. To produce the desirable shape of crystal melt interface we slant under different angles vertical generatrix in a cylindrical disk and made chasing on faceplates of a disk. It was ascertained that a disk with conical generatrix formed more intensive convective flows from a faceplate with larger diameter. It was shown that at CdTe VGF crystal growth rate about 10 mm/h application of AVC technique made it possible to produce convex interface for 2 in. crystal diameter.

Soluble CD30 in normotensive pregnant women with isolated fetal intrauterine growth restriction: a comparison with preeclamptic women.

PubMed

Laskowska, Marzena; Laskowska, Katarzyna; Oleszczuk, Jan

2010-11-01

This study investigated the serum concentration of soluble CD30 (sCD30) in pregnant women with isolated fetal intrauterine growth restriction, in pregnancies complicated by preeclampsia with and without accompanying intrauterine growth restriction, and in normotensive healthy pregnant controls. Lower serum concentrations of sCD30 were observed in the group of normotensive pregnant women with a growth-restricted fetus in comparison with the group of healthy pregnant controls, and also in comparison with both preeclamptic groups of pregnant women with and without fetal growth restriction. The concentration of sCD30 in maternal serum from preeclamptic women did not differ in comparison with values from healthy controls or pregnancies complicated by isolated fetal intrauterine growth restriction. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Opioid maintenance therapy restores CD4+ T cell function by normalizing CD4+CD25(high) regulatory T cell frequencies in heroin user.

PubMed

Riss, Gina-Lucia; Chang, Dae-In; Wevers, Carolin; Westendorf, Astrid M; Buer, Jan; Scherbaum, Norbert; Hansen, Wiebke

2012-08-01

There is an increasing body of evidence that heroin addiction is associated with severe alterations in immune function, which might contribute to an increased risk to contract infectious diseases like hepatitis B and C or HIV. However, the impact of heroin consumption on the CD4(+) T cell compartment is not well understood. Therefore, we analyzed the frequency and functional phenotype of CD4(+) T cells as well as immune-suppressive CD4(+)CD25(high) regulatory T cells (Tregs) isolated from the peripheral blood of opiate addicts currently abusing heroin (n=27) in comparison to healthy controls (n=25) and opiate addicts currently in opioid maintenance treatment (OMT; n=27). Interestingly, we detected a significant increase in the percentage of CD4(+)CD25(high) Tregs in the peripheral blood of heroin addicted patients in contrast to patients in OMT. The proliferative response of CD4(+) T cells upon stimulation with anti-CD3 and anti-CD28 antibodies was significantly decreased in heroin users, but could be restored by depletion of CD25(high) regulatory T cells from CD4(+) T cells to similar values as observed from healthy controls and patients in OMT. These results suggest that impaired immune responses observed in heroin users are related to the expansion of CD4(+)CD25(high) Tregs and more importantly, can be restored by OMT. Copyright © 2012 Elsevier Inc. All rights reserved.

Antibody-Independent Control of γ-Herpesvirus Latency via B Cell Induction of Anti-Viral T Cell Responses

PubMed Central

McClellan, Kelly B; Gangappa, Shivaprakash; Speck, Samuel H; Virgin, Herbert W.

2006-01-01

B cells can use antibody-dependent mechanisms to control latent viral infections. It is unknown whether this represents the sole function of B cells during chronic viral infection. We report here that hen egg lysozyme (HEL)-specific B cells can contribute to the control of murine γ-herpesvirus 68 (γHV68) latency without producing anti-viral antibody. HEL-specific B cells normalized defects in T cell numbers and proliferation observed in B cell−/− mice during the early phase of γHV68 latency. HEL-specific B cells also reversed defects in CD8 and CD4 T cell cytokine production observed in B cell−/− mice, generating CD8 and CD4 T cells necessary for control of latency. Furthermore, HEL-specific B cells were able to present virally encoded antigen to CD8 T cells. Therefore, B cells have antibody independent functions, including antigen presentation, that are important for control of γ-herpesvirus latency. Exploitation of this property of B cells may allow enhanced vaccine responses to chronic virus infection. PMID:16789842

Qualitative features of the HIV-specific CD8+ T-cell response associated with immunologic control.

PubMed

Hersperger, Adam R; Migueles, Stephen A; Betts, Michael R; Connors, Mark

2011-05-01

Over the past 2 years, a clearer picture has emerged regarding the properties of HIV-specific CD8+ T cells associated with immunologic control of HIV replication. These properties represent a potential mechanism by which rare patients might control HIV replication in the absence of antiretroviral therapy. This review addresses the background and recent findings that have lead to our current understanding of these mechanism(s). Patients with immunologic control of HIV are not distinguished by targeted specificities, or greater numbers or breadth of their HIV-specific CD8+ T-cell response. For this reason, recent work has focused greater attention on qualitative features of this response. The qualitative features most closely associated with immunologic control of HIV are related to the granule-exocytosis-mediated elimination of HIV-infected CD4 T cells. The ability of HIV-specific CD8+ T cells to increase their contents of proteins known to mediate cytotoxicity, such as granzyme B and perforin, appears to be a critical means by which HIV-specific cytotoxic capacity is regulated. Investigation from multiple groups has now focused upon HIV-specific CD8+ T-cell granule-exocytosis-mediated cytotoxicity as a correlate of immunologic control of HIV. In the near future, a more detailed understanding of the qualities associated with immunologic control may provide critical insights regarding the necessary features of a response that should be stimulated by immunotherapies or T-cell-based vaccines.

Amniotic membrane traps and induces apoptosis of inflammatory cells in ocular surface chemical burn

PubMed Central

Liu, Ting; Zhai, Hualei; Xu, Yuanyuan; Dong, Yanling; Sun, Yajie; Zang, Xinjie

2012-01-01

Purpose Severe chemical burns can cause necrosis of ocular surface tissues following the infiltration of inflammatory cells. It has been shown that amniotic membrane transplantation (AMT) is an effective treatment for severe chemical burns, but the phenotypes of cells that infiltrate the amniotic membrane and the clinical significance of these cellular infiltrations have not previously been reported. The present work studies the inflammation cell traps and apoptosis inducing roles of the amniotic membrane after AMT in patients with acute chemical burns. Methods A total of 30 patients with acute alkaline burns were classified as having either moderate or severe burns. In all participants, AMT was performed within one week of his/her injury. After 7–9 days, the transplanted amniotic membranes were removed. Histopathological and immunohistochemical techniques were used for the examination and detection of infiltrating cells, and tests for the expression of CD (cluster of differentiation)15, CD68, CD3, CD20, CD57, CD31, CD147, and CD95 (Fas) were performed. A TUNEL (TdT-mediated dUTP nick end labeling) assay was used to confirm apoptosis of the infiltrating cells. Three patients with herpes simplex-induced keratitis who had undergone AMT to treat persistent epithelium defects were used as a control group. Amniotic membrane before transplantation was used as another control. Results After amniotic membrane transplantation, the number of infiltrating cells in patients with severe burns was significantly higher than in patients with moderate burns or in control patients (p<0.05). Among the severe burns patients, CD15 and CD68 were widely expressed in the infiltrating cells, and CD3, CD20, and CD57 were only found in a small number of cells. Occasionally, CD31-positive cells were found in the amniotic membranes. More cells that were CD147, Fas, and TUNEL positive were found in patients with severe burns than in patients with moderate burns or in control patients. Conclusions Neutrophils and macrophages were the main cells that had infiltrated into the amniotic membrane during the acute phase of healing from a chemical burns. AMT can trap different inflammatory cells and induce apoptosis of inflammatory cells in acute ocular chemical burns. PMID:22876141

CD40 ligand blockade induces CD4+ T cell tolerance and linked suppression.

PubMed

Honey, K; Cobbold, S P; Waldmann, H

1999-11-01

The CD40-CD40 ligand (CD40L) interaction is a key event in the initiation of an adaptive immune response, and as such the therapeutic value of CD40L blockade has been studied in many experimental models of tissue transplantation and autoimmune disease. In rodents, transplantation of allogeneic tissues under the cover of anti-CD40L Abs has resulted in prolonged graft survival but not tolerance. In this report, we show that failure to induce tolerance probably results from the inability of anti-CD40L Abs to prevent graft rejection elicited by the CD8+ T cell subset. When the CD8+ T cell population is controlled independently, using anti-CD8 Abs, then tolerance is possible. Transplantation tolerance induced by anti-CD4 mAbs can often be associated with dominant regulation, manifested as infectious tolerance and linked suppression, both of which are mediated by CD4+ T cells. We show here that CD4+ T cells rendered tolerant using anti-CD40L therapy exhibit the same regulatory property of linked suppression, as demonstrated by their ability to accept grafts expressing third party Ags only if they are expressed in conjunction with the tolerated Ags. This observation of linked suppression reveals a hitherto undocumented consequence of CD40L blockade that suggests the tolerant state is maintained by a dominant regulatory mechanism. Our results suggest that, although anti-CD40L Abs are attractive clinical immunotherapeutic agents, additional therapies to control aggressive CD8+ T cell responses may be required.

Reduction of CD147 surface expression on primary T cells leads to enhanced cell proliferation.

PubMed

Biegler, Brian; Kasinrerk, Watchara

2012-12-01

CD147 is a ubiquitously expressed membrane glycoprotein that has numerous functional associations in health and disease. However, the molecular mechanisms by which CD147 participates in these processes are unclear. Establishing physiologically relevant silencing of CD147 in primary T cells could provide clues essential for elucidating some aspects of CD147 biology. To date, achieving the knockdown of CD147 in primary T cells has remained elusive. Utilizing RNA interference and the Nucleofector transfection system, we were able to reduce the expression of CD147 in primary T cells. Comparison of basic functions, such as proliferation and CD25 expression, were then made between control populations and populations with reduced expression. Up-regulation of CD147 was found upon T-cell activation, indicating a role in T-cell responses. To better understand the possible importance of this up-regulation, we knocked down the expression of CD147 using RNA interference. When compared to control populations the CD147 knockdown populations exhibited increased proliferation. This alteration of cell proliferation, however, was not linked to a change in CD25 expression. We achieved reduction of CD147 surface expression in primary T cells by siRNA-mediated gene silencing. Our results point to CD147 having a possible negative regulatory role in T cell-mediated immune responses.

Crohn's disease and early exposure to domestic refrigeration.

PubMed

Malekzadeh, Fatemeh; Alberti, Corinne; Nouraei, Mehdi; Vahedi, Homayoon; Zaccaria, Isabelle; Meinzer, Ulrich; Nasseri-Moghaddam, Siavosh; Sotoudehmanesh, Rasoul; Momenzadeh, Sara; Khaleghnejad, Reza; Rashtak, Shahrooz; Olfati, Golrokh; Malekzadeh, Reza; Hugot, Jean-Pierre

2009-01-01

Environmental risk factors playing a causative role in Crohn's Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development. We thus conducted a pilot case control study to explore the association of CD with the exposure to domestic refrigeration in childhood. Using a standard questionnaire we interviewed 199 CD cases and 207 age-matched patients with irritable bowel syndrome (IBS) as controls. Cases and controls were followed by the same gastroenterologists of tertiary referral clinics in Tehran, Iran. The questionnaire focused on the date of the first acquisition of home refrigerator and freezer. Data were analysed by a multivariate logistic model. The current age was in average 34 years in CD cases and the percentage of females in the case and control groups were respectively 48.3% and 63.7%. Patients were exposed earlier than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01-4.29), P = 0.05). Comparable results were obtained looking for the exposure to freezer at home. Finally, among the other recorded items reflecting the hygiene and comfort at home, we also found personal television, car and washing machine associated with CD. This study supports the opinion that CD is associated with exposure to domestic refrigeration, among other household factors, during childhood.

Crohn's Disease and Early Exposure to Domestic Refrigeration

PubMed Central

Malekzadeh, Fatemeh; Alberti, Corinne; Nouraei, Mehdi; Vahedi, Homayoon; Zaccaria, Isabelle; Meinzer, Ulrich; Nasseri-Moghaddam, Siavosh; Sotoudehmanesh, Rasoul; Momenzadeh, Sara; Khaleghnejad, Reza; Rashtak, Shahrooz; Olfati, Golrokh; Malekzadeh, Reza; Hugot, Jean-Pierre

2009-01-01

Background Environmental risk factors playing a causative role in Crohn's Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development. We thus conducted a pilot case control study to explore the association of CD with the exposure to domestic refrigeration in childhood. Methodology/Principal Findings Using a standard questionnaire we interviewed 199 CD cases and 207 age-matched patients with irritable bowel syndrome (IBS) as controls. Cases and controls were followed by the same gastroenterologists of tertiary referral clinics in Tehran, Iran. The questionnaire focused on the date of the first acquisition of home refrigerator and freezer. Data were analysed by a multivariate logistic model. The current age was in average 34 years in CD cases and the percentage of females in the case and control groups were respectively 48.3% and 63.7%. Patients were exposed earlier than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01–4.29), P = 0.05). Comparable results were obtained looking for the exposure to freezer at home. Finally, among the other recorded items reflecting the hygiene and comfort at home, we also found personal television, car and washing machine associated with CD. Conclusion This study supports the opinion that CD is associated with exposure to domestic refrigeration, among other household factors, during childhood. PMID:19177167

Alterations of the Subgingival Microbiota in Pediatric Crohn's Disease Studied Longitudinally in Discovery and Validation Cohorts

PubMed Central

Kelsen, Judith; Bittinger, Kyle; Pauly-Hubbard, Helen; Posivak, Leah; Grunberg, Stephanie; Baldassano, Robert; Lewis, James D; Wu, Gary D; Bushman, Frederic D

2016-01-01

Background Oral manifestations are common in Crohn's disease (CD). Here we characterized the subgingival microbiota in pediatric CD patients initiating therapy and after 8 weeks to identify microbial community features associated with CD and therapy. Methods Pediatric CD patients were recruited from The Children's Hospital of Pennsylvania. Healthy control subjects were recruited from primary care or orthopedics clinic. Subgingival plaque samples were collected at initiation of therapy and after 8 weeks. Treatment exposures included 5-ASAs, immunomodualtors, steroids, and infliximab. The microbiota was characterized by 16S rRNA gene sequencing. The study was repeated in separate discovery (35 CD, 43 healthy) and validation cohorts (43 CD, 31 healthy). Results A majority of subjects in both cohorts demonstrated clinical response after 8 weeks of therapy (discovery cohort 88%, validation cohort 79%). At week 0, both antibiotic exposure and disease state were associated with differences in bacterial community composition. Seventeen genera were identified in the discovery cohort as candidate biomarkers, of which 11 were confirmed in the validation cohort. Capnocytophaga, Rothia, and TM7 were more abundant in CD relative to healthy controls. Other bacteria were reduced in abundance with antibiotic exposure among CD subjects. CD-associated genera were not enriched compared to healthy controls after 8 weeks of therapy. Conclusions Subgingival microbial community structure differed with CD and antibiotic use. Results in the discovery cohort were replicated in a separate validation cohort. Several potentially pathogenic bacterial lineages were associated with CD but were not diminished in abundance by antibiotic treatment, suggesting targets for additional surveillance. PMID:26288001

Alterations of the Subgingival Microbiota in Pediatric Crohn's Disease Studied Longitudinally in Discovery and Validation Cohorts.

PubMed

Kelsen, Judith; Bittinger, Kyle; Pauly-Hubbard, Helen; Posivak, Leah; Grunberg, Stephanie; Baldassano, Robert; Lewis, James D; Wu, Gary D; Bushman, Frederic D

2015-12-01

Oral manifestations are common in Crohn's disease (CD). Here we characterized the subgingival microbiota in pediatric patients with CD initiating therapy and after 8 weeks to identify microbial community features associated with CD and therapy. Pediatric patients with CD were recruited from The Children's Hospital of Pennsylvania. Healthy control subjects were recruited from primary care or orthopedics clinic. Subgingival plaque samples were collected at initiation of therapy and after 8 weeks. Treatment exposures included 5-ASAs, immunomodulators, steroids, and infliximab. The microbiota was characterized by 16S rRNA gene sequencing. The study was repeated in separate discovery (35 CD, 43 healthy) and validation cohorts (43 CD, 31 healthy). Most subjects in both cohorts demonstrated clinical response after 8 weeks of therapy (discovery cohort 88%, validation cohort 79%). At week 0, both antibiotic exposure and disease state were associated with differences in bacterial community composition. Seventeen genera were identified in the discovery cohort as candidate biomarkers, of which 11 were confirmed in the validation cohort. Capnocytophaga, Rothia, and TM7 were more abundant in CD relative to healthy controls. Other bacteria were reduced in abundance with antibiotic exposure among CD subjects. CD-associated genera were not enriched compared with healthy controls after 8 weeks of therapy. Subgingival microbial community structure differed with CD and antibiotic use. Results in the discovery cohort were replicated in a separate validation cohort. Several potentially pathogenic bacterial lineages were associated with CD but were not diminished in abundance by antibiotic treatment, suggesting targets for additional surveillance.

CD4+  CD25+  GARP+ regulatory T cells display a compromised suppressive function in patients with dilated cardiomyopathy.

PubMed

Wei, Yuzhen; Yu, Kunwu; Wei, Hui; Su, Xin; Zhu, Ruirui; Shi, Huairui; Sun, Haitao; Luo, Quan; Xu, Wenbin; Xiao, Junhui; Zhong, Yucheng; Zeng, Qiutang

2017-07-01

Dilated cardiomyopathy (DCM) is a lethal inflammatory heart disease and closely connected with dysfunction of the immune system. Glycoprotein A repetitions predominant (GARP) expressed on activated CD4 + T cells with suppressive activity has been established. This study aimed to investigate the frequency and function of circulating CD4 +  CD25 +  GARP + regulatory T (Treg) cells in DCM. Forty-five DCM patients and 46 controls were enrolled in this study. There was a significant increase in peripheral T helper type 1 (Th1) and Th17 number and their related cytokines [interferon-γ (IFN-γ), interleukin (IL-17)], and an obvious decrease in Treg number, transforming growth factor-β 1 (TGF-β 1 ) levels and the expression of forkhead box P3 (FOXP3) and GARP in patients with DCM compared with controls. In addition, the suppressive function of CD4 +  CD25 +  GARP + Treg cells was impaired in DCM patients upon T-cell receptor stimulation detected using CFSE dye. Lower level of TGF-β 1 and higher levels of IFN-γ and IL-17 detected using ELISA were found in supernatants of the cultured CD4 +  CD25 +  GARP + Treg cells in DCM patients compared with controls. Together, our results indicate that CD4 +  CD25 +  GARP + Treg cells are defective in DCM patients and GARP seems to be a better molecular definition of the regulatory phenotype. Therefore, it might be an attractive stategy to pay more attention to GARP in DCM patients. © 2017 John Wiley & Sons Ltd.

The familial basis of facial emotion recognition deficits in adolescents with conduct disorder and their unaffected relatives.

PubMed

Sully, K; Sonuga-Barke, E J S; Fairchild, G

2015-07-01

There is accumulating evidence of impairments in facial emotion recognition in adolescents with conduct disorder (CD). However, the majority of studies in this area have only been able to demonstrate an association, rather than a causal link, between emotion recognition deficits and CD. To move closer towards understanding the causal pathways linking emotion recognition problems with CD, we studied emotion recognition in the unaffected first-degree relatives of CD probands, as well as those with a diagnosis of CD. Using a family-based design, we investigated facial emotion recognition in probands with CD (n = 43), their unaffected relatives (n = 21), and healthy controls (n = 38). We used the Emotion Hexagon task, an alternative forced-choice task using morphed facial expressions depicting the six primary emotions, to assess facial emotion recognition accuracy. Relative to controls, the CD group showed impaired recognition of anger, fear, happiness, sadness and surprise (all p < 0.005). Similar to probands with CD, unaffected relatives showed deficits in anger and happiness recognition relative to controls (all p < 0.008), with a trend toward a deficit in fear recognition. There were no significant differences in performance between the CD probands and the unaffected relatives following correction for multiple comparisons. These results suggest that facial emotion recognition deficits are present in adolescents who are at increased familial risk for developing antisocial behaviour, as well as those who have already developed CD. Consequently, impaired emotion recognition appears to be a viable familial risk marker or candidate endophenotype for CD.

The impact of mode of delivery on outcomes in patients with perianal Crohn's disease

PubMed Central

Cheng, Alice G; Oxford, Emily C; Sauk, Jenny; Nguyen, Deanna D; Yajnik, Vijay; Friedman, Sonia; Ananthakrishnan, Ashwin N

2014-01-01

Introduction Crohn's disease (CD) often affects women during the reproductive years. While several studies have examined the impact of pregnancy on luminal disease, limited literature exists in those with perianal CD. Decision regarding mode of delivery is a unique challenge in such patients due to concerns regarding the effect of pelvic floor trauma during delivery on pre-existing perianal involvement. Methods We performed a retrospective chart review of CD patients with established perianal disease undergoing either vaginal delivery or Caesarean section (C-section) at our institutions. We examined the occurrence of symptomatic perianal disease flares within 5 years after delivery in such women compared to non-pregnant CD controls. We also compared the occurrence of such flares between the two modes of delivery in women with established perianal CD. Results We identified 61 pregnant CD patients with established perianal disease (11 vaginal delivery, 50 via C-section) and 61 non-pregnant CD controls with perianal disease. One-third of the C-sections were primarily for obstetric indications. Six of the vaginal deliveries were complicated. Approximately 36% of cases had a symptomatic perianal flare within 1 year after delivery. This was similar across both modes of delivery (p=0.53), and similar to non-pregnant CD patients. There was no difference in the rates of perianal surgical intervention or luminal disease flares in our population based on mode of delivery, or between pregnant CD patients and non-pregnant CD controls. Conclusion We observed no difference in risk of symptomatic perianal flares in patients with established perianal CD delivering vaginally or via C-section. PMID:24918322

CD44 Splice Variants as Potential Players in Alzheimer's Disease Pathology.

PubMed

Pinner, Elhanan; Gruper, Yaron; Ben Zimra, Micha; Kristt, Don; Laudon, Moshe; Naor, David; Zisapel, Nava

2017-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive deficits, deposition of amyloid-β (Aβ) plaques, intracellular neurofibrillary tangles, and neuronal cell death. Neuroinflammation is commonly believed to participate in AD pathogenesis. CD44 is an inflammation-related gene encoding a widely-distributed family of alternatively spliced cell surface glycoproteins that have been implicated in inflammation, metastases, and inflammation-linked neuronal injuries. Here we investigated the expression patterns of CD44S (which does not contain any alternative exon) and CD44 splice variants in postmortem hippocampal samples from AD patients and matched non-AD controls. The expression of CD44S and CD44 splice variants CD44V3, CD44V6, and CD44V10 was significantly higher in AD patients compared to non-AD controls. Immunohistochemistry of human hippocampal sections revealed that CD44S differentially localized to neuritic plaques and astrocytes, whereas CD44V3, CD44V6, and CD44V10 expression was mostly neuronal. Consistent with these findings, we found that the expression of CD44V6 and CD44V10 was induced by Aβ peptide in neuroblastoma cells and primary neurons. Furthermore, in loss of function studies we found that both CD44V10-specific siRNA and CD44V10 antibody protected neuronal cells from Aβ-induced toxicity, suggesting a causal relationship between CD44V10 and neuronal cell death. These data indicate that certain CD44 splice variants contribute to AD pathology and that CD44V10 inhibition may serve as a new neuroprotective treatment strategy for this disease.

Effect of porcine circovirus type 2 (PCV2) on the function of splenic CD11c+ dendritic cells in mice.

PubMed

Wang, Xiaobo; Chen, Ligong; Yuan, Wanzhe; Li, Yanqin; Li, Limin; Li, Tanqing; Li, Huanrong; Song, Qinye

2017-05-01

Porcine circovirus-associated disease (PCVAD) caused by porcine circovirus type 2 (PCV2) is an important disease in the global pig industry. Dendritic cells (DCs) are the primary immune cells capable of initiating adaptive immune responses as well as major target cells of PCV2. To determine whether PCV2 affects the immune functions of DCs, we evaluated the expression of endocytosis and co-stimulatory molecules on DCs (CD11c + ) from PCV2-infected mouse spleen by flow cytometry (FCM). We also analyzed the main cytokines secreted by DCs (CD11c + ) and activation of CD4 + and CD8 + T cells by DCs (CD11c + ) through measurement of cytokine secretion, using ELISA. Compared with control mice, PCV2 did not affect the endocytic activity of DCs but it significantly enhanced TNF-α secretion and markedly decreased IFN-α secretion. Subsets of CD40 + , MHCII + CD40 + and CD137L + CD86 + DCs did not increase obviously, but MHCII + CD40 - and CD137L - CD80 + /CD86 + DCs increased significantly in PCV2-infected mouse spleen. Under the stimulation of DCs from PCV2-infected mouse, secretion of IFN-γ by CD4 + and CD8 + T cells and of IL-12 by CD8 + T cells was significantly lower than in control mice, while secretion of IL-4 by CD4 + T cells was remarkably higher. These results indicate that PCV2 modulates cytokine secretion and co-stimulatory molecule expression of DCs, and alters activation of CD4 + and CD8 + T cells by DCs. The immunomodulatory effects of PCV2 on DCs might be related to the host's immune dysfunction and persistent infection with this virus.

Creation of the TXP parenting questionnaire and study of its psychometric properties.

PubMed

Benito, Ana; Calvo, Gema; Real-López, Matías; Gallego, María José; Francés, Sonia; Turbi, Ángel; Haro, Gonzalo

2018-01-15

Parenting is linked to conduct disorders (CD) and substance related disorders (SRD) in adolescents, but with differences according to cultural context. A questionnaire with two versions (parenting questionnaire TXP-A for adolescents and TXP-C  for primary caregivers) was designed using the Delphi method to evaluate parenting practices related to CD and SRD in a Spanish population. It was validated in a community sample of 631 adolescents aged between 14 and 16 and their caregivers. Results suggest a 29-item TXP-A questionnaire with bifactorial structure: affection-communication and control-structure, with high internal (Cronbach’s alpha=0.89) and test-retest (intraclass correlation coefficient=0.94) reliabilities. Both factors are related to SRD (r=0.273, p<0.001) and with most of the psychopathological dimensions studied. The total score and affection-communication are related to dissocial disorder (t=3.259, p=0.001) and its severity (r=-0,119; p=0.003). Inter-observer reliability between adolescents and caregivers is low, in part because the 16-item TXP-C has a different bifactorial structure: affection-communication and prosocial values. TXP-C’s internal (Cronbach’s alpha=0.87) and test-retest (intraclass correlation coefficient=0.94) reliabilities are high. The total score and affection-communication were related to dissocial disorder (t=2.586; p=0.010) but TXP-C did not discriminate according to SRD. In conclusion, the TXP-A questionnaire for adolescents seems to be a reliable, valid and unbiased instrument that evaluates the perception of parenting practices, relating higher affection-communication and control-structure to less psychopathology and alcohol and drug use. TXP-C also seems to be reliable and unbiased, but shows less evidence of validity regarding substance use and psychopathology. .

Obesity suppresses circulating level and function of endothelial progenitor cells and heart function

PubMed Central

2012-01-01

Background and aim This study tested the hypothesis that obesity suppresses circulating number as well as the function of endothelial progenitor cells (EPCs) and left ventricular ejection fraction (LVEF). Methods High fat diet (45 Kcal% fat) was given to 8-week-old C57BL/6 J mice (n = 8) for 20 weeks to induce obesity (group 1). Another age-matched group (n = 8) were fed with control diet for 20 weeks as controls (group 2). The animals were sacrificed at the end of 20 weeks after obesity induction. Results By the end of study period, the heart weight, body weight, abdominal fat weight, serum levels of total cholesterol and fasting blood sugar were remarkably higher in group 1 than in group 2 (all p<0.01). The circulating level of EPCs (C-kit/CD31, Sca-1/KDR, CXCR4/CD34) was significantly lower in group 1 than in group 2 (p<0.03) at 18 h after critical limb ischemia induction. The angiogenesis and migratory ability of bone marrow-derived EPCs was remarkably impaired in group 1 compared to that in group 2 (all p<0.01). The repair ability of aortic endothelium damage by lipopolysaccharide was notably attenuated in group 1 compared with that in group 2 (p<0.01). Collagen deposition (Sirius red staining) and fibrotic area (Masson's Trichrome staining) in LV myocardium were notably increased in group 1 compared with group 2 (p<0.001). LVEF was notably lower, whereas LV end-diastolic and end-systolic dimensions were remarkably higher in group 1 than in group 2 (all p<0.001). Conclusions Obesity diminished circulating EPC level, impaired the recovery of damaged endothelium, suppressed EPC angiogenesis ability and LVEF, and increased LV remodeling. PMID:22747715

Progress on CD-DVD laser microfabrication method to develop cell culture scaffolds integrating biomimetic characteristics

NASA Astrophysics Data System (ADS)

Hautefeuille, Mathieu; Vázquez-Victorio, Genaro; Cruz-Ramírez, Aaron; Cabriales, Lucia; Jiménez-Diaz, Edgar; Escutia-Guadarrama, Lidia; López-Aparicio, Jehú; Pérez-Calixto, Daniel; Cano-Jorge, Mariel; Nieto-Rivera, Brenda; Sánchez-Olvera, Raúl

2018-02-01

The development of organ-on-chip and biological scaffolds is currently requiring simpler methods to microstructure biocompatible materials in three dimensions, fabricate structural and functional elements in biomaterials or modify the physicochemical properties of desired substrates. With the aim of creating simple, cost-effective alternatives to conventional existing techniques to produce such platforms with very specific properties, a low-power CD-DVD laser pickup head was recycled and mounted on a programmable three-axis micro-displacement system in order to modify the surface of polymeric materials in a local fashion. Thanks to a specially-designed method using a strongly absorbing additive coating the materials of interest, it has been possible to establish and precisely control processes useful in microtechnology for biomedical applications and normally restricted to much less affordable high-power lasers. In this work, we present our latest progress regarding the application of our fabrication technique to the development of organ-on-chip platforms thanks to the simple integration of several biomimetic characteristics typically achieved with traditional, less cost-effective microtechnology methods in one step or through replica-molding. Our straightforward approach indeed enables great control of local laser microablation for true on-demand biomimetic micropatterned designs in several transparent polymers and hydrogels of tunable stiffness and is allowing integration of microfluidics, microelectronics, optical waveguides, surface microstructuring and even transfer of superficial protein micropatterns on a variety of biocompatible materials. The results presented here were validated using hepatic and fibroblasts cell lines to demonstrate the viability of our procedure for organ-on-chip development and show the impact of such features in cell culture.

Prevalence of transfusion-transmitted Chagas disease among multitransfused patients in Brazil

PubMed Central

De Paula, Erich V; Goncales, Neiva SL; Xueref, Serge; Addas-Carvalho, Marcelo; Gilli, Simone CO; Angerami, Rodrigo N; Goncales, Fernando L

2008-01-01

Background Blood transfusion has always been an important route for Chagas Disease (CD) transmission. The high prevalence of CD in Latin America and its lifelong asymptomatic clinical picture pose a threat for the safety of the blood supply. The outcome of measures designed to improve transfusion safety can be assessed by evaluating the prevalence of CD among multitransfused patients Methods In order to assess the impact of CD control measures on the safety of the blood supply, an observational cross-sectional study was designed to determine the prevalence of CD in 351 highly transfused patients, in which vectorial transmission was excluded. This study compared patients that received transfusion products before (n = 230) and after (n = 121) 1997, when measures to control transfusion-transmitted CD were fully implemented in Brazil. Results The study group consisted of 351 patients exposed to high numbers of blood products during their lifetime (median number of units transfused = 51, range 10–2086). A higher prevalence of transfusion-transmitted CD (1.30%) was observed among multitransfused patients that received their first transfusion before 1997, compared with no cases of transfusion-transmitted CD among multitransfused patients transfused after that year. The magnitude of the exposure to blood products was similar among both groups (mean number of units transfused per year of exposure = 25.00 ± 26.46 and 23.99 ± 30.58 respectively; P = 0.75, Mann-Whitney test). Conclusion Multiple initiatives aimed to control vector and parental transmission of CD can significantly decrease transfusion-transmitted CD in Brazil. Our data suggest that mandatory donor screening for CD represents the most important measure to interrupt transmission of CD by blood transfusions. PMID:18199334

Immune responses and ultrastructural changes of hemocytes in freshwater crab Sinopotamon henanense exposed to elevated cadmium.

PubMed

Qin, Qin; Qin, Shengjuan; Wang, Lan; Lei, Wenwen

2012-01-15

Cadmium (Cd) is one of the most toxic heavy metals that can impact immunological parameters in aquatic animals. To investigate the immunotoxicity and ultrastructural changes of hemocytes, specimens of Sinopotamon henanense were exposed to different concentrations of cadmium and the differences in immunologic parameters between Cd exposure groups and control groups were investigated. Total hemocyte count (THC) in Cd-exposure groups were decreased significantly when compared with the control groups, especially in the groups treated with higher Cd concentrations and longer exposure time, while no significant differences were observed in the proportions of the three types of hemocytes. Phenoloxidase (PO) activities were significantly higher in Cd-exposure groups than the control groups. Superoxide dismutase (SOD) activities gradually increased in 7.25 and 14.5 mg L⁻¹ Cd groups, but in other higher Cd groups, they showed first increase and following decrease with the exposure time prolonged. Acid phosphatase (ACP) activities were induced at 48 h, and then decreased, while alkaline phosphatase (AKP) activities increased gradually until 96 h. Electron microscopic results showed that nucleus, mitochondria and rough endoplasm recutulum (rER) of three types of hemocytes were sensitive to acute Cd toxicity. In Cd-exposed groups, chromatin condensation, nucleus deformation and nucleus envelope rupture were noted. Additionally, mitochondrial dilation and rER degranulation were observed in Cd-treated crabs. These results suggested that immune response and organelles of hemocyte of S. henanense were impacted by Cd exposure, and the changes of these immunologic parameters reflect changes in crab immune response capability consequent to Cd exposure. Copyright © 2011 Elsevier B.V. All rights reserved.

Paediatric Crohn disease patients with stricturing behaviour exhibit ileal granulocyte–macrophage colony-stimulating factor (GM-CSF) autoantibody production and reduced neutrophil bacterial killing and GM-CSF bioactivity

PubMed Central

Jurickova, I; Collins, M H; Chalk, C; Seese, A; Bezold, R; Lake, K; Allmen, D; Frischer, J S; Falcone, R A; Trapnell, B C; Denson, L A

2013-01-01

Granulocyte–macrophage colony-stimulating factor (GM-CSF) autoantibodies are associated with stricturing behaviour in Crohn disease (CD). We hypothesized that CD ileal lamina propria mononuclear cells (LPMC) would produce GM-CSF autoantibodies and peripheral blood (PB) samples would contain GM-CSF neutralizing capacity (NC). Paediatric CD and control PBMC and ileal biopsies or LPMC were isolated and cultured and GM-CSF, immunoglobulin (Ig)G and GM-CSF autoantibodies production were measured by enzyme-linked immunosorbent assay (ELISA). Basal and GM-CSF-primed neutrophil bacterial killing and signal transducer and activator of transcription 5 (STAT5) tyrosine phosphorylation (pSTAT5) were measured by flow cytometry. GM-CSF autoantibodies were enriched within total IgG for LPMC isolated from CD ileal strictures and proximal margins compared to control ileum. Neutrophil bacterial killing was reduced in CD patients compared to controls. Within CD, neutrophil GM-CSF-dependent STAT5 activation and bacterial killing were reduced as GM-CSF autoantibodies increased. GM-CSF stimulation of pSTAT5 did not vary between controls and CD patients in washed PB granulocytes in which serum was removed. However, GM-CSF stimulation of pSTAT5 was reduced in whole PB samples from CD patients. These data were used to calculate the GM-CSF NC. CD patients with GM-CSF NC greater than 25% exhibited a fourfold higher rate of stricturing behaviour and surgery. The likelihood ratio (95% confidence interval) for stricturing behaviour for patients with elevation in both GM-CSF autoantibodies and GM-CSF NC was equal to 5 (2, 11). GM-CSF autoantibodies are produced by LPMC isolated from CD ileal resection specimens and are associated with reduced neutrophil bacterial killing. CD peripheral blood contains GM-CSF NC, which is associated with increased rates of stricturing behaviour. PMID:23600834

Dominant-negative TLR5 polymorphism reduces adaptive immune response to flagellin and negatively associates with Crohn's disease.

PubMed

Gewirtz, Andrew T; Vijay-Kumar, Matam; Brant, Steven R; Duerr, Richard H; Nicolae, Dan L; Cho, Judy H

2006-06-01

Crohn's disease (CD) is associated with elevated adaptive immunity to commensal microbes, with flagellin being a dominant antigen. In light of heightened awareness of the importance of innate immunity in regulating adaptive immunity and ambiguity as to the role of CD-associated immune responses in CD pathophysiology, we sought to determine whether natural acquisition of immune responses to flagellin were regulated by the innate immune flagellin receptor toll-like receptor 5 (TLR5) and determine whether persons carrying a recently defined common dominant-negative TLR5 polymorphism (TLR5-stop) might be protected from developing CD. Carriage rates of a recently defined dominant-negative TLR5 polymorphism (TLR5-stop) and levels of serum immunoreactivity to bacterial products were measured in inflammatory bowel disease patients, first-degree relatives, and unrelated controls. We observed that, in healthy subjects, persons carrying TLR5-stop had significantly lower levels of flagellin-specific IgG and IgA but had similar levels of total and LPS-specific Ig. Moreover, we observed that, among Jewish subjects, the carriage rate of TLR5-stop (in heterozygous state) was significantly less in CD patients, but not ulcerative colitis (UC) patients, compared with unaffected relatives and unrelated controls (5.4, 0.9, 6.0, and 6.5% for unaffected relatives, CD, UC, and unrelated Jewish controls, respectively, n = 296, 215, 185, and 416, respectively; P = 0.037 by likelihood calculation for CD vs. controls), indicating that TLR5-stop can protect persons of Jewish ethnicity against CD. We did not observe a significant association of TLR5-stop with CD in a non-Jewish cohort (11.1, 10.4, and 11.7% for unaffected relatives, CD, and UC, respectively; n = 841, 543, and 300 for unaffected relatives, respectively). These results demonstrate that natural acquisition of immune responses to flagellin are regulated by TLR5 and suggest that immune responses to flagellin are not merely associated with CD but rather promote the pathogenic response.

Implications of gluten exposure period, CD clinical forms, and HLA typing in the association between celiac disease and dental enamel defects in children. A case-control study.

PubMed

Majorana, Alessandra; Bardellini, Elena; Ravelli, Alberto; Plebani, Alessandro; Polimeni, Antonella; Campus, Guglielmo

2010-03-01

The association between coeliac disease (CD) and dental enamel defects (DED) is well known. The aim of this study was to investigate the prevalence of DED in children with CD and to specifically find the association of DED and gluten exposure period, CD clinical forms, HLA class II haplotype. This study was designed as a matched case-control study: 250 children were enrolled (125 coeliac children - 79 female and 46 male, 7.2 +/- 2.8 years and 125 healthy children). Data about age at CD diagnosis, CD clinical form, and HLA haplotype were recorded. Dental enamel defects were detected in 58 coeliac subjects (46.4%) against seven (5.6%) controls (P < 0.005). We found an association between DED and gluten exposure period, as among CD subjects the mean age at CD diagnosis was significantly (P = 0.0004) higher in the group with DED (3.41 +/- 1.27) than without DED (1.26 +/- 0.7). DED resulted more frequent (100%) in atypical and silent CD forms than in the typical one (30.93%). The presence of HLA DR 52-53 and DQ7antigens significantly increased the risk of DED (P = 0.0017) in coeliac children. Our results confirmed a possible correlation between HLA antigens and DED.

[The role of Cd-binding proteins and phytochelatins in the formation of cadmium resistance in Nicotiana plumbaginifolia cell lines].

PubMed

Fenik, S I; Solodushko, V G; Kaliniak, T B; Blium, Ia B

2007-01-01

Nicotiana plumbaginifolia callus lines with the equal resistance to cadmium have been produced under different selective conditions--either without inhibition of the phytochelatin synthesis (line Cd-R) or in the presence of the inhibitor butionine sulfoximine (line Cd-Ri). The level of phytochelatin synthesis in the line Cd-R five-fold exceeded the control value and in the line Cd-Ri it was twice as much as in the control. It was shown that in the control line mainly three cadmium-binding proteins are expressed of the molecular weihgts 41, 34 and 19 kD. The common feature of the both resistant lines is the expression of the cadmium-binding proteins of 40, 37 and 19 kD. The resistant lines differ with respect to the synthesis of relatively low-molecular cadmium-binding proteins. The proteins of the molecular weights 12.5, 11.5 and 9 kD are expressed in the line Cd-R, while the proteins of 13 and 10 kD are expressed in the line Cd-Ri. It was supposed that both the phytochelatins and the Cd-binding proteins contribute to the resisitance of N. plumbaginifolia callus lines to cadmium and the lack of the phytochelatins can be equilibrated by the changes in the low-molecular Cd-binding protein synthesis.

Nano-hetero functional materials for photocatalytic hydrogen generation

NASA Astrophysics Data System (ADS)

Tongying, Pornthip

This dissertation focuses on designing nanomaterials and investigating their photocatalytic response for H2 generation. Hydrogen has gained a lot of attention as a new source of sustainable energy. It can be used to directly generate power in fuel cells and to produce liquid fuels such as methanol. Water splitting is an ideal (clean) way of producing H2 because it uses water and sunlight, two renewable resources. To explore the use of nanostructures and particularly nanostructure heterojunctions for photocatalytic H2 generation, four different systems have been synthesized: (i) CdSe nanowires (NWs), (ii) CdSe/CdS core/shell NWs, (iii) CdSe NWs decorated with Au or Pt nanoparticles, and (iv) CdSe/CdS NWs decorated with Au or Pt nanoparticles. This is motivated by (a) the fact that CdSe NWs absorb light from the UV to the near infrared (b) the NW morphology simultaneously enables us to explore the role of nanoscale dimensionality in photocatalytic processes (c) a CdS coating can enhance photogenerated carrier lifetimes, and (d) metal nanoparticles are catalytically active and can also enhance charge separation efficiencies. Charge separation and charge transfer across interfaces are key aspects in the design of efficient photocatalysts for solar energy conversion. Femtosecond transient differential absorption (TDA) spectroscopy has been used as a tool to reveal how semiconductor/semiconductor and metal/semiconductor heterojunctions affect the charge separation and hydrogen generation efficiencies of these hybrid photocatalysts. The use of this technique in concert with hydrogen evolution tests also reveal how CdS, CdSe and metal NP interact within metal NP decorated CdSe and CdSe/CdS NWs during photocatalytic hydrogen generation reactions. Electron transfer events across both semiconductor/semiconductor and metal/semiconductor heterojunctions are followed to identify where H 2 is evolved and the role each heterojunction plays in determining a system's overall efficiency. To extend my study beyond 1D CdSe NWs, 2D CdSe nanosheets (NSs) have been synthesized. The use of cation exchange allows synthesizing micrometer-sized crystalline thin CdSe nanosheets (NSs), otherwise difficult to produce directly through solution-based methods. Starting from cubic-phased Cu2-xSe NSs as a template, CdSe NSs are obtained by cation exchange of copper to cadmium. This exchange reaction preserves the 2D morphology of the starting NSs and also retains the cubic crystal structure. Resulting CdSe NSs have a lateral size up to 6 mum and an average of thickness approximately 6 nm. Such large lateral dimensions are advantageous for single sheet optical measurements and for applications in optical and electronic devices.

Supplementation of conventional freezing medium with a combination of catalase and trehalose results in better protection of surface molecules and functionality of hematopoietic cells.

PubMed

Sasnoor, Lalita M; Kale, Vaijayanti P; Limaye, Lalita S

2003-10-01

Our previous studies had shown that a combination of the bio-antioxidant catalase and the membrane stabilizer trehalose in the conventional freezing mixture affords better cryoprotection to hematopoietic cells as judged by clonogenic assays. In the present investigation, we extended these studies using several parameters like responsiveness to growth factors, expression of growth factor receptors, adhesion assays, adhesion molecule expression, and long-term culture-forming ability. Cells were frozen with (test cells) or without additives (control cells) in the conventional medium containing 10% dimethylsulfoxide (DMSO). Experiments were done on mononuclear cells (MNC) from cord blood/fetal liver hematopoietic cells (CB/FL) and CD34(+) cells isolated from frozen MNC. Our results showed that the responsiveness of test cells to the two early-acting cytokines, viz. interleukin-3 (IL-3) and stem cell factor (SCF) in CFU assays was better than control cells as seen by higher colony formation at limiting concentrations of these cytokines. We, therefore, analyzed the expression of these two growth factor receptors by flow cytometry. We found that in cryopreserved test MNC, as well as CD34(+) cells isolated from them, the expression of both cytokine receptors was two- to three-fold higher than control MNC and CD34(+) cells isolated from them. Adhesion assays carried out with CB/FL-derived CD34(+) cells and KG1a cells showed significantly higher adherence of test cells to M210B4 than respective control cells. Cryopreserved test MNC as well as CD34(+) cells isolated from them showed increased expression of adhesion molecules like CD43, CD44, CD49d, and CD49e. On isolated CD34(+) cells and KG1a cells, there was a two- to three-fold increase in a double-positive population expressing CD34/L-selectin in test cells as compared to control cells. Long-term cultures (LTC) were set up with frozen MNC as well as with CD34(+) cells. Clonogenic cells from LTC were enumerated at the end of the fifth week. There was a significantly increased formation of CFU from test cells than from control cells, indicating better preservation of early progenitors in test cells. Our results suggest that use of a combination of catalase and trehalose as a supplement in the conventional freezing medium results in better protection of growth factor receptors, adhesion molecules, and functionality of hematopoietic cells, yielding a better graft quality.

Decreased gene expression of CD2AP in Chinese patients with sporadic Alzheimer's disease.

PubMed

Tao, Qing-Qing; Liu, Zhi-Jun; Sun, Yi-Min; Li, Hong-Lei; Yang, Ping; Liu, De-Shan; Jiang, Bin; Li, Xiao-Yan; Xu, Jian-Feng; Wu, Zhi-Ying

2017-08-01

Many sporadic Alzheimer's disease (SAD) risk genes have been identified in the last decades, but most of them have not been consistently accepted. Here, we sought to identify SAD-associated genes and their potential mechanisms involved in SAD pathogenesis. A 2-stage design was employed. In stage 1, 95 variants in 75 genes that were previously reported as SAD-risk genes in Caucasian populations were evaluated in 1857 subjects (422 SAD patients and 1435 controls). In stage 2, a subset of promising variants found in stage 1 were further evaluated in an independent cohort of 1001 subjects (254 SAD and 747 controls). Variants in CD2AP were significantly associated with SAD risk in our subjects. Furthermore, CD2AP gene expression in peripheral blood lymphocytes (PBL) from 209 SAD patients and 213 controls was determined. CD2AP gene expression in PBL was significantly decreased in patients with SAD as compared with controls. Our study suggests that CD2AP is an SAD-risk gene in Chinese Han population and CD2AP gene expression is decreased in the PBL of patients with SAD, indicating its possible systemic involvement in SAD. Copyright © 2017 Elsevier Inc. All rights reserved.

The effects of a human patient simulator vs. a CD-ROM on performance.

PubMed

Johnson, Don; Corrigan, Theresa; Gulickson, Gary; Holshouser, Elizabeth; Johnson, Sabine

2012-10-01

Military health care personnel need to have skills relative to caring for patients on the battlefield. No studies have compared the two teaching strategies of using the human patient simulator (HPS) and a CD-ROM in caring for combat injuries. The objective of this study was to determine if there were statistically significant differences in HPS and CD-ROM educational strategies relative to caring for patients who have trauma. A pretest/post-test prospective experimental design was used. Anesthesia students were randomly assigned to one of three groups: HPS, CD-ROM, or a control group. A valid and reliable instrument, Combat Performance, was used to evaluate the participant's ability to give care to trauma patients. A repeated analysis of variance and a least significant difference post hoc test were used to analyze the data. The HPS group performed better than the CD-ROM and control groups relative to performance (p = 0.001). There was no difference between the CD-ROM and control group (p = 0.171). We speculate that the HPS group performed better than the CD-ROM group because of the realism. In this study, the HPS method of instruction was a more effective method of teaching than the CD-ROM approach.

The C(-260)>T gene polymorphism in the promoter of the CD14 monocyte receptor gene is not associated with acute myocardial infarction.

PubMed

Longobardo, M T; Cefalù, A B; Pezzino, F; Noto, D; Emmanuele, G; Barbagallo, C M; Fiore, B; Monastero, R; Castello, A; Molini, V; Notarbartolo, A; Travali, S; Averna, M R

2003-11-01

CD surface molecules mediates cell activation and signaling. In particular, CD14 on blood monocytes mediate monocyte/macrophage activation by lipopolysaccharide. Lipopolysaccharide and its receptor, CD14, have been implicated in atherogenesis. It has been recently shown that a C(-260)T polymorphism in the promoter of the CD14 receptor may be a risk factor for coronary artery disease. Recently this association has been questioned because no increased risk was found with the T allele, even in the homozygous state. In the present study we investigated a possible association between the C(-260)T polymorphism in the CD14 promoter and acute myocardial infarction. Two hundred and thrteen patients with and acute myocardial infarction 213 healthy controls were included in the study. Genotype frequencies of the C(-260)T polymorphism in the CD14 promoter were determined by polimerase chain reaction and the amplified product was cleaved with HaeIII. The frequency of the T allele was not significantly different in patients compared with controls. In this study we were not able to detect differences of frequency of the allele T (-260) in the promoter of the CD14 receptor gene in survivors of myocardial infarction and controls.

Molecular structures of the inclusion complexes beta-cyclodextrin-1,2-bis(4-aminophenyl)ethane and beta-cyclodextrin-4,4'-diaminobiphenyl; packing of dimeric beta-cyclodextrin inclusion complexes.

PubMed

Giastas, Petros; Yannakopoulou, Konstantina; Mavridis, Irene M

2003-04-01

The present investigation is part of an ongoing study on the influence of the long end-functonalized guest molecules DBA and BNZ in the crystal packing of beta-cyclodextrin (betaCD) dimeric complexes. The title compounds are 2:2 host:guest complexes showing limited host-guest hydrogen bonding at the primary faces of the betaCD dimers. Within the betaCD cavity the guests exhibit mutual pi...pi interactions and between betaCD dimers perpendicular NH...pi interactions. The DBA guest molecule exhibits one extended and two bent conformations in the complex. The BNZ guest molecule is not planar inside betaCD, in contrast to the structure of BNZ itself, which indicates that the cavity isolates the molecules and forbids the pi...pi stacking of the aromatic rings. NMR spectroscopy studies show that in aqueous solution both DBA and BNZ form strong complexes that have 1:1 stoichiometry and structures similar to the solid state ones. The relative packing of the dimers is the same in both complexes. The axes of two adjacent dimers form an angle close to 20 degrees and have a lateral displacement approximately 2.45 A, both of which characterize the screw-channel mode of packing. Although the betaCD/BNZ complex indeed crystallizes in a space group characterizing the latter mode, the betaCD/DBA complex crystallizes in a space group with novel dimensions not resembling any of the packing modes reported so far. The new lattice is attributed to the three conformations exhibited by the guest in the crystals. However, this lattice can be transformed into another, which is isostructural to that of the betaCD/BNZ inclusion complex, if the conformation of the guest is not taken into account.

CD47 Receptor Globally Regulates Metabolic Pathways That Control Resistance to Ionizing Radiation*

PubMed Central

Miller, Thomas W.; Soto-Pantoja, David R.; Schwartz, Anthony L.; Sipes, John M.; DeGraff, William G.; Ridnour, Lisa A.; Wink, David A.; Roberts, David D.

2015-01-01

Modulating tissue responses to stress is an important therapeutic objective. Oxidative and genotoxic stresses caused by ionizing radiation are detrimental to healthy tissues but beneficial for treatment of cancer. CD47 is a signaling receptor for thrombospondin-1 and an attractive therapeutic target because blocking CD47 signaling protects normal tissues while sensitizing tumors to ionizing radiation. Here we utilized a metabolomic approach to define molecular mechanisms underlying this radioprotective activity. CD47-deficient cells and cd47-null mice exhibited global advantages in preserving metabolite levels after irradiation. Metabolic pathways required for controlling oxidative stress and mediating DNA repair were enhanced. Some cellular energetics pathways differed basally in CD47-deficient cells, and the global declines in the glycolytic and tricarboxylic acid cycle metabolites characteristic of normal cell and tissue responses to irradiation were prevented in the absence of CD47. Thus, CD47 mediates signaling from the extracellular matrix that coordinately regulates basal metabolism and cytoprotective responses to radiation injury. PMID:26311851

Value of HIV patients with regular follow-up as in-house internal controls of flow cytometry measurement of lymphocyte subsets.

PubMed

de Carvalho Bittencourt, Marcelo; Kohler, Chantal; Henard, Sandrine; Rabaud, Christian; Béné, Marie C; Faure, Gilbert C

2013-01-01

Quality assessment in flow cytometry cannot obey the same rules as those applicable to the measurement of chemical analytes. However, regular follow-up of known patients may provide a robust in-house control of cell subsets evaluation. Sequential blood samples assessed for 32 HIV patients over several years and showing good stability were retrospectively assessed to establish coefficient of variations of the percentages of CD3+, CD4+, CD8+ cells, and CD4+ absolute counts (ACs). Mean relative standard variations for the whole cohort were of 0.04, 0.14, 0.08, and 0.18 for CD3%, CD4%, CD8%, and CD4 ACs, respectively. In-house follow-up of regularly checked compliant patients is a good alternative to traditional and costly repeatability and reproducibility studies for the validation of routine flow cytometry. © 2013 International Clinical Cytometry Society. Copyright © 2013 International Clinical Cytometry Society.

Value of HIV patients with regular follow-up as in-house internal controls of flow cytometry measurement of lymphocyte subsets.

PubMed

de Carvalho Bittencourt, Marcelo; Kohler, Chantal; Henard, Sandrine; Rabaud, Christian; Béné, Marie C; Faure, Gilbert C

2013-07-08

Background. Quality assessment in flow cytometry cannot obey the same rules as those applicable to the measurement of chemical analytes. However, regular follow-up of known patients may provide a robust in-house control of cell subsets evaluation. Methods. Sequential blood samples assessed for 32 HIV patients over several years and showing good stability were retrospectively assessed to establish coefficient of variations of the percentages of CD3+, CD4+, CD8+ cells and CD4+ absolute counts. Results. Mean relative standard variations for the whole cohort were of 0.04, 0.14, 0.08 and 0.18 for CD3%, CD4% CD8% and CD4 absolute counts respectively. Discussion. In-house follow up of regularly checked compliant patients is a good alternative to traditional and costly repeatability and reproducibility studies for the validation of routine flow cytometry. © 2013 Clinical Cytometry Society. Copyright © 2013 Clinical Cytometry Society.

Effects of Space Flight on Neutrophil Functions in Astronauts

NASA Technical Reports Server (NTRS)

Kaur, Indreshpal; Valadez, Victoria A.; Simons, Elizabeth R.; Pierson, Duane L.

2000-01-01

Neutrophil phagocytosis, oxidative burst, degranulation, and the expression of selected surface markers were studied in 25 astronauts following 4 space shuttle missions. Space flight duration ranged from 5 to 11 days. Blood specimens were obtained 10 days before launch, immediately after landing, and again at 3 days after landing. The number of neutrophils increased at landing by 85%. Phagocytosis of Escherichia coli (E. coli) and oxidative burst following the medium length (9 to 11 days) missions were lower than the control mean values. Whereas, following the short-duration (5 days) mission, these functions were unchanged from control values. No consistent changes in degranulation were observed following either short or medium length space missions. The expression of CD16, CD32, CD11a, CD11b, CD11c, L-selectin and CD36 were measured and found to be variable. Specifically, CD16 and CD32 did not correlate with the changes in oxidative burst. Mission duration appears to be a factor in phagocytic and oxidative functions.

Targeting peripheral blood pro-inflammatory cytotoxic lymphocytes by inhibiting CD137 expression: novel potential treatment for COPD.

PubMed

Hodge, Greg; Holmes, Mark; Jersmann, Hubertus; Reynolds, Paul N; Hodge, Sandra

2014-05-15

We have shown that chronic obstructive pulmonary disease (COPD) is associated with increased production of pro-inflammatory cytokines and the cytotoxic mediator, granzyme B by peripheral blood steroid resistant CD28nullCD137 + CD8+ T cells and granzyme B by NKT-like and NK cells. We hypothesized that we could target these pro-inflammatory/cytotoxic lymphocytes by inhibiting co-stimulation through CD137. Isolated PBMC from patients with COPD and healthy controls were stimulated with phytohaemagglutinin (PHA) ± blocking anti-CD137 ± 10(-6) M methylprednislone (MP) (±stimulatory anti-CD137 ± control antibodies). Pro-inflammatory cytokine profiles and expression of granzyme B, by T, NKT-like CD28 ± subsets and NK cells were determined using flow cytometry. There was a significant decrease in the percentage of T, NKT-like subsets and NK cells producing IFNγ, TNFα and granzyme B in all subjects in the presence of anti-CD137 blocking antibody compared with PHA alone (eg, 60% decrease in CD8 + granzyme B + cells) or MP. Stimulatory anti-CD137 was associated with an increase in the percentage of pro-inflammatory/cytotoxic cells. The inhibitory effect of anti-CD137 on IFNγ, TNFα and granzyme B production by CD28null cells was greater than by CD28+ cells. Blocking CD137 expression is associated with downregulation of IFNγ, TNFα and granzyme B by CD8+ T and NKT-like and NK cells. Targeting CD137 may have novel therapeutic implications for patients with COPD.

Comparison of basophil activation tests using CD63 or CD203c expression in patients with insect venom allergy.

PubMed

Eberlein-König, B; Varga, R; Mempel, M; Darsow, U; Behrendt, H; Ring, J

2006-09-01

Flow cytometric basophil activation tests have been developed as cellular tests for in vitro diagnosis of IgE-mediated reactions. Different activation markers (CD63 or CD203c) with distinct ways of regulation have been used after stimulation with various allergens. It was the aim of the present study to compare basophil activation tests by measuring both CD63 and CD203c upregulation in patients with insect venom allergy. 43 patients with a history of insect venom anaphylaxis were examined. A careful allergy history was taken, and skin tests and determination of specific IgE-antibodies were performed. Basophil activation tests (BAT) using CD63 or CD203c expression were done after stimulation with different concentrations of bee and wasp venom extracts. 25 healthy subjects with negative history of insect venom allergy were studied as controls. The CD203c protocol showed a slightly higher sensitivity than the CD63 protocol (97% vs. 89%) with regard to patients' history. The magnitude of basophil response was higher with CD203c in comparison to CD63 for both insect venoms. Specificity was 100% for the CD63 protocol and 89% for the CD203c protocol with regard to controls with negative history and negative RAST. These results support the reliability of basophil activation tests using either CD63 or CD203c as cellular tests in the in vitro diagnosis of patients with bee or wasp venom allergy with a slightly higher sensitivity for the CD203c protocol.

HLA-B*57 and IFNL4-Related Polymorphisms Are Associated With Protection Against HIV-1 Disease Progression in Controllers

PubMed Central

Dominguez-Molina, Beatriz; Tarancon-Diez, Laura; Hua, Stephane; Abad-Molina, Cristina; Rodriguez-Gallego, Esther; Machmach, Kawthar; Vidal, Francesc; Tural, Cristina; Moreno, Santiago; Goñi, María José; Ramírez de Arellano, Elena; del Val, Margarita; Gonzalez-Escribano, María Francisca; Del Romero, Jorge; Rodriguez, Carmen; Capa, Laura; Viciana, Pompeyo; Alcamí, José; Yu, Xu G.; Walker, Bruce D.; Leal, Manuel; Lichterfeld, Mathias

2017-01-01

Abstract Background. Human immunodeficiency virus type 1 (HIV-1) controllers maintain HIV-1 viremia at low levels (normally <2000 HIV-RNA copies/mL) without antiretroviral treatment. However, some HIV-1 controllers have evidence of immunologic progression with marked CD4+ T-cell decline. We investigated host genetic factors associated with protection against CD4+ T-cell loss in HIV-1 controllers. Methods. We analyzed the association of interferon-lambda 4 (IFNL4)–related polymorphisms and human leukocyte antigen (HLA)-B haplotypes within long-term nonprogressor HIV-1 controllers (LTNP-Cs; defined by maintaining CD4+ T-cells counts >500 cells/mm3 for more than 7 years after HIV-1 diagnosis) vs non-LTNP-Cs who developed CD4+ T-cell counts <500 cells/mm3. Both a Spanish study cohort (n = 140) and an international validation cohort (n = 914) were examined. Additionally, in a subgroup of individuals, HIV-1–specific T-cell responses and soluble cytokines were analyzed. Results. HLA-B*57 was independently associated with the LTNP-C phenotype (odds ratio [OR], 3.056 [1.029–9.069]; P = .044 and OR, 1.924 [1.252–2.957]; P = .003) while IFNL4 genotypes represented independent factors for becoming non-LTNP-C (TT/TT, ss469415590; OR, 0.401 [0.171–0.942]; P = .036 or A/A, rs12980275; OR, 0.637 [0.434–0.934]; P = .021) in the Spanish and validation cohorts, respectively, after adjusting for sex, age at HIV-1 diagnosis, IFNL4-related polymorphisms, and different HLA-B haplotypes. LTNP-Cs showed lower plasma induced protein 10 (P = .019) and higher IFN-γ (P = .02) levels than the HIV-1 controllers with diminished CD4+ T-cell numbers. Moreover, LTNP-Cs exhibited higher quantities of interleukin (IL)2+CD57- and IFN-γ +CD57- HIV-1–specific CD8+ T cells (P = .002 and .041, respectively) than non-LTNP-Cs. Conclusions. We defined genetic markers able to segregate stable HIV-1 controllers from those who experience CD4+ T-cell decline. These findings allow for identification of HIV-1 controllers at risk for immunologic progression and provide avenues for personalized therapeutic interventions and precision medicine for optimizing clinical care of these individuals. PMID:27986689

Shear localization and size-dependent strength of YCd 6 quasicrystal approximant at the micrometer length scale

DOE PAGES

Song, Gyuho; Kong, Tai; Dusoe, Keith J.; ...

2018-01-24

Mechanical properties of materials are strongly dependent of their atomic arrangement as well as the sample dimension, particularly at the micrometer length scale. Here in this study, we investigated the small-scale mechanical properties of single-crystalline YCd 6, which is a rational approximant of the icosahedral Y-Cd quasicrystal. In situ microcompression tests revealed that shear localization always occurs on {101} planes, but the shear direction is not constrained to any particular crystallographic directions. Furthermore, the yield strengths show the size dependence with a power law exponent of 0.4. Shear localization on {101} planes and size-dependent yield strength are explained in termsmore » of a large interplanar spacing between {101} planes and the energetics of shear localization process, respectively. The mechanical behavior of the icosahedral Y-Cd quasicrystal is also compared to understand the influence of translational symmetry on the shear localization process in both YCd 6 and Y-Cd quasicrystal micropillars. Finally, the results of this study will provide an important insight in a fundamental understanding of shear localization process in novel complex intermetallic compounds.« less

Shear localization and size-dependent strength of YCd 6 quasicrystal approximant at the micrometer length scale

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

Song, Gyuho; Kong, Tai; Dusoe, Keith J.

Mechanical properties of materials are strongly dependent of their atomic arrangement as well as the sample dimension, particularly at the micrometer length scale. Here in this study, we investigated the small-scale mechanical properties of single-crystalline YCd 6, which is a rational approximant of the icosahedral Y-Cd quasicrystal. In situ microcompression tests revealed that shear localization always occurs on {101} planes, but the shear direction is not constrained to any particular crystallographic directions. Furthermore, the yield strengths show the size dependence with a power law exponent of 0.4. Shear localization on {101} planes and size-dependent yield strength are explained in termsmore » of a large interplanar spacing between {101} planes and the energetics of shear localization process, respectively. The mechanical behavior of the icosahedral Y-Cd quasicrystal is also compared to understand the influence of translational symmetry on the shear localization process in both YCd 6 and Y-Cd quasicrystal micropillars. Finally, the results of this study will provide an important insight in a fundamental understanding of shear localization process in novel complex intermetallic compounds.« less

Theoretical study of β- and γ-cyclodextrin complexes with ferrocene-containing azoles

NASA Astrophysics Data System (ADS)

Kiselev, S. S.; Snegur, L. V.; Simenel, A. A.; Davankov, V. A.; Il'in, M. M.; Borisov, Yu. A.

2017-12-01

The interaction between cyclodextrins (β- and γ-CD) and ferrocenyl azoles (i.e., pyrazole ferrocenes (I, III-V) and benzimidazole ferrocenes (VI, VII)), along with 1-ferrocenylethanol (II), each in the form of (R)- and (S)-enantiomers, in forming inclusion complexes is studied for the first time using detailed quantum chemical calculations. Compounds are calculated in terms of the density functional theory (DFT), using the Becke-Lee-Yang-Parr (B3LYP) approach in the 6-31G* basis sets. For the considered CD complexes with enantiomers of I-VII, structures in which a guest partially enters a host cavity from the side of the heterocyclic substituent (pyrazole or benzimidazole) are found to be energetically advantageous. It is shown that for successful resolution of (R,S)-enantiomers on chiral phases containing cyclodextrins, we must consider the interaction between outer hydroxyl groups on the CD cone's surface, in addition to the correspondence of geometric dimensions. The calculated data correlate well with the data from the chromatographic separation of guest enantiomers on cyclodextrin sorbents.

CD22 ligand-binding and signaling domains reciprocally regulate B-cell Ca2+ signaling

PubMed Central

Müller, Jennifer; Obermeier, Ingrid; Wöhner, Miriam; Brandl, Carolin; Mrotzek, Sarah; Angermüller, Sieglinde; Maity, Palash C.; Reth, Michael; Nitschke, Lars

2013-01-01

A high proportion of human B cells carry B-cell receptors (BCRs) that are autoreactive. Inhibitory receptors such as CD22 can downmodulate autoreactive BCR responses. With its extracellular domain, CD22 binds to sialic acids in α2,6 linkages in cis, on the surface of the same B cell or in trans, on other cells. Sialic acids are self ligands, as they are abundant in vertebrates, but are usually not expressed by pathogens. We show that cis-ligand binding of CD22 is crucial for the regulation of B-cell Ca2+ signaling by controlling the CD22 association to the BCR. Mice with a mutated CD22 ligand-binding domain of CD22 showed strongly reduced Ca2+ signaling. In contrast, mice with mutated CD22 immunoreceptor tyrosine-based inhibition motifs have increased B-cell Ca2+ responses, increased B-cell turnover, and impaired survival of the B cells. Thus, the CD22 ligand-binding domain has a crucial function in regulating BCR signaling, which is relevant for controlling autoimmunity. PMID:23836650

CD22 ligand-binding and signaling domains reciprocally regulate B-cell Ca2+ signaling.

PubMed

Müller, Jennifer; Obermeier, Ingrid; Wöhner, Miriam; Brandl, Carolin; Mrotzek, Sarah; Angermüller, Sieglinde; Maity, Palash C; Reth, Michael; Nitschke, Lars

2013-07-23

A high proportion of human B cells carry B-cell receptors (BCRs) that are autoreactive. Inhibitory receptors such as CD22 can downmodulate autoreactive BCR responses. With its extracellular domain, CD22 binds to sialic acids in α2,6 linkages in cis, on the surface of the same B cell or in trans, on other cells. Sialic acids are self ligands, as they are abundant in vertebrates, but are usually not expressed by pathogens. We show that cis-ligand binding of CD22 is crucial for the regulation of B-cell Ca(2+) signaling by controlling the CD22 association to the BCR. Mice with a mutated CD22 ligand-binding domain of CD22 showed strongly reduced Ca(2+) signaling. In contrast, mice with mutated CD22 immunoreceptor tyrosine-based inhibition motifs have increased B-cell Ca(2+) responses, increased B-cell turnover, and impaired survival of the B cells. Thus, the CD22 ligand-binding domain has a crucial function in regulating BCR signaling, which is relevant for controlling autoimmunity.

Autoimmune Lymphoproliferative Syndrome-FAS Patients Have an Abnormal Regulatory T Cell (Treg) Phenotype but Display Normal Natural Treg-Suppressive Function on T Cell Proliferation.

PubMed

Mazerolles, Fabienne; Stolzenberg, Marie-Claude; Pelle, Olivier; Picard, Capucine; Neven, Benedicte; Fischer, Alain; Magerus-Chatinet, Aude; Rieux-Laucat, Frederic

2018-01-01

Autoimmune lymphoproliferative syndrome (ALPS) with FAS mutation (ALPS-FAS) is a nonmalignant, noninfectious, lymphoproliferative disease with autoimmunity. Given the central role of natural regulatory T cells (nTregs) in the control of lymphoproliferation and autoimmunity, we assessed nTreg-suppressive function in 16 patients with ALPS-FAS. The proportion of CD25 high CD127 low Tregs was lower in ALPS-FAS patients than in healthy controls. This subset was correlated with a reduced CD25 expression in CD3 + CD4 + T cells from ALPS patients and thus an abnormally low proportion of CD25 high FOXP3 + Helios + T cells. The ALPS patients also displayed a high proportion of naïve Treg (FOXP3 low CD45RA + ) and an unusual subpopulation (CD4 + CD127 low CD15s + CD45RA + ). Despite this abnormal phenotype, the CD25 high CD127 low Tregs' suppressive function was unaffected. Furthermore, conventional T cells from FAS -mutated patients showed normal levels of sensitivity to Treg suppression. An abnormal Treg phenotype is observed in circulating lymphocytes of ALPS patients. However, these Tregs displayed a normal suppressive function on T effector proliferation in vitro . This is suggesting that lymphoproliferation observed in ALPS patients does not result from Tregs functional defect or T effector cells insensitivity to Tregs suppression.

Synthesis and spectroscopic study of CdS nanoparticles using hydrothermal method

NASA Astrophysics Data System (ADS)

AL-Mamoori, Mohammed H. K.; Mahdi, Dunia K.; Al-Shrefi, Saif M.

2018-05-01

In this work, cadmium sulfide nanoparticles (powder) with diameter 50.8 nm was prepared using hydrothermal method. The structural and optical properties of CdS nanoparticles was studied by X-ray diffraction, FESEM, EDS, FTIR, UV-Diffuse Reflectance spectroscopy and Photoluminance spectrum. X-ray diffraction reveal the formation the purity of prepared phase of CdS particles with hexagonal wurtzite structure with particle size 31.8nm by using sheerer equation. The energy dispersion scattering (EDS) examination explains that the sample is composed of a large amount of Cd and S which are exactly CdS nanoparticles and there is a very small trace of (Zn) and (O) element observed because of there is a small pollutions in the measurement place of samples. FESEM shows the spherical shape of nanoparticles with around 50.8 nm diameter. The optical absorption spectral study identified the red shift of the sample in comparison to bulk ZnO in three dimensions. Photoluminance spectrum (PL) at room temperature showed that there are two luminescence peaks at 433.14 nm and 518.21nm. Samples demonstrate a sharp emission band at around 433.18 nm, which is attributed to the typical exciton luminescence. The broad band at 518.21nm which were attributed to the trapped luminescence. The green emission band at 518.21 nm was associated with the emission due to electronic transition from the conduction band to an accepter level due to interstitial sulphur ion.

TH1/TH2 cytokines and soluble CD30 levels in kidney allograft patients with donor bone marrow cell infusion.

PubMed

Solgi, G; Amirzagar, A A; Pourmand, G; Mehrsai, A R; Taherimahmoudi, M; Baradaran, N; Nicknam, M H; Ebrahimi Rad, M R; Saraji, A; Asadpoor, A A; Moheiydin, M; Nikbin, B

2009-09-01

We investigated the relevance of donor bone marrow cell infusion (DBMI) and serum levels of interferon-gamma (IFN-gamma), interleukin-10 (IL-10), and soluble CD30 (sCD30) in kidney recipients. We analyzed the allograft outcomes correlated with sCD30, IFN-gamma, and IL-10 levels using pre- and posttransplantation sera from 40 live donor renal transplants (20 patients with DBMI [2.1 x 10(9) +/- 1.3 x 10(9) mononuclear cells/body] and 20 controls). Patients with acute rejection episodes (ARE)-3/20 DBMI and 6/20 controls-showed increased sCD30 and IFN-gamma as well as decreased IL-10 posttransplantation compared with nonrejectors. Significant differences were observed for sCD30 and IFN-gamma levels: 59.54 vs 30.92 ng/mL (P = .02) and 11.91 vs 3.01 pg/mL (P = .01), respectively. Comparison of pre- and posttransplant levels of IFN-gamma, IL-10, and sCD30 in ARE patients showed higher levels in posttransplant sera except for IFN-gamma in controls (6.37 vs 11.93; P = .01). Increased IFN-gamma and IL-10 were correlated with rejection (r = .93; P = .008). sCD30 correlated with serum creatinine among ARE patients in control and DBMI groups (r = .89; P = .019; and r = 1.00; P < .0001, respectively). Higher levels of sCD30, IFN-gamma, and IL-10 posttransplantation in rejecting patients provided evidence for coexistence of cellular and humoral responses in ARE. There appeared to be a down-regulatory effect of infusion on alloresponses.

Is there a relationship between outer retinal destruction and choroidal changes in cone dystrophy?

PubMed

Ayyildiz, Onder; Ozge, Gokhan; Kucukevcilioglu, Murat; Ozgonul, Cem; Mumcuoglu, Tarkan; Durukan, Ali Hakan; Mutlu, Fatih Mehmet

2016-01-01

The aim of the present study was to use enhanced depth imaging optical coherence tomography (EDI-OCT) to investigate choroidal changes in patients with cone dystrophy (CD) and to correlate these findings with clinical and electroretinography (ERG) findings. This case-control study included 40 eyes of 20 patients with CD and 40 eyes of 40 age- and refraction-matched healthy individuals. Choroidal thickness (CT) measurements were obtained under the foveal center and at 500 and 1,500 μm from the nasal and temporal regions to the center of the fovea, respectively. EDI-OCT and ERG data were analyzed, and the correlations of CT with the best-corrected visual acuity (BCVA) and the central foveal thickness (CFT) were evaluated. The mean subfoveal CTs in the CD and control groups were 240.70 ± 70.78 and 356.18 ± 48.55 μm, respectively. The subfoveal CT was significantly thinner in patients with CD than in the controls (p<0.001). The patients with CD also had significantly thinner choroids than the controls at each measurement location relative to the fovea (p<0.001). The subfoveal CT in the CD group correlated with CFT (p=0.012), but no significant correlation was found between the subfoveal CT and BCVA or photopic ERG responses. The present study demonstrated a significant thinning of the choroid in patients with CD. EDI-OCT is a useful technique for describing the choroidal changes occurring in CD. Future studies investigating the association between choroidal changes and outer retinal destruction or the disease stage may provide a better understanding of the pathophysiology of CD.

The effect of character contextual diversity on eye movements in Chinese sentence reading.

PubMed

Chen, Qingrong; Zhao, Guoxia; Huang, Xin; Yang, Yiming; Tanenhaus, Michael K

2017-12-01

Chen, Huang, et al. (Psychonomic Bulletin & Review, 2017) found that when reading two-character Chinese words embedded in sentence contexts, contextual diversity (CD), a measure of the proportion of texts in which a word appears, affected fixation times to words. When CD is controlled, however, frequency did not affect reading times. Two experiments used the same experimental designs to examine whether there are frequency effects of the first character of two-character words when CD is controlled. In Experiment 1, yoked triples of characters from a control group, a group matched for character CD that is lower in frequency, and a group matched in frequency with the control group, but higher in character CD, were rotated through the same sentence frame. In Experiment 2 each character from a larger set was embedded in a separate sentence frame, allowing for a larger difference in log frequency compared to Experiment 1 (0.8 and 0.4, respectively). In both experiments, early and later eye movement measures were significantly shorter for characters with higher CD than for characters with lower CD, with no effects of character frequency. These results place constraints on models of visual word recognition and suggest ways in which Chinese can be used to tease apart the nature of context effects in word recognition and language processing in general.

[Changes of FoxP3, CD4(+)CD25(+) regulatory T cells, TLR2 and TLR9 in children with infectious mononucleosis].

PubMed

Wang, Qiang; Wang, Zuo-Feng; Cao, Mei; Wang, Zhi-Ying

2013-04-01

The aim of this study was to investigate the effects of TLR2, TLR9, CD4(+)CD25(+) regulatory T cells (Treg) and transcription factor FoxP3 in the pathogenesis of children with infectious mononucleosis (IM). Thirty-five acute IM patients admitted in our hospital from April 2010 to January 2011 were enrolled in this study. Thirty-five healthy subjects were taken as control. The thirty-five patients before treatment were considered as patients in acute stage, after treatment and without clinical symptom they were thought as patients in recovery stage. The expression levels of TLR2, TLR9 and FoxP3 mRNA were detected by real time PCR using SYBR Green I. The expression of T lymphocyte subset CD4(+)CD25(+) in peripheral blood mononuclear cells was detected by flow cytometry. The results showed that the relative levels of TLR2 mRNA (4.03 ± 0.56), TLR9 mRNA (8.88 ± 1.56) in peripheral blood mononuclear cells of IM patients in acute stage were significantly higher than those of the controls [TLR2 mRNA (2.22 ± 0.57), TLR9 mRNA (3.63 ± 1.30)] and IM patients in recovery stage [TLR2 mRNA (2.76 ± 0.83), TLR9 mRNA (5.34 ± 1.60)] (P < 0.01). The result of CD4(+)CD25(+) (2.38 ± 1.32%) and relative level of FoxP3 mRNA(2.82 ± 0.90) in peripheral blood mononuclear cells of IM patients in acute stage were lower than those of the control [CD4(+)CD25(+) (7.85 ± 1.97%), FoxP3 mRNA (4.65 ± 1.23) ] (P < 0.01). There was no significant difference in CD4(+)CD25(+) (6.81 ± 1.84%), FoxP3 mRNA(4.11 ± 1.37) levels between IM patients in recovery stage and the controls (P > 0.05). It is concluded that the expression of CD4(+)CD25(+)regulatory T cells is reduced, and its special transcription factor FoxP3 mRNA is down-regulated, but expression levels of TLR2 mRNA, TLR9 mRNA are up-regulated in IM patients of acute stage.

CD4+CD73+ T cells are associated with lower T-cell activation and C reactive protein levels and are depleted in HIV-1 infection regardless of viral suppression

PubMed Central

Schuler, Patrick J.; Macatangay, Bernard J.C.; Saze, Zenichiro; Jackson, Edwin K.; Riddler, Sharon A.; Buchanan, William G.; Hilldorfer, Benedict B.; Mellors, John W.; Whiteside, Theresa L.; Rinaldo, Charles R.

2013-01-01

Background The role of the adenosine (ADO) suppression pathway, specifically CD39-expressing and CD73-expressing CD4+ T cells in HIV-1 infection is unclear. Methods We evaluated the frequency and numbers of CD4+CD39+ and CD4+CD73+ T cells, activated T cells, and plasma C reactive protein (CRP) levels in 36 HIV-1-positive individuals and 10 normal controls (NC). Low-level plasma viremia was evaluated using single copy assay. Mass spectrometry was used to measure hydrolysis of ATP by ectoenzyme-expressing CD4+ T cells, whereas cyclic adenosine monophosphate (cAMP) levels were measured using enzyme immunoassay. Suppression of T-cell function by exogenous ADO and CD4+CD73+ T cells was tested by flow cytometry. Results CD39 and CD73 are expressed in different CD4+ T-cell subsets. CD4+CD73+ T cells do not express CD25 and FOXP3, and their frequency and numbers were lower in HIV-1-positive individuals regardless of virologic suppression (P = 0.005 and P < 0.001, respectively). CD4+CD73+ numbers inversely correlated with CD4+CD38+DR+ (P = 0.002), CD8+CD38+DR+ T-cell frequency (P = 0.05), and plasma CRP levels (P = 0.01). Both subsets are required for hydrolysis of exogenous ATP to ADO and can increase CD4+ T-cell cAMP levels when incubated with exogenous ATP. Low-level viremia did not correlate with activated T-cell frequency. In vitro, ADO suppressed T-cell activation and cytokine expression. CD4+CD73+ T cells suppressed T-cell proliferation only in the presence of exogenous 5′-AMP. Conclusion The ADO-producing CD4+CD73+ subset of T cells is depleted in HIV-1-positive individuals regardless of viral suppression and may play a key role in controlling HIV-1-associated immune activation. PMID:24005375

Development and evaluation of an interactive CD-ROM for children with leukemia and their families.

PubMed

Dragone, Mary Alice; Bush, Patricia J; Jones, Judith K; Bearison, David J; Kamani, Sharmila

2002-04-01

To meet the need for an interactive software product to educate children with leukemia, ages 4-11 years, and their families about the disease and its treatment, we developed and evaluated an interactive, comprehensive, multimedia CD-ROM product, Kidz with Leukemia: A Space Adventure. The prototype was tested using a randomized controlled experimental design. Children with leukemia and their parents were randomized to receive either the newly developed CD-ROM or the book You and Leukemia by Lynn Baker. Health care providers (HCPs) and other content/technical experts evaluated only the CD-ROM. Data were collected on children's health locus of control, their understanding of leukemia, and the satisfaction of participants with their assigned intervention. Children in the CD-ROM group, compared with those in the book group, showed increased feelings of control over their health. Although there was a high level of satisfaction with the CD-ROM among all users, younger children and their parents were most satisfied. In conclusion, the CD-ROM, Kidz with Leukemia: A Space Adventure, was found to be a useful, engaging, and empowering tool for children with leukemia and can serve as a model for developing future health-related educational materials.

Selenium, selenoprotein genes and Crohn's disease in a case-control population from Auckland, New Zealand.

PubMed

Gentschew, Liljana; Bishop, Karen S; Han, Dug Yeo; Morgan, Angharad R; Fraser, Alan G; Lam, Wen Jiun; Karunasinghe, Nishi; Campbell, Bobbi; Ferguson, Lynnette R

2012-09-01

New Zealand has one of the highest incidence rates of Crohn's Disease (CD), whilst the serum selenium status of New Zealanders is amongst the lowest in the world. A prospective case-control study in Auckland, New Zealand considered serum selenium as a potential CD risk factor. Serum selenium levels were significantly lower in CD patients compared to controls (101.8 ± 1.02 vs. 111.1 ± 1.01 ng/mL) (p = 5.91 × 10(-8)). Recent detailed studies in the United Kingdom have suggested an optimal serum level around 122 ng/mL, making the average CD patient in New Zealand selenium deficient. Of the 29 single nucleotide polymorphisms (SNPs) tested, 13 were found to significantly interact with serum selenium on CD. After adjustment for multiple testing, a significant interaction with serum selenium on CD was found for three SNPs, namely rs17529609 and rs7901303 in the gene SEPHS1, and rs1553153 in the gene SEPSECS. These three SNPs have not been reported elsewhere as being significantly associated with selenium or CD. It is unclear as to whether lower selenium levels are a cause or an effect of the disease.

Selenium, Selenoprotein Genes and Crohn’s Disease in a Case-Control Population from Auckland, New Zealand

PubMed Central

Gentschew, Liljana; Bishop, Karen S.; Han, Dug Yeo; Morgan, Angharad R.; Fraser, Alan G.; Lam, Wen Jiun; Karunasinghe, Nishi; Campbell, Bobbi; Ferguson, Lynnette R.

2012-01-01

New Zealand has one of the highest incidence rates of Crohn’s Disease (CD), whilst the serum selenium status of New Zealanders is amongst the lowest in the world. A prospective case-control study in Auckland, New Zealand considered serum selenium as a potential CD risk factor. Serum selenium levels were significantly lower in CD patients compared to controls (101.8 ± 1.02 vs. 111.1 ± 1.01 ng/mL) (p = 5.91 × 10−8). Recent detailed studies in the United Kingdom have suggested an optimal serum level around 122 ng/mL, making the average CD patient in New Zealand selenium deficient. Of the 29 single nucleotide polymorphisms (SNPs) tested, 13 were found to significantly interact with serum selenium on CD. After adjustment for multiple testing, a significant interaction with serum selenium on CD was found for three SNPs, namely rs17529609 and rs7901303 in the gene SEPHS1, and rs1553153 in the gene SEPSECS. These three SNPs have not been reported elsewhere as being significantly associated with selenium or CD. It is unclear as to whether lower selenium levels are a cause or an effect of the disease. PMID:23112913

Release of soluble CD30 after allogeneic stimulation is mediated by memory T cells and regulated by IFN-γ and IL-2.

PubMed

Velásquez, Sonia Y; García, Luis F; Opelz, Gerhard; Alvarez, Cristiam M; Süsal, Caner

2013-07-27

Membrane CD30 is an important costimulatory molecule for activated T lymphocytes, and serum level of soluble CD30 (sCD30) is considered a marker for predicting outcome in kidney transplantation. We investigated the kinetics of CD30 expression on CD4 and CD8 T-cell populations and the source of sCD30 during alloimmune responses in vitro. The effect of neutralizing antibodies against interferon (IFN)-γ and other cytokines on sCD30 release and the involvement of metalloproteinases ADAM10 and ADAM17/TACE that are responsible for sCD30 shedding were also assessed. Memory phenotypes and CD30 expression on allostimulated CD3 lymphocytes were evaluated in dialysis patients and matched controls. Allogeneic stimulation resulted in conversion of naive responder cells to central memory CD4 cells (P<0.001 at 96 hr) and effector CD8 cells (P<0.01 at 120 hr), which was accompanied by increased CD30 expression. Release of sCD30 was attributed mainly to central memory cells, and neutralization of IFN-γ (P<0.001) and interleukin (IL)-2 (P<0.001) impaired the release of sCD30 during allostimulation but did not alter the levels of ADAM10 and ADAM17/TACE. CD30 expression was modulated in dialysis patients in a similar way as in healthy controls. Allostimulation results in the up-regulation of the T-cell activation marker CD30 on CD4 as well as CD8 memory T cells and increased release of sCD30 from these cells in an IFN-γ- and IL-2-dependent manner. These results may explain clinical findings on the suitability of sCD30 and IFN-γ- and IL-2-producing T cells for immune monitoring of kidney transplant recipients before and after transplantation.

Low numbers of CD8+ T lymphocytes in hereditary haemochromatosis are explained by a decrease of the most mature CD8+ effector memory T cells.

PubMed

Macedo, M F; Porto, G; Costa, M; Vieira, C P; Rocha, B; Cruz, E

2010-03-01

Low CD8(+) T lymphocyte numbers have long been described in hereditary haemochromatosis (HH). Recently, two conserved haplotypes localized near the microsatellite D6S105 at the major histocompatibility complex (MHC) class I region were described predicting the clinical expression of HH and the CD8(+) T lymphocyte numbers. The A-A-T haplotype was associated with a severe clinical expression of HH and low CD8(+) T lymphocyte numbers, while the G-G-G haplotype was associated with a milder clinical expression of HH and high CD8(+) T lymphocyte numbers. As CD8(+) T lymphocytes are a very heterogeneous population, in this study we analysed the CD8(+) subpopulations of naive, central memory (T(CM)) and effector memory (T(EM)), and further subsets of CD8(+) T(EM) cells in 47 HH patients and 68 controls. In addition, association studies were conducted between the conserved haplotypes and the CD8(+) T cell subpopulations in HH. Variations of the numbers of naive and central memory cells with age were similar between HH patients and controls. For T(EM) cells and the T(EM) CD27(-)CD28(-) subset no effect of age was observed in HH [R(2) = 0.001, not significant (n.s.) and R(2) = 0.01, n.s., respectively] contrasting with the increasing of these subpopulations with age in controls (R(2) = 0.09, P = 0.017 and R(2) = 0.22, P = 0.0005, respectively). Interestingly, patients homozygous for the A-A-T haplotype have lower numbers of CD8(+) T(EM) cells due especially to lower numbers of T(EM) CD27(-)CD28(-) (0.206 +/- 0.119 and 0.066 +/- 0.067 x 10(6) cells/ml, respectively) than patients carrying the G-G-G haplotype (0.358 +/- 0.195 and 0.246 +/- 0.202 x 10(6) cells/ml, respectively). This may suggest an inability of HH patients to differentiate the CD8(+) T cells into the most mature phenotype.

CD98 regulates vascular smooth muscle cell proliferation in atherosclerosis.

PubMed

Baumer, Yvonne; McCurdy, Sara; Alcala, Martin; Mehta, Nehal; Lee, Bog-Hieu; Ginsberg, Mark H; Boisvert, William A

2017-01-01

Vascular smooth muscle cells (VSMC) migrate and proliferate to form a stabilizing fibrous cap that encapsulates atherosclerotic plaques. CD98 is a transmembrane protein made of two subunits, CD98 heavy chain (CD98hc) and one of six light chains, and is known to be involved in cell proliferation and survival. Because the influence of CD98hc on atherosclerosis development is unknown, our aim was to determine if CD98hc expressed on VSMC plays a role in shaping the morphology of atherosclerotic plaques by regulating VSMC function. In addition to determining the role of CD98hc in VSMC proliferation and apoptosis, we utilized mice with SMC-specific deletion of CD98hc (CD98hc fl/fl SM22αCre + ) to determine the effects of CD98hc deficiency on VSMC function in atherosclerotic plaque. After culturing for 5 days in vitro, CD98hc -/- VSMC displayed dramatically reduced cell counts, reduced proliferation, as well as reduced migration compared to control VSMC. Analysis of aortic VSCM after 8 weeks of HFD showed a reduction in CD98hc -/- VSMC proliferation as well as increased apoptosis compared to controls. A long-term atherosclerosis study using SMC-CD98hc -/- /ldlr -/- mice was performed. Although total plaque area was unchanged, CD98hc -/- mice showed reduced presence of VSMC within the plaque (2.1 ± 0.4% vs. 4.3 ± 0.4% SM22α-positive area per plaque area, p < 0.05), decreased collagen content, as well as increased necrotic core area (25.8 ± 1.9% vs. 10.9 ± 1.6%, p < 0.05) compared to control ldlr -/- mice. We conclude that CD98hc is required for VSMC proliferation, and that its deficiency leads to significantly reduced presence of VSMC in the neointima. Thus, CD98hc expression in VSMC contributes to the formation of plaques that are morphologically more stable, and thereby protects against atherothrombosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Low numbers of CD8+ T lymphocytes in hereditary haemochromatosis are explained by a decrease of the most mature CD8+ effector memory T cells

PubMed Central

Macedo, M F; Porto, G; Costa, M; Vieira, C P; Rocha, B; Cruz, E

2010-01-01

Low CD8+ T lymphocyte numbers have long been described in hereditary haemochromatosis (HH). Recently, two conserved haplotypes localized near the microsatellite D6S105 at the major histocompatibility complex (MHC) class I region were described predicting the clinical expression of HH and the CD8+ T lymphocyte numbers. The A-A-T haplotype was associated with a severe clinical expression of HH and low CD8+ T lymphocyte numbers, while the G-G-G haplotype was associated with a milder clinical expression of HH and high CD8+ T lymphocyte numbers. As CD8+ T lymphocytes are a very heterogeneous population, in this study we analysed the CD8+ subpopulations of naive, central memory (TCM) and effector memory (TEM), and further subsets of CD8+ TEM cells in 47 HH patients and 68 controls. In addition, association studies were conducted between the conserved haplotypes and the CD8+ T cell subpopulations in HH. Variations of the numbers of naive and central memory cells with age were similar between HH patients and controls. For TEM cells and the TEM CD27−CD28− subset no effect of age was observed in HH [R2 = 0·001, not significant (n.s.) and R2 = 0·01, n.s., respectively] contrasting with the increasing of these subpopulations with age in controls (R2 = 0·09, P = 0·017 and R2 = 0·22, P = 0·0005, respectively). Interestingly, patients homozygous for the A-A-T haplotype have lower numbers of CD8+ TEM cells due especially to lower numbers of TEM CD27−CD28− (0·206 ± 0·119 and 0·066 ± 0·067 × 106 cells/ml, respectively) than patients carrying the G-G-G haplotype (0·358 ± 0·195 and 0·246 ± 0·202 × 106 cells/ml, respectively). This may suggest an inability of HH patients to differentiate the CD8+ T cells into the most mature phenotype. PMID:20015273

Emodin suppresses cadmium-induced osteoporosis by inhibiting osteoclast formation.

PubMed

Chen, Xiao; Ren, Shuai; Zhu, Guoying; Wang, Zhongqiu; Wen, Xiaolin

2017-09-01

Environmental level of cadmium (Cd) exposure can induce bone loss. Emodin, a naturally compound found in Asian herbal medicines, could influence osteoblast/osteoclast differentiation. However, the effects of emodin on Cd-induced bone damage are not clarified. The aim of this study was to investigate the role of emodin on Cd-induced osteoporosis. Sprague-Dawley male rats were divided into three groups which were given 0mg/L, 50mg Cd/L and 50mg Cd/L plus emodin (50mg/kg body weight). Bone histological investigation, microCT analysis, metabolic biomarker determination and immunohistochemical staining were performed at the 12th week. The bone mass and bone microstructure index of rats treated with Cd were obviously lower than in control. Cd markedly enhanced the osteoclast formation compared with control. Emodin significantly abolished the Cd-induced bone microstructure damage (p<0.05), osteoclast formation and increase of tartrate-resistant acid phosphatase 5b level (p<0.05). Our data further showed that emodin attenuated the Cd-induced inhibition of osteoprotegerin expression and stimulation of receptor activator for nuclear factor-κ B ligand expression. Our data show that emodin suppresses the Cd-induced osteoporosis by inhibiting osteoclast formation. Copyright © 2017 Elsevier B.V. All rights reserved.

CD147 overexpression may serve as a promising diagnostic and prognostic marker for gastric cancer: evidence from original research and literature.

PubMed

Hu, Chenghao; Dong, Xiaoxia; Wu, Junbo; Xiao, Feifan; Shang, Jun; Liu, Liang; Yang, Yuan; Luo, Dongmei; Li, Qiuting; Song, Qian; Yang, Jingcheng; Zhang, Chengdong; Shen, Li; Luo, Zhiguo

2017-05-09

Gastric cancer (GC) is one of the most common malignancies worldwide. The expression of CD147 protein is associated with GC. However, the clinical role of CD147 in GC has not been investigated extensively. Hence, we focused on studying the association between the expression of CD147 and clinicopathological features of GC patients in this study. Firstly, sixteen publications (1752 cases and 391 controls) and one from our own original research (143 cases) were included in the meta-analysis to obtain a more precise estimation of the diagnostic value of CD147. The results showed that expression rate of CD147 in the GC group is higher than that in control group. Moreover, gender, TNM stage, lymph node metastasis, and depth of invasion are all associated with CD147. Further, sections of gastric tissue from 143 cases underwent immunohistochemical staining for evaluation of CD147 protein expression. Our retrospective analysis demonstrated CD147 protein expression was significantly associated with clinical N stage, and tumor stage. Meanwhile, it can also serve as an independent prognosis biomarker. In conclusion, our results support the role of CD147 as a good indicator of diagnosis and prognosis.

Solving next generation (1x node) metrology challenges using advanced CDSEM capabilities: tilt, high energy and backscatter imaging

NASA Astrophysics Data System (ADS)

Zhang, Xiaoxiao; Snow, Patrick W.; Vaid, Alok; Solecky, Eric; Zhou, Hua; Ge, Zhenhua; Yasharzade, Shay; Shoval, Ori; Adan, Ofer; Schwarzband, Ishai; Bar-Zvi, Maayan

2015-03-01

Traditional metrology solutions are facing a range of challenges at the 1X node such as three dimensional (3D) measurement capabilities, shrinking overlay and critical dimension (CD) error budgets driven by multi-patterning and via in trench CD measurements. Hybrid metrology offers promising new capabilities to address some of these challenges but it will take some time before fully realized. This paper explores new capabilities currently offered on the in-line Critical Dimension Scanning Electron Microscope (CD-SEM) to address these challenges and enable the CD-SEM to move beyond measuring bottom CD using top down imaging. Device performance is strongly correlated with Fin geometry causing an urgent need for 3D measurements. New beam tilting capabilities enhance the ability to make 3D measurements in the front-end-of-line (FEOL) of the metal gate FinFET process in manufacturing. We explore these new capabilities for measuring Fin height and build upon the work communicated last year at SPIE1. Furthermore, we extend the application of the tilt beam to the back-end-of-line (BEOL) trench depth measurement and demonstrate its capability in production targeting replacement of the existing Atomic Force Microscope (AFM) measurements by including the height measurement in the existing CDSEM recipe to reduce fab cycle time. In the BEOL, another increasingly challenging measurement for the traditional CD-SEM is the bottom CD of the self-aligned via (SAV) in a trench first via last (TFVL) process. Due to the extremely high aspect ratio of the structure secondary electron (SE) collection from the via bottom is significantly reduced requiring the use of backscatter electrons (BSE) to increase the relevant image quality. Even with this solution, the resulting images are difficult to measure with advanced technology nodes. We explore new methods to increase measurement robustness and combine this with novel segmentation-based measurement algorithm generated specifically for BSE images. The results will be contrasted with data from previously used methods to quantify the improvement. We also compare the results to electrical test data to evaluate and quantify the measurement performance improvements. Lastly, according to International Technology Roadmap for Semiconductors (ITRS) from 2013, the overlay 3 sigma requirement will be 3.3 nm in 2015 and 2.9 nm in 2016. Advanced lithography requires overlay measurement in die on features resembling the device geometry. However, current optical overlay measurement is performed in the scribe line on large targets due to optical diffraction limit. In some cases, this limits the usefulness of the measurement since it does not represent the true behavior of the device. We explore using high voltage imaging to help address this urgent need. Novel CD-SEM based overlay targets that optimize the restrictions of process geometry and SEM technique were designed and spread out across the die. Measurements are done on these new targets both after photolithography and etch. Correlation is drawn between the two measurements. These results will also be compared to conventional optical overlay measurement approaches and we will discuss the possibility of using this capability in high volume manufacturing.

Production of interleukin-2 (IL-2) and expression of IL-2 receptor in patients with IgA nephropathy.

PubMed

Lee, T W; Kim, M J

1992-01-01

IL-2 production has been measured in several disease including type I diabetes mellitus, systemic lupus erythematosus, acquired immunodeficiency syndrome and active pulmonary sarcoidosis and its pathogenetic role was suggested. In IgA nephropathy, altered T cell subsets were reported to be associated with increased synthesis of IgA. The altered IL-2 production and the expression of IL-2 receptor might be involved in the pathogenesis of IgA nephropathy. To investigate the role of T cell mediated immunity in the pathogenesis of IgA nephropathy, the immune parameters such as T cell subsets, NK cell activity, interleukin-2 (IL-2) production and IL-2 receptor expression on peripheral blood mononuclear cells (PBMC) were measured before and/or after phytohemagglutinin (PHA) stimulation in 15 patients with IgA nephropathy. Age and sex matched 15 healthy controls and the correlations between the IL-2 production and immune parameters were evaluated. The mean percentages of T helper/inducer cells (CD4), T suppressor/cytotoxic cells (CD8) and the CD4/CD8 ratio of the patients were not different from those of controls and the proportions of CD8 CD11b cell in the patients (21.0 +/- 3.6%) were significantly lower than those in controls (30.5 +/- 5.3%) (p < 0.005). The production of IL-2 by fresh PBMC of both patients and controls was in undetectable ranges. The production of IL-2 by PHA stimulated PBMC of patients was significantly higher than that of controls (140.03 +/- 43.2 U/ml vs 106.5 +/- 42.1 U/ml, p < 0.05). The proportions of lymphocytes expressing the IL-2 receptor (CD25) before the stimulation with PHA in patients were 1.22 +/- 1.00 percent and were not different from those in controls (1.12 +/- 0.78 percent). The correlations between the production of IL-2 and the concentrations of serum IgA, the degrees of histologic alterations and the proportions of CD8 and CD8CD11b cells were not significant. There was a weak tendency of a positive correlation (p < 0.1) between the production of IL-2 and the proportions of CD4 cells, and the CD4/CD8 ratio showed a significant correlation with the production of IL-2 (p < 0.05). After PHA stimulation, the mean percentages of lymphocytes expressing the IL-2 receptors in patients were increased to 47.6 +/- 8.9 percents which is higher than those (40.4 +/- 9.9%) in controls (p < 0.05). The NK cell activity of the patients was higher than that of controls (75.6 +/- 19.6% vs 56.1 +/- 16.2%, p < 0.005), and was well correlated with the production of IL-2 by PBMC (r = 0.89, p < 0.05). It seemed that patients with IgA nephropathy have an 'latent' cellular immunoregulatory dysfunction that becomes apparent on the stimulation of extrinsic antigens or mitogens.

Prevalence of irritable bowel syndrome-type symptoms in patients with celiac disease: a meta-analysis.

PubMed

Sainsbury, Anita; Sanders, David S; Ford, Alexander C

2013-04-01

Patients with celiac disease (CD) often report symptoms compatible with irritable bowel syndrome (IBS). However, the prevalence of these symptoms in patients with CD and their relation to adherence to a gluten-free diet (GFD) have not been assessed systematically. We searched MEDLINE, EMBASE, and EMBASE Classic (through July 2012) to identify cross-sectional surveys or case-control studies reporting prevalence of IBS-type symptoms in adult patients (≥ 16 years old) with established CD. The number of individuals with symptoms meeting criteria for IBS was extracted for each study, according to case or control status and adherence to a GFD. Pooled prevalence and odds ratios (ORs), with 95% confidence intervals (CIs), were calculated. We analyzed data from 7 studies with 3383 participants. The pooled prevalence of IBS-type symptoms in all patients with CD was 38.0% (95% CI, 27.0%-50.0%). The pooled OR for IBS-type symptoms was higher in patients with CD than in controls (5.60; 95% CI, 3.23-9.70). In patients who were nonadherent with a GFD, the pooled OR for IBS-type symptoms, compared with those who were strictly adherent, was 2.69 (95% CI, 0.75-9.56). There was also a trend toward a higher OR for IBS-type symptoms among patients who did not adhere to the GFD, compared with controls (12.42; 95% CI, 6.84-11.75), compared with that observed for adherent CD patients vs controls (4.28; 95% CI, 1.56-11.75). IBS-type symptoms occur frequently in patients with CD and are more common than among controls. Adherence to a GFD might be associated with a reduction in symptoms. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Influenza virus infection in mice after exposure to coal dust and diesel engine emissions

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

Hahon, N.; Booth, J.A.; Green, F.

1985-06-01

Influenza virus infection initiated after aerosol exposure of CD-1, white Swiss mice for durations of 1, 3, and 6 months to respirable particulates maintained at 2 mg/m3 of either coal dust (CD), diesel engine emissions (DEE), a combination of both (CD/DEE), or to filtered air (control) was studied. The course of infection in mice previously exposed for 1 month to various particulates did not differ appreciably among the four animal groups with respect to mortality, virus growth in lungs, interferon levels, or hemagglutinin antibody response. In mice exposed for 3 and 6 months to different particulates, the mortality response wasmore » similar among all animal groups. However, the percentage of animals showing lung consolidation was significantly higher in the 3-month groups exposed to DEE (96.5%) and CD/DEE (97%) than in the control (61.2%); in the 6-month groups, the percentages were twice that of the control for both DEE- and CD/DEE-exposed animals. Complementing these observations of both 3- and 6-month-exposed animals was the higher virus growth levels attained in the DEE and CD/DEE animals with concomitant depressed interferon levels which were the inverse of findings noted in the control group. Hemagglutinin-antibody levels in particulate-exposed animals, especially at the 6-month interval, were fourfold less than the control. Histopathologic examination of lungs revealed no qualitative differences in the inflammatory response at any one specified time interval of exposure to influenza virus among the control and particulate-exposed animal groups. However, there were differences in severity of reaction in relation to the particulate component of the exposures. Focal macular collections of pigment-laden macrophages were seen only in DEE and CD/DEE but not in CD animals after 3- and 6-month exposures.« less

Interethnic diversity of the CD209 (rs4804803) gene promoter polymorphism in African but not American sickle cell disease.

PubMed

Noble, Jenelle A; Duru, Kimberley C; Guindo, Aldiouma; Yi, Li; Imumorin, Ikhide G; Diallo, Dapa A; Thomas, Bolaji N

2015-01-01

Elucidating the genomic diversity of CD209 gene promoter polymorphism could assist in clarifying disease pathophysiology as well as contribution to co-morbidities. CD209 gene promoter polymorphism has been shown to be associated with susceptibility to infection. We hypothesize that CD209 mutant variants occur at a higher frequency among Africans and in sickle cell disease. We analyzed the frequency of the CD209 gene (rs4804803) in healthy control and sickle cell disease (SCD) populations and determined association with disease. Genomic DNA was extracted from blood samples collected from 145 SCD and 231 control Africans (from Mali), 331 SCD and 379 control African Americans and 159 Caucasians. Comparative analysis among and between groups was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Per ethnic diversification, we found significant disparity in genotypic (23.4% versus 16.9% versus 3.2%) and allelic frequencies (48.7% versus 42.1% versus 19.8%) of the homozygote mutant variant of the CD209 (snp 309A/G) gene promoter between Africans, African Americans and Caucasians respectively. Comparative evaluation between disease and control groups reveal a significant difference in genotypic (10.4% versus 23.4%; p = 0.002) and allelic frequencies (39.7% versus 48.7%; p = 0.02) of the homozygote mutant variant in African SCD and healthy controls respectively, an observation that is completely absent among Americans. Comparing disease groups, we found no difference in the genotypic (p = 0.19) or allelic (p = 0.72) frequencies of CD209 homozygote mutant variant between Africans and Americans with sickle cell disease. The higher frequency of CD209 homozygote mutant variants in the African control group reveals a potential impairment of the capacity to mount an immune response to infectious diseases, and possibly delineate susceptibility to or severity of infectious co-morbidities within and between groups.

Interethnic diversity of the CD209 (rs4804803) gene promoter polymorphism in African but not American sickle cell disease

PubMed Central

Noble, Jenelle A.; Duru, Kimberley C.; Guindo, Aldiouma; Yi, Li; Imumorin, Ikhide G.; Diallo, Dapa A.

2015-01-01

Elucidating the genomic diversity of CD209 gene promoter polymorphism could assist in clarifying disease pathophysiology as well as contribution to co-morbidities. CD209 gene promoter polymorphism has been shown to be associated with susceptibility to infection. We hypothesize that CD209 mutant variants occur at a higher frequency among Africans and in sickle cell disease. We analyzed the frequency of the CD209 gene (rs4804803) in healthy control and sickle cell disease (SCD) populations and determined association with disease. Genomic DNA was extracted from blood samples collected from 145 SCD and 231 control Africans (from Mali), 331 SCD and 379 control African Americans and 159 Caucasians. Comparative analysis among and between groups was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Per ethnic diversification, we found significant disparity in genotypic (23.4% versus 16.9% versus 3.2%) and allelic frequencies (48.7% versus 42.1% versus 19.8%) of the homozygote mutant variant of the CD209 (snp 309A/G) gene promoter between Africans, African Americans and Caucasians respectively. Comparative evaluation between disease and control groups reveal a significant difference in genotypic (10.4% versus 23.4%; p = 0.002) and allelic frequencies (39.7% versus 48.7%; p = 0.02) of the homozygote mutant variant in African SCD and healthy controls respectively, an observation that is completely absent among Americans. Comparing disease groups, we found no difference in the genotypic (p = 0.19) or allelic (p = 0.72) frequencies of CD209 homozygote mutant variant between Africans and Americans with sickle cell disease. The higher frequency of CD209 homozygote mutant variants in the African control group reveals a potential impairment of the capacity to mount an immune response to infectious diseases, and possibly delineate susceptibility to or severity of infectious co-morbidities within and between groups. PMID:25755928

CD4 T Cell Depletion Exacerbates Acute Mycobacterium tuberculosis While Reactivation of Latent Infection Is Dependent on Severity of Tissue Depletion in Cynomolgus Macaques

PubMed Central

Lin, Philana Ling; Rutledge, Tara; Green, Angela M.; Bigbee, Matthew; Fuhrman, Carl; Klein, Edwin

2012-01-01

Abstract CD4 T cells are believed to be important in protection against Mycobacterium tuberculosis, but the relative contribution to control of initial or latent infection is not known. Antibody-mediated depletion of CD4 T cells in M. tuberculosis-infected cynomolgus macaques was used to study the role of CD4 T cells during acute and latent infection. Anti-CD4 antibody severely reduced levels of CD4 T cells in blood, airways, and lymph nodes. Increased pathology and bacterial burden were observed in CD4-depleted monkeys during the first 8 weeks of infection compared to controls. CD4-depleted monkeys had greater interferon (IFN)-γ expression and altered expression of CD8 T cell activation markers. During latent infection, CD4 depletion resulted in clinical reactivation in only three of six monkeys. Reactivation was associated with lower CD4 T cells in the hilar lymph nodes. During both acute and latent infection, CD4 depletion was associated with reduced percentages of CXCR3+ expressing CD8 T cells, reported to be involved in T cell recruitment, regulatory function, and effector and memory T cell maturation. CXCR3+ CD8 T cells from hilar lymph nodes had more mycobacteria-specific cytokine expression and greater coexpression of multiple cytokines compared to CXCR3− CD8 T cells. CD4 T cells are required for protection against acute infection but reactivation from latent infection is dependent on the severity of depletion in the draining lymph nodes. CD4 depletion influences CD8 T cell function. This study has important implications for human HIV–M. tuberculosis coinfection. PMID:22480184

Selenium supplementation prevents metabolic and transcriptomic responses to cadmium in mouse lung.

PubMed

Hu, Xin; Chandler, Joshua D; Fernandes, Jolyn; Orr, Michael L; Hao, Li; Uppal, Karan; Neujahr, David C; Jones, Dean P; Go, Young-Mi

2018-04-12

The protective effect of selenium (Se) on cadmium (Cd) toxicity is well documented, but underlying mechanisms are unclear. Male mice fed standard diet were given Cd (CdCl 2 , 18 μmol/L) in drinking water with or without Se (Na 2 SeO 4, 20 μmol/L) for 16 weeks. Lungs were analyzed for Cd concentration, transcriptomics and metabolomics. Data were analyzed with biostatistics, bioinformatics, pathway enrichment analysis, and combined transcriptome-metabolome-wide association study. Mice treated with Cd had higher lung Cd content (1.7 ± 0.4 pmol/mg protein) than control mice (0.8 ± 0.3 pmol/mg protein) or mice treated with Cd and Se (0.4 ± 0.1 pmol/mg protein). Gene set enrichment analysis of transcriptomics data showed that Se prevented Cd effects on inflammatory and myogenesis genes and diminished Cd effects on several other pathways. Similarly, Se prevented Cd-disrupted metabolic pathways in amino acid metabolism and urea cycle. Integrated transcriptome and metabolome network analysis showed that Cd treatment had a network structure with fewer gene-metabolite clusters compared to control. Centrality measurements showed that Se counteracted changes in a group of Cd-responsive genes including Zdhhc11, (protein-cysteine S-palmitoyltransferase), Ighg1 (immunoglobulin heavy constant gamma-1) and associated changes in metabolite concentrations. Co-administration of Se with Cd prevented Cd increase in lung and prevented Cd-associated pathway and network responses of the transcriptome and metabolome. Se protection against Cd toxicity in lung involves complex systems responses. Environmental Cd stimulates proinflammatory and profibrotic signaling. The present results indicate that dietary or supplemental Se could be useful to mitigate Cd toxicity. Published by Elsevier B.V.

Circulating Bone Marrow-Derived CD45-/CD34+/CD133+/VEGF+ Endothelial Progenitor Cells in Adults with Crohn's Disease.

PubMed

Boltin, Doron; Kamenetsky, Zvi; Perets, Tsachi Tsadok; Snir, Yifat; Sapoznikov, Boris; Schmilovitz-Weiss, Hemda; Ablin, Jacob Nadav; Dickman, Ram; Niv, Yaron

2017-03-01

Circulating endothelial progenitor cells (EPCs) are bone marrow-derived stem cells able to migrate to sites of damaged endothelium and differentiate into endothelial cells. Altered EPC level and function have been described in various inflammatory diseases and have been shown to augment vasculogenesis in murine models. Previous studies of EPC in the context of Crohn's disease (CD) have yielded conflicting results. To determine whether the circulating levels of EPCs are changed in the context of CD. CD patients and healthy controls were recruited. Disease activity was assessed by CDAI. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by FACS analysis using anti-CD34, anti-VEGF receptor-2, anti-CD133, and anti-CD45 markers. Eighty-three subjects, including 32 CD patients and 51 controls were recruited, including 19 (59.4 %) and 23 (45 %) males (p = 0.26), aged 34.8 ± 14.9 and 43.3 ± 18.5 years (p = 0.64), in cases and controls, respectively. Mean CDAI was 147 ± 97, disease duration was 12.7 ± 11.1 years, and 28 (87.5 %) were receiving biologics for a mean duration of 21.7 ± 16.8 months. The mean level of peripheral EPCs in CD patients was 0.050 ± 0.086 percent and 0.007 ± 0.013 % in controls (p < 0.01). There was no significant correlation between EPC levels and age (r = -0.13, p = 0.47), CDAI (r = -0.26, p = 0.15), disease duration (r = -0.04, p = 0.84), or duration of treatment with biologics (r = 0.004, p = 0.99). EPCs are elevated in patients with CD. Further studies are needed to examine the function of EPCs and their possible role as a marker of disease severity or therapeutic response.

Immunological role of CD4+CD28null T lymphocytes, natural killer cells, and interferon-gamma in pediatric patients with sickle cell disease: relation to disease severity and response to therapy.

PubMed

ElAlfy, Mohsen Saleh; Adly, Amira Abdel Moneam; Ebeid, Fatma Soliman ElSayed; Eissa, Deena Samir; Ismail, Eman Abdel Rahman; Mohammed, Yasser Hassan; Ahmed, Manar Elsayed; Saad, Aya Sayed

2018-06-20

Sickle cell disease (SCD) is associated with alterations in immune phenotypes. CD4 + CD28 null T lymphocytes have pro-inflammatory functions and are linked to vascular diseases. To assess the percentage of CD4 + CD28 null T lymphocytes, natural killer cells (NK), and IFN-gamma levels, we compared 40 children and adolescents with SCD with 40 healthy controls and evaluated their relation to disease severity and response to therapy. Patients with SCD steady state were studied, focusing on history of frequent vaso-occlusive crisis, hydroxyurea therapy, and IFN-gamma levels. Analysis of CD4 + CD28 null T lymphocytes and NK cells was done by flow cytometry. Liver and cardiac iron overload were assessed. CD4 + CD28 null T lymphocytes, NK cells, and IFN-gamma levels were significantly higher in patients than controls. Patients with history of frequent vaso-occlusive crisis and those with vascular complications had higher percentage of CD4 + CD28 null T lymphocytes and IFN-gamma while levels were significantly lower among hydroxyurea-treated patients. CD4 + CD28 null T lymphocytes were positively correlated to transfusional iron input while these cells and IFN-gamma were negatively correlated to cardiac T2* and duration of hydroxyurea therapy. NK cells were correlated to HbS and indirect bilirubin. Increased expression of CD4 + CD28 null T lymphocytes highlights their role in immune dysfunction and pathophysiology of SCD complications.

Personality disorders and normal personality dimensions in obsessive-compulsive disorder.

PubMed

Samuels, J; Nestadt, G; Bienvenu, O J; Costa, P T; Riddle, M A; Liang, K Y; Hoehn-Saric, R; Grados, M A; Cullen, B A

2000-11-01

Little is known about personality disorders and normal personality dimensions in relatives of patients with obsessive-compulsive disorder (OCD). To determine whether specific personality characteristics are part of a familial spectrum of OCD. Clinicians evaluated personality disorders in 72 OCD case and 72 control probands and 198 case and 207 control first-degree relatives. The selfcompleted Revised NEO Personality Inventory was used for assessment of normal personality dimensions. The prevalence of personality disorders and scores on normal personality dimensions were compared between case and control probands and between case and control relatives. Case probands and case relatives had a high prevalence of obsessive-compulsive personality disorder (OCPD) and high neuroticism scores. Neuroticism was associated with OCPD in case but not control relatives. Neuroticism and OCPD may share a common familial aetiology with OCD.

Cervical sensorimotor control in idiopathic cervical dystonia: A cross-sectional study.

PubMed

De Pauw, Joke; Mercelis, Rudy; Hallemans, Ann; Michiels, Sarah; Truijen, Steven; Cras, Patrick; De Hertogh, Willem

2017-09-01

Patients with idiopathic adult-onset cervical dystonia (CD) experience an abnormal head posture and involuntary muscle contractions. Although the exact areas affected in the central nervous system remain uncertain, impaired functions in systems stabilizing the head and neck are apparent such as the somatosensory and sensorimotor integration systems. The aim of the study is to investigate cervical sensorimotor control dysfunction in patients with CD. Cervical sensorimotor control was assessed by a head repositioning task in 24 patients with CD and 70 asymptomatic controls. Blindfolded participants were asked to reposition their head to a previously memorized neutral head position (NHP) following an active movement (flexion, extension, left, and right rotation). The repositioning error (joint position error, JPE) was registered via 3D motion analysis with an eight-camera infrared system (VICON ® T10). Disease-specific characteristics of all patients were obtained via the Tsui scale, Cervical Dystonia Impact Profile (CDIP-58), and Toronto Western Spasmodic Rating Scale. Patients with CD showed larger JPE than controls (mean difference of 1.5°, p  <   .006), and systematically 'overshoot', i.e. surpassed the NHP, whereas control subjects 'undershoot', i.e. fall behind the NHP. The JPE did not correlate with disease-specific characteristics. Cervical sensorimotor control is impaired in patients with CD. As cervical sensorimotor control can be trained, this might be a potential treatment option for therapy, adjuvant to botulinum toxin injections.

Cadmium: Simulation of environmental control strategies to reduce exposure

NASA Astrophysics Data System (ADS)

Yost, K. J.; Miles, L. J.; Greenkorn, R. A.

1981-07-01

The effects of selected environmental control strategies on human dietary and respiratory exposure to environmental cadmium (Cd) have been simulated. For each control strategy, mean Cd dietary and respiratory exposures are presented for a twenty-year simulation period. Human exposures related to cadmium are associated with both process waste disposal and product disposal. Dietary exposure is by far the dominant mechanism for Cd intake. Dietary exposure related to aqueous discharges is primarily a result of municipal sludge landspreading, whereas that associated with emissions to the atmosphere derives mainly from the deposition on cropland of airborne particulates from product incineration. Only relatively small dietary exposure reductions are possible through restrictions on any single Cd use. Combinations of waste management and environmental control measures promise greater reductions in dietary and respiratory exposure than those achievable through use restrictions.

CD16+ monocytes control T-cell subset development in immune thrombocytopenia

PubMed Central

Zhong, Hui; Bao, Weili; Li, Xiaojuan; Miller, Allison; Seery, Caroline; Haq, Naznin; Bussel, James

2012-01-01

Immune thrombocytopenia (ITP) results from decreased platelet production and accelerated platelet destruction. Impaired CD4+ regulatory T-cell (Treg) compartment and skewed Th1 and possibly Th17 responses have been described in ITP patients. The trigger for aberrant T-cell polarization remains unknown. Because monocytes have a critical role in development and polarization of T-cell subsets, we explored the contribution of monocyte subsets in control of Treg and Th development in patients with ITP. Unlike circulating classic CD14hiCD16− subpopulation, the CD16+ monocyte subset was expanded in ITP patients with low platelet counts on thrombopoietic agents and positively correlated with T-cell CD4+IFN-γ+ levels, but negatively with circulating CD4+CD25hiFoxp3+ and IL-17+ Th cells. Using a coculture model, we found that CD16+ ITP monocytes promoted the expansion of IFN-γ+CD4+ cells and concomitantly inhibited the proliferation of Tregs and IL-17+ Th cells. Th-1–polarizing cytokine IL-12, secreted after direct contact of patient T-cell and CD16+ monocytes, was responsible for the inhibitory effect on Treg and IL-17+CD4+ cell proliferation. Our findings are consistent with ITP CD16+ monocytes promoting Th1 development, which in turn negatively regulates IL-17 and Treg induction. This underscores the critical role of CD16+ monocytes in the generation of potentially pathogenic Th responses in ITP. PMID:22915651

Characterization of naïve, memory and effector T cells in progressive multiple sclerosis.

PubMed

Nielsen, Birgitte Romme; Ratzer, Rikke; Börnsen, Lars; von Essen, Marina Rode; Christensen, Jeppe Romme; Sellebjerg, Finn

2017-09-15

We characterized naïve, central memory (CM), effector memory (EM) and terminally differentiated effector memory (TEMRA) CD4 + and CD8 + T cells and their expression of CD49d and CD26 in peripheral blood in patients with multiple sclerosis (MS) and healthy controls. CD26 + CD28 + CD4 + TEMRA T cells were increased in all subtypes of MS, and CD26 + CD28 + CD8 + TEMRA T cells were increased in relapsing-remitting and secondary progressive MS. Conversely, in progressive MS, CD49d + CM T cells were decreased and natalizumab increased the circulating number of all six subsets but reduced the frequency of most subsets expressing CD49d and CD26. Copyright © 2017 Elsevier B.V. All rights reserved.

Fault Tolerant Paradigms

DTIC Science & Technology

2016-02-26

say that A is a JL(m,d,)-embedding of S into Cm. Linear JL(m,d,)-embeddings are closely related to the Restricted Isometry Property [9, 4, 18...holds ∀x ∈ Cd containing at most s nonzero coordinates. In this case we will say that A is RIP(s,). In particular, the following theorem due to Krahmer...implement reliable edge detector functions, especially in the presence of noise. Needless to say , the same issues exist in two dimensions, as

CD81 controls immunity to Listeria infection through rac-dependent inhibition of proinflammatory mediator release and activation of cytotoxic T cells.

PubMed

Martínez del Hoyo, Gloria; Ramírez-Huesca, Marta; Levy, Shoshana; Boucheix, Claude; Rubinstein, Eric; Minguito de la Escalera, María; González-Cintado, Leticia; Ardavín, Carlos; Veiga, Esteban; Yáñez-Mó, María; Sánchez-Madrid, Francisco

2015-06-15

Despite recent evidence on the involvement of CD81 in pathogen binding and Ag presentation by dendritic cells (DCs), the molecular mechanism of how CD81 regulates immunity during infection remains to be elucidated. To investigate the role of CD81 in the regulation of defense mechanisms against microbial infections, we have used the Listeria monocytogenes infection model to explore the impact of CD81 deficiency in the innate and adaptive immune response against this pathogenic bacteria. We show that CD81(-/-) mice are less susceptible than wild-type mice to systemic Listeria infection, which correlates with increased numbers of inflammatory monocytes and DCs in CD81(-/-) spleens, the main subsets controlling early bacterial burden. Additionally, our data reveal that CD81 inhibits Rac/STAT-1 activation, leading to a negative regulation of the production of TNF-α and NO by inflammatory DCs and the activation of cytotoxic T cells by splenic CD8α(+) DCs. In conclusion, this study demonstrates that CD81-Rac interaction exerts an important regulatory role on the innate and adaptive immunity against bacterial infection and suggests a role for CD81 in the development of novel therapeutic targets during infectious diseases. Copyright © 2015 by The American Association of Immunologists, Inc.

Microvascular dysfunction following multi-walled carbon nanotube exposure is mediated by thrombospondin-1 receptor CD47.

PubMed

Mandler, W Kyle; Nurkiewicz, Timothy R; Porter, Dale W; Kelley, Eric E; Olfert, I Mark

2018-05-21

Pulmonary exposure to multi-walled carbon nanotubes (MWCNT) disrupts peripheral microvascular function. Thrombospondin-1 (TSP-1) is highly expressed during lung injury and has been shown to alter microvascular reactivity. It is unclear exactly how TSP-1 exerts effects on vascular function, but we hypothesized that the TSP-1 receptor CD47 may mediate changes in vasodilation.Wildtype (WT) or CD47 knockout (CD47 KO) C57B6/J-background animals were exposed to 50 µg of MWCNT or saline control via pharyngeal aspiration. Twenty-four hours post-exposure, intravital microscopy was performed to assess arteriolar dilation and venular leukocyte adhesion and rolling. To assess tissue redox status, electron paramagnetic resonance and NOx measurements were performed, while inflammatory biomarkers were measured via multiplex assay.Vasodilation was impaired in the WT+MWCNT group compared to control (57±9% vs 90±2% relaxation), while CD47 KO animals showed no impairment (108±8% relaxation). Venular leukocyte adhesion and rolling increased by > 2-fold, while the CD47 KO group showed no change. Application of the antioxidant apocynin rescued normal leukocyte activity in the WT+MWCNT group. Lung and plasma NOx were reduced in the WT+MWCNT group by 47% and 32%, respectively, while the CD47 KO groups were unchanged from control. Some inflammatory cytokines were increased in the CD47+MWCNT group only.In conclusion, TSP-1 is an important ligand mediating MWCNT-induced microvascular dysfunction, and CD47 is a component of this dysregulation. CD47 activation likely disrupts nitric oxide (•NO) signaling and promotes leukocyte-endothelial interactions. Impaired •NO production, signaling, and bioavailability is linked to a variety of cardiovascular diseases in which TSP-1/CD47 may play an important role.

Collecting duct-specific knockout of nitric oxide synthase 3 impairs water excretion in a sex-dependent manner

PubMed Central

Gao, Yang; Stuart, Deborah; Pollock, Jennifer S.; Takahishi, Takamune

2016-01-01

Nitric oxide (NO) inhibits collecting duct (CD) Na+ and water reabsorption. Mice with CD-specific knockout (KO) of NO synthase 1 (NOS1) have salt-sensitive hypertension. In contrast, the role of NOS3 in CD salt and water reabsorption is unknown. Mice with CD NOS3 KO were generated with loxP-flanked exons 9–12 (encodes the calmodulin binding site) of the NOS3 gene and the aquaporin-2 promoter-Cre transgene. There were no differences between control and CD NOS3 KO mice, irrespective of sex, in food intake, water intake, urine volume, urinary Na+ or K+ excretion, plasma renin concentration, blood pressure, or pulse during 7 days of normal (0.3%), high (3.17%), or low (0.03%) Na+ intake. Blood pressure was similar between genotypes during DOCA-high salt. CD NOS3 KO did not alter urine volume or urine osmolality after water deprivation. In contrast, CD NOS3 KO male, but not female, mice had lower urine volume and higher urine osmolality over the course of 7 days of water loading compared with control mice. Male, but not female, CD NOS3 KO mice had reduced urinary nitrite+nitrate excretion compared with controls after 7 days of water loading. Urine AVP and AVP-stimulated cAMP accumulation in isolated inner medullary CD were similar between genotypes. Western analysis did not reveal a significant effect of CD NOS3 KO on renal aquaporin expression. In summary, these data suggest that CD NOS3 may be involved in the diuretic response to a water load in a sex-specific manner; the mechanism of this effect remains to be determined. PMID:27707708

Effects of cadmium, estradiol-17beta and their interaction on gonadal condition and metamorphosis of male and female African clawed frog, Xenopus laevis

USGS Publications Warehouse

Sharma, Bibek; Patino, Reynaldo

2010-01-01

To assess interaction effects between cadmium (Cd, a putative xenoestrogen) and estradiol-17beta (E(2)) on sex differentiation and metamorphosis, Xenopus laevis were exposed to solvent-control (0.005% ethanol), Cd (10microgL(-1)), E(2) (1microgL(-1)), or Cd and E(2) (Cd+E(2)) in FETAX medium from fertilization to 75d postfertilization. Each treatment was applied to four aquaria, each with 30 fertilized eggs. Mortality was recorded and animals were sampled as they completed metamorphosis (Nieuwkoop and Faber stage 66). Gonadal sex of individuals (including >or= tadpoles NF stage 55 at day 75) was determined gross-morphologically and used to compute sex ratios. Time course and percent completion of metamorphosis, snout-vent length (SVL), hindlimb length (HLL) and weight were analyzed for each gender separately. Survival rates did not differ among treatments. The E(2) and Cd+E(2) treatments significantly skewed sex ratios towards females; however, no sex-ratio differences were observed between the control and Cd treatments or between the E(2) and Cd+E(2) treatments. Time course of metamorphosis was generally delayed and percent completion of metamorphosis was generally reduced in males and females exposed to Cd, E(2) or their combination compared to control animals. In males, but not females, the effect of Cd+E(2) was greater than that of individual chemicals. Weight at completion of metamorphosis was reduced only in females and only by the Cd+E(2) treatment. In conclusion, although Cd at an environmentally relevant concentration did not exhibit direct or indirect feminizing effects in Xenopus tadpoles, the metal and E(2) both had similar inhibitory effects on metamorphosis that were of greater magnitude in males than females.

Effects of cadmium, estradiol-17β and their interaction on gonadal condition and metamorphosis of male and female African clawed frog, Xenopus laevis

USGS Publications Warehouse

Sharma, Bibek; Patino, Reynaldo

2010-01-01

To assess interaction effects between cadmium (Cd, a putative xenoestrogen) and estradiol-17?? (E2) on sex differentiation and metamorphosis, Xenopus laevis were exposed to solvent-control (0.005% ethanol), Cd (10 ??g L-1), E2 (1 ??g L-1), or Cd and E2 (Cd + E2) in FETAX medium from fertilization to 75 d postfertilization. Each treatment was applied to four aquaria, each with 30 fertilized eggs. Mortality was recorded and animals were sampled as they completed metamorphosis (Nieuwkoop and Faber stage 66). Gonadal sex of individuals (including tadpoles ???NF stage 55 at day 75) was determined gross-morphologically and used to compute sex ratios. Time course and percent completion of metamorphosis, snout-vent length (SVL), hindlimb length (HLL) and weight were analyzed for each gender separately. Survival rates did not differ among treatments. The E2 and Cd + E2 treatments significantly skewed sex ratios towards females; however, no sex-ratio differences were observed between the control and Cd treatments or between the E2 and Cd + E2 treatments. Time course of metamorphosis was generally delayed and percent completion of metamorphosis was generally reduced in males and females exposed to Cd, E2 or their combination compared to control animals. In males, but not females, the effect of Cd + E2 was greater than that of individual chemicals. Weight at completion of metamorphosis was reduced only in females and only by the Cd + E2 treatment. In conclusion, although Cd at an environmentally relevant concentration did not exhibit direct or indirect feminizing effects in Xenopus tadpoles, the metal and E2 both had similar inhibitory effects on metamorphosis that were of greater magnitude in males than females.

Regulation of ecto-apyrase CD39 (ENTPD1) expression by phosphodiesterase III (PDE3)

PubMed Central

Baek, Amy E.; Kanthi, Yogendra; Sutton, Nadia R.; Liao, Hui; Pinsky, David J.

2013-01-01

The ectoenzyme CD39 suppresses thrombosis and inflammation by suppressing ATP and ADP to AMP. However, mechanisms of CD39 transcriptional and post-translational regulation are not well known. Here we show that CD39 levels are modulated by inhibition of phosphodiesterase 3 (PDE3). RAW macrophages and human umbilical vein endothelial cells (HUVECs) were treated with the PDE3 inhibitors cilostazol and milrinone, then analyzed using qRT-PCR, immunoprecipitation/Western blot, immunofluorescent staining, radio-thin-layer chromatography, a malachite green assay, and ELISA. HUVECs expressed elevated CD39 protein (2-fold [P<0.05] for cilostazol and 2.5-fold [P<0.01] for milrinone), while macrophage CD39 mRNA and protein were both elevated after PDE3 inhibition. HUVEC ATPase activity increased by 25% with cilostazol and milrinone treatment (P<0.05 and P<0.01, respectively), as did ADPase activity (47% and 61%, P<0.001). There was also a dose-dependent elevation of soluble CD39 after treatment with 8-Br-cAMP, with maximal elevation of 60% more CD39 present compared to controls (1 mM, P<0.001). Protein harvested after 8-Br-cAMP treatment showed that ubiquitination of CD39 was decreased by 43% compared to controls. A DMSO or PBS vehicle control was included for each experiment based on solubility of cilostazol, milrinone, and 8-Br-cAMP. These results indicate that PDE3 inhibition regulates endothelial CD39 at a post-translational level.—Baek, A. E., Kanthi, Y., Sutton, N. R., Liao, H., Pinsky, D. J. Regulation of ecto-apyrase CD39 (ENTPD1) expression by phosphodiesterase III (PDE3). PMID:23901069