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  1. Highly Pathological Influenza A Virus Infection Is Associated with Augmented Expression of PD-1 by Functionally Compromised Virus-Specific CD8+ T Cells

    PubMed Central

    Rutigliano, John A.; Sharma, Shalini; Morris, Melissa Y.; Oguin, Thomas H.; McClaren, Jennifer L.; Doherty, Peter C.

    2014-01-01

    ABSTRACT One question that continues to challenge influenza A research is why some strains of virus are so devastating compared to their more mild counterparts. We approached this question from an immunological perspective, investigating the CD8+ T cell response in a mouse model system comparing high- and low-pathological influenza virus infections. Our findings reveal that the early (day 0 to 5) viral titer was not the determining factor in the outcome of disease. Instead, increased numbers of antigen-specific CD8+ T cells and elevated effector function on a per-cell basis were found in the low-pathological infection and correlated with reduced illness and later-time-point (day 6 to 10) viral titer. High-pathological infection was associated with increased PD-1 expression on influenza virus-specific CD8+ T cells, and blockade of PD-L1 in vivo led to reduced virus titers and increased CD8+ T cell numbers in high- but not low-pathological infection, though T cell functionality was not restored. These data show that high-pathological acute influenza virus infection is associated with a dysregulated CD8+ T cell response, which is likely caused by the more highly inflamed airway microenvironment during the early days of infection. Therapeutic approaches specifically aimed at modulating innate airway inflammation may therefore promote efficient CD8+ T cell activity. IMPORTANCE PMID:24257598

  2. Establishment of functional influenza virus-specific CD8(+) T cell memory pools after intramuscular immunization.

    PubMed

    Wang, Zhongfang; Chua, Brendon Y; Ramos, Javier Vega; Parra, Sergio M Quiñones; Fairmaid, Emily; Brown, Lorena E; Jackson, David C; Kedzierska, Katherine

    2015-09-22

    The emergence of the avian-origin influenza H7N9 virus and its pandemic potential has highlighted the ever-present need to develop vaccination approaches to induce cross-protective immunity. In this study, we examined the establishment of cross-reactive CD8(+) T cell immunity in mice following immunization with live A/Puerto Rico/8/1934 (PR8; H1N1) influenza virus via two non-productive inoculation routes. We found that immunization via the intramuscular (IM) route established functional influenza-virus specific memory CD8(+) T cell pools capable of cross-reactive recall responses. Epitope-specific primary, memory and recall CD8(+) T-cell responses induced by the IM route, highly relevant to human influenza immunisations, were of comparable magnitude and quality to those elicited by the intraperitoneal (IP) priming, commonly used in mice. Furthermore, IM immunisation resulted in lower lung viral titres following heterologous challenge with A/Aichi/68 (X31; H3N2) compared to the IP route. Examining the ability of DCs from lymphoid organs to present viral antigen revealed that immune induction following IM immunization occurred in draining lymph nodes, while immunization via the IP route resulted in the priming of responses in distal lymphoid organs, indicative of a systemic distribution of antigen. No major differences in the pulmonary cytokine environment of immunized animals following X31 challenge were observed that could account for the improved heterologous protection induced by the IM route. However, while both routes induced similar levels of PR8-specific antibodies, higher levels of cross-reactive antibodies against X31 were induced following IM inoculation. Our data demonstrate how non-replicative routes of infection can induce efficient cross-reactive CD8(+) T cell responses and strong strain-specific antibody responses, with the additional benefit from IM priming of enhanced heterosubtypic antibody production. PMID:26277069

  3. Functional aspects of intrahepatic hepatitis B virus-specific T cells induced by therapeutic DNA vaccination.

    PubMed

    Brass, Anette; Frelin, Lars; Milich, David R; Sällberg, Matti; Ahlén, Gustaf

    2015-03-01

    Current therapies for the hepatitis B virus (HBV), a major cause of severe liver disease, suppress viral replication but replication rebounds if therapy is withdrawn. It is widely accepted that immune activation is needed to control replication off-therapy. To specifically activate T cells crossreactive between the hepatitis B core and e antigens (HBcAg/HBeAg) in chronically infected patients, we developed a therapeutic vaccine candidate. The vaccine encompass codon-optimized HBcAg and IL-12 expressing plasmids delivered using targeted high-pressure injection combined with in vivo electroporation. One dose of the vaccine primed a B-cell-independent polyfunctional T-cell response, in wild-type, and in HBeAg-transgenic mice with an impaired ability to respond to HBc/eAg. The response peaked at 2 weeks and contracted at week 6 after vaccination. Coadministration of IL-12 improved antibody levels, and T-cell expansion and functionality. The vaccine primed T cells that, 2 weeks after a single dose, cleared hepatocytes transiently expressing HBcAg in vaccinated wild-type and HBeAg-transgenic mice. However, 4 weeks later, these functional responses were lost. Booster doses after 8-12 weeks effectively restored function and expansion of the rapidly contracting T cells. Thus, this vaccine strategy primes functional HBcAg-specific T cells in a host with dysfunctional response to HBV.

  4. The DNase of gammaherpesviruses impairs recognition by virus-specific CD8+ T cells through an additional host shutoff function.

    PubMed

    Zuo, Jianmin; Thomas, Wendy; van Leeuwen, Daphne; Middeldorp, Jaap M; Wiertz, Emmanuel J H J; Ressing, Maaike E; Rowe, Martin

    2008-03-01

    The DNase/alkaline exonuclease (AE) genes are well conserved in all herpesvirus families, but recent studies have shown that the AE proteins of gammaherpesviruses such as Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) exhibit an additional function which shuts down host protein synthesis. One correlate of this additional shutoff function is that levels of cell surface HLA molecules are downregulated, raising the possibility that shutoff/AE genes of gammaherpesviruses might contribute to viral immune evasion. In this study, we show that both BGLF5 (EBV) and SOX (KSHV) shutoff/AE proteins do indeed impair the ability of virus-specific CD8+ T-cell clones to recognize endogenous antigen via HLA class I. Random mutagenesis of the BGLF5 gene enabled us to genetically separate the shutoff and AE functions and to demonstrate that the shutoff function was the critical factor determining whether BGLF5 mutants can impair T-cell recognition. These data provide further evidence that EBV has multiple mechanisms to modulate HLA class I-restricted T-cell responses, thus enabling the virus to replicate and persist in the immune-competent host.

  5. Persistent Enteric Murine Norovirus Infection Is Associated with Functionally Suboptimal Virus-Specific CD8 T Cell Responses

    PubMed Central

    Tomov, Vesselin T.; Osborne, Lisa C.; Dolfi, Douglas V.; Sonnenberg, Gregory F.; Monticelli, Laurel A.; Mansfield, Kathleen; Virgin, Herbert W.

    2013-01-01

    Norovirus (NV) gastroenteritis is a major contributor to global morbidity and mortality, yet little is known about immune mechanisms leading to NV control. Previous studies using the murine norovirus (MNV) model have established a key role for T cells in MNV clearance. Despite these advances, important questions remain regarding the magnitude, location, and dynamics of the MNV-specific T cell response. To address these questions, we identified MNV-specific major histocompatibility complex (MHC) class I immunodominant epitopes using an overlapping peptide screen. One of these epitopes (amino acids 519 to 527 of open reading frame 2 [ORF2519-527]) was highly conserved among all NV genogroups. Using MHC class I peptide tetramers, we tracked MNV-specific CD8 T cells in lymphoid and mucosal sites during infection with two MNV strains with distinct biological behaviors, the acutely cleared strain CW3 and the persistent strain CR6. Here, we show that enteric MNV infection elicited robust T cell responses primarily in the intestinal mucosa and that MNV-specific CD8 T cells dynamically regulated the expression of surface molecules associated with activation, differentiation, and homing. Furthermore, compared to MNV-CW3 infection, chronic infection with MNV-CR6 resulted in fewer and less-functional CD8 T cells, and this difference was evident as early as day 8 postinfection. Finally, MNV-specific CD8 T cells were capable of reducing the viral load in persistently infected Rag1−/− mice, suggesting that these cells are a crucial component of NV immunity. Collectively, these data provide fundamental new insights into the adaptive immune response to two closely related NV strains with distinct biological behaviors and bring us closer to understanding the correlates of protective antiviral immunity in the intestine. PMID:23596300

  6. Distinct Metabolic Requirements of Exhausted and Functional Virus-Specific CD8 T Cells in the Same Host.

    PubMed

    Schurich, Anna; Pallett, Laura J; Jajbhay, Danyal; Wijngaarden, Jessica; Otano, Itziar; Gill, Upkar S; Hansi, Navjyot; Kennedy, Patrick T; Nastouli, Eleni; Gilson, Richard; Frezza, Christian; Henson, Sian M; Maini, Mala K

    2016-08-01

    T cells undergo profound metabolic changes to meet the increased energy demands of maintaining an antiviral response. We postulated that differences in metabolic reprogramming would shape the efficacy of CD8 T cells mounted against persistent viral infections. We found that the poorly functional PD-1(hi) T cell response against hepatitis B virus (HBV) had upregulated the glucose transporter, Glut1, an effect recapitulated by oxygen deprivation to mimic the intrahepatic environment. Glut1(hi) HBV-specific T cells were dependent on glucose supplies, unlike the more functional cytomegalovirus (CMV)-specific T cells that could utilize oxidative phosphorylation in the absence of glucose. The inability of HBV-specific T cells to switch to oxidative phosphorylation was accompanied by increased mitochondrial size and lower mitochondrial potential, indicative of mitochondrial dysfunction. Interleukin (IL)-12, which recovers HBV-specific T cell effector function, increased their mitochondrial potential and reduced their dependence on glycolysis. Our findings suggest that mitochondrial defects limit the metabolic plasticity of exhausted HBV-specific T cells. PMID:27452473

  7. Cytomegalovirus Infection Leads to Development of High Frequencies of Cytotoxic Virus-Specific CD4+ T Cells Targeted to Vascular Endothelium.

    PubMed

    Pachnio, Annette; Ciaurriz, Miriam; Begum, Jusnara; Lal, Neeraj; Zuo, Jianmin; Beggs, Andrew; Moss, Paul

    2016-09-01

    Cytomegalovirus (CMV) infection elicits a very strong and sustained intravascular T cell immune response which may contribute towards development of accelerated immune senescence and vascular disease in older people. Virus-specific CD8+ T cell responses have been investigated extensively through the use of HLA-peptide tetramers but much less is known regarding CMV-specific CD4+ T cells. We used a range of HLA class II-peptide tetramers to investigate the phenotypic and transcriptional profile of CMV-specific CD4+ T cells within healthy donors. We show that such cells comprise an average of 0.45% of the CD4+ T cell pool and can reach up to 24% in some individuals (range 0.01-24%). CMV-specific CD4+ T cells display a highly differentiated effector memory phenotype and express a range of cytokines, dominated by dual TNF-α and IFN-γ expression, although substantial populations which express IL-4 were seen in some donors. Microarray analysis and phenotypic expression revealed a profile of unique features. These include the expression of CX3CR1, which would direct cells towards fractalkine on activated endothelium, and the β2-adrenergic receptor, which could permit rapid response to stress. CMV-specific CD4+ T cells display an intense cytotoxic profile with high level expression of granzyme B and perforin, a pattern which increases further during aging. In addition CMV-specific CD4+ T cells demonstrate strong cytotoxic activity against antigen-loaded target cells when isolated directly ex vivo. PD-1 expression is present on 47% of cells but both the intensity and distribution of the inhibitory receptor is reduced in older people. These findings reveal the marked accumulation and unique phenotype of CMV-specific CD4+ T cells and indicate how such T cells may contribute to the vascular complications associated with CMV in older people. PMID:27606804

  8. Cytomegalovirus Infection Leads to Development of High Frequencies of Cytotoxic Virus-Specific CD4+ T Cells Targeted to Vascular Endothelium

    PubMed Central

    Begum, Jusnara; Lal, Neeraj; Zuo, Jianmin; Beggs, Andrew; Moss, Paul

    2016-01-01

    Cytomegalovirus (CMV) infection elicits a very strong and sustained intravascular T cell immune response which may contribute towards development of accelerated immune senescence and vascular disease in older people. Virus-specific CD8+ T cell responses have been investigated extensively through the use of HLA-peptide tetramers but much less is known regarding CMV-specific CD4+ T cells. We used a range of HLA class II-peptide tetramers to investigate the phenotypic and transcriptional profile of CMV-specific CD4+ T cells within healthy donors. We show that such cells comprise an average of 0.45% of the CD4+ T cell pool and can reach up to 24% in some individuals (range 0.01–24%). CMV-specific CD4+ T cells display a highly differentiated effector memory phenotype and express a range of cytokines, dominated by dual TNF-α and IFN-γ expression, although substantial populations which express IL-4 were seen in some donors. Microarray analysis and phenotypic expression revealed a profile of unique features. These include the expression of CX3CR1, which would direct cells towards fractalkine on activated endothelium, and the β2-adrenergic receptor, which could permit rapid response to stress. CMV-specific CD4+ T cells display an intense cytotoxic profile with high level expression of granzyme B and perforin, a pattern which increases further during aging. In addition CMV-specific CD4+ T cells demonstrate strong cytotoxic activity against antigen-loaded target cells when isolated directly ex vivo. PD-1 expression is present on 47% of cells but both the intensity and distribution of the inhibitory receptor is reduced in older people. These findings reveal the marked accumulation and unique phenotype of CMV-specific CD4+ T cells and indicate how such T cells may contribute to the vascular complications associated with CMV in older people. PMID:27606804

  9. Impact of HLA-B alleles, epitope binding affinity, functional avidity, and viral coinfection on the immunodominance of virus-specific CTL responses.

    PubMed

    Bihl, Florian; Frahm, Nicole; Di Giammarino, Loriana; Sidney, John; John, Mina; Yusim, Karina; Woodberry, Tonia; Sango, Kaori; Hewitt, Hannah S; Henry, Leah; Linde, Caitlyn H; Chisholm, John V; Zaman, Tauheed M; Pae, Eunice; Mallal, Simon; Walker, Bruce D; Sette, Alessandro; Korber, Bette T; Heckerman, David; Brander, Christian

    2006-04-01

    Immunodominance is variably used to describe either the most frequently detectable response among tested individuals or the strongest response within a single individual, yet factors determining either inter- or intraindividual immunodominance are still poorly understood. More than 90 individuals were tested against 184 HIV- and 92 EBV-derived, previously defined CTL epitopes. The data show that HLA-B-restricted epitopes were significantly more frequently recognized than HLA-A- or HLA-C-restricted epitopes. HLA-B-restricted epitopes also induced responses of higher magnitude than did either HLA-A- or HLA-C-restricted epitopes, although this comparison only reached statistical significance for EBV epitopes. For both viruses, the magnitude and frequency of recognition were correlated with each other, but not with the epitope binding affinity to the restricting HLA allele. The presence or absence of HIV coinfection did not impact EBV epitope immunodominance patterns significantly. Peptide titration studies showed that the magnitude of responses was associated with high functional avidity, requiring low concentration of cognate peptide to respond in in vitro assays. The data support the important role of HLA-B alleles in antiviral immunity and afford a better understanding of the factors contributing to inter- and intraindividual immunodominance.

  10. Functionality of Dengue Virus Specific Memory T Cell Responses in Individuals Who Were Hospitalized or Who Had Mild or Subclinical Dengue Infection

    PubMed Central

    Jeewandara, Chandima; Adikari, Thiruni N.; Gomes, Laksiri; Fernando, Samitha; Fernando, R. H.; Perera, M. K. T.; Ariyaratne, Dinuka; Kamaladasa, Achala; Salimi, Maryam; Prathapan, Shamini

    2015-01-01

    Background Although antibody responses to dengue virus (DENV) in naturally infected individuals have been extensively studied, the functionality of DENV specific memory T cell responses in relation to clinical disease severity is incompletely understood. Methodology/Principal findings Using ex vivo IFNγ ELISpot assays, and by determining cytokines produced in ELISpot supernatants, we investigated the functionality of DENV-specific memory T cell responses in a large cohort of individuals from Sri Lanka (n=338), who were naturally infected and were either hospitalized due to dengue or had mild or sub clinical dengue infection. We found that T cells of individuals with both past mild or sub clinical dengue infection and who were hospitalized produced multiple cytokines when stimulated with DENV-NS3 peptides. However, while DENV-NS3 specific T cells of those with mild/sub clinical dengue infection were more likely to produce only granzyme B (p=0.02), those who were hospitalized were more likely to produce both TNFα and IFNγ (p=0.03) or TNFα alone. We have also investigated the usefulness of a novel T cell based assay, which can be used to determine the past infecting DENV serotype. 92.4% of DENV seropositive individuals responded to at least one DENV serotype of this assay and none of the seronegatives responded. Individuals who were seronegative, but had received the Japanese encephalitis vaccine too made no responses, suggesting that the peptides used in this assay did not cross react with the Japanese encephalitis virus. Conclusions/significance The types of cytokines produced by DENV-specific memory T cells appear to influence the outcome of clinical disease severity. The novel T cell based assay, is likely to be useful in determining the past infecting DENV serotype in immune-epidemiological studies and also in dengue vaccine trials. PMID:25875020

  11. CD8 sup + T lymphocytes of patients with AIDS maintain normal broad cytolytic function despite the loss of human immunodeficiency virus-specific cytotoxicity

    SciTech Connect

    Pantaleo, G.; De Maria, A.; Koenig, S.; Butini, L.; Moss, B.; Lane, H.C.; Fauci, A.S. ); Baseler, M. )

    1990-06-01

    In this study, the authors have investigated the potential mechanisms responsible for the loss of human immunodeficiency virus type 1 (HIV-1)-specific cytolytic activity in the advanced stages of HIV-1 infection. They have demonstrated that HIV-1-specific cytotoxic T lymphocytes are predominantly contained within the CD8{sup +}DR{sup +} subset. Furthermore, they have shown by a redirected killing assay that there is a dichotomy between HIV-1-specific cytolytic activity and broad cytolytic potential since the cytolytic machinery of CD8{sup +}DR{sup +} cells is still functioning even in patients with AIDS who have lost their HIV-1-specific cytolytic activity. In addition, by comparative analysis of these two types of cytolytic activity over time they have demonstrated a progressive loss of HIV-1-specific cytolytic activity in the advanced stages of the disease, whereas the cytolytic potential remained unchanged regardless of the clinical stage. On the basis of these results, they propose that the loss of HIV-1-specific cytolytic activity in HIV-1-infected individuals may result at least in part from a progressive decrease in the pool of HIV-1-specific cytotoxic T lymphocytes belonging to the CD8{sup +}DR{sup +} subset whose ability to expand has been impaired.

  12. Production of genetically modified Epstein-Barr virus-specific cytotoxic T cells for adoptive transfer to patients at high risk of EBV-associated lymphoproliferative disease.

    PubMed

    Smith, C A; Ng, C Y; Heslop, H E; Holladay, M S; Richardson, S; Turner, E V; Loftin, S K; Li, C; Brenner, M K; Rooney, C M

    1995-04-01

    EBV-induced lymphoproliferative disease (EBV-LPD) is a disorder most commonly associated with the immunocompromise that follows allogeneic organ transplantation. In patients receiving T cell-depleted bone marrow from HLA-mismatched or HLA-matched unrelated donors, the incidence of EBV-LPD is particularly high, ranging from 5 to 30%. Administration of EBV-specific cytotoxic T lymphocytes may be one means of preventing and treating this disease. We now describe a method that allows the routine and timely preparation of large numbers of such cells to allow their safe administration to bone marrow transplant recipients. We also describe how these cells may be genetically marked before infusion, to determine their fate and disposition in vivo.

  13. Virus-Specific Messenger RNA and Nascent Polypeptides in Polyribosomes of Cells Replicating Murine Sarcoma-Leukemia Viruses

    PubMed Central

    Vecchio, G.; Tsuchida, N.; Shanmugam, G.; Green, M.

    1973-01-01

    We present evidence that virus-specific RNA is present in polyribosomes of transformed cells replicating the murine sarcoma-leukemia virus complex and that it serves as messenger RNA for the synthesis of viral-coded proteins. Both virus-specific RNA (detected by hybridization with the [3H]DNA product of the viral RNA-directed DNA polymerase) and nascent viral polypeptides (measured by precipitation with antiserum to purified virus) were found in membrane-bound and free polyribosomes. Membrane-bound polyribosomes contained a higher content of both virus-specific RNA and nascent viral polypeptides. From 60 to 70% of viral RNA sequences were released from polyribosomes with EDTA, consistent with a function as messenger RNA. Maximum amounts of both virus-specific RNA and nascent viral polypeptides were found in the polyribosome region sedimenting at about 350 S. PMID:4352969

  14. Variola Virus-Specific Diagnostic Assays: Characterization, Sensitivity, and Specificity

    PubMed Central

    Kondas, Ashley V.; Olson, Victoria A.; Li, Yu; Abel, Jason; Laker, Miriam; Rose, Laura; Wilkins, Kimberly; Turner, Jonathan; Kline, Richard

    2015-01-01

    A public health response relies upon rapid and reliable confirmation of disease by diagnostic assays. Here, we detail the design and validation of two variola virus-specific real-time PCR assays, since previous assays cross-reacted with newly identified cowpox viruses. The assay specificity must continually be reassessed as other closely related viruses are identified. PMID:25673790

  15. Variola virus-specific diagnostic assays: characterization, sensitivity, and specificity.

    PubMed

    Kondas, Ashley V; Olson, Victoria A; Li, Yu; Abel, Jason; Laker, Miriam; Rose, Laura; Wilkins, Kimberly; Turner, Jonathan; Kline, Richard; Damon, Inger K

    2015-04-01

    A public health response relies upon rapid and reliable confirmation of disease by diagnostic assays. Here, we detail the design and validation of two variola virus-specific real-time PCR assays, since previous assays cross-reacted with newly identified cowpox viruses. The assay specificity must continually be reassessed as other closely related viruses are identified.

  16. Influenza Virus-Specific Neutralizing IgM Antibodies Persist for a Lifetime

    PubMed Central

    Skountzou, Ioanna; Satyabhama, Lakshmipriyadarshini; Stavropoulou, Anastasia; Ashraf, Zuhha; Esser, E. Stein; Vassilieva, Elena; Koutsonanos, Dimitrios; Compans, Richard

    2014-01-01

    Detection of immunoglobulin M (IgM) antibodies has long been used as an important diagnostic tool for identifying active viral infections, but their relevance in later stages has not been clearly defined in vivo. In this study, we followed the kinetics, longevity, and function of influenza virus-specific IgM antibodies for 2 years following sublethal infection of mice with live mouse-adapted A/PR/8/34 virus or immunization with formalin-inactivated virus. These groups mounted robust protective immune responses and survived lethal challenges with 50× 50% lethal dose (LD50) mouse-adapted A/PR/8/34 virus 600 days after the primary exposure. Surprisingly, the virus-specific IgM antibodies persisted along with IgG antibodies, and we found a significantly higher number of IgM-positive (IgM+) virus-specific plasma cells than IgG+ plasma cells that persisted for at least 9 months postexposure. The IgM antibodies were functional as they neutralized influenza virus in the presence of complement just as well as IgG antibodies did. PMID:25165027

  17. Peptide Map Comparison of Infectious Pancreatic Necrosis Virus-Specific Polypeptides

    PubMed Central

    Dobos, Peter; Rowe, David

    1977-01-01

    An investigation of virus-specific protein synthesis in infectious pancreatic necrosis virus (IPNV)-infected rainbow trout gonad cells was undertaken to find a relationship between the coding capacity of the virus genome (two segments of double-stranded RNA of 2.5 × 106 and 2.3 × 106 molecular weight) and the sizes and relative amounts of virus-specific proteins. Using polyacrylamide slabgel electrophoresis and autoradiography, eight distinct virus-specific polypeptides were detected in infected, [35S]methionine-labeled cells. These proteins may be grouped into three size classes on the basis of molecular weight: (i) large, α (90,000); (ii) medium, β1 (59,000), β2 (58,000), and β3 (57,000); and (iii) small, γ1 (29,000), γ1A (28,000), γ2 (27,000), and γ3 (25,000). The combined molecular weight of these polypetides (373,000) is beyond the coding capacity of the virus genome. Purified IPNV contained polypeptides α, β3, γ1, and γ1A. Pulse-chase experiments and tryptic peptide map comparisons revealed that only four of the eight intracellular proteins were primary gene products, namely, α, β1, γ1, and β2, with a combined molecular weight of 205,000. Of these primary gene products only the α polypeptide was found to be stable, whereas the other three underwent intracellular proteolytic cleavage during virus morphogenesis. Polypeptide β1 was cleaved to generate β2 and β3; γ1 was trimmed to produce γ1A, and the only nonstructural primary gene product, γ2, was found to be a precursor of γ3. These results suggest that IPNV possesses a unique mechanism to synthesize three size classes of proteins using mRNA transcripts from two high-molecular-weight double-stranded RNA genome segments. Images PMID:563479

  18. Longitudinal analysis of feline leukemia virus-specific cytotoxic T lymphocytes: correlation with recovery from infection.

    PubMed

    Flynn, J Norman; Dunham, Stephen P; Watson, Vivien; Jarrett, Oswald

    2002-03-01

    Feline leukemia virus (FeLV) is a common naturally occurring gammaretrovirus of domestic cats that is associated with degenerative diseases of the hematopoietic system, immunodeficiency, and neoplasia. Although the majority of cats exposed to FeLV develop a transient infection and recover, a proportion of cats become persistently viremic and many subsequently develop fatal diseases. To define the dominant host immune effector mechanisms responsible for the outcome of infection, we studied the longitudinal changes in FeLV-specific cytotoxic T lymphocytes (CTLs) in a group of naïve cats following oronasal exposure to FeLV. Using (51)Cr release assays to measure ex vivo virus-specific cytotoxicity, the emerging virus-specific CTL response was correlated with modulations in viral burden as assessed by detection of infectious virus, FeLV p27 capsid antigen, and proviral DNA in the blood. High levels of circulating FeLV-specific effector CTLs appeared before virus neutralizing antibodies in cats that recovered from exposure to FeLV. In contrast, persistent viremia was associated with a silencing of virus-specific humoral and cell-mediated host immune effector mechanisms. A single transfer of between 2 x 10(7) and 1 x 10(8) autologous, antigen-activated lymphoblasts was associated with a downmodulation in viral burden in vivo. The results suggest an important role for FeLV-specific CTLs in retroviral immunity and demonstrate the potential to modulate disease outcome by the adoptive transfer of antigen-specific T cells in vivo.

  19. Two small virus-specific polypeptides are produced during infection with Sindbis virus.

    PubMed Central

    Welch, W J; Sefton, B M

    1979-01-01

    We have identified and characterized two small virus-specific polypeptides which are produced during infection of cells with Sindbis virus, but which are not incorporated into the mature virion. The larger of these is a glycoprotein with an approximate molecular weight of 9,800 and is found predominantly in the medium of infected cells. Three independent lines of evidence demonstrate conclusively that this 9,800-dalton glycoprotein is produced during the proteolytic conversion of the precursor polypeptide, PE2, to the virion glycoprotein E2. This small glycoprotein is therefore analogous to the virion glycoprotein E3 of the very closely related alphavirus, Semliki Forest virus. The 9,800-dalton glycoprotein of Sindbis virus, unlike the E3 glycoprotein of Semliki Forest virus, is not, however, present in the viral particle. The other virus-specific polypeptide is 4,200 daltons in size, does not appear to be a glycoprotein, and is neither incorporated into the mature virus nor released into the culture medium. The gene for this small polypeptide is present in the viral 26S mRNA (the mRNA which encodes all the viral structural polypeptides) and appears to be located in the portion of the mRNA which encodes the two viral glycoproteins. The possibility that this 4,200-dalton polypeptide functions as a signal peptide during the synthesis of the viral membrane glycoproteins is discussed. Images PMID:448798

  20. Rapid and massive virus-specific plasmablast responses during acute dengue virus infection in humans.

    PubMed

    Wrammert, Jens; Onlamoon, Nattawat; Akondy, Rama S; Perng, Guey C; Polsrila, Korakot; Chandele, Anmol; Kwissa, Marcin; Pulendran, Bali; Wilson, Patrick C; Wittawatmongkol, Orasri; Yoksan, Sutee; Angkasekwinai, Nasikarn; Pattanapanyasat, Kovit; Chokephaibulkit, Kulkanya; Ahmed, Rafi

    2012-03-01

    Humoral immune responses are thought to play a major role in dengue virus-induced immunopathology; however, little is known about the plasmablasts producing these antibodies during an ongoing infection. Herein we present an analysis of plasmablast responses in patients with acute dengue virus infection. We found very potent plasmablast responses that often increased more than 1,000-fold over the baseline levels in healthy volunteers. In many patients, these responses made up as much 30% of the peripheral lymphocyte population. These responses were largely dengue virus specific and almost entirely made up of IgG-secreting cells, and plasmablasts reached very high numbers at a time after fever onset that generally coincided with the window where the most serious dengue virus-induced pathology is observed. The presence of these large, rapid, and virus-specific plasmablast responses raises the question as to whether these cells might have a role in dengue immunopathology during the ongoing infection. These findings clearly illustrate the need for a detailed understanding of the repertoire and specificity of the antibodies that these plasmablasts produce.

  1. Detection of Bovine viral diarrhea virus-specific neutralizing antibodies in fresh colostrum: a modification of the virus neutralization test.

    PubMed

    Bedekovic, Tomislav; Mihaljevic, Zeljko; Jungic, Andreja; Lemo, Nina; Lojkic, Ivana; Cvetnic, Zeljko; Cac, Zeljko

    2013-03-01

    To eliminate cytotoxic effects of colostrum on cells, a modified virus neutralization test (VNT) for the detection of Bovine viral diarrhea virus-specific neutralizing antibodies in colostrum was developed. The new test was compared to the World Organization for Animal Health-recommended VNT and the results evaluated. The agreement of the new test compared to the standard VNT was determined to be 98%, whereas sensitivity and specificity of the modified VNT compared to the standard VNT were 100%. Bovine viral diarrhea virus-specific antibodies were detected in 42 sera samples and 38 colostrum samples. The antibody titers in serum and colostrum showed a high correlation (n = 56, r = 0.9719, P < 0.001). The modified virus neutralization technique described herein succeeds in eliminating cytotoxic effects and can be readily applied for the detection of specific antibodies against other infectious agents in colostrum. PMID:23417081

  2. Cell-based antiviral screening against coronaviruses: Developing virus-specific and broad-spectrum inhibitors

    PubMed Central

    Kilianski, Andy; Baker, Susan C.

    2014-01-01

    To combat the public health threat from emerging coronaviruses (CoV), the development of antiviral therapies with either virus-specific or pan-CoV activities is necessary. An important step in antiviral drug development is the screening of potential inhibitors in cell-based systems. The recent emergence of the Middle East respiratory syndrome (MERS)-CoV necessitates adapting methods that have been used to identify antivirals against the severe, acute respiratory syndrome (SARS)-CoV and developing new approaches to more efficiently screen antiviral drugs. In this article we review cell-based assays using infectious virus (BSL-3) and surrogate assays (BSL-2) that can be implemented to accelerate antiviral development against MERS-CoV and future emergent coronaviruses. This paper forms part of a series of invited articles in Antiviral Research on “From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.” PMID:24269477

  3. CD123 redirected multiple virus-specific T cells for acute myeloid leukemia.

    PubMed

    Zhou, Li; Liu, Xin; Wang, Xingbing; Sun, Zimin; Song, Xiao-Tong

    2016-02-01

    Hematopoietic stem cell transplantation (HSCT) has been increasingly used as a curative treatment for acute myeloid leukemia (AML). However, relapse rates after HSCT in complete remission (CR) are reported between 30% and 70%. In addition, numerous studies suggested that secondary viral infection from a variety of viruses including Epstein-Barr virus (EBV), adenovirus (Adv), and cytomegalovirus (CMV) are among the most common causes of death post-HSCT. Currently, chimeric antigen receptor (CAR)-based T cells have been developed to treat AML in clinical studies, while virus-specific cytotoxic T cells (VST) have been proven to be able to effectively prevent or treat viral infection after HSCT. Thus it would be desirable to develop T cells with the ability of simultaneously targeting AML relapse and viral infection. In this article, we now describe the generation of VST cells that are engineered to express CAR for a specific AML cell-surface antigen CD123 (CD123-CAR-VST). Using Dendritic cells (DCs) pulsed with EBV, Adv, and CMV peptides as sources of viral antigens, we generated VST from A2 donor peripheral mononuclear cells (PBMC). VST were then transduced with retroviral vector encoding CD123-CAR to generate CD123-CAR-VST. We demonstrated that CD123-CAR-VST recognized EBV, Adv, and CMV epitopes and had HLA-restricted virus-specific cytotoxic effector function against EBV target. In addition, CD123-CAR-VST retained the specificity against CD123-positive AML cell lines such as MOLM13 and THP-1 in vitro. Thus our results suggested that CD123-CAR-VST might be a valuable candidate to simultaneously prevent or treat relapse and viral infection in AML HSCT recipients. PMID:26740053

  4. A Good Manufacturing Practice procedure to engineer donor virus-specific T cells into potent anti-leukemic effector cells

    PubMed Central

    van Loenen, Marleen M.; de Boer, Renate; van Liempt, Ellis; Meij, Pauline; Jedema, Inge; Falkenburg, J.H. Frederik; Heemskerk, Mirjam H.M.

    2014-01-01

    A sequential, two-step procedure in which T-cell-depleted allogeneic stem cell transplantation is followed by treatment with donor lymphocyte infusion at 6 months can significantly reduce the risk and severity of graft-versus-host disease, with postponed induction of the beneficial graft-versus-leukemia effect. However, patients with high-risk leukemia have a substantial risk of relapse early after transplantation, at a time when administration of donor lymphocytes has a high likelihood of resulting in graft-versus-host disease, disturbing a favorable balance between the graft-versus-leukemia effect and graft-versus-host disease. New therapeutic modalities are, therefore, required to allow early administration of T cells capable of exerting a graft-versus-leukemia effect without causing graft-versus-host disease. Here we describe the isolation of virus-specific T cells using Streptamer-based isolation technology and subsequent transfer of the minor histocompatibility antigen HA-1-specific T-cell receptor using retroviral vectors. Isolation of virus-specific T cells and subsequent transduction with HA-1-T-cell receptor resulted in rapid in vitro generation of highly pure, dual-specific T cells with potent anti-leukemic reactivity. Due to the short production procedure of only 10–14 days and the defined specificity of the T cells, administration of virus-specific T cells transduced with the HA-1-T-cell receptor as early as 8 weeks after allogeneic stem cell transplantation is feasible. (This clinical trial is registered at www.clinicaltrialsregister.eu as EudraCT number 2010-024625-20). PMID:24334296

  5. A Good Manufacturing Practice procedure to engineer donor virus-specific T cells into potent anti-leukemic effector cells.

    PubMed

    van Loenen, Marleen M; de Boer, Renate; van Liempt, Ellis; Meij, Pauline; Jedema, Inge; Falkenburg, J H Frederik; Heemskerk, Mirjam H M

    2014-04-01

    A sequential, two-step procedure in which T-cell-depleted allogeneic stem cell transplantation is followed by treatment with donor lymphocyte infusion at 6 months can significantly reduce the risk and severity of graft-versus-host disease, with postponed induction of the beneficial graft-versus-leukemia effect. However, patients with high-risk leukemia have a substantial risk of relapse early after transplantation, at a time when administration of donor lymphocytes has a high likelihood of resulting in graft-versus-host disease, disturbing a favorable balance between the graft-versus-leukemia effect and graft-versus-host disease. New therapeutic modalities are, therefore, required to allow early administration of T cells capable of exerting a graft-versus-leukemia effect without causing graft-versus-host disease. Here we describe the isolation of virus-specific T cells using Streptamer-based isolation technology and subsequent transfer of the minor histocompatibility antigen HA-1-specific T-cell receptor using retroviral vectors. Isolation of virus-specific T cells and subsequent transduction with HA-1-T-cell receptor resulted in rapid in vitro generation of highly pure, dual-specific T cells with potent anti-leukemic reactivity. Due to the short production procedure of only 10-14 days and the defined specificity of the T cells, administration of virus-specific T cells transduced with the HA-1-T-cell receptor as early as 8 weeks after allogeneic stem cell transplantation is feasible. (This clinical trial is registered at www.clinicaltrialsregister.eu as EudraCT number 2010-024625-20).

  6. Reduction of otherwise remarkably stable virus-specific cytotoxic T lymphocyte memory by heterologous viral infections

    PubMed Central

    1996-01-01

    Experimental analyses of the acute cytotoxic T lymphocyte (CTL) response to viruses have focused on studying these infections in immunologically naive hosts. In the natural environment, however, viral CTL responses occur in hosts that are already immune to other infectious agents. To address which factors contribute to the maintenance and waning of immunological memory, the following study examined the frequencies of virus-specific CTL precursor cells (pCTL) not only using the usual experimental paradigm where mice undergo acute infections with a single virus, and in mice immune to a single virus, but also in immune mice after challenge with various heterologous viruses. As determined by limiting dilution assays, the pCTL frequency (p/f) per CD8+ T cell specific for lymphocytic choriomeningitis virus (LCMV), Pichinde virus (PV), or vaccinia virus (VV) increased during the acute infections, peaking at days 7-8 with frequencies as high as 1/27-1/74. Acute viral infections such as these elicit major expansions in the CD8+ T cell number, which has been reported to undergo apoptosis and decline after most of the viral antigen has been cleared. Although the decline in the total number of virus-specific pCTL after their peak in the acute infection was substantial, for all three viruses the virus- specific p/f per CD8+ T cell decreased only two- to fourfold and remained at these high levels with little fluctuation for well over a year. The ratios of the three immunodominant peptide-specific to total LCMV-specific clones remained unchanged between days 7 and 8 of acute infection and long-term memory, suggesting that the apoptotic events did not discriminate on the basis of T cell receptor specificity, but instead nonspecifically eliminated a large proportion of the activated T cells. However, when one to five heterologous viruses (LCMV, PV, VV, murine cytomegalovirus, and vesicular stomatitis virus) were sequentially introduced into this otherwise stable memory pool, the

  7. Monoclonal antibody against IFN-gamma inhibits Moloney murine sarcoma virus-specific cytotoxic T lymphocyte differentiation

    SciTech Connect

    Zanovello, P.; Vallerani, E.; Biasi, G.; Landolfo, S.; Collavo, D.

    1988-02-15

    The role of autochthonous IFN- production was evaluated in immune reactions to Moloney murine sarcoma virus (M-MSV)-induced tumors which are characterized by spontaneous regression mainly caused by virus-specific CTL activity. A functional IFN- depletion, induced by repeated administration of mAb anti-IFN- at the site of virus inoculation, prevented tumor regression in M-MSV-injected mice. Moreover, this antibody inhibited in vitro both proliferation and differentiation of M-MSV-specific T lymphocytes obtained in bulk cultures, but not growth and lytic activity of the already differentiated virus-specific CTL clone CHM-14 stimulated with rIL-2 and relevant tumor Ag. In addition, in mice receiving mAb treatment the frequency of M-MSV-specific CTL precursors, evaluated by means of limiting dilution analysis, was strongly reduced in comparison with that of control mice injected only with virus. Because CTL secrete IFN- following antigenic stimulation, the possibility that non-T effector cells recruited by this lymphokine might mediate tumor regression was also considered. Adoptive immunotherapy experiments, performed in T cell-deficient (Tx + BM) and in sublethally irradiated mice, demonstrated that transfer of CHM-14 CTL clone, which secretes IFN-, was able to counteract M-MSV tumor growth despite the local mAb anti-IFN- treatment which may have prevented host cell recruitment. Moreover, repeated local rIFN- inoculations in Tx + BM mice did not counteract M-MSV tumor progression, thus confirming that other IFN- properties such as non-T cell recruitment, antiviral or anti-proliferative IFN- activities have little or no relevance when M-MSV-specific CTL are lacking. On the whole, these results indicate that in M-MSV-injected mice, tumor enhancement after mAb anti-IFN- treatment is principally caused by impaired differentiation of virus-specific CTL precursors.

  8. Manufacture of tumor- and virus-specific T lymphocytes for adoptive cell therapies

    PubMed Central

    Wang, X; Rivière, I

    2015-01-01

    Adoptive transfer of tumor-infiltrating lymphocytes (TILs) and genetically engineered T lymphocytes expressing chimeric antigen receptors (CARs) or conventional alpha/beta T-cell receptors (TCRs), collectively termed adoptive cell therapy (ACT), is an emerging novel strategy to treat cancer patients. Application of ACT has been constrained by the ability to isolate and expand functional tumor-reactive T cells. The transition of ACT from a promising experimental regimen to an established standard of care treatment relies largely on the establishment of safe, efficient, robust and cost-effective cell manufacturing protocols. The manufacture of cellular products under current good manufacturing practices (cGMPs) has a critical role in the process. Herein, we review current manufacturing methods for the large-scale production of clinical-grade TILs, virus-specific and genetically modified CAR or TCR transduced T cells in the context of phase I/II clinical trials as well as the regulatory pathway to get these complex personalized cellular products to the clinic. PMID:25721207

  9. Mutant HLA-A2 antigens as restricting elements for virus-specific cytotoxic T cells.

    PubMed

    Gaston, J S; Wallace, L E; Rickinson, A B; Epstein, M A; Pious, D

    1984-01-01

    Mutants of the EB virus-transformed cell line T5-1 (HLA-A1, 2; B8, 27), bearing well-characterized alterations in HLA-A2 antigen expression and unable to bind the HLA-A2-specific monoclonal antibody BB7.2, have been tested for their susceptibility to EB virus-specific cytolysis using effector T-cell preparations functionally restricted through relevant HLA antigens. Initial experiments first confirmed that the parent line T5-1 was susceptible to cytolysis by both "common" A2-restricted and B27-restricted effector cells. While those T5-1 mutants with little or no surface A2 expression were not lysed by A2-restricted effectors, those targets with quantitatively normal expression of mutant A2 molecules were as susceptible to A2-restricted lysis as the parent line itself. In contrast, all the T5-1 mutant lines were susceptible to B27-restricted cytolysis. The results demonstrate that experimentally induced mutations of HLA-A2 antigen structure, affecting a serologically defined site on the molecule, can occur without altering that same molecule's expression of the T cell-restricting determinant(s). Such experimentally induced mutations are quite different from the naturally occurring "variant" A2 antigens which are present within the serologically defined A2 antigen group and which show changes at the T cell-restricting site. PMID:6329950

  10. Manufacture of tumor- and virus-specific T lymphocytes for adoptive cell therapies.

    PubMed

    Wang, X; Rivière, I

    2015-03-01

    Adoptive transfer of tumor-infiltrating lymphocytes (TILs) and genetically engineered T lymphocytes expressing chimeric antigen receptors (CARs) or conventional alpha/beta T-cell receptors (TCRs), collectively termed adoptive cell therapy (ACT), is an emerging novel strategy to treat cancer patients. Application of ACT has been constrained by the ability to isolate and expand functional tumor-reactive T cells. The transition of ACT from a promising experimental regimen to an established standard of care treatment relies largely on the establishment of safe, efficient, robust and cost-effective cell manufacturing protocols. The manufacture of cellular products under current good manufacturing practices (cGMPs) has a critical role in the process. Herein, we review current manufacturing methods for the large-scale production of clinical-grade TILs, virus-specific and genetically modified CAR or TCR transduced T cells in the context of phase I/II clinical trials as well as the regulatory pathway to get these complex personalized cellular products to the clinic. PMID:25721207

  11. PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection

    PubMed Central

    Petrovas, Constantinos; Casazza, Joseph P.; Brenchley, Jason M.; Price, David A.; Gostick, Emma; Adams, William C.; Precopio, Melissa L.; Schacker, Timothy; Roederer, Mario; Douek, Daniel C.; Koup, Richard A.

    2006-01-01

    Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8+ T cells and the effect of manipulating signaling through PD-1 on the survival, proliferation, and cytokine function of these cells. PD-1 expression was found to be low on naive CD8+ T cells and increased on memory CD8+ T cells according to antigen specificity. Memory CD8+ T cells specific for poorly controlled chronic persistent virus (HIV) more frequently expressed PD-1 than memory CD8+ T cells specific for well-controlled persistent virus (cytomegalovirus) or acute (vaccinia) viruses. PD-1 expression was independent of maturational markers on memory CD8+ T cells and was not directly associated with an inability to produce cytokines. Importantly, the level of PD-1 surface expression was the primary determinant of apoptosis sensitivity of virus-specific CD8+ T cells. Manipulation of PD-1 led to changes in the ability of the cells to survive and expand, which, over several days, affected the number of cells expressing cytokines. Therefore, PD-1 is a major regulator of apoptosis that can impact the frequency of antiviral T cells in chronic infections such as HIV, and could be manipulated to improve HIV-specific CD8+ T cell numbers, but possibly not all functions in vivo. PMID:16954372

  12. Genetic polymorphisms associated with rubella virus-specific cellular immunity following MMR vaccination.

    PubMed

    Kennedy, Richard B; Ovsyannikova, Inna G; Haralambieva, Iana H; Lambert, Nathaniel D; Pankratz, V Shane; Poland, Gregory A

    2014-11-01

    Rubella virus causes a relatively benign disease in most cases, although infection during pregnancy can result in serious birth defects. An effective vaccine has been available since the early 1970s and outbreaks typically do not occur among highly vaccinated (≥2 doses) populations. Nevertheless, considerable inter-individual variation in immune response to rubella immunization does exist, with single-dose seroconversion rates ~95 %. Understanding the mechanisms behind this variability may provide important insights into rubella immunity. In the current study, we examined associations between single nucleotide polymorphisms (SNPs) in selected cytokine, cytokine receptor, and innate/antiviral genes and immune responses following rubella vaccination in order to understand genetic influences on vaccine response. Our approach consisted of a discovery cohort of 887 subjects aged 11-22 at the time of enrollment and a replication cohort of 542 older adolescents and young adults (age 18-40). Our data indicate that SNPs near the butyrophilin genes (BTN3A3/BTN2A1) and cytokine receptors (IL10RB/IFNAR1) are associated with variations in IFNγ secretion and that multiple SNPs in the PVR gene, as well as SNPs located in the ADAR gene, exhibit significant associations with rubella virus-specific IL-6 secretion. This information may be useful, not only in furthering our understanding immune responses to rubella vaccine, but also in identifying key pathways for targeted adjuvant use to boost immunity in those with weak or absent immunity following vaccination.

  13. Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma.

    PubMed

    Pule, Martin A; Savoldo, Barbara; Myers, G Doug; Rossig, Claudia; Russell, Heidi V; Dotti, Gianpietro; Huls, M Helen; Liu, Enli; Gee, Adrian P; Mei, Zhuyong; Yvon, Eric; Weiss, Heidi L; Liu, Hao; Rooney, Cliona M; Heslop, Helen E; Brenner, Malcolm K

    2008-11-01

    Cytotoxic T lymphocytes (CTLs) directed to nonviral tumor-associated antigens do not survive long term and have limited antitumor activity in vivo, in part because such tumor cells typically lack the appropriate costimulatory molecules. We therefore engineered Epstein-Barr virus (EBV)-specific CTLs to express a chimeric antigen receptor directed to the diasialoganglioside GD2, a nonviral tumor-associated antigen expressed by human neuroblastoma cells. We reasoned that these genetically engineered lymphocytes would receive optimal costimulation after engagement of their native receptors, enhancing survival and antitumor activity mediated through their chimeric receptors. Here we show in individuals with neuroblastoma that EBV-specific CTLs expressing a chimeric GD2-specific receptor indeed survive longer than T cells activated by the CD3-specific antibody OKT3 and expressing the same chimeric receptor but lacking virus specificity. Infusion of these genetically modified cells seemed safe and was associated with tumor regression or necrosis in half of the subjects tested. Hence, virus-specific CTLs can be modified to function as tumor-directed effector cells.

  14. Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma

    PubMed Central

    Pule, Martin A; Savoldo, Barbara; Myers, G Doug; Rossig, Claudia; Russell, Heidi V; Dotti, Gianpietro; Huls, M Helen; Liu, Enli; Gee, Adrian P; Mei, Zhuyong; Yvon, Eric; Weiss, Heidi L; Liu, Hao; Rooney, Cliona M; Heslop, Helen E; Brenner, Malcolm K

    2009-01-01

    Cytotoxic T lymphocytes (CTLs) directed to nonviral tumor–associated antigens do not survive long term and have limited antitumor activity in vivo, in part because such tumor cells typically lack the appropriate costimulatory molecules. We therefore engineered Epstein-Barr virus (EBV)-specific CTLs to express a chimeric antigen receptor directed to the diasialoganglioside GD2, a nonviral tumor–associated antigen expressed by human neuroblastoma cells. We reasoned that these genetically engineered lymphocytes would receive optimal costimulation after engagement of their native receptors, enhancing survival and antitumor activity mediated through their chimeric receptors. Here we show in individuals with neuroblastoma that EBV-specific CTLs expressing a chimeric GD2-specific receptor indeed survive longer than T cells activated by the CD3-specific antibody OKT3 and expressing the same chimeric receptor but lacking virus specificity. Infusion of these genetically modified cells seemed safe and was associated with tumor regression or necrosis in half of the subjects tested. Hence, virus-specific CTLs can be modified to function as tumor-directed effector cells. PMID:18978797

  15. Expression of the Human Cytomegalovirus UL11 Glycoprotein in Viral Infection and Evaluation of Its Effect on Virus-Specific CD8 T Cells

    PubMed Central

    Gabaev, Ildar; Elbasani, Endrit; Ameres, Stefanie; Steinbrück, Lars; Stanton, Richard; Döring, Marius; Lenac Rovis, Tihana; Kalinke, Ulrich; Jonjic, Stipan; Moosmann, Andreas

    2014-01-01

    ABSTRACT The human cytomegalovirus (CMV) UL11 open reading frame (ORF) encodes a putative type I transmembrane glycoprotein which displays remarkable amino acid sequence variability among different CMV isolates, suggesting that it represents an important virulence factor. In a previous study, we have shown that UL11 can interact with the cellular receptor tyrosine phosphatase CD45, which has a central role for signal transduction in T cells, and treatment of T cells with large amounts of a soluble UL11 protein inhibited their proliferation. In order to analyze UL11 expression in CMV-infected cells, we constructed CMV recombinants whose genomes either encode tagged UL11 versions or carry a stop mutation in the UL11 ORF. Moreover, we examined whether UL11 affects the function of virus-specific cytotoxic T lymphocytes (CTLs). We found that the UL11 ORF gives rise to several proteins due to both posttranslational modification and alternative translation initiation sites. Biotin labeling of surface proteins on infected cells indicated that only highly glycosylated UL11 forms are present at the plasma membrane, whereas less glycosylated UL11 forms were found in the endoplasmic reticulum. We did not find evidence of UL11 cleavage or secretion of a soluble UL11 version. Cocultivation of CTLs recognizing different CMV epitopes with fibroblasts infected with a UL11 deletion mutant or the parental strain revealed that under the conditions applied UL11 did not influence the activation of CMV-specific CD8 T cells. For further studies, we propose to investigate the interaction of UL11 with CD45 and the functional consequences in other immune cells expressing CD45. IMPORTANCE Human cytomegalovirus (CMV) belongs to those viruses that extensively interfere with the host immune response, yet the precise function of many putative immunomodulatory CMV proteins remains elusive. Previously, we have shown that the CMV UL11 protein interacts with the leukocyte common antigen CD45, a

  16. Virus-specific RNA synthesis in interferon-treated mouse cells productively infected with Moloney murine leukemia virus.

    PubMed Central

    Fan, H; MacIsaac, P

    1978-01-01

    Mouse cells productively infected with Moloney murine leukemia virus were treated with interferon, and intracellular virus-specific RNA was studied by hybridization with complementary DNA. The steady-state concentration of virus-specific RNA in interferon-treated cells was somewhat greater than that in untreated cells, and the rates of virus-specific RNA synthesis were approximately equal in treated and untreated cells. PMID:691118

  17. Immune response to herpes simplex virus infections: virus-specific antibodies in sera from patients with recurrent facial infections.

    PubMed

    Zweerink, H J; Stanton, L W

    1981-02-01

    Radioimmunoprecipitation assays were used to identify antibodies against a number of herpes simplex virus type 1-specific antigens in serum samples from individuals with recurrent facial herpes virus infections and from seropositive individuals without recurrent infections. Individuals with recurrent infections contributed three sequential serum samples each: immediately after the appearance of lesions, 3 weeks later, and 3 months later. Antibodies against at least 18 viral polypeptides were present in all positive sera: these included antibodies against the major nucleocapsid polypeptide (approximate molecular weight, 150,000) and against two glycopolypeptides with molecular weights of 115,000 to 130,000. No significant differences were observed between the serum samples in regard to their virus-specific antibody composition. The high-molecular-weight glycopolypeptides were partially purified and used in quantitative titration experiments. All sera tested were equally reactive with this material. It was concluded that under the experimental conditions an individual's susceptibility to recurrent herpetic infections could not be correlated with quantitative or qualitative changes in the levels of virus-specific antibodies.

  18. Processing of virus-specific glycoproteins of varicella zoster virus

    SciTech Connect

    Namazue, J.; Campo-Vera, H.; Kitamura, K.; Okuno, T.; Yamanishi, K.

    1985-05-01

    Monoclonal antibodies to varicella zoster virus (VZV) glycoproteins were used to study the processing of three glycoproteins with molecular weights of 83K-94K (gp 2), 64K (gp 3), and 55K (gp 5). Immunoprecipitation experiments performed with VZV-infected cells, pulse labeled with (/sup 3/H)glucosamine in the presence of tunicamycin, suggest that O-linked oligosaccharide is present on the glycoprotein of gp 2. Use of the enzyme endo-beta-N-acetylglucosaminidase H revealed that the fully processed form of gp 3 had high-mannose type and that of gp 5 had only complex type of N-linked oligosaccharides. Experiments with monensin suggest that the precursor form (116K) of gp 3 is cleaved during the processing from Golgi apparatus to cell surface membrane. The extension of O-linked oligosaccharide chain and the complex type of N-linked oligosaccharide chains also occurs during this processing.

  19. Reassessing the detection of B-virus-specific serum antibodies.

    PubMed

    Katz, David; Shi, Wei; Wildes, Martin J; Krug, Peter W; Hilliard, Julia K

    2012-12-01

    B virus, a natural pathogen of macaques, can cause a fatal zoonotic disease in humans. Serologic screening of macaques by titration ELISA (tELISA, screening test) and by Western blot analysis (WBA, confirmatory test) is one of the principle measures to prevent human infection. Here we slightly modified these 2 tests and reevaluated their correlation. We developed a high-throughput tELISA and used it to screen 278 sera simultaneously against the homologous BV antigen and the heterologous antigens of Papiine herpesvirus 2 and Human herpesvirus 1. More sera (35.6%) were positive by the BV-ELISA than by the HVP2-ELISA (21.6%) or HSV1-ELISA (19.8%). The superiority of the homologous tELISA over the heterologous tELISA was prominent in low-titer sera. WBA confirmed only 21% of the tELISA-positive sera with low or intermediate antibody titers. These sera might have contained antibodies to conformational epitopes that could not be detected by WBA, in which denatured antigens are used, but that could be detected by tELISA, which detects both linear and conformational epitopes. WBA confirmed 82% of the tELISA high-titer sera. However, WBA defined the remaining 18% of sera, which were negative by tELISA, as nonnegative. This finding can be attributed to the difficulties encountered with the subjective interpretation of results by WBA. Together, the current results indicate the inadequacy of WBA as a confirmatory assay for sera with low antibody titers.

  20. Virus-specific antibodies in sera from patients with genital herpes simplex virus infection.

    PubMed Central

    Zweerink, H J; Corey, L

    1982-01-01

    Virus-specific antibodies against a number of herpes simplex virus type 2 antigens were determined by radioimmunoprecipitation assays in sequential serum samples obtained from 12 patients with initial genital herpes simplex virus infection. The progressive appearance of antibodies to virus-specific antigens was observed; antibodies against a 130,000-molecular-weight glycoprotein complex appeared first, followed by antibodies against the major nucleocapsid polypeptide and then antibodies against a number of other viral antigens, including a polypeptide with a molecular weight of 62,000. Patients who developed a wide variety of antibodies to viral polypeptides shortly after resolution of their initial episode seemed to experience more severe initial infections and more recurrences than did those who reacted poorly with these virus-specific antigens. This was most apparent with respect to antibodies to virus-specific polypeptides with molecular weights between 30,000 and 43,000. Antibody specificity did not change during the course of follow-up regardless of whether serum samples were taken shortly before, during, or after recurrent episodes. Glycoprotein-specific antibodies were quantitated with the purified 130,000-molecular-weight glycoprotein material. No significant fluctuations in these antibody titers were observed before or after recurrences of the disease. Images PMID:7118244

  1. Influenza Virus-Specific Immunological Memory Is Enhanced by Repeated Social Defeat

    PubMed Central

    Mays, Jacqueline W.; Bailey, Michael T.; Hunzeker, John T.; Powell, Nicole D.; Papenfuss, Tracey; Karlsson, Erik A; Padgett, David A.; Sheridan, John F.

    2011-01-01

    Immunological memory (MEM) development is affected by stress-induced neuroendocrine mediators. Current knowledge about how a behavioral interaction, such as social defeat, alters the development of adaptive immunity, and MEM is incomplete. In this study, the experience of social disruption stress (SDR) prior to a primary influenza viral infection enhanced the frequency and function of the T cell memory pool. Socially stressed mice had a significantly enlarged population of CD8+ T cells specific for the immunodominant NP366–74 epitope of A/PR/8/34 virus in lung and spleen tissues at 6–12 wk after primary infection (resting memory). Moreover, during resting memory, SDR-MEM mice responded with an enhanced footpad delayed-type hypersensitivity response, and more IFN-γ–producing CD4+ T cells were detected after ex vivo stimulation. When mice were rechallenged with A/PR/8/34 virus, SDR-MEM mice terminated viral gene expression significantly earlier than MEM mice and generated a greater DbNP366–74CD8+ T cell response in the lung parenchyma and airways. This enhancement was specific to the T cell response. SDR-MEM mice had significantly attenuated anti-influenza IgG titers during resting memory. Similar experiments in which mice were primed with X-31 influenza and challenged with A/PR/8/34 virus elicited similar enhancements in the splenic and lung airway Db NP366–74CD8+ T cell populations in SDR-MEM mice. This study demonstrates that the experience of repeated social defeat prior to a primary viral infection significantly enhances virus-specific memory via augmentation of memory T cell populations and suggests that social stressors should be carefully considered in the design and analysis of future studies on antiviral immunity. PMID:20083672

  2. Virus-Specific Proteins Synthesized in Cells Infected with RNA+ Temperature-Sensitive Mutants of Sindbis Virus

    PubMed Central

    Scheele, Christina M.; Pfefferkorn, E. R.

    1970-01-01

    All Sindbis virus temperature-sensitive mutants defective in “late” functions were systematically surveyed by acrylamide-gel electrophoresis for similarities and differences in the intracellular pattern of virus-specific proteins synthesized at the permissive and nonpermissive temperatures. Only cells infected with mutants of complementation group C showed an altered pattern. At the nonpermissive temperature, these mutants failed to induce the synthesis of a polypeptide corresponding to the nucleocapsid protein and instead overproduced a protein of higher molecular weight than either viral structural protein. This defect was shown to be irreversible by the finding that 3H-leucine incorporated at 41.5 C specifically failed to appear in the nucleocapsid of virions subsequently released at 29 C. Attempts to demonstrate a precursor protein in wild-type infections were inconclusive. PMID:5461887

  3. Human Leukocyte Antigen (HLA) A*1101-Restricted Epstein-Barr Virus-Specific T-cell Receptor Gene Transfer to Target Nasopharyngeal Carcinoma.

    PubMed

    Zheng, Yong; Parsonage, Greg; Zhuang, Xiaodong; Machado, Lee R; James, Christine H; Salman, Asmaa; Searle, Peter F; Hui, Edwin P; Chan, Anthony T C; Lee, Steven P

    2015-10-01

    Infusing virus-specific T cells is effective treatment for rare Epstein-Barr virus (EBV)-associated posttransplant lymphomas, and more limited success has been reported using this approach to treat a far more common EBV-associated malignancy, nasopharyngeal carcinoma (NPC). However, current approaches using EBV-transformed lymphoblastoid cell lines to reactivate EBV-specific T cells for infusion take 2 to 3 months of in vitro culture and favor outgrowth of T cells targeting viral antigens expressed within EBV(+) lymphomas, but not in NPC. Here, we explore T-cell receptor (TCR) gene transfer to rapidly and reliably generate T cells specific for the NPC-associated viral protein LMP2. We cloned a human leukocyte antigen (HLA) A*1101-restricted TCR, which would be widely applicable because 40% of NPC patients carry this HLA allele. Studying both the wild-type and modified forms, we have optimized expression of the TCR and demonstrated high-avidity antigen-specific function (proliferation, cytotoxicity, and cytokine release) in both CD8(+) and CD4(+) T cells. The engineered T cells also inhibited LMP2(+) epithelial tumor growth in a mouse model. Furthermore, transduced T cells from patients with advanced NPC lysed LMP2-expressing NPC cell lines. Using this approach, within a few days large numbers of high-avidity LMP2-specific T cells can be generated reliably to treat NPC, thus providing an ideal clinical setting to test TCR gene transfer without the risk of autoimmunity through targeting self-antigens.

  4. Adoptive Immunotherapy using Regulatory T cells and Virus-specific T cells Derived from Cord Blood

    PubMed Central

    Hanley, Patrick J.; Bollard, Catherine M.; Brunstein, Claudio G

    2014-01-01

    Cord blood transplantation, an alternative to traditional stem cell transplants (bone marrow or peripheral blood stem cell transplantation), is an attractive option for patients lacking suitable stem cell transplant donors. Cord blood units have also proven to be a valuable donor source for the development of cellular therapeutics. Virus-specific T cells and regulatory T cells are two cord blood derived products that have shown promise in early phase clinical trials to prevent and/or treat viral infections and graft-versus-host disease (GvHD), respectively. Here we describe how current strategies utilizing cord blood-derived regulatory T cells and virus-specific T cells have been developed to improve outcomes for cord blood transplant recipients. PMID:25632003

  5. The transcription factor Zbtb32 controls the proliferative burst of virus-specific natural killer cells responding to infection.

    PubMed

    Beaulieu, Aimee M; Zawislak, Carolyn L; Nakayama, Toshinori; Sun, Joseph C

    2014-06-01

    Natural killer (NK) cells are innate lymphocytes that exhibit many features of adaptive immunity, including clonal proliferation and long-lived memory. Here we demonstrate that the BTB-ZF transcription factor Zbtb32 (also known as ROG, FAZF, TZFP and PLZP) was essential for the proliferative burst and protective capacity of virus-specific NK cells. Signals from proinflammatory cytokines were both necessary and sufficient to induce high expression of Zbtb32 in NK cells. Zbtb32 facilitated NK cell proliferation during infection by antagonizing the anti-proliferative factor Blimp-1 (Prdm1). Our data support a model in which Zbtb32 acts as a cellular 'hub' through which proinflammatory signals instruct a 'proliferation-permissive' state in NK cells, thereby allowing their prolific expansion in response to viral infection.

  6. Dengue virus protein recognition by virus-specific murine CD8+ cytotoxic T lymphocytes.

    PubMed Central

    Rothman, A L; Kurane, I; Lai, C J; Bray, M; Falgout, B; Men, R; Ennis, F A

    1993-01-01

    The identification of the protein targets for dengue virus-specific T lymphocytes may be useful for planning the development of subunit vaccines against dengue. We studied the recognition by murine dengue virus-specific major histocompatibility complex class I-restricted, CD8+ cytotoxic T lymphocytes (CTL) of dengue virus proteins using recombinant vaccinia viruses containing segments of the dengue virus genome. CTL from H-2k mice recognized a single serotype-cross-reactive epitope on the nonstructural (NS) protein NS3. CTL from H-2b mice recognized a serotype-cross-reactive epitope that was localized to NS4a or NS4b. CTL from H-2d mice recognized at least three epitopes: a serotype-specific epitope on one of the structural proteins, a serotype-cross-reactive epitope on NS3, and a serotype-cross-reactive epitope on NS1 or NS2a. Our findings demonstrate the limited recognition of dengue virus proteins by CTL from three inbred mouse strains and the predominance of CTL epitopes on dengue virus nonstructural proteins, particularly NS3. Since human dengue virus-specific CTL show similar patterns of recognition, these findings suggest that nonstructural proteins should be considered in designing vaccines against dengue. PMID:7678307

  7. Plasma membrane associated, virus-specific polypeptides required for the formation of target antigen complexes recognized by virus-specific cytotoxic T lymphocytes

    SciTech Connect

    Domber, E.A.

    1986-01-01

    These studies were undertaken to define some of the poxvirus-specific target antigens which are synthesized in infected cells and recognized by vaccinia virus-specific CTLs (VV-CTLs). Since vaccinia virus infected, unmanipulated target cells express numerous virus-specific antigens on the plasma membrane, attempts were made to manipulate expression of the poxvirus genome after infection so that one or a few defined virus-specified antigens were expressed on the surface of infected cells. In vitro (/sup 51/Cr)-release assays determined that viral DNA synthesis and expression of late viral proteins were not necessary to form a target cell which was fully competent for lysis by VV-CTLs. Under the conditions employed in these experiments, 90-120 minutes of viral protein synthesis were necessary to produce a competent cell for lysis by VV-CTLs. In order to further inhibit the expression of early viral proteins in infected cells, partially UV-inactivated vaccinia virus was employed to infect target cells. It was determined that L-cells infected with virus preparations which had been UV-irradiated for 90 seconds were fully competent for lysis by VV-CTLs. Cells infected with 90 second UV-irr virus expressed 3 predominant, plasma membrane associated antigens of 36-37K, 27-28K, and 19-17K. These 3 viral antigens represent the predominant membrane-associated viral antigens available for interaction with class I, major histocompatibility antigens and hence are potential target antigens for VV-CTLs.

  8. Virus-Specific CD8(+) T Cells Cross-Reactive to Donor-Alloantigen Are Transiently Present in the Circulation of Kidney Transplant Recipients Infected With CMV and/or EBV.

    PubMed

    Heutinck, K M; Yong, S L; Tonneijck, L; van den Heuvel, H; van der Weerd, N C; van der Pant, K A M I; Bemelman, F J; Claas, F H J; Ten Berge, I J M

    2016-05-01

    T cells play a dual role in transplantation: They mediate transplant rejection and are crucial for virus control. Memory T cells generated in response to pathogens can cross-react to alloantigen, a phenomenon called heterologous immunity. Virus-specific CD8(+) T cells cross-reacting to donor-alloantigen might affect alloimmune responses and hamper tolerance induction following transplantation. Here, we longitudinally studied these cross-reactive cells in peripheral blood of 25 kidney transplant recipients with a cytomegalovirus and/or Epstein-Barr virus infection. Cross-reactive T cells were identified by flow cytometry as virus-specific T cells that proliferate in response to donor cells in a mixed-lymphocyte reaction. In 13 of 25 patients, we found cross-reactivity to donor cells for at least 1 viral epitope before (n = 7) and/or after transplantation (n = 8). Cross-reactive T cells were transiently present in the circulation, and their precursor frequency did not increase following transplantation or viral infection. Cross-reactive T cells expressed interferon-γ and CD107a in response to both alloantigen and viral peptide and resembled virus-specific T cells in phenotype and function. Their presence was not associated with impaired renal function, proteinuria, or rejection. In conclusion, virus-specific T cells that cross-react to donor-alloantigen are transiently detectable in the circulation of kidney transplant recipients. PMID:26603974

  9. Simian immunodeficiency virus-specific CD8+ lymphocyte response in acutely infected rhesus monkeys.

    PubMed Central

    Yasutomi, Y; Reimann, K A; Lord, C I; Miller, M D; Letvin, N L

    1993-01-01

    To assess the possible role of cytotoxic T lymphocytes (CTLs) in containing the spread of human immunodeficiency virus in acutely infected individuals, the temporal evolution of the virus-specific CD8+ lymphocyte response was defined in simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys. A brief period of SIVmac plasma antigenemia was seen 9 to 16 days following intravenous infection with SIVmac, ending as the absolute number of CD8+ peripheral blood lymphocytes (PBLs) increased. In a prospective assessment of the ability of CD8+ lymphocytes of these monkeys to suppress SIVmac replication in autologous PBLs, inhibitory activity was detected as early as 4 days, with a more pronounced effect 12 to 16 days following infection. SIVmac Gag- and Nef-specific CD8+ effector cell activities were demonstrable in PBLs of animals by 2 weeks following virus inoculation. In fact, SIVmac-specific CTL precursors were documented in the PBLs of rhesus monkeys 4 to 6 days after SIVmac infection. These studies indicate that AIDS virus-specific CD8+ CTLs are present in PBLs within days of infection and may play an important role in containing the early spread of virus. PMID:8437240

  10. Deletion mapping of the rotavirus metalloprotein NS53 (NSP1): the conserved cysteine-rich region is essential for virus-specific RNA binding.

    PubMed Central

    Hua, J; Chen, X; Patton, J T

    1994-01-01

    NS53 (NSP1), the gene 5 product of the group A rotaviruses, is a minor nonstructural protein of 486 to 495 amino acids which binds zinc and contains an amino-terminal highly conserved cysteine-rich region that may form one or two zinc fingers. To study the structure-function of the gene 5 product, wild-type and mutant forms of NS53 were produced by using a recombinant baculovirus expression system and a recombinant vaccinia virus/T7 (vTF7-3) expression system. Analysis of the RNA-binding activity of the wild-type NS53 immobilized onto protein A-Sepharose beads with NS53-specific antiserum showed that the protein exhibited specific affinity for all 11 rotavirus mRNAs. The use of short virus-specific RNA probes indicated that NS53 specifically recognizes an element located near the 5' ends of viral mRNAs. Analysis of the RNA-binding activity of deletion mutants of NS53 showed that the RNA-binding domain resides within the first 81 amino acids of the protein and that the highly conserved cysteine-rich region within this region of the protein is essential for the activity. Gel electrophoresis and Western immunoblot analyses of intracellular fractions derived from infected cells revealed that large amounts of NS53 were present in the cytosol and in association with the cytoskeletal matrix. Indirect immunofluorescence analysis of cells programmed to transiently express mutant forms of NS53 using vTF7-3 indicated that the intracellular localization domain resides between amino acids 84 and 176 of NS53. Together, these data show that the RNA-binding domain and the intracellular localization domain lie upstream from the region of NS53 previously determined not to be essential for replication of rotaviruses in cell culture (J. Hua and J. T. Patton, Virology 198:567-576, 1994). Images PMID:8189533

  11. Elevated levels of total and dengue virus-specific immunoglobulin E in patients with varying disease severity.

    PubMed

    Koraka, Penelopie; Murgue, Bernadette; Deparis, Xavier; Setiati, Tatty E; Suharti, Catarina; van Gorp, Eric C M; Hack, C E; Osterhaus, Albert D M E; Groen, Jan

    2003-05-01

    The kinetics of total and dengue virus-specific immunoglobulin E (IgE) were studied in serial serum samples obtained from 168 patients, 41 of whom suffered from primary dengue virus infection and 127 suffered from secondary dengue virus infection. Seventy-one patients were classified as dengue fever, 30 as dengue hemorrhagic fever, and 67 as dengue shock syndrome. A control group included single serum samples from patients with a herpes virus infection (n = 14), non-dengue febrile patients (n = 10), and healthy blood donors (n = 10). Patients with dengue virus infection had higher levels of total and dengue virus-specific IgE than non-dengue patients (P < 0.05). Patients with secondary dengue virus infections had not significantly increased levels of both total and dengue virus-specific IgE in the acute phase of disease compared to patients with primary dengue virus infections. Dengue virus-specific IgE was significantly higher in dengue hemorrhagic fever and/or dengue shock syndrome patients compared to dengue fever and non-dengue patients (P < 0.05). In conclusion, this study showed elevated total and dengue virus-specific IgE serum antibody levels in the acute stage of disease. Therefore, measurement of both total and dengue virus-specific IgE serum antibodies can be used as an additional prognostic marker in the development of severe complications in dengue virus infections. In addition, the presence and increase of dengue virus-specific IgE serum antibodies in patients with dengue virus infections is suggestive of the pathogenetic role that IgE may play in the hemostatic disorders observed in dengue hemorrhagic fever and dengue shock syndrome.

  12. Influenza virus-specific RNA and protein syntheses in cells infected with temperature-sensitive mutants defective in the genome segment encoding nonstructural proteins.

    PubMed

    Wolstenholme, A J; Barrett, T; Nichol, S T; Mahy, B W

    1980-07-01

    Virus-specific protein and RNA syntheses have been analyzed in chicken embryo fibroblast cells infected with two group IV temperature-sensitive (ts) mutants of influenza A (fowl plague) virus in which the ts lesion maps in RNA segment 8 (J. W. Almond, D. McGeoch, and R. D. Barry, Virology 92:416-427, 1979), known to code to code for two nonstructural proteins, NS1 and NS2. Both mutants induced the synthesis of similar amounts of all the early virus-specific proteins (P1, P2, P3, NP, and NS1) at temperatures that were either permissive (34 degrees C) or nonpermissive (40.5 degrees C) for replication. However, the synthesis of M protein, which normally accumulates late in infection, was greatly reduced in ts mutant-infected cells at 40.5 degrees C compared to 34 degrees C. The NS2 protein was not detected at either temperature in cells infected with one mutant (mN3), and was detected only at the permissive temperature in cells infected with mutant ts47. There was no overall reduction in polyadenylated (A+) complementary RNA, which functions as mRNA, in cells infected with these mutants at 40.5 degrees C compared to 34 degrees C, nor was there any evidence of selective accumulation of this type of RNA within the nucleus at the nonpermissive temperature. No significant differences in ts mutant virion RNA transcriptase activity were detected by assays in vitro at 31 and 40.5 degrees C compared to wild-type virus. Virus-specific non-polyadenylated (A-) complementary RNA, which is believed to act as the template for new virion RNA production, accumulated normally in cells at both 34 and 40.5 degrees C, but at 40.5 degrees C accumulation of new virion RNA was reduced by greater than 90% when compared to accumulation at 34 degrees C.

  13. In Vitro Synthesis of Rous Sarcoma Virus-Specific RNA is Catalyzed by a DNA-Dependent RNA Polymerase

    PubMed Central

    Rymo, L.; Parsons, J. T.; Coffin, J. M.; Weissmann, C.

    1974-01-01

    Synthesis of Rous sarcoma virus RNA was examined in vitro with a new assay for radioactive virus-specific RNA. Nuclei from infected and uninfected cells were incubated with ribonucleoside [α-32P]triphosphates, Mn++, Mg++ and (NH4)2SO4. Incorporation into total and viral RNA proceeded with similar kinetics for up to 25 min at 37°. About 0.5% of the RNA synthesized by the infected system was scored as virus-specific, compared to 0.03% of the RNA from the uninfected system and 0.005% of the RNA synthesized by monkey kidney cell nuclei. Preincubation with DNase or actinomycin D completely suppressed total and virus-specific RNA synthesis. α-Amanitin, a specific inhibitor of eukaryotic RNA polymerase II, completely inhibited virus-specific RNA synthesis, while reducing total RNA synthesis by only 50%. We conclude that tumor virus-specific RNA is synthesized on a DNA template, most probably by the host's RNA polymerase II. PMID:4368801

  14. Ethnicity and difference in dengue virus-specific memory T cell responses in Cuban individuals.

    PubMed

    de la C Sierra, Beatriz; García, Gissell; Pérez, Ana B; Morier, Luis; Alvarez, Mayling; Kourí, Gustavo; Guzmán, María G

    2006-01-01

    The different risk factors associated with dengue hemorrhagic fever pathogenesis needs yet additional clarification. The exceptional epidemiological circumstances in Cuba allow their evaluation in a well-defined situation. In the present study the memory T cell response of 80 Cuban donors previously infected with dengue-1 and dengue-2 during the 1977 and 1981 epidemics, and belonging to different ethnic groups, was examined. White people showed, in contrast to black people, stronger and remarkably cross-reactive dengue virus-specific memory CD4(+) T lymphocyte proliferation and interferon-gamma release. The observed variation in T cell response according to ethnicity could be related to the immunopathogenesis of dengue hemorrhagic fever, and may partially explain the epidemiological evidence that black individuals are at lower risk for the most severe dengue clinical course compared with white individuals.

  15. High throughput reproducible cantilever functionalization

    SciTech Connect

    Evans, Barbara R; Lee, Ida

    2014-01-21

    A method for functionalizing cantilevers is provided that includes providing a holder having a plurality of channels each having a width for accepting a cantilever probe and a plurality of probes. A plurality of cantilever probes are fastened to the plurality of channels of the holder by the spring clips. The wells of a well plate are filled with a functionalization solution, wherein adjacent wells in the well plate are separated by a dimension that is substantially equal to a dimension separating adjacent channels of the plurality of channels. Each cantilever probe that is fastened within the plurality of channels of the holder is applied to the functionalization solution that is contained in the wells of the well plate.

  16. High throughout reproducible cantilever functionalization

    SciTech Connect

    Evans, Barbara R; Lee, Ida

    2014-11-25

    A method for functionalizing cantilevers is provided that includes providing a holder having a plurality of channels each having a width for accepting a cantilever probe and a plurality of probes. A plurality of cantilever probes are fastened to the plurality of channels of the holder by the spring clips. The wells of a well plate are filled with a functionalization solution, wherein adjacent wells in the well plate are separated by a dimension that is substantially equal to a dimension separating adjacent channels of the plurality of channels. Each cantilever probe that is fastened within the plurality of channels of the holder is applied to the functionalization solution that is contained in the wells of the well plate.

  17. Polymorphisms in HLA-DPB1 are associated with differences in rubella virus-specific humoral immunity after vaccination.

    PubMed

    Lambert, Nathaniel D; Haralambieva, Iana H; Kennedy, Richard B; Ovsyannikova, Inna G; Pankratz, Vernon Shane; Poland, Gregory A

    2015-03-15

    Vaccination with live attenuated rubella virus induces a strong immune response in most individuals. However, small numbers of subjects never reach or maintain protective antibody levels, and there is a high degree of variability in immune response. We have previously described genetic polymorphisms in HLA and other candidate genes that are associated with interindividual differences in humoral immunity to rubella virus. To expand our previous work, we performed a genome-wide association study (GWAS) to discover single-nucleotide polymorphisms (SNPs) associated with rubella virus-specific neutralizing antibodies. We identified rs2064479 in the HLA-DPB1 genetic region as being significantly associated with humoral immune response variations after rubella vaccination (P = 8.62 × 10(-8)). All other significant SNPs in this GWAS were located near the HLA-DPB1 gene (P ≤ 1 × 10(-7)). These findings demonstrate that polymorphisms in HLA-DPB1 are strongly associated with interindividual differences in neutralizing antibody levels to rubella vaccination and represent a validation of our previous HLA work.

  18. Polymorphisms in HLA-DPB1 are associated with differences in rubella virus-specific humoral immunity after vaccination.

    PubMed

    Lambert, Nathaniel D; Haralambieva, Iana H; Kennedy, Richard B; Ovsyannikova, Inna G; Pankratz, Vernon Shane; Poland, Gregory A

    2015-03-15

    Vaccination with live attenuated rubella virus induces a strong immune response in most individuals. However, small numbers of subjects never reach or maintain protective antibody levels, and there is a high degree of variability in immune response. We have previously described genetic polymorphisms in HLA and other candidate genes that are associated with interindividual differences in humoral immunity to rubella virus. To expand our previous work, we performed a genome-wide association study (GWAS) to discover single-nucleotide polymorphisms (SNPs) associated with rubella virus-specific neutralizing antibodies. We identified rs2064479 in the HLA-DPB1 genetic region as being significantly associated with humoral immune response variations after rubella vaccination (P = 8.62 × 10(-8)). All other significant SNPs in this GWAS were located near the HLA-DPB1 gene (P ≤ 1 × 10(-7)). These findings demonstrate that polymorphisms in HLA-DPB1 are strongly associated with interindividual differences in neutralizing antibody levels to rubella vaccination and represent a validation of our previous HLA work. PMID:25293367

  19. Regulated production of an influenza virus spliced mRNA mediated by virus-specific products.

    PubMed

    Smith, D B; Inglis, S C

    1985-09-01

    The influenza virus NS2 mRNA is generated through processing by cellular enzymes of a transcript (the NS1 mRNA) of virion RNA segment 8. Production of this mRNA is altered in cells infected with a mutant of influenza A (fowl plague) virus. The proportion of segment 8 transcripts which accumulated in a spliced form was found to be considerably lower in mutant virus-infected cells than in cells infected with wild-type virus, and the amplification in production of NS2 mRNA relative to that of the NS1 mRNA, which normally occurs during infection with wild-type virus, was not observed with the mutant. The NS1 mRNA specified by the mutant virus has unaltered splice recognition sites and was apparently processed normally during a mixed infection with a strain of virus which is wild-type for production of NS2 mRNA. These results suggest that the production of NS2 mRNA is regulated by virus-specific products; these products may act by increasing the efficiency of splicing of NS1 mRNA.

  20. Developmental functional adaptation to high altitude: review.

    PubMed

    Frisancho, A Roberto

    2013-01-01

    Various approaches have been used to understand the origins of the functional traits that characterize the Andean high-altitude native. Based on the conceptual framework of developmental functional adaptation which postulates that environmental influences during the period of growth and development have long lasting effects that may be expressed during adulthood, we initiated a series of studies addressed at determining the pattern of physical growth and the contribution of growth and development to the attainment of full functional adaptation to high-altitude of low and high altitude natives living under rural and urban conditions. Current research indicate that: (a) the pattern of growth at high altitude due to limited nutritional resources, physical growth in body size is delayed but growth in lung volumes is accelerated because of hypoxic stress); (b) low-altitude male and female urban natives can attain a full functional adaptation to high altitude by exposure to high-altitude hypoxia during the period of growth and development; (c) both experimental studies on animals and comparative human studies indicate that exposure to high altitude during the period of growth and development results in the attainment of a large residual lung volume; (d) this developmentally acquired enlarged residual lung volume and its associated increase in alveolar area when combined with the increased tissue capillarization and moderate increase in red blood cells and hemoglobin concentration contributes to the successful functional adaptation of the Andean high-altitude native to hypoxia; and (e) any specific genetic traits that are related to the successful functional adaptation of Andean high-altitude natives have yet to be identified.

  1. Water Production Functions for High Plains Crops

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Water Production Functions for High Plains Crops Water consumptive use by a crop can be reduced through limited (deficit) irrigation. If the reduced consumptive use (CU) can be quantified, the saved water can be transferred to other users. If the value of the transferred water is greater than the fa...

  2. Virus-specific T lymphocytes home to the skin during natural dengue infection.

    PubMed

    Rivino, Laura; Kumaran, Emmanuelle A; Thein, Tun-Linn; Too, Chien Tei; Gan, Victor Chih Hao; Hanson, Brendon J; Wilder-Smith, Annelies; Bertoletti, Antonio; Gascoigne, Nicholas R J; Lye, David Chien; Leo, Yee Sin; Akbar, Arne N; Kemeny, David M; MacAry, Paul A

    2015-03-11

    Dengue, which is the most prevalent mosquito-borne viral disease afflicting human populations, causes a spectrum of clinical symptoms that include fever, muscle and joint pain, maculopapular skin rash, and hemorrhagic manifestations. Patients infected with dengue develop a broad antigen-specific T lymphocyte response, but the phenotype and functional properties of these cells are only partially understood. We show that natural infection induces dengue-specific CD8(+) T lymphocytes that are highly activated and proliferating, exhibit antiviral effector functions, and express CXCR3, CCR5, and the skin-homing marker cutaneous lymphocyte-associated antigen (CLA). In the same patients, bystander human cytomegalovirus -specific CD8(+) T cells are also activated during acute dengue infection but do not express the same tissue-homing phenotype. We show that CLA expression by circulating dengue-specific CD4(+) and CD8(+) T cells correlates with their in vivo ability to traffic to the skin during dengue infection. The juxtaposition of dengue-specific T cells with virus-permissive cell types at sites of possible dengue exposure represents a previously uncharacterized form of immune surveillance for this virus. These findings suggest that vaccination strategies may need to induce dengue-specific T cells with similar homing properties to provide durable protection against dengue viruses. PMID:25761891

  3. Virus-specific T lymphocytes home to the skin during natural dengue infection.

    PubMed

    Rivino, Laura; Kumaran, Emmanuelle A; Thein, Tun-Linn; Too, Chien Tei; Gan, Victor Chih Hao; Hanson, Brendon J; Wilder-Smith, Annelies; Bertoletti, Antonio; Gascoigne, Nicholas R J; Lye, David Chien; Leo, Yee Sin; Akbar, Arne N; Kemeny, David M; MacAry, Paul A

    2015-03-11

    Dengue, which is the most prevalent mosquito-borne viral disease afflicting human populations, causes a spectrum of clinical symptoms that include fever, muscle and joint pain, maculopapular skin rash, and hemorrhagic manifestations. Patients infected with dengue develop a broad antigen-specific T lymphocyte response, but the phenotype and functional properties of these cells are only partially understood. We show that natural infection induces dengue-specific CD8(+) T lymphocytes that are highly activated and proliferating, exhibit antiviral effector functions, and express CXCR3, CCR5, and the skin-homing marker cutaneous lymphocyte-associated antigen (CLA). In the same patients, bystander human cytomegalovirus -specific CD8(+) T cells are also activated during acute dengue infection but do not express the same tissue-homing phenotype. We show that CLA expression by circulating dengue-specific CD4(+) and CD8(+) T cells correlates with their in vivo ability to traffic to the skin during dengue infection. The juxtaposition of dengue-specific T cells with virus-permissive cell types at sites of possible dengue exposure represents a previously uncharacterized form of immune surveillance for this virus. These findings suggest that vaccination strategies may need to induce dengue-specific T cells with similar homing properties to provide durable protection against dengue viruses.

  4. Executive functioning in highly talented soccer players.

    PubMed

    Verburgh, Lot; Scherder, Erik J A; van Lange, Paul A M; Oosterlaan, Jaap

    2014-01-01

    Executive functions might be important for successful performance in sports, particularly in team sports requiring quick anticipation and adaptation to continuously changing situations in the field. The executive functions motor inhibition, attention and visuospatial working memory were examined in highly talented soccer players. Eighty-four highly talented youth soccer players (mean age 11.9), and forty-two age-matched amateur soccer players (mean age 11.8) in the age range 8 to 16 years performed a Stop Signal task (motor inhibition), the Attention Network Test (alerting, orienting, and executive attention) and a visuospatial working memory task. The highly talented soccer players followed the talent development program of the youth academy of a professional soccer club and played at the highest national soccer competition for their age. The amateur soccer players played at a regular soccer club in the same geographical region as the highly talented soccer players and play in a regular regional soccer competition. Group differences were tested using analyses of variance. The highly talented group showed superior motor inhibition as measured by stop signal reaction time (SSRT) on the Stop Signal task and a larger alerting effect on the Attention Network Test, indicating an enhanced ability to attain and maintain an alert state. No group differences were found for orienting and executive attention and visuospatial working memory. A logistic regression model with group (highly talented or amateur) as dependent variable and executive function measures that significantly distinguished between groups as predictors showed that these measures differentiated highly talented soccer players from amateur soccer players with 89% accuracy. Highly talented youth soccer players outperform youth amateur players on suppressing ongoing motor responses and on the ability to attain and maintain an alert state; both may be essential for success in soccer.

  5. Executive Functioning in Highly Talented Soccer Players

    PubMed Central

    Verburgh, Lot; Scherder, Erik J. A.; van Lange, Paul A.M.; Oosterlaan, Jaap

    2014-01-01

    Executive functions might be important for successful performance in sports, particularly in team sports requiring quick anticipation and adaptation to continuously changing situations in the field. The executive functions motor inhibition, attention and visuospatial working memory were examined in highly talented soccer players. Eighty-four highly talented youth soccer players (mean age 11.9), and forty-two age-matched amateur soccer players (mean age 11.8) in the age range 8 to 16 years performed a Stop Signal task (motor inhibition), the Attention Network Test (alerting, orienting, and executive attention) and a visuospatial working memory task. The highly talented soccer players followed the talent development program of the youth academy of a professional soccer club and played at the highest national soccer competition for their age. The amateur soccer players played at a regular soccer club in the same geographical region as the highly talented soccer players and play in a regular regional soccer competition. Group differences were tested using analyses of variance. The highly talented group showed superior motor inhibition as measured by stop signal reaction time (SSRT) on the Stop Signal task and a larger alerting effect on the Attention Network Test, indicating an enhanced ability to attain and maintain an alert state. No group differences were found for orienting and executive attention and visuospatial working memory. A logistic regression model with group (highly talented or amateur) as dependent variable and executive function measures that significantly distinguished between groups as predictors showed that these measures differentiated highly talented soccer players from amateur soccer players with 89% accuracy. Highly talented youth soccer players outperform youth amateur players on suppressing ongoing motor responses and on the ability to attain and maintain an alert state; both may be essential for success in soccer. PMID:24632735

  6. Grafting functional antioxidants on highly crosslinked polyethylene

    NASA Astrophysics Data System (ADS)

    Al-Malaika, S.; Riasat, S.; Lewucha, C.

    2016-05-01

    The problem of interference of antioxidants, such as hindered phenols, with peroxide-initiated crosslinking of polyethylene was addressed through the use of functional (reactive) graftable antioxidants (g-AO). Reactive derivatives of hindered phenol and hindered amine antioxidants were synthesised, characterised and used to investigate their grafting reactions in high density polyethylene; both non-crosslinked (PE) and highly peroxide-crosslinked (PEXa). Assessment of the extent of in-situ grafting of the antioxidants, their retention after exhaustive solvent extraction in PE and PEXa, and the stabilising performance of the grafted antioxidants (g-AO) in the polymer were examined and benchmarked against conventionally stabilised crosslinked & non-crosslinked polyethylene. It was shown that the functional antioxidants graft to a high extent in PEXa, and that the level of interference of the g-AOs with the polymer crosslinking process was minimal compared to that of conventional antioxidants which bear the same antioxidant function. The much higher level of retention of the g-AOs in PEXa after exhaustive solvent extraction, compared to that of the corresponding conventional antioxidants, accounts for their superior long-term thermal stabilising performance under severe extractive conditions.

  7. A fusion inhibitor prevents spread of immunodeficiency viruses, but not activation of virus-specific T cells, by dendritic cells.

    PubMed

    Frank, I; Stössel, H; Gettie, A; Turville, S G; Bess, J W; Lifson, J D; Sivin, I; Romani, N; Robbiani, M

    2008-06-01

    Dendritic cells (DCs) play a key role in innate immune responses, and their interactions with T cells are critical for the induction of adaptive immunity. However, immunodeficiency viruses are efficiently captured by DCs and can be transmitted to and amplified in CD4(+) T cells, with potentially deleterious effects on the induction of immune responses. In DC-T-cell cocultures, contact with CD4(+), not CD8(+), T cells preferentially facilitated virus movement to and release at immature and mature DC-T-cell contact sites. This occurred within 5 min of DC-T-cell contact. While the fusion inhibitor T-1249 did not prevent virus capture by DCs or the release of viruses at the DC-T-cell contact points, it readily blocked virus transfer to and amplification in CD4(+) T cells. Higher doses of T-1249 were needed to block the more robust replication driven by mature DCs. Virus accumulated in DCs within T-1249-treated cocultures but these DCs were actually less infectious than DCs isolated from untreated cocultures. Importantly, T-1249 did not interfere with the stimulation of virus-specific CD4(+) and CD8(+) T-cell responses when present during virus-loading of DCs or for the time of the DC-T-cell coculture. These results provide clues to identifying strategies to prevent DC-driven virus amplification in CD4(+) T cells while maintaining virus-specific immunity, an objective critical in the development of microbicides and therapeutic vaccines.

  8. Detection of virus-specific antigen in the nuclei or nucleoli of cells infected with Zika or Langat virus.

    PubMed

    Buckley, A; Gould, E A

    1988-08-01

    Two monoclonal antibodies (MAbs) with molecular specificities for either the viral envelope glycoprotein (MAb 541) or the non-structural NS1 glycoprotein (MAb 109) were derived using West Nile and yellow fever (YF) viruses respectively. Their antigenic reactivity with a large number of flaviviruses was tested by indirect immunofluorescence microscopy. Both produced cytoplasmic fluorescent staining patterns with the homologous virus against which they were raised. Additionally, MAb 541 reacted with two substrains of YF virus whereas MAb 109 reacted with Bussuquara, YF and Ntaya viruses. These reactions were exclusively cytoplasmic. Two unexpected patterns of fluorescent labelling were observed when the antibodies were tested with Zika and Langat viruses. MAb 541 produced fluorescent staining of the nuclei, but not the cytoplasm, of cells infected with Zika virus and MAb 109 labelled only the nucleoli of cells infected with Langat virus. Double-labelling experiments showed that the nuclear fluorescent label was confined to virus-infected cells, and antibody absorption experiments with virus-infected cell packs confirmed the virus specificity of the nuclear antigen. The unexpected presence of virus-specific antigen in the nuclei or nucleoli of Zika or Langat virus-infected cells brings into question the role of the nucleus in flavivirus replication.

  9. High Speed SPM of Functional Materials

    SciTech Connect

    Huey, Bryan D.

    2015-08-14

    The development and optimization of applications comprising functional materials necessitates a thorough understanding of their static and dynamic properties and performance at the nanoscale. Leveraging High Speed SPM and concepts enabled by it, efficient measurements and maps with nanoscale and nanosecond temporal resolution are uniquely feasible. This includes recent enhancements for topographic, conductivity, ferroelectric, and piezoelectric properties as originally proposed, as well as newly developed methods or improvements to AFM-based mechanical, friction, thermal, and photoconductivity measurements. The results of this work reveal fundamental mechanisms of operation, and suggest new approaches for improving the ultimate speed and/or efficiency, of data storage systems, magnetic-electric sensors, and solar cells.

  10. Prolonged Exposure to HIV Reinforces a Poised Epigenetic Program for PD-1 Expression in Virus-specific CD8 T Cells

    PubMed Central

    Youngblood, Ben; Noto, Alessandra; Porichis, Filippos; Akondy, Rama S.; Ndhlovu, Zaza M.; Austin, James W.; Bordi, Rebeka; Procopio, Francesco A.; Miura, Toshiyuki; Allen, Todd M.; Sidney, John; Sette, Alessandro; Walker, Bruce D.; Ahmed, Rafi; Boss, Jeremy M.; Sékaly, Rafick-Pierre; Kaufmann, Daniel E.

    2013-01-01

    Antigen-specific CD8 T cells play a critical role in controlling HIV infection but eventually lose antiviral functions in part because of expression and signaling through the inhibitory PD-1 receptor. To better understand the impact of prolonged TCR ligation on regulation of PD-1 expression in HIV-specific CD8 T cells we investigated the capacity of virus-specific CD8 T cells to modify the PD-1 epigenetic program following reduction in viral load. We observed that the transcriptional regulatory region was unmethylated in the PD-1hi HIV-specific CD8 T cells while it remained methylated in donor matched naïve cells at acute and chronic stages of infection. Surprisingly, the PD-1 promoter remained unmethylated in HIV-specific CD8 T cells from subjects with a viral load controlled by antiviral therapy for greater than 2 years or from elite controllers. Together these data demonstrate that the epigenetic program at the PD-1 locus becomes fixed following prolonged exposure to HIV virus. PMID:23772031

  11. Epstein-Barr virus-specific cytotoxic T lymphocytes as probes of HLA polymorphism. Heterogeneity of T cell-restricting determinants associated with the serologically defined HLA-A2 antigen.

    PubMed

    Gaston, J S; Rickinson, A B; Epstein, M A

    1983-08-01

    Epstein-Barr (EB) virus-specific effector T cell lines were established from nine virus-immune donors positive for the serologically defined HLA-A2 antigen; of these, four lines contained a demonstrable A2-restricted cytotoxic component. When these four effector populations were each tested on the same panel of EB virus-transformed lines from 20 HLA-A2-positive individuals, 16 of the target cell lines were consistently killed at levels above 25% of the relevant autologous cell lysis. Cytotoxicity appeared to be mediated through a restricting determinant associated with the 'common A2' antigen that these lines shared; indeed the lysis could be specifically blocked by high concentrations of an HLA-A2-specific monoclonal antibody. In contrast, 4 out of 20 target cell lines were not killed by HLA-A2-restricted effector cells, even though they did express the serologically defined A2 antigen and were found in other tests to be susceptible to EB virus-specific cytolysis restricted through other HLA-A or -B antigens on their surface. These results suggest that EB virus-specific cytotoxic T cells can distinguish between serologically identical HLA-A2 molecules via the heterogeneity of their T cell-restricting determinants. Data from one of the effector cell populations further suggested that a serologically defined cross-reaction between the otherwise distinct HLA-A2 and -Bw57 antigens might also be reflected in a cross-reactivity of T cell-restricting determinants. PMID:6193217

  12. Mitochondrial function at extreme high altitude.

    PubMed

    Murray, Andrew J; Horscroft, James A

    2016-03-01

    At high altitude, barometric pressure falls and with it inspired P(O2), potentially compromising O2 delivery to the tissues. With sufficient acclimatisation, the erythropoietic response increases red cell mass such that arterial O2 content (C(aO2)) is restored; however arterial P(O2)(P(aO2)) remains low, and the diffusion of O2 from capillary to mitochondrion is impaired. Mitochondrial respiration and aerobic capacity are thus limited, whilst reactive oxygen species (ROS) production increases. Restoration of P(aO2) with supplementary O2 does not fully restore aerobic capacity in acclimatised individuals, possibly indicating a peripheral impairment. With prolonged exposure to extreme high altitude (>5500 m), muscle mitochondrial volume density falls, with a particular loss of the subsarcolemmal population. It is not clear whether this represents acclimatisation or deterioration, but it does appear to be regulated, with levels of the mitochondrial biogenesis factor PGC-1α falling, and shows similarities to adapted Tibetan highlanders. Qualitative changes in mitochondrial function also occur, and do so at more moderate high altitudes with shorter periods of exposure. Electron transport chain complexes are downregulated, possibly mitigating the increase in ROS production. Fatty acid oxidation capacity is decreased and there may be improvements in biochemical coupling at the mitochondrial inner membrane that enhance O2 efficiency. Creatine kinase expression falls, possibly impairing high-energy phosphate transfer from the mitochondria to myofibrils. In climbers returning from the summit of Everest, cardiac energetic reserve (phosphocreatine/ATP) falls, but skeletal muscle energetics are well preserved, possibly supporting the notion that mitochondrial remodelling is a core feature of acclimatisation to extreme high altitude. PMID:26033622

  13. Varicella-zoster virus-specific antibody responses in 50-59-year-old recipients of zoster vaccine.

    PubMed

    Levin, Myron J; Schmader, Kenneth E; Gnann, John W; McNeil, Shelly A; Vesikari, Timo; Betts, Robert F; Keay, Susan; Stek, Jon E; Bundick, Nickoya D; Su, Shu-Chih; Zhao, Yanli; Li, Xiaoming; Chan, Ivan S F; Annunziato, Paula W; Parrino, Janie

    2013-11-01

    Prevaccination and 6-week postvaccination samples from the immunogenicity substudy (n = 2269) of the zoster vaccine (ZV) efficacy trial (N = 22 439) in 50-59-year-old subjects were examined for varicella-zoster virus-specific antibody responses to vaccination. The varicella-zoster virus geometric mean titer (GMT) and geometric mean fold rise were higher in ZV recipients than in placebo recipients (GMT, 660.0 vs 293.1 glycoprotein enzyme-linked immunosorbent assay units/mL [P < .001], respectively; geometric mean fold rise, 2.31 vs 1.00 [P < .025]). In each group there was a strong inverse correlation between postvaccination GMT and risk of subsequent herpes zoster. Although these data provide strong evidence that relates ZV-induced antibody and the risk of herpes zoster, a protective threshold was not determined. Clinical Trials Registration. NCT00534248.

  14. Type I interferon suppresses virus-specific B cell responses by modulating CD8+ T cell differentiation

    PubMed Central

    Moseman, E. Ashley; Wu, Tuoqi; de la Torre, Juan Carlos; Schwartzberg, Pamela L.; McGavern, Dorian B.

    2016-01-01

    Studies have established a role for T cells in resolving persistent viral infections, yet emerging evidence indicates that both T and B cells are required to control some viruses. During persistent infection, a marked lag or failure to generate neutralizing antibodies is commonly observed and likely contributes to an inability to control certain pathogens. Using lymphocytic choriomeningitis virus (LCMV) as a model, we have examined how a persistent viral infection can suppress neutralizing humoral immunity. By tracking the fate of virus-specific B cells in vivo, we report that LCMV-specific B cells were rapidly deleted within a few days of persistent infection, and this deletion was completely reversed by blockade of type I interferon (IFN-I) signaling. Early interference with IFN-I signaling promoted survival and differentiation of LCMV-specific B cells, which accelerated the generation of neutralizing antibodies. This marked improvement in antiviral humoral immunity did not rely on the cessation of IFN-I signaling in B cells but on alterations in the virus-specific CD8+ T cell response. Using two-photon microscopy and in vivo calcium imaging, we observed that cytotoxic T lymphocytes (CTLs) productively engaged and killed LCMV-specific B cells in a perforin-dependent manner within the first few days of infection. Blockade of IFN-I signaling protected LCMV-specific B cells by promoting CTL dysfunction. Therapeutic manipulation of this pathway may facilitate efforts to promote humoral immunity during persistent viral infection in humans. Our findings illustrate how events that occur early after infection can disturb the resultant adaptive response and contribute to viral persistence. PMID:27812556

  15. Moderate local and systemic respiratory syncytial virus-specific T-cell responses upon mild or subclinical RSV infection.

    PubMed

    de Waal, L; Koopman, L P; van Benten, I J; Brandenburg, A H; Mulder, P G H; de Swart, R L; Fokkens, W J; Neijens, H J; Osterhaus, A D M E

    2003-06-01

    Respiratory syncytial virus (RSV) infections are a major cause of severe respiratory disease in infants. It has been shown that there is an increased frequency of childhood wheezing in ex-bronchiolitic preteen children. This was postulated to be mediated by a vigorous virus-specific Th2 response influencing the further development of the immune system. Little is known about the possible role of the immune response to clinically mild RSV infections in this respect. We have studied the RSV-specific cellular immune response in infants with a laboratory-confirmed RSV upper respiratory tract infection (URTI; n = 13, mean age 12 months, range 2-22 months) in comparison with infants with non-RSV mediated URTI (n = 9, mean age 9.3 months, range 4-18 months) or infants with severe RSV bronchiolitis (n = 11, mean age 2.3 months, range 1-6 months). RSV-specific cytokine-producing cells were enumerated using the ELISPOT method in peripheral blood mononuclear cells and nasal brush T-cells, collected during the acute and convalescent phase of the infection. Mixed Th1 (IFN-gamma) and Th2 (IL-4 and IL-13) responses were detected in all three groups. Frequencies of RSV-specific T-cells were lower in both URTI groups than in the RSV bronchiolitis group, and not significantly different between the RSV URTI and the non-RSV URTI group. The absence of vigorous virus-specific Th2 responses upon mild RSV infection does not support the hypothesis that these infections influence the development of the immune system and that they predispose for the development of atopic disease. PMID:12696123

  16. Influenza B virus-specific CD8+ T-lymphocytes strongly cross-react with viruses of the opposing influenza B lineage.

    PubMed

    van de Sandt, Carolien E; Dou, YingYing; Vogelzang-van Trierum, Stella E; Westgeest, Kim B; Pronk, Mark R; Osterhaus, Albert D M E; Fouchier, Ron A M; Rimmelzwaan, Guus F; Hillaire, Marine L B

    2015-08-01

    Influenza B viruses fall in two antigenically distinct lineages (B/Victoria/2/1987 and B/Yamagata/16/1988 lineage) that co-circulate with influenza A viruses of the H3N2 and H1N1 subtypes during seasonal epidemics. Infections with influenza B viruses contribute considerably to morbidity and mortality in the human population. Influenza B virus neutralizing antibodies, elicited by natural infections or vaccination, poorly cross-react with viruses of the opposing influenza B lineage. Therefore, there is an increased interest in identifying other correlates of protection which could aid the development of broadly protective vaccines. blast analysis revealed high sequence identity of all viral proteins. With two online epitope prediction algorithms, putative conserved epitopes relevant for study subjects used in the present study were predicted. The cross-reactivity of influenza B virus-specific polyclonal CD8+ cytotoxic T-lymphocyte (CTL) populations obtained from HLA-typed healthy study subjects, with intra-lineage drift variants and viruses of the opposing lineage, was determined by assessing their in vitro IFN-γ response and lytic activity. Here, we show for the first time, to the best of our knowledge, that CTLs directed to viruses of the B/Victoria/2/1987 lineage cross-react with viruses of the B/Yamagata/16/1988 lineage and vice versa.

  17. Human Influenza A Virus-Specific CD8+ T-Cell Response Is Long-lived.

    PubMed

    van de Sandt, Carolien E; Hillaire, Marine L B; Geelhoed-Mieras, Martina M; Osterhaus, Albert D M E; Fouchier, Ron A M; Rimmelzwaan, Guus F

    2015-07-01

    Animal and human studies have demonstrated the importance of influenza A virus (IAV)-specific CD8(+) cytotoxic T lymphocytes (CTLs) in heterosubtypic cross-protective immunity. Using peripheral blood mononuclear cells obtained intermittently from healthy HLA-typed blood donors between 1999 and 2012, we were able to demonstrate that IAV-specific CTLs are long-lived. Intercurrent IAV infections transiently increase the frequency of functionally distinct subsets of IAV-specific CTLs, in particular effector and effector memory T cells.

  18. The Characterization of Varicella Zoster Virus Specific T Cells In Skin and Blood During Ageing

    PubMed Central

    Vukmanovic-Stejic, Milica; Sandhu, Daisy; Seidel, Judith A.; Patel, Neil; Sobande, Toni O.; Agius, Elaine; Jackson, Sarah E.; Fuentes-Duculan, Judilyn; Suarez-Farinas, Mayte; Mabbott, Neil A.; Lacy, Katie E.; Ogg, Graham; Nestle, Frank O; Krueger, James G.; Rustin, Malcolm H.A.; Akbar, Arne N.

    2015-01-01

    The varicella-zoster virus (VZV) re-activation increases during ageing. Although the effects of VZV re-activation are observed in the skin (shingles) the number or functional capacity of cutaneous VZV specific T cells have not been investigated. The numbers of circulating IFN-γ secreting VZV specific CD4+ T cells are significantly decreased in old subjects however other measures of VZV-specific CD4+ T cells, including proliferative capacity to VZV antigen stimulation and identification of VZV-specific CD4+ T cells with a MHC class II tetramer (epitope of IE-63 protein), were similar in both age groups. The majority of T cells in the skin of both age groups expressed CD69, a characteristic of skin resident T cells. VZV-specific CD4+ T cells were significantly increased in the skin compared to the blood in young and old subjects and their function was similar in both age groups. In contrast the number of Foxp3+ regulatory T cells (Tregs) and expression of the inhibitory receptor PD-1 on CD4+ T cells were significantly increased in the skin of older humans. Therefore VZV-specific CD4+ T cells in the skin of older individuals are functionally competent. However their activity may be restricted by multiple inhibitory influences in situ. PMID:25734814

  19. Functional stress modification after high condylectomy surgery.

    PubMed

    Alexandridis, C; Caputo, A A; Eliades, G C

    1991-07-01

    Surgical removal of the head of the condyles inevitably leads to radical redistribution of loads applied to the mandible. The nature of this redistribution can have important implications on the surgical approach and subsequent reconstructive procedures. The purpose of this investigation was to visualize photoelastically the functionally delivered stresses after high condylectomy surgery. Three identical models of a dentate human mandible were constructed from a photoelastic material. One mandible simulated a unilateral and the other simulated a bilateral high condylectomy. The third mandible had both condyles intact and served as basis for comparisons. Silicone implants were placed on the sectioned condylar heads. The condyles, with the silicone implants, were fitted into simulated fossae and the mandibles were loaded unilaterally and bilaterally. The resulting stresses were observed and photographed in the field of a circular polariscope. Substantial differences in load-generated stresses were observed as a result of both unilateral and bilateral condylectomies, compared to the normal case. The most severe stress conditions occurred with the unilateral condylectomy, where stresses associated with torsion were most evident. PMID:1890533

  20. Characterization of antigen-presenting properties of tumour cells using virus-specific cytotoxic T lymphocytes.

    PubMed

    Spierings, D C; Agsteribbe, E; Wilschut, J; Huckriede, A

    2000-04-01

    Immunotherapy of tumours by induction of tumour-specific cytotoxic T-lymphocytes (CTLs) will only be effective for tumours with a functional antigen processing and presentation machinery. However, many tumours are known to down-regulate expression of major histocompatibility complex (MHC) class I molecules and/or to impair antigen processing. It is therefore desirable to evaluate the ability of a given tumour to present antigenic epitopes before developing an immunotherapy protocol. In this study we have used influenza virus as a tool to determine the antigen-presenting capacities of the murine neuroblastoma C1300 cell line NB41A3, a frequently used model for human neuroblastoma. Immunofluorescence analyses revealed low and moderate expression of MHC class I molecules Dd and Kk respectively. Nevertheless, infected NB41 A3 cells were lysed efficiently by influenza-specific CTLs. These results demonstrate that all steps of the antigen-processing pathway function properly in the NB tumour cells, and that the limited MHC class I expression suffices for efficient recognition by CTLs. In addition, lysis of the NB tumour cells shows that the cells are susceptible to CTL-induced apoptosis, a pathway that is often impaired in tumour cells. These characteristics make neuroblastoma a suitable target for immunotherapy. The presented assay allows evaluation of various immunological properties of tumour cells and, thus, represents a valuable tool to assess whether a given tumour will be susceptible to immunotherapy or not.

  1. Theory of Bessel Functions of High Rank

    NASA Astrophysics Data System (ADS)

    Qi, Zhi

    In this thesis, we shall study fundamental Bessel functions for GL n (F) arising from the Voronoǐ summation formula as well as Bessel functions for GL2 (F) and GL 3 (F) occurring in the Kuznetsov trace formula, where n is any positive integer and F = R or C.

  2. Tomato cultivar tolerant to Tomato leaf curl New Delhi virus infection induces virus-specific short interfering RNA accumulation and defence-associated host gene expression.

    PubMed

    Sahu, Pranav Pankaj; Rai, Neeraj K; Chakraborty, Supriya; Singh, Major; Chandrappa, Prasanna H; Ramesh, Bandarupalli; Chattopadhyay, Debasis; Prasad, Manoj

    2010-07-01

    Tomato leaf curl New Delhi virus (ToLCNDV) infection causes significant yield loss in tomato. The availability of a conventional tolerance source against this virus is limited in tomato. To understand the molecular mechanism of virus tolerance in tomato, the abundance of viral genomic replicative intermediate molecules and virus-directed short interfering RNAs (siRNAs) by the host plant in a naturally tolerant cultivar H-88-78-1 and a susceptible cultivar Punjab Chhuhara at different time points after agroinfection was studied. We report that less abundance of viral replicative intermediate in the tolerant cultivar may have a correlation with a relatively higher accumulation of virus-specific siRNAs. To study defence-related host gene expression in response to ToLCNDV infection, the suppression subtractive hybridization technique was used. A library was prepared from tolerant cultivar H-88-78-1 between ToLCNDV-inoculated and Agrobacterium mock-inoculated plants of this cultivar at 21 days post-inoculation (dpi). A total of 106 nonredundant transcripts was identified and classified into 12 different categories according to their putative functions. By reverse Northern analysis and quantitative real-time polymerase chain reaction (qRT-PCR), we identified the differential expression pattern of 106 transcripts, 34 of which were up-regulated (>2.5-fold induction). Of these, eight transcripts showed more than four fold induction. qRT-PCR analysis was carried out to obtain comparative expression profiling of these eight transcripts between Punjab Chhuhara and H-88-78-1 on ToLCNDV infection. The expression patterns of these transcripts showed a significant increase in differential expression in the tolerant cultivar, mostly at 14 and 21 dpi, in comparison with that in the susceptible cultivar, as analysed by qRT-PCR. The probable direct and indirect relationship of siRNA accumulation and up-regulated transcripts with the ToLCNDV tolerance mechanism is discussed. PMID

  3. Presence of 5'-terminal cap structures in virus-specific RNA from feline leukemia virus-infected cells.

    PubMed Central

    Thomason, A R; Friderici, K H; Velicer, L F; Rottman, F

    1978-01-01

    The F-422 line of feline thymus tumor cells, chronically infected with the Rickard strain of feline leukemia virus (R-FeLV), was labeled with 32P, and the total cytoplasmic RNA was isolated. The RNA was centrifuged through sucrose gradients, and R-FeLV virus-specific RNA (vRNA) was located by hybridization of portions of the gradient fractions to R-FeLV complementary DNA. vRNA classes with average sedimentation coefficients of approximately 36S, 28S, 23S, and 15S were identified. Each class of RNA was recovered by hybridized with mercurated R-FeLV complementary DNA, and the hybrids were chromatographed on columns of sulfhydryl-Sepharose to separate them from unhybridized cellular RNA. Although insufficient amount of 36S and 28S vRNA were obtained for further analysis, the 23S and 15S VRNA classes were analyzed to determine the nature of their 5' termini. Each of these vRNA classes was found to contain stoichiometric amounts of cap structures per unit length of RNA, consistent with the presence of one cap per molecule. The structure of the 23S vRNA cap was found to be m7G5'ppp5'GmpAp, whereas that of the 15S vRNA cap was m7G5'ppp5'GmpGp. PMID:207884

  4. Profile and persistence of the virus-specific neutralizing humoral immune response in human survivors of Sudan ebolavirus (Gulu).

    PubMed

    Sobarzo, Ariel; Groseth, Allison; Dolnik, Olga; Becker, Stephan; Lutwama, Julius Julian; Perelman, Eddie; Yavelsky, Victoria; Muhammad, Majidat; Kuehne, Ana I; Marks, Robert S; Dye, John M; Lobel, Leslie

    2013-07-15

    To better understand humoral immunity following ebolavirus infection, a serological study of the humoral immune response against the individual viral proteins of Sudan ebolavirus (Gulu) in human survivors was performed. An enzyme-linked immunosorbent assay specific for full-length recombinant viral proteins NP, VP30, VP40, and GP1-649 (GP lacking the transmembrane domain) of Sudan ebolavirus (Gulu) was used as well as a plaque reduction neutralization test. Serum samples from human survivors, which were collected up to 10 years following recovery, were screened and analyzed. Results demonstrate that samples obtained 10 years following infection contain virus-specific antibodies that can neutralize virus. Neutralization correlates well with immunoreactivity against the viral proteins NP, VP30, and GP1-649. Sera from individuals who died or those with no documented infection but immunoreactive to ebolavirus did not neutralize. This work provides insight into the duration, profile of immunoreactivity, and neutralization capacity of the humoral immune response in ebolavirus survivors. PMID:23585686

  5. Plasmid DNA initiates replication of yellow fever vaccine in vitro and elicits virus-specific immune response in mice.

    PubMed

    Tretyakova, Irina; Nickols, Brian; Hidajat, Rachmat; Jokinen, Jenny; Lukashevich, Igor S; Pushko, Peter

    2014-11-01

    Yellow fever (YF) causes an acute hemorrhagic fever disease in tropical Africa and Latin America. To develop a novel experimental YF vaccine, we applied iDNA infectious clone technology. The iDNA represents plasmid that encodes the full-length RNA genome of 17D vaccine downstream from a cytomegalovirus (CMV) promoter. The vaccine was designed to transcribe the full-length viral RNA and to launch 17D vaccine virus in vitro and in vivo. Transfection with 10 ng of iDNA plasmid was sufficient to start replication of vaccine virus in vitro. Safety of the parental 17D and iDNA-derived 17D viruses was confirmed in AG129 mice deficient in receptors for IFN-α/β/γ. Finally, direct vaccination of BALB/c mice with a single 20 μg dose of iDNA plasmid resulted in seroconversion and elicitation of virus-specific neutralizing antibodies in animals. We conclude that iDNA immunization approach combines characteristics of DNA and attenuated vaccines and represents a promising vaccination strategy for YF.

  6. Water Production Functions For High Plains Crops

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing demands on limited water supplies will require maximizing crop production per unit water. Field studies are being carried out near Greeley, Colorado to develop water production functions for crops grown in the Great Plains. These yield per unit water relationships can be used to determi...

  7. HIV-1 evades virus-specific IgG2 and IgA class switching by targeting systemic and intestinal B cells via long-range intercellular conduits

    PubMed Central

    Xu, Weifeng; Santini, Paul A.; Sullivan, John S.; He, Bing; Shan, Meimei; Ball, Susan C.; Dyer, Wayne B.; Ketas, Thomas J.; Chadburn, Amy; Cohen-Gould, Leona; Knowles, Daniel M.; Chiu, April; Sanders, Rogier W.; Chen, Kang; Cerutti, Andrea

    2009-01-01

    Contact-dependent communication between immune cells generates protection, but also facilitates viral spread. We found that macrophages formed long-range actin-propelled conduits in response to negative factor (Nef), a human immunodeficiency virus type-1 (HIV-1) protein with immunosuppressive functions. Conduits attenuated immunoglobulin G2 (IgG2) and IgA class switching in systemic and intestinal lymphoid follicles by shuttling Nef from infected macrophages to B cells through a guanine exchange factor-dependent pathway involving the amino-terminal anchor, central core and carboxy-terminal flexible loop of Nef. By showing stronger virus-specific IgG2 and IgA responses in patients harboring Nef-deficient virions, our data suggest that HIV-1 exploits intercellular highways as a “Trojan horse” to deliver Nef to B cells and evade humoral immunity systemically and at mucosal sites of entry. PMID:19648924

  8. Plasmid DNA initiates replication of yellow fever vaccine in vitro and elicits virus-specific immune response in mice

    SciTech Connect

    Tretyakova, Irina; Nickols, Brian; Hidajat, Rachmat; Jokinen, Jenny; Lukashevich, Igor S.; Pushko, Peter

    2014-11-15

    Yellow fever (YF) causes an acute hemorrhagic fever disease in tropical Africa and Latin America. To develop a novel experimental YF vaccine, we applied iDNA infectious clone technology. The iDNA represents plasmid that encodes the full-length RNA genome of 17D vaccine downstream from a cytomegalovirus (CMV) promoter. The vaccine was designed to transcribe the full-length viral RNA and to launch 17D vaccine virus in vitro and in vivo. Transfection with 10 ng of iDNA plasmid was sufficient to start replication of vaccine virus in vitro. Safety of the parental 17D and iDNA-derived 17D viruses was confirmed in AG129 mice deficient in receptors for IFN-α/β/γ. Finally, direct vaccination of BALB/c mice with a single 20 μg dose of iDNA plasmid resulted in seroconversion and elicitation of virus-specific neutralizing antibodies in animals. We conclude that iDNA immunization approach combines characteristics of DNA and attenuated vaccines and represents a promising vaccination strategy for YF. - Highlights: • The iDNA{sup ®} platform combines advantages of DNA and live attenuated vaccines. • Yellow fever (YF) 17D vaccine was launched from iDNA plasmid in vitro and in vivo. • Safety of iDNA-generated 17D virus was confirmed in AG129 mice. • BALB/c mice seroconverted after a single-dose vaccination with iDNA. • YF virus-neutralizing response was elicited in iDNA-vaccinated mice.

  9. Characterisation of virus-specific peripheral blood cell cytokine responses following vaccination or infection with classical swine fever viruses.

    PubMed

    Graham, Simon P; Everett, Helen E; Johns, Helen L; Haines, Felicity J; La Rocca, S Anna; Khatri, Meenakshi; Wright, Ian K; Drew, Trevor; Crooke, Helen R

    2010-04-21

    Existing live attenuated classical swine fever virus (CSFV) vaccines provide a rapid onset of complete protection but pose problems in discriminating infected amongst vaccinated animals. With a view to providing additional information on the cellular mechanisms that may contribute to protection, which in turn may aid the development of the next generation of CSFV vaccines, we explored the kinetics of the cytokine responses from peripheral blood cells of pigs vaccinated with an attenuated C-strain vaccine strain and/or infected with a recent CSFV isolate. Peripheral blood cells were isolated over the course of vaccination/infection and stimulated in vitro with C-strain or UK2000/7.1 viruses. Virus-specific responses of peripheral blood cells isolated from C-strain vaccinated pigs were dominated by the production of IFN-gamma. IFN-gamma production in response to the C-strain virus was first detected in vaccinates 9 days post-vaccination and was sustained over the period of observation. In contrast, cells from challenge control animals did not secrete IFN-gamma in response to stimulation with C-strain or UK2000/7.1 viruses. Supernatants from UK2000/7.1 infected animals contained significant levels of pro-inflammatory cytokines from day 8 post-infection and these cytokines were present in both virus and mock stimulated cultures. The results suggest that the C-strain virus is a potent inducer of a type-1 T cell response, which may play a role in the protection afforded by such vaccines, whereas the pro-inflammatory cytokine responses observed in cultures from infected pigs may reflect a pathological pro-inflammatory cascade initiated in vivo following the replication and spread of CSFV.

  10. Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs

    PubMed Central

    Li, Jane; Smith, Corey; Edwards, Jarem; Sierro, Frederic; Feng, Carl G.; Khanna, Rajiv; Bell, Andrew; Hislop, Andrew D.; Tangye, Stuart G.; Rickinson, Alan B.; Gebhardt, Thomas; Britton, Warwick J.

    2016-01-01

    Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103—, and were retained within the spleen and tonsils in the absence of recent T cell stimulation. These two types of memory cells were distinct not only in their phenotype and transcriptional profile, but also in their anatomical localization within tonsils and spleen. The EBV-specific, but not CMV-specific, CD8+ memory T cells preferentially accumulated in the tonsils and acquired a phenotype that ensured their retention at the epithelial sites where EBV replicates. In vitro studies revealed that the cytokine IL-15 can potentiate the retention of circulating effector memory CD8+ T cells by down-regulating the expression of sphingosine-1-phosphate receptor, required for T cell exit from tissues, and its transcriptional activator, Kruppel-like factor 2 (KLF2). Within the tonsils the expression of IL-15 was detected in regions where CD8+ T cells localized, further supporting a role for this cytokine in T cell retention. Together this study provides evidence for the compartmentalization of distinct types of resident memory T cells that could contribute to the long-term protection against persisting viral infections. PMID:27540722

  11. Water Production Functions For High Plains Crops

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Declining water supplies is the critical resource issue for irrigated agriculture in the High Plains and much of the western U.S. Farmers need to maximize production per unit water consumed to remain economically viable and sustain irrigated agriculture. The Agricultural Research Service (ARS) Wat...

  12. Demonstration of Aleutian disease virus-specific lymphocyte response in mink with progressive Aleutian disease: comparison of sapphire and pastel mink infected with different virus strains.

    PubMed

    Race, R E; Bloom, M E; Coe, J E

    1983-09-01

    Lymphocyte blastogenesis was used to study the antiviral lymphocyte response of sapphire (Aleutian) and pastel (nonAleutian) mink inoculated with Pullman or Utah 1 Aleutian disease virus (ADV). Both mink genotypes developed a virus-specific response when inoculated with Utah 1 ADV. In contrast, after inoculation of Pullman ADV, sapphire mink had a positive virus-specific response, whereas pastel mink did not. Response occurred late after infection (8 wk) and correlated with the development of progressive Aleutian disease (AD). The response to keyhole limpet hemocyanin (KLH) and concanavalin A (Con A) was also determined. Most mink of either genotype, inoculated with either virus strain, maintained an anti-KLH response during disease. Most mink also responded to Con A, although some exhibited suppressed Con A response late in the disease course. These results indicated that mink develop an anti-ADV lymphocyte response during progressive AD and are not immunosuppressed with regard to other antigens or mitogens.

  13. Challenging Stereotypes: Sexual Functioning of Single Adults with High Functioning Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Byers, E. Sandra; Nichols, Shana; Voyer, Susan D.

    2013-01-01

    This study examined the sexual functioning of single adults (61 men, 68 women) with high functioning autism and Asperger syndrome living in the community with and without prior relationship experience. Participants completed an on-line questionnaire assessing autism symptoms, psychological functioning, and various aspects of sexual functioning. In…

  14. Overview of Unpolarized Structure Function Measurements at High x

    SciTech Connect

    Holt, Roy J.

    2011-09-21

    A motivation and overview for recent measurements of unpolarized structure functions for the nucleon will be presented. Particular attention will be given to new experiments aimed at providing new high-x data.

  15. Virus-specific HLA-restricted lysis of herpes simplex virus-infected human monocytes and macrophages mediated by cytotoxic T lymphocytes

    SciTech Connect

    Torpey, D.J. III

    1987-01-01

    Freshly-isolated peripheral blood human monocytes and 5 day in vitro cultured macrophages were infected with herpes simplex virus type 1 (HSV-1), labeled with /sup 51/Cr, and used as target cells in a 12-14 hour cell-mediated cytotoxicity assay. Mononuclear leukocytes (MNL) from HSV-1 non-immune individuals, whether unstimulated or stimulated with HSV-1 antigen, did not mediate significant lysis of either target cell. HSV-immune MNL, both freshly-isolated and cultured for 5 days without antigen, demonstrated only low levels of natural killer (NK) cell-mediate lysis. MNL from HSV-immune individuals incubated for 5 days in vitro with HSV-1 antigen mediated significant virus-specific lysis of both target cells. Mean virus-specific lysis of autologous monocytes was 8.5(/+-/2.0)% compared to a three-fold greater virus-specific lysis of autologous macrophages. Greater than 70% of this lytic activity was mediated by Leu-11-negative, T3-positive cytotoxic T lymphocytes (CTL). Allogeneic target cells lacking a common HLA determinant were not significantly lysed while T8-positive CTL mediated infrequent lysis of target cells sharing a common HLA-A and/or HLA-B determinant. T4-positive lymphocytes were demonstrated to be the predominant cell mediating lysis of autologous target cells and allogeneic target cells sharing both HLA-A and/or HLA-B plus HLA-DR determinants with the CTL; the T4-positive cell was the sole CTL mediator of lysis of allogeneic target cells having a common HLA-DR determinant.

  16. Alterations to Functional Analysis Methodology to Clarify the Functions of Low Rate, High Intensity Problem Behavior

    PubMed Central

    Davis, Barbara J; Kahng, SungWoo; Schmidt, Jonathan; Bowman, Lynn G; Boelter, Eric W

    2012-01-01

    Current research provides few suggestions for modifications to functional analysis procedures to accommodate low rate, high intensity problem behavior. This study examined the results of the extended duration functional analysis procedures of Kahng, Abt, and Schonbachler (2001) with six children admitted to an inpatient hospital for the treatment of severe problem behavior. Results of initial functional analyses (Iwata, Dorsey, Slifer, Bauman, & Richman, 1982/1994) were inconclusive for all children because of low levels of responding. The altered functional analyses, which changed multiple variables including the duration of the functional analysis (i.e., 6 or 7 hrs), yielded clear behavioral functions for all six participants. These results add additional support for the utility of an altered analysis of low rate, high intensity problem behavior when standard functional analyses do not yield differentiated results. PMID:23326628

  17. Detection of virus-specific RNA in simian sarcoma-leukemia virus-infected cells in in situ hybridization to viral complementary DNA.

    PubMed Central

    Kaufman, S L; Gallo, R C; Miller, N R

    1979-01-01

    An in situ molecular hybridization system which will detect retrovirus RNA in the cytoplasm of individual virus-infected cells has been developed. The technique was applied to cells infected with simian sarcoma-leukemia virus, where the virus-specific RNA was detected by hybridization to simian sarcoma-leukemia virus 3H-labeled complementary DNA. The system is useful for detecting viral RNA-containing cells in the presence of an excess of virus-negative cells and for determining which type of cell in a heterogenous population is expressing viral RNA. Images PMID:224220

  18. Rare species support vulnerable functions in high-diversity ecosystems.

    PubMed

    Mouillot, David; Bellwood, David R; Baraloto, Christopher; Chave, Jerome; Galzin, Rene; Harmelin-Vivien, Mireille; Kulbicki, Michel; Lavergne, Sebastien; Lavorel, Sandra; Mouquet, Nicolas; Paine, C E Timothy; Renaud, Julien; Thuiller, Wilfried

    2013-01-01

    Around the world, the human-induced collapses of populations and species have triggered a sixth mass extinction crisis, with rare species often being the first to disappear. Although the role of species diversity in the maintenance of ecosystem processes has been widely investigated, the role of rare species remains controversial. A critical issue is whether common species insure against the loss of functions supported by rare species. This issue is even more critical in species-rich ecosystems where high functional redundancy among species is likely and where it is thus often assumed that ecosystem functioning is buffered against species loss. Here, using extensive datasets of species occurrences and functional traits from three highly diverse ecosystems (846 coral reef fishes, 2,979 alpine plants, and 662 tropical trees), we demonstrate that the most distinct combinations of traits are supported predominantly by rare species both in terms of local abundance and regional occupancy. Moreover, species that have low functional redundancy and are likely to support the most vulnerable functions, with no other species carrying similar combinations of traits, are rarer than expected by chance in all three ecosystems. For instance, 63% and 98% of fish species that are likely to support highly vulnerable functions in coral reef ecosystems are locally and regionally rare, respectively. For alpine plants, 32% and 89% of such species are locally and regionally rare, respectively. Remarkably, 47% of fish species and 55% of tropical tree species that are likely to support highly vulnerable functions have only one individual per sample on average. Our results emphasize the importance of rare species conservation, even in highly diverse ecosystems, which are thought to exhibit high functional redundancy. Rare species offer more than aesthetic, cultural, or taxonomic diversity value; they disproportionately increase the potential breadth of functions provided by ecosystems across

  19. Rare Species Support Vulnerable Functions in High-Diversity Ecosystems

    PubMed Central

    Mouillot, David; Bellwood, David R.; Baraloto, Christopher; Chave, Jerome; Galzin, Rene; Harmelin-Vivien, Mireille; Kulbicki, Michel; Lavergne, Sebastien; Lavorel, Sandra; Mouquet, Nicolas; Paine, C. E. Timothy; Renaud, Julien; Thuiller, Wilfried

    2013-01-01

    Around the world, the human-induced collapses of populations and species have triggered a sixth mass extinction crisis, with rare species often being the first to disappear. Although the role of species diversity in the maintenance of ecosystem processes has been widely investigated, the role of rare species remains controversial. A critical issue is whether common species insure against the loss of functions supported by rare species. This issue is even more critical in species-rich ecosystems where high functional redundancy among species is likely and where it is thus often assumed that ecosystem functioning is buffered against species loss. Here, using extensive datasets of species occurrences and functional traits from three highly diverse ecosystems (846 coral reef fishes, 2,979 alpine plants, and 662 tropical trees), we demonstrate that the most distinct combinations of traits are supported predominantly by rare species both in terms of local abundance and regional occupancy. Moreover, species that have low functional redundancy and are likely to support the most vulnerable functions, with no other species carrying similar combinations of traits, are rarer than expected by chance in all three ecosystems. For instance, 63% and 98% of fish species that are likely to support highly vulnerable functions in coral reef ecosystems are locally and regionally rare, respectively. For alpine plants, 32% and 89% of such species are locally and regionally rare, respectively. Remarkably, 47% of fish species and 55% of tropical tree species that are likely to support highly vulnerable functions have only one individual per sample on average. Our results emphasize the importance of rare species conservation, even in highly diverse ecosystems, which are thought to exhibit high functional redundancy. Rare species offer more than aesthetic, cultural, or taxonomic diversity value; they disproportionately increase the potential breadth of functions provided by ecosystems across

  20. Recursion-based depletion of human immunodeficiency virus-specific naive CD4(+) T cells may facilitate persistent viral replication and chronic viraemia leading to acquired immunodeficiency syndrome.

    PubMed

    Tsukamoto, Tetsuo; Yamamoto, Hiroyuki; Okada, Seiji; Matano, Tetsuro

    2016-09-01

    Although antiretroviral therapy has made human immunodeficiency virus (HIV) infection a controllable disease, it is still unclear how viral replication persists in untreated patients and causes CD4(+) T-cell depletion leading to acquired immunodeficiency syndrome (AIDS) in several years. Theorists tried to explain it with the diversity threshold theory in which accumulated mutations in the HIV genome make the virus so diverse that the immune system will no longer be able to recognize all the variants and fail to control the viraemia. Although the theory could apply to a number of cases, macaque AIDS models using simian immunodeficiency virus (SIV) have shown that failed viral control at the set point is not always associated with T-cell escape mutations. Moreover, even monkeys without a protective major histocompatibility complex (MHC) allele can contain replication of a super infected SIV following immunization with a live-attenuated SIV vaccine, while those animals are not capable of fighting primary SIV infection. Here we propose a recursion-based virus-specific naive CD4(+) T-cell depletion hypothesis through thinking on what may happen in individuals experiencing primary immunodeficiency virus infection. This could explain the mechanism for impairment of virus-specific immune response in the course of HIV infection.

  1. Recursion-based depletion of human immunodeficiency virus-specific naive CD4(+) T cells may facilitate persistent viral replication and chronic viraemia leading to acquired immunodeficiency syndrome.

    PubMed

    Tsukamoto, Tetsuo; Yamamoto, Hiroyuki; Okada, Seiji; Matano, Tetsuro

    2016-09-01

    Although antiretroviral therapy has made human immunodeficiency virus (HIV) infection a controllable disease, it is still unclear how viral replication persists in untreated patients and causes CD4(+) T-cell depletion leading to acquired immunodeficiency syndrome (AIDS) in several years. Theorists tried to explain it with the diversity threshold theory in which accumulated mutations in the HIV genome make the virus so diverse that the immune system will no longer be able to recognize all the variants and fail to control the viraemia. Although the theory could apply to a number of cases, macaque AIDS models using simian immunodeficiency virus (SIV) have shown that failed viral control at the set point is not always associated with T-cell escape mutations. Moreover, even monkeys without a protective major histocompatibility complex (MHC) allele can contain replication of a super infected SIV following immunization with a live-attenuated SIV vaccine, while those animals are not capable of fighting primary SIV infection. Here we propose a recursion-based virus-specific naive CD4(+) T-cell depletion hypothesis through thinking on what may happen in individuals experiencing primary immunodeficiency virus infection. This could explain the mechanism for impairment of virus-specific immune response in the course of HIV infection. PMID:27515208

  2. The effect of high altitude on olfactory functions.

    PubMed

    Altundağ, Aytuğ; Salihoglu, Murat; Çayönü, Melih; Cingi, Cemal; Tekeli, Hakan; Hummel, Thomas

    2014-03-01

    It is known that high-altitude trips cause nasal congestion, impaired nasal mucociliary transport rate, and increased nasal resistance, due to decreased partial oxygen pressure and dry air. It is also known that olfactory perception is affected by barometric pressure and humidity. The aim of the present study was to investigate whether olfactory function changes in relation to high altitude in a natural setting. The present study included 41 volunteers with no history of chronic rhinosinusitis or nasal polyposis. The study group consisted of 31 men (76 %) and 10 women (24 %); the mean age of the study population was 38 ± 10 years. Olfactory testing was conducted using "Sniffin' Sticks" at a high altitude (2,200 ms) and at sea level. Odor test scores for threshold and identification were significantly better at sea level than at high altitude (p < 0.001). The major finding of this investigation was that olfactory functions are decreased at high altitudes.

  3. Applications in high-content functional protein microarrays.

    PubMed

    Moore, Cedric D; Ajala, Olutobi Z; Zhu, Heng

    2016-02-01

    Protein microarray technology provides a versatile platform for characterization of hundreds to thousands of proteins in a parallel and high-throughput manner. Over the last decade, applications of functional protein microarrays in particular have flourished in studying protein function at a systems level and have led to the construction of networks and pathways describing these functions. Relevant areas of research include the detection of various binding properties of proteins, the study of enzyme-substrate relationships, the analysis of host-microbe interactions, and profiling antibody specificity. In addition, discovery of novel biomarkers in autoimmune diseases and cancers is emerging as a major clinical application of functional protein microarrays. In this review, we will summarize the recent advances of functional protein microarrays in both basic and clinical applications. PMID:26599287

  4. High Pressure NMR Methods for Characterizing Functional Substates of Proteins.

    PubMed

    Kalbitzer, Hans Robert

    2015-01-01

    Proteins usually exist in multiple conformational states in solution. High pressure NMR spectroscopy is a well-suited method to identify these states. In addition, these states can be characterized by their thermodynamic parameters, the free enthalpies at ambient pressure, the partial molar volumes, and the partial molar compressibility that can be obtained from the analysis of the high pressure NMR data. Two main types of states of proteins exist, functional states and folding states. There is a strong link between these two types, the functional states represent essential folding states (intermediates), other folding states may have no functional meaning (optional folding states). In this chapter, this concept is tested on the Ras protein, an important proto-oncogen in humans where all substates required by theory can be identified experimentally by high pressure NMR spectroscopy. Finally, we show how these data can be used to develop allosteric inhibitors of proteins. PMID:26174382

  5. Immunodominant Dengue Virus-Specific CD8+ T Cell Responses Are Associated with a Memory PD-1+ Phenotype

    PubMed Central

    de Alwis, Ruklanthi; Bangs, Derek J.; Angelo, Michael A.; Cerpas, Cristhiam; Fernando, Anira; Sidney, John; Peters, Bjoern; Gresh, Lionel; Balmaseda, Angel; de Silva, Aruna D.; Harris, Eva; Sette, Alessandro

    2016-01-01

    cells express high levels of the receptor programmed death 1 protein (PD-1), while those from disease-susceptible alleles do not. Not only does this represent a possible correlate of immunodominance, but it raises the hypothesis that PD-1 might be a regulator that prevents excessive damage while preserving antiviral function. Further, as this study employs distinct populations (Nicaraguan and Sri Lankan donors), we also confirmed that this pattern holds despite geographic and ethnic differences. This finding indicates that HLA type is the major determinant in shaping T cell responses. PMID:26912627

  6. Functional over-redundancy and high functional vulnerability in global fish faunas on tropical reefs.

    PubMed

    Mouillot, David; Villéger, Sébastien; Parravicini, Valeriano; Kulbicki, Michel; Arias-González, Jesus Ernesto; Bender, Mariana; Chabanet, Pascale; Floeter, Sergio R; Friedlander, Alan; Vigliola, Laurent; Bellwood, David R

    2014-09-23

    When tropical systems lose species, they are often assumed to be buffered against declines in functional diversity by the ability of the species-rich biota to display high functional redundancy: i.e., a high number of species performing similar functions. We tested this hypothesis using a ninefold richness gradient in global fish faunas on tropical reefs encompassing 6,316 species distributed among 646 functional entities (FEs): i.e., unique combinations of functional traits. We found that the highest functional redundancy is located in the Central Indo-Pacific with a mean of 7.9 species per FE. However, this overall level of redundancy is disproportionately packed into few FEs, a pattern termed functional over-redundancy (FOR). For instance, the most speciose FE in the Central Indo-Pacific contains 222 species (out of 3,689) whereas 38% of FEs (180 out of 468) have no functional insurance with only one species. Surprisingly, the level of FOR is consistent across the six fish faunas, meaning that, whatever the richness, over a third of the species may still be in overrepresented FEs whereas more than one third of the FEs are left without insurance, these levels all being significantly higher than expected by chance. Thus, our study shows that, even in high-diversity systems, such as tropical reefs, functional diversity remains highly vulnerable to species loss. Although further investigations are needed to specifically address the influence of redundant vs. vulnerable FEs on ecosystem functioning, our results suggest that the promised benefits from tropical biodiversity may not be as strong as previously thought. PMID:25225388

  7. Functional over-redundancy and high functional vulnerability in global fish faunas on tropical reefs.

    PubMed

    Mouillot, David; Villéger, Sébastien; Parravicini, Valeriano; Kulbicki, Michel; Arias-González, Jesus Ernesto; Bender, Mariana; Chabanet, Pascale; Floeter, Sergio R; Friedlander, Alan; Vigliola, Laurent; Bellwood, David R

    2014-09-23

    When tropical systems lose species, they are often assumed to be buffered against declines in functional diversity by the ability of the species-rich biota to display high functional redundancy: i.e., a high number of species performing similar functions. We tested this hypothesis using a ninefold richness gradient in global fish faunas on tropical reefs encompassing 6,316 species distributed among 646 functional entities (FEs): i.e., unique combinations of functional traits. We found that the highest functional redundancy is located in the Central Indo-Pacific with a mean of 7.9 species per FE. However, this overall level of redundancy is disproportionately packed into few FEs, a pattern termed functional over-redundancy (FOR). For instance, the most speciose FE in the Central Indo-Pacific contains 222 species (out of 3,689) whereas 38% of FEs (180 out of 468) have no functional insurance with only one species. Surprisingly, the level of FOR is consistent across the six fish faunas, meaning that, whatever the richness, over a third of the species may still be in overrepresented FEs whereas more than one third of the FEs are left without insurance, these levels all being significantly higher than expected by chance. Thus, our study shows that, even in high-diversity systems, such as tropical reefs, functional diversity remains highly vulnerable to species loss. Although further investigations are needed to specifically address the influence of redundant vs. vulnerable FEs on ecosystem functioning, our results suggest that the promised benefits from tropical biodiversity may not be as strong as previously thought.

  8. Functional over-redundancy and high functional vulnerability in global fish faunas on tropical reefs

    PubMed Central

    Mouillot, David; Villéger, Sébastien; Parravicini, Valeriano; Kulbicki, Michel; Arias-González, Jesus Ernesto; Bender, Mariana; Chabanet, Pascale; Floeter, Sergio R.; Friedlander, Alan; Vigliola, Laurent; Bellwood, David R.

    2014-01-01

    When tropical systems lose species, they are often assumed to be buffered against declines in functional diversity by the ability of the species-rich biota to display high functional redundancy: i.e., a high number of species performing similar functions. We tested this hypothesis using a ninefold richness gradient in global fish faunas on tropical reefs encompassing 6,316 species distributed among 646 functional entities (FEs): i.e., unique combinations of functional traits. We found that the highest functional redundancy is located in the Central Indo-Pacific with a mean of 7.9 species per FE. However, this overall level of redundancy is disproportionately packed into few FEs, a pattern termed functional over-redundancy (FOR). For instance, the most speciose FE in the Central Indo-Pacific contains 222 species (out of 3,689) whereas 38% of FEs (180 out of 468) have no functional insurance with only one species. Surprisingly, the level of FOR is consistent across the six fish faunas, meaning that, whatever the richness, over a third of the species may still be in overrepresented FEs whereas more than one third of the FEs are left without insurance, these levels all being significantly higher than expected by chance. Thus, our study shows that, even in high-diversity systems, such as tropical reefs, functional diversity remains highly vulnerable to species loss. Although further investigations are needed to specifically address the influence of redundant vs. vulnerable FEs on ecosystem functioning, our results suggest that the promised benefits from tropical biodiversity may not be as strong as previously thought. PMID:25225388

  9. Did Michelangelo (1475-1564) have high-functioning autism?

    PubMed

    Arshad, Muhammad; Fitzgerald, Michael

    2004-05-01

    In this paper evidence is presented that Michelangelo met the criteria for Asperger's disorder, or high-functioning autism. The evidence relates to his single-minded work routine, unusual lifestyle, limited interests, poor social and communication skills, and issues of life control. Depression and various medical conditions, including gout, renal colic and renal stones, did not stop his obsessive working habits.

  10. Who Are Most, Average, or High-Functioning Adults?

    ERIC Educational Resources Information Center

    Gregg, Noel; Coleman, Chris; Lindstrom, Jennifer; Lee, Christopher

    2007-01-01

    The growing number of high-functioning adults seeking accommodations from testing agencies and postsecondary institutions presents an urgent need to ensure reliable and valid diagnostic decision making. The potential for this population to make significant contributions to society will be greater if we provide the learning and testing…

  11. Effective Interventions for Individuals with High-Functional Autism

    ERIC Educational Resources Information Center

    Huang, Ann X.; Wheeler, John J.

    2006-01-01

    The diagnosis of high functioning autism (HFA) is not the end of comprehensive assessments. Since the 1970s, although a great deal of research has focused on developing effective educational approaches and interventions for children with autism, there is an increasing need to develop differentially effective educational approaches or interventions…

  12. Audiovisual Integration in High Functioning Adults with Autism

    ERIC Educational Resources Information Center

    Keane, Brian P.; Rosenthal, Orna; Chun, Nicole H.; Shams, Ladan

    2010-01-01

    Autism involves various perceptual benefits and deficits, but it is unclear if the disorder also involves anomalous audiovisual integration. To address this issue, we compared the performance of high-functioning adults with autism and matched controls on experiments investigating the audiovisual integration of speech, spatiotemporal relations, and…

  13. Differentiating High-Functioning Autism and Social Phobia

    ERIC Educational Resources Information Center

    Tyson, Katherine E.; Cruess, Dean G.

    2012-01-01

    Both high-functioning autism (HFA) and social phobia (SP) involve profound social interaction deficits. Although these disorders share some similar symptoms, they are conceptualized as distinct. Because both HFA and SP are defined behaviorally, the degree of overlap between the two disorders may result in misinterpretation of symptoms. However,…

  14. Neuropsychological Profile in High Functioning Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Narzisi, Antonio; Muratori, Filippo; Calderoni, Sara; Fabbro, Franco; Urgesi, Cosimo

    2013-01-01

    A comprehensive investigation of the neuropsychological strengths and weaknesses of children with autism may help to better describe their cognitive abilities and to design appropriate interventions. To this end we compared the NEPSY-II profiles of 22 children with high-functioning autism spectrum disorders (HFASD) with those of 44 healthy control…

  15. Speech-and-Gesture Integration in High Functioning Autism

    ERIC Educational Resources Information Center

    Silverman, Laura B.; Bennetto, Loisa; Campana, Ellen; Tanenhaus, Michael K.

    2010-01-01

    This study examined iconic gesture comprehension in autism, with the goal of assessing whether cross-modal processing difficulties impede speech-and-gesture integration. Participants were 19 adolescents with high functioning autism (HFA) and 20 typical controls matched on age, gender, verbal IQ, and socio-economic status (SES). Gesture…

  16. Recreational Participation of Children with High Functioning Autism

    ERIC Educational Resources Information Center

    Potvin, Marie-Christine; Snider, Laurie; Prelock, Patricia; Kehayia, Eva; Wood-Dauphinee, Sharon

    2013-01-01

    The recreation of children with High Functioning Autism (HFA) is not well understood. The objective of this cross-sectional study was to compare the recreational engagement of children with HFA and their typically developing peers. Children with HFA (n = 30) and peers (n = 31) were similar on key characteristics that may impact recreation except…

  17. Thought Disorder in High-Functioning Autistic Adults.

    ERIC Educational Resources Information Center

    Dykens, Elisabeth; And Others

    1991-01-01

    This evaluation of thought disorders in 11 high functioning autistic young adults and older adolescents found poverty of speech, poor reality testing, perceptual distortions, and areas of cognitive slippage. In comparison with a schizophrenic reference group, autistic subjects demonstrated more poverty of speech and less illogic as well as similar…

  18. Inferential Language in High-Function Children with Autism.

    ERIC Educational Resources Information Center

    Dennis, Maureen; Lazenby, Anne L.; Lockyer, Linda

    2001-01-01

    A study involving eight high-functioning children with autism found they could define words, identify multiple meanings for ambiguous words, and make inferences from mental state verbs to given or presupposed knowledge. However, they failed to infer what mental state verbs implied in context and to make inferences about social scripts. (Contains…

  19. A functional language approach in high-speed digital simulation

    NASA Technical Reports Server (NTRS)

    Ercegovac, M. D.; Lu, S.-L.

    1983-01-01

    A functional programming approach for a multi-microprocessor architecture is presented. The language, based on Backus FP, its intermediate form and the translation process are discussed and illustrated with an example. The approach allows performance analysis to be performed at a high level as an aid in program partitioning.

  20. High School Students' Understanding of the Function Concept

    ERIC Educational Resources Information Center

    Dubinsky, Ed; Wilson, Robin T.

    2013-01-01

    This paper is a study of part of the Algebra Project's program for underrepresented high school students from the lowest quartile of academic achievement, social and economic status. The study focuses on students' learning the concept of function. The curriculum and pedagogy are part of an innovative, experimental approach designed and implemented…

  1. Executive Function Impairments in High IQ Adults with ADHD

    ERIC Educational Resources Information Center

    Brown, Thomas E.; Reichel, Philipp C.; Quinlan, Donald M.

    2009-01-01

    Objectives: To demonstrate that high IQ adults diagnosed with ADHD suffer from executive function (EF) impairments that: a) can be identified with a combination of standardized measures and self-report data; and b) occur more commonly in this group than in the general population. Method: 157 ADHD adults with IQ greater than or equal to 120 were…

  2. High-density lipoprotein functionality in coronary artery disease.

    PubMed

    Kosmas, Constantine E; Christodoulidis, Georgios; Cheng, Jeh-wei; Vittorio, Timothy J; Lerakis, Stamatios

    2014-06-01

    The role of high-density lipoprotein (HDL) in cardiovascular atheroprotection is well established. Epidemiological data have clearly demonstrated an inverse relationship between HDL levels and the risk for coronary artery disease, which is independent of the low-density lipoprotein levels. However, more recent data provide evidence that high HDL levels are not always protective and that under certain conditions may even confer an increased risk. Thus, a new concept has arisen, which stresses the importance of HDL functionality, rather than HDL concentration per se, in the assessment of cardiovascular risk. HDL functionality is genetically defined but can also be modified by several environmental and lifestyle factors, such as diet, smoking or certain pharmacologic interventions. Furthermore, HDL is consisted of a heterogeneous group of particles with major differences in their structural, biological and functional properties. Recently, the cholesterol efflux capacity from macrophages was proven to be an excellent metric of HDL functionality, because it was shown to have a strong inverse relationship with the risk of angiographically documented coronary artery disease, independent of the HDL and apolipoprotein A-1 levels, although it may not actually predict the prospective risk for cardiovascular events. Thus, improving the quality of HDL may represent a better therapeutic target than simply raising the HDL level, and assessment of HDL function may prove informative in refining our understanding of HDL-mediated atheroprotection.

  3. High School Teachers' Attitudes toward the Inclusion of Students with High-Functioning Autism

    ERIC Educational Resources Information Center

    Kieran, Laura Perran

    2012-01-01

    Few researchers have examined teachers' perceptions of the inclusion of students with autism spectrum disorders at the high school level. The purpose of this mixed methods sequential explanatory study was to examine teachers' attitudes and perceived needs in teaching high school students with high-functioning autism (HFA). Cognitive constructivism…

  4. Protection Against Lethal Sendai Virus Infection by in vivo Priming of Virus-Specific Cytotoxic T Lymphocytes with a Free Synthetic Peptide

    NASA Astrophysics Data System (ADS)

    Kast, W. Martin; Roux, Laurent; Curren, Joseph; Blom, Hendrika J. J.; Voordouw, Arie C.; Meloen, Rob H.; Kolakofsky, Daniel; Melief, Cornelis J. M.

    1991-03-01

    The only peptide of Sendai virus that is recognized by cytotoxic T lymphocytes (CTL) in B6 mice was found with (i) the use of recombinant vaccinia virus constructs containing separate genes of Sendai virus and (ii) a set of overlapping peptides completely spanning the identified nucleoprotein (NP) gene product. This immunodominant NP peptide is recognized by Sendai virus-specific CTL that are known to have therapeutic effects in vivo. By subcutaneous immunization, this peptide induced Sendai virus and NP peptide-specific CTL memory responses in vivo. Most importantly, mice that had been immunized with this peptide were protected against a lethal virus dose, indicating that viral peptides can be used as antiviral T-cell vaccines. The induction of T-cell memory by free peptide immunization potentially has wide applicability in biology and medicine, including protection against infectious disease.

  5. High temporal resolution functional MRI with partial separability model.

    PubMed

    Ngo, Giang-Chau; Holtrop, Joseph L; Fu, Maojing; Lam, Fan; Sutton, Bradley P

    2015-01-01

    Even though the hemodynamic response is a slow phenomenon, high temporal resolution in functional fMRI can enable better differentiation between the signal of interest and physiological noise or increase the statistical power of functional studies. To increase the temporal resolution, several methods have been developed to decrease the repetition time, TR, such as simultaneous multi-slice imaging and MR encephalography approaches. In this work, a method using a fast acquisition and a partial separability model is presented to achieve a multi-slice fMRI protocol at a temporal resolution of 75 ms. The method is demonstrated on a visual block task. PMID:26738022

  6. Japanese encephalitis virus infection of mouse cell lines: ability to prime mice for generation of virus specific cytotoxic T lymphocytes and differences in CTL recognisable viral determinants.

    PubMed

    Murali-Krishna, K; Ravi, V; Manjunath, R

    1995-01-01

    Ten different mouse cell lines were examined for Japanese encephalitis virus (JEV) infection in vitro and then tested for their ability to generate virus specific cytotoxic T lymphocytes (CTL). Among all cell lines examined, Neuro 2a (a neuroblastoma) was readily infected with JEV as examined by immunofluorescence and viral replication. Among other cells, P388D1, RAW 264.7 (Macrophage origin), Sp2/0 (B-cell Hybridoma), YAC-1 (T-cell lymphoma), and L929 (Fibroblast) were semipermissive to JEV infection. The cytopathic effects caused by progressive JEV infection varied from cell line to cell line. In the case of YAC-1 cells long-term viral antigen expression was observed without significant alterations in cell viability. Intermediate degrees of cytopathicity are seen in RAW 264.7 and L929 cells while infection of PS, Neuro 2a, P388D1 and Sp2/0 caused major viability losses. All infected cell lines were able to prime adult BALB/c (H-2d) mice for the generation of secondary JEV specific CTL. In contrast to YAC-1, the permissive neuroblastoma cell line Neuro 2a (H-2KkDd) was found to be least efficient in its ability to stimulate anti-viral CTL generation. Cold target competition studies demonstrated that both Neuro 2a and YAC-1 (H-2KkDd) cells expressed similar viral determinants that are recognised by CTL, suggesting that the reason for the lower ability of Neuro 2a to stimulate anti-viral CTL was not due to lack of viral CTL determinants. These findings demonstrate that a variety of mouse cell lines can be infected with Japanese encephalitis virus, and that these infected cells could be utilised to generate virus specific CTL in BALB/c mice.

  7. Selection of restriction specificities of virus-specific cytotoxic T cells in the thymus: no evidence for a crucial role of antigen-presenting cells

    SciTech Connect

    Zinkernagel, R.M.

    1982-12-01

    The proposal was tested that (P1 X P2) F1 leads to P1 irradiation bone marrow chimeras expressed predominantly P1-restricted T cells because donor derived stem cells were exposed to recipient derived antigen-presenting cells in the thymus. Because P1 recipient-derived antigen-presenting cells are replaced only slowly after 6-8 wk by (P1 X P2) donor-derived antigen-presenting cells in the thymus and because replenished pools of mature T cells may by then prevent substantial numbers of P2-restricted T cells to be generated, a large portion of thymus cells and mature T cells were eliminated using the following treatments of 12-20-wk-old (P1 X P2) F1 leads to P1 irradiation bone marrow chimeras: (a) cortisone plus antilymphocyte serum, (b) Cytoxan, (c) three doses of sublethal irradiation (300 rad) 2d apart, and (d) lethal irradiation (850 rad) and reconstitution with T cell-depleted (P1 X P2) F1 stem cells. 12-20 wk after this second treatment, (P1 X P2) leads to P1 chimeras were infected with vaccinia-virus. Virus-specific cytotoxic T cell reactivity was expressed by chimeric T cells of (P1 X P(2) F1 origin and was restricted predominantly to P1. Virus-specific cytotoxic T cells, therefore, do not seem to be selected to measurable extent by the immigrating donor-derived antigen-presenting cells in the thymus; their selection depends apparently from the recipient-derived radioresistant thymus cells.

  8. Perspectives on functional adaptation of the high altitude native.

    PubMed

    Frisancho, A R

    1983-01-01

    The major physiological processes that enable humans to attain a complete acclimatization to high altitude are briefly reviewed. The available data indicate that: (a) complete acclimatization to high altitude is associated with changes of environmentally modifiable functional traits such as lung volume but not associated with the expression of genetically controlled features such as chest size; (b) as judged by measurements of maximal aerobic power, the high altitude native has attained at high altitude an adaptation that is comparable to that attained by the low altitude native at sea level; the available information suggests that such adaptation is acquired through growth and development in an hypoxic environment; at present, however, we do not know the developmental modifications that occur within each component of the oxygen transport system, such as ventilation, pulmonary diffusion, and oxygen transport, that enable a sea level native to attain a complete functional adaptation to high altitude; and (c) at comparable altitudes among high altitude natives, there are some inter-regional differences in hemopoietic response, so that the samples derived from mining regions of the Andes are characterized by higher hemoglobin concentration than those derived from non-mining areas or the Himalayas. The source of these differences remains to be investigated. PMID:6364176

  9. Functionalized Materials From Elastomers to High Performance Thermoplastics

    SciTech Connect

    Laura Ann Salazar

    2003-05-31

    Synthesis and incorporation of functionalized materials continues to generate significant research interest in academia and in industry. If chosen correctly, a functional group when incorporated into a polymer can deliver enhanced properties, such as adhesion, water solubility, thermal stability, etc. The utility of these new materials has been demonstrated in drug-delivery systems, coatings, membranes and compatibilizers. Two approaches exist to functionalize a material. The desired moiety can be added to the monomer either before or after polymerization. The polymers used range from low glass transition temperature elastomers to high glass transition temperature, high performance materials. One industrial example of the first approach is the synthesis of Teflon(reg. sign). Poly(tetrafluoroethylene) (PTFE or Teflon(reg. sign)) is synthesized from tetrafluoroethylene, a functionalized monomer. The resulting material has significant property differences from the parent, poly(ethylene). Due to the fluorine in the polymer, PTFE has excellent solvent and heat resistance, a low surface energy and a low coefficient of friction. This allows the material to be used in high temperature applications where the surface needs to be nonabrasive and nonstick. This material has a wide spread use in the cooking industry because it allows for ease of cooking and cleaning as a nonstick coating on cookware. One of the best examples of the second approach, functionalization after polymerization, is the vulcanization process used to make tires. Natural rubber (from the Hevea brasiliensis) has a very low glass transition temperature, is very tacky and would not be useful to make tires without synthetic alteration. Goodyear's invention was the vulcanization of polyisoprene by crosslinking the material with sulfur to create a rubber that was tough enough to withstand the elements of weather and road conditions. Due to the development of polymerization techniques to make cis

  10. Temperament as a Predictor of Symptomotology and Adaptive Functioning in Adolescents with High-Functioning Autism

    ERIC Educational Resources Information Center

    Schwartz, Caley B.; Henderson, Heather A.; Inge, Anne P.; Zahka, Nicole E.; Coman, Drew C.; Kojkowski, Nicole M.; Hileman, Camilla M.; Mundy, Peter C.

    2009-01-01

    Variation in temperament is characteristic of all people but is rarely studied as a predictor of individual differences among individuals with autism. Relative to a matched comparison sample, adolescents with High-Functioning Autism (HFA) reported lower levels of Surgency and higher levels of Negative Affectivity. Variability in temperament…

  11. High functional diversity stimulates diversification in experimental microbial communities

    PubMed Central

    Jousset, Alexandre; Eisenhauer, Nico; Merker, Monika; Mouquet, Nicolas; Scheu, Stefan

    2016-01-01

    There is a growing awareness that biodiversity not only drives ecosystem services but also affects evolutionary dynamics. However, different theories predict contrasting outcomes on when do evolutionary processes occur within a context of competition. We tested whether functional diversity can explain diversification patterns. We tracked the survival and diversification of a focal bacterial species (Pseudomonas fluorescens) growing in bacterial communities of variable diversity and composition. We found that high functional diversity reduced the fitness of the focal species and, at the same time, fostered its diversification. This pattern was linked to resource competition: High diversity increased competition on a portion of the resources while leaving most underexploited. The evolved phenotypes of the focal species showed a better use of underexploited resources, albeit at a cost of lower overall growth rates. As a result, diversification alleviated the impact of competition on the fitness of the focal species. We conclude that biodiversity can stimulate evolutionary diversification, provided that sufficient alternative niches are available. PMID:27386573

  12. High functional diversity stimulates diversification in experimental microbial communities.

    PubMed

    Jousset, Alexandre; Eisenhauer, Nico; Merker, Monika; Mouquet, Nicolas; Scheu, Stefan

    2016-06-01

    There is a growing awareness that biodiversity not only drives ecosystem services but also affects evolutionary dynamics. However, different theories predict contrasting outcomes on when do evolutionary processes occur within a context of competition. We tested whether functional diversity can explain diversification patterns. We tracked the survival and diversification of a focal bacterial species (Pseudomonas fluorescens) growing in bacterial communities of variable diversity and composition. We found that high functional diversity reduced the fitness of the focal species and, at the same time, fostered its diversification. This pattern was linked to resource competition: High diversity increased competition on a portion of the resources while leaving most underexploited. The evolved phenotypes of the focal species showed a better use of underexploited resources, albeit at a cost of lower overall growth rates. As a result, diversification alleviated the impact of competition on the fitness of the focal species. We conclude that biodiversity can stimulate evolutionary diversification, provided that sufficient alternative niches are available.

  13. Atypical Categorization in Children with High Functioning Autism Spectrum Disorder

    PubMed Central

    Church, Barbara A.; Krauss, Maria S.; Lopata, Christopher; Toomey, Jennifer A.; Thomeer, Marcus L.; Coutinho, Mariana V.; Volker, Martin A.; Mercado, Eduardo

    2010-01-01

    Children with autism spectrum disorder process many perceptual and social events differently from typically developing children, suggesting that they may also form and recognize categories differently. We used a dot pattern categorization task and prototype comparison modeling to compare categorical processing in children with high functioning autism spectrum disorder and matched typical controls. We were interested in whether there were differences in how children with autism use average similarity information about a category to make decisions. During testing, the group with autism spectrum disorder endorsed prototypes less and was seemingly less sensitive to differences between to-be-categorized items and the prototype. The findings suggest that individuals with high functioning autism spectrum disorder are less likely to use overall average similarity when forming categories or making categorical decisions. Such differences in category formation and use may negatively impact processing of socially relevant information, such as facial expressions. PMID:21169581

  14. High-resolution mapping of protein sequence-function relationships.

    PubMed

    Fowler, Douglas M; Araya, Carlos L; Fleishman, Sarel J; Kellogg, Elizabeth H; Stephany, Jason J; Baker, David; Fields, Stanley

    2010-09-01

    We present a large-scale approach to investigate the functional consequences of sequence variation in a protein. The approach entails the display of hundreds of thousands of protein variants, moderate selection for activity and high-throughput DNA sequencing to quantify the performance of each variant. Using this strategy, we tracked the performance of >600,000 variants of a human WW domain after three and six rounds of selection by phage display for binding to its peptide ligand. Binding properties of these variants defined a high-resolution map of mutational preference across the WW domain; each position had unique features that could not be captured by a few representative mutations. Our approach could be applied to many in vitro or in vivo protein assays, providing a general means for understanding how protein function relates to sequence.

  15. High-throughput siRNA-based functional target validation.

    PubMed

    Xin, Hong; Bernal, Alejandro; Amato, Frank A; Pinhasov, Albert; Kauffman, Jack; Brenneman, Douglas E; Derian, Claudia K; Andrade-Gordon, Patricia; Plata-Salamán, Carlos R; Ilyin, Sergey E

    2004-06-01

    The drug discovery process pursued by major pharmaceutical companies for many years starts with target identification followed by high-throughput screening (HTS) with the goal of identifying lead compounds. To accomplish this goal, significant resources are invested into automation of the screening process or HTS. Robotic systems capable of handling thousands of data points per day are implemented across the pharmaceutical sector. Many of these systems are amenable to handling cell-based screening protocols as well. On the other hand, as companies strive to develop innovative products based on novel mechanisms of action(s), one of the current bottlenecks of the industry is the target validation process. Traditionally, bioinformatics and HTS groups operate separately at different stages of the drug discovery process. The authors describe the convergence and integration of HTS and bioinformatics to perform high-throughput target functional identification and validation. As an example of this approach, they initiated a project with a functional cell-based screen for a biological process of interest using libraries of small interfering RNA (siRNA) molecules. In this protocol, siRNAs function as potent gene-specific inhibitors. siRNA-mediated knockdown of the target genes is confirmed by TaqMan analysis, and genes with impacts on biological functions of interest are selected for further analysis. Once the genes are confirmed and further validated, they may be used for HTS to yield lead compounds.

  16. High Ulnar Nerve Injuries: Nerve Transfers to Restore Function.

    PubMed

    Patterson, Jennifer Megan M

    2016-05-01

    Peripheral nerve injuries are challenging problems. Nerve transfers are one of many options available to surgeons caring for these patients, although they do not replace tendon transfers, nerve graft, or primary repair in all patients. Distal nerve transfers for the treatment of high ulnar nerve injuries allow for a shorter reinnervation period and improved ulnar intrinsic recovery, which are critical to function of the hand. PMID:27094893

  17. Effects of simulated heliox diving at high altitudes on blood cells, liver functions and renal functions.

    PubMed

    Hu, Hui-Jun; Fan, Dan-Feng; Lv, Yan; Zhang, Yu; Yang, Chen; Zhao, Ling; Zhao, Ru-Gang; Pan, Xiao-Wen

    2013-01-01

    The aim of the present study was to examine the effects of simulated heliox diving at high altitudes on divers' blood cells, liver functions and renal functions. In this experiment, four divers lived for nine consecutive days in a dual-function high-low pressure chamber, which simulated air pressure at an altitude of 3,000 meters and at a 30-meter depth; an altitude of 4,000 meters and 30-meter depth; and at an altitude of 5,200 meters and 30 meters and 50 meters in depth. Total time underwater was 60 minutes. The subjects breathed heliox (with oxygen at 40% and helium at 60%) during the simulated 30-meter dive from zero altitude to 30 meters and while remaining underwater; they breathed air while ascending from 30 meters to 18. They breathed heliox (with oxygen at 26.7% and helium at 73.3%) in the simulated dive from zero altitude to 50 meters underwater, in remaining underwater and in ascending from 50 meters to 29; air while ascending from 29 meters to 18. Pure oxygen was breathed while ascending from 18 meters to the surface; then air. Results indicated: (1) the correlating indices of routine blood, liver and renal functions, and urine routine were all within normal reference ranges; and (2) the indices tested at other periods of time were not significantly different (p > 0.05) from the results at zero-meter level and 3,000-meter level. The study suggests that the heliox diving processes at different high altitudes simulated in this experiment have no significant impact upon divers' blood routine, liver functions and renal functions.

  18. High-temperature asymptotics of supersymmetric partition functions

    DOE PAGESBeta

    Ardehali, Arash Arabi

    2016-07-05

    We study the supersymmetric partition function of 4d supersymmetric gauge theories with a U(1) R-symmetry on Euclidean S3 × Sβ1, with S3 the unit-radius squashed three-sphere, and β the circumference of the circle. For superconformal theories, this partition function coincides (up to a Casimir energy factor) with the 4d superconformal index. The partition function can be computed exactly using the supersymmetric localization of the gauge theory path-integral. It takes the form of an elliptic hypergeometric integral, which may be viewed as a matrix-integral over the moduli space of the holonomies of the gauge fields around Sβ1. At high temperatures (βmore » → 0, corresponding to the hyperbolic limit of the elliptic hypergeometric integral) we obtain from the matrix-integral a quantum effective potential for the holonomies. The effective potential is proportional to the temperature. Therefore the high-temperature limit further localizes the matrix-integral to the locus of the minima of the potential. If the effective potential is positive semi-definite, the leading high-temperature asymptotics of the partition function is given by the formula of Di Pietro and Komargodski, and the subleading asymptotics is connected to the Coulomb branch dynamics on R3 × S1. In theories where the effective potential is not positive semi-definite, the Di Pietro-Komargodski formula needs to be modified. In particular, this modification occurs in the SU(2) theory of Intriligator-Seiberg-Shenker, and the SO(N) theory of Brodie-Cho-Intriligator, both believed to exhibit “misleading” anomaly matchings, and both believed to yield interacting superconformal field theories with c < a. Lastly, two new simple tests for dualities between 4d supersymmetric gauge theories emerge as byproducts of our analysis.« less

  19. Printing Proteins as Microarrays for High-Throughput Function Determination

    NASA Astrophysics Data System (ADS)

    MacBeath, Gavin; Schreiber, Stuart L.

    2000-09-01

    Systematic efforts are currently under way to construct defined sets of cloned genes for high-throughput expression and purification of recombinant proteins. To facilitate subsequent studies of protein function, we have developed miniaturized assays that accommodate extremely low sample volumes and enable the rapid, simultaneous processing of thousands of proteins. A high-precision robot designed to manufacture complementary DNA microarrays was used to spot proteins onto chemically derivatized glass slides at extremely high spatial densities. The proteins attached covalently to the slide surface yet retained their ability to interact specifically with other proteins, or with small molecules, in solution. Three applications for protein microarrays were demonstrated: screening for protein-protein interactions, identifying the substrates of protein kinases, and identifying the protein targets of small molecules.

  20. High-x structure function of the virtually free neutron

    NASA Astrophysics Data System (ADS)

    Cosyn, Wim; Sargsian, Misak M.

    2016-05-01

    The pole extrapolation method is applied to the semi-inclusive inelastic electron scattering off the deuteron with tagged spectator protons to extract the high-x structure function of the neutron. This approach is based on the extrapolation of the measured cross sections at different momenta of the spectator proton to the nonphysical pole of the bound neutron in the deuteron. The advantage of the method is in the possibility of suppression of the nuclear effects in a maximally model-independent way. The neutron structure functions obtained in this way demonstrate a surprising x dependence at x ≥0.6 and 1.6 ≤Q2≤3.38 GeV2 , indicating a possible rise of the neutron-to-proton structure functions ratio. If the observed rise is valid in the true deep inelastic region then it may indicate new dynamics in the generation of high-x quarks in the nucleon. One such mechanism we discuss is the possible dominance of short-range isosinglet quark-quark correlations that can enhance the d -quark distribution in the proton.

  1. Partial reconstitution of virus-specific memory CD8{sup +} T cells following whole body {gamma}-irradiation

    SciTech Connect

    Grayson, Jason M. . E-mail: jgrayson@wfubmc.edu; Laniewski, Nathan G.; Holbrook, Beth C.

    2006-04-25

    CD8{sup +} memory T cells are critical in providing immunity to viral infection. Previous studies documented that antigen-specific CD8{sup +} memory T cells are more resistant to radiation-induced apoptosis than naive T cells. Here, we determined the number and in vivo function of memory CD8{sup +} T cells as immune reconstitution progressed following irradiation. Immediately following irradiation, the number of memory CD8{sup +} T cells declined 80%. As reconstitution progressed, the number of memory cells reached a zenith at 33% of pre-irradiation levels, and was maintained for 120 days post-irradiation. In vitro, memory CD8{sup +} T cells were able to produce cytokines at all times post-irradiation, but when adoptively transferred, they were not able to expand upon rechallenge immediately following irradiation, but regained this ability as reconstitution progressed. When proliferation was examined in vitro, irradiated memory CD8{sup +} T cells were able to respond to mitogenic growth but were unable to divide.

  2. Soluble, High Molecular Weight Polysilsesquioxanes with Carboxylate Functionalities

    SciTech Connect

    RAHIMIAN,KAMYAR; LOY,DOUGLAS A.; WHEELER,DAVID R.

    2000-07-14

    Trialkoxysilyl-containing monomers of the type (RO){sub 3}Si(CH{sub 2}){sub 3}C(O)OtBu (R = Me, Et) were prepared by hydrosilation of the corresponding vinylic tert-butyl esters CH{sub 3}CHCH{sub 2}C(O)OtBu. Acid- or base-catalyzed polymerization of the monomers leads to very high molecular weight polymers with relatively narrow polydispersities. The polymerization results in complete condensation of the alkoxy groups while the tert-butyl ester functionality remains fully intact. Partial or full deprotection of the tert-butyl group can easily be achieved to yield the corresponding carboxylic acid polymers. The ester and carboxylic acid functionalities of these new materials allow for their potential use in a variety of applications such as scavenging of heavy metals.

  3. Attachment in adults with high-functioning autism.

    PubMed

    Taylor, Emma L; Target, Mary; Charman, Tony

    2008-06-01

    This study assessed attachment security in adults with high-functioning autism spectrum disorders, using the Adult Attachment Interview (AAI; George, Kaplan, & Main, 1996). Of 20 participants, three were classified as securely attached, the same proportion as would be expected in a general clinical sample. Participants' AAIs were less coherent and lower in reflective function than those of controls, who were matched for attachment status and mood disorder. A parallel interview suggested that some aspects of participants' responses were influenced by their general discourse style, while other AAI scale scores appeared to reflect their state of mind with respect to attachment more specifically. There was little evidence that attachment security was related to IQ, autistic symptomatology or theory of mind. This study suggests that adults with autism can engage with the AAI and produce scoreable narratives of their attachment experiences, and a minority demonstrate secure attachment. PMID:18773316

  4. High Resolution Radial Distribution Function of Pure Amorphous Silicon

    SciTech Connect

    Laaziri, K.; Roorda, S.; Chicoine, M.; Kycia, S.; Robertson, J.L.; Wang, J.; Moss, S.C.

    1999-04-01

    The structure factor S(Q) of high purity amorphous Si membranes prepared by ion implantation was measured over an extended Q range (0.03{endash}55 {Angstrom} {sup {minus}1} ). Calculation of the first neighbor shell coordination (C{sub 1} ) as a function of maximum Q indicates that measurement of S(Q) out to at least 40 {Angstrom}{sup {minus}1} is required to reliably determine the radial distribution function (RDF). A 2{percent} change in C{sub 1} and subtle changes in the rest of the RDF were observed upon annealing, consistent with point defect removal. After annealing at 600thinsp{degree}C, C{sub 1}=3.88 , which would explain why amorphous Si is less dense than crystalline Si. {copyright} {ital 1999} {ital The American Physical Society}

  5. Identification of a dengue virus-specific HLA-A*0201-restricted CD8+ T cell epitope.

    PubMed

    Wen, Jinsheng; Duan, Zhiliang; Jiang, Lifang

    2010-04-01

    In this study, a combination of epitope-prediction programs and in vitro assays was used to identify dengue virus (DENV)-specific CD8(+) T cell epitopes. Peripheral blood mononuclear cells (PBMCs) isolated from patients who recovered from dengue fever were stimulated with candidate epitope peptides derived from DENV, which were predicted by using SYFPEITHI and RANKpep epitope-prediction programs. The IFN-gamma ELISpot results and the results of intracellular staining of IFN-gamma showed that peptides NS4b_40 (TLYAVATTI), E_256 (QEGAMHTAL), NS3_205 (LPAIVREAI), NS5_210 (SRNSTHEMY), and NS3_207 (AIVREAIKR) could induce the recall response of CD8(+) T cells. Furthermore, the results of the MHC-peptide complex stabilization assay revealed that peptide NS4b_40 (TLYAVATTI) has a high affinity for HLA-A*0201 molecules. The IFN-gamma ELISpot results and staining of intracellular IFN-gamma confirmed that this peptide could induce high-level CD8(+) T cell response in HLA-A*0201 positive PBMCs. Peptide NS4b_40 (TLYAVATTI) was identified as a novel DENV-specific HLA-A*0201-restricted CD8(+) T cell epitope.

  6. Acrolein impairs the cholesterol transport functions of high density lipoproteins.

    PubMed

    Chadwick, Alexandra C; Holme, Rebecca L; Chen, Yiliang; Thomas, Michael J; Sorci-Thomas, Mary G; Silverstein, Roy L; Pritchard, Kirkwood A; Sahoo, Daisy

    2015-01-01

    High density lipoproteins (HDL) are considered athero-protective, primarily due to their role in reverse cholesterol transport, where they transport cholesterol from peripheral tissues to the liver for excretion. The current study was designed to determine the impact of HDL modification by acrolein, a highly reactive aldehyde found in high abundance in cigarette smoke, on the cholesterol transport functions of HDL. HDL was chemically-modified with acrolein and immunoblot and mass spectrometry analyses confirmed apolipoprotein crosslinking, as well as acrolein adducts on apolipoproteins A-I and A-II. The ability of acrolein-modified HDL (acro-HDL) to serve as an acceptor of free cholesterol (FC) from COS-7 cells transiently expressing SR-BI was significantly decreased. Further, in contrast to native HDL, acro-HDL promotes higher neutral lipid accumulation in murine macrophages as judged by Oil Red O staining. The ability of acro-HDL to mediate efficient selective uptake of HDL-cholesteryl esters (CE) into SR-BI-expressing cells was reduced compared to native HDL. Together, the findings from our studies suggest that acrolein modification of HDL produces a dysfunctional particle that may ultimately promote atherogenesis by impairing functions that are critical in the reverse cholesterol transport pathway.

  7. Psychosocial functioning in a group of Swedish adults with Asperger syndrome or high-functioning autism.

    PubMed

    Engström, I; Ekström, L; Emilsson, B

    2003-03-01

    This study reports on psychosocial functioning in Swedish adults with Asperger syndrome (AS) or high-functioning autism (HFA). A systematically selected sample of patients and relatives was interviewed concerning their psychosocial situation. The majority was living independently. All persons but one were unemployed. None was married and none had children. Only a few had some kind of partner. Most persons needed a high level of public and/or private support. The overall adjustment was rated good in 12 percent, fair in 75 percent and poor in 12 percent. Adult persons with AS/HFA have extensive need for support from their families and/or society. This information is important in order to provide adequate interventions that are in accordance with the expressed needs of the individuals themselves.

  8. Dengue virus specific dual HLA binding T cell epitopes induce CD8+ T cell responses in seropositive individuals

    PubMed Central

    Comber, Joseph D; Karabudak, Aykan; Huang, Xiaofang; Piazza, Paolo A; Marques, Ernesto T A; Philip, Ramila

    2015-01-01

    Dengue virus infects an estimated 300 million people each year and even more are at risk of becoming infected as the virus continues to spread into new areas. Despite the increase in viral prevalence, no anti-viral medications or vaccines are approved for treating or preventing infection. CD8+ T cell responses play a major role in viral clearance. Therefore, effective vaccines that induce a broad, multi-functional T cell response with substantial cross-reactivity between all virus serotypes can have major impacts on reducing infection rates and infection related complications. Here, we took an immunoproteomic approach to identify novel MHC class I restricted T cell epitopes presented by dengue virus infected cells, representing the natural and authentic targets of the T cell response. Using this approach we identified 4 novel MHC-I restricted epitopes: 2 with the binding motif for HLA-A24 molecules and 2 with both HLA-A2 and HLA-A24 binding motifs. These peptides were able to activate CD8+ T cell responses in both healthy, seronegative individuals and in seropositive individuals who have previously been infected with dengue virus. Importantly, the dual binding epitopes activated pre-existing T cell precursors in PBMCs obtained from both HLA-A2+ and HLA-A24+ seropositive individuals. Together, the data indicate that these epitopes are immunologically relevant T cell activating peptides presented on infected cells during a natural infection and therefore may serve as candidate antigens for the development of effective multi-serotype specific dengue virus vaccines. PMID:25668665

  9. Dengue virus specific dual HLA binding T cell epitopes induce CD8+ T cell responses in seropositive individuals.

    PubMed

    Comber, Joseph D; Karabudak, Aykan; Huang, Xiaofang; Piazza, Paolo A; Marques, Ernesto T A; Philip, Ramila

    2014-01-01

    Dengue virus infects an estimated 300 million people each year and even more are at risk of becoming infected as the virus continues to spread into new areas. Despite the increase in viral prevalence, no anti-viral medications or vaccines are approved for treating or preventing infection. CD8+ T cell responses play a major role in viral clearance. Therefore, effective vaccines that induce a broad, multi-functional T cell response with substantial cross-reactivity between all virus serotypes can have major impacts on reducing infection rates and infection related complications. Here, we took an immunoproteomic approach to identify novel MHC class I restricted T cell epitopes presented by dengue virus infected cells, representing the natural and authentic targets of the T cell response. Using this approach we identified 4 novel MHC-I restricted epitopes: 2 with the binding motif for HLA-A24 molecules and 2 with both HLA-A2 and HLA-A24 binding motifs. These peptides were able to activate CD8+ T cell responses in both healthy, seronegative individuals and in seropositive individuals who have previously been infected with dengue virus. Importantly, the dual binding epitopes activated pre-existing T cell precursors in PBMCs obtained from both HLA-A2+ and HLA-A24+ seropositive individuals. Together, the data indicate that these epitopes are immunologically relevant T cell activating peptides presented on infected cells during a natural infection and therefore may serve as candidate antigens for the development of effective multi-serotype specific dengue virus vaccines. PMID:25668665

  10. Reconciling Phylogeny and Function During Plant Litter Decomposition by High-Throughput Functional Metagenomics

    NASA Astrophysics Data System (ADS)

    Nyyssonen, M.; Weihe, C.; Goulden, M.; Treseder, K. K.; Martiny, J.; Martiny, A.; Allison, S. D.; Brodie, E. L.

    2012-12-01

    Integrating information on microbial diversity and functionality with ecosystem processes may be critical to predicting how ecosystems respond to environmental change. While theoretical models can be used to link microbial processes to environmental responses and rates, accurate predictions of ecosystem functioning would benefit from detailed information on microbial community composition and function. In this study, our aim was to identify functional traits involved in plant litter decomposition, a model process for carbon cycling, from decomposing plant litter. The overall goal is then to link these traits with individual microbial taxa and use this information to build predictive trait-based models of ecosystem responses to global change. In order to identify activities involved in plant litter decomposition we used automated high-throughput assays for functional screening of metagenomic fosmid libraries prepared from decomposing plant litter. Litter was collected over 15 month period from a global change field experiment undergoing rainfall and nitrogen manipulations. We identified over 600 cellulose, hemicellulose, chitin and starch hydrolyzing clones following screening of over 300,000 clones. The frequency of positive clones was ten times lower during dry season but no significant differences in hit rates were observed between different treatments. The positive clones were shotgun sequenced on the Illumina sequencing platform and the identified hydrolytic genes were shown to represent variety bacterial taxonomic groups including Proteobacteria and Bacteroidetes.

  11. Nitroborazines as potential high energy materials: density functional theoretical calculations.

    PubMed

    Janning, Jay D; Ball, David W

    2010-05-01

    As part of a search for new high energy density materials, we used density functional theoretical calculations to determine the thermochemical properties of various nitro-substituted borazine molecules. Optimized geometries, vibrational frequencies and spectra, and enthalpies of formation and combustion were determined for nitroborazine, dinitroborazine, trinitroborazine, and methyltrinitroborazine with substituents on either the boron atoms or the nitrogen atoms of the parent borazine ring. Our results indicate that the specific enthalpy of combustion ranged from 4 to 11 kJ g(-1), with increasing substitution of nitro groups lowering the energy of combustion per unit mass.

  12. [Psychoeducational intervention in high ability: intellectual functioning and extracurricular enrichment].

    PubMed

    Sastre-Riba, Sylvia

    2014-02-24

    The 'new paradigm' defines the high intellectual ability as a potential that should crystallize progressively throughout development. Its main feature is a high intellectual initial multidimensional potential, which is transformed so that, being a person with high intellectual ability is the result of a developmental process from a neurobiological substrate and the incidence of variables (psychosocial and education) which determines its manifestation more or less stable and optimal to excellence. It is interesting to know the effectiveness of psychoeducational intervention of the extracurricular enrichment programs and their effects on the expression of differential functioning and the optimization of the management of cognitive resources that lead to excellence. An extracurricular enrichment program is described and evaluated through: 1) the stability of the intellectual measures; 2) the satisfaction level of participants and families. Participants are 58 high ability students on the enrichment program and 25 parents. Intellectual profiles are obtained on T1-T2 and calculated their stability by regression analysis, the CSA and CSA-P questionnaires were applied in order to know the participants and families' satisfaction measure. Results show the basic stability of intellectual profiles with five cases of instability among the 58 profiles obtained, and a high satisfaction with the results obtained in the domain of cognitive and personal management among the participants. PMID:25252674

  13. [Psychoeducational intervention in high ability: intellectual functioning and extracurricular enrichment].

    PubMed

    Sastre-Riba, Sylvia

    2014-02-24

    The 'new paradigm' defines the high intellectual ability as a potential that should crystallize progressively throughout development. Its main feature is a high intellectual initial multidimensional potential, which is transformed so that, being a person with high intellectual ability is the result of a developmental process from a neurobiological substrate and the incidence of variables (psychosocial and education) which determines its manifestation more or less stable and optimal to excellence. It is interesting to know the effectiveness of psychoeducational intervention of the extracurricular enrichment programs and their effects on the expression of differential functioning and the optimization of the management of cognitive resources that lead to excellence. An extracurricular enrichment program is described and evaluated through: 1) the stability of the intellectual measures; 2) the satisfaction level of participants and families. Participants are 58 high ability students on the enrichment program and 25 parents. Intellectual profiles are obtained on T1-T2 and calculated their stability by regression analysis, the CSA and CSA-P questionnaires were applied in order to know the participants and families' satisfaction measure. Results show the basic stability of intellectual profiles with five cases of instability among the 58 profiles obtained, and a high satisfaction with the results obtained in the domain of cognitive and personal management among the participants.

  14. Preclinical and Clinical Performance of the Efoora Test, a Rapid Test for Detection of Human Immunodeficiency Virus-Specific Antibodies

    PubMed Central

    Arens, Max Q.; Mundy, Linda M.; Amsterdam, Daniel; Barrett, J. Tom; Bigg, Dan; Bruckner, David; Hanna, Bruce; Prince, Harry; Purington, Timothy; Hanna, Todd; Hewitt, Ross; Kalinka, Carolyn; Koppes, Thomas; Maxwell, Sarz; Moe, Ardis; Doymaz, Mehmet; Poulter, Melinda; Saber-Tehrani, Maryam; Simard, Lorenzo; Wilkins-Carmody, Donna; Vidaver, John; Berger, Cheryl; Davis, Alan H.; Alzona, Mortimer T.

    2005-01-01

    Barriers to effective diagnostic testing for human immunodeficiency virus type 1 (HIV-1) infection can be reduced with simple, reliable, and rapid detection methods. Our objective was to determine the accuracy, sensitivity, and specificity of a new rapid, lateral-flow immunochromatographic HIV-1 antibody detection device. Preclinical studies were performed using seroconversion, cross-reaction, and interference panels, archived clinical specimens, and fresh whole blood. In a multicenter, prospective clinical trial, a four-sample matrix of capillary (fingerstick) whole-blood specimens and venous whole blood, plasma, and serum was tested for HIV-1 antibodies with the Efoora HIV rapid test (Efoora Inc., Buffalo Grove, IL) and compared with an enzyme immunoassay (EIA) (Abbott Laboratories) licensed by the Food and Drug Administration. Western blot and nucleic acid test supplemental assays were employed to adjudicate discordant samples. Preclinical testing of seroconversion panels showed that antibodies were often detected earlier by the rapid test than by a reference EIA. No significant interference or cross-reactions were observed. Testing of 4,984 archived specimens yielded a sensitivity of 99.2% and a specificity of 99.7%. A prospective multicenter clinical study with 2,954 adult volunteers demonstrated sensitivity and specificity for the Efoora HIV rapid test of 99.8% (95% confidence interval [CI], 99.3 and 99.98%) and 99.0% (95% CI, 98.5 and 99.4%), respectively. Reactive rapid HIV-1 antibody detection was confirmed in 99.6% of those with a known HIV infection (n = 939), 5.2% of those in the high-risk group (n = 1,003), and 0.1% of those in the low-risk group (n = 1,012). For 21 (0.71%) patients, there was discordance between the results of the rapid test and the confirmatory EIA/Western blot tests. We conclude that the Efoora HIV rapid test is a simple, rapid assay for detection of HIV-1 antibodies, with high sensitivity and specificity compared to a standardized

  15. In Vitro Translation of Uukuniemi Virus-Specific RNAs: Identification of a Nonstructural Protein and a Precursor to the Membrane Glycoproteins

    PubMed Central

    Ulmanen, Ismo; Seppälä, Päivi; Pettersson, Ralf F.

    1981-01-01

    We isolated the virus-specific RNA species from Uukuniemi virus-infected chicken embryo cells and fractionated them by sucrose gradient centrifugation. In addition to three RNA species cosedimenting with the three viral RNA segments L (29S), M (23S), and S (17S), a fourth major RNA species, sedimenting at about 12S (S2), was found early in the infection. Annealing experiments indicated that the cytoplasmic L and M RNA species consisted of both plus and minus strands, with the plus strands in slight excess. Most of the S1 RNA was of negative polarity, whereas S2 was of positive polarity. The S2 RNA specifically annealed to the virion S RNA segment, indicating that it is transcribed from this segment. In vitro translation of the individual RNA species in micrococcal nuclease-treated cell-free reticulocyte extracts showed that an mRNA cosedimenting with the virion M RNA directed the synthesis of a virus-specific 110,000-dalton polypeptide (p110). This polypeptide could be immunoprecipitated with antiserum prepared against purified virions. When translation was carried out in the presence of dog pancreas microsomes, p110 was absent. Instead, an immunoprecipitable polypeptide band, with a molecular weight of about 70,000 and migrating between the virion surface glycoproteins G1 and G2, was observed. It is thus likely that the glycoproteins are synthesized as a precursor (p110), which during translation is cleaved roughly in the middle to yield G1 and G2. The 12S RNA species directed the synthesis of the nucleocapsid protein and a novel polypeptide with an apparent molecular weight of about 30,000. The latter was not precipitated with antivirion serum and was absent from lysates programmed with the corresponding RNA fraction from a mock-infected extract. Since, in addition, it was not found in purified virions and was present in the cytoplasm of infected cells but not in uninfected cells, it probably represents a nonstructural polypeptide. Images PMID:7194383

  16. Immunogenicity of recombinant HBsAg/HCV particles in mice pre-immunised with hepatitis B virus-specific vaccine.

    PubMed

    Netter, Hans J; Woo, Wai-Ping; Tindle, Robert; Macfarlan, Roderick I; Gowans, Eric J

    2003-06-20

    Due to their spatial structure virus-like particles (VLPs) generally induce effective immune responses. VLPs derived from the small envelope protein (HBsAg-S) of hepatitis B virus (HBV) comprise the HBV vaccine. Modified HBsAs-S VLPs, carrying the immunodominant hypervariable region (HVR1) of the hepatitis C virus (HCV) envelope protein E2 within the exposed 'a'-determinant region (HBsAg/HVR1-VLPs), elicited HVR1-specific antibodies in mice. A high percentage of the human population is positive for anti-HBsAg antibodies (anti-HBs), either through vaccination or natural infection. We, therefore, determined if pre-existing anti-HBs could influence immunisation with modified VLPs. Mice were immunised with a commercial HBV vaccine, monitored to ensure an anti-HBs response, then immunised with HBsAg/HVR1-VLPs. The resulting anti-HVR1 antibody titre was similar in mice with or without pre-existing anti-HBs. This suggests that HBsAg/HVR1-VLPs induce a primary immune response to HVR1 in anti-HBs positive mice and, hence, they may be used successfully in individuals already immunised with the HBV vaccine.

  17. In-silico search of virus-specific host microRNAs regulating avian influenza virus NS1 expression.

    PubMed

    Asaf, V N Muhasin; Kumar, Amod; Raut, Ashwin Ashok; Bhatia, Sandeep; Mishra, Anamika

    2015-06-01

    Avian influenza is a highly contagious viral infection caused by avian influenza virus type A of the family Orthomyxoviridae primarily affecting the avian species. The non-structural protein 1 (NS1) encoded by the NS1 gene of the virus is critical in establishing the infection. NS1 protein acts to suppress the virus-induced host interferon response and also inhibit Protein kinase R activation thereby helping the virus to establish the infection. MicroRNAs (miRNA) are small regulatory endogenous non-coding RNAs of ~22 nucleotides in length located within introns of coding and non-coding genes, exons of non-coding genes or inter-genic regions. miRNAs can target the gene at various sites and effectively reduce or shut down its expression. In this study, set of differentially expressed chicken miRNA identified by deep sequencing H5N1 infected and SPF chicken lung were computationally analyzed, to identify targets in the NS1 gene. 300 differentially expressed miRNAs were then analyzed individually for target sites in gi|147667147|gb|EF362422.1| influenza A virus (A/chicken/India/NIV33487/06(H5N1)) segment 8, complete sequence using RNAhybrid 2.2. The analysis yielded gga-miR-1658* as the potential miRNA which is targeting the NS1 gene of H5N1 genome.

  18. High-frequency health data and spline functions.

    PubMed

    Martín-Rodríguez, Gloria; Murillo-Fort, Carlos

    2005-03-30

    Seasonal variations are highly relevant for health service organization. In general, short run movements of medical magnitudes are important features for managers in this field to make adequate decisions. Thus, the analysis of the seasonal pattern in high-frequency health data is an appealing task. The aim of this paper is to propose procedures that allow the analysis of the seasonal component in this kind of data by means of spline functions embedded into a structural model. In the proposed method, useful adaptions of the traditional spline formulation are developed, and the resulting procedures are capable of capturing periodic variations, whether deterministic or stochastic, in a parsimonious way. Finally, these methodological tools are applied to a series of daily emergency service demand in order to capture simultaneous seasonal variations in which periods are different.

  19. Post-error adaptation in adults with high functioning autism.

    PubMed

    Bogte, Hans; Flamma, Bert; van der Meere, Jaap; van Engeland, Herman

    2007-04-01

    Deficits in executive function (EF), i.e. function of the prefrontal cortex, may be central in the etiology of autism. One of the various aspects of EF is error detection and adjusting behavior after an error. In cognitive tests, adults normally slow down their responding on the next trial after making an error, a compensatory mechanism geared toward improving performance on subsequent trials, and a faculty critically associated with activity in the anterior cingulate cortex (ACC). The current study evaluated post-error slowing in people with high functioning autism (HFA) (n=36), taking symptom severity into account, compared to the performance of a normal control group (n=32). Symptom severity in the HFA group was defined in terms of level of adaptation: living independently (outpatients; n=12) and living residentially (inpatients; n=24). Half the group of inpatients was on medication; the results of their performance were analyzed separately. A computerized version of a memory search task was used with two response probability conditions. The subjects in the control group adjusted their reaction time (RT) substantially after an error, while the group of participants with HFA appeared to be overall slow, with no significant adjustment of RT after an error. This finding remained significant if the medication factor was taken into account, and was independent of the degree of severity of the autistic disorder, as defined by the dichotomy 'inpatient versus outpatient'. Possible causes and implications of the finding are discussed.

  20. Highly Elastic Micropatterned Hydrogel for Engineering Functional Cardiac Tissue

    PubMed Central

    Annabi, Nasim; Tsang, Kelly; Mithieux, Suzanne M.; Nikkhah, Mehdi; Ameri, Afshin

    2013-01-01

    Heart failure is a major international health issue. Myocardial mass loss and lack of contractility are precursors to heart failure. Surgical demand for effective myocardial repair is tempered by a paucity of appropriate biological materials. These materials should conveniently replicate natural human tissue components, convey persistent elasticity, promote cell attachment, growth and conformability to direct cell orientation and functional performance. Here, microfabrication techniques are applied to recombinant human tropoelastin, the resilience-imparting protein found in all elastic human tissues, to generate photocrosslinked biological materials containing well-defined micropatterns. These highly elastic substrates are then used to engineer biomimetic cardiac tissue constructs. The micropatterned hydrogels, produced through photocrosslinking of methacrylated tropoelastin (MeTro), promote the attachment, spreading, alignment, function, and intercellular communication of cardiomyocytes by providing an elastic mechanical support that mimics their dynamic mechanical properties in vivo. The fabricated MeTro hydrogels also support the synchronous beating of cardiomyocytes in response to electrical field stimulation. These novel engineered micropatterned elastic gels are designed to be amenable to 3D modular assembly and establish a versatile, adaptable foundation for the modeling and regeneration of functional cardiac tissue with potential for application to other elastic tissues. PMID:24319406

  1. Developing high-performance cross-functional teams: Understanding motivations, functional loyalties, and teaming fundamentals

    SciTech Connect

    Miller, M.A.

    1996-08-01

    Teamwork is the key to the future of effective technology management. Today`s technologies and markets have become too complex for individuals to work alone. Global competition, limited resources, cost consciousness, and time pressures have forced organizations and project managers to encourage teamwork. Many of these teams will be cross-functional teams that can draw on a multitude of talents and knowledge. To develop high-performing cross-functional teams, managers must understand motivations, functional loyalties, and the different backgrounds of the individual team members. To develop a better understanding of these issues, managers can learn from experience and from literature on teams and teaming concepts. When studying the literature to learn about cross-functional teaming, managers will find many good theoretical concepts, but when put into practice, these concepts have varying effects. This issue of varying effectiveness is what drives the research for this paper. The teaming concepts were studied to confirm or modify current understanding. The literature was compared with a {open_quotes}ground truth{close_quotes}, a survey of the reality of teaming practices, to examine the teaming concepts that the literature finds to be critical to the success of teams. These results are compared to existing teams to determine if such techniques apply in real-world cases.

  2. Development of a particle agglutination assay system for detecting Japanese encephalitis virus-specific human IgM, using hydroxyapatite-coated nylon beads.

    PubMed

    Yamamoto, Akira; Nakayama, Mikio; Kurosawa, Yae; Sugo, Ken; Karasawa, Hideharu; Ogawa, Tetsuro; Takasaki, Tomohiko; Tashiro, Masato; Kurane, Ichiro

    2002-07-01

    Japanese encephalitis virus-specific IgM is a reliable indicator for serodiagnosis of Japanese encephalitis. A particle agglutination (PA) assay system was developed to detect anti-Japanese encephalitis virus IgM in human serum samples. The newly developed PA assay consisted of hydroxyapatite-coated nylon beads and V-bottom 96-well microplates. Hydroxyapatite-coated nylon beads were coated with Japanese encephalitis virus antigens. Japanese encephalitis virus antigen-coated, hydroxyapatite-coated nylon beads agglutinated in the IgM-captured wells when anti-Japanese encephalitis virus IgM-positive serum samples were used. A button pattern was formed at the bottom of the wells when anti-Japanese encephalitis virus IgM-negative serum samples were used. Thirty anti-Japanese encephalitis virus IgM-positive serum samples from Japanese encephalitis-confirmed cases were tested by the PA assay. All these serum samples were determined to be Japanese encephalitis virus IgM-positive. IgM titers determined by the PA assay corresponded to those determined by enzyme-linked immunosorbent assay. The titers were consistent in two independent PA assays. These results indicate that the newly developed PA assay is a reliable method for detecting anti-Japanese encephalitis virus IgM in human serum samples and that this assay will be a suitable diagnostic system especially in rural areas of Asia.

  3. Retinol binding protein and vitamin D associations with serum antibody isotypes, serum influenza virus-specific neutralizing activities and airway cytokine profiles.

    PubMed

    Jones, B G; Oshansky, C M; Bajracharya, R; Tang, L; Sun, Y; Wong, S S; Webby, R; Thomas, P G; Hurwitz, J L

    2016-02-01

    Vitamin A supports the induction of immunoglobulin (Ig)A responses at mucosal surfaces in mice, but much less is known about the influence of vitamins on antibody isotype expression in humans. To address this knowledge gap, we examined 46 residual blood samples from adults and children, some of whom were experiencing influenza virus infections of the respiratory tract. Assays were performed for retinol binding protein (RBP, a surrogate for vitamin A), vitamin D (a related vitamin) and antibody isotypes. Results showed that all but two tested samples exhibited RBP and/or vitamin D insufficiencies or deficiencies. Vitamin D correlated with blood IgM and IgG3, while RBP correlated with IgG4 and IgA. RBP also correlated positively with age and with influenza virus-specific antibody neutralization titres. Individuals with low blood RBP levels exhibited the highest frequencies of over-expressed cytokines and growth factors in nasal wash samples, an indication of inflamed mucosal tissues. While cause-effect relationships were not discerned, results support a hypothesis that vitamins directly influence B cell isotype expression in humans, and by so doing may help protect mucosal surfaces from respiratory viral disease. PMID:26425827

  4. Peste des petits ruminants virus-like particles induce both complete virus-specific antibodies and virus neutralizing antibodies in mice.

    PubMed

    Liu, Fuxiao; Wu, Xiaodong; Zou, Yanli; Li, Lin; Wang, Zhiliang

    2015-03-01

    Peste des petits ruminants virus (PPRV), an etiological agent of peste des petits ruminants (PPR), is classified into the genus Morbillivirus in the family Paramyxoviridae. In a previous study, a recombinant baculovirus has been constructed to co-express the PPRV matrix (M), haemagglutinin (H) and nucleocapsid (N) proteins in insect cells, causing budding of PPR virus-like particles (VLPs) from insect cell membranes by viewing of ultrathin section with a transmission electron microscope. In this follow-up study, these PPR VLPs were purified by sucrose density gradient centrifugation for immunizing mice twice. Three weeks post-primary immunization and 2 weeks post-secondary immunization, all serum samples were obtained and subsequently subjected to indirect ELISA detection on complete virus-specific antibodies. In addition, all serum samples, which were collected 2 weeks post-secondary immunization, were used for virus neutralization test on PPRV neutralizing antibodies. The results showed that the purified PPR VLPs induced both types of antibodies mentioned above in mice, indicating a given potential of VLP-based vaccine candidate against PPR. PMID:25486084

  5. Neuroimaging of the Functional and Structural Networks Underlying Visuospatial vs. Linguistic Reasoning in High-Functioning Autism

    ERIC Educational Resources Information Center

    Sahyoun, Cherif P.; Belliveau, John W.; Soulieres, Isabelle; Schwartz, Shira; Mody, Maria

    2010-01-01

    High-functioning individuals with autism have been found to favor visuospatial processing in the face of typically poor language abilities. We aimed to examine the neurobiological basis of this difference using functional magnetic resonance imaging and diffusion tensor imaging. We compared 12 children with high functioning autism (HFA) to 12 age-…

  6. Highly adaptive tests for group differences in brain functional connectivity.

    PubMed

    Kim, Junghi; Pan, Wei

    2015-01-01

    Resting-state functional magnetic resonance imaging (rs-fMRI) and other technologies have been offering evidence and insights showing that altered brain functional networks are associated with neurological illnesses such as Alzheimer's disease. Exploring brain networks of clinical populations compared to those of controls would be a key inquiry to reveal underlying neurological processes related to such illnesses. For such a purpose, group-level inference is a necessary first step in order to establish whether there are any genuinely disrupted brain subnetworks. Such an analysis is also challenging due to the high dimensionality of the parameters in a network model and high noise levels in neuroimaging data. We are still in the early stage of method development as highlighted by Varoquaux and Craddock (2013) that "there is currently no unique solution, but a spectrum of related methods and analytical strategies" to learn and compare brain connectivity. In practice the important issue of how to choose several critical parameters in estimating a network, such as what association measure to use and what is the sparsity of the estimated network, has not been carefully addressed, largely because the answers are unknown yet. For example, even though the choice of tuning parameters in model estimation has been extensively discussed in the literature, as to be shown here, an optimal choice of a parameter for network estimation may not be optimal in the current context of hypothesis testing. Arbitrarily choosing or mis-specifying such parameters may lead to extremely low-powered tests. Here we develop highly adaptive tests to detect group differences in brain connectivity while accounting for unknown optimal choices of some tuning parameters. The proposed tests combine statistical evidence against a null hypothesis from multiple sources across a range of plausible tuning parameter values reflecting uncertainty with the unknown truth. These highly adaptive tests are not only

  7. Highly adaptive tests for group differences in brain functional connectivity.

    PubMed

    Kim, Junghi; Pan, Wei

    2015-01-01

    Resting-state functional magnetic resonance imaging (rs-fMRI) and other technologies have been offering evidence and insights showing that altered brain functional networks are associated with neurological illnesses such as Alzheimer's disease. Exploring brain networks of clinical populations compared to those of controls would be a key inquiry to reveal underlying neurological processes related to such illnesses. For such a purpose, group-level inference is a necessary first step in order to establish whether there are any genuinely disrupted brain subnetworks. Such an analysis is also challenging due to the high dimensionality of the parameters in a network model and high noise levels in neuroimaging data. We are still in the early stage of method development as highlighted by Varoquaux and Craddock (2013) that "there is currently no unique solution, but a spectrum of related methods and analytical strategies" to learn and compare brain connectivity. In practice the important issue of how to choose several critical parameters in estimating a network, such as what association measure to use and what is the sparsity of the estimated network, has not been carefully addressed, largely because the answers are unknown yet. For example, even though the choice of tuning parameters in model estimation has been extensively discussed in the literature, as to be shown here, an optimal choice of a parameter for network estimation may not be optimal in the current context of hypothesis testing. Arbitrarily choosing or mis-specifying such parameters may lead to extremely low-powered tests. Here we develop highly adaptive tests to detect group differences in brain connectivity while accounting for unknown optimal choices of some tuning parameters. The proposed tests combine statistical evidence against a null hypothesis from multiple sources across a range of plausible tuning parameter values reflecting uncertainty with the unknown truth. These highly adaptive tests are not only

  8. Numerical methods for high-dimensional probability density function equations

    NASA Astrophysics Data System (ADS)

    Cho, H.; Venturi, D.; Karniadakis, G. E.

    2016-01-01

    In this paper we address the problem of computing the numerical solution to kinetic partial differential equations involving many phase variables. These types of equations arise naturally in many different areas of mathematical physics, e.g., in particle systems (Liouville and Boltzmann equations), stochastic dynamical systems (Fokker-Planck and Dostupov-Pugachev equations), random wave theory (Malakhov-Saichev equations) and coarse-grained stochastic systems (Mori-Zwanzig equations). We propose three different classes of new algorithms addressing high-dimensionality: The first one is based on separated series expansions resulting in a sequence of low-dimensional problems that can be solved recursively and in parallel by using alternating direction methods. The second class of algorithms relies on truncation of interaction in low-orders that resembles the Bogoliubov-Born-Green-Kirkwood-Yvon (BBGKY) framework of kinetic gas theory and it yields a hierarchy of coupled probability density function equations. The third class of algorithms is based on high-dimensional model representations, e.g., the ANOVA method and probabilistic collocation methods. A common feature of all these approaches is that they are reducible to the problem of computing the solution to high-dimensional equations via a sequence of low-dimensional problems. The effectiveness of the new algorithms is demonstrated in numerical examples involving nonlinear stochastic dynamical systems and partial differential equations, with up to 120 variables.

  9. Optimizing high performance computing workflow for protein functional annotation.

    PubMed

    Stanberry, Larissa; Rekepalli, Bhanu; Liu, Yuan; Giblock, Paul; Higdon, Roger; Montague, Elizabeth; Broomall, William; Kolker, Natali; Kolker, Eugene

    2014-09-10

    Functional annotation of newly sequenced genomes is one of the major challenges in modern biology. With modern sequencing technologies, the protein sequence universe is rapidly expanding. Newly sequenced bacterial genomes alone contain over 7.5 million proteins. The rate of data generation has far surpassed that of protein annotation. The volume of protein data makes manual curation infeasible, whereas a high compute cost limits the utility of existing automated approaches. In this work, we present an improved and optmized automated workflow to enable large-scale protein annotation. The workflow uses high performance computing architectures and a low complexity classification algorithm to assign proteins into existing clusters of orthologous groups of proteins. On the basis of the Position-Specific Iterative Basic Local Alignment Search Tool the algorithm ensures at least 80% specificity and sensitivity of the resulting classifications. The workflow utilizes highly scalable parallel applications for classification and sequence alignment. Using Extreme Science and Engineering Discovery Environment supercomputers, the workflow processed 1,200,000 newly sequenced bacterial proteins. With the rapid expansion of the protein sequence universe, the proposed workflow will enable scientists to annotate big genome data. PMID:25313296

  10. NCBI GEO: archive for high-throughput functional genomic data.

    PubMed

    Barrett, Tanya; Troup, Dennis B; Wilhite, Stephen E; Ledoux, Pierre; Rudnev, Dmitry; Evangelista, Carlos; Kim, Irene F; Soboleva, Alexandra; Tomashevsky, Maxim; Marshall, Kimberly A; Phillippy, Katherine H; Sherman, Patti M; Muertter, Rolf N; Edgar, Ron

    2009-01-01

    The Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI) is the largest public repository for high-throughput gene expression data. Additionally, GEO hosts other categories of high-throughput functional genomic data, including those that examine genome copy number variations, chromatin structure, methylation status and transcription factor binding. These data are generated by the research community using high-throughput technologies like microarrays and, more recently, next-generation sequencing. The database has a flexible infrastructure that can capture fully annotated raw and processed data, enabling compliance with major community-derived scientific reporting standards such as 'Minimum Information About a Microarray Experiment' (MIAME). In addition to serving as a centralized data storage hub, GEO offers many tools and features that allow users to effectively explore, analyze and download expression data from both gene-centric and experiment-centric perspectives. This article summarizes the GEO repository structure, content and operating procedures, as well as recently introduced data mining features. GEO is freely accessible at http://www.ncbi.nlm.nih.gov/geo/.

  11. Optimizing high performance computing workflow for protein functional annotation.

    PubMed

    Stanberry, Larissa; Rekepalli, Bhanu; Liu, Yuan; Giblock, Paul; Higdon, Roger; Montague, Elizabeth; Broomall, William; Kolker, Natali; Kolker, Eugene

    2014-09-10

    Functional annotation of newly sequenced genomes is one of the major challenges in modern biology. With modern sequencing technologies, the protein sequence universe is rapidly expanding. Newly sequenced bacterial genomes alone contain over 7.5 million proteins. The rate of data generation has far surpassed that of protein annotation. The volume of protein data makes manual curation infeasible, whereas a high compute cost limits the utility of existing automated approaches. In this work, we present an improved and optmized automated workflow to enable large-scale protein annotation. The workflow uses high performance computing architectures and a low complexity classification algorithm to assign proteins into existing clusters of orthologous groups of proteins. On the basis of the Position-Specific Iterative Basic Local Alignment Search Tool the algorithm ensures at least 80% specificity and sensitivity of the resulting classifications. The workflow utilizes highly scalable parallel applications for classification and sequence alignment. Using Extreme Science and Engineering Discovery Environment supercomputers, the workflow processed 1,200,000 newly sequenced bacterial proteins. With the rapid expansion of the protein sequence universe, the proposed workflow will enable scientists to annotate big genome data.

  12. Endothelial function in normotensive and high-normal hypertensive subjects.

    PubMed

    Plavnik, F L; Ajzen, S A; Christofalo, D M J; Barbosa, C S P; Kohlmann, O

    2007-06-01

    To evaluate the impact of a mild increment in blood pressure level on endothelial function, we evaluated 61 healthy volunteers (24 women, 37 men, and aged 35-50 years). All subjects underwent a blood chemistry panel to exclude any metabolic abnormalities and were submitted to a Doppler ultrasound of the brachial artery to assess endothelial function. We assessed the endothelial response to reactive hyperaemia and exogenous nitric oxide administration considering an increase in systolic blood pressure (SBP) at each 10-mm Hg interval. Our study population was divided as follows: SBP <115 mm Hg (SG1, n=13), SBP > or =115 mm Hg and <125 mm Hg (SG2, n=20), SBP > or = 125 mm Hg and <135 mm Hg (SG3, n=13) and SBP > or = 135 mm Hg and < 140 mm Hg (SG4, n=15). We found a significant difference in flow-mediated dilation among SG2, SG3 and SG4, 16.2+/-5.6, 13.4+/-5.2 and 11.5+/-3.6%, P<0.05, respectively). After nitrate administration, we observed a nonsignificant decrease in brachial artery dilation among groups, P=0.217. Our data showed in a healthy normotensive population, without any risk factor for atherosclerotic disease that small increases in SBP but not in diastolic blood pressure may impair endothelial function even in subjects considered as high-normal, meaning that this population deserves more attention than usually ascribed to intervene and prevent complications, as endothelial dysfunction may represent an early change in those who develop hypertension later in life. PMID:17287837

  13. Highly efficient electroosmotic flow through functionalized carbon nanotube membranes

    NASA Astrophysics Data System (ADS)

    Wu, Ji; Gerstandt, Karen; Majumder, Mainak; Zhan, Xin; Hinds, Bruce J.

    2011-08-01

    Carbon nanotube membranes with inner diameter ranging from 1.5-7 nm were examined for enhanced electroosmotic flow. After functionalization via electrochemical diazonium grafting and carbodiimide coupling reaction, it was found that neutral caffeine molecules can be efficiently pumped via electroosmosis. An electroosmotic velocity as high as 0.16 cm s-1 V-1 has been observed. Power efficiencies were 25-110 fold improved compared to related nanoporous materials, which has important applications in chemical separations and compact medical devices. Nearly ideal electroosmotic flow was seen in the case where the mobile cation diameter nearly matched the inner diameter of the single-walled carbon nanotube resulting in a condition of using one ion is to pump one neutral molecule at equivalent concentrations.

  14. Self-monitoring of gaze in high functioning autism.

    PubMed

    Grynszpan, Ouriel; Nadel, Jacqueline; Martin, Jean-Claude; Simonin, Jérôme; Bailleul, Pauline; Wang, Yun; Gepner, Daniel; Le Barillier, Florence; Constant, Jacques

    2012-08-01

    Atypical visual behaviour has been recently proposed to account for much of social misunderstanding in autism. Using an eye-tracking system and a gaze-contingent lens display, the present study explores self-monitoring of eye motion in two conditions: free visual exploration and guided exploration via blurring the visual field except for the focal area of vision. During these conditions, thirteen students with High Functioning Autism Spectrum Disorders (HFASD) and fourteen typical individuals were presented naturalistic and interactive social stimuli using virtual reality. Fixation data showed a weaker modulation of eye movements according to the conditions in the HFASD group, thus suggesting impairments in self-monitoring of gaze. Moreover, the gaze-contingent lens induced a visual behaviour whereby social understanding scores were correlated with the time spent gazing at faces. The device could be useful for treating gaze monitoring deficiencies in HFASD. PMID:22102292

  15. Emotion regulation in Asperger's syndrome and high-functioning autism.

    PubMed

    Samson, Andrea C; Huber, Oswald; Gross, James J

    2012-08-01

    It is generally thought that individuals with Asperger's syndrome and high-functioning autism (AS/HFA) have deficits in theory of mind. These deficits have been previously linked to problems with social cognition. However, we reasoned that AS/HFA individuals' Theory of Mind deficits also might lead to problems with emotion regulation. To assess emotional functioning in AS/HFA, 27 AS/HFA adults (16 women) and 27 age-, gender-, and education-matched typically developing (TD) participants completed a battery of measures of emotion experience, labeling, and regulation. With respect to emotion experience, individuals with AS/HFA reported higher levels of negative emotions, but similar levels of positive emotions, compared with TD individuals. With respect to emotion labeling, individuals with AS/HFA had greater difficulties identifying and describing their emotions, with approximately two-thirds exceeding the cutoff for alexithymia. With respect to emotion regulation, individuals with AS/HFA used reappraisal less frequently than TD individuals and reported lower levels of reappraisal self-efficacy. Although AS/HFA individuals used suppression more frequently than TD individuals, no difference in suppression self-efficacy was found. It is important to note that these differences in emotion regulation were evident even when controlling for emotion experience and labeling. Implications of these deficits are discussed, and future research directions are proposed.

  16. Development of an artificial-antigen-presenting-cell-based assay for the detection of low-frequency virus-specific CD8(+) T cells in whole blood, with application for measles virus.

    PubMed

    Ndhlovu, Zaza M; Angenendt, Monika; Heckel, Diana; Schneck, Jonathan P; Griffin, Diane E; Oelke, Mathias

    2009-07-01

    Evaluation of the immune responses induced by childhood vaccines requires measurement of T-cell, as well as antibody, responses. However, cellular immune responses are often not analyzed because of technical hurdles and the volume of blood required. Therefore, a sensitive and specific assay for antigen-specific T cells that utilizes a small volume of blood would facilitate new vaccine evaluation. We developed a novel assay for quantifying virus-specific CD8(+) T cells that combines the use of HLA-A2 immunoglobulin-based artificial antigen-presenting cells (aAPCs) for stimulation of antigen-specific CD8(+) T cells in whole blood with quantitative real-time reverse transcription-PCR (qRT-PCR) to detect gamma interferon (IFN-gamma) mRNA. This assay was optimized using a well-established cytomegalovirus (CMV) CD8(+) T-cell system. The aAPC-qRT-PCR assay had comparable sensitivity to intracellular cytokine staining (ICS) in detecting CMV-specific CD8(+) T cells with a detection limit of less than 0.004%. The assay was applied to the detection of low-frequency measles virus (MV)-specific CD8(+) T cells by stimulating blood from five MV-immune HLA-A*0201 donors with four different MV-specific peptides (MV peptide aAPCs). Stimulation with three of the MV peptide aAPCs resulted in significant increases in IFN-gamma mRNA ranging from 3.3- to 13.5-fold. Our results show that the aAPC-qRT-PCR assay is highly sensitive and specific and can be standardized for screening MV-specific CD8(+) T cells in vaccine trials. The technology should be transferable to analysis of CD8(+) T-cell responses to other antigens. PMID:19494085

  17. Expansion and diversification of virus-specific T cells following immunization of human immunodeficiency virus type 1 (HIV-1)-infected individuals with a recombinant modified vaccinia virus Ankara/HIV-1 Gag vaccine.

    PubMed

    Dorrell, Lucy; Yang, Hongbing; Ondondo, Beatrice; Dong, Tao; di Gleria, Kati; Suttill, Annie; Conlon, Christopher; Brown, Denise; Williams, Patricia; Bowness, Paul; Goonetilleke, Nilu; Rostron, Tim; Rowland-Jones, Sarah; Hanke, Tomás; McMichael, Andrew

    2006-05-01

    Affordable therapeutic strategies that induce sustained control of human immunodeficiency virus type 1 (HIV-1) replication and are tailored to the developing world are urgently needed. Since CD8(+) and CD4(+) T cells are crucial to HIV-1 control, stimulation of potent cellular responses by therapeutic vaccination might be exploited to reduce antiretroviral drug exposure. However, therapeutic vaccines tested to date have shown modest immunogenicity. In this study, we performed a comprehensive analysis of the changes in virus-specific CD8(+) and CD4(+) T-cell responses occurring after vaccination of 16 HIV-1-infected individuals with a recombinant modified vaccinia virus Ankara-vectored vaccine expressing the consensus HIV-1 clade A Gag p24/p17 sequences and multiple CD8(+) T-cell epitopes during highly active antiretroviral therapy. We observed significant amplification and broadening of CD8(+) and CD4(+) gamma interferon responses to vaccine-derived epitopes in the vaccinees, without rebound viremia, but not in two unvaccinated controls followed simultaneously. Vaccine-driven CD8(+) T-cell expansions were also detected by tetramer reactivity, predominantly in the CD45RA(-) CCR7(+) or CD45RA(-) CCR7(-) compartments, and persisted for at least 1 year. Expansion was associated with a marked but transient up-regulation of CD38 and perforin within days of vaccination. Gag-specific CD8(+) and CD4(+) T-cell proliferation also increased postvaccination. These data suggest that immunization with MVA.HIVA is a feasible strategy to enhance potentially protective T-cell responses in individuals with chronic HIV-1 infection.

  18. Alternative effector-function profiling identifies broad HIV-specific T-cell responses in highly HIV-exposed individuals who remain uninfected.

    PubMed

    Ruiz-Riol, Marta; Llano, Anuska; Ibarrondo, Javier; Zamarreño, Jennifer; Yusim, Karina; Bach, Vanessa; Mothe, Beatriz; Perez-Alvarez, Susana; Fernandez, Marco A; Requena, Gerard; Meulbroek, Michael; Pujol, Ferran; Leon, Agathe; Cobarsi, Patricia; Korber, Bette T; Clotet, Bonaventura; Ganoza, Carmela; Sanchez, Jorge; Coll, Josep; Brander, Christian

    2015-03-15

    The characterization of host immune responses to human immunodeficiency virus (HIV) in HIV controllers and individuals with high exposure but seronegativity to HIV (HESN) is needed to guide the development of effective preventive and therapeutic vaccine candidates. However, several technical hurdles severely limit the definition of an effective virus-specific T-cell response. By using a toggle-peptide approach, which takes HIV sequence diversity into account, and a novel, boosted cytokine staining/flow cytometry strategy, we here describe new patterns of T-cell responses to HIV that would be missed by standard assays. Importantly, this approach also allows detection of broad and strong virus-specific T-cell responses in HESN individuals that are characterized by a T-helper type 1 cytokine-like effector profile and produce cytokines that have been associated with potential control of HIV infection, including interleukin 10, interleukin 13, and interleukin 22. These results establish a novel approach to improve the current understanding of HIV-specific T-cell immunity and identify cellular immune responses and individual cytokines as potential markers of relative HIV resistance. As such, the findings also help develop similar strategies for more-comprehensive assessments of host immune responses to other human infections and immune-mediated disorders. PMID:25249264

  19. Alternative Effector-Function Profiling Identifies Broad HIV-Specific T-Cell Responses in Highly HIV-Exposed Individuals Who Remain Uninfected

    PubMed Central

    Ruiz-Riol, Marta; Llano, Anuska; Ibarrondo, Javier; Zamarreño, Jennifer; Yusim, Karina; Bach, Vanessa; Mothe, Beatriz; Perez-Alvarez, Susana; Fernandez, Marco A.; Requena, Gerard; Meulbroek, Michael; Pujol, Ferran; Leon, Agathe; Cobarsi, Patricia; Korber, Bette T.; Clotet, Bonaventura; Ganoza, Carmela; Sanchez, Jorge; Coll, Josep; Brander, Christian

    2015-01-01

    The characterization of host immune responses to human immunodeficiency virus (HIV) in HIV controllers and individuals with high exposure but seronegativity to HIV (HESN) is needed to guide the development of effective preventive and therapeutic vaccine candidates. However, several technical hurdles severely limit the definition of an effective virus-specific T-cell response. By using a toggle-peptide approach, which takes HIV sequence diversity into account, and a novel, boosted cytokine staining/flow cytometry strategy, we here describe new patterns of T-cell responses to HIV that would be missed by standard assays. Importantly, this approach also allows detection of broad and strong virus-specific T-cell responses in HESN individuals that are characterized by a T-helper type 1 cytokine–like effector profile and produce cytokines that have been associated with potential control of HIV infection, including interleukin 10, interleukin 13, and interleukin 22. These results establish a novel approach to improve the current understanding of HIV-specific T-cell immunity and identify cellular immune responses and individual cytokines as potential markers of relative HIV resistance. As such, the findings also help develop similar strategies for more-comprehensive assessments of host immune responses to other human infections and immune-mediated disorders. PMID:25249264

  20. Alternative effector-function profiling identifies broad HIV-specific T-cell responses in highly HIV-exposed individuals who remain uninfected.

    PubMed

    Ruiz-Riol, Marta; Llano, Anuska; Ibarrondo, Javier; Zamarreño, Jennifer; Yusim, Karina; Bach, Vanessa; Mothe, Beatriz; Perez-Alvarez, Susana; Fernandez, Marco A; Requena, Gerard; Meulbroek, Michael; Pujol, Ferran; Leon, Agathe; Cobarsi, Patricia; Korber, Bette T; Clotet, Bonaventura; Ganoza, Carmela; Sanchez, Jorge; Coll, Josep; Brander, Christian

    2015-03-15

    The characterization of host immune responses to human immunodeficiency virus (HIV) in HIV controllers and individuals with high exposure but seronegativity to HIV (HESN) is needed to guide the development of effective preventive and therapeutic vaccine candidates. However, several technical hurdles severely limit the definition of an effective virus-specific T-cell response. By using a toggle-peptide approach, which takes HIV sequence diversity into account, and a novel, boosted cytokine staining/flow cytometry strategy, we here describe new patterns of T-cell responses to HIV that would be missed by standard assays. Importantly, this approach also allows detection of broad and strong virus-specific T-cell responses in HESN individuals that are characterized by a T-helper type 1 cytokine-like effector profile and produce cytokines that have been associated with potential control of HIV infection, including interleukin 10, interleukin 13, and interleukin 22. These results establish a novel approach to improve the current understanding of HIV-specific T-cell immunity and identify cellular immune responses and individual cytokines as potential markers of relative HIV resistance. As such, the findings also help develop similar strategies for more-comprehensive assessments of host immune responses to other human infections and immune-mediated disorders.

  1. T helper cells in cytotoxic T lymphocyte development: role of L3T4(+)-dependent and -independent T helper cell pathways in virus-specific and alloreactive cytotoxic T lymphocyte responses.

    PubMed

    Ciavarra, R P

    1990-02-01

    I have compared the requirements for T helper (Th) cell function during the generation of virus-specific and alloreactive cytotoxic thymus (T)-derived lymphocyte (CTL) responses. Restimulation of vesicular stomatitis virus (VSV)-immune T cells (VSV memory CTLs) with VSV-infected stimulators resulted in the generation of class I-restricted, VSV-specific CTLs. Progression of VSV memory CTLs (Lyt-1-2+) into VSV-specific CTLs required inductive signals derived from VSV-induced, Lyt-1+2- Th cells because: (i) cultures depleted by negative selection of Lyt-1+ T cells failed to generate CTLs; (ii) titration of VSV memory CTLs into a limiting dilution (LD) microculture system depleted of Th cells generated curves which were not consistent with a single limiting cell type; (iii) LD analysis of VSV memory CTLs did produce single-hit curves in the presence of Lyt-1+2- T cells sensitized against VSV; and (iv) monoclonal anti-L3T4 antibody completely abrogated CTL generation against VSV. Similar results were also obtained with Sendai virus (SV), a member of the paramyxovirus family. The notion that a class II-restricted, L3T4+ Th cell plays an obligatory role in the generation of CTLs against these viruses is also supported by the observation that purified T cell lymphoblasts (class II antigen negative) failed to function as antigen-presenting cells for CTL responses against VSV and SV. T cell lymphoblasts were efficiently lysed by class I-restricted, anti-VSV and -SV CTLs, indicating that activated T cells expressed the appropriate viral peptides for CTL recognition. Furthermore, heterogeneity in the VSV-induced Th cell population was detected by LD analysis, suggesting that at least two types of Th cells were required for the generation of an anti-VSV CTL response. VSV-induced Th cell function could not simply be replaced by exogenous IL-2 because this lymphokine induced cytotoxic cells that had the characteristics of lymphokine-activated killer (LAK) cells and not anti

  2. Frequencies of Virus-Specific CD4+ and CD8+ T Lymphocytes Secreting Gamma Interferon after Acute Natural Rotavirus Infection in Children and Adults

    PubMed Central

    Jaimes, María C.; Rojas, Olga Lucía; González, Ana María; Cajiao, Isabela; Charpilienne, Annie; Pothier, Pierre; Kohli, Evelyne; Greenberg, Harry B.; Franco, Manuel A.; Angel, Juana

    2002-01-01

    Human rotavirus-specific CD4+ and CD8+ T-cell responses in peripheral blood lymphocytes were studied using a flow cytometric assay that detects the intracellular accumulation of cytokines after short-term in vitro antigen stimulation. The frequencies of virus-specific T cells that secrete gamma interferon and interleukin-13 (IL-13) were determined in adults and children during the acute or convalescent phase of rotavirus-induced diarrhea, in asymptomatically infected adults and laboratory workers who worked with human stool samples containing rotavirus, and in healthy adults. Significantly higher frequencies of rotavirus-specific interferon gamma-secreting CD8+ and CD4+ T cells, but not IL-13-secreting T cells, were detected in symptomatically infected adults and exposed laboratory workers than in healthy adults and children with acute rotavirus diarrhea. The levels of rotavirus-specific T cells returned to levels found in healthy adults by 32 days after the onset of rotavirus diarrhea in most adult subjects. Children with rotavirus diarrhea had undetectable or very low levels of CD4+ and CD8+ T cells that secrete gamma interferon. Adult cytomegalovirus-seropositive individuals had frequencies of cytomegalovirus-specific T cells that secrete gamma interferon that were approximately 20 times the level of rotavirus-specific T cells. This result suggests that rotavirus is a relatively poor inducer of circulating memory T cells that secrete gamma interferon. The frequencies of gamma interferon-secreting CD4+ and CD8+ T cells and the frequencies of IL-13-secreting CD4+ T cells responding to the T-cell superantigen staphylococcal enterotoxin B (SEB) were lower in children than in adults. In both adults and children, the frequencies of CD4+ cells secreting gamma interferon in response to SEB were higher than the frequencies of cells secreting IL-13. PMID:11967291

  3. K562-Derived Whole-Cell Vaccine Enhances Antitumor Responses of CAR-Redirected Virus-Specific Cytotoxic-T Lymphocytes in vivo

    PubMed Central

    Caruana, Ignazio; Weber, Gerrit; Ballard, Brandon Corde’; Wood, Michael Scott; Savoldo, Barbara; Dotti, Gianpietro

    2015-01-01

    Purpose Adoptive transfer of Epstein Barr Virus (EBV)- and Cytomegalovirus (CMV)-specific cytotoxic T cells (CTLs) genetically modified to express a Chimeric Antigen Receptor (CAR) induces objective tumor responses in clinical trials. In vivo expansion and persistence of these cells is crucial to achieve sustained clinical responses. We aimed to develop an off-the-shelf whole-cell vaccine to boost CAR-redirected virus-specific CTLs in vivo after adoptive transfer. As proof of principle, we validated our vaccine approach by boosting CMV-specific CTLs (CMV-CTLs) engineered with a CAR that targets the GD2 antigen. Experimental Design We generated the whole-cell vaccine by engineering the K562 cell line to express the CMV-pp65 protein and the immune stimulatory molecules CD40L and OX40L. Single-cell-derived clones were used to stimulate CMV-CTLs in vitro and in vivo in a xenograft model. We also assessed whether the in vivo boosting of CAR-redirected CMV-CTLs with the whole-cell vaccine enhances the antitumor responses. Finally, we addressed potential safety concerns by including the inducible safety switch caspase9 (iC9) gene in the whole-cell vaccine. Results We found that K562 expressing CMV-pp65, CD40L and OX40L effectively stimulates CMV-specific responses in vitro by promoting antigen cross-presentation to professional antigen-presenting cells (APCs). Vaccination also enhances antitumor effects of CAR-redirected CMV-CTLs in xenograft tumor models. Activation of the iC9 gene successfully induces growth arrest of engineered K562 implanted in mice. Conclusions Vaccination with a whole-cell vaccine obtained from K562 engineered to express CMV-pp65, CD40L, OX40L and iC9 can safely enhance the antitumor effects of CAR-redirected CMV-CTLs. PMID:25691731

  4. Lift outs: how to acquire a high-functioning team.

    PubMed

    Groysberg, Boris; Abrahams, Robin

    2006-12-01

    More and more, expanding companies are hiring high-functioning groups of people who have been working together effectively within one company and can rapidly come up to speed in a new environment. These lifted-out teams don't need to get acquainted with one another or to establish shared values, mutual accountability, or group norms; their long-standing relationships and trust help them make an impact very quickly. Of course, the process is not without risks: A failed lift out can lead to loss of money, opportunity, credibility, and even native talent. Boris Groysberg and Robin Abrahams studied more than 40 high-profile moves and interviewed team leaders in multiple industries and countries to examine the risks and opportunities that lift outs present. They concluded that, regardless of industry, nationality, or size of the team, a successful lift out unfolds over four consecutive, interdependent stages that must be meticulously managed. In the courtship stage, the hiring company and the leader of the targeted team determine whether the proposed move is, in fact, a good idea, and then define their business goals and discuss strategies. At the same time, the team leader discusses the potential move with the other members of his or her group to assess their level of interest and prepare them for the change. The second stage involves the integration of the team leader with the new company's top leadership. This part of the process ensures the team's access to senior executives-the most important factor in a lift out's success. Operational integration is the focus of the third stage. Ideally, teams will start out working with the same or similar clients, vendors, and industry standards. The fourth stage entails full cultural integration. To succeed, the lifted-out team members must be willing to re-earn credibility by proving their value and winning their new colleagues' trust.

  5. Lift outs: how to acquire a high-functioning team.

    PubMed

    Groysberg, Boris; Abrahams, Robin

    2006-12-01

    More and more, expanding companies are hiring high-functioning groups of people who have been working together effectively within one company and can rapidly come up to speed in a new environment. These lifted-out teams don't need to get acquainted with one another or to establish shared values, mutual accountability, or group norms; their long-standing relationships and trust help them make an impact very quickly. Of course, the process is not without risks: A failed lift out can lead to loss of money, opportunity, credibility, and even native talent. Boris Groysberg and Robin Abrahams studied more than 40 high-profile moves and interviewed team leaders in multiple industries and countries to examine the risks and opportunities that lift outs present. They concluded that, regardless of industry, nationality, or size of the team, a successful lift out unfolds over four consecutive, interdependent stages that must be meticulously managed. In the courtship stage, the hiring company and the leader of the targeted team determine whether the proposed move is, in fact, a good idea, and then define their business goals and discuss strategies. At the same time, the team leader discusses the potential move with the other members of his or her group to assess their level of interest and prepare them for the change. The second stage involves the integration of the team leader with the new company's top leadership. This part of the process ensures the team's access to senior executives-the most important factor in a lift out's success. Operational integration is the focus of the third stage. Ideally, teams will start out working with the same or similar clients, vendors, and industry standards. The fourth stage entails full cultural integration. To succeed, the lifted-out team members must be willing to re-earn credibility by proving their value and winning their new colleagues' trust. PMID:17183798

  6. Comparison of social cognitive functioning in schizophrenia and high functioning autism: more convergence than divergence

    PubMed Central

    Couture, S. M.; Penn, D. L.; Losh, M.; Adolphs, R.; Hurley, R.; Piven, J.

    2009-01-01

    Background Individuals with schizophrenia and individuals with high-functioning autism (HFA) seem to share some social, behavioral and biological features. Although marked impairments in social cognition have been documented in both groups, little empirical work has compared the social cognitive functioning of these two clinical groups. Method Forty-four individuals with schizophrenia, 36 with HFA and 41 non-clinical controls completed a battery of social cognitive measures that have been linked previously to specific brain regions. Results The results indicate that the individuals with schizophrenia and HFA were both impaired on a variety of social cognitive tasks relative to the non-clinical controls, but did not differ from one another. When individuals with schizophrenia were divided into negative symptom and paranoid subgroups, exploratory analyses revealed that individuals with HFA may be more similar, in terms of the pattern of social cognition impairments, to the negative symptom group than to the paranoia group. Conclusions Our findings provide further support for similarities in social cognition deficits between HFA and schizophrenia, which have a variety of implications for future work on gene–brain–behavior relationships. PMID:19671209

  7. Design of highly stable functional GroEL minichaperones.

    PubMed Central

    Wang, Q.; Buckle, A. M.; Foster, N. W.; Johnson, C. M.; Fersht, A. R.

    1999-01-01

    GroEL minichaperones have potential in the biotechnology industry for the refolding of recombinant proteins. With the aim of enhancing and widening their use, we have created two highly stable functional variants of minichaperone GroEL(193-345). A sequence alignment of 130 members of the chaperonin 60 (Cpn60) family was used to design 37 single mutations. Two small-to-large mutations, A223T, A223V and one similar-size mutation, M233L, all located in the hydrophobic core were found to stabilize the protein by more than 1 kcal mol(-1) each. Six stabilizing mutations were combined, yielding two multiple mutants that were 6.99 and 6.15 kcal mol(-1) more stable than wild-type protein. Even though some of the substituted residue pairs are close to each other in the protein structure, the energetic effects of mutation are approximately additive. In particular, the stabilizing substitution A223T is unexpected and would have been missed by purely structural analysis. In the light of previously reported successes employing similar methods with several other proteins, our results show that a homology based approach is a simple and efficient method of increasing the stability of a protein. PMID:10548065

  8. Screening for high-performance piezoelectrics using high-throughput density functional theory

    NASA Astrophysics Data System (ADS)

    Armiento, Rickard; Kozinsky, Boris; Fornari, Marco; Ceder, Gerbrand

    2011-07-01

    We present a large-scale density functional theory (DFT) investigation of the ABO3 chemical space in the perovskite crystal structure, with the aim of identifying those that are relevant for forming piezoelectric materials. Screening criteria on the DFT results are used to select 49 compositions, which can be seen as the fundamental building blocks from which to create alloys with potentially good piezoelectric performance. This screening finds all the alloy end points used in three well-known high-performance piezoelectrics. The energy differences between different structural distortions, deformation, coupling between the displacement of the A and B sites, spontaneous polarization, Born effective charges, and stability is analyzed in each composition. We discuss the features that cause the high piezoelectric performance of the well-known piezoelectric lead zirconate titanate (PZT), and investigate to what extent these features occur in other compositions. We demonstrate how our results can be useful in the design of isovalent alloys with high piezoelectric performance.

  9. Do high functioning persons with autism present superior spatial abilities?

    PubMed

    Caron, M-J; Mottron, L; Rainville, C; Chouinard, S

    2004-01-01

    This series of experiments was aimed at assessing spatial abilities in high functioning individuals with autism (HFA), using a human-size labyrinth. In the context of recent findings that the performance of individuals with HFA was superior to typically developing individuals in several non-social cognitive operations, it was expected that the HFA group would outperform a typically developing comparison group matched on full-scale IQ. Results showed that individuals with autism performed all spatial tasks at a level at least equivalent to the typically developing comparison group. No differences between groups were found in route and survey tasks. Superior performance for individuals with HFA was found in tasks involving maps, in the form of superior accuracy in graphic cued recall of a path, and shorter learning times in a map learning task. We propose that a superior ability to detect [Human Perception and Performance 27 (3) (2001) 719], match [Journal of Child Psychology and Psychiatry 34 (1993) 1351] and reproduce [Journal of Child Psychology and Psychiatry 40 (5) (1999) 743] simple visual elements yields superior performance in tasks relying on the detection and graphic reproduction of the visual elements composing a map. Enhanced discrimination, detection, and memory for visually simple patterns in autism may account for the superior performance of persons with autism on visuo-spatial tasks that heavily involve pattern recognition, either in the form of recognizing and memorizing landmarks or in detecting the similarity between map and landscape features. At a neuro-anatomical level, these findings suggest an intact dorso-lateral pathway, and enhanced performance in non social tasks relying on the infero-temporal pathway. PMID:14728920

  10. High-temperature asymptotics of supersymmetric partition functions

    NASA Astrophysics Data System (ADS)

    Ardehali, Arash Arabi

    2016-07-01

    We study the supersymmetric partition function of 4d supersymmetric gauge theories with a U(1) R-symmetry on Euclidean S 3 × S β 1 , with S 3 the unit-radius squashed three-sphere, and β the circumference of the circle. For superconformal theories, this partition function coincides (up to a Casimir energy factor) with the 4d superconformal index.

  11. Peer Mentoring Intervention Teaching Adaptive Skills to Individuals with High Functioning Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    McCarville, Edel

    2013-01-01

    Individuals with High Functioning ASD's (HFA) often have difficulties with adaptive functioning. Due to these deficits in independent functioning, many individuals with High-Functioning ASD's have limitations in adulthood. This study investigated if individuals with HFA would have a greater likelihood of learning independent adaptive daily living…

  12. High Precision Prediction of Functional Sites in Protein Structures

    PubMed Central

    Buturovic, Ljubomir; Wong, Mike; Tang, Grace W.; Altman, Russ B.; Petkovic, Dragutin

    2014-01-01

    We address the problem of assigning biological function to solved protein structures. Computational tools play a critical role in identifying potential active sites and informing screening decisions for further lab analysis. A critical parameter in the practical application of computational methods is the precision, or positive predictive value. Precision measures the level of confidence the user should have in a particular computed functional assignment. Low precision annotations lead to futile laboratory investigations and waste scarce research resources. In this paper we describe an advanced version of the protein function annotation system FEATURE, which achieved 99% precision and average recall of 95% across 20 representative functional sites. The system uses a Support Vector Machine classifier operating on the microenvironment of physicochemical features around an amino acid. We also compared performance of our method with state-of-the-art sequence-level annotator Pfam in terms of precision, recall and localization. To our knowledge, no other functional site annotator has been rigorously evaluated against these key criteria. The software and predictive models are incorporated into the WebFEATURE service at http://feature.stanford.edu/wf4.0-beta. PMID:24632601

  13. Design for a high field combined function superferric magnet

    NASA Astrophysics Data System (ADS)

    Gupta, R. C.; Morgan, G. H.

    A combined function superferric magnet option was investigated for the Relativistic Heavy Ion Collider (RHIC). The option requires the maximum value of the field in the magnet to be much higher than that achieved in any existing combined function accelerator magnet. A model is presented in which a good field quality can be maintained up to 2T. It is done by carefully designing the yoke structure and positioning the coils in such a way that the iron poles tend to saturate evenly across the gap. A cold iron model might be necessary for this magnet.

  14. Impact of IQ Discrepancy on Executive Function in High-Functioning Autism: Insight into Twice Exceptionality

    ERIC Educational Resources Information Center

    Kalbfleisch, M. Layne; Loughan, Ashlee R.

    2012-01-01

    We examined the impact of IQ discrepancy (IQD) within (1) and above (1+) one standard deviation on executive function in HFA using the BRIEF. We hypothesized that IQD would benefit executive function. IQD 1 is hallmarked by deficits in BRIEF indices and subscales inhibit, shift, initiate, working memory, planning and organization, and monitor…

  15. Functional Sub-states by High-pressure Macromolecular Crystallography.

    PubMed

    Dhaussy, Anne-Claire; Girard, Eric

    2015-01-01

    At the molecular level, high-pressure perturbation is of particular interest for biological studies as it allows trapping conformational substates. Moreover, within the context of high-pressure adaptation of deep-sea organisms, it allows to decipher the molecular determinants of piezophily. To provide an accurate description of structural changes produced by pressure in a macromolecular system, developments have been made to adapt macromolecular crystallography to high-pressure studies. The present chapter is an overview of results obtained so far using high-pressure macromolecular techniques, from nucleic acids to virus capsid through monomeric as well as multimeric proteins.

  16. The Contribution of Executive Functions to Participation in School Activities of Children with High Functioning Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Zingerevich, Chaya; Patricia D., LaVesser

    2009-01-01

    This study describes the contribution of executive functions to participation in school activities of children diagnosed with ASD ages 6-9 years while controlling for sensory processing. Twenty-four children, ages 73-112 months (S.D. = 11.4), diagnosed with high functioning ASD were assessed with the Wisconsin Card Sorting Test. Their teachers…

  17. Maternal Recurrent Mood Disorders and High-Functioning Autism

    ERIC Educational Resources Information Center

    Cohen, Ira L.; Tsiouris, John A.

    2006-01-01

    A quantitative examination was made of the association of parental mood and anxiety disorders with severity of disability within a large sample of young children with Pervasive Developmental Disorder (PDD). Maternal recurrent mood disorders were associated with elevated cognitive and adaptive functioning in their affected children, parent reports…

  18. Highly energetic compositions based on functionalized carbon nanomaterials.

    PubMed

    Yan, Qi-Long; Gozin, Michael; Zhao, Feng-Qi; Cohen, Adva; Pang, Si-Ping

    2016-03-01

    In recent years, research in the field of carbon nanomaterials (CNMs), such as fullerenes, expanded graphite (EG), carbon nanotubes (CNTs), graphene, and graphene oxide (GO), has been widely used in energy storage, electronics, catalysts, and biomaterials, as well as medical applications. Regarding energy storage, one of the most important research directions is the development of CNMs as carriers of energetic components by coating or encapsulation, thus forming safer advanced nanostructures with better performances. Moreover, some CNMs can also be functionalized to become energetic additives. This review article covers updated preparation methods for the aforementioned CNMs, with a more specific orientation towards the use of these nanomaterials in energetic compositions. The effects of these functionalized CNMs on thermal decomposition, ignition, combustion and the reactivity properties of energetic compositions are significant and are discussed in detail. It has been shown that the use of functionalized CNMs in energetic compositions greatly improves their combustion performances, thermal stability and sensitivity. In particular, functionalized fullerenes, CNTs and GO are the most appropriate candidate components in nanothermites, solid propellants and gas generators, due to their superior catalytic properties as well as facile preparation methods.

  19. Highly energetic compositions based on functionalized carbon nanomaterials

    NASA Astrophysics Data System (ADS)

    Yan, Qi-Long; Gozin, Michael; Zhao, Feng-Qi; Cohen, Adva; Pang, Si-Ping

    2016-02-01

    In recent years, research in the field of carbon nanomaterials (CNMs), such as fullerenes, expanded graphite (EG), carbon nanotubes (CNTs), graphene, and graphene oxide (GO), has been widely used in energy storage, electronics, catalysts, and biomaterials, as well as medical applications. Regarding energy storage, one of the most important research directions is the development of CNMs as carriers of energetic components by coating or encapsulation, thus forming safer advanced nanostructures with better performances. Moreover, some CNMs can also be functionalized to become energetic additives. This review article covers updated preparation methods for the aforementioned CNMs, with a more specific orientation towards the use of these nanomaterials in energetic compositions. The effects of these functionalized CNMs on thermal decomposition, ignition, combustion and the reactivity properties of energetic compositions are significant and are discussed in detail. It has been shown that the use of functionalized CNMs in energetic compositions greatly improves their combustion performances, thermal stability and sensitivity. In particular, functionalized fullerenes, CNTs and GO are the most appropriate candidate components in nanothermites, solid propellants and gas generators, due to their superior catalytic properties as well as facile preparation methods.

  20. Highly Conductive Aromatic Functionalized Multi-Walled Carbon Nanotube for Inkjet Printable High Performance Supercapacitor Electrodes

    PubMed Central

    Attri, Pankaj

    2015-01-01

    We report the functionalization of multiwalled carbon nanotubes (MWCNT) via the 1,3-dipolar [3+2] cycloaddition of aromatic azides, which resulted in a detangled CNT as shown by transmission electron microscopy (TEM). Carboxylic moieties (-COOH) on aromatic azide result in highly stable aqueous dispersion (max. conc. ~ 10 mg/mL H2O), making the suitable for inkjet printing. Printed patterns on polyethylene terephthalate (PET) flexible substrate exhibit low sheet resistivity ~65 Ω. cm, which is attributed to enhanced conductivity. Fabricated Supercapacitors (SC) assembled using these printed substrates exhibit good electrochemical performance in organic as well as aqueous electrolytes. High energy and power density (57.8 Wh/kg and 0.85 kW/kg) in 1M H2SO4 aqueous electrolyte demonstrate the excellent performance of the proposed supercapacitor. Capacitive retention varies from ~85–94% with columbic efficiency ~95% after 1000 charge/discharge cycles in different electrolytes, demonstrating the excellent potential of the device for futuristic power applications. PMID:26153688

  1. Highly Conductive Aromatic Functionalized Multi-Walled Carbon Nanotube for Inkjet Printable High Performance Supercapacitor Electrodes.

    PubMed

    Ujjain, Sanjeev K; Bhatia, Rohit; Ahuja, Preety; Attri, Pankaj

    2015-01-01

    We report the functionalization of multiwalled carbon nanotubes (MWCNT) via the 1,3-dipolar [3+2] cycloaddition of aromatic azides, which resulted in a detangled CNT as shown by transmission electron microscopy (TEM). Carboxylic moieties (-COOH) on aromatic azide result in highly stable aqueous dispersion (max. conc. ~ 10 mg/mL H2O), making the suitable for inkjet printing. Printed patterns on polyethylene terephthalate (PET) flexible substrate exhibit low sheet resistivity ~65 Ω. cm, which is attributed to enhanced conductivity. Fabricated Supercapacitors (SC) assembled using these printed substrates exhibit good electrochemical performance in organic as well as aqueous electrolytes. High energy and power density (57.8 Wh/kg and 0.85 kW/kg) in 1M H2SO4 aqueous electrolyte demonstrate the excellent performance of the proposed supercapacitor. Capacitive retention varies from ~85-94% with columbic efficiency ~95% after 1000 charge/discharge cycles in different electrolytes, demonstrating the excellent potential of the device for futuristic power applications. PMID:26153688

  2. [High energy shockwave-induced acute changes in renal function].

    PubMed

    Li, B Y

    1992-09-01

    Attempting to understand the effects of HESW on renal function, we studied prospectively 40 patients with nephrolithiasis in 4 groups, using different number of pulsation and the same voltage to identify different effects. Stone burdens and position were similar in these groups. Each group received 1,500, 2,000, 2,500, or 3,000 pulses respectively at 12.5 kV from JT-3 lithotripter. In all groups, the levels of urinary NAG, beta 2MG, ALB and serum beta 2MG were significantly increased at day 1-3 after ESWL (P < 0.001), and then decreased to the levels of pre-ESWL except serum beta 2MG and urinary NAG levels of group C and D at day 7 after ESWL, which were significantly higher (P < 0.05) than those of pre-ESWL. There was significant correlation between either urinary NAG (r = 0.977, P < 0.05) or urinary beta 2MG (r = 0.933, P < 0.001) and the number of pulses at day 3 post-ESWL. In addition, there was a significant difference in urinary NAG levels between group D and group A, B or C at day 3 post-ESWL, and the same was true in urinary beta 2MG levels between group C or D and group A or B. These findings suggested that shock wave induced acute changes in renal function and transient renal tubular damages, and that the tubular damages might last longer more than 7 days, although these functional changes recovered within one week. The changes were related to the energy levels of shock wave, and the degree of renal damage would increase when the energy level was above 12.5 kV x 2,500 pulses.

  3. High-resolution functional profiling of the norovirus genome.

    PubMed

    Thorne, Lucy; Bailey, Dalan; Goodfellow, Ian

    2012-11-01

    Human noroviruses (HuNoV) are a major cause of nonbacterial gastroenteritis worldwide, yet details of the life cycle and replication of HuNoV are relatively unknown due to the lack of an efficient cell culture system. Studies with murine norovirus (MNV), which can be propagated in permissive cells, have begun to probe different aspects of the norovirus life cycle; however, our understanding of the specific functions of the viral proteins lags far behind that of other RNA viruses. Genome-wide functional profiling by insertional mutagenesis can reveal protein domains essential for replication and can lead to generation of tagged viruses, which has not yet been achieved for noroviruses. Here, transposon-mediated insertional mutagenesis was used to create 5 libraries of mutagenized MNV infectious clones, each containing a 15-nucleotide sequence randomly inserted within a defined region of the genome. Infectious virus was recovered from each library and was subsequently passaged in cell culture to determine the effect of each insertion by insertion-specific fluorescent PCR profiling. Genome-wide profiling of over 2,000 insertions revealed essential protein domains and confirmed known functional motifs. As validation, several insertion sites were introduced into a wild-type clone, successfully allowing the recovery of infectious virus. Screening of a number of reporter proteins and epitope tags led to the generation of the first infectious epitope-tagged noroviruses carrying the FLAG epitope tag in either NS4 or VP2. Subsequent work confirmed that epitope-tagged fully infectious noroviruses may be of use in the dissection of the molecular interactions that occur within the viral replication complex. PMID:22915807

  4. Functionalized oxepines via fragmentation of highly strained epoxides.

    PubMed

    Leyhane, Andrew J; Snapper, Marc L

    2006-11-01

    [Structure: see text] Epoxidation of highly strained cyclobutenes followed by thermal rearrangement provides a new entry into oxepine-containing bicyclo[5.3.0] ring systems. In contrast to the rearrangement of the corresponding cyclopropanated systems, the strained epoxides in this study are believed to fragment through two competing pathways leading to a mixture of diastereomeric 5-7 ring systems.

  5. How much of virus-specific CD8 T cell reactivity is detected with a peptide pool when compared to individual peptides?

    PubMed

    Zhang, Wenji; Moldovan, Ioana; Targoni, Oleg S; Subbramanian, Ramu A; Lehmann, Paul V

    2012-10-29

    Immune monitoring of T cell responses increasingly relies on the use of peptide pools. Peptides, when restricted by the same HLA allele, and presented from within the same peptide pool, can compete for HLA binding sites. What impact such competition has on functional T cell stimulation, however, is not clear. Using a model peptide pool that is comprised of 32 well-defined viral epitopes from Cytomegalovirus, Epstein-Barr virus, and Influenza viruses (CEF peptide pool), we assessed peptide competition in PBMC from 42 human subjects. The magnitude of the peptide pool-elicited CD8 T cell responses was a mean 79% and a median 77% of the sum of the CD8 T cell responses elicited by the individual peptides. Therefore, while the effect of peptide competition was evident, it was of a relatively minor magnitude. By studying the dose-response curves for individual CEF peptides, we show that several of these peptides are present in the CEF-pool at concentrations that are orders of magnitude in excess of what is needed for the activation threshold of the CD8 T cells. The presence of such T cells with very high functional avidity for the viral antigens can explain why the effect of peptide competition is relatively minor within the CEF-pool.

  6. Highly reflective polymeric substrates functionalized utilizing atomic layer deposition

    SciTech Connect

    Zuzuarregui, Ana Gregorczyk, Keith E.; Coto, Borja; Ruiz de Gopegui, Unai; Barriga, Javier; Rodríguez, Jorge; Knez, Mato

    2015-08-10

    Reflective surfaces are one of the key elements of solar plants to concentrate energy in the receivers of solar thermal electricity plants. Polymeric substrates are being considered as an alternative to the widely used glass mirrors due to their intrinsic and processing advantages, but optimizing both the reflectance and the physical stability of polymeric mirrors still poses technological difficulties. In this work, polymeric surfaces have been functionalized with ceramic thin-films by atomic layer deposition. The characterization and optimization of the parameters involved in the process resulted in surfaces with a reflection index of 97%, turning polymers into a real alternative to glass substrates. The solution we present here can be easily applied in further technological areas where seemingly incompatible combinations of polymeric substrates and ceramic coatings occur.

  7. Independence of Hot and Cold Executive Function Deficits in High-Functioning Adults with Autism Spectrum Disorder

    PubMed Central

    Zimmerman, David L.; Ownsworth, Tamara; O'Donovan, Analise; Roberts, Jacqueline; Gullo, Matthew J.

    2016-01-01

    Individuals with autistic spectrum disorder (ASD) display diverse deficits in social, cognitive and behavioral functioning. To date, there has been mixed findings on the profile of executive function deficits for high-functioning adults (IQ > 70) with ASD. A conceptual distinction is commonly made between “cold” and “hot” executive functions. Cold executive functions refer to mechanistic higher-order cognitive operations (e.g., working memory), whereas hot executive functions entail cognitive abilities supported by emotional awareness and social perception (e.g., social cognition). This study aimed to determine the independence of deficits in hot and cold executive functions for high-functioning adults with ASD. Forty-two adults with ASD (64% male, aged 18–66 years) and 40 age and gender matched controls were administered The Awareness of Social Inference Test (TASIT; emotion recognition and social inference), Letter Number Sequencing (working memory) and Hayling Sentence Completion Test (response initiation and suppression). Between-group analyses identified that the ASD group performed significantly worse than matched controls on all measures of cold and hot executive functions (d = 0.54 − 1.5). Hierarchical multiple regression analyses revealed that the ASD sample performed more poorly on emotion recognition and social inference tasks than matched controls after controlling for cold executive functions and employment status. The findings also indicated that the ability to recognize emotions and make social inferences was supported by working memory and response initiation and suppression processes. Overall, this study supports the distinction between hot and cold executive function impairments for adults with ASD. Moreover, it advances understanding of higher-order impairments underlying social interaction difficulties for this population which, in turn, may assist with diagnosis and inform intervention programs. PMID:26903836

  8. Independence of Hot and Cold Executive Function Deficits in High-Functioning Adults with Autism Spectrum Disorder.

    PubMed

    Zimmerman, David L; Ownsworth, Tamara; O'Donovan, Analise; Roberts, Jacqueline; Gullo, Matthew J

    2016-01-01

    Individuals with autistic spectrum disorder (ASD) display diverse deficits in social, cognitive and behavioral functioning. To date, there has been mixed findings on the profile of executive function deficits for high-functioning adults (IQ > 70) with ASD. A conceptual distinction is commonly made between "cold" and "hot" executive functions. Cold executive functions refer to mechanistic higher-order cognitive operations (e.g., working memory), whereas hot executive functions entail cognitive abilities supported by emotional awareness and social perception (e.g., social cognition). This study aimed to determine the independence of deficits in hot and cold executive functions for high-functioning adults with ASD. Forty-two adults with ASD (64% male, aged 18-66 years) and 40 age and gender matched controls were administered The Awareness of Social Inference Test (TASIT; emotion recognition and social inference), Letter Number Sequencing (working memory) and Hayling Sentence Completion Test (response initiation and suppression). Between-group analyses identified that the ASD group performed significantly worse than matched controls on all measures of cold and hot executive functions (d = 0.54 - 1.5). Hierarchical multiple regression analyses revealed that the ASD sample performed more poorly on emotion recognition and social inference tasks than matched controls after controlling for cold executive functions and employment status. The findings also indicated that the ability to recognize emotions and make social inferences was supported by working memory and response initiation and suppression processes. Overall, this study supports the distinction between hot and cold executive function impairments for adults with ASD. Moreover, it advances understanding of higher-order impairments underlying social interaction difficulties for this population which, in turn, may assist with diagnosis and inform intervention programs.

  9. Independence of Hot and Cold Executive Function Deficits in High-Functioning Adults with Autism Spectrum Disorder.

    PubMed

    Zimmerman, David L; Ownsworth, Tamara; O'Donovan, Analise; Roberts, Jacqueline; Gullo, Matthew J

    2016-01-01

    Individuals with autistic spectrum disorder (ASD) display diverse deficits in social, cognitive and behavioral functioning. To date, there has been mixed findings on the profile of executive function deficits for high-functioning adults (IQ > 70) with ASD. A conceptual distinction is commonly made between "cold" and "hot" executive functions. Cold executive functions refer to mechanistic higher-order cognitive operations (e.g., working memory), whereas hot executive functions entail cognitive abilities supported by emotional awareness and social perception (e.g., social cognition). This study aimed to determine the independence of deficits in hot and cold executive functions for high-functioning adults with ASD. Forty-two adults with ASD (64% male, aged 18-66 years) and 40 age and gender matched controls were administered The Awareness of Social Inference Test (TASIT; emotion recognition and social inference), Letter Number Sequencing (working memory) and Hayling Sentence Completion Test (response initiation and suppression). Between-group analyses identified that the ASD group performed significantly worse than matched controls on all measures of cold and hot executive functions (d = 0.54 - 1.5). Hierarchical multiple regression analyses revealed that the ASD sample performed more poorly on emotion recognition and social inference tasks than matched controls after controlling for cold executive functions and employment status. The findings also indicated that the ability to recognize emotions and make social inferences was supported by working memory and response initiation and suppression processes. Overall, this study supports the distinction between hot and cold executive function impairments for adults with ASD. Moreover, it advances understanding of higher-order impairments underlying social interaction difficulties for this population which, in turn, may assist with diagnosis and inform intervention programs. PMID:26903836

  10. A functional protein retention and release multilayer with high stability

    NASA Astrophysics Data System (ADS)

    Nie, Kun; An, Qi; Zhang, Yihe

    2016-04-01

    Effective and robust interfacial protein retention lies at the heart of the fabrication of protein-based functional interfaces, which is potentially applicable in catalysis, medical therapy, antifouling, and smart devices, but remains challenging due to the sensitive nature of proteins. This study reports a general protein retention strategy to spatial-temporally confine various types of proteins at interfacial regions. The proteins were preserved in mesoporous silica nanoparticles embedded in covalently woven multilayers. It is worth noting that the protein retention strategy effectively preserves the catalytic capabilities of the proteins, and the multilayer structure is robust enough to withstand the bubbling catalytic reactions and could be repeatedly used due to conservation of proteins. The spatiotemporal retention of proteins could be adjusted by varying the number of capping layers. Furthermore, we demonstrate that the protein-loaded interfacial layers could not only be used to construct catalytic-active interfaces, but also be integrated as the power-generating unit to propel a macroscopic floating device.Effective and robust interfacial protein retention lies at the heart of the fabrication of protein-based functional interfaces, which is potentially applicable in catalysis, medical therapy, antifouling, and smart devices, but remains challenging due to the sensitive nature of proteins. This study reports a general protein retention strategy to spatial-temporally confine various types of proteins at interfacial regions. The proteins were preserved in mesoporous silica nanoparticles embedded in covalently woven multilayers. It is worth noting that the protein retention strategy effectively preserves the catalytic capabilities of the proteins, and the multilayer structure is robust enough to withstand the bubbling catalytic reactions and could be repeatedly used due to conservation of proteins. The spatiotemporal retention of proteins could be adjusted by

  11. Memristive crypto primitive for building highly secure physical unclonable functions

    NASA Astrophysics Data System (ADS)

    Gao, Yansong; Ranasinghe, Damith C.; Al-Sarawi, Said F.; Kavehei, Omid; Abbott, Derek

    2015-08-01

    Physical unclonable functions (PUFs) exploit the intrinsic complexity and irreproducibility of physical systems to generate secret information. The advantage is that PUFs have the potential to provide fundamentally higher security than traditional cryptographic methods by preventing the cloning of devices and the extraction of secret keys. Most PUF designs focus on exploiting process variations in Complementary Metal Oxide Semiconductor (CMOS) technology. In recent years, progress in nanoelectronic devices such as memristors has demonstrated the prevalence of process variations in scaling electronics down to the nano region. In this paper, we exploit the extremely large information density available in nanocrossbar architectures and the significant resistance variations of memristors to develop an on-chip memristive device based strong PUF (mrSPUF). Our novel architecture demonstrates desirable characteristics of PUFs, including uniqueness, reliability, and large number of challenge-response pairs (CRPs) and desirable characteristics of strong PUFs. More significantly, in contrast to most existing PUFs, our PUF can act as a reconfigurable PUF (rPUF) without additional hardware and is of benefit to applications needing revocation or update of secure key information.

  12. Memristive crypto primitive for building highly secure physical unclonable functions

    PubMed Central

    Gao, Yansong; Ranasinghe, Damith C.; Al-Sarawi, Said F.; Kavehei, Omid; Abbott, Derek

    2015-01-01

    Physical unclonable functions (PUFs) exploit the intrinsic complexity and irreproducibility of physical systems to generate secret information. The advantage is that PUFs have the potential to provide fundamentally higher security than traditional cryptographic methods by preventing the cloning of devices and the extraction of secret keys. Most PUF designs focus on exploiting process variations in Complementary Metal Oxide Semiconductor (CMOS) technology. In recent years, progress in nanoelectronic devices such as memristors has demonstrated the prevalence of process variations in scaling electronics down to the nano region. In this paper, we exploit the extremely large information density available in nanocrossbar architectures and the significant resistance variations of memristors to develop an on-chip memristive device based strong PUF (mrSPUF). Our novel architecture demonstrates desirable characteristics of PUFs, including uniqueness, reliability, and large number of challenge-response pairs (CRPs) and desirable characteristics of strong PUFs. More significantly, in contrast to most existing PUFs, our PUF can act as a reconfigurable PUF (rPUF) without additional hardware and is of benefit to applications needing revocation or update of secure key information. PMID:26239669

  13. High resolution multiplexed functional imaging in live embyros (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Xu, Dongli; Peng, Leilei

    2016-03-01

    Optical projection tomography (OPT) creates isotropic 3D imaging of tissue. Two approaches exist today: Wide-field OPT illuminates the entire sample and acquires projection images with a camera; Scanning-laser optical tomography (SLOT) generates the projection with a moving laser beam and point detector. SLOT has superior light collecting efficiency than wide-field optical tomography, making it ideal for tissue fluorescence imaging. Regardless the approach, traditional OPT has to compromise between the resolution and the depth of view. In traditional SLOT, the focused Gaussian beam diverges quickly from the focused plane, making it impossible to achieve high resolution imaging through a large volume specimen. We report using Bessel beam instead of Gaussian beam to perform SLOT. By illuminating samples with a narrow Bessel beam throughout an extended depth, high-resolution projection images can be measured in large volume. Under Bessel illumination, the projection image contains signal from annular-rings of the Bessel beam. Traditional inverse Radon transform of these projections will result in ringing artifacts in reconstructed imaging. Thus a modified 3D filtered back projection algorithm is developed to perform tomography reconstructing of Bessel-illuminated projection images. The resulting 3D imaging is free of artifact and achieved cellular resolution in extended sample volume. The system is applied to in-vivo imaging of transgenic Zebrafish embryos. Results prove Bessel SLOT a promising imaging method in development biology research.

  14. Structure–Function Relationships in Highly Modified Shoots of Cactaceae

    PubMed Central

    MAUSETH, JAMES D.

    2006-01-01

    • Background and Aims Cacti are extremely diverse structurally and ecologically, and so modified as to be intimidating to many biologists. Yet all have the same organization as most dicots, none differs fundamentally from Arabidopsis or other model plants. This review explains cactus shoot structure, discusses relationships between structure, ecology, development and evolution, and indicates areas where research on cacti is necessary to test general theories of morphogenesis. • Scope Cactus leaves are diverse; all cacti have foliage leaves; many intermediate stages in evolutionary reduction of leaves are still present; floral shoots often have large, complex leaves whereas vegetative shoots have microscopic leaves. Spines are modified bud scales, some secrete sugar as extra-floral nectaries. Many cacti have juvenile/adult phases in which the flowering adult phase (a cephalium) differs greatly from the juvenile; in some, one side of a shoot becomes adult, all other sides continue to grow as the juvenile phase. Flowers are inverted: the exterior of a cactus ‘flower’ is a hollow vegetative shoot with internodes, nodes, leaves and spines, whereas floral organs occur inside, with petals physically above stamens. Many cacti have cortical bundles vascularizing the cortex, however broad it evolves to be, thus keeping surface tissues alive. Great width results in great weight of weak parenchymatous shoots, correlated with reduced branching. Reduced numbers of shoot apices is compensated by great increases in number of meristematic cells within individual SAMs. Ribs and tubercles allow shoots to swell without tearing during wet seasons. Shoot epidermis and cortex cells live and function for decades then convert to cork cambium. Many modifications permit water storage within cactus wood itself, adjacent to vessels. PMID:16820405

  15. Measurement of the nucleon structure function using high energy muons

    SciTech Connect

    Meyers, P.D.

    1983-12-01

    We have measured the inclusive deep inelastic scattering of muons on nucleons in iron using beams of 93 and 215 GeV muons. To perform this measurement, we have built and operated the Multimuon Spectrometer (MMS) in the muon beam at Fermilab. The MMS is a magnetized iron target/spectrometer/calorimeter which provides 5.61 kg/cm/sup 2/ of target, 9% momentum resolution on scattered muons, and a direct measure of total hadronic energy with resolution sigma/sub nu/ = 1.4..sqrt..nu(GeV). In the distributed target, the average beam energies at the interaction are 88.0 and 209 GeV. Using the known form of the radiatively-corrected electromagnetic cross section, we extract the structure function F/sub 2/(x,Q/sup 2/) with a typical precision of 2% over the range 5 < Q/sup 2/ < 200 GeV/sup 2//c/sup 2/. We compare our measurements to the predictions of lowest order quantum chromodynamics (QCD) and find a best fit value of the QCD scale parameter ..lambda../sub LO/ = 230 +- 40/sup stat/ +- 80/sup syst/ MeV/c, assuming R = 0 and without applying Fermi motion corrections. Comparing the cross sections at the two beam energies, we measure R = -0.06 +- 0.06/sup stat/ +- 0.11/sup syst/. Our measurements show qualitative agreement with QCD, but quantitative comparison is hampered by phenomenological uncertainties. The experimental situation is quite good, with substantial agreement between our measurements and those of others. 86 references.

  16. Use of Gilliam Asperger's disorder scale in differentiating high and low functioning autism and ADHD.

    PubMed

    Mayes, Susan Dickerson; Calhoun, Susan L; Murray, Michael J; Morrow, Jill D; Yurich, Kirsten K L; Cothren, Shiyoko; Purichia, Heather; Bouder, James N

    2011-02-01

    Little is known about the validity of Gilliam Asperger's Disorder Scale (GADS), although it is widely used. This study of 199 children with high functioning autism or Asperger's disorder, 195 with low functioning autism, and 83 with attention deficit hyperactivity disorder (ADHD) showed high classification accuracy (autism vs. ADHD) for clinicians' GADS Quotients (92%), and somewhat lower accuracy (77%) for parents' Quotients. Both children with high and low functioning autism had clinicians' Quotients (M=99 and 101, respectively) similar to the Asperger's Disorder mean of 100 for the GADS normative sample. Children with high functioning autism scored significantly higher on the cognitive patterns subscale than children with low functioning autism, and the latter had higher scores on the remaining subscales: social interaction, restricted patterns of behavior, and pragmatic skills. Using the clinicians' Quotient and Cognitive Patterns score, 70% of children were correctly identified as having high or low functioning autism or ADHD.

  17. Decreasing Disruptive Vocalizations of a Student with High-Functioning Autism across Three General Education Classrooms

    ERIC Educational Resources Information Center

    Banda, Devender R.; Hart, Stephanie L.; Kercood, Suneeta

    2012-01-01

    The authors conducted this study to decrease disruptive vocalizations in a 3rd-grade student with high-functioning autism across 3 general education classrooms. They used direct and indirect approaches of functional behavior assessment to determine the function of the disruptive behavior. Results indicated that the behavior was maintained by…

  18. Mathematics for High School, Elementary Functions (Part 1). Commentary for Teachers. Preliminary Edition.

    ERIC Educational Resources Information Center

    Allen, Frank B.; And Others

    This is part one of a two-part manual for teachers using SMSG high school text materials. Each chapter contains a commentary on the text, answers to exercises, and a set of illustrative test questions. Chapter topics include sets, relations and functions, polynomial functions, and algebra of polynomial functions. (MP)

  19. Vibrational spectroscopy: Can density functional theory cope with highly electronegative atoms?

    NASA Astrophysics Data System (ADS)

    Petković, Milena

    2010-12-01

    Vibrational properties of molecules composed solely of highly electronegative atoms are studied by means of density functional methods. Performance of different combinations of exchange and correlation functionals is tested. It is demonstrated that certain functionals can successfully simulate infrared spectra of systems containing only fluorine, oxygen and nitrogen.

  20. Advanced Inverter Functions to Support High Levels of Distributed Solar: Policy and Regulatory Considerations (Brochure)

    SciTech Connect

    Not Available

    2014-11-01

    This paper explains how advanced inverter functions (sometimes called 'smart inverters') contribute to the integration of high levels of solar PV generation onto the electrical grid and covers the contributions of advanced functions to maintaining grid stability. Policy and regulatory considerations associated with the deployment of advanced inverter functions are also introduced.

  1. The adjuvant effect of a non-toxic mutant of heat-labile enterotoxin of Escherichia coli for the induction of measles virus-specific CTL responses after intranasal co-immunization with a synthetic peptide.

    PubMed Central

    Partidos, C D; Pizza, M; Rappuoli, R; Steward, M W

    1996-01-01

    The intranasal route has been shown to be effective for immunization. However, immunization via this route may require the use of potent and safe adjuvant. The construction of non-toxic mutants of heat labile enterotoxin of Escherichia coli (LT), which is a potent mucosal adjuvant, is a major breakthrough for the development of mucosal vaccines. In this study we have assessed the ability of an LT mutant (LTK63) to act as an adjuvant following intranasal co-immunization with a peptide corresponding to a measles virus cytotoxic T lymphocyte (CTL) epitope. LTK63 was more effective at potentiating the in vivo induction of peptide-specific and measles virus-specific CTL responses than was administration of the peptide in saline. A concentration of 10 micrograms/dose of LTK63 was found to be the most effective in potentiating the in vivo priming of peptide-specific and measles virus-specific CTL responses. These findings highlight the potential of the non-toxic mutant of LT as a safe mucosal adjuvant for use in humans. PMID:9014810

  2. Children with High-Functioning Autism and Asperger's Syndrome: Can We Differentiate Their Cognitive Profiles?

    ERIC Educational Resources Information Center

    Planche, Pascale; Lemonnier, Eric

    2012-01-01

    The aim of this study was to investigate whether children with high-functioning autism (HFA) and Asperger's syndrome (AS) can be differentiated from each other and from typically developing children on their cognitive profiles. The present study included a total of 45 participants: children with autism (high-functioning autism or Asperger's…

  3. Anxiety in High-Functioning Autism: A Pilot Study of Experience Sampling Using a Mobile Platform

    ERIC Educational Resources Information Center

    Hare, Dougal Julian; Gracey, Carolyn; Wood, Christopher

    2016-01-01

    Anxiety and stress are everyday issues for many people with high-functioning autism, and while cognitive-behavioural therapy is the treatment of choice for the management of anxiety, there are challenges in using it with people with high-functioning autism. This study used modified experience sampling techniques to examine everyday anxiety and…

  4. An Investigation of Upper Limb Motor Function in High Functioning Autism and Asperger's Disorder Using a Repetitive Fitts' Aiming Task

    ERIC Educational Resources Information Center

    Papadopoulos, Nicole; McGinley, Jennifer; Tonge, Bruce J.; Bradshaw, John L.; Saunders, Kerryn; Rinehart, Nicole J.

    2012-01-01

    There is now a growing body of research examining movement difficulties in children diagnosed with high functioning autism (HFA) and Asperger's disorder (AD). Despite this, few studies have investigated the kinematic components of movement that may be disrupted in children diagnosed with these disorders. The current study investigated rapid aiming…

  5. Abnormal Functional Specialization within Medial Prefrontal Cortex in High-Functioning Autism: A Multi-Voxel Similarity Analysis

    ERIC Educational Resources Information Center

    Gilbert, Sam J.; Meuwese, Julia D. I.; Towgood, Karren J.; Frith, Christopher D.; Burgess, Paul W.

    2009-01-01

    Multi-voxel pattern analyses have proved successful in "decoding" mental states from fMRI data, but have not been used to examine brain differences associated with atypical populations. We investigated a group of 16 (14 males) high-functioning participants with autism spectrum disorder (ASD) and 16 non-autistic control participants (12 males)…

  6. Heightened self-reactivity associated with selective survival, but not expansion, of naïve virus-specific CD8+ T cells in aged mice

    PubMed Central

    Quinn, Kylie M.; Zaloumis, Sophie G.; Cukalac, Tania; Kan, Wan-Ting; Sng, Xavier Y. X.; Mirams, Michiko; Watson, Katherine A.; Doherty, Peter C.; Thomas, Paul G.; Handel, Andreas; La Gruta, Nicole L.

    2016-01-01

    In advanced age, decreased CD8+ cytotoxic T-lymphocyte (CTL) responses to novel pathogens and cancer is paralleled by a decline in the number and function of naïve CTL precursors (CTLp). Although the age-related fall in CD8+ T-cell numbers is well established, neither the underlying mechanisms nor the extent of variation for different epitope specificities have been defined. Furthermore, naïve CD8+ T cells expressing high levels of CD44 accumulate with age, but it is unknown whether this accumulation reflects their preferential survival or an age-dependent driver of CD8+ T-cell proliferation. Here, we track the number and phenotype of four influenza A virus (IAV)-specific CTLp populations in naïve C57BL/6 (B6) mice during aging, and compare T-cell receptor (TCR) clonal diversity for the CD44hi and CD44lo subsets of one such population. We show differential onset of decline for several IAV-specific CD8+ T-cell populations with advanced age that parallel age-associated changes in the B6 immunodominance hierarchy, suggestive of distinct impacts of aging on different epitope-specific populations. Despite finding no evidence of clonal expansions in an aged, epitope-specific TCR repertoire, nonrandom alterations in TCR usage were observed, along with elevated CD5 and CD8 coreceptor expression. Collectively, these data demonstrate that naïve CD8+ T cells expressing markers of heightened self-recognition are selectively retained, but not clonally expanded, during aging. PMID:26787864

  7. Highly multiplexed profiling of single-cell effector functions reveals deep functional heterogeneity in response to pathogenic ligands

    PubMed Central

    Lu, Yao; Xue, Qiong; Eisele, Markus R.; Sulistijo, Endah S.; Brower, Kara; Han, Lin; Amir, El-ad David; Pe’er, Dana; Miller-Jensen, Kathryn; Fan, Rong

    2015-01-01

    Despite recent advances in single-cell genomic, transcriptional, and mass-cytometric profiling, it remains a challenge to collect highly multiplexed measurements of secreted proteins from single cells for comprehensive analysis of functional states. Herein, we combine spatial and spectral encoding with polydimethylsiloxane (PDMS) microchambers for codetection of 42 immune effector proteins secreted from single cells, representing the highest multiplexing recorded to date for a single-cell secretion assay. Using this platform to profile differentiated macrophages stimulated with lipopolysaccharide (LPS), the ligand of Toll-like receptor 4 (TLR4), reveals previously unobserved deep functional heterogeneity and varying levels of pathogenic activation. Uniquely protein profiling on the same single cells before and after LPS stimulation identified a role for macrophage inhibitory factor (MIF) to potentiate the activation of LPS-induced cytokine production. Advanced clustering analysis identified functional subsets including quiescent, polyfunctional fully activated, partially activated populations with different cytokine profiles. This population architecture is conserved throughout the cell activation process and prevails as it is extended to other TLR ligands and to primary macrophages derived from a healthy donor. This work demonstrates that the phenotypically similar cell population still exhibits a large degree of intrinsic heterogeneity at the functional and cell behavior level. This technology enables full-spectrum dissection of immune functional states in response to pathogenic or environmental stimulation, and opens opportunities to quantify deep functional heterogeneity for more comprehensive and accurate immune monitoring. PMID:25646488

  8. Convergent Findings of Altered Functional and Structural Brain Connectivity in Individuals with High Functioning Autism: A Multimodal MRI Study.

    PubMed

    Mueller, Sophia; Keeser, Daniel; Samson, Andrea C; Kirsch, Valerie; Blautzik, Janusch; Grothe, Michel; Erat, Okan; Hegenloh, Michael; Coates, Ute; Reiser, Maximilian F; Hennig-Fast, Kristina; Meindl, Thomas

    2013-01-01

    Brain tissue changes in autism spectrum disorders seem to be rather subtle and widespread than anatomically distinct. Therefore a multimodal, whole brain imaging technique appears to be an appropriate approach to investigate whether alterations in white and gray matter integrity relate to consistent changes in functional resting state connectivity in individuals with high functioning autism (HFA). We applied diffusion tensor imaging (DTI), voxel-based morphometry (VBM) and resting state functional connectivity magnetic resonance imaging (fcMRI) to assess differences in brain structure and function between 12 individuals with HFA (mean age 35.5, SD 11.4, 9 male) and 12 healthy controls (mean age 33.3, SD 9.0, 8 male). Psychological measures of empathy and emotionality were obtained and correlated with the most significant DTI, VBM and fcMRI findings. We found three regions of convergent structural and functional differences between HFA participants and controls. The right temporo-parietal junction area and the left frontal lobe showed decreased fractional anisotropy (FA) values along with decreased functional connectivity and a trend towards decreased gray matter volume. The bilateral superior temporal gyrus displayed significantly decreased functional connectivity that was accompanied by the strongest trend of gray matter volume decrease in the temporal lobe of HFA individuals. FA decrease in the right temporo-parietal region was correlated with psychological measurements of decreased emotionality. In conclusion, our results indicate common sites of structural and functional alterations in higher order association cortex areas and may therefore provide multimodal imaging support to the long-standing hypothesis of autism as a disorder of impaired higher-order multisensory integration.

  9. Convergent Findings of Altered Functional and Structural Brain Connectivity in Individuals with High Functioning Autism: A Multimodal MRI Study

    PubMed Central

    Samson, Andrea C.; Kirsch, Valerie; Blautzik, Janusch; Grothe, Michel; Erat, Okan; Hegenloh, Michael; Coates, Ute; Reiser, Maximilian F.; Hennig-Fast, Kristina; Meindl, Thomas

    2013-01-01

    Brain tissue changes in autism spectrum disorders seem to be rather subtle and widespread than anatomically distinct. Therefore a multimodal, whole brain imaging technique appears to be an appropriate approach to investigate whether alterations in white and gray matter integrity relate to consistent changes in functional resting state connectivity in individuals with high functioning autism (HFA). We applied diffusion tensor imaging (DTI), voxel-based morphometry (VBM) and resting state functional connectivity magnetic resonance imaging (fcMRI) to assess differences in brain structure and function between 12 individuals with HFA (mean age 35.5, SD 11.4, 9 male) and 12 healthy controls (mean age 33.3, SD 9.0, 8 male). Psychological measures of empathy and emotionality were obtained and correlated with the most significant DTI, VBM and fcMRI findings. We found three regions of convergent structural and functional differences between HFA participants and controls. The right temporo-parietal junction area and the left frontal lobe showed decreased fractional anisotropy (FA) values along with decreased functional connectivity and a trend towards decreased gray matter volume. The bilateral superior temporal gyrus displayed significantly decreased functional connectivity that was accompanied by the strongest trend of gray matter volume decrease in the temporal lobe of HFA individuals. FA decrease in the right temporo-parietal region was correlated with psychological measurements of decreased emotionality. In conclusion, our results indicate common sites of structural and functional alterations in higher order association cortex areas and may therefore provide multimodal imaging support to the long-standing hypothesis of autism as a disorder of impaired higher-order multisensory integration. PMID:23825652

  10. QCD Precision Measurements and Structure Function Extraction at a High Statistics, High Energy Neutrino Scattering Experiment: NuSOnG

    SciTech Connect

    Adams, T.; Batra, P.; Bugel, Leonard G.; Camilleri, Leslie Loris; Conrad, Janet Marie; de Gouvea, A.; Fisher, Peter H.; Formaggio, Joseph Angelo; Jenkins, J.; Karagiorgi, Georgia S.; Kobilarcik, T.R.; /Fermilab /Texas U.

    2009-06-01

    We extend the physics case for a new high-energy, ultra-high statistics neutrino scattering experiment, NuSOnG (Neutrino Scattering On Glass) to address a variety of issues including precision QCD measurements, extraction of structure functions, and the derived Parton Distribution Functions (PDFs). This experiment uses a Tevatron-based neutrino beam to obtain a sample of Deep Inelastic Scattering (DIS) events which is over two orders of magnitude larger than past samples. We outline an innovative method for fitting the structure functions using a parameterized energy shift which yields reduced systematic uncertainties. High statistics measurements, in combination with improved systematics, will enable NuSOnG to perform discerning tests of fundamental Standard Model parameters as we search for deviations which may hint of 'Beyond the Standard Model' physics.

  11. QCD Precision Measurements and Structure Function Extraction at a High Statistics, High Energy Neutrino Scattering Experiment:. NuSOnG

    NASA Astrophysics Data System (ADS)

    Adams, T.; Batra, P.; Bugel, L.; Camilleri, L.; Conrad, J. M.; de Gouvêa, A.; Fisher, P. H.; Formaggio, J. A.; Jenkins, J.; Karagiorgi, G.; Kobilarcik, T. R.; Kopp, S.; Kyle, G.; Loinaz, W. A.; Mason, D. A.; Milner, R.; Moore, R.; Morfín, J. G.; Nakamura, M.; Naples, D.; Nienaber, P.; Olness, F. I.; Owens, J. F.; Pate, S. F.; Pronin, A.; Seligman, W. G.; Shaevitz, M. H.; Schellman, H.; Schienbein, I.; Syphers, M. J.; Tait, T. M. P.; Takeuchi, T.; Tan, C. Y.; van de Water, R. G.; Yamamoto, R. K.; Yu, J. Y.

    We extend the physics case for a new high-energy, ultra-high statistics neutrino scattering experiment, NuSOnG (Neutrino Scattering On Glass) to address a variety of issues including precision QCD measurements, extraction of structure functions, and the derived Parton Distribution Functions (PDF's). This experiment uses a Tevatron-based neutrino beam to obtain a sample of Deep Inelastic Scattering (DIS) events which is over two orders of magnitude larger than past samples. We outline an innovative method for fitting the structure functions using a parametrized energy shift which yields reduced systematic uncertainties. High statistics measurements, in combination with improved systematics, will enable NuSOnG to perform discerning tests of fundamental Standard Model parameters as we search for deviations which may hint of "Beyond the Standard Model" physics.

  12. Self-awareness of functional impairment in individuals at clinical high-risk for psychosis

    PubMed Central

    Olvet, Doreen M.; Carrión, Ricardo E.; Auther, Andrea M.; Cornblatt, Barbara A.

    2013-01-01

    Aims A major public health concern associated with schizophrenia is the long-term disability that involves an inability to function independently in the community. An individual’s self-awareness of functional impairment may be a significant factor contributing to long-term disability. In fact, subjective interpretation of one’s illness impacts treatment participation and adherence, and is linked to poor outcomes. However, it remains unclear how illness-related functional impairment is perceived by individuals prior to the onset of psychosis. This study aims to examine the relationship between clinician-based and self-report assessments of functioning, as well as the contribution of clinical symptoms to this relationship in individuals at clinical high-risk for psychosis. Methods The Sheehan Disability Scale, a self-rated instrument, was used to measure disruption in daily functioning in social and role functioning due to symptoms in a sample of 73 treatment-seeking patients at clinical high-risk for psychosis and 50 healthy controls. Results Relative to healthy controls, clinical high-risk patients self-reported significant disruptions in social and role functioning. In addition, a specific relationship emerged in that clinician-rated measures of functioning and depression were related to disability scores. Conclusions These findings suggest that clinical high-risk patients are significantly disturbed by their illness. Self-reported disruption of daily functioning was associated with clinician-rated functioning and depressive symptoms, further highlighting the impact of functional impairments on the level of distress experienced by patients in the early phases of the illness. Intervention strategies that repair functional impairment before the onset of psychosis may prevent long-term disability. PMID:23968457

  13. Cost-impact of young adults with high-functioning autistic spectrum disorder.

    PubMed

    Järbrink, Krister; McCrone, Paul; Fombonne, Eric; Zandén, Håkan; Knapp, Martin

    2007-01-01

    There is a general lack of information about the economic impact of autistic spectrum disorder (ASD), particularly regarding adults and those with high-functioning ASD. In this study, the societal economic consequences of ASD were investigated using a sample of young high-functioning adults in need of employment support. A methodology for the collection of cost information was developed and information about how to avoid obstacles in the collection process was obtained. Today, many people with ASD who would be able to function in open employment do not get this opportunity. This study demonstrated that ASD results in high costs and indicates that a lack of supported employment programmes for people with ASD may have negative resource consequences for the economy. The study also contributes towards a methodology of economically evaluating supported employment programs as well as other interventions for people with high-functioning ASD.

  14. Brief Report: Feasibility of Social Cognition and Interaction Training for Adults with High Functioning Autism

    ERIC Educational Resources Information Center

    Turner-Brown, Lauren M.; Perry, Timothy D.; Dichter, Gabriel S.; Bodfish, James W.; Penn, David L.

    2008-01-01

    The goal of this study was to evaluate the feasibility and utility of a group-based cognitive behavioral intervention to improve social-cognitive functioning in adults with high-functioning autism (HFA). We modified the treatment manual of a previously validated intervention, Social Cognition and Interaction Training (SCIT), for optimal use with…

  15. Verbal Memory Deficits in Relation to Organization Strategy in High- and Low-Functioning Autistic Children

    ERIC Educational Resources Information Center

    Cheung, Mei-chun; Chan, Agnes S.; Sze, Sophia L.; Leung, Winnie W.; To, Cho Yee

    2010-01-01

    The present study examined the verbal memory profile and its relation to organizational strategies in high-functioning (Hi-AUT) and low-functioning (Lo-AUT) children with autism. Twenty-two Hi-AUT and 16 Lo-AUT, and 22 age-, gender- and handedness-matched normal children (NC) were required to remember a list of semantically related words for…

  16. Associations between Conceptual Reasoning, Problem Solving, and Adaptive Ability in High-Functioning Autism

    ERIC Educational Resources Information Center

    Williams, Diane L.; Mazefsky, Carla A.; Walker, Jon D.; Minshew, Nancy J.; Goldstein, Gerald

    2014-01-01

    Abstract thinking is generally highly correlated with problem-solving ability which is predictive of better adaptive functioning. Measures of conceptual reasoning, an ecologically-valid laboratory measure of problem-solving, and a report measure of adaptive functioning in the natural environment, were administered to children and adults with and…

  17. Effects of Observing Eye Contact on Gaze Following in High-Functioning Autism

    ERIC Educational Resources Information Center

    Böckler, Anne; Timmermans, Bert; Sebanz, Natalie; Vogeley, Kai; Schilbach, Leonhard

    2014-01-01

    Observing eye contact between others enhances the tendency to subsequently follow their gaze and has been suggested to function as a social signal that adds meaning to an upcoming action or event. The present study investigated effects of observed eye contact in high-functioning autism (HFA). Two faces on a screen either looked at or away from…

  18. Social Competence Intervention for Youth with Asperger Syndrome and High-Functioning Autism: An Initial Investigation

    ERIC Educational Resources Information Center

    Stichter, Janine P.; Herzog, Melissa J.; Visovsky, Karen; Schmidt, Carla; Randolph, Jena; Schultz, Tia; Gage, Nicholas

    2010-01-01

    Individuals with high functioning autism (HFA) or Asperger Syndrome (AS) exhibit difficulties in the knowledge or correct performance of social skills. This subgroup's social difficulties appear to be associated with deficits in three social cognition processes: theory of mind, emotion recognition and executive functioning. The current study…

  19. Facial Emotion Recognition in Children with High Functioning Autism and Children with Social Phobia

    ERIC Educational Resources Information Center

    Wong, Nina; Beidel, Deborah C.; Sarver, Dustin E.; Sims, Valerie

    2012-01-01

    Recognizing facial affect is essential for effective social functioning. This study examines emotion recognition abilities in children aged 7-13 years with High Functioning Autism (HFA = 19), Social Phobia (SP = 17), or typical development (TD = 21). Findings indicate that all children identified certain emotions more quickly (e.g., happy [less…

  20. Perception of Dialect Variation by Young Adults with High-Functioning Autism

    ERIC Educational Resources Information Center

    Clopper, Cynthia G.; Rohrbeck, Kristin L.; Wagner, Laura

    2012-01-01

    The linguistic profile of people with Autism spectrum disorders typically involves intact perceptual processing, accompanied by deficits in the social functions of language. In a series of three experiments, the impact of this profile on the perception of regional dialect was examined. Young adults with High-Functioning Autism exhibited similar…

  1. Brain Structure and Resting-State Functional Connectivity in University Professors with High Academic Achievement

    ERIC Educational Resources Information Center

    Li, Weiwei; Yang, Wenjing; Li, Wenfu; Li, Yadan; Wei, Dongtao; Li, Huimin; Qiu, Jiang; Zhang, Qinglin

    2015-01-01

    Creative persons play an important role in technical innovation and social progress. There is little research on the neural correlates with researchers with high academic achievement. We used a combined structural (regional gray matter volume, rGMV) and functional (resting-state functional connectivity analysis, rsFC) approach to examine the…

  2. Health-Related Quality of Life in Children with High-Functioning Autism

    ERIC Educational Resources Information Center

    Potvin, Marie-Christine; Snider, Laurie; Prelock, Patricia A.; Wood-Dauphinee, Sharon; Kehayia, Eva

    2015-01-01

    The health-related quality of life of school-aged children with high-functioning autism is poorly understood. The objectives of this study were to compare the health-related quality of life of children with high-functioning autism to that of typically developing peers and to compare child-self and parent-proxy reports of health-related quality of…

  3. Health-related quality of life in children with high-functioning autism.

    PubMed

    Potvin, Marie-Christine; Snider, Laurie; Prelock, Patricia A; Wood-Dauphinee, Sharon; Kehayia, Eva

    2015-01-01

    The health-related quality of life of school-aged children with high-functioning autism is poorly understood. The objectives of this study were to compare the health-related quality of life of children with high-functioning autism to that of typically developing peers and to compare child-self and parent-proxy reports of health-related quality of life of children. A cross-sectional study of children with high-functioning autism (n = 30) and peers (n = 31) was conducted using the Pediatric Quality of Life Inventory 4.0 Generic Core Scales. Children with high-functioning autism had significantly poorer health-related quality of life than peers whether reported by themselves (p < .001) or their parents (p < .001), although disagreement (intra-class coefficient = -.075) between children and parental scores suggested variance in points of view. This study specifically investigated health-related quality of life in children with high-functioning autism as compared to a sample of peers, from the child's perspective. It strengthens earlier findings that children with high-functioning autism experience poorer health-related quality of life than those without this disorder and points to the importance of clinicians working with families to identify areas in a child's life that promote or hinder their sense of well-being.

  4. Advancing biodiversity-ecosystem functioning science using high-density tree-based experiments over functional diversity gradients.

    PubMed

    Tobner, Cornelia M; Paquette, Alain; Reich, Peter B; Gravel, Dominique; Messier, Christian

    2014-03-01

    Increasing concern about loss of biodiversity and its effects on ecosystem functioning has triggered a series of manipulative experiments worldwide, which have demonstrated a general trend for ecosystem functioning to increase with diversity. General mechanisms proposed to explain diversity effects include complementary resource use and invoke a key role for species' functional traits. The actual mechanisms by which complementary resource use occurs remain, however, poorly understood, as well as whether they apply to tree-dominated ecosystems. Here we present an experimental approach offering multiple innovative aspects to the field of biodiversity-ecosystem functioning (BEF) research. The International Diversity Experiment Network with Trees (IDENT) allows research to be conducted at several hierarchical levels within individuals, neighborhoods, and communities. The network investigates questions related to intraspecific trait variation, complementarity, and environmental stress. The goal of IDENT is to identify some of the mechanisms through which individuals and species interact to promote coexistence and the complementary use of resources. IDENT includes several implemented and planned sites in North America and Europe, and uses a replicated design of high-density tree plots of fixed species-richness levels varying in functional diversity (FD). The design reduces the space and time needed for trees to interact allowing a thorough set of mixtures varying over different diversity gradients (specific, functional, phylogenetic) and environmental conditions (e.g., water stress) to be tested in the field. The intention of this paper is to share the experience in designing FD-focused BEF experiments with trees, to favor collaborations and expand the network to different conditions. PMID:24241640

  5. Calculation of the vacuum Green's function valid for high toroidal mode number in tokamaks.

    NASA Astrophysics Data System (ADS)

    Chance, Morrell; Turnbull, Alan

    2005-10-01

    The present evaluation of the Green's function used for the magmetic scalar potential in vacuum calculations for axisymmetric geometry in the vacuum segments of gato, pest and other mhd stability codes has been found to be deficient for moderately high toroidal mode numbers. This was due to the loss of numerical precision arising from the upward recursion relation used for generating the functions to high mode numbers. The recursion is initiated from the complete elliptic integrals of the first and second kinds. To ameliorate this, a direct integration of the integral representation of the function was crafted to achieve the necessary high accuracy for moderately high mode numbers. At very high mode numbers the loss of numerical precision due to the oscillatory behavior of the integrand is further avoided by judiciously deforming the integration contour in the complex plane. Machine precision, roughly 14 -- 16 digits, accuracy can be achieved by using a combination of both these techniques.

  6. Abnormal functional specialization within medial prefrontal cortex in high-functioning autism: a multi-voxel similarity analysis

    PubMed Central

    Meuwese, Julia D.I.; Towgood, Karren J.; Frith, Christopher D.; Burgess, Paul W.

    2009-01-01

    Multi-voxel pattern analyses have proved successful in ‘decoding’ mental states from fMRI data, but have not been used to examine brain differences associated with atypical populations. We investigated a group of 16 (14 males) high-functioning participants with autism spectrum disorder (ASD) and 16 non-autistic control participants (12 males) performing two tasks (spatial/verbal) previously shown to activate medial rostral prefrontal cortex (mrPFC). Each task manipulated: (i) attention towards perceptual versus self-generated information and (ii) reflection on another person's mental state (‘mentalizing'versus ‘non-mentalizing’) in a 2 × 2 design. Behavioral performance and group-level fMRI results were similar between groups. However, multi-voxel similarity analyses revealed strong differences. In control participants, the spatial distribution of activity generalized significantly between task contexts (spatial/verbal) when examining the same function (attention/mentalizing) but not when comparing different functions. This pattern was disrupted in the ASD group, indicating abnormal functional specialization within mrPFC, and demonstrating the applicability of multi-voxel pattern analysis to investigations of atypical populations. PMID:19174370

  7. The phase-integral method for radiative transfer problems with highly-peaked phase functions

    NASA Technical Reports Server (NTRS)

    Fricke, C. L.

    1978-01-01

    Complete solutions to the radiative transfer equation, including both azimuth and depth dependence, are provided by the discrete-ordinate method of Chandrasekhar, but these solutions are often limited because of large computer requirements. This paper presents a 'phase-integral' method which greatly reduces the number of discrete ordinates needed in the solution for highly peaked phase functions. A composite quadrature method is shown to be effective in further reducing the number of discrete ordinates required for highly anisotropic phase functions. Examples are given to indicate convergence requirements and expected accuracy in the complete solution for Henyey-Greenstein and cloud-type phase functions.

  8. Next-Generation High-Throughput Functional Annotation of Microbial Genomes

    PubMed Central

    Baric, Ralph S.; Damania, Blossom; Miller, Samuel I.; Rubin, Eric J.

    2016-01-01

    ABSTRACT Host infection by microbial pathogens cues global changes in microbial and host cell biology that facilitate microbial replication and disease. The complete maps of thousands of bacterial and viral genomes have recently been defined; however, the rate at which physiological or biochemical functions have been assigned to genes has greatly lagged. The National Institute of Allergy and Infectious Diseases (NIAID) addressed this gap by creating functional genomics centers dedicated to developing high-throughput approaches to assign gene function. These centers require broad-based and collaborative research programs to generate and integrate diverse data to achieve a comprehensive understanding of microbial pathogenesis. High-throughput functional genomics can lead to new therapeutics and better understanding of the next generation of emerging pathogens by rapidly defining new general mechanisms by which organisms cause disease and replicate in host tissues and by facilitating the rate at which functional data reach the scientific community. PMID:27703071

  9. Separation of heavy metals from water by functionalized glycidyl methacrylate poly (high internal phase emulsions).

    PubMed

    Huš, Sebastjan; Kolar, Mitja; Krajnc, Peter

    2016-03-11

    Removal of silver, lead and cadmium ions from both model solutions and real contaminated water was achieved, in a flow through manner, by using highly porous functionalized poly(glycidyl methacrylate) materials, prepared by the polymerisation of high internal phase emulsions (polyHIPE), with significant sorption differences between metals allowing for selective removal. PolyHIPEs, initially prepared from glycidyl methacrylate as a functional monomer, were functionalized with pentaerythritol tetrakis(3-mercaptopropionate), 1,9-nonanedithiol and 2-aminobenzenethiol via the epoxy ring opening on the polymer supports and applied in a flow-through manner via encasements into dedicated disk holders. Capacity of 21.7mg Ag per gram of polymer was found for 1,9-nonanedithiol functionalized polymers, while the capacity was decreasing with the decreasing ionic radius of the metal; the dynamics of sorption also depended on metal ion size and furthermore on the thiol used for the polymer functionalization.

  10. Virtual reality social cognition training for young adults with high-functioning autism.

    PubMed

    Kandalaft, Michelle R; Didehbani, Nyaz; Krawczyk, Daniel C; Allen, Tandra T; Chapman, Sandra B

    2013-01-01

    Few evidence-based social interventions exist for young adults with high-functioning autism, many of whom encounter significant challenges during the transition into adulthood. The current study investigated the feasibility of an engaging Virtual Reality Social Cognition Training intervention focused on enhancing social skills, social cognition, and social functioning. Eight young adults diagnosed with high-functioning autism completed 10 sessions across 5 weeks. Significant increases on social cognitive measures of theory of mind and emotion recognition, as well as in real life social and occupational functioning were found post-training. These findings suggest that the virtual reality platform is a promising tool for improving social skills, cognition, and functioning in autism.

  11. West Nile virus-specific CD4 T cells exhibit direct anti-viral cytokine secretion and cytotoxicity and are sufficient for antiviral protection

    PubMed Central

    Brien, James D.; Uhrlaub, Jennifer L.; Nikolich-Zugich, Janko

    2012-01-01

    CD4 T cells have been shown to be necessary for the prevention of encephalitis during West Nile virus infection. However, the mechanisms used by antigen-specific CD4 T cells to protect mice from West Nile virus encephalitis remain incompletely understood. Contrary to the belief that CD4 T cells are protective because they merely maintain the CD8 T cell response and improve antibody production, we here provide evidence for the direct anti-viral activity of CD4 T cells which functions to protect the host from WNV encephalitis. In adoptive transfers, naïve CD4 T cells protected a significant number of lethally infected RAG−/− mice, demonstrating the protective effect of CD4 T cells independent of B cells and CD8 T cells. To shed light on the mechanism of this protection, we defined the peptide specificities of the CD4 T cells responding to West Nile virus infection in C57BL/6 (H-2b) mice, and used these peptides to characterize the in vivo function of antiviral CD4 T cells. WNV-specific CD4 T cells produced IFN-γ and IL-2, but also showed potential for in vivo and ex vivo cytotoxicity. Furthermore, peptide vaccination using CD4 epitopes conferred protection against lethal West Nile virus infection in immunocompetent mice. These results demonstrate the role of direct effector function of antigen-specific CD4 T cell in preventing severe West Nile virus disease. PMID:19050276

  12. Picture This: Exploring the Lived Experience of High-Functioning Stroke Survivors Using Photovoice.

    PubMed

    Maratos, Marie; Huynh, Linh; Tan, Julia; Lui, Jordon; Jarus, Tal

    2016-07-01

    An increasing number of high-functioning stroke survivors are present with minimal functional impairments and are often discharged with reduced access to community reintegration. Our objectives were to explore the lived experience of high-functioning stroke survivors and to identify gaps in community and rehabilitation services. Photovoice was used with five high-functioning stroke survivors to photo-document their experiences. A modified inductive thematic analysis was used, and meanings behind the photographs were elicited through four focus group sessions followed by photography exhibitions. Five themes emerged: lack of understanding and consideration for persons with disability, emotional and behavioral impacts after stroke, self-reliance and dependence on others, importance of appropriate and accessible services, and financial determinants of quality of life. By including service users' voices; investing in adapted, community-based programs; and providing educational programs for creating attitudinal change among service providers, the polarization between who can and cannot access services will be reduced. PMID:27194645

  13. Do Individuals with High Functioning Autism Have the IQ Profile Associated with Nonverbal Learning Disability?

    ERIC Educational Resources Information Center

    Williams, Diane L.; Goldstein, Gerald; Kojkowski, Nicole; Minshew, Nancy J.

    2008-01-01

    Previously researchers have noted a high level of occurrence of the IQ profile associated with nonverbal learning disability (NLD) in Asperger syndrome (ASP) but not in high functioning autism (HFA). We examined the IQ profile scores of a large sample of children (n=69) and adults (n=77) with HFA, stringently diagnosed according to ADOS, ADI-R,…

  14. Emulation and Mimicry in School Students with Typical Development and with High Functioning Autism

    ERIC Educational Resources Information Center

    Jiménez, Luis; Lorda, María José; Méndez, Cástor

    2014-01-01

    Two samples of participants with typical development (TD) and high functioning autism performed an imitation task where the goal was of high or low salience, and where the modeled action complied with or was contrary to the end-state comfort (ESC) effect. Imitation was affected by the ESC effect in both groups, and participants with autism…

  15. DPP4-inhibitor improves neuronal insulin receptor function, brain mitochondrial function and cognitive function in rats with insulin resistance induced by high-fat diet consumption.

    PubMed

    Pipatpiboon, Noppamas; Pintana, Hiranya; Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2013-03-01

    High-fat diet (HFD) consumption has been demonstrated to cause peripheral and neuronal insulin resistance, and brain mitochondrial dysfunction in rats. Although the dipeptidyl peptidase-4 inhibitor, vildagliptin, is known to improve peripheral insulin sensitivity, its effects on neuronal insulin resistance and brain mitochondrial dysfunction caused by a HFD are unknown. We tested the hypothesis that vildagliptin prevents neuronal insulin resistance, brain mitochondrial dysfunction, learning and memory deficit caused by HFD. Male rats were divided into two groups to receive either a HFD or normal diet (ND) for 12 weeks, after which rats in each group were fed with either vildagliptin (3 mg/kg/day) or vehicle for 21 days. The cognitive function was tested by the Morris Water Maze prior to brain removal for studying neuronal insulin receptor (IR) and brain mitochondrial function. In HFD rats, neuronal insulin resistance and brain mitochondrial dysfunction were demonstrated, with impaired learning and memory. Vildagliptin prevented neuronal insulin resistance by restoring insulin-induced long-term depression and neuronal IR phosphorylation, IRS-1 phosphorylation and Akt/PKB-ser phosphorylation. It also improved brain mitochondrial dysfunction and cognitive function. Vildagliptin effectively restored neuronal IR function, increased glucagon-like-peptide 1 levels and prevented brain mitochondrial dysfunction, thus attenuating the impaired cognitive function caused by HFD.

  16. Functional second harmonic generation microscopy probes molecular dynamics with high temporal resolution

    PubMed Central

    Förderer, Moritz; Georgiev, Tihomir; Mosqueira, Matias; Fink, Rainer H. A.; Vogel, Martin

    2016-01-01

    Second harmonic generation (SHG) microscopy is a powerful tool for label free ex vivo or in vivo imaging, widely used to investigate structure and organization of endogenous SHG emitting proteins such as myosin or collagen. Polarization resolved SHG microscopy renders supplementary information and is used to probe different molecular states. This development towards functional SHG microscopy is calling for new methods for high speed functional imaging of dynamic processes. In this work we present two approaches with linear polarized light and demonstrate high speed line scan measurements of the molecular dynamics of the motor protein myosin with a time resolution of 1 ms in mammalian muscle cells. Such a high speed functional SHG microscopy has high potential to deliver new insights into structural and temporal molecular dynamics under ex vivo or in vivo conditions. PMID:26977360

  17. Low functional β-diversity despite high taxonomic β-diversity among tropical estuarine fish communities.

    PubMed

    Villéger, Sébastien; Ramos Miranda, Julia; Flores Hernandez, Domingo; Mouillot, David

    2012-01-01

    The concept of β-diversity, defined as dissimilarity among communities, has been widely used to investigate biodiversity patterns and community assembly rules. However, in ecosystems with high taxonomic β-diversity, due to marked environmental gradients, the level of functional β-diversity among communities is largely overlooked while it may reveal processes shaping community structure. Here, decomposing biodiversity indices into α (local) and γ (regional) components, we estimated taxonomic and functional β-diversity among tropical estuarine fish communities, through space and time. We found extremely low functional β-diversity values among fish communities (<1.5%) despite high dissimilarity in species composition and species dominance. Additionally, in contrast to the high α and γ taxonomic diversities, α and γ functional diversities were very close to the minimal value. These patterns were caused by two dominant functional groups which maintained a similar functional structure over space and time, despite the strong dissimilarity in taxonomic structure along environmental gradients. Our findings suggest that taxonomic and functional β-diversity deserve to be quantified simultaneously since these two facets can show contrasting patterns and the differences can in turn shed light on community assembly rules.

  18. Exceptional functional recovery and return to high-impact sports after Van Nes rotationplasty.

    PubMed

    Harris, Joshua D; Trinh, Thai Q; Scharschmidt, Thomas J; Mayerson, Joel L

    2013-01-01

    Rotationplasty involves wide resection of lower-extremity malignancy and approximately 180° rotation of the tibia to allow the ankle to function similarly to the former knee joint. It is most commonly used for sarcomas around the knee, such as the distal femur and proximal tibia, in adolescent and young adult patients and is an option for patients with proximal femoral focal deficiency (congenital short femur). Rotationplasty is an alternative to ablative procedures when functional outcome is a consideration or when resection of involved areas and endoprosthetic reconstruction is not possible. This article describes functional status and return to competitive sport after rotationplasty for a lower-extremity bone sarcoma with 3-year follow-up. Despite a postoperative course complicated by a distal tibial physeal injury and femoral neck stress fracture, the patient recovered fully by 1 year postoperatively. Pain free at rest and with activity and with no loss of function, the patient is a successful athlete, playing basketball and baseball and skiing competitively. The patient used a custom-made prosthesis that likely played a role in his high level of function. The patient's high function is evidenced by a maximal or near-maximal possible score on all subsections of the Short Form 36 health survey. Although this level of function is exemplary, it may be more expected in younger, more active, highly motivated, and emotionally and socially mature individuals. PMID:23276345

  19. Exceptional functional recovery and return to high-impact sports after Van Nes rotationplasty.

    PubMed

    Harris, Joshua D; Trinh, Thai Q; Scharschmidt, Thomas J; Mayerson, Joel L

    2013-01-01

    Rotationplasty involves wide resection of lower-extremity malignancy and approximately 180° rotation of the tibia to allow the ankle to function similarly to the former knee joint. It is most commonly used for sarcomas around the knee, such as the distal femur and proximal tibia, in adolescent and young adult patients and is an option for patients with proximal femoral focal deficiency (congenital short femur). Rotationplasty is an alternative to ablative procedures when functional outcome is a consideration or when resection of involved areas and endoprosthetic reconstruction is not possible. This article describes functional status and return to competitive sport after rotationplasty for a lower-extremity bone sarcoma with 3-year follow-up. Despite a postoperative course complicated by a distal tibial physeal injury and femoral neck stress fracture, the patient recovered fully by 1 year postoperatively. Pain free at rest and with activity and with no loss of function, the patient is a successful athlete, playing basketball and baseball and skiing competitively. The patient used a custom-made prosthesis that likely played a role in his high level of function. The patient's high function is evidenced by a maximal or near-maximal possible score on all subsections of the Short Form 36 health survey. Although this level of function is exemplary, it may be more expected in younger, more active, highly motivated, and emotionally and socially mature individuals.

  20. The Inhibitory Receptor NKG2A Sustains Virus-Specific CD8⁺ T Cells in Response to a Lethal Poxvirus Infection.

    PubMed

    Rapaport, Aaron S; Schriewer, Jill; Gilfillan, Susan; Hembrador, Ed; Crump, Ryan; Plougastel, Beatrice F; Wang, Yaming; Le Friec, Gaelle; Gao, Jian; Cella, Marina; Pircher, Hanspeter; Yokoyama, Wayne M; Buller, R Mark L; Colonna, Marco

    2015-12-15

    CD8(+) T cells and NK cells protect from viral infections by killing virally infected cells and secreting interferon-γ. Several inhibitory receptors limit the magnitude and duration of these anti-viral responses. NKG2A, which is encoded by Klrc1, is a lectin-like inhibitory receptor that is expressed as a heterodimer with CD94 on NK cells and activated CD8(+) T cells. Previous studies on the impact of CD94/NKG2A heterodimers on anti-viral responses have yielded contrasting results and the in vivo function of NKG2A remains unclear. Here, we generated Klrc1(-/-) mice and found that NKG2A is selectively required for resistance to ectromelia virus (ECTV). NKG2A functions intrinsically within ECTV-specific CD8(+) T cells to limit excessive activation, prevent apoptosis, and preserve the specific CD8(+) T cell response. Thus, although inhibitory receptors often cause T cell exhaustion and viral spreading during chronic viral infections, NKG2A optimizes CD8(+) T cell responses during an acute poxvirus infection. PMID:26680205

  1. Obesity and diabetes as accelerators of functional decline: can lifestyle interventions maintain functional status in high risk older adults?

    PubMed

    Anton, Stephen D; Karabetian, Christy; Naugle, Kelly; Buford, Thomas W

    2013-09-01

    Obesity and diabetes are known risk factors for the development of physical disability among older adults. With the number of seniors with these conditions rising worldwide, the prevention and treatment of physical disability in these persons have become a major public health challenge. Sarcopenia, the progressive loss of muscle mass and strength, has been identified as a common pathway associated with the initial onset and progression of physical disability among older adults. A growing body of evidence suggests that metabolic dysregulation associated with obesity and diabetes accelerates the progression of sarcopenia, and subsequently functional decline in older adults. The focus of this brief review is on the contributions of obesity and diabetes in accelerating sarcopenia and functional decline among older adults. We also briefly discuss the underexplored interaction between obesity and diabetes that may further accelerate sarcopenia and place obese older adults with diabetes at particularly high risk of disability. Finally, we review findings from studies that have specifically tested the efficacy of lifestyle-based interventions in maintaining the functional status of older persons with obesity and/or diabetes.

  2. Osteocalcin protects pancreatic beta cell function and survival under high glucose conditions

    SciTech Connect

    Kover, Karen; Yan, Yun; Tong, Pei Ying; Watkins, Dara; Li, Xiaoyu; Tasch, James; Hager, Melissa; Clements, Mark; Moore, Wayne V.

    2015-06-19

    Diabetes is characterized by progressive beta cell dysfunction and loss due in part to oxidative stress that occurs from gluco/lipotoxicity. Treatments that directly protect beta cell function and survival in the diabetic milieu are of particular interest. A growing body of evidence suggests that osteocalcin, an abundant non-collagenous protein of bone, supports beta cell function and proliferation. Based on previous gene expression data by microarray, we hypothesized that osteocalcin protects beta cells from glucose-induced oxidative stress. To test our hypothesis we cultured isolated rat islets and INS-1E cells in the presence of normal, high, or high glucose ± osteocalcin for up to 72 h. Oxidative stress and viability/mitochondrial function were measured by H{sub 2}O{sub 2} assay and Alamar Blue assay, respectively. Caspase 3/7 activity was also measured as a marker of apoptosis. A functional test, glucose stimulated insulin release, was conducted and expression of genes/protein was measured by qRT-PCR/western blot/ELISA. Osteocalcin treatment significantly reduced high glucose-induced H{sub 2}O{sub 2} levels while maintaining viability/mitochondrial function. Osteocalcin also significantly improved glucose stimulated insulin secretion and insulin content in rat islets after 48 h of high glucose exposure compared to untreated islets. As expected sustained high glucose down-regulated gene/protein expression of INS1 and BCL2 while increasing TXNIP expression. Interestingly, osteocalcin treatment reversed the effects of high glucose on gene/protein expression. We conclude that osteocalcin can protect beta cells from the negative effects of glucose-induced oxidative stress, in part, by reducing TXNIP expression, thereby preserving beta cell function and survival. - Highlights: • Osteocalcin reduces glucose-induced oxidative stress in beta cells. • Osteocalcin preserves beta cell function and survival under stress conditions. • Osteocalcin reduces glucose

  3. An investigation into the relationship between age and physiological function in highly active older adults

    PubMed Central

    Pollock, Ross D; Carter, Scott; Velloso, Cristiana P; Duggal, Niharika A; Lord, Janet M; Lazarus, Norman R; Harridge, Stephen D R

    2015-01-01

    Despite extensive research, the relationship between age and physiological function remains poorly characterised and there are currently no reliable markers of human ageing. This is probably due to a number of confounding factors, particularly in studies of a cross-sectional nature. These include inter-subject genetic variation, as well as inter-generational differences in nutrition, healthcare and insufficient levels of physical activity as well as other environmental factors. We have studied a cohort of highly and homogeneously active older male (n = 84) and female (n = 41) cyclists aged 55–79 years who it is proposed represent a model for the study of human ageing free from the majority of confounding factors, especially inactivity. The aim of the study was to identify physiological markers of ageing by assessing the relationship between function and age across a wide range of indices. Each participant underwent a detailed physiological profiling which included measures of cardiovascular, respiratory, neuromuscular, metabolic, endocrine and cognitive functions, bone strength, and health and well-being. Significant associations between age and function were observed for many functions. The maximal rate of oxygen consumption ( showed the closest association with age (r = −0.443 to −0.664; P < 0.001), but even here the variance in age for any given level was high, precluding the clear identification of the age of any individual. The results of this cross-sectional study suggest that even when many confounding variables are removed the relationship between function and healthy ageing is complex and likely to be highly individualistic and that physical activity levels must be taken into account in ageing studies. Key Points The relationship between age and physiological function remains poorly defined and there are no physiological markers that can be used to reliably predict the age of an individual. This could be due to a variety of confounding

  4. High-Density Lipoprotein Proteomics: Identifying New Drug Targets and Biomarkers by Understanding Functionality

    PubMed Central

    Gordon, Scott; Durairaj, Anita; Lu, Jason L.; Davidson, W. Sean

    2010-01-01

    Recent proteomics studies on human plasma high-density lipoprotein (HDL) have discovered up to 50 individual protein constituents. Many of these have known functions that vary surprisingly from the lipid transport roles commonly thought to mediate HDL’s ability to protect from coronary artery disease. Given newly discovered roles in inflammation, protease inhibition, complement regulation, and innate immunity, many have begun to view HDL as a broad collection of distinct particle subfamilies, each distinguished by unique protein compositions and functions. Herein we review recent applications of high-resolution proteomics to HDL and summarize evidence supporting the idea of HDL functional subspeciation. These studies have set the stage for a more complete understanding of the molecular basis of HDL functional heterogeneity and hold promise for the identification of new biomarkers that can predict disease or evaluate the success of clinical interventions. PMID:20625533

  5. Iodoindazoles with Selective Magnesiation at Position 3: A Route to Highly Functionalized Indazoles.

    PubMed

    Lam, Bao Vy; Berhault, Yohann; Stiebing, Silvia; Fossey, Christine; Cailly, Thomas; Collot, Valérie; Fabis, Frédéric

    2016-03-18

    A unique route to highly functionalized indazoles is described. A regioselective magnesiation at position 3 of 4-, 5-, 6- and 7-iodo-2-THP-indazoles (THP=tetrahydropyranyl) has been developed using TMPMgCl⋅LiCl (TMP=2,2,6,6-tetramethylpiperidyl). The obtained magnesiate can be trapped by different electrophiles to introduce a wide range of functional groups including halogens, thioalkyls, alcohols, aldehydes, ketones, amides, or esters at position 3. Once this position is functionalized, the iodine atoms can be further reacted through metal-halogen exchange or cross-coupling strategies. Finally, N-substitution reactions allow the synthesis of a variety of highly functionalized indazoles giving access to these valuable scaffolds through a simple and unique route. PMID:26879134

  6. An integrated probabilistic approach for gene function prediction using multiple sources of high-throughput data.

    PubMed

    Zhang, Chao; Joshi, Trupti; Lin, Guan Ning; Xu, Dong

    2008-01-01

    Characterising gene function is one of the major challenging tasks in the post-genomic era. Various approaches have been developed to integrate multiple sources of high-throughput data to predict gene function. Most of those approaches are just used for research purpose and have not been implemented as publicly available tools. Even for those implemented applications, almost all of them are still web-based 'prediction servers' that have to be managed by specialists. This paper introduces a systematic method for integrating various sources of high-throughput data to predict gene function and analyse our prediction results and evaluates its performances based on the competition for mouse gene function prediction (MouseFunc). A stand-alone Java-based software package 'GeneFAS' is freely available at http://digbio. missouri.eduigenefas.

  7. Avoiding high relative air humidity during critical stages of leaf ontogeny is decisive for stomatal functioning.

    PubMed

    Fanourakis, Dimitrios; Carvalho, Susana M P; Almeida, Domingos P F; Heuvelink, Ep

    2011-07-01

    Plants of several species, if grown at high relative air humidity (RH ≥85%), develop stomata that fail to close fully in case of low leaf water potential. We studied the effect of a reciprocal change in RH, at different stages of leaf expansion of Rosa hybrida grown at moderate (60%) or high (95%) RH, on the stomatal closing ability. This was assessed by measuring the leaf transpiration rate in response to desiccation once the leaves had fully expanded. For leaves that started expanding at high RH but completed their expansion after transfer to moderate RH, the earlier this switch took place the better the stomatal functioning. Leaves initially expanding at moderate RH and transferred to high RH exhibited poor stomatal functioning, even when this transfer occurred very late during leaf expansion. Applying a daily abscisic acid (ABA) solution to the leaves of plants grown at continuous high RH was effective in inducing stomatal closure at low water potential, if done before full leaf expansion (FLE). After FLE, stomatal functioning was no longer affected either by the RH or ABA level. The results indicate that the degree of stomatal adaptation depends on both the timing and duration of exposure to high RH. It is concluded that stomatal functionality is strongly dependent on the humidity at which the leaf completed its expansion. The data also show that the effect of ambient RH and the alleviating role of ABA are restricted to the period of leaf expansion. PMID:21457269

  8. Development of a High-Throughput Functional Screen Using Nanowell-Assisted Cell Patterning.

    PubMed

    Ozkumur, Ayca Yalcin; Goods, Brittany A; Love, J Christopher

    2015-09-01

    Living-cell-based screens can facilitate lead discovery of functional therapeutics of interest. A versatile and scalable method is reported that uses dense arrays of nanowells for imparting defined patterns on monolayers of cells. It is shown that this approach can coordinate a multi-component biological assay by designing and implementing a high-throughput, functional nanoliter-scale neutralization assay to identify neutralizing antibodies against HIV.

  9. Geochip: A high throughput genomic tool for linking community structure to functions

    SciTech Connect

    Van Nostrand, Joy D.; Liang, Yuting; He, Zhili; Li, Guanghe; Zhou, Jizhong

    2009-01-30

    GeoChip is a comprehensive functional gene array that targets key functional genes involved in the geochemical cycling of N, C, and P, sulfate reduction, metal resistance and reduction, and contaminant degradation. Studies have shown the GeoChip to be a sensitive, specific, and high-throughput tool for microbial community analysis that has the power to link geochemical processes with microbial community structure. However, several challenges remain regarding the development and applications of microarrays for microbial community analysis.

  10. High-throughput approaches to understanding gene function and mapping network architecture in bacteria.

    PubMed

    Brochado, Ana Rita; Typas, Athanasios

    2013-04-01

    Advances in sequencing technology have provided an unprecedented view of bacterial diversity, along with a daunting number of novel genes. Within this new reality lies the challenge of developing large-scale approaches to assign function to the new genes and place them in pathways. Here, we highlight recent advances on this front, focusing on how high-throughput gene-gene, gene-drug and drug-drug interactions can yield functional and mechanistic inferences in bacteria. PMID:23403119

  11. Interpersonal sensitivity and functioning impairment in youth at ultra-high risk for psychosis.

    PubMed

    Masillo, A; Valmaggia, L R; Saba, R; Brandizzi, M; Lindau, J F; Solfanelli, A; Curto, M; Narilli, F; Telesforo, L; Kotzalidis, G D; Di Pietro, D; D'Alema, M; Girardi, P; Fiori Nastro, P

    2016-01-01

    A personality trait that often elicits poor and uneasy interpersonal relationships is interpersonal sensitivity. The aim of the present study was to explore the relationship between interpersonal sensitivity and psychosocial functioning in individuals at ultra-high risk for psychosis as compared to help-seeking individuals who screened negative for an ultra-high risk of psychosis. A total sample of 147 adolescents and young adult who were help seeking for emerging mental health problems participated in the study. The sample was divided into two groups: 39 individuals who met criteria for an ultra-high-risk mental state (UHR), and 108 (NS). The whole sample completed the Interpersonal Sensitivity Measure (IPSM) and the Global Functioning: Social and Role Scale (GF:SS; GF:RS). Mediation analysis was used to explore whether attenuated negative symptoms mediated the relationship between interpersonal sensitivity and social functioning. Individuals with UHR state showed higher IPSM scores and lower GF:SS and GF:RS scores than NS participants. A statistically negative significant correlation between two IPSM subscales (Interpersonal Awareness and Timidity) and GF:SS was found in both groups. Our results also suggest that the relationship between the aforementioned aspects of interpersonal sensitivity and social functioning was not mediated by negative prodromal symptoms. This study suggests that some aspects of interpersonal sensitivity were associated with low level of social functioning. Assessing and treating interpersonal sensitivity may be a promising therapeutic target to improve social functioning in young help-seeking individuals.

  12. High noise correlation between the functionally connected neurons in emergent V1 microcircuits.

    PubMed

    Bharmauria, Vishal; Bachatene, Lyes; Cattan, Sarah; Chanauria, Nayan; Rouat, Jean; Molotchnikoff, Stéphane

    2016-02-01

    Neural correlations (noise correlations and cross-correlograms) are widely studied to infer functional connectivity between neurons. High noise correlations between neurons have been reported to increase the encoding accuracy of a neuronal population; however, low noise correlations have also been documented to play a critical role in cortical microcircuits. Therefore, the role of noise correlations in neural encoding is highly debated. To this aim, through multi-electrodes, we recorded neuronal ensembles in the primary visual cortex of anaesthetized cats. By computing cross-correlograms, we divulged the functional network (microcircuit) between neurons within an ensemble in relation to a specific orientation. We show that functionally connected neurons systematically exhibit higher noise correlations than functionally unconnected neurons in a microcircuit that is activated in response to a particular orientation. Furthermore, the mean strength of noise correlations for the connected neurons increases steeply than the unconnected neurons as a function of the resolution window used to calculate noise correlations. We suggest that neurons that display high noise correlations in emergent microcircuits feature functional connections which are inevitable for information encoding in the primary visual cortex.

  13. Reversion of somatic mutations of the respiratory syncytial virus-specific human monoclonal antibody Fab19 reveal a direct relationship between association rate and neutralizing potency.

    PubMed

    Bates, John T; Keefer, Christopher J; Utley, Thomas J; Correia, Bruno E; Schief, William R; Crowe, James E

    2013-04-01

    The role of affinity in determining neutralizing potency of mAbs directed against viruses is not well understood. We investigated the kinetic, structural, and functional advantage conferred by individual naturally occurring somatic mutations in the Ab H chain V region of Fab19, a well-described neutralizing human mAb directed to respiratory syncytial virus. Comparison of the affinity-matured Ab Fab19 with recombinant Fab19 Abs that were variants containing reverted amino acids from the inferred unmutated ancestor sequence revealed the molecular basis for affinity maturation of this Ab. Enhanced binding was achieved through mutations in the third H chain CDR (HCDR3) that conferred a markedly faster on-rate and a desirable increase in antiviral neutralizing activity. In contrast, most somatic mutations in the HCDR1 and HCDR2 regions did not significantly enhance Ag binding or antiviral activity. We observed a direct relationship between the measured association rate (Kon) for F protein and antiviral activity. Modeling studies of the structure of the Ag-Ab complex suggested the HCDR3 loop interacts with the antigenic site A surface loop of the respiratory syncytial virus F protein, previously shown to contain the epitope for this Ab by experimentation. These studies define a direct relationship of affinity and neutralizing activity for a viral glycoprotein-specific human mAb.

  14. Three of the four nucleocapsid proteins of Marburg virus, NP, VP35, and L, are sufficient to mediate replication and transcription of Marburg virus-specific monocistronic minigenomes.

    PubMed

    Mühlberger, E; Lötfering, B; Klenk, H D; Becker, S

    1998-11-01

    This paper describes the first reconstituted replication system established for a member of the Filoviridae, Marburg virus (MBGV). MBGV minigenomes containing the leader and trailer regions of the MBGV genome and the chloramphenicol acetyltransferase (CAT) gene were constructed. In MBGV-infected cells, these minigenomes were replicated and encapsidated and could be passaged. Unlike most other members of the order Mononegavirales, filoviruses possess four proteins presumed to be components of the nucleocapsid (NP, VP35, VP30, and L). To determine the protein requirements for replication and transcription, a reverse genetic system was established for MBGV based on the vaccinia virus T7 expression system. Northern blot analysis of viral RNA revealed that three nucleocapsid proteins (NP, VP35, and L) were essential and sufficient for transcription as well as replication and encapsidation. These data indicate that VP35, rather than VP30, is the functional homologue of rhabdo- and paramyxovirus P proteins. The reconstituted replication system was profoundly affected by the NP-to-VP35 expression ratio. To investigate whether CAT gene expression was achieved entirely by mRNA or in part by full-length plus-strand minigenomes, a copy-back minireplicon containing the CAT gene but lacking MBGV-specific transcriptional start sites was employed in the artificial replication system. This construct was replicated without accompanying CAT activity. It was concluded that the CAT activity reflected MBGV-specific transcription and not replication. PMID:9765419

  15. Smart sampling and incremental function learning for very large high dimensional data.

    PubMed

    Loyola R, Diego G; Pedergnana, Mattia; Gimeno García, Sebastián

    2016-06-01

    Very large high dimensional data are common nowadays and they impose new challenges to data-driven and data-intensive algorithms. Computational Intelligence techniques have the potential to provide powerful tools for addressing these challenges, but the current literature focuses mainly on handling scalability issues related to data volume in terms of sample size for classification tasks. This work presents a systematic and comprehensive approach for optimally handling regression tasks with very large high dimensional data. The proposed approach is based on smart sampling techniques for minimizing the number of samples to be generated by using an iterative approach that creates new sample sets until the input and output space of the function to be approximated are optimally covered. Incremental function learning takes place in each sampling iteration, the new samples are used to fine tune the regression results of the function learning algorithm. The accuracy and confidence levels of the resulting approximation function are assessed using the probably approximately correct computation framework. The smart sampling and incremental function learning techniques can be easily used in practical applications and scale well in the case of extremely large data. The feasibility and good results of the proposed techniques are demonstrated using benchmark functions as well as functions from real-world problems.

  16. Containment of simian immunodeficiency virus infection in vaccinated macaques: correlation with the magnitude of virus-specific pre- and postchallenge CD4+ and CD8+ T cell responses.

    PubMed

    Hel, Zdenek; Nacsa, Janos; Tryniszewska, Elzbieta; Tsai, Wen-Po; Parks, Robyn Washington; Montefiori, David C; Felber, Barbara K; Tartaglia, James; Pavlakis, George N; Franchini, Genoveffa

    2002-11-01

    Macaques infected with the SIV strain SIVmac251 develop a disease closely resembling human AIDS characterized by high viremia, progressive loss of CD4(+) T cells, occurrence of opportunistic infection, cachexia, and lymphomas. We report in this study that vaccination with the genetically attenuated poxvirus vector expressing the structural Ags of SIVmac (NYVAC-SIV-gag, pol, env) in combination with priming with DNA-SIV-gag, env resulted in significant suppression of viremia within 2 mo after mucosal exposure to the highly pathogenic SIVmac251 in the majority of vaccinated macaques. The control of viremia in these macaques was long lasting and inversely correlated to the level of both pre- and postchallenge Gag-specific lymphoproliferative responses, as well as to the level of total SIV-specific CD4(+) T lymphocyte responses at the peak of acute viremia as detected by intracellular cytokine-staining assay. Viremia containment also correlated with the frequency of the immunodominant Gag(181-189)CM9 epitope-specific CD8(+) T cells present before the challenge or expanded during acute infection. These data indicate, for the first time, the importance of vaccine-induced CD4(+) Th cell responses as an immune correlate of viremia containment. The results presented in this work also further demonstrate the potential of a DNA-prime/attenuated poxvirus-boost vaccine regimen in an animal model that well mirrors human AIDS.

  17. Retrospective comparison of functional and radiological outcome, between two contemporary high flexion knee designs

    PubMed Central

    Kapoor, Vikash; Chatterjee, Daipayan; Hazra, Sutanu; Chatterjee, Anirban; Garg, Parag; Debnath, Kaustav; Mandal, Soham; Sarkar, Sudipto

    2016-01-01

    Introduction: Patient satisfaction after total knee replacement (TKR) depends on the amount of pain relief and the functional activities achieved. An important criterion of good functional outcome is the amount of flexion achieved and whether the patient can manage high flexion activities. In order to increase the amount of safe flexion, various implant designs have been developed. This study aims to compare the outcome after TKR using two contemporary high flexion knee designs: Sigma CR150 High Flex Knee prosthesis (Depuy, Warsaw, Indiana) and NexGen High Flex Knee prosthesis (Zimmer, Warsaw, Indiana). Material: A retrospective study was conducted with 100 cases of each design and their functional and radiological outcome was assessed after two years of follow-up. Results: The two groups had comparable results in terms of subjective satisfaction, range of motion achieved and radiological outcome. Depuy group fared better than Zimmer in terms of functional outcome (modified Oxford knee score). Conclusion: Depuy group was found to have fared better than Zimmer in terms of functional outcome. However, it is very difficult to rate one design above the other based on our small sample size and short duration of follow-up. PMID:27748254

  18. Prepulse Inhibition of the Acoustic Startle Reflex in High Functioning Autism

    PubMed Central

    Gruendler, Theo O. J.; Vogeley, Kai; Klosterkötter, Joachim; Kuhn, Jens

    2014-01-01

    Background High functioning autism is an autism spectrum disorder that is characterized by deficits in social interaction and communication as well as repetitive and restrictive behavior while intelligence and general cognitive functioning are preserved. According to the weak central coherence account, individuals with autism tend to process information detail-focused at the expense of global form. This processing bias might be reflected by deficits in sensorimotor gating, a mechanism that prevents overstimulation during the transformation of sensory input into motor action. Prepulse inhibition is an operational measure of sensorimotor gating, which indicates an extensive attenuation of the startle reflex that occurs when a startling pulse is preceded by a weaker stimulus, the prepulse. Methods In the present study, prepulse inhibition of acoustic startle was compared between 17 adults with high functioning autism and 17 sex-, age-, and intelligence-matched controls by means of electromyography. Results Results indicate that participants with high functioning autism exhibited significantly higher startle amplitudes than the control group. However, groups did not differ with regard to PPI or habituation of startle. Discussion These findings challenge the results of two previous studies that reported prepulse inhibition deficits in high-functioning autism and suggest that sensorimotor gating is only impaired in certain subgroups with autism spectrum disorder. PMID:24643088

  19. Tunable catalytic properties of bi-functional mixed oxides in ethanol conversion to high value compounds

    DOE PAGESBeta

    Ramasamy, Karthikeyan K.; Gray, Michel; Job, Heather; Smith, Colin; Wang, Yong

    2016-02-03

    Here, a highly versatile ethanol conversion process to selectively generate high value compounds is presented here. By changing the reaction temperature, ethanol can be selectively converted to >C2 alcohols/oxygenates or phenolic compounds over hydrotalcite derived bi-functional MgO–Al2O3 catalyst via complex cascade mechanism. Reaction temperature plays a role in whether aldol condensation or the acetone formation is the path taken in changing the product composition. This article contains the catalytic activity comparison between the mono-functional and physical mixture counterpart to the hydrotalcite derived mixed oxides and the detailed discussion on the reaction mechanisms.

  20. Hypervariable domains of nsP3 proteins of New World and Old World alphaviruses mediate formation of distinct, virus-specific protein complexes.

    PubMed

    Foy, Niall J; Akhrymuk, Maryna; Akhrymuk, Ivan; Atasheva, Svetlana; Bopda-Waffo, Alain; Frolov, Ilya; Frolova, Elena I

    2013-02-01

    Alphaviruses are a group of single-stranded RNA viruses with genomes of positive polarity. They are divided into two geographically isolated groups: the Old World and the New World alphaviruses. Despite their similar genome organizations and virion structures, they differ in many aspects of pathogenesis and interaction with the host cell. Here we present new data highlighting previously unknown differences between these two groups. We found that nsP3 proteins of Sindbis virus (SINV) and Venezuelan equine encephalitis virus (VEEV) form cytoplasmic complexes with different morphologies and protein compositions. Unlike the amorphous aggregates formed by SINV nsP3 and other Old World alphavirus-specific nsP3s, VEEV nsP3 forms unique, large spherical structures with striking symmetry. Moreover, VEEV nsP3 does not interact with proteins previously identified as major components of SINV nsP3 complexes, such as G3BP1 and G3BP2. Importantly, the morphology of the complexes and the specificity of the interaction with cellular proteins are largely determined by the hypervariable domain (HVD) of nsP3. Replacement of the VEEV nsP3 HVD with the corresponding domain of SINV nsP3 rendered this protein capable of interaction with G3BPs. Conversely, replacement of the SINV nsP3 HVD with that of VEEV abolished SINV nsP3's interaction with G3BPs. The replacement of natural HVDs with those from heterologous viruses did not abrogate virus replication, despite these fragments demonstrating very low levels of sequence identity. Our data suggest that in spite of the differences in morphology and composition of the SINV- and VEEV-specific nsP3 complexes, it is likely that they have similar functions in virus replication and modification of the cellular environment.

  1. Hypervariable Domains of nsP3 Proteins of New World and Old World Alphaviruses Mediate Formation of Distinct, Virus-Specific Protein Complexes

    PubMed Central

    Foy, Niall J.; Akhrymuk, Maryna; Akhrymuk, Ivan; Atasheva, Svetlana; Bopda-Waffo, Alain; Frolov, Ilya

    2013-01-01

    Alphaviruses are a group of single-stranded RNA viruses with genomes of positive polarity. They are divided into two geographically isolated groups: the Old World and the New World alphaviruses. Despite their similar genome organizations and virion structures, they differ in many aspects of pathogenesis and interaction with the host cell. Here we present new data highlighting previously unknown differences between these two groups. We found that nsP3 proteins of Sindbis virus (SINV) and Venezuelan equine encephalitis virus (VEEV) form cytoplasmic complexes with different morphologies and protein compositions. Unlike the amorphous aggregates formed by SINV nsP3 and other Old World alphavirus-specific nsP3s, VEEV nsP3 forms unique, large spherical structures with striking symmetry. Moreover, VEEV nsP3 does not interact with proteins previously identified as major components of SINV nsP3 complexes, such as G3BP1 and G3BP2. Importantly, the morphology of the complexes and the specificity of the interaction with cellular proteins are largely determined by the hypervariable domain (HVD) of nsP3. Replacement of the VEEV nsP3 HVD with the corresponding domain of SINV nsP3 rendered this protein capable of interaction with G3BPs. Conversely, replacement of the SINV nsP3 HVD with that of VEEV abolished SINV nsP3's interaction with G3BPs. The replacement of natural HVDs with those from heterologous viruses did not abrogate virus replication, despite these fragments demonstrating very low levels of sequence identity. Our data suggest that in spite of the differences in morphology and composition of the SINV- and VEEV-specific nsP3 complexes, it is likely that they have similar functions in virus replication and modification of the cellular environment. PMID:23221551

  2. Escape from neutralization by the respiratory syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by changes in on-rate of binding to the fusion protein.

    PubMed

    Bates, John T; Keefer, Christopher J; Slaughter, James C; Kulp, Daniel W; Schief, William R; Crowe, James E

    2014-04-01

    The role of binding kinetics in determining neutralizing potency for antiviral antibodies is poorly understood. While it is believed that increased steady-state affinity correlates positively with increased virus-neutralizing activity, the relationship between association or dissociation rate and neutralization potency is unclear. We investigated the effect of naturally-occurring antibody resistance mutations in the RSV F protein on the kinetics of binding to palivizumab. Escape from palivizumab-mediated neutralization of RSV occurred with reduced association rate (Kon) for binding to RSV F protein, while alteration of dissociation rate (Koff) did not significantly affect neutralizing activity. Interestingly, linkage of reduced Kon with reduced potency mirrored the effect of increased Kon found in a high-affinity enhanced potency palivizumab variant (motavizumab). These data suggest that association rate is the dominant factor driving neutralization potency for antibodies to RSV F protein antigenic site A and determines the potency of antibody somatic variants or efficiency of escape of viral glycoprotein variants.

  3. Attenuation of S-cone function at high altitude assessed by electroretinography.

    PubMed

    Schatz, Andreas; Dominik Fischer, M; Schommer, Kai; Zrenner, Eberhart; Bartz-Schmidt, Karl-Ulrich; Gekeler, Florian; Willmann, Gabriel

    2014-04-01

    As impaired S-cone function has been reported psychophysically this study assessed S-cone function during high altitude exposure using electroretinography (ERG) and investigated a possible association with severity of acute mountain sickness (AMS). This work is related to the Tübingen High Altitude Ophthalmology (THAO) study. Standard ERG equipment was used (Diagnosys LLC, Cambridge, UK) with special protocol settings to extract S-cone function. Twelve subjects were analyzed in the current study and examinations were performed in Tübingen, Germany (341m) as baseline and thereafter at the Capanna Margherita, Italy (4559m) at high altitude. Results were compared using a paired t-test. Correlations between ERG measurements and oxygen saturation (SpO2), heart rate (HR) and scores of acute mountain sickness (AMS-C and LL) were calculated using Pearson's correlation coefficients. Amplitudes of S-cone b-waves decreased significantly at high altitude (p=0.02). No significant changes were observed for implicit times of b-waves (p=0.63), a-waves (p=0.75) or for a-wave amplitudes (p=0.78). The incidence of AMS was 50% at high altitude according to AMS-C and LL scores (AMS-C⩾0.7 and LL⩾5). Heart rate increased to 84±10min(-1) and SpO2 decreased to 71.9±5.7% at high altitude. No significant correlation was found between S-cone ERG parameters and SpO2, HR, AMS-C and LL. For the first time our study defines a significant impairment of S-cone function at high altitude time using objective state of the art examination methods. No correlation between the functional impairment of S-cones and levels of AMS was detected. PMID:24576750

  4. Viruses as Modulators of Mitochondrial Functions

    PubMed Central

    Anand, Sanjeev K.; Tikoo, Suresh K.

    2013-01-01

    Mitochondria are multifunctional organelles with diverse roles including energy production and distribution, apoptosis, eliciting host immune response, and causing diseases and aging. Mitochondria-mediated immune responses might be an evolutionary adaptation by which mitochondria might have prevented the entry of invading microorganisms thus establishing them as an integral part of the cell. This makes them a target for all the invading pathogens including viruses. Viruses either induce or inhibit various mitochondrial processes in a highly specific manner so that they can replicate and produce progeny. Some viruses encode the Bcl2 homologues to counter the proapoptotic functions of the cellular and mitochondrial proteins. Others modulate the permeability transition pore and either prevent or induce the release of the apoptotic proteins from the mitochondria. Viruses like Herpes simplex virus 1 deplete the host mitochondrial DNA and some, like human immunodeficiency virus, hijack the host mitochondrial proteins to function fully inside the host cell. All these processes involve the participation of cellular proteins, mitochondrial proteins, and virus specific proteins. This review will summarize the strategies employed by viruses to utilize cellular mitochondria for successful multiplication and production of progeny virus. PMID:24260034

  5. Characterization of the pseudorabies virus-specific immunoglobulin M response and evaluation of its diagnostic use in pigs with preexisting immunity to the virus.

    PubMed Central

    Kimman, T G

    1993-01-01

    Despite preexisting immunity to pseudorabies virus (PRV), pigs may become infected and may or may not show clinical signs of disease. To investigate whether detection of immunoglobulin M (IgM) antibodies to PRV is suitable for diagnosis of recent infection in pigs with (or without) preexisting immunity, the IgM responses of pigs were examined after both experimental and natural infections. Upon inoculation of seronegative pigs with a low dose of a mildly virulent strain of PRV, IgM was first detectable at day 7 postinoculation (p.i.), reached a maximum at day 14 p.i., and became undetectable again at about days 32 to 36 p.i. In inoculated pigs with maternal antibodies against PRV, the IgM response began later and ended sooner, and peak titers were also lower. In immune pigs with maternally derived antibodies, there was apparently no correlation between the virulence of the inoculated strain and the IgM response. The suitability of the IgM enzyme-linked immunosorbent assay (ELISA) for detection of recent infection in the field was compared with that of the virus neutralization (VN) assay and with an ELISA which specifically detects antibodies directed to glycoprotein I (gI) of PRV. Paired sera were obtained from pigs suspected of PRV infection in an area endemic for PRV infection in which vaccination against PRV is often applied. Practically all pigs had antibodies to PRV in the acute phase of the disease. Compared with the VN assay, the specificity of the IgM ELISA was high but its sensitivity was low. However, all three serotests apparently failed to detect some PRV infections. The IgM ELISA appeared to be especially useful as a diagnostic aid for detection of recent infections in pigs with high levels of neutralizing and gI antibodies, probably maternally derived, in the acute phase of the disease. Such pigs may fail to develop a significant rise in VN antibody titer. The IgM ELISA may be the only serotest for monitoring infections in such pigs. PMID:8408547

  6. Escape from neutralization by the respiratory syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by changes in on-rate of binding to the fusion protein

    PubMed Central

    Bates, John T.; Keefer, Christopher J.; Slaughter, James C.; Kulp, Daniel W.; Schiefd, William R.; Crowe, James E.

    2014-01-01

    The role of binding kinetics in determining neutralizing potency for antiviral antibodies is poorly understood. While it is believed that increased steady-state affinity correlates positively with increased virus-neutralizing activity, the relationship between association or dissociation rate and neutralization potency is unclear. We investigated the effect of naturally-occurring antibody resistance mutations in the RSV F protein on the kinetics of binding to palivizumab. Escape from palivizumab-mediated neutralization of RSV occurred with reduced association rate (Kon) for binding to RSV F protein, while alteration of dissociation rate (Koff) did not significantly affect neutralizing activity. Interestingly, linkage of reduced Kon with reduced potency mirrored the effect of increased Kon found in a high-affinity enhanced potency palivizumab variant (motavizumab). These data suggest that association rate is the dominant factor driving neutralization potency for antibodies to RSV F protein antigenic site A and determines the potency of antibody somatic variants or efficiency of escape of viral glycoprotein variants. PMID:24725940

  7. Escape from neutralization by the respiratory syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by changes in on-rate of binding to the fusion protein

    SciTech Connect

    Bates, John T.; Keefer, Christopher J.; Slaughter, James C.; Kulp, Daniel W.; Schief, William R.

    2014-04-15

    The role of binding kinetics in determining neutralizing potency for antiviral antibodies is poorly understood. While it is believed that increased steady-state affinity correlates positively with increased virus-neutralizing activity, the relationship between association or dissociation rate and neutralization potency is unclear. We investigated the effect of naturally-occurring antibody resistance mutations in the RSV F protein on the kinetics of binding to palivizumab. Escape from palivizumab-mediated neutralization of RSV occurred with reduced association rate (K{sub on}) for binding to RSV F protein, while alteration of dissociation rate (K{sub off}) did not significantly affect neutralizing activity. Interestingly, linkage of reduced K{sub on} with reduced potency mirrored the effect of increased K{sub on} found in a high-affinity enhanced potency palivizumab variant (motavizumab). These data suggest that association rate is the dominant factor driving neutralization potency for antibodies to RSV F protein antigenic site A and determines the potency of antibody somatic variants or efficiency of escape of viral glycoprotein variants. - Highlights: • The relationship of affinity to neutralization for virus antibodies is uncertain. • Palivizumab binds to RSV escape mutant fusion proteins, but with reduced affinity. • Association rate (K{sub on}) correlated well with the potency of neutralization.

  8. Diagnostic and functional structure of a high-resolution thyroid nodule clinic.

    PubMed

    Fernández-García, José Carlos; Mancha-Doblas, Isabel; Ortega-Jiménez, María Victoria; Ruiz-Escalante, José Francisco; Castells-Fusté, Ignasi; Tofé-Povedano, Santiago; Argüelles-Jiménez, Iñaki; Tinahones, Francisco José

    2014-01-01

    Appearance of a thyroid nodule has become a daily occurrence in clinical practice. Adequate thyroid nodule assessment requires several diagnostic tests and multiple medical appointments, which results in a substantial delay in diagnosis. Implementation of a high-resolution thyroid nodule clinic largely avoids these drawbacks by condensing in a single appointment all tests required for adequate evaluation of thyroid nodule. This paper reviews the diagnostic and functional structure of a high-resolution thyroid nodule clinic.

  9. Functional genomic and high-content screening for target discovery and deconvolution

    PubMed Central

    Heynen-Genel, Susanne; Pache, Lars; Chanda, Sumit K

    2014-01-01

    Introduction Functional genomic screens apply knowledge gained from the sequencing of the human genome toward rapid methods of identifying genes involved in cellular function based on a specific phenotype. This approach has been made possible through the use of advances in both molecular biology and automation. The utility of this approach has been further enhanced through the application of image-based high content screening, an automated microscopy and quantitative image analysis platform. These approaches can significantly enhance acquisition of novel targets for drug discovery. Areas covered Both the utility and potential issues associated with functional genomic screening approaches are discussed along with examples that illustrate both. The considerations for high content screening applied to functional genomics are also presented. Expert opinion Functional genomic and high content screening are extremely useful in the identification of new drug targets. However, the technical, experimental, and computational parameters have an enormous influence on the results. Thus, although new targets are identified, caution should be applied toward interpretation of screening data in isolation. Genomic screens should be viewed as an integral component of a target identification campaign that requires both the acquisition of orthogonal data, as well as a rigorous validation strategy. PMID:22860749

  10. Expansion and Protection by a Virus-Specific NK Cell Subset Lacking Expression of the Inhibitory NKR-P1B Receptor during Murine Cytomegalovirus Infection.

    PubMed

    Rahim, Mir Munir A; Wight, Andrew; Mahmoud, Ahmad Bakur; Aguilar, Oscar A; Lee, Seung-Hwan; Vidal, Silvia M; Carlyle, James R; Makrigiannis, Andrew P

    2016-09-15

    NK cells play a major role in immune defense against human and murine CMV (MCMV) infection. Although the MCMV genome encodes for MHC class I-homologous decoy ligands for inhibitory NK cell receptors to evade detection, some mouse strains have evolved activating receptors, such as Ly49H, to recognize these ligands and initiate an immune response. In this study, we demonstrate that approximately half of the Ly49H-expressing (Ly49H(+)) NK cells in the spleen and liver of C57BL/6 mice also express the inhibitory NKR-P1B receptor. During MCMV infection, the NKR-P1B(-)Ly49H(+) NK cell subset proliferates to constitute the bulk of the NK cell population. This NK cell subset also confers better protection against MCMV infection compared with the NKR-P1B(+)Ly49H(+) subset. The two populations are composed of cells that differ in their surface expression of receptors such as Ly49C/I and NKG2A/C/E, as well as developmental markers, CD27 and CD11b, and the high-affinity IL-2R (CD25) following infection. Although the NKR-P1B(+) NK cells can produce effector molecules such as IFNs and granzymes, their proliferation is inhibited during infection. A similar phenotype in MCMV-infected Clr-b-deficient mice, which lack the ligand for NKR-P1B, suggests the involvement of ligands other than the host Clr-b. Most interestingly, genetic deficiency of the NKR-P1B, but not Clr-b, results in accelerated virus clearance and recovery from MCMV infection. This study is particularly significant because the mouse NKR-P1B:Clr-b receptor:ligand system represents the closest homolog of the human NKR-P1A:LLT1 system and may have a direct relevance to human CMV infection. PMID:27511735

  11. Multicenter Evaluation of a New, Automated Enzyme-Linked Immunoassay for Detection of Human Immunodeficiency Virus-Specific Antibodies and Antigen

    PubMed Central

    Sickinger, Eva; Stieler, Myriam; Kaufman, Boris; Kapprell, Hans-Peter; West, Daniel; Sandridge, Arnold; Devare, Sushil; Schochetman, Gerald; Hunt, J. C.; Daghfal, David

    2004-01-01

    A collaborative multicenter study was conducted to evaluate the sensitivity, specificity, and precision of a three-step, fully automated, qualitative microparticle-based enzyme-linked immunoassay (AxSYM HIV Ag/Ab Combo; Abbott Laboratories), designed to simultaneously detect (i) antibodies against human immunodeficiency virus type 1 (HIV-1) and/or type 2 (HIV-2) and (ii) HIV p24 antigen. A significant reduction in the HIV seroconversion window was achieved by combining detection of HIV antibodies and antigen into a single assay format. For 22 selected, commercial HIV seroconversion panels, the mean time of detection with the combined-format HIV antigen-antibody assay was reduced by 6.15 days compared to that with a similar third-generation single-format HIV antibody assay. The quantitative sensitivity of the combination assay for the p24 antigen (17.5 pg/ml by use of the p24 quantitative panel VIH SFTS96′) was nearly equivalent to that of single-format antigen tests. The combination assay demonstrated sensitive (100%) detection of anti-HIV immunoglobulin in specimens from individuals in CDC stages A, B, and C and from individuals infected with different HIV-1 group M subtypes, group O, or HIV-2. The apparent specificity for hospitalized patients (n = 1,938) was 99.90%. In a random population of 7,900 volunteer blood donors, the specificity (99.87%) was comparable to that of a third-generation single-format HIV antibody assay (99.92%) on the same donor specimens. In addition, the combination assay was robust to potential interfering specimens. The precision of the combination was high, with intra- and interrun variances of ≤9.3% for each precision panel specimen or assay control and ≤5.3% for the negative assay control. PMID:14715727

  12. Reduced Transplacental Transfer of a Subset of Epstein-Barr Virus-Specific Antibodies to Neonates of Mothers Infected with Plasmodium falciparum Malaria during Pregnancy.

    PubMed

    Ogolla, Sidney; Daud, Ibrahim I; Asito, Amolo S; Sumba, Odada P; Ouma, Collins; Vulule, John; Middeldorp, Jaap M; Dent, Arlene E; Mehta, Saurabh; Rochford, Rosemary

    2015-11-01

    Over 35% of children in a region of malaria endemicity are infected with Epstein-Barr virus (EBV) by 6 months of age. This susceptibility may be linked to impaired transplacental transfer of antibodies. In this study, we determined the effect of malaria exposure during pregnancy on the transfer of EBV-specific maternal antibodies in a region of western Kenya that experiences endemic malaria. Pregnant mothers were recruited and followed up until delivery to determine levels of neonatal malaria exposure. Levels of EBV lytic (viral capsid antigen [VCA], Z transcriptional activator [Zta], and early diffuse antigen complex [EAd]) and EBV latent (EBV nuclear antigen-1 (EBNA1]) and tetanus-specific IgG antibodies were measured in 70 paired maternal and cord blood samples using a Luminex-bead-based assay. A high proportion (63%) of the infants were exposed to malaria in utero. Levels of EBV- and tetanus-specific antibodies were similar in malaria-infected mothers and in mothers who had no detectable malaria infection. Malaria-exposed neonates had significantly lower levels of anti-EBNA1, anti-Zta, and anti-EAd antibodies than were seen in their mothers. In utero malaria exposure resulted in significant reductions in transplacental transfer of anti-VCA-p18 and anti-EBNA1 antibodies of 13% and 22%, respectively. Neonates received significantly low levels of anti-Zta and anti-EAd antibodies irrespective of malaria exposure levels. In multivariate analysis, in utero malaria exposure was associated with a significant reduction in the transfer of anti-VCA-p18 and anti-EBNA1 antibodies to the neonates (P = 0.0234 and P = 0.0017, respectively). Malaria during pregnancy results in differential levels of transfer of EBV-specific antibodies from the mother to the fetus. The impaired transplacental transfer of some antibodies may lead to the malaria-exposed neonates being susceptible to early EBV infection. PMID:26376931

  13. High frame rate retrospectively triggered Cine MRI for assessment of murine diastolic function.

    PubMed

    Coolen, Bram F; Abdurrachim, Desiree; Motaal, Abdallah G; Nicolay, Klaas; Prompers, Jeanine J; Strijkers, Gustav J

    2013-03-01

    To assess left ventricular (LV) diastolic function in mice with Cine MRI, a high frame rate (>60 frames per cardiac cycle) is required. For conventional electrocardiography-triggered Cine MRI, the frame rate is inversely proportional to the pulse repetition time (TR). However, TR cannot be lowered at will to increase the frame rate because of gradient hardware, spatial resolution, and signal-to-noise limitations. To overcome these limitations associated with electrocardiography-triggered Cine MRI, in this paper, we introduce a retrospectively triggered Cine MRI protocol capable of producing high-resolution high frame rate Cine MRI of the mouse heart for addressing left ventricular diastolic function. Simulations were performed to investigate the influence of MRI sequence parameters and the k-space filling trajectory in relation to the desired number of frames per cardiac cycle. An optimized protocol was applied in vivo and compared with electrocardiography-triggered Cine for which a high-frame rate could only be achieved by several interleaved acquisitions. Retrospective high frame rate Cine MRI proved superior to the interleaved electrocardiography-triggered protocols. High spatial-resolution Cine movies with frames rates up to 80 frames per cardiac cycle were obtained in 25 min. Analysis of left ventricular filling rate curves allowed accurate determination of early and late filling rates and revealed subtle impairments in left ventricular diastolic function of diabetic mice in comparison with nondiabetic mice.

  14. Atom-centered symmetry functions for constructing high-dimensional neural network potentials

    NASA Astrophysics Data System (ADS)

    Behler, Jörg

    2011-02-01

    Neural networks offer an unbiased and numerically very accurate approach to represent high-dimensional ab initio potential-energy surfaces. Once constructed, neural network potentials can provide the energies and forces many orders of magnitude faster than electronic structure calculations, and thus enable molecular dynamics simulations of large systems. However, Cartesian coordinates are not a good choice to represent the atomic positions, and a transformation to symmetry functions is required. Using simple benchmark systems, the properties of several types of symmetry functions suitable for the construction of high-dimensional neural network potential-energy surfaces are discussed in detail. The symmetry functions are general and can be applied to all types of systems such as molecules, crystalline and amorphous solids, and liquids.

  15. Centralized PI control for high dimensional multivariable systems based on equivalent transfer function.

    PubMed

    Luan, Xiaoli; Chen, Qiang; Liu, Fei

    2014-09-01

    This article presents a new scheme to design full matrix controller for high dimensional multivariable processes based on equivalent transfer function (ETF). Differing from existing ETF method, the proposed ETF is derived directly by exploiting the relationship between the equivalent closed-loop transfer function and the inverse of open-loop transfer function. Based on the obtained ETF, the full matrix controller is designed utilizing the existing PI tuning rules. The new proposed ETF model can more accurately represent the original processes. Furthermore, the full matrix centralized controller design method proposed in this paper is applicable to high dimensional multivariable systems with satisfactory performance. Comparison with other multivariable controllers shows that the designed ETF based controller is superior with respect to design-complexity and obtained performance.

  16. Effects of high-energy ultrasound on the functional properties of proteins.

    PubMed

    Higuera-Barraza, O A; Del Toro-Sanchez, C L; Ruiz-Cruz, S; Márquez-Ríos, E

    2016-07-01

    In recent years, high-energy ultrasound has been used as an alternative to improve the functional properties of various proteins, such as from milk, eggs, soy and poultry. The benefits of implementing this technology depend on the inherent characteristics of the protein source and the intensity and amplitude of the ultrasound, as well as on the pH, temperature, ionic strength, time, and all of the variables that have an effect on the physicochemical properties of proteins. Therefore, it is necessary to establish the optimal conditions for each type of food. The use of ultrasound is a promising technique in food technology with a low impact on the environment, and it has thus become known as a green technology. Therefore, this review focuses on the application of high-energy ultrasound to food; its effects on the functional properties of proteins; and how different conditions such as the frequency, time, amplitude, temperature, and protein concentration affect the functional properties.

  17. Investigation of a Solution-Processable, Nonspecific Surface Modifier for Low Cost, High Work Function Electrodes.

    PubMed

    Hinckley, Allison C; Wang, Congcong; Pfattner, Raphael; Kong, Desheng; Zhou, Yan; Ecker, Ben; Gao, Yongli; Bao, Zhenan

    2016-08-01

    We demonstrate the ability of the highly fluorinated, chemically inert copolymer poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) to significantly increase the work function of a variety of common electrode materials. The work function change is hypothesized to occur via physisorption of the polymer layer and formation of a surface dipole at the polymer/conductor interface. When incorporated into organic solar cells, an interlayer of PVDF-HFP at an Ag anode increases the open circuit voltage by 0.4 eV and improves device power conversion efficiency by approximately an order of magnitude relative to Ag alone. Solution-processable in air, PVDF-HFP thin films provide one possible route toward achieving low cost, nonreactive, high work function electrodes. PMID:27428045

  18. Perception of dialect variation by young adults with high-functioning autism.

    PubMed

    Clopper, Cynthia G; Rohrbeck, Kristin L; Wagner, Laura

    2012-05-01

    The linguistic profile of people with Autism spectrum disorders typically involves intact perceptual processing, accompanied by deficits in the social functions of language. In a series of three experiments, the impact of this profile on the perception of regional dialect was examined. Young adults with High-Functioning Autism exhibited similar performance to a typically developing comparison group in regional dialect classification and localness rating tasks, suggesting that they can use indexical information in speech to make judgments about the regional background of unfamiliar talkers. However, the participants with High-Functioning Autism were less able to differentiate among the dialects in a language attitudes task, suggesting that they do not share social stereotypes related to dialect variation with the typically developing comparison group.

  19. Parents' Criticisms and Attributions about Their Adult Children with High Functioning Autism or Schizophrenia

    ERIC Educational Resources Information Center

    Wasserman, Stephanie; Weisman de Mamani, Amy; Mundy, Peter

    2010-01-01

    The current study examined the criticism component of expressed emotion (EE) and attributions in parents of adults diagnosed with schizophrenia/schizoaffective disorder (S/SA) or high functioning autism/Asperger's. Consistent with study hypotheses, parents of adults diagnosed with autism/Asperger's disorder exhibited lower levels of high…

  20. Linguistic Characteristics of Individuals with High Functioning Autism and Asperger Syndrome

    ERIC Educational Resources Information Center

    Seung, Hye Kyeung

    2007-01-01

    This study examined the linguistic characteristics of high functioning individuals with autism and Asperger syndrome. Each group consisted of 10 participants who were matched on sex, chronological age, and intelligence scores. Participants generated a narrative after watching a brief video segment of the Social Attribution Task video. Each…

  1. Heterogeneity in Learning Style in Asperger Syndrome and High-Functioning Autism

    ERIC Educational Resources Information Center

    Tsatsanis, Katharine D.

    2004-01-01

    Although children and adolescents with high-functioning autism and Asperger syndrome present with some similar clinical features and challenges, heterogeneity of learning style coupled with the predominance of specific "packages" of materials and methods tends to understate the need for individualization when designing an educational and/or a…

  2. Social Development in Individuals with High Functioning Autism and Asperger Disorder

    ERIC Educational Resources Information Center

    Koegel, Robert L.

    2007-01-01

    Until recently, and even in many current research circles, social behavior in individuals with autism spectrum disorders (including those with high functioning autism or Asperger disorder) was considered to be unmodifiable. Mundy, Henderson, Inge, and Coman and McGee and Daly shed new light on this concept of intractability, suggesting that…

  3. Social Skills Training for Adolescents with Asperger Syndrome and High-Functioning Autism

    ERIC Educational Resources Information Center

    Tse, Jeanie; Strulovitch, Jack; Tagalakis, Vicki; Meng, Linyan; Fombonne, Eric

    2007-01-01

    The effectiveness of a social skills training group for adolescents with Asperger syndrome and high-functioning autism (AS/HFA) was evaluated. Parents of six groups of adolescents (n = 46, 61% male, mean age 14.6) completed questionnaires immediately before and after the 12-week group. Parents and adolescents were surveyed regarding their…

  4. Contemporary Outcome Research and Programming Guidelines for Asperger Syndrome and High-Functioning Autism

    ERIC Educational Resources Information Center

    Tsatsanis, Katharine D.; Foley, Christine; Donehower, Claire

    2004-01-01

    In recent years, there has been an extraordinary surge of interest in achieving a greater understanding of the needs of children and adolescents with Asperger syndrome and high-functioning autism, and with this increase in attention, research has provided a range of directions with respect to treatment guidelines. However, there is also a need for…

  5. Speech-in-Noise Perception in High-Functioning Individuals with Autism or Asperger's Syndrome

    ERIC Educational Resources Information Center

    Alcantara, Jose I.; Weisblatt, Emma J. L.; Moore, Brian C. J.; Bolton, Patrick F.

    2004-01-01

    Background: High-functioning individuals with autism (HFA) or Asperger's syndrome (AS) commonly report difficulties understanding speech in situations where there is background speech or noise. The objective of this study was threefold: (1) to verify the validity of these reports; (2) to quantify the difficulties experienced; and (3) to propose…

  6. Sexual Behavior in High-Functioning Male Adolescents and Young Adults with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Hellemans, Hans; Colson, Kathy; Verbraeken, Christine; Vermeiren, Robert; Deboutte, Dirk

    2007-01-01

    Group home caregivers of 24 institutionalized, male, high-functioning adolescents and young adults with Autism Spectrum Disorder, were interviewed with the Interview Sexuality Autism. Most subjects were reported to express sexual interest and to display some kind of sexual behavior. Knowledge of socio-sexual skills existed, but practical use was…

  7. Do Adults with High Functioning Autism or Asperger Syndrome Differ in Empathy and Emotion Recognition?

    ERIC Educational Resources Information Center

    Montgomery, Charlotte B.; Allison, Carrie; Lai, Meng-Chuan; Cassidy, Sarah; Langdon, Peter E.; Baron-Cohen, Simon

    2016-01-01

    The present study examined whether adults with high functioning autism (HFA) showed greater difficulties in (1) their self-reported ability to empathise with others and/or (2) their ability to read mental states in others' eyes than adults with Asperger syndrome (AS). The Empathy Quotient (EQ) and "Reading the Mind in the Eyes" Test…

  8. Distinct Patterns of Grey Matter Abnormality in High-Functioning Autism and Asperger's Syndrome

    ERIC Educational Resources Information Center

    McAlonan, Grainne M.; Suckling, John; Wong, Naikei; Cheung, Vinci; Lienenkaemper, Nina; Cheung, Charlton; Chua, Siew E.

    2008-01-01

    Background: Autism exists across a wide spectrum and there is considerable debate as to whether children with Asperger's syndrome, who have normal language milestones, should be considered to comprise a subgroup distinct other from high-functioning children with autism (HFA), who have a history of delayed language development. Magnetic resonance…

  9. Pragmatic Inferences in High-Functioning Adults with Autism and Asperger Syndrome

    ERIC Educational Resources Information Center

    Pijnacker, Judith; Hagoort, Peter; Buitelaar, Jan; Teunisse, Jan-Pieter; Geurts, Bart

    2009-01-01

    Although people with autism spectrum disorders (ASD) often have severe problems with pragmatic aspects of language, little is known about their pragmatic reasoning. We carried out a behavioral study on high-functioning adults with autistic disorder (n = 11) and Asperger syndrome (n = 17) and matched controls (n = 28) to investigate whether they…

  10. Review of Social Skills Training Groups for Youth with Asperger Syndrome and High Functioning Autism

    ERIC Educational Resources Information Center

    Cappadocia, M. Catherine; Weiss, Jonathan A.

    2011-01-01

    Although social skills deficits represent core symptoms of Asperger Syndrome and High Functioning Autism, there is limited research investigating the empirical validity of social skills interventions currently being used with these populations. This literature review compares three types of social skills training groups: traditional, cognitive…

  11. Global-Local Visual Processing in High Functioning Children with Autism: Structural vs. Implicit Task Biases

    ERIC Educational Resources Information Center

    Iarocci, Grace; Burack, Jacob A.; Shore, David I.; Mottron, Laurent; Enns, James T.

    2006-01-01

    Global-local processing was examined in high-functioning children with autism and in groups of typically developing children. In experiment 1, the effects of structural bias were tested by comparing visual search that favored access to either local or global targets. The children with autism were not unusually sensitive to either level of visual…

  12. A Comparison of Repetitive Behaviors in Aspergers Disorder and High Functioning Autism

    ERIC Educational Resources Information Center

    Cuccaro, Michael L.; Nations, Laura; Brinkley, Jason; Abramson, Ruth K.; Wright, Harry H.; Hall, Alicia; Gilbert, John; Pericak-Vance, Margaret A.

    2007-01-01

    In this study we compared 33 IQ and age matched pairs of individuals with Aspergers Disorder (ASP) and high functioning autism (HFA) on measures of repetitive behavior. On the Repetitive Behavior Scale-Revised (RBS-R), the ASP and HFA groups showed no differences in RBS-R Intensity score (severity) score or Frequency score (number of problems…

  13. Facial Encoding of Children with High-Functioning Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Volker, Martin A.; Lopata, Christopher; Smith, Donna A.; Thomeer, Marcus L.

    2009-01-01

    Facial encoding of a sample of children with high-functioning autism spectrum disorders (HFASD) was compared to facial encoding of matched typically developing children. Each participant was photographed after being prompted to enact a facial expression for six basic emotions. Raters evaluated (a) the extent to which the photo reflected the…

  14. The Experiences and Needs of Female Adults with High-Functioning Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Baldwin, Susanna; Costley, Debra

    2016-01-01

    There is limited large-scale research into the lived experiences of female adults who have an autism spectrum disorder with no co-occurring intellectual disability. Drawing on the findings of an Australia-wide survey, this report presents self-report data from n = 82 women with high-functioning autism spectrum disorder in the areas of health,…

  15. Preparing Transition-Age Students with High-Functioning Autism Spectrum Disorders for Meaningful Work

    ERIC Educational Resources Information Center

    Lee, Gloria K.; Carter, Erik W.

    2012-01-01

    This article provides an overview of promising essential elements for fostering vocational success among students with high-functioning autism spectrum disorders (HFASDs) by drawing literature from the fields of school-to-work transition for post-secondary students and vocational rehabilitation for individuals with disabilities. We highlight seven…

  16. Avoidant Attachment Style Indicates Job Adaptation of People with High Functional Autistic Spectrum Disorders

    ERIC Educational Resources Information Center

    Yokotani, Kenji

    2011-01-01

    The aim of the present study was to investigate whether or not the avoidant attachment style indicates job adaptation of people with High Functional Autistic Spectrum Disorders (HFASD). HFASD are groups of developmental disorders characterized by impairment of social interaction and normal level of intelligence. Twenty-two people with HFASD…

  17. Investigating Multitasking in High-Functioning Adolescents with Autism Spectrum Disorders Using the Virtual Errands Task

    ERIC Educational Resources Information Center

    Rajendran, Gnanathusharan; Law, Anna S.; Logie, Robert H.; van der Meulen, Marian; Fraser, Diane; Corley, Martin

    2011-01-01

    Using a modified version of the Virtual Errands Task (VET; McGeorge et al. in "Presence-Teleop Virtual Environ" 10(4):375-383, 2001), we investigated the executive ability of multitasking in 18 high-functioning adolescents with ASD and 18 typically developing adolescents. The VET requires multitasking (Law et al. in "Acta Psychol" 122(1):27-44,…

  18. The Syndrome of Hyperlexia vs. High Functioning Autism and Asperger's Syndrome.

    ERIC Educational Resources Information Center

    Kupperman, Phyllis; Bligh, Sally; Barouski, Kathy

    This paper addresses the different characteristics of children with hyperlexia, high functioning autism, and Asperger's Syndrome. It describes the pattern of development of 20 children with the characteristics of hyperlexia (precocious reading development and disordered language acquisition, accompanied with concomitant social and behavioral…

  19. Examining the Effects of Functional Assessment-Based Interventions with High School Students

    ERIC Educational Resources Information Center

    Bruhn, Allison L.; Kaldenberg, Erica; Bappe, Kemlyn Tan; Brandsmeier, Brian; Rila, Ashley; Lanphier, Lindsay; Lewis, Megan; Slater, Alexandra

    2016-01-01

    In two studies, the systematic approach to designing functional assessment-based interventions (FABIs) created by Umbreit, Ferro, Liaupsin, and Lane (2007) was used with high school students receiving special education services in self-contained classrooms reserved for students with persistent behavior problems. In Study 1, an AB design was used…

  20. The Modality Shift Experiment in Adults and Children with High Functioning Autism

    ERIC Educational Resources Information Center

    Williams, Diane L.; Goldstein, Gerald; Minshew, Nancy J.

    2013-01-01

    This study used the modality shift experiment, a relatively simple reaction time measure to visual and auditory stimuli, to examine attentional shifting within and across modalities in 33 children and 42 adults with high-functioning autism as compared to matched numbers of age- and ability-matched typical controls. An exaggerated "modality shift…

  1. Brief Report: Biochemical Correlates of Clinical Impairment in High Functioning Autism and Asperger's Disorder

    ERIC Educational Resources Information Center

    Kleinhans, Natalia M.; Richards, Todd; Weaver, Kurt E.; Liang, Olivia; Dawson, Geraldine; Aylward, Elizabeth

    2009-01-01

    Amygdala dysfunction has been proposed as a critical contributor to social impairment in autism spectrum disorders (ASD). The current study investigated biochemical abnormalities in the amygdala in 20 high functioning adults with autistic disorder or Asperger's disorder and 19 typically developing adults matched on age and IQ. Magnetic resonance…

  2. Narrative Skills in Young Adults with High-Functioning Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Rollins, Pamela Rosenthal

    2014-01-01

    In this study, the author investigated narrative performances of 10 high-functioning young adults with Autism Spectrum Disorders (ASD) across personal and storybook narratives. Narratives were elicited with genre-specific procedures and then transcribed and scored using the narrative scoring scheme (NSS). One-tailed paired-sample t tests were…

  3. Cognitive Differences in Pictorial Reasoning between High-Functioning Autism and Asperger's Syndrome

    ERIC Educational Resources Information Center

    Sahyoun, Cherif P.; Soulieres, Isabelle; Belliveau, John W.; Mottron, Laurent; Mody, Maria

    2009-01-01

    We investigated linguistic and visuospatial processing during pictorial reasoning in high-functioning autism (HFA), Asperger's syndrome (ASP), and age and IQ-matched typically developing participants (CTRL), using three conditions designed to differentially engage linguistic mediation or visuospatial processing (visuospatial, V; semantic, S;…

  4. Teaching Children with High-Functioning Autism Spectrum Disorders to Write Persuasive Essays

    ERIC Educational Resources Information Center

    Asaro-Saddler, Kristie; Bak, Nicole

    2012-01-01

    In this single-subject design study, we examined the effects of an intervention targeting planning and self-regulation strategy use on the persuasive writing of children with high-functioning autism spectrum disorders (ASD). Three 8- to 9-year-old children with ASD in third and fourth grades learned a mnemonic-based strategy for planning and…

  5. Brief Report: Judicial Attitudes Regarding the Sentencing of Offenders with High Functioning Autism

    ERIC Educational Resources Information Center

    Berryessa, Colleen M.

    2016-01-01

    This brief report presents preliminary data on the attitudes of judges on the sentencing of offenders with High Functioning Autism (HFA). Semi-structured telephone interviews were conducted with twenty-one California Superior Court Judges. Interviews were qualitatively coded and constant comparative analysis was utilized. Findings revealed that…

  6. Participation in Daily Activities of Young Adults with High Functioning Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    McCollum, Mary; LaVesser, Patti; Berg, Christine

    2016-01-01

    Young adults with an autism spectrum disorder (ASD) struggle to assume adult roles. This research assessed the feasibility of using the Adolescent and Young Adult Activity Card Sort (AYA-ACS) with emerging adults with high functioning ASD. Two phases were utilized during this research: (1) comparing the activity participation reported by emerging…

  7. Superior Nonverbal Intelligence in Children with High-Functioning Autism or Asperger's Syndrome

    ERIC Educational Resources Information Center

    Chen, Fei; Planche, Pascale; Lemonnier, Eric

    2010-01-01

    Some early studies showed discordance in cognitive strengths and weaknesses in individuals with high-functioning autism (HFA) or Asperger's syndrome (AS). The present study administered the French version of Colored Raven's Progressive Matrices in 14 children with HFA/AS and in 26 chronological age matched peers with typical development. We found…

  8. High fat fed heart failure animals have enhanced mitochondrial function and acyl-coa dehydrogenase activities

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have previously shown that administration of high fat in heart failure (HF) increased mitochondrial respiration and did not alter left ventricular (LV) function. PPARalpha is a nuclear transcription factor that activates expression of genes involved in fatty acid uptake and utilization. We hypoth...

  9. Adolescents with High-Functioning Autism: An Investigation of Comorbid Anxiety and Depression

    ERIC Educational Resources Information Center

    Hammond, Rachel K.; Hoffman, Jennifer M.

    2014-01-01

    Adolescents with high-functioning autism (HFA) possess core social and pragmatic deficits, which interfere with normal relationship development. At a time when friendships are increasingly important, many adolescents with HFA realize they are different from their peers. Initial research has indicated that adolescence is the time when symptoms of…

  10. The Use of Grammatical Morphemes by Mandarin-Speaking Children with High Functioning Autism

    ERIC Educational Resources Information Center

    Zhou, Peng; Crain, Stephen; Gao, Liqun; Tang, Ye; Jia, Meixiang

    2015-01-01

    The present study investigated the production of grammatical morphemes by Mandarin-speaking children with high functioning autism. Previous research found that a subgroup of English-speaking children with autism exhibit deficits in the use of grammatical morphemes that mark tense. In order to see whether this impairment in grammatical morphology…

  11. Gestalt Perception and Local-Global Processing in High-Functioning Autism

    ERIC Educational Resources Information Center

    Bolte, Sven; Holtmann, Martin; Poustka, Fritz; Scheurich, Armin; Schmidt, Lutz

    2007-01-01

    This study examined gestalt perception in high-functioning autism (HFA) and its relation to tasks indicative of local visual processing. Data on of gestalt perception, visual illusions (VI), hierarchical letters (HL), Block Design (BD) and the Embedded Figures Test (EFT) were collected in adult males with HFA, schizophrenia, depression and…

  12. Online Processing of Sentences Containing Noun Modification in Young Children with High-Functioning Autism

    ERIC Educational Resources Information Center

    Bavin, Edith L.; Prendergast, Luke A.; Kidd, Evan; Baker, Emma; Dissanayake, Cheryl

    2016-01-01

    Background: There is variability in the language of children with autism, even those who are high functioning. However, little is known about how they process language structures in real time, including how they handle potential ambiguity, and whether they follow referential constraints. Previous research with older autism spectrum disorder (ASD)…

  13. Inclusion for Students with High-Functioning Autism Spectrum Disorders: Definitions and Decision Making

    ERIC Educational Resources Information Center

    Sansosti, Jenine M.; Sansosti, Frank J.

    2012-01-01

    General education placements are believed to offer numerous benefits for students with high-functioning autism spectrum disorders (HFASDs), yet decisions about including students with HFASDs remain controversial. This article presents data from a qualitative analysis of definitions and decision making considerations for a school district with a…

  14. Basic Reading Skills in High-Functioning Swedish Children with Autism Spectrum Disorders or Attention Disorder

    ERIC Educational Resources Information Center

    Asberg, Jakob; Dahlgren, SvenOlof; Dahlgren Sandberg, Annika

    2008-01-01

    High-functioning children with autism spectrum disorders (ASD) have been reported to have an early success in reading. Children with attention disorders such as DAMP or ADHD, on the other hand, often struggle acquiring reading skills. The primary aim of the study was two-fold: (a) to compare reading performance of children with ASD, DAMP and…

  15. Do Social Attribution Skills Improve with Age in Children with High Functioning Autism Spectrum Disorders?

    ERIC Educational Resources Information Center

    Bal, Elgiz; Yerys, Benjamin E.; Sokoloff, Jennifer L.; Celano, Mark J.; Kenworthy, Lauren; Giedd, Jay N.; Wallace, Gregory L.

    2013-01-01

    Age-related changes in social attribution skills were assessed using the "Triangles Playing Tricks" task in 7-17 year old high functioning children with ASDs (n = 41) and in typically developing (TD) children (n = 58) matched on age, IQ, and sex ratio. Children with ASDs gave responses that received lower intentionality and appropriateness ratings…

  16. White Matter Integrity and Pictorial Reasoning in High-Functioning Children with Autism

    ERIC Educational Resources Information Center

    Sahyoun, Cherif P.; Belliveau, John W.; Mody, Maria

    2010-01-01

    The current study investigated the neurobiological role of white matter in visuospatial versus linguistic processing abilities in autism using diffusion tensor imaging. We examined differences in white matter integrity between high-functioning children with autism (HFA) and typically developing controls (CTRL), in relation to the groups' response…

  17. Brain Mapping of Language and Auditory Perception in High-Functioning Autistic Adults: A PET Study.

    ERIC Educational Resources Information Center

    Muller, R-A.; Behen, M. E.; Rothermel, R. D.; Chugani, D. C.; Muzik, O.; Mangner, T. J.; Chugani, H. T.

    1999-01-01

    A study used positron emission tomography (PET) to study patterns of brain activation during auditory processing in five high-functioning adults with autism. Results found that participants showed reversed hemispheric dominance during the verbal auditory stimulation and reduced activation of the auditory cortex and cerebellum. (CR)

  18. Reading Comprehension Profiles of High-Functioning Students on the Autism Spectrum: A Grounded Theory

    ERIC Educational Resources Information Center

    Williamson, Pamela; Carnahan, Christina R.; Jacobs, Jennifer A.

    2012-01-01

    Using a constructivist grounded theory approach, this study sought to understand what influences reading comprehension and how meaning is made from text among high-functioning individuals with autism spectrum disorder (ASD). Using a think-aloud procedure, 13 individuals ages 7-13 with ASD read 16 passages at their instructional reading level.…

  19. Sex Differences in WISC-III Profiles of Children with High-Functioning Pervasive Developmental Disorders

    ERIC Educational Resources Information Center

    Koyama, Tomonori; Kamio, Yoko; Inada, Naoko; Kurita, Hiroshi

    2009-01-01

    Using the Japanese version of the Wechsler Intelligence Scale for Children-Third Edition (WISC-III), 26 girls with high-functioning (IQ greater than or equal to 70) pervasive developmental disorders (HFPDD) (mean age, 8.2 years) were compared with 116 boys with HFPDD (mean age, 9.0 years). Compared with the boys, the girls scored significantly…

  20. Sexual Attitudes and Knowledge of High-Functioning Adolescents and Adults with Autism.

    ERIC Educational Resources Information Center

    Ousley, Opal Y.; Mesibov, Gary B.

    1991-01-01

    Interviews with 21 high-functioning adults with autism and 20 mildly to moderately mentally retarded adults without autism indicated that the mentally retarded group had more sexual experiences, with no intergroup differences in sexual knowledge or interest. Intelligence quotient was positively correlated with knowledge scores and males had…

  1. Urinary Cortisol Circadian Rhythm in a Group of High-Functioning Children with Autism.

    ERIC Educational Resources Information Center

    Richdale, Amanda L.; Prior, Margot R.

    1992-01-01

    This study found no evidence for abnormal temporal placement of the basal urinary cortisol circadian rhythm in a group of 18 high-functioning children (ages 4-14) with autism. There was a tendency toward cortisol hypersecretion during the day, predominantly in autistic children who were integrated into the normal school system. (Author/JDD)

  2. Treating Anxiety Disorders in Children with High Functioning Autism Spectrum Disorders: A Controlled Trial

    ERIC Educational Resources Information Center

    Chalfant, Anne Marie; Rapee, Ron; Carroll, Louisa

    2007-01-01

    A family-based, cognitive behavioural treatment for anxiety in 47 children with comorbid anxiety disorders and High Functioning Autism Spectrum Disorder (HFA) was evaluated. Treatment involved 12 weekly group sessions and was compared with a waiting list condition. Changes between pre- and post-treatment were examined using clinical interviews as…

  3. Brief Report: Additive and Subtractive Counterfactual Reasoning of Children with High-Functioning Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Begeer, Sander; Terwogt, Mark Meerum; Lunenburg, Patty; Stegge, Hedy

    2009-01-01

    The development of additive ("If only I had done...") and subtractive ("If only I had not done....") counterfactual reasoning was examined in children with High Functioning Autism Spectrum Disorders (HFASD) (n = 72) and typically developing controls (n = 71), aged 6-12 years. Children were presented four stories where they could generate…

  4. Monthly high dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Importance: Vitamin D deficiency has been associated with poor physical performance. Objective: To determine the effectiveness of high dose vitamin D in lowering the risk of functional decline. Design, Setting, and Participants: One-year double-blind, randomized clinical trial conducted in Zurich,...

  5. Atypical Visual Orienting to Gaze- and Arrow-Cues in Adults with High Functioning Autism

    ERIC Educational Resources Information Center

    Vlamings, Petra H. J. M.; Stauder, Johannes E. A.; van Son, Ilona A. M.; Mottron, Laurent

    2005-01-01

    The present study investigates visual orienting to directional cues (arrow or eyes) in adults with high functioning autism (n = 19) and age matched controls (n = 19). A choice reaction time paradigm is used in which eye-or arrow direction correctly (congruent) or incorrectly (incongruent) cues target location. In typically developing participants,…

  6. Processing of Ironic Language in Children with High-Functioning Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Pexman, Penny M.; Rostad, Kristin R.; McMorris, Carly A.; Climie, Emma A.; Stowkowy, Jacqueline; Glenwright, Melanie R.

    2011-01-01

    We examined processing of verbal irony in three groups of children: (1) 18 children with high-functioning Autism Spectrum Disorder (HFASD), (2) 18 typically-developing children, matched to the first group for verbal ability, and (3) 18 typically-developing children matched to the first group for chronological age. We utilized an irony…

  7. Enhancing Reading Comprehension among Students with High-Functioning Autism Spectrum Disorder: A Randomized Pilot Study

    ERIC Educational Resources Information Center

    Roux, Catherine; Dion, Eric; Barrette, Anne

    2015-01-01

    Reading with comprehension is a challenge for students with high-functioning autism spectrum disorder. Unfortunately, research has little to offer to teachers trying to help these students. The present study pilots a new intervention targeting vocabulary, main idea identification, anaphoric relations, and text structure. Students (N = 13, M…

  8. Perception of Talker Age by Young Adults with High-Functioning Autism

    ERIC Educational Resources Information Center

    Clopper, Cynthia G.; Rohrbeck, Kristin L.; Wagner, Laura

    2013-01-01

    People with high-functioning Autism (HFA) can accurately identify social categories from speech, but they have more difficulty connecting linguistic variation in the speech signal to social stereotypes associated with those categories. In the current study, the perception and evaluation of talker age by young adults with HFA was examined. The…

  9. Do Individuals with High-Functioning Autism Who Speak a Tone Language Show Intonation Deficits?

    ERIC Educational Resources Information Center

    Chan, Kary K. L.; To, Carol K. S.

    2016-01-01

    This study investigated whether intonation deficits were observed in 19 Cantonese-speaking adults with high-functioning autism (HFA) when compared to 19 matched neurotypical (NT) controls. This study also investigated the use of sentence-final particles (SFPs) and their relationship with intonation in both groups. Standard deviations…

  10. Virtual Reality Social Cognition Training for Young Adults with High-Functioning Autism

    ERIC Educational Resources Information Center

    Kandalaft, Michelle R.; Didehbani, Nyaz; Krawczyk, Daniel C.; Allen, Tandra T.; Chapman, Sandra B.

    2013-01-01

    Few evidence-based social interventions exist for young adults with high-functioning autism, many of whom encounter significant challenges during the transition into adulthood. The current study investigated the feasibility of an engaging Virtual Reality Social Cognition Training intervention focused on enhancing social skills, social cognition,…

  11. Virtual-Reality-Based Social Interaction Training for Children with High-Functioning Autism

    ERIC Educational Resources Information Center

    Ke, Fengfeng; Im, Tami

    2013-01-01

    Employing the multiple-baseline across-subjects design, the authors examined the implementation and potential effect of a virtual-reality-based social interaction program on the interaction and communication performance of children with high functioning autism. The data were collected via behavior observation and analysis, questionnaires, and…

  12. Identity and Language Functions: High School Chinese Immigrant Students' Code-Switching Dilemmas in ESL Classes

    ERIC Educational Resources Information Center

    Liang, Xiaoping

    2006-01-01

    This study examines classroom code-switching in relation to individual and group identity and to functional use of two languages. It investigates how high school Chinese immigrant students perceive the use of first language (L1) and second language (L2) in class, and how they use these languages during group activities. The interview data…

  13. Sensory Sensitivities and Performance on Sensory Perceptual Tasks in High-Functioning Individuals with Autism

    ERIC Educational Resources Information Center

    Minshew, Nancy J.; Hobson, Jessica A.

    2008-01-01

    Most reports of sensory symptoms in autism are second hand or observational, and there is little evidence of a neurological basis. Sixty individuals with high-functioning autism and 61 matched typical participants were administered a sensory questionnaire and neuropsychological tests of elementary and higher cortical sensory perception. Thirty-two…

  14. Teaching Organizational Skills to Children with High Functioning Autism and Asperger's Syndrome

    ERIC Educational Resources Information Center

    Dorminy, Kimberly Powers; Luscre, Deanna; Gast, David L.

    2009-01-01

    A multiple baseline design across participants was used to evaluate the effectiveness of a file box system plus self-monitoring on the organizational skills of four fourth and fifth grade students with high functioning autism (HFA) and Asperger's Syndrome (AS). Instruction took place in general education classrooms and consisted of teaching…

  15. Summer Treatment Program Improves Behavior of Children with High-Functioning Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Mitchell, Elisabeth Sheridan; Mrug, Sylvie; Patterson, Cryshelle S.; Bailey, Kirstin J.; Bart Hodgens, J.

    2015-01-01

    This study evaluated the effects of a behavioral summer treatment program for children with high-functioning autism spectrum disorder (HFASD). Twenty boys (M = 9.2 years) diagnosed with HFASD participated in the 6-week program across 6 years. Detailed daily behavioral data were collected on a variety of positive and negative social behaviors.…

  16. Thought Disorder in Asperger Syndrome: Comparison with High-Functioning Autism.

    ERIC Educational Resources Information Center

    Ghaziuddin, Mohammad; And Others

    1995-01-01

    This study compared Rorschach test performance of 12 subjects with Asperger syndrome (AS) and 12 subjects with high-functioning autism (HFA, mean age 12 years). AS subjects demonstrated a trend toward greater levels of disorganized thinking than the HFA group and were more likely to be classified as "introversive." The test did not differentiate…

  17. Supporting the Spectrum Hypothesis: Self-Reported Temperament in Children and Adolescents with High Functioning Autism

    ERIC Educational Resources Information Center

    Burrows, Catherine A.; Usher, Lauren V.; Schwartz, Caley B.; Mundy, Peter C.; Henderson, Heather A.

    2016-01-01

    This study tested the "spectrum hypothesis," which posits that children and adolescents with high functioning autism (HFA) differ "quantitatively" but not "qualitatively" from typically developing peers on self-reported temperament. Temperament refers to early-appearing, relatively stable behavioral and emotional…

  18. Lexical and Affective Prosody in Children with High-Functioning Autism

    ERIC Educational Resources Information Center

    Grossman, Ruth B.; Bemis, Rhyannon H.; Skwerer, Daniela Plesa; Tager-Flusberg, Helen

    2010-01-01

    Purpose: To investigate the perception and production of lexical stress and processing of affective prosody in adolescents with high-functioning autism (HFA). We hypothesized preserved processing of lexical and affective prosody but atypical lexical prosody production. Method: Sixteen children with HFA and 15 typically developing (TD) peers…

  19. Pragmatic Inference Abilities in Individuals with Asperger Syndrome or High-Functioning Autism. A Review

    ERIC Educational Resources Information Center

    Loukusa, Soile; Moilanen, Irma

    2009-01-01

    This review summarizes studies involving pragmatic language comprehension and inference abilities in individuals with Asperger syndrome or high-functioning autism. Systematic searches of three electronic databases, selected journals, and reference lists identified 20 studies meeting the inclusion criteria. These studies were evaluated in terms of:…

  20. Cultivation of Empathy in Individuals with High-Functioning Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Jaarsma, Pier

    2013-01-01

    High-functioning individuals with autism spectrum disorder (HF-ASD) typically lack cognitive empathy, compromising their moral agency from both a Kantian and a Humean perspective. Nevertheless, they are capable of exhibiting moral behavior, and sometimes, they exhibit what may be deemed "super-moral" behavior. The empathy deficit poses,…

  1. An Examination of Embedding Character Education into the Daily Functions of High School Instrumental Music Ensembles

    ERIC Educational Resources Information Center

    Sours, James P.

    2009-01-01

    This study was conducted to examine the effectiveness of embedding character education into the daily functions of instrumental music ensembles at Franklin High School in Portland Oregon. The participants in the study were the students of the researcher which may have been a delimitation. Their ages were from 14 to 19 years. Students from…

  2. The Role of Causal and Intentional Judgments in Moral Reasoning in Individuals with High Functioning Autism

    ERIC Educational Resources Information Center

    Buon, Marine; Dupoux, Emmanuel; Jacob, Pierre; Chaste, Pauline; Leboyer, Marion; Zalla, Tiziana

    2013-01-01

    In the present study, we investigated the ability to assign moral responsibility and punishment in adults with high functioning autism or Asperger Syndrome (HFA/AS), using non-verbal cartoons depicting an aggression, an accidental harm or a mere coincidence. Participants were asked to evaluate the agent's causal and intentional roles, his…

  3. Judgments of Social Awkwardness from Brief Exposure to Children with and without High-Functioning Autism

    ERIC Educational Resources Information Center

    Grossman, Ruth B

    2015-01-01

    We form first impressions of many traits based on very short interactions. This study examines whether typical adults judge children with high-functioning autism to be more socially awkward than their typically developing peers based on very brief exposure to still images, audio-visual, video-only, or audio-only information. We used video and…

  4. Perception and Lateralization of Spoken Emotion by Youths with High-Functioning Forms of Autism

    ERIC Educational Resources Information Center

    Baker, Kimberly F.; Montgomery, Allen A.; Abramson, Ruth

    2010-01-01

    The perception and the cerebral lateralization of spoken emotions were investigated in children and adolescents with high-functioning forms of autism (HFFA), and age-matched typically developing controls (TDC). A dichotic listening task using nonsense passages was used to investigate the recognition of four emotions: happiness, sadness, anger, and…

  5. Work, Postsecondary Education, and Psychosocial Functioning Following the Transition from High School

    ERIC Educational Resources Information Center

    Aseltine, Robert H., Jr.; Gore, Susan

    2005-01-01

    Through a two-wave panel study of emerging adults, the authors examine how living situation, work and school roles, and experiences in those roles affect psychosocial functioning following the transition from high school. Enrollment in college programs and fulltime work are associated with lower levels of depressed mood and more positive quality…

  6. Attentional Blink in Young People with High-Functioning Autism and Asperger's Disorder

    ERIC Educational Resources Information Center

    Rinehart, Nicole; Tonge, Bruce; Brereton, Avril; Bradshaw, John

    2010-01-01

    The aim of the study was to examine the temporal characteristics of information processing in individuals with high-functioning autism and Asperger's disorder using a rapid serial visual presentation paradigm. The results clearly showed that such people demonstrate an attentional blink of similar magnitude to comparison groups. This supports the…

  7. Social Skills Training for Children with Asperger Syndrome and High-Functioning Autism

    ERIC Educational Resources Information Center

    White, Susan Williams

    2011-01-01

    This practical, research-based guide provides a wealth of tools and strategies for implementing social skills training in school or clinical settings. Numerous case examples illustrate common social difficulties experienced by children with Asperger syndrome and high-functioning autism; the impact on peer relationships, school performance, and…

  8. Sensory Responsiveness as a Predictor of Social Severity in Children with High Functioning Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Hilton, Claudia L.; Harper, Jacquelyn D.; Kueker, Rachel Holmes; Lang, Andrea Runzi; Abbacchi, Anna M.; Todorov, Alexandre; LaVesser, Patricia D.

    2010-01-01

    This study examines the relationship between sensory responsiveness and social severity in children with high functioning autism spectrum disorders (HFASD; N = 36) and age-matched controls (N = 26) between 6 and 10 years old. Significant relationships were found between social responsiveness scale scores and each of the six sensory profile sensory…

  9. Self-Management for Children with High-Functioning Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Wilkinson, Lee A.

    2008-01-01

    Supporting children with autism spectrum disorders in the general education classroom presents a unique challenge to the teachers and schools that serve them. This article addresses the utility of self-management as a proactive strategy for increasing the task engagement and compliant behavior of high-functioning students with autism. The author…

  10. High Functioning Children with Autism Spectrum Disorder: A Novel Test of Multitasking

    ERIC Educational Resources Information Center

    Mackinlay, Rachael; Charman, Tony; Karmiloff-Smith, Annette

    2006-01-01

    High functioning children with a diagnosis of autism or Asperger's syndrome (HF-ASD) often experience difficulties organising goal-directed actions in their day-to-day lives, requiring support to schedule daily activities. This study aimed to capture these everyday difficulties experimentally using multitasking, a methodology that taps into the…

  11. Emotion Perception in Music in High-Functioning Adolescents with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Quintin, Eve-Marie; Bhatara, Anjali; Poissant, Helene; Fombonne, Eric; Levitin, Daniel J.

    2011-01-01

    Individuals with Autism Spectrum Disorders (ASD) succeed at a range of musical tasks. The ability to recognize musical emotion as belonging to one of four categories (happy, sad, scared or peaceful) was assessed in high-functioning adolescents with ASD (N = 26) and adolescents with typical development (TD, N = 26) with comparable performance IQ,…

  12. Personal Perspectives about Sustaining Inclusion in School Environments for Children with High Functioning Autism

    ERIC Educational Resources Information Center

    Wiatr, Jeanne Malecki

    2016-01-01

    Students, at a partial hospital setting in Western Tennessee with high functioning autism spectrum disorders (HFASD) were being removed from general education classrooms. Researchers have indicated that restrictive settings preclude interaction with neurotypical peers and access to general education experiences. The purpose of this case study was…

  13. Psychological and Neurobehavioral Comparisons of Children with Asperger's Disorder versus High-Functioning Autism

    ERIC Educational Resources Information Center

    Thede, Linda L.; Coolidge, Frederick L.

    2007-01-01

    This study investigated personality and neurobehavioral differences between 16 children with Asperger's Disorder, 15 children with High-Functioning Autism (HFA), and 31 controls, all ranging in age from 5-17 years, M age = 10.7 years, SD = 3.0. Parents rated their children's behaviors on a 44-item autistic symptoms survey and on the 200-item…

  14. High-Functioning Autism and Asperger's Disorder: Utility and Meaning for Families

    ERIC Educational Resources Information Center

    Ruiz Calzada, Luisa; Pistrang, Nancy; Mandy, William P. L.

    2012-01-01

    We used framework analysis to investigate the utility of pervasive developmental disorder diagnoses, interviewing young people (aged 9-16 years) with high-functioning autistic disorder (AD) and Asperger's disorder (AsD), and their parents. Twenty two participants from ten families described both gains and costs resulting from diagnosis. Perceived…

  15. Social Competence Intervention for Elementary Students with Aspergers Syndrome and High Functioning Autism

    ERIC Educational Resources Information Center

    Stichter, Janine P.; O'Connor, Karen V.; Herzog, Melissa J.; Lierheimer, Kristin; McGhee, Stephanie D.

    2012-01-01

    Despite frequent reports of academic success, individuals with high functioning autism or Aspergers Syndrome (HFA/AS) often manifest deficits in social abilities. These deficits can lead to daily difficulties, and negative long-term outcomes. Deficits in social competency are evident in this population from an early age, as children with HFA/AS…

  16. Binding of Multiple Features in Memory by High-Functioning Adults with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Bowler, Dermot M.; Gaigg, Sebastian B.; Gardiner, John M.

    2014-01-01

    Diminished episodic memory and diminished use of semantic information to aid recall by individuals with autism spectrum disorder (ASD) are both thought to result from diminished relational binding of elements of complex stimuli. To test this hypothesis, we asked high-functioning adults with ASD and typical comparison participants to study grids in…

  17. 'Here's the Weavery Looming Up': Verbal Humour in a Woman with High-Functioning Autism.

    ERIC Educational Resources Information Center

    Werth, Abigail; Perkins, Michael; Boucher, Jill

    2001-01-01

    A case study of a 29-year-old woman with high functioning autism is presented. Examples of her use of puns, jokes, neologisms, "portmanteau" words, irreverent humor, irony, sarcasm, and word play based on her obsessional interests are provided and discussed in relation to current theories of autism and of normal humor. (Contains references.)…

  18. An Examination of Handedness and Footedness in Children with High Functioning Autism and Asperger Syndrome

    ERIC Educational Resources Information Center

    Markoulakis, R.; Scharoun, S. M.; Bryden, P. J.; Fletcher, P. C.

    2012-01-01

    Motor control deficits have been documented in children with high functioning autism and Asperger syndrome (HFA/AS), but the extent to which these disorders affect the children's footedness must be delineated. Twelve typically developing (TD) children and 12 children with HFA/AS, ages 6-9 years, were recruited. Motor control skills were assessed…

  19. How Stimulus and Task Complexity Affect Monitoring in High-Functioning Adults with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Koolen, Sophieke; Vissers, Constance Th. W. M.; Egger, Jos I. M.; Verhoeven, Ludo

    2014-01-01

    The present study examined whether individuals with autism spectrum disorder (ASD) are able to update and monitor working memory representations of visual input, and whether performance is influenced by stimulus and task complexity. 15 high-functioning adults with ASD and 15 controls were asked to allocate either elements of abstract figures or…

  20. Repetitive Behavior Profiles in Asperger Syndrome and High-Functioning Autism

    ERIC Educational Resources Information Center

    South, Mikle; Ozonoff, Sally; McMahon, William M.

    2005-01-01

    Although repetitive behaviors are a core diagnostic domain for autism spectrum disorders, research in this area has been neglected. This study had two major aims (1) to provide a detailed characterization of repetitive behaviors in individuals with Asperger Syndrome (AS), high-functioning autism (HFA), and typically developing controls (TD); and…

  1. Numerical evaluation of the incomplete airy functions and their application to high frequency scattering and diffraction

    NASA Technical Reports Server (NTRS)

    Constantinides, E. D.; Marhefka, R. J.

    1992-01-01

    The incomplete Airy integrals serve as canonical functions for the uniform ray optical solutions to several high frequency scattering and diffraction problems that involve a class of integrals characterized by two stationary points that are arbitrarily close to one another or to an integration endpoint. Integrals of such analytical properties describe transition region phenomena associated with composite shadow boundaries. An efficient and accurate method for computing the incomplete Airy functions would make the solutions to such problems useful for engineering purposes. Here, a convergent series solution form for the incomplete Airy functions is derived. Asymptotic expansions involving several terms were also developed and serve as large argument approximations. The combination of the series solution form with the asymptotic formulae provides for an efficient and accurate computation of the incomplete Airy functions. Validation of accuracy is accomplished using direct numerical integration data.

  2. Executive functions and consumption of fruits/ vegetables and high saturated fat foods in young adults.

    PubMed

    Limbers, Christine A; Young, Danielle

    2015-05-01

    Executive functions play a critical role in regulating eating behaviors and have been shown to be associated with overeating which over time can result in overweight and obesity. There has been a paucity of research examining the associations among healthy dietary behaviors and executive functions utilizing behavioral rating scales of executive functioning. The objective of the present cross-sectional study was to evaluate the associations among fruit and vegetable consumption, intake of foods high in saturated fat, and executive functions using the Behavioral Rating Inventory of Executive Functioning-Adult Version. A total of 240 university students completed the Behavioral Rating Inventory of Executive Functioning-Adult Version, the 26-Item Eating Attitudes Test, and the Diet subscale of the Summary of Diabetes Self-Care Activities Questionnaire. Multiple linear regression analysis was conducted with two separate models in which fruit and vegetable consumption and saturated fat intake were the outcomes. Demographic variables, body mass index, and eating styles were controlled for in the analysis. Better initiation skills were associated with greater intake of fruits and vegetables in the last 7 days (standardized beta = -0.17; p < 0.05). Stronger inhibitory control was associated with less consumption of high fat foods in the last 7 days (standardized beta = 0.20; p < 0.05) in the multiple linear regression analysis. Executive functions that predict fruit and vegetable consumption are distinct from those that predict avoidance of foods high in saturated fat. Future research should investigate whether continued skill enhancement in initiation and inhibition following standard behavioral interventions improves long-term maintenance of weight loss.

  3. Selective Loss of Early Differentiated, Highly Functional PD1high CD4 T Cells with HIV Progression

    PubMed Central

    Paris, Robert M.; Petrovas, Constantinos; Ferrando-Martinez, Sara; Moysi, Eirini; Boswell, Kristin L.; Archer, Eva; Yamamoto, Takuya; Ambrozak, David; Casazza, Joseph P.; Haubrich, Richard; Connors, Mark; Ake, Julie; Kim, Jerome H.; Koup, Richard A.

    2015-01-01

    The role of PD-1 expression on CD4 T cells during HIV infection is not well understood. Here, we describe the differential expression of PD-1 in CD127high CD4 T cells within the early/intermediate differentiated (EI) (CD27highCD45RAlow) T cell population among uninfected and HIV-infected subjects, with higher expression associated with decreased viral replication (HIV-1 viral load). A significant loss of circulating PD-1highCTLA-4low CD4 T cells was found specifically in the CD127highCD27highCD45RAlow compartment, while initiation of antiretroviral treatment, particularly in subjects with advanced disease, reversed these dynamics. Increased HIV-1 Gag DNA was also found in PD-1high compared to PD-1low ED CD4 T cells. In line with an increased susceptibility to HIV infection, PD-1 expression in this CD4 T cell subset was associated with increased activation and expression of the HIV co-receptor, CCR5. Rather than exhaustion, this population produced more IFN-g, MIP1-a, IL-4, IL-10, and IL-17a compared to PD-1low EI CD4 T cells. In line with our previous findings, PD-1high EI CD4 T cells were also characterized by a high expression of CCR7, CXCR5 and CCR6, a phenotype associated with increased in vitro B cell help. Our data show that expression of PD-1 on early-differentiated CD4 T cells may represent a population that is highly functional, more susceptible to HIV infection and selectively lost in chronic HIV infection. PMID:26678998

  4. Vaccine-Induced Simian Immunodeficiency Virus-Specific CD8+ T-Cell Responses Focused on a Single Nef Epitope Select for Escape Variants Shortly after Infection

    PubMed Central

    Tully, Damien C.; Cruz, Michael A.; Power, Karen A.; Veloso de Santana, Marlon G.; Bean, David J.; Ogilvie, Colin B.; Gadgil, Rujuta; Lima, Noemia S.; Magnani, Diogo M.; Ejima, Keisuke; Allison, David B.; Piatak, Michael; Altman, John D.; Parks, Christopher L.; Rakasz, Eva G.; Capuano, Saverio; Galler, Ricardo; Bonaldo, Myrna C.; Lifson, Jeffrey D.; Allen, Todd M.; Watkins, David I.

    2015-01-01

    ABSTRACT Certain major histocompatibility complex class I (MHC-I) alleles (e.g., HLA-B*27) are enriched among human immunodeficiency virus type 1 (HIV-1)-infected individuals who suppress viremia without treatment (termed “elite controllers” [ECs]). Likewise, Mamu-B*08 expression also predisposes rhesus macaques to control simian immunodeficiency virus (SIV) replication. Given the similarities between Mamu-B*08 and HLA-B*27, SIV-infected Mamu-B*08+ animals provide a model to investigate HLA-B*27-mediated elite control. We have recently shown that vaccination with three immunodominant Mamu-B*08-restricted epitopes (Vif RL8, Vif RL9, and Nef RL10) increased the incidence of elite control in Mamu-B*08+ macaques after challenge with the pathogenic SIVmac239 clone. Furthermore, a correlate analysis revealed that CD8+ T cells targeting Nef RL10 was correlated with improved outcome. Interestingly, this epitope is conserved between SIV and HIV-1 and exhibits a delayed and atypical escape pattern. These features led us to postulate that a monotypic vaccine-induced Nef RL10-specific CD8+ T-cell response would facilitate the development of elite control in Mamu-B*08+ animals following repeated intrarectal challenges with SIVmac239. To test this, we vaccinated Mamu-B*08+ animals with nef inserts in which Nef RL10 was either left intact (group 1) or disrupted by mutations (group 2). Although monkeys in both groups mounted Nef-specific cellular responses, only those in group 1 developed Nef RL10-specific CD8+ T cells. These vaccine-induced effector memory CD8+ T cells did not prevent infection. Escape variants emerged rapidly in the group 1 vaccinees, and ultimately, the numbers of ECs were similar in groups 1 and 2. High-frequency vaccine-induced CD8+ T cells focused on a single conserved epitope and therefore did not prevent infection or increase the incidence of elite control in Mamu-B*08+ macaques. IMPORTANCE Since elite control of chronic-phase viremia is a classic

  5. The neural basis of deictic shifting in linguistic perspective-taking in high-functioning autism

    PubMed Central

    Liu, Yanni; Williams, Diane L.; Keller, Timothy A.; Minshew, Nancy J.; Just, Marcel Adam

    2011-01-01

    Personal pronouns, such as ‘I’ and ‘you’, require a speaker/listener to continuously re-map their reciprocal relation to their referent, depending on who is saying the pronoun. This process, called ‘deictic shifting’, may underlie the incorrect production of these pronouns, or ‘pronoun reversals’, such as referring to oneself with the pronoun ‘you’, which has been reported in children with autism. The underlying neural basis of deictic shifting, however, is not understood, nor has the processing of pronouns been studied in adults with autism. The present study compared the brain activation pattern and functional connectivity (synchronization of activation across brain areas) of adults with high-functioning autism and control participants using functional magnetic resonance imaging in a linguistic perspective-taking task that required deictic shifting. The results revealed significantly diminished frontal (right anterior insula) to posterior (precuneus) functional connectivity during deictic shifting in the autism group, as well as reliably slower and less accurate behavioural responses. A comparison of two types of deictic shifting revealed that the functional connectivity between the right anterior insula and precuneus was lower in autism while answering a question that contained the pronoun ‘you’, querying something about the participant’s view, but not when answering a query about someone else’s view. In addition to the functional connectivity between the right anterior insula and precuneus being lower in autism, activation in each region was atypical, suggesting over reliance on individual regions as a potential compensation for the lower level of collaborative interregional processing. These findings indicate that deictic shifting constitutes a challenge for adults with high-functioning autism, particularly when reference to one’s self is involved, and that the functional collaboration of two critical nodes, right anterior insula

  6. A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence.

    PubMed

    Spain, S L; Pedroso, I; Kadeva, N; Miller, M B; Iacono, W G; McGue, M; Stergiakouli, E; Smith, G D; Putallaz, M; Lubinski, D; Meaburn, E L; Plomin, R; Simpson, M A

    2016-08-01

    Although individual differences in intelligence (general cognitive ability) are highly heritable, molecular genetic analyses to date have had limited success in identifying specific loci responsible for its heritability. This study is the first to investigate exome variation in individuals of extremely high intelligence. Under the quantitative genetic model, sampling from the high extreme of the distribution should provide increased power to detect associations. We therefore performed a case-control association analysis with 1409 individuals drawn from the top 0.0003 (IQ >170) of the population distribution of intelligence and 3253 unselected population-based controls. Our analysis focused on putative functional exonic variants assayed on the Illumina HumanExome BeadChip. We did not observe any individual protein-altering variants that are reproducibly associated with extremely high intelligence and within the entire distribution of intelligence. Moreover, no significant associations were found for multiple rare alleles within individual genes. However, analyses using genome-wide similarity between unrelated individuals (genome-wide complex trait analysis) indicate that the genotyped functional protein-altering variation yields a heritability estimate of 17.4% (s.e. 1.7%) based on a liability model. In addition, investigation of nominally significant associations revealed fewer rare alleles associated with extremely high intelligence than would be expected under the null hypothesis. This observation is consistent with the hypothesis that rare functional alleles are more frequently detrimental than beneficial to intelligence.

  7. Simultaneous virus-specific detection of the two cassava brown streak-associated viruses by RT-PCR reveals wide distribution in East Africa, mixed infections, and infections in Manihot glaziovii.

    PubMed

    Mbanzibwa, D R; Tian, Y P; Tugume, A K; Mukasa, S B; Tairo, F; Kyamanywa, S; Kullaya, A; Valkonen, J P T

    2011-02-01

    The expanding cassava brown streak disease (CBSD) epidemic in East Africa is caused by two ipomoviruses (genus Ipomovirus; Potyviridae), namely, Cassava brown streak virus (CBSV), and Ugandan cassava brown streak virus (UCBSV) that was described recently. A reverse transcription polymerase chain reaction (RT-PCR) based diagnostic method was developed in this study for simultaneous virus-specific detection of the two viruses. Results showed that CBSV and UCBSV are distributed widely in the highlands (> 1000 m above the sea level) of the Lake Victoria zone in Uganda and Tanzania and also in the Indian Ocean costal lowlands of Tanzania. Isolates of UCBSV from the Lake Victoria zone were placed to two phylogenetic clusters in accordance with their origin in Uganda or Tanzania, respectively. Mixed infections with CBSV and UCBSV were detected in many cassava plants in the areas surveyed. CBSV was also detected in the perennial species Manihot glaziovii (DNA-barcoded in this study) in Tanzania, which revealed the first virus reservoir other than cassava. The method for detection of CBSV and UCBSV described in this study has important applications for plant quarantine, resistance breeding of cassava, and studies on epidemiology and control of CBSD in East Africa.

  8. Antibody-capture enzyme-linked immunosorbent assays that use enzyme-labelled antigen for detection of virus-specific immunoglobulin M, A and G in patients with varicella or herpes zoster.

    PubMed Central

    van Loon, A. M.; van der Logt, J. T.; Heessen, F. W.; Heeren, M. C.; Zoll, J.

    1992-01-01

    Antibody-capture enzyme-linked immunosorbent assays (AC-ELISA) which use enzyme-labelled antigen were developed for detection of varicella-zoster virus-(VZV) specific IgM, IgA and IgG antibody in patients with varicella or herpes zoster and in sera from healthy individuals. All 18 patients with varicella developed a VZV-IgM and a VZV-IgG response, 17 also a VZV-IgA response. In contrast, all 19 patients with herpes zoster were shown to be positive for VZV-IgA whereas only 13 of these reacted positively for VZV-IgM. A VZV-IgM response was detected in only two sera from 100 healthy individuals and an IgA response in only one. The presence of virus-specific IgA and IgG in the cerebrospinal fluid as determined by AC-ELISA was a useful indicator of VZV infection of the central nervous system. By AC-ELISA, VZV-IgG was detected predominantly in sera from patients with acute or recent VZV infection. Only 14 sera from 100 healthy individuals were positive for VZV-IgG by AC-ELISA, whereas all were positive by an indirect ELISA. These results indicate that AC-ELISA's may be useful assays for determination for acute or recurrent VZV infection, but are not suitable for determination of past infection with this virus. PMID:1312479

  9. Quantitative high-pressure pair distribution function analysis of nanocrystalline gold

    NASA Astrophysics Data System (ADS)

    Martin, C. David; Antao, Sytle M.; Chupas, Peter J.; Lee, Peter L.; Shastri, Sarvjit D.; Parise, John B.

    2005-02-01

    Using a diamond anvil cell with high-energy monochromatic x rays, we have studied the total scattering of nanocrystalline gold to 20Å-1 at pressures up to 10GPa in a hydrostatic alcohol pressure-medium. Through direct Fourier transformation of the structure function [S(Q)], pair distribution functions (PDFs) [G(r)] are calculated without Kaplow-type iterative corrections. Quantitative high-pressure PDF (QHP-PDF) analysis is performed via full-profile least-squares modeling and confirmed through comparison of Rietveld analysis of Bragg diffraction. The quality of the high pressure PDFs obtained demonstrates the integrity of our technique and suggests the feasibility of future QHP-PDF studies of liquids, disordered solids, and materials at phase transition under pressure.

  10. The experiences and needs of female adults with high-functioning autism spectrum disorder.

    PubMed

    Baldwin, Susanna; Costley, Debra

    2016-05-01

    There is limited large-scale research into the lived experiences of female adults who have an autism spectrum disorder with no co-occurring intellectual disability. Drawing on the findings of an Australia-wide survey, this report presents self-report data from n = 82 women with high-functioning autism spectrum disorder in the areas of health, education, employment, social and community activities. Where relevant, comparisons are provided with the male subset of the same study population; however, in the majority of analyses, no discernible gender differences emerged. The findings highlight the diverse and complex challenges faced by women with high-functioning autism spectrum disorder, including high levels of mental health disorder, unmet support needs in education settings and the workplace, and social exclusion and isolation.

  11. Functional Knowledge Transfer for High-accuracy Prediction of Under-studied Biological Processes

    PubMed Central

    Rowland, Jessica; Guan, Yuanfang; Bongo, Lars A.; Burdine, Rebecca D.; Troyanskaya, Olga G.

    2013-01-01

    A key challenge in genetics is identifying the functional roles of genes in pathways. Numerous functional genomics techniques (e.g. machine learning) that predict protein function have been developed to address this question. These methods generally build from existing annotations of genes to pathways and thus are often unable to identify additional genes participating in processes that are not already well studied. Many of these processes are well studied in some organism, but not necessarily in an investigator's organism of interest. Sequence-based search methods (e.g. BLAST) have been used to transfer such annotation information between organisms. We demonstrate that functional genomics can complement traditional sequence similarity to improve the transfer of gene annotations between organisms. Our method transfers annotations only when functionally appropriate as determined by genomic data and can be used with any prediction algorithm to combine transferred gene function knowledge with organism-specific high-throughput data to enable accurate function prediction. We show that diverse state-of-art machine learning algorithms leveraging functional knowledge transfer (FKT) dramatically improve their accuracy in predicting gene-pathway membership, particularly for processes with little experimental knowledge in an organism. We also show that our method compares favorably to annotation transfer by sequence similarity. Next, we deploy FKT with state-of-the-art SVM classifier to predict novel genes to 11,000 biological processes across six diverse organisms and expand the coverage of accurate function predictions to processes that are often ignored because of a dearth of annotated genes in an organism. Finally, we perform in vivo experimental investigation in Danio rerio and confirm the regulatory role of our top predicted novel gene, wnt5b, in leftward cell migration during heart development. FKT is immediately applicable to many bioinformatics techniques and will

  12. Functional ultrasound imaging of intrinsic connectivity in the living rat brain with high spatiotemporal resolution

    PubMed Central

    Osmanski, Bruno-Félix; Pezet, Sophie; Ricobaraza, Ana; Lenkei, Zsolt; Tanter, Mickael

    2014-01-01

    Long-range coherences in spontaneous brain activity reflect functional connectivity. Here we propose a novel, highly resolved connectivity mapping approach, using ultrafast functional ultrasound (fUS), which enables imaging of cerebral microvascular haemodynamics deep in the anaesthetized rodent brain, through a large thinned-skull cranial window, with pixel dimensions of 100 μm × 100 μm in-plane. The millisecond-range temporal resolution allows unambiguous cancellation of low-frequency cardio-respiratory noise. Both seed-based and singular value decomposition analysis of spatial coherences in the low-frequency (<0.1 Hz) spontaneous fUS signal fluctuations reproducibly report, at different coronal planes, overlapping high-contrast, intrinsic functional connectivity patterns. These patterns are similar to major functional networks described in humans by resting-state fMRI, such as the lateral task-dependent network putatively anticorrelated with the midline default-mode network. These results introduce fUS as a powerful novel neuroimaging method, which could be extended to portable systems for three-dimensional functional connectivity imaging in awake and freely moving rodents. PMID:25277668

  13. Liver disease alters high-density lipoprotein composition, metabolism and function.

    PubMed

    Trieb, Markus; Horvath, Angela; Birner-Gruenberger, Ruth; Spindelboeck, Walter; Stadlbauer, Vanessa; Taschler, Ulrike; Curcic, Sanja; Stauber, Rudolf E; Holzer, Michael; Pasterk, Lisa; Heinemann, Akos; Marsche, Gunther

    2016-07-01

    High-density lipoproteins (HDL) are important endogenous inhibitors of inflammatory responses. Functional impairment of HDL might contribute to the excess mortality experienced by patients with liver disease, but the effect of cirrhosis on HDL metabolism and function remain elusive. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function using apolipoprotein (apo) B-depleted sera from patients with compensated cirrhosis, patients with acutely decompensated cirrhosis and healthy controls. We observed that sera of cirrhotic patients showed reduced levels of HDL-cholesterol and profoundly suppressed activities of several enzymes involved in HDL maturation and metabolism. Native gel electrophoresis analyses revealed that cirrhotic serum HDL shifts towards the larger HDL2 subclass. Proteomic assessment of isolated HDL identified several proteins, including apoA-I, apoC-III, apoE, paraoxonase 1 and acute phase serum amyloid A to be significantly altered in cirrhotic patients. With regard to function, these alterations in levels, composition and structure of HDL were strongly associated with metrics of function of apoB-depleted sera, including cholesterol efflux capability, paraoxonase activity, the ability to inhibit monocyte production of cytokines and endothelial regenerative activities. Of particular interest, cholesterol efflux capacity appeared to be strongly associated with liver disease mortality. Our findings may be clinically relevant and improve our ability to monitor cirrhotic patients at high risk. PMID:27106140

  14. Liver disease alters high-density lipoprotein composition, metabolism and function.

    PubMed

    Trieb, Markus; Horvath, Angela; Birner-Gruenberger, Ruth; Spindelboeck, Walter; Stadlbauer, Vanessa; Taschler, Ulrike; Curcic, Sanja; Stauber, Rudolf E; Holzer, Michael; Pasterk, Lisa; Heinemann, Akos; Marsche, Gunther

    2016-07-01

    High-density lipoproteins (HDL) are important endogenous inhibitors of inflammatory responses. Functional impairment of HDL might contribute to the excess mortality experienced by patients with liver disease, but the effect of cirrhosis on HDL metabolism and function remain elusive. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function using apolipoprotein (apo) B-depleted sera from patients with compensated cirrhosis, patients with acutely decompensated cirrhosis and healthy controls. We observed that sera of cirrhotic patients showed reduced levels of HDL-cholesterol and profoundly suppressed activities of several enzymes involved in HDL maturation and metabolism. Native gel electrophoresis analyses revealed that cirrhotic serum HDL shifts towards the larger HDL2 subclass. Proteomic assessment of isolated HDL identified several proteins, including apoA-I, apoC-III, apoE, paraoxonase 1 and acute phase serum amyloid A to be significantly altered in cirrhotic patients. With regard to function, these alterations in levels, composition and structure of HDL were strongly associated with metrics of function of apoB-depleted sera, including cholesterol efflux capability, paraoxonase activity, the ability to inhibit monocyte production of cytokines and endothelial regenerative activities. Of particular interest, cholesterol efflux capacity appeared to be strongly associated with liver disease mortality. Our findings may be clinically relevant and improve our ability to monitor cirrhotic patients at high risk.

  15. Effects of High Dietary HEME Iron and Radiation on Cardiovascular Function

    NASA Technical Reports Server (NTRS)

    Westby, Christian M.; Brown, A. K.; Platts, S. H.

    2012-01-01

    The radiation related health risks to astronauts is of particular concern to NASA. Data support that exposure to radiation is associated with a number of disorders including a heightened risk for cardiovascular diseases. Independent of radiation, altered nutrient status (e.g. high dietary iron) also increases ones risk for cardiovascular disease. However, it is unknown whether exposure to radiation in combination with high dietary iron further increases ones cardiovascular risk. The intent of our proposal is to generate compulsory data examining the combined effect of radiation exposure and iron overload on sensitivity to radiation injury to address HRP risks: 1) Risk Factor of Inadequate Nutrition; 2) Risk of Cardiac Rhythm Problems; and 3) Risk of Degenerative Tissue or other Health Effects from Space Radiation. Towards our goal we propose two distinct pilot studies using the following specific aims: Vascular Aim 1: To determine the short-term consequences of the independent and combined effects of exposure to gamma radiation and elevated body iron stores on measures of endothelial function and cell viability and integrity. We hypothesize that animals that have high body iron stores and are exposed to gamma radiation will show a greater reduction in endothelial dependent nitric oxid production and larger pathological changes in endothelial integrity than animals that have only 1 of those treatments (either high iron stores or exposure to gamma radiation). Vascular Aim 2: Identify and compare the effects of gamma radiation and elevated body iron stores on the genetic and epigenetic regulation of proteins associated with endothelial cell function. We hypothesize that modifications of epigenetic control and posttranslational expression of proteins associated with endothelial cell function will be differentially altered in rats with high body iron stores and exposed to gamma radiation compared to rats with only 1 type of treatment. Cardiac Aim 1: To determine the

  16. In search of joy in practice: a report of 23 high-functioning primary care practices.

    PubMed

    Sinsky, Christine A; Willard-Grace, Rachel; Schutzbank, Andrew M; Sinsky, Thomas A; Margolius, David; Bodenheimer, Thomas

    2013-01-01

    We highlight primary care innovations gathered from high-functioning primary care practices, innovations we believe can facilitate joy in practice and mitigate physician burnout. To do so, we made site visits to 23 high-performing primary care practices and focused on how these practices distribute functions among the team, use technology to their advantage, improve outcomes with data, and make the job of primary care feasible and enjoyable as a life's vocation. Innovations identified include (1) proactive planned care, with previsit planning and previsit laboratory tests; (2) sharing clinical care among a team, with expanded rooming protocols, standing orders, and panel management; (3) sharing clerical tasks with collaborative documentation (scribing), nonphysician order entry, and streamlined prescription management; (4) improving communication by verbal messaging and in-box management; and (5) improving team functioning through co-location, team meetings, and work flow mapping. Our observations suggest that a shift from a physician-centric model of work distribution and responsibility to a shared-care model, with a higher level of clinical support staff per physician and frequent forums for communication, can result in high-functioning teams, improved professional satisfaction, and greater joy in practice. PMID:23690328

  17. Highly surface functionalized carbon nano-onions for bright light bioimaging

    NASA Astrophysics Data System (ADS)

    Frasconi, Marco; Maffeis, Viviana; Bartelmess, Juergen; Echegoyen, Luis; Giordani, Silvia

    2015-12-01

    Carbon-based nanomaterials functionalized with fluorescent and water-soluble groups have emerged as platforms for biological imaging because of their low toxicity and ability to be internalized by cells. The development of imaging probes based on carbon nanomaterials for biomedical studies requires the understanding of their biological response as well as the efficient and safety exposition of the nanomaterial to the cell compartment where it is designed to operate. Here, we present a fluorescent probe based on surface functionalized carbon nano-onions (CNOs) for biological imaging. The modification of CNOs by chemical oxidation of the defects on the outer shell of these carbon nanoparticles results in an extensive surface functionalization with carboxyl groups. We have obtained fluorescently labelled CNOs by a reaction involving the amide bond formation between fluoresceinamine and the carboxylic acids groups on the surface of the CNOs. The functionalized CNOs display high emission properties and dispersability in water due to the presence of high surface coverage of carboxylic acid groups that translate in an efficient fluorescent probe for in vitro imaging of HeLa cells, without significant cytotoxicity. The resulting nanomaterial represents a promising platform for biological imaging applications due to the high dispersability in water, its efficient internalization by cancer cells and localization in specific cell compartments.

  18. Sleep Patterns in Adults with a Diagnosis of High-Functioning Autism Spectrum Disorder

    PubMed Central

    Baker, Emma K.; Richdale, Amanda L.

    2015-01-01

    Study Objectives: To examine sleep patterns and sleep problems and their relationship with daytime functioning in adults with a diagnosis of an autism spectrum disorder and no comorbid intellectual disability (high-functioning autism spectrum disorder [HFASD]) compared to neurotypical (NT) adults. Design: Cross-sectional. Setting: Home-based study. Participants: 36 adults with HFASD and 36 age-, intelligence quotient- and sex-matched NT adults. Measurements: Participants completed an online questionnaire battery including the Pittsburgh Sleep Quality Index (PSQI), a 14-d sleep wake diary and 14-d actigraphy data collection. Results: Adults with HFASD had significantly more general sleep disturbances and higher scores on the PSQI, longer sleep onset latencies (actigraphy), and poorer sleep efficiency (diary) and these results remained significant after accounting for the False Discovery Rate. Those adults with HFASD who did not have a comorbid diagnosis of anxiety/depression had significantly shorter total sleep time (diary and actigraphy) compared to NT adults. Compared to NT adults, the HFASD group self-reported significantly poorer refreshment scores upon waking in the morning and higher scores on the daytime dysfunction due to sleepiness subscale of the PSQI. Conclusions: These findings support the notion that problems related to sleep, in particular insomnia, continue into adulthood in individuals with high-functioning autism spectrum disorder. Citation: Baker EK, Richdale AL. Sleep patterns in adults with a diagnosis of high-functioning autism spectrum disorder. SLEEP 2015;38(11):1765–1774. PMID:26237770

  19. In Search of Joy in Practice: A Report of 23 High-Functioning Primary Care Practices

    PubMed Central

    Sinsky, Christine A.; Willard-Grace, Rachel; Schutzbank, Andrew M.; Sinsky, Thomas A.; Margolius, David; Bodenheimer, Thomas

    2013-01-01

    We highlight primary care innovations gathered from high-functioning primary care practices, innovations we believe can facilitate joy in practice and mitigate physician burnout. To do so, we made site visits to 23 high-performing primary care practices and focused on how these practices distribute functions among the team, use technology to their advantage, improve outcomes with data, and make the job of primary care feasible and enjoyable as a life’s vocation. Innovations identified include (1) proactive planned care, with previsit planning and previsit laboratory tests; (2) sharing clinical care among a team, with expanded rooming protocols, standing orders, and panel management; (3) sharing clerical tasks with collaborative documentation (scribing), nonphysician order entry, and streamlined prescription management; (4) improving communication by verbal messaging and in-box management; and (5) improving team functioning through co-location, team meetings, and work flow mapping. Our observations suggest that a shift from a physician-centric model of work distribution and responsibility to a shared-care model, with a higher level of clinical support staff per physician and frequent forums for communication, can result in high-functioning teams, improved professional satisfaction, and greater joy in practice. PMID:23690328

  20. Theory of melting at high pressures: Amending density functional theory with quantum Monte Carlo

    SciTech Connect

    Shulenburger, L.; Desjarlais, M. P.; Mattsson, T. R.

    2014-10-01

    We present an improved first-principles description of melting under pressure based on thermodynamic integration comparing Density Functional Theory (DFT) and quantum Monte Carlo (QMC) treatments of the system. The method is applied to address the longstanding discrepancy between density functional theory (DFT) calculations and diamond anvil cell (DAC) experiments on the melting curve of xenon, a noble gas solid where van der Waals binding is challenging for traditional DFT methods. The calculations show excellent agreement with data below 20 GPa and that the high-pressure melt curve is well described by a Lindemann behavior up to at least 80 GPa, a finding in stark contrast to DAC data.

  1. Large-Deformation Displacement Transfer Functions for Shape Predictions of Highly Flexible Slender Aerospace Structures

    NASA Technical Reports Server (NTRS)

    Ko, William L.; Fleischer, Van Tran

    2013-01-01

    Large deformation displacement transfer functions were formulated for deformed shape predictions of highly flexible slender structures like aircraft wings. In the formulation, the embedded beam (depth wise cross section of structure along the surface strain sensing line) was first evenly discretized into multiple small domains, with surface strain sensing stations located at the domain junctures. Thus, the surface strain (bending strains) variation within each domain could be expressed with linear of nonlinear function. Such piecewise approach enabled piecewise integrations of the embedded beam curvature equations [classical (Eulerian), physical (Lagrangian), and shifted curvature equations] to yield closed form slope and deflection equations in recursive forms.

  2. Synthesis of highly functionalized polycyclic quinoxaline derivatives using visible-light photoredox catalysis.

    PubMed

    He, Zhi; Bae, Minwoo; Wu, Jie; Jamison, Timothy F

    2014-12-22

    A mild and facile method for preparing highly functionalized pyrrolo[1,2-a]quinoxalines and other nitrogen-rich heterocycles, each containing a quinoxaline core or an analogue thereof, has been developed. The novel method features a visible-light-induced decarboxylative radical coupling of ortho-substituted arylisocyanides and radicals generated from phenyliodine(III) dicarboxylate reagents and exhibits excellent functional group compatibility. A wide range of quinoxaline heterocycles have been prepared. Finally, a telescoped preparation of these polycyclic compounds by integration of the in-line isocyanide formation and photochemical cyclization has been established in a three-step continuous-flow system.

  3. Correlation Function Approach for Estimating Thermal Conductivity in Highly Porous Fibrous Materials

    NASA Technical Reports Server (NTRS)

    Martinez-Garcia, Jorge; Braginsky, Leonid; Shklover, Valery; Lawson, John W.

    2011-01-01

    Heat transport in highly porous fiber networks is analyzed via two-point correlation functions. Fibers are assumed to be long and thin to allow a large number of crossing points per fiber. The network is characterized by three parameters: the fiber aspect ratio, the porosity and the anisotropy of the structure. We show that the effective thermal conductivity of the system can be estimated from knowledge of the porosity and the correlation lengths of the correlation functions obtained from a fiber structure image. As an application, the effects of the fiber aspect ratio and the network anisotropy on the thermal conductivity is studied.

  4. High-Throughput Density Functional Theory Categorization of Ferroelectric Ternary Perovskite Oxides for Use as High-Performance Piezoelectrics

    NASA Astrophysics Data System (ADS)

    Armiento, Rickard; Kozinsky, Boris; Fornari, Marco; Ceder, Gerbrand

    2011-03-01

    We present a nearly exhaustive density functional theory (DFT) survey over the chemical space of perovskite compounds on ABO3 form, with the aim of identifying alloy end points for new piezoelectric materials. Our screening criteria on the DFT results selects 85 relevant compounds, among which all well known alloy end points for high performance piezoelectrics are present. We analyze the compounds with respect to macroscopic polarization, born effective charges, and energy differences between different structure distortions. We discuss the energy features that cause the high piezoelectric performance of the well known piezoelectric lead zirconate titanate (PZT), and to what extent these features are rare among the found compounds. The results are used to discuss relevant isovalent alloys of the selected compounds.

  5. Early effects of high-fat diet on neurovascular function and focal ischemic brain injury.

    PubMed

    Li, Weiguo; Prakash, Roshini; Chawla, Dhruv; Du, Wenting; Didion, Sean P; Filosa, Jessica A; Zhang, Quanguang; Brann, Darrell W; Lima, Victor V; Tostes, Rita C; Ergul, Adviye

    2013-06-01

    Obesity is a risk factor for stroke, but the early effects of high-fat diet (HFD) on neurovascular function and ischemic stroke outcomes remain unclear. The goal of this study was to test the hypotheses that HFD beginning early in life 1) impairs neurovascular coupling, 2) causes cerebrovascular dysfunction, and 3) worsens short-term outcomes after cerebral ischemia. Functional hyperemia and parenchymal arteriole (PA) reactivity were measured in rats after 8 wk of HFD. The effect of HFD on basilar artery function after middle cerebral artery occlusion (MCAO) and associated O-GlcNAcylation were assessed. Neuronal cell death, infarct size, hemorrhagic transformation (HT) frequency/severity, and neurological deficit were evaluated after global ischemia and transient MCAO. HFD caused a 10% increase in body weight and doubled adiposity without a change in lipid profile, blood glucose, and blood pressure. Functional hyperemia and PA relaxation were decreased with HFD. Basilar arteries from stroked HFD rats were more sensitive to contractile factors, and acetylcholine-mediated relaxation was impaired. Vascular O-GlcNAcylated protein content was increased with HFD. This group also showed greater mortality rate, infarct volume, HT occurrence rate, and HT severity and poor functional outcome compared with the control diet group. These results indicate that HFD negatively affects neurovascular coupling and cerebrovascular function even in the absence of dyslipidemia. These early cerebrovascular changes may be the cause of greater cerebral injury and poor outcomes of stroke in these animals. PMID:23576615

  6. Tensor polarization dependent fragmentation functions and e+e-→V π X at high energies

    NASA Astrophysics Data System (ADS)

    Chen, Kai-bao; Yang, Wei-hua; Wei, Shu-yi; Liang, Zuo-tang

    2016-08-01

    We present the systematic results for three-dimensional fragmentation functions of spin-1 hadrons defined via the quark-quark correlator. There are totally 72 such fragmentation functions, among them 18 are twist-2, 36 are twist-3 and 18 are twist-4. We also present the relationships between the twist-3 parts and those defined via the quark-gluon-quark correlator obtained from the QCD equation of motion. We show that the two particle semi-inclusive hadron production process e+e-→V π X at high energies is one of the best places to study the three-dimensional tensor polarization dependent fragmentation functions. We present the general kinematic analysis of this process and show that the cross section should be expressed in terms of 81 independent structure functions. After that we present parton model results for the hadronic tensor, the structure functions, and the azimuthal and spin asymmetries in terms of these gauge invariant fragmentation functions at the leading order perturbative quantum chromodynamics up to twist-3.

  7. More of the same: high functional redundancy in stream fish assemblages from tropical agroecosystems.

    PubMed

    Casatti, Lilian; Teresa, Fabrício Barreto; Zeni, Jaquelini de Oliveira; Ribeiro, Mariela Domiciano; Brejão, Gabriel Lourenço; Ceneviva-Bastos, Mônica

    2015-06-01

    In this study, we investigated the influence of environmental variables (predictor variables) on the species richness, species diversity, functional diversity, and functional redundancy (response variables) of stream fish assemblages in an agroecosystem that harbor a gradient of degradation. We hypothesized that, despite presenting high richness or diversity in some occasions, fish communities will be more functionally redundant with stream degradation. Species richness, species diversity, and functional redundancy were predicted by the percentage of grass on the banks, which is a characteristic that indicates degraded conditions, whereas the percentage of coarse substrate in the stream bottom was an important predictor of all response variables and indicates more preserved conditions. Despite being more numerous and diverse, the groups of species living in streams with an abundance of grass on the banks perform similar functions in the ecosystem. We found that riparian and watershed land use had low predictive power in comparison to the instream habitat. If there is any interest in promoting ecosystem functions and fish diversity, conservation strategies should seek to restore forests in watersheds and riparian buffers, protect instream habitats from siltation, provide wood debris, and mitigate the proliferation of grass on stream banks. Such actions will work better if they are planned together with good farming practices because these basins will continue to be used for agriculture and livestock in the future.

  8. More of the same: high functional redundancy in stream fish assemblages from tropical agroecosystems.

    PubMed

    Casatti, Lilian; Teresa, Fabrício Barreto; Zeni, Jaquelini de Oliveira; Ribeiro, Mariela Domiciano; Brejão, Gabriel Lourenço; Ceneviva-Bastos, Mônica

    2015-06-01

    In this study, we investigated the influence of environmental variables (predictor variables) on the species richness, species diversity, functional diversity, and functional redundancy (response variables) of stream fish assemblages in an agroecosystem that harbor a gradient of degradation. We hypothesized that, despite presenting high richness or diversity in some occasions, fish communities will be more functionally redundant with stream degradation. Species richness, species diversity, and functional redundancy were predicted by the percentage of grass on the banks, which is a characteristic that indicates degraded conditions, whereas the percentage of coarse substrate in the stream bottom was an important predictor of all response variables and indicates more preserved conditions. Despite being more numerous and diverse, the groups of species living in streams with an abundance of grass on the banks perform similar functions in the ecosystem. We found that riparian and watershed land use had low predictive power in comparison to the instream habitat. If there is any interest in promoting ecosystem functions and fish diversity, conservation strategies should seek to restore forests in watersheds and riparian buffers, protect instream habitats from siltation, provide wood debris, and mitigate the proliferation of grass on stream banks. Such actions will work better if they are planned together with good farming practices because these basins will continue to be used for agriculture and livestock in the future. PMID:25822887

  9. More of the Same: High Functional Redundancy in Stream Fish Assemblages from Tropical Agroecosystems

    NASA Astrophysics Data System (ADS)

    Casatti, Lilian; Teresa, Fabrício Barreto; Zeni, Jaquelini de Oliveira; Ribeiro, Mariela Domiciano; Brejão, Gabriel Lourenço; Ceneviva-Bastos, Mônica

    2015-06-01

    In this study, we investigated the influence of environmental variables (predictor variables) on the species richness, species diversity, functional diversity, and functional redundancy (response variables) of stream fish assemblages in an agroecosystem that harbor a gradient of degradation. We hypothesized that, despite presenting high richness or diversity in some occasions, fish communities will be more functionally redundant with stream degradation. Species richness, species diversity, and functional redundancy were predicted by the percentage of grass on the banks, which is a characteristic that indicates degraded conditions, whereas the percentage of coarse substrate in the stream bottom was an important predictor of all response variables and indicates more preserved conditions. Despite being more numerous and diverse, the groups of species living in streams with an abundance of grass on the banks perform similar functions in the ecosystem. We found that riparian and watershed land use had low predictive power in comparison to the instream habitat. If there is any interest in promoting ecosystem functions and fish diversity, conservation strategies should seek to restore forests in watersheds and riparian buffers, protect instream habitats from siltation, provide wood debris, and mitigate the proliferation of grass on stream banks. Such actions will work better if they are planned together with good farming practices because these basins will continue to be used for agriculture and livestock in the future.

  10. Relevance Rank Platform (RRP) for Functional Filtering of High Content Protein-Protein Interaction Data.

    PubMed

    Pokharel, Yuba Raj; Saarela, Jani; Szwajda, Agnieszka; Rupp, Christian; Rokka, Anne; Lal Kumar Karna, Shibendra; Teittinen, Kaisa; Corthals, Garry; Kallioniemi, Olli; Wennerberg, Krister; Aittokallio, Tero; Westermarck, Jukka

    2015-12-01

    High content protein interaction screens have revolutionized our understanding of protein complex assembly. However, one of the major challenges in translation of high content protein interaction data is identification of those interactions that are functionally relevant for a particular biological question. To address this challenge, we developed a relevance ranking platform (RRP), which consist of modular functional and bioinformatic filters to provide relevance rank among the interactome proteins. We demonstrate the versatility of RRP to enable a systematic prioritization of the most relevant interaction partners from high content data, highlighted by the analysis of cancer relevant protein interactions for oncoproteins Pin1 and PME-1. We validated the importance of selected interactions by demonstration of PTOV1 and CSKN2B as novel regulators of Pin1 target c-Jun phosphorylation and reveal previously unknown interacting proteins that may mediate PME-1 effects via PP2A-inhibition. The RRP framework is modular and can be modified to answer versatile research problems depending on the nature of the biological question under study. Based on comparison of RRP to other existing filtering tools, the presented data indicate that RRP offers added value especially for the analysis of interacting proteins for which there is no sufficient prior knowledge available. Finally, we encourage the use of RRP in combination with either SAINT or CRAPome computational tools for selecting the candidate interactors that fulfill the both important requirements, functional relevance, and high confidence interaction detection.

  11. Hydrazide functionalized core-shell magnetic nanocomposites for highly specific enrichment of N-glycopeptides.

    PubMed

    Liu, Liting; Yu, Meng; Zhang, Ying; Wang, Changchun; Lu, Haojie

    2014-05-28

    In view of the biological significance of glycosylation for human health, profiling of glycoproteome from complex biological samples is highly inclined toward the discovery of disease biomarkers and clinical diagnosis. Nevertheless, because of the existence of glycopeptides at relatively low abundances compared with nonglycosylated peptides and glycan microheterogeneity, glycopeptides need to be highly selectively enriched from complex biological samples for mass spectrometry analysis. Herein, a new type of hydrazide functionalized core-shell magnetic nanocomposite has been synthesized for highly specific enrichment of N-glycopeptides. The nanocomposites with both the magnetic core and the polymer shell hanging high density of hydrazide groups were prepared by first functionalization of the magnetic core with polymethacrylic acid by reflux precipitation polymerization to obtain the Fe3O4@poly(methacrylic acid) (Fe3O4@PMAA) and then modification of the surface of Fe3O4@PMAA with adipic acid dihydrazide (ADH) to obtain Fe3O4@poly(methacrylic hydrazide) (Fe3O4@PMAH). The abundant hydrazide groups toward highly specific enrichment of glycopeptides and the magnetic core make it suitable for large-scale, high-throughput, and automated sample processing. In addition, the hydrophilic polymer surface can provide low nonspecific adsorption of other peptides. Compared to commercially available hydrazide resin, Fe3O4@PMAH improved more than 5 times the signal-to-noise ratio of standard glycopeptides. Finally, this nanocomposite was applied in the profiling of N-glycoproteome from the colorectal cancer patient serum. In total, 175 unique glycopeptides and 181 glycosylation sites corresponding to 63 unique glycoproteins were identified in three repeated experiments, with the specificities of the enriched glycopeptides and corresponding glycoproteins of 69.6% and 80.9%, respectively. Because of all these attractive features, we believe that this novel hydrazide functionalized

  12. Alcohol Mixed With Energy Drinks: Associations with Risky Drinking and Functioning in High School

    PubMed Central

    Tucker, Joan S.; Troxel, Wendy M.; Ewing, Brett A.; D’Amico, Elizabeth J.

    2016-01-01

    Background Mixing alcohol with energy drinks is associated with heavier drinking and related problems among college students. However, little is known about how high school drinkers who mix alcohol with energy drinks (AmED) compare to those who do not (AwoED). This study compares high school AmED and AwoED users on their alcohol use during middle and high school, as well as key domains of functioning in high school. Methods Two surveys were conducted three years apart in adolescents initially recruited from 16 middle schools in Southern California. The analytic sample consists of 696 past month drinkers. Multivariable models compared AmED and AwoED users on alcohol use, mental health, social functioning, academic orientation, delinquency and other substance use at age 17, and on their alcohol use and related cognitions at age 14. Results AmED was reported by 13% of past month drinkers. AmED and AwoED users did not differ on alcohol use or cognitions in middle school, but AmED users drank more often, more heavily, and reported more negative consequences in high school. AmED users were also more likely to report poor grades, delinquent behavior, substance use-related unsafe driving, public intoxication, and drug use than AwoED users in high school. Group differences were not found on mental health, social functioning, or academic aspirations. Conclusions AmED use is common among high school drinkers. The higher risk behavioral profile of these young AmED users, which includes drug use and substance use-related unsafe driving, is a significant cause for concern and warrants further attention. PMID:27522534

  13. High potency olfactory receptor agonists discovered by virtual high-throughput screening: molecular probes for receptor structure and olfactory function

    PubMed Central

    Triballeau, Nicolas; Van Name, Eric; Laslier, Guillaume; Cai, Diana; Paillard, Guillaume; Sorensen, Peter W.; Hoffmann, Rémy; Bertrand, Hugues-Olivier; Ngai, John; Acher, Francine C.

    2008-01-01

    The detection and discrimination of diverse chemical structures by the vertebrate olfactory system is accomplished by the recognition of odorous ligands by their cognate receptors. In the present study we used a computational high-throughput screening strategy to discover novel high affinity agonists of an olfactory G protein-coupled receptor tuned to recognize amino acid ligands. Functional testing of the top candidates validated several agonists with potencies higher than any of the receptor’s known natural ligands. Computational modeling revealed molecular interactions involved in ligand recognition by this receptor, and further highlighted interactions that have been conserved in evolutionarily divergent amino acid receptors. Significantly, the top compounds display robust activities as odorants in vivo, and include a natural product that may be used to signal the presence of bacteria in the aquatic environment. Our virtual screening approach should be applicable to the identification of new bioactive molecules for probing the structure of chemosensory receptors and the function of chemosensory systems in vivo. PMID:19081373

  14. Social competence intervention for youth with Asperger Syndrome and high-functioning autism: an initial investigation.

    PubMed

    Stichter, Janine P; Herzog, Melissa J; Visovsky, Karen; Schmidt, Carla; Randolph, Jena; Schultz, Tia; Gage, Nicholas

    2010-09-01

    Individuals with high functioning autism (HFA) or Asperger Syndrome (AS) exhibit difficulties in the knowledge or correct performance of social skills. This subgroup's social difficulties appear to be associated with deficits in three social cognition processes: theory of mind, emotion recognition and executive functioning. The current study outlines the development and initial administration of the group-based Social Competence Intervention (SCI), which targeted these deficits using cognitive behavioral principles. Across 27 students age 11-14 with a HFA/AS diagnosis, results indicated significant improvement on parent reports of social skills and executive functioning. Participants evidenced significant growth on direct assessments measuring facial expression recognition, theory of mind and problem solving. SCI appears promising, however, larger samples and application in naturalistic settings are warranted.

  15. Risk Factors for Depression in Children and Adolescents with High Functioning Autism Spectrum Disorders.

    PubMed

    De-la-Iglesia, Myriam; Olivar, José-Sixto

    2015-01-01

    The objective of our study was to examine, discuss, and provide proposals on diagnostic comorbidity of depression in children and adolescents with high functioning autism spectrum disorder (HFASD) in the following aspects. (1) Prevalence. It was concluded that there are an elevated depression rate and the need for longitudinal studies to determine prevalence and incidence based on functioning level, autistic symptoms, gender, age, type of depression, prognosis, duration, and treatment. (2) Explicative Hypotheses and Vulnerability. The factors that present the greatest specific risk are higher cognitive functioning, self-awareness of deficit, capacity for introspection, stressful life events, adolescence, quality of social relationships, and alexithymia. (3) Risk of Suicide. The need for control and detection of suicidal tendencies and bullying is emphasised. (4) Depressive Symptoms. Indicators for early detection are proposed and their overlap with HFASD is analysed, examining the assessment techniques used and arguing that specific adapted tests are needed.

  16. Risk Factors for Depression in Children and Adolescents with High Functioning Autism Spectrum Disorders

    PubMed Central

    De-la-Iglesia, Myriam; Olivar, José-Sixto

    2015-01-01

    The objective of our study was to examine, discuss, and provide proposals on diagnostic comorbidity of depression in children and adolescents with high functioning autism spectrum disorder (HFASD) in the following aspects. (1) Prevalence. It was concluded that there are an elevated depression rate and the need for longitudinal studies to determine prevalence and incidence based on functioning level, autistic symptoms, gender, age, type of depression, prognosis, duration, and treatment. (2) Explicative Hypotheses and Vulnerability. The factors that present the greatest specific risk are higher cognitive functioning, self-awareness of deficit, capacity for introspection, stressful life events, adolescence, quality of social relationships, and alexithymia. (3) Risk of Suicide. The need for control and detection of suicidal tendencies and bullying is emphasised. (4) Depressive Symptoms. Indicators for early detection are proposed and their overlap with HFASD is analysed, examining the assessment techniques used and arguing that specific adapted tests are needed. PMID:26413564

  17. An industrial perspective on utilizing functional ion channel assays for high throughput screening.

    PubMed

    Worley, Jennings F; Main, Martin J

    2002-01-01

    The ability to apply large-scale screening formats to measures of ion channel function offers immense opportunities for drug discovery and academic research. Technologies have been developed over the last several years that now provide the ability to screen large numbers of compounds and natural products on ion channel function to find novel drugs. Application of these technologies has vastly improved the capabilities of ion channel drug discovery and provides an avenue to accelerate discoveries of ion channel biology. These advances have largely arisen from the development and application of instruments and reporters of membrane potential and ion movements in cells used to measure functional activity of ion channels. This article endeavors to describe the practical applications of these technologies in developing, validating, and implementing high throughput screening assay formats to different types of ion channels.

  18. High density lipoprotein and metabolic disease: Potential benefits of restoring its functional properties

    PubMed Central

    Klancic, Teja; Woodward, Lavinia; Hofmann, Susanna M.; Fisher, Edward A.

    2016-01-01

    Background High density lipoproteins (HDLs) are thought to be atheroprotective and to reduce the risk of cardiovascular disease (CVD). Besides their antioxidant, antithrombotic, anti-inflammatory, anti-apoptotic properties in the vasculature, HDLs also improve glucose metabolism in skeletal muscle. Scope of the review Herein, we review the functional role of HDLs to improve metabolic disorders, especially those involving insulin resistance and to induce regression of CVD with a particular focus on current pharmacological treatment options as well as lifestyle interventions, particularly exercise. Major conclusions Functional properties of HDLs continue to be considered important mediators to reverse metabolic dysfunction and to regress atherosclerotic cardiovascular disease. Lifestyle changes are often recommended to reduce the risk of CVD, with exercise being one of the most important of these. Understanding how exercise improves HDL function will likely lead to new approaches to battle the expanding burden of obesity and the metabolic syndrome. PMID:27110484

  19. Thioetherification of chloroheteroarenes: a binuclear catalyst promotes wide scope and high functional-group tolerance.

    PubMed

    Platon, Mélanie; Wijaya, Novi; Rampazzi, Vincent; Cui, Luchao; Rousselin, Yoann; Saeys, Mark; Hierso, Jean-Cyrille

    2014-09-22

    A constrained binuclear palladium catalyst system affords selective thioetherification of a wide range of functionalized arenethiols with chloroheteroaromatic partners with the highest turnover numbers (TONs) reported to date and tolerates a large variety of reactive functions. The scope of this system includes the coupling of thiophenols with six- and five-membered 2-chloroheteroarenes (i.e., functionalized pyridine, pyrazine, quinoline, pyrimidine, furane, and thiazole) and 3-bromoheteroarenes (i.e., pyridine and furane). Electron-rich congested thiophenols and fluorinated thiophenols are also suitable partners. The coupling of unprotected amino-2-chloropyridines with thiophenol and the successful employment of synthetically valuable chlorothiophenols are described with the same catalyst system. DFT studies attribute the high performance of this binuclear palladium catalyst to the decreased stability of thiolate-containing resting states. Palladium loading was as low as 0.2 mol %, which is important for industrial application and is a step forward in solving catalyst activation/deactivation problems.

  20. Highly functionalized 2-oxopiperazine-based peptidomimetics: an approach to PAR1 antagonists.

    PubMed

    Valdivielso, Ángel M; Ventosa-Andrés, Pilar; Tato, Francisco; Fernández-Ibañez, M Ángeles; Pappos, Ioannis; Tsopanoglou, Nikos E; García-López, M Teresa; Gutiérrez-Rodríguez, Marta; Herranz, Rosario

    2013-01-01

    A series of pseudodipeptide-based chiral 1,3,4,5-tetrasubstituted-2-oxopiperazines has been designed and synthesized as potential PAR1 antagonists. These highly functionalized piperazines were synthesized from aromatic and basic amino acid derived Ψ[CH(CN)NH]pseudodipeptides through a four step pathway that involves reduction of the cyano group to build the 2-oxopiperazine ring, followed by selective functionalization at the N₄-, N₁-positions, and at the exocyclic moiety at position C5. This regioselective functionalization required the fine tuning of reaction conditions. All new compounds were screened as inhibitors of human platelet aggregation induced by the PAR1 agonist SFLLRN and as cytotoxic agents in human cancer cell lines. Some of the compounds displayed moderate PAR1 antagonist activity, while, others were cytotoxic at μM concentration. No correlation was observed between both types of activities. PMID:24158013

  1. Thioetherification of chloroheteroarenes: a binuclear catalyst promotes wide scope and high functional-group tolerance.

    PubMed

    Platon, Mélanie; Wijaya, Novi; Rampazzi, Vincent; Cui, Luchao; Rousselin, Yoann; Saeys, Mark; Hierso, Jean-Cyrille

    2014-09-22

    A constrained binuclear palladium catalyst system affords selective thioetherification of a wide range of functionalized arenethiols with chloroheteroaromatic partners with the highest turnover numbers (TONs) reported to date and tolerates a large variety of reactive functions. The scope of this system includes the coupling of thiophenols with six- and five-membered 2-chloroheteroarenes (i.e., functionalized pyridine, pyrazine, quinoline, pyrimidine, furane, and thiazole) and 3-bromoheteroarenes (i.e., pyridine and furane). Electron-rich congested thiophenols and fluorinated thiophenols are also suitable partners. The coupling of unprotected amino-2-chloropyridines with thiophenol and the successful employment of synthetically valuable chlorothiophenols are described with the same catalyst system. DFT studies attribute the high performance of this binuclear palladium catalyst to the decreased stability of thiolate-containing resting states. Palladium loading was as low as 0.2 mol %, which is important for industrial application and is a step forward in solving catalyst activation/deactivation problems. PMID:25112971

  2. Risk Factors for Depression in Children and Adolescents with High Functioning Autism Spectrum Disorders.

    PubMed

    De-la-Iglesia, Myriam; Olivar, José-Sixto

    2015-01-01

    The objective of our study was to examine, discuss, and provide proposals on diagnostic comorbidity of depression in children and adolescents with high functioning autism spectrum disorder (HFASD) in the following aspects. (1) Prevalence. It was concluded that there are an elevated depression rate and the need for longitudinal studies to determine prevalence and incidence based on functioning level, autistic symptoms, gender, age, type of depression, prognosis, duration, and treatment. (2) Explicative Hypotheses and Vulnerability. The factors that present the greatest specific risk are higher cognitive functioning, self-awareness of deficit, capacity for introspection, stressful life events, adolescence, quality of social relationships, and alexithymia. (3) Risk of Suicide. The need for control and detection of suicidal tendencies and bullying is emphasised. (4) Depressive Symptoms. Indicators for early detection are proposed and their overlap with HFASD is analysed, examining the assessment techniques used and arguing that specific adapted tests are needed. PMID:26413564

  3. Pushing the limits of high-resolution functional MRI using a simple high-density multi-element coil design.

    PubMed

    Petridou, N; Italiaander, M; van de Bank, B L; Siero, J C W; Luijten, P R; Klomp, D W J

    2013-01-01

    Recent studies have shown that functional MRI (fMRI) can be sensitive to the laminar and columnar organization of the cortex based on differences in the spatial and temporal characteristics of the blood oxygenation level-dependent (BOLD) signal originating from the macrovasculature and the neuronal-specific microvasculature. Human fMRI studies at this scale of the cortical architecture, however, are very rare because the high spatial/temporal resolution required to explore these properties of the BOLD signal are limited by the signal-to-noise ratio. Here, we show that it is possible to detect BOLD signal changes at an isotropic spatial resolution as high as 0.55 mm at 7 T using a high-density multi-element surface coil with minimal electronics, which allows close proximity to the head. The coil comprises of very small, 1 × 2-cm(2) , elements arranged in four flexible modules of four elements each (16-channel) that can be positioned within 1 mm from the head. As a result of this proximity, tissue losses were five-fold greater than coil losses and sufficient to exclude preamplifier decoupling. When compared with a standard 16-channel head coil, the BOLD sensitivity was approximately 2.2-fold higher for a high spatial/temporal resolution (1 mm isotropic/0.4 s), multi-slice, echo planar acquisition, and approximately three- and six-fold higher for three-dimensional echo planar images acquired with isotropic resolutions of 0.7 and 0.55 mm, respectively. Improvements in parallel imaging performance (geometry factor) were up to around 1.5-fold with increasing acceleration factor, and improvements in fMRI detectability (temporal signal-to-noise ratio) were up to around four-fold depending on the distance to the coil. Although deeper lying structures may not benefit from the design, most fMRI questions pertain to the neocortex which lies within approximately 4 cm from the surface. These results suggest that the resolution of fMRI (at 7 T) can approximate levels that are

  4. Highly Efficient Differentiation of Functional Hepatocytes From Human Induced Pluripotent Stem Cells

    PubMed Central

    Ma, Xiaocui; Tschudy-Seney, Benjamin; Roll, Garrett; Behbahan, Iman Saramipoor; Ahuja, Tijess P.; Tolstikov, Vladimir; Wang, Charles; McGee, Jeannine; Khoobyari, Shiva; Nolta, Jan A.; Willenbring, Holger

    2013-01-01

    Human induced pluripotent stem cells (hiPSCs) hold great potential for use in regenerative medicine, novel drug development, and disease progression/developmental studies. Here, we report highly efficient differentiation of hiPSCs toward a relatively homogeneous population of functional hepatocytes. hiPSC-derived hepatocytes (hiHs) not only showed a high expression of hepatocyte-specific proteins and liver-specific functions, but they also developed a functional biotransformation system including phase I and II metabolizing enzymes and phase III transporters. Nuclear receptors, which are critical for regulating the expression of metabolizing enzymes, were also expressed in hiHs. hiHs also responded to different compounds/inducers of cytochrome P450 as mature hepatocytes do. To follow up on this observation, we analyzed the drug metabolizing capacity of hiHs in real time using a novel ultraperformance liquid chromatography-tandem mass spectrometry. We found that, like freshly isolated primary human hepatocytes, the seven major metabolic pathways of the drug bufuralol were found in hiHs. In addition, transplanted hiHs engrafted, integrated, and proliferated in livers of an immune-deficient mouse model, and secreted human albumin, indicating that hiHs also function in vivo. In conclusion, we have generated a method for the efficient generation of hepatocytes from induced pluripotent stem cells in vitro and in vivo, and it appears that the cells function similarly to primary human hepatocytes, including developing a complete metabolic function. These results represent a significant step toward using patient/disease-specific hepatocytes for cell-based therapeutics as well as for pharmacology and toxicology studies. PMID:23681950

  5. Behavioral measures of implicit theory of mind in adults with high functioning autism.

    PubMed

    Deschrijver, Eliane; Bardi, Lara; Wiersema, Jan R; Brass, Marcel

    2016-01-01

    Theory of mind (ToM) research has shown that adults with high functioning autism (HFA) demonstrate typical performance on tasks that require explicit belief reasoning, despite clear social difficulties in everyday life situations. In the current study, we used implicit belief manipulations that are task-irrelevant and therefore less susceptible to strategies. In a ball-detection task, it was shown that neurotypical individuals detect a ball faster if an agent believed the ball was present. We predicted that adults with high functioning autism (HFA) would not show this effect. While we found a numerical difference in the hypothesized direction, we did not find a reliable group effect. Interestingly, the implicit ToM-index showed a strong negative correlation with both self-reported and observational measures of social difficulties in the HFA group. This suggests that the relationship between implicit ToM reasoning and the symptomatology of HFA might be subtler than assumed.

  6. Highly efficient potentiometric glucose biosensor based on functionalized InN quantum dots

    NASA Astrophysics Data System (ADS)

    Alvi, N. H.; Soto Rodriguez, P. E. D.; Gómez, V. J.; Kumar, Praveen; Amin, G.; Nur, O.; Willander, M.; Nötzel, R.

    2012-10-01

    We present a fast, highly sensitive, and efficient potentiometric glucose biosensor based on functionalized InN quantum-dots (QDs). The InN QDs are grown by molecular beam epitaxy. The InN QDs are bio-chemically functionalized through physical adsorption of glucose oxidase (GOD). GOD enzyme-coated InN QDs based biosensor exhibits excellent linear glucose concentration dependent electrochemical response against an Ag/AgCl reference electrode over a wide logarithmic glucose concentration range (1 × 10-5 M to 1 × 10-2 M) with a high sensitivity of 80 mV/decade. It exhibits a fast response time of less than 2 s with good stability and reusability and shows negligible response to common interferents such as ascorbic acid and uric acid. The fabricated biosensor has full potential to be an attractive candidate for blood sugar concentration detection in clinical diagnoses.

  7. Facile and green synthesis of highly stable L-cysteine functionalized copper nanoparticles

    NASA Astrophysics Data System (ADS)

    Kumar, Nikhil; Upadhyay, Lata Sheo Bachan

    2016-11-01

    A simple eco-friendly method for L-cysteine capped copper nanoparticles (CCNPs) synthesis in aqueous solution has been developed. Glucose and L-cysteine were used as reducing agent and capping/functionalizing agent, respectively. Different parameters such as capping agent concentration, pH, reaction temperature, and reducing agent concentration were optimized during the synthesis. The L-cysteine capped copper nanoparticle were characterized by ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, Particle size and zeta potential analyser, and high resolution transmission electron microscopy. Spherical shaped cysteine functionalized/capped copper nanoparticles with an average size of 40 nm were found to be highly stable at room temperature (RT) for a period of 1 month

  8. The relationship between moral judgment and cooperation in children with high-functioning autism.

    PubMed

    Li, Jing; Zhu, Liqi; Gummerum, Michaela

    2014-03-07

    This study investigated moral judgment in children with high-functioning autism and their cooperation in prisoner's dilemma game with partners of different moralities. Thirty-eight 6- to 12-year-old high-functioning autistic (HFA) children and 31 typically developing (TD) children were recruited. Children were asked to judge story protagonists' morality. After making this moral judgment correctly, they were asked to play with the morally nice and the morally naughty child in a repeated prisoner's dilemma game. Results showed that both HFA and TD children made correct moral judgments, and that HFA children might even have more rigid criteria for what constitutes morally naughty acts. HFA children's cooperation did not differ depending on the morality of the interaction partner, while TD children showed higher cooperation when interacting with the morally nice than the morally naughty child did. Thus, partner's morality did influence TD children's but not HFA children's subsequent cooperation.

  9. Self responses along cingulate cortex reveal quantitative neural phenotype for high functioning autism

    PubMed Central

    Chiu, Pearl H.; Kayali, M. Amin; Kishida, Kenneth T.; Tomlin, Damon; Klinger, Laura G.; Klinger, Mark R.; Montague, P. Read

    2014-01-01

    Summary Attributing behavioral outcomes correctly to oneself or to other agents is essential for all productive social exchange. We approach this issue in high-functioning males with autism spectrum disorder (ASD) using two separate fMRI paradigms. First, using a visual imagery task, we extract a basis set for responses along the cingulate cortex of control subjects that reveals an agent-specific eigenvector (self eigenmode) associated with imagining oneself executing a specific motor act. Second, we show that the same self eigenmode arises during one's own decision (the self phase) in an interpersonal exchange game (iterated trust game). Third, using this exchange game, we show that ASD males exhibit a severely diminished self eigenmode when playing the game with a human partner. This diminished response covaries parametrically with their behaviorally assessed symptom severity suggesting its value as an objective endophenotype. These findings may provide a quantitative assessment tool for high functioning ASD. PMID:18255038

  10. The use of grammatical morphemes by Mandarin-speaking children with high functioning autism.

    PubMed

    Zhou, Peng; Crain, Stephen; Gao, Liqun; Tang, Ye; Jia, Meixiang

    2015-05-01

    The present study investigated the production of grammatical morphemes by Mandarin-speaking children with high functioning autism. Previous research found that a subgroup of English-speaking children with autism exhibit deficits in the use of grammatical morphemes that mark tense. In order to see whether this impairment in grammatical morphology can be generalised to children with autism from other languages, the present study examined whether or not high-functioning Mandarin-speaking children with autism also exhibit deficits in using grammatical morphemes that mark aspect. The results show that Mandarin-speaking children with autism produced grammatical morphemes significantly less often than age-matched and IQ-matched TD peers as well as MLU-matched TD peers. The implications of these findings for understanding the grammatical abilities of children with autism were discussed. PMID:25381192

  11. Effect of high doses of gamma radiation on the functional characteristics of amniotic membrane

    NASA Astrophysics Data System (ADS)

    Singh, Rita; Purohit, Sumita; Chacharkar, M. P.

    2007-06-01

    The effect of different doses of gamma radiation viz. 25, 36 and 50 kGy on the chemical and functional characteristics of the amniotic membrane was studied. The change in the chemical structure of amniotic membranes at high doses of gamma irradiation was evaluated by means of Infrared (IR) Spectroscopy. The degradation of amnion on irradiation with gamma rays could produce a relative variation in IR absorption troughs. This kind of variation was absent in the samples irradiated to doses of 25, 36 and 50 kGy indicating no qualitative change in the material property of amnion. No significant differences in the water absorption capacity and water vapour transmission rate of amniotic membranes irradiated to different doses were observed. Impermeability of the amniotic membranes to different microorganisms was also not affected at high doses of gamma radiation. Gamma irradiation at doses of 25-50 kGy did not evoke undesirable changes in the functional properties of the amniotic membrane.

  12. Facile synthesis of boronic acid-functionalized magnetic carbon nanotubes for highly specific enrichment of glycopeptides

    NASA Astrophysics Data System (ADS)

    Ma, Rongna; Hu, Junjie; Cai, Zongwei; Ju, Huangxian

    2014-02-01

    A stepwise strategy was developed to synthesize boronic acid functionalized magnetic carbon nanotubes (MCNTs) for highly specific enrichment of glycopeptides. The MCNTs were synthesized by a solvothermal reaction of Fe3+ loaded on the acid-treated CNTs and modified with 1-pyrenebutanoic acid N-hydroxysuccinimidyl ester (PASE) to bind aminophenylboronic acid (APBA) via an amide reaction. The introduction of PASE could bridge the MCNT and APBA, suppress the nonspecific adsorption and reduce the steric hindrance among the bound molecules. Due to the excellent structure of the MCNTs, the functionalization of PASE and then APBA on MCNTs was quite simple, specific and effective. The glycopeptides enrichment and separation with a magnetic field could be achieved by their reversible covalent binding with the boronic group of APBA-MCNTs. The exceptionally large specific surface area and the high density of boronic acid groups of APBA-MCNTs resulted in rapid and highly efficient enrichment of glycopeptides, even in the presence of large amounts of interfering nonglycopeptides. The functional MCNTs possessed high selectivity for enrichment of 21 glycopeptides from the digest of horseradish peroxidase demonstrated by MALDI-TOF mass spectrometric analysis showing more glycopeptides detected than the usual 9 glycopeptides with commercially available APBA-agarose. The proposed system showed better specificity for glycopeptides even in the presence of non-glycopeptides with 50 times higher concentration. The boronic acid functionalized MCNTs provide a promising selective enrichment platform for precise glycoproteomic analysis.A stepwise strategy was developed to synthesize boronic acid functionalized magnetic carbon nanotubes (MCNTs) for highly specific enrichment of glycopeptides. The MCNTs were synthesized by a solvothermal reaction of Fe3+ loaded on the acid-treated CNTs and modified with 1-pyrenebutanoic acid N-hydroxysuccinimidyl ester (PASE) to bind aminophenylboronic acid

  13. Revealing complex function, process and pathway interactions with high-throughput expression and biological annotation data.

    PubMed

    Singh, Nitesh Kumar; Ernst, Mathias; Liebscher, Volkmar; Fuellen, Georg; Taher, Leila

    2016-10-20

    The biological relationships both between and within the functions, processes and pathways that operate within complex biological systems are only poorly characterized, making the interpretation of large scale gene expression datasets extremely challenging. Here, we present an approach that integrates gene expression and biological annotation data to identify and describe the interactions between biological functions, processes and pathways that govern a phenotype of interest. The product is a global, interconnected network, not of genes but of functions, processes and pathways, that represents the biological relationships within the system. We validated our approach on two high-throughput expression datasets describing organismal and organ development. Our findings are well supported by the available literature, confirming that developmental processes and apoptosis play key roles in cell differentiation. Furthermore, our results suggest that processes related to pluripotency and lineage commitment, which are known to be critical for development, interact mainly indirectly, through genes implicated in more general biological processes. Moreover, we provide evidence that supports the relevance of cell spatial organization in the developing liver for proper liver function. Our strategy can be viewed as an abstraction that is useful to interpret high-throughput data and devise further experiments.

  14. High-throughput mutagenesis reveals functional determinants for DNA targeting by activation-induced deaminase

    PubMed Central

    Gajula, Kiran S.; Huwe, Peter J.; Mo, Charlie Y.; Crawford, Daniel J.; Stivers, James T.; Radhakrishnan, Ravi; Kohli, Rahul M.

    2014-01-01

    Antibody maturation is a critical immune process governed by the enzyme activation-induced deaminase (AID), a member of the AID/APOBEC DNA deaminase family. AID/APOBEC deaminases preferentially target cytosine within distinct preferred sequence motifs in DNA, with specificity largely conferred by a small 9–11 residue protein loop that differs among family members. Here, we aimed to determine the key functional characteristics of this protein loop in AID and to thereby inform our understanding of the mode of DNA engagement. To this end, we developed a methodology (Sat-Sel-Seq) that couples saturation mutagenesis at each position across the targeting loop, with iterative functional selection and next-generation sequencing. This high-throughput mutational analysis revealed dominant characteristics for residues within the loop and additionally yielded enzymatic variants that enhance deaminase activity. To rationalize these functional requirements, we performed molecular dynamics simulations that suggest that AID and its hyperactive variants can engage DNA in multiple specific modes. These findings align with AID's competing requirements for specificity and flexibility to efficiently drive antibody maturation. Beyond insights into the AID-DNA interface, our Sat-Sel-Seq approach also serves to further expand the repertoire of techniques for deep positional scanning and may find general utility for high-throughput analysis of protein function. PMID:25064858

  15. Functional role of anthocyanins in high-light winter leaves of the evergreen herb Galax urceolata.

    PubMed

    Hughes, N M; Neufeld, H S; Burkey, K O

    2005-12-01

    High-light leaves of the evergreen herb Galax urceolata exhibit a striking color change from green to red during winter months due to anthocyanin synthesis in outermost mesophyll cells. Here we investigate three possible functions of this color change. To test the hypothesis that anthocyanins function as light attenuators, maximum photosystem II efficiency (F(v)/F(m)) of red and green leaves was measured during and after exposure to wavelengths either strongly or poorly absorbed by anthocyanin. To determine whether anthocyanins elevate radical-scavenging capacity, antioxidant activity of red and green leaves was assessed using the alpha,alpha-diphenyl-beta-picrylhydrazyl assay. Nonstructural carbohydrate levels were analyzed to test the hypothesis that anthocyanins function as a carbon sink. Declines in F(v)/F(m) under white and green light were significantly greater for green than red leaves, but were comparable under red light. Anthocyanin content positively correlated with antioxidant activity. Although levels of anthocyanins did not appear to be related to nonstructural carbohydrate concentration, high levels of sugars may be necessary for their photo-induction. Results suggest that anthocyanins function as light attenuators and may also contribute to the antioxidant pool in winter leaves.

  16. Study and application of a high-pressure water jet multi-functional flow test system.

    PubMed

    Shi, Huaizhong; Li, Gensheng; Huang, Zhongwei; Li, Jingbin; Zhang, Yi

    2015-12-01

    As the exploration and development of oil and gas focus more and more on deeper formation, hydraulic issues such as high-pressure water jet rock breaking, wellbore multiphase flow law, cuttings carrying efficiency, and hydraulic fracturing technique during the drilling and completion process have become the key points. To accomplish related researches, a high-pressure water jet multi-functional flow test system was designed. The following novel researches are carried out: study of high-pressure water jet characteristics under confining pressure, wellbore multiphase flow regime, hydraulic pressure properties of down hole tools during jet fracturing and pulsed cavitation jet drilling, and deflector's friction in radial jet drilling. The validity and feasibility of the experimental results provided by the system with various test modules have proved its importance in the research of the high-pressure water jet and well completion technology. PMID:26724077

  17. Ionic photoacid generators containing functionalized semifluorinated sulfonates for high-resolution lithography

    NASA Astrophysics Data System (ADS)

    Yi, Yi; Ayothi, Ramakrishnan; Ober, Christopher K.; Yueh, Wang; Cao, Heidi

    2008-03-01

    To meet the challenges for resist materials raised by high resolution lithography technologies, tailor-made photoacid generators (PAGs) with controlled acid diffusion and improved miscibility with polymers are very important. We have developed new ionic PAGs containing functionalized semifluorinated sulfonates. These PAGs have excellent solubility in polymer matrices and common organic solvents, high thermal stability, high acid strength and low volatility of the generated acids, and make them attractive PAGs for high resolution lithography. In this contribution, the preparation and characterization of several new ionic PAGs, the influence of the host matrix on PAG properties, and a comparison of their lithographic performance are presented. Specifically their lithographic performance at EUV wavelength is discussed.

  18. Study and application of a high-pressure water jet multi-functional flow test system.

    PubMed

    Shi, Huaizhong; Li, Gensheng; Huang, Zhongwei; Li, Jingbin; Zhang, Yi

    2015-12-01

    As the exploration and development of oil and gas focus more and more on deeper formation, hydraulic issues such as high-pressure water jet rock breaking, wellbore multiphase flow law, cuttings carrying efficiency, and hydraulic fracturing technique during the drilling and completion process have become the key points. To accomplish related researches, a high-pressure water jet multi-functional flow test system was designed. The following novel researches are carried out: study of high-pressure water jet characteristics under confining pressure, wellbore multiphase flow regime, hydraulic pressure properties of down hole tools during jet fracturing and pulsed cavitation jet drilling, and deflector's friction in radial jet drilling. The validity and feasibility of the experimental results provided by the system with various test modules have proved its importance in the research of the high-pressure water jet and well completion technology.

  19. Study and application of a high-pressure water jet multi-functional flow test system

    NASA Astrophysics Data System (ADS)

    Shi, Huaizhong; Li, Gensheng; Huang, Zhongwei; Li, Jingbin; Zhang, Yi

    2015-12-01

    As the exploration and development of oil and gas focus more and more on deeper formation, hydraulic issues such as high-pressure water jet rock breaking, wellbore multiphase flow law, cuttings carrying efficiency, and hydraulic fracturing technique during the drilling and completion process have become the key points. To accomplish related researches, a high-pressure water jet multi-functional flow test system was designed. The following novel researches are carried out: study of high-pressure water jet characteristics under confining pressure, wellbore multiphase flow regime, hydraulic pressure properties of down hole tools during jet fracturing and pulsed cavitation jet drilling, and deflector's friction in radial jet drilling. The validity and feasibility of the experimental results provided by the system with various test modules have proved its importance in the research of the high-pressure water jet and well completion technology.

  20. High dietary fructose does not exacerbate the detrimental consequences of high fat diet on basilar artery function.

    PubMed

    Toklu, H Z; Muller-Delp, J; Sakaraya, Y; Oktay, S; Kirichenko, N; Matheny, M; Carter, C S; Morgan, D; Strehler, K Y E; Tumer, N; Scarpace, P J

    2016-04-01

    The objective of the study was to determine the effects of a high fat (HF) diet alone or with high fructose (HF/F) on functional and structural changes in the basilar arteries and cardiovascular health parameters in rats. Male Sprague Dawley rats were fed either a HF (30%) or HF/F (30/40%) diet for 12 weeks. The basilar artery was cannulated in a pressurized system (90 cm H2O) and vascular responses to KCl (30 - 120 mM), endothelin (10(-11) - 10(-7) M), acetylcholine (ACh) (10(-10) - 10(-4) M), diethylamine (DEA)-NONO-ate (10(-10) - 10(-4) M), and papaverine (10(-10) - 10(-4) M) were evaluated. Rats were also monitored for food intake, body weight, blood lipids, blood pressure, and heart rate. At death, asymmetrical dimethyl arginine level (ADMA) and leptin were assayed in serum. Although there was no significant difference in weight gain and food intake, HF and HF/F diets increased body fat composition and decreased the lean mass. HF/F diet accelerated the development of dyslipidemia. Although resting blood pressure remained unchanged, stress caused a significant elevation in blood pressure and a modest increase in heart rate in HF fed rats. Both HF and HF/F diet resulted in decreased response to endothelium-dependent and -independent relaxation, whereas increased basilar artery wall thickness was observed only in HF group. Serum leptin levels positively correlated with wall thickness. Moreover serum ADMA was increased and eNOS immunofluorescence was significantly decreased with both diets. These data suggest that the presence of high fructose in a HF diet does not exacerbate the detrimental consequences of a HF diet on basilar artery function. PMID:27226180

  1. Filtered Mass Density Function for Design Simulation of High Speed Airbreathing Propulsion Systems

    NASA Technical Reports Server (NTRS)

    Givi, P.; Madnia, C. K.; Gicquel, L. Y. M.; Sheikhi, M. R. H.; Drozda, T. G.

    2002-01-01

    The objective of this research is to improve and implement the filtered mass density function (FDF) methodology for large eddy simulation (LES) of high speed reacting turbulent flows. NASA is interested in the design of various components involved in air breathing propulsion systems such as the scramjet. There is a demand for development of robust tools that can aid in the design procedure. The physics of high speed reactive flows is rich with many complexities. LES is regarded as one of the most promising means of simulating turbulent reacting flows.

  2. Stable aqueous dispersions of noncovalently functionalized graphene from graphite and their multifunctional high-performance applications.

    PubMed

    An, Xiaohong; Simmons, Trevor; Shah, Rakesh; Wolfe, Christopher; Lewis, Kim M; Washington, Morris; Nayak, Saroj K; Talapatra, Saikat; Kar, Swastik

    2010-11-10

    We present a scalable and facile technique for noncovalent functionalization of graphene with 1-pyrenecarboxylic acid that exfoliates single-, few-, and multilayered graphene flakes into stable aqueous dispersions. The exfoliation mechanism is established using stringent control experiments and detailed characterization steps. Using the exfoliated graphene, we demonstrate highly sensitive and selective conductometric sensors (whose resistance rapidly changes >10,000% in saturated ethanol vapor), and ultracapacitors with extremely high specific capacitance (∼ 120 F/g), power density (∼ 105 kW/kg), and energy density (∼ 9.2 Wh/kg).

  3. High-speed label-free functional photoacoustic microscopy of mouse brain in action.

    PubMed

    Yao, Junjie; Wang, Lidai; Yang, Joon-Mo; Maslov, Konstantin I; Wong, Terence T W; Li, Lei; Huang, Chih-Hsien; Zou, Jun; Wang, Lihong V

    2015-05-01

    We present fast functional photoacoustic microscopy (PAM) for three-dimensional high-resolution, high-speed imaging of the mouse brain, complementary to other imaging modalities. We implemented a single-wavelength pulse-width-based method with a one-dimensional imaging rate of 100 kHz to image blood oxygenation with capillary-level resolution. We applied PAM to image the vascular morphology, blood oxygenation, blood flow and oxygen metabolism in both resting and stimulated states in the mouse brain.

  4. High-speed Label-free Functional Photoacoustic Microscopy of Mouse Brain in Action

    PubMed Central

    Yao, Junjie; Wang, Lidai; Yang, Joon-Mo; Maslov, Konstantin I.; Wong, Terence T. W.; Li, Lei; Huang, Chih-Hsien; Zou, Jun; Wang, Lihong V.

    2015-01-01

    We present fast functional photoacoustic microscopy (PAM), which is capable of three-dimensional high-resolution high-speed imaging of the mouse brain, complementary to other imaging modalities. A single-wavelength pulse-width-based method was implemented to image blood oxygenation with capillary-level resolution and a one-dimensional imaging rate of 100 kHz. We applied PAM to image the vascular morphology, blood oxygenation, blood flow, and oxygen metabolism in the brain in both resting and stimulated states. PMID:25822799

  5. Rapid assembly of structurally defined and highly functionalized conjugated dienes via tethered enyne metathesis.

    PubMed

    Yao, Q

    2001-06-28

    [reaction: see text] Conjugated dienes are versatile building blocks in organic synthesis, and the development of new methods for their synthesis remains an important topic in modern synthetic organic chemistry. We describe here an expedient synthesis of highly functionalized conjugated dienes through sequential silicon-tethered ring-closing enyne metathesis mediated by Grubbs' Ru carbene catalysts and Tamao oxidation. Notable attributes of this methodology include short synthetic manipulations and the structural complexity it confers on the resulting diene moiety. PMID:11418051

  6. Rapid assembly of structurally defined and highly functionalized conjugated dienes via tethered enyne metathesis.

    PubMed

    Yao, Q

    2001-06-28

    [reaction: see text] Conjugated dienes are versatile building blocks in organic synthesis, and the development of new methods for their synthesis remains an important topic in modern synthetic organic chemistry. We describe here an expedient synthesis of highly functionalized conjugated dienes through sequential silicon-tethered ring-closing enyne metathesis mediated by Grubbs' Ru carbene catalysts and Tamao oxidation. Notable attributes of this methodology include short synthetic manipulations and the structural complexity it confers on the resulting diene moiety.

  7. Social Anxiety in High-Functioning Children and Adolescents with Autism and Asperger Syndrome

    ERIC Educational Resources Information Center

    Kuusikko, Sanna; Pollock-Wurman, Rachel; Jussila, Katja; Carter, Alice S.; Mattila, Marja-Leena; Ebeling, Hanna; Pauls, David L.; Moilanen, Irma

    2008-01-01

    We examined social anxiety and internalizing symptoms using the Social Phobia and Anxiety Inventory for Children (SPAI-C), the Social Anxiety Scale for Children -Revised (SASC-R), and the Child Behavior Checklist (CBCL) in a sample of fifty-four high-functioning subjects with autism or Asperger syndrome (HFA/AS) (M = 11.2 plus or minus 1.7 years)…

  8. A high time resolution study of the solar wind-magnetosphere energy coupling function

    NASA Technical Reports Server (NTRS)

    Akasofu, S.-I.; Carbary, J. F.; Meng, C.-I.; Sullivan, J. P.; Lepping, R. P.

    1982-01-01

    A high time resolution study of the relationships between the solar wind-magnetosphere energy coupling function and the total energy dissipation rate of the magnetosphere is made using 5-min average values of solar wind data and of the geomagnetic indices AE and Dst. All the results are essentially the same as those obtained by the earlier studies which were based on the hourly average data set. Therefore, it is confirmed that the magnetosphere is primarily a driven system

  9. High-Q polymer resonators with spatially controlled photo-functionalization for biosensing applications

    NASA Astrophysics Data System (ADS)

    Beck, Torsten; Mai, Martin; Grossmann, Tobias; Wienhold, Tobias; Hauser, Mario; Mappes, Timo; Kalt, Heinz

    2013-03-01

    We demonstrate the applicability of polymeric whispering gallery mode resonators fabricated on silicon as biosensors. Optical measurements on the passive resonators in the visible spectral range yield Q-factors as high as 1.3×107. Local, covalent surface functionalization, is achieved by spatially controlled UV-exposure of a derivative of the photoreactive crosslinker benzophenone. Protein detection is shown using the specific binding of the biotin-streptavidin system.

  10. Local Release of Highly Loaded Antibodies from Functionalized Nanoporous Support for Cancer Immunotherapy

    SciTech Connect

    Lei, Chenghong; Liu, P.; Chen, Baowei; Mao, Yumeng; Engelmann, Heather E.; Shin, Yongsoon; Jaffar, Jade; Hellstrom, Ingegerd; Liu, Jun; Hellstrom, Karl E.

    2010-05-26

    We report that antibodies can be loaded in functionalized mesoporous silica (FMS) with super-high density to provide long-lasting local release at a given site. Preliminary data indicate that FMS-antibody injected directly into a mouse melanoma induces a greater inhibition of tumor growth than seen in various controls, including the antibody injected intraperitoneally. Our findings introduce a novel approach for local delivery of therapeutically active proteins to tumors and potentially, other diseases.

  11. Does hypoxia impair ovarian function in Bolivian women indigenous to high altitude?

    PubMed

    Vitzthum, V J; Ellison, P T; Sukalich, S; Caceres, E; Spielvogel, H

    2000-01-01

    Fertility appears to be reduced in at least some high altitude populations relative to their counterparts at lower elevations. Inferring from the difficulties with reproduction of newcomers to high altitude and from animal experiments, it has been hypothesized that this apparent reduction is the result of hypoxia acting to reduce fecundity and/or increase fetal loss. In humans, however, several behavioral as well as biological factors may affect fertility levels. These many factors have been organized by demographers into a framework of seven proximate determinants that includes fecundability (the monthly probability of conception) of which successful ovulation is one component. To test whether ovarian function is impaired in women indigenous to high altitude, we measured salivary progesterone (P) in a sample (n = 20) of Quechua women (aged 19-42 years) residing at 3,100 m. It was found that mean luteal P = 179 pmol/L and mean midluteal P = 243 pmol/L, levels that fall about midway in the range of known values for several populations and are higher than some lower altitude populations. These findings suggest that hypoxia does not appear to significantly impair ovarian function in those with lifelong residence at high altitude. There are, however, several factors common to many high altitude populations that may act to reduce fecundability and fertility including intercourse patterns (affected by marriage and migration practices), prolonged lactation, dietary insufficiency, and hard labor.

  12. Prediction of Functional Outcome in Individuals at Clinical High Risk for Psychosis

    PubMed Central

    Carrión, Ricardo E.; McLaughlin, Danielle; Goldberg, Terry E.; Auther, Andrea M.; Olsen, Ruth H.; Olvet, Doreen M.; Correll, Christoph U.; Cornblatt, Barbara A.

    2014-01-01

    Importance A major public health concern associated with schizophrenia and psychotic disorders is the long-term disability that involves impaired cognition, lack of social support, and an inability to function independently in the community. A critical goal of early detection and intervention studies in psychosis is therefore to understand the factors leading to this often profound impairment. Objective To develop a predictive model of functional (social and role) outcome in a clinical high-risk sample for psychosis. Design Prospective, naturalistic, longitudinal 3- to 5-year follow-up study. Setting The Recognition and Prevention Program in New York, a research clinic located in the Zucker Hillside Hospital in New York. Participants One hundred one treatment-seeking patients at clinical high risk for psychosis. Ninety-two (91%) were followed up prospectively for a mean (SD) of 3 (1.6) years. Intervention Neurocognitive and clinical assessment. Main Outcomes and Measures The primary outcome variables were social and role functioning at the last follow-up visit. Results Poor social outcome was predicted by reduced processing speed (odds ratio [OR], 1.38; 95% CI, 1.050-1.823; P = .02), impaired social functioning at baseline (OR, 1.85; 95% CI, 1.258-2.732; P = .002), and total disorganized symptoms (OR, 5.06; 95% CI, 1.548-16.527; P = .007). Reduced performance on tests for verbal memory (OR, 1.74; 95% CI, 1.169-2.594; P = .006), role functioning at baseline (OR, 1.34; 95% CI, 1.053-1.711; P = .02), and motor disturbances (OR, 1.77; 95% CI, 1.060-2.969; P = .03) predicted role outcome. The areas under the curve for the social and role prediction models were 0.824 (95% CI, 0.736-0.913; P < .001) and 0.77 (95% CI, 0.68-0.87; P < .001), respectively, demonstrating a high discriminative ability. In addition, poor functional outcomes were not entirely dependent on the development of psychosis, because 40.3% and 45.5% of nonconverters at clinical high risk had poor social

  13. Simultaneous electropolymerization and electro-click functionalization for highly versatile surface platforms.

    PubMed

    Rydzek, Gaulthier; Terentyeva, Tatyana G; Pakdel, Amir; Golberg, Dmitri; Hill, Jonathan P; Ariga, Katsuhiko

    2014-05-27

    Simple preparation methods of chemically versatile and highly functionalizable surfaces remain rare and present a challenging research objective. Here, we demonstrate a simultaneous electropolymerization and electro-click functionalization process (SEEC) for one-pot self-construction of aniline- and naphthalene-based functional polymer films where both polymerization and click functionalization are triggered by applying electrochemical stimuli. Cyclic voltammetry (CV) can be applied for the simultaneous oxidation of 4-azidoaniline and the reduction of Cu(II) ions, resulting in polymerization of the former, and the Cu(I)-catalyzed alkyne/azide cycloaddition ("click" chemistry). Properties of the films obtained can be tuned by varying their morphology, their chemically "clicked" content, or by postconstruction functionalization. To demonstrate this, the CV scan rates, component monomers, and "clicked" molecules were varied. Covalent postconstruction immobilization of horseradish peroxidase was also performed. Consequently, pseudocapacitance and enzyme activity were affected. SEEC provides surface scientists an easy access to a wide range of functionalization possibilities in several fields including sensors, fuel cells, photovoltaics, and biomaterials.

  14. Cognitive functional magnetic resonance imaging at very-high-field: eye movement control.

    PubMed

    Luna, B; Sweeney, J A

    1999-02-01

    The oculomotor system, which optimizes visual interaction with the environment, provides a valuable model system for probing the building blocks of higher-order cognition. Attention shifting, working memory, and inhibition of prepotent responses can be investigated in healthy individuals and patients with brain disorders. Although the neurophysiology of the oculomotor system has been well characterized at the single-cell level in nonhuman primates, its functional architecture in humans determined by evoked response procedures and studies of patients with focal lesions has been limited. Available evidence points to a widely distributed set of neocortical and subcortical brain regions involved in the control of eye movements, including brain stem, cerebellum, thalamus, striatum, and parietal and frontal cortices. The advent of functional magnetic resonance imaging provides a noninvasive manner of localizing, at high spatial resolution, the brain systems that subserve different aspects of sensory and cognitive processes in humans. Functional magnetic resonance imaging studies have already delineated the brain systems subserving sensorimotor and cognitive control of eye movements in adult and pediatric populations. Hence, the combination of functional magnetic resonance imaging and eye movement procedures can be used to probe the integrity of the brain in neurological and psychiatric disorders as well as provide a window into the changes in brain function subserving cognitive development. PMID:10389669

  15. The brains of high functioning autistic individuals do not synchronize with those of others☆

    PubMed Central

    Salmi, J.; Roine, U.; Glerean, E.; Lahnakoski, J.; Nieminen-von Wendt, T.; Tani, P.; Leppämäki, S.; Nummenmaa, L.; Jääskeläinen, I.P.; Carlson, S.; Rintahaka, P.; Sams, M.

    2013-01-01

    Multifaceted and idiosyncratic aberrancies in social cognition characterize autism spectrum disorders (ASDs). To advance understanding of underlying neural mechanisms, we measured brain hemodynamic activity with functional magnetic resonance imaging (fMRI) in individuals with ASD and matched-pair neurotypical (NT) controls while they were viewing a feature film portraying social interactions. Pearson's correlation coefficient was used as a measure of voxelwise similarity of brain activity (InterSubject Correlations—ISCs). Individuals with ASD showed lower ISC than NT controls in brain regions implicated in processing social information including the insula, posterior and anterior cingulate cortex, caudate nucleus, precuneus, lateral occipital cortex, and supramarginal gyrus. Curiously, also within NT group, autism-quotient scores predicted ISC in overlapping areas, including, e.g., supramarginal gyrus and precuneus. In ASD participants, functional connectivity was decreased between the frontal pole and the superior frontal gyrus, angular gyrus, superior parietal lobule, precentral gyrus, precuneus, and anterior/posterior cingulate gyrus. Taken together these results suggest that ISC and functional connectivity measure distinct features of atypical brain function in high-functioning autistic individuals during free viewing of acted social interactions. Our ISC results suggest that the minds of ASD individuals do not ‘tick together’ with others while perceiving identical dynamic social interactions. PMID:24273731

  16. Identification of high-level functional/system requirements for future civil transports

    NASA Technical Reports Server (NTRS)

    Swink, Jay R.; Goins, Richard T.

    1992-01-01

    In order to accommodate the rapid growth in commercial aviation throughout the remainder of this century, the Federal Aviation Administration (FAA) is faced with a formidable challenge to upgrade and/or modernize the National Airspace System (NAS) without compromising safety or efficiency. A recurring theme in both the Aviation System Capital Investment Plan (CIP), which has replaced the NAS Plan, and the new FAA Plan for Research, Engineering, and Development (RE&D) rely on the application of new technologies and a greater use of automation. Identifying the high-level functional and system impacts of such modernization efforts on future civil transport operational requirements, particularly in terms of cockpit functionality and information transfer, was the primary objective of this project. The FAA planning documents for the NAS of the 2005 era and beyond were surveyed; major aircraft functional capabilities and system components required for such an operating environment were identified. A hierarchical structured analysis of the information processing and flows emanating from such functional/system components were conducted and the results documented in graphical form depicting the relationships between functions and systems.

  17. Autonomic arousal explains social cognitive abilities in high-functioning adults with autism spectrum disorder.

    PubMed

    Mathersul, Danielle; McDonald, Skye; Rushby, Jacqueline A

    2013-09-01

    Empirical research into behavioural profiles and autonomic responsivity in individuals with autism spectrum disorders (ASDs) is highly variable and inconsistent. Two preliminary studies of children with ASDs suggest that there may be subgroups of ASDs depending on their resting arousal levels, and that these subgroups show different profiles of autonomic responsivity. The aim of the present study was to determine whether (i) adults with high-functioning ASDs may be separated into subgroups according to variation in resting arousal; and (ii) these ASD arousal subgroups differ in their behavioural profiles for basic emotion recognition, judgements of trustworthiness, and cognitive and affective empathy. Thirty high-functioning adults with ASDs and 34 non-clinical controls participated. Resting arousal was determined as the average skin conductance (SCL) across a 2 min resting period. There was a subgroup of ASD adults with significantly lower resting SCL. These individuals demonstrated poorer emotion recognition, tended to judge faces more negatively, and had atypical relationships between SCL and affective empathy. In contrast, low cognitive empathy was a feature of all ASD adults. These findings have important implications for clinical interventions and future studies investigating autonomic functioning in ASDs.

  18. High maneuverability guidewire with functionally graded properties using new superelastic alloys.

    PubMed

    Sutou, Y; Yamauchi, K; Suzuki, M; Furukawa, A; Omori, T; Takagi, T; Kainuma, R; Nishida, M; Ishida, K

    2006-01-01

    Nitinol shape memory alloys (SMAs) are attracting considerable attention as core materials for medical guidewires because of their excellent flexibility and shape retention. However, since Nitinol guidewires possess low rigidity, the pushability and torquability of the guidewires are insufficient. On the other hand, although guidewires made of stainless steel have high pushability, plastic deformation occurs easily. We have developed a new class of superelastic guidewires with functionally graded properties from the tip to the end by using new SMA core materials such as Cu-Al-Mn-based or Ni-free Ti-Mo-Sn SMAs. The tip portion of the guidewire shows excellent superelasticity (SE), while the body portion possesses high rigidity. These functionally graded characteristics can be realized by microstructural control. These guidewires with functionally graded properties show excellent pushability and torquability and are considerably easier to handle than conventional guidewires with Nitinol or stainless steel cores. Moreover, a metallic catheter using a Ni-free Ti-based SMA with high biocompatibility is introduced.

  19. Highly regio- and enantioselective multiple oxy- and amino-functionalizations of alkenes by modular cascade biocatalysis

    PubMed Central

    Wu, Shuke; Zhou, Yi; Wang, Tianwen; Too, Heng-Phon; Wang, Daniel I. C.; Li, Zhi

    2016-01-01

    New types of asymmetric functionalizations of alkenes are highly desirable for chemical synthesis. Here, we develop three novel types of regio- and enantioselective multiple oxy- and amino-functionalizations of terminal alkenes via cascade biocatalysis to produce chiral α-hydroxy acids, 1,2-amino alcohols and α-amino acids, respectively. Basic enzyme modules 1–4 are developed to convert alkenes to (S)-1,2-diols, (S)-1,2-diols to (S)-α-hydroxyacids, (S)-1,2-diols to (S)-aminoalcohols and (S)-α-hydroxyacids to (S)-α-aminoacids, respectively. Engineering of enzyme modules 1 & 2, 1 & 3 and 1, 2 & 4 in Escherichia coli affords three biocatalysts over-expressing 4–8 enzymes for one-pot conversion of styrenes to the corresponding (S)-α-hydroxyacids, (S)-aminoalcohols and (S)-α-aminoacids in high e.e. and high yields, respectively. The new types of asymmetric alkene functionalizations provide green, safe and useful alternatives to the chemical syntheses of these compounds. The modular approach for engineering multi-step cascade biocatalysis is useful for developing other new types of one-pot biotransformations for chemical synthesis. PMID:27297777

  20. Extra-galactic high-energy transients: event rate density and luminosity function

    NASA Astrophysics Data System (ADS)

    Sun, Hui; Zhang, Bing; Li, Zhuo

    2015-08-01

    Several types of extra-galactic high-energy transients have been discovered, which include high-luminosity and low-luminosity long-duration gamma-ray bursts (GRBs), short-duration GRBs, supernova shock breakouts (SBOs), and tidal disruption events (TDEs) without or with a relativistic jet. In this paper, we apply a unified method to systematically study the reshift-dependent event rate densities and luminosity functions of these extra-galactic high-energy transients. We consider star formation history as the tracer of the redshift distribution for long GRBs and SBOs. For short GRBs, we consider the compact star merger model to introduce several possible merger delay time distribution models. For TDEs, we consider the mass distribution of supermassive black holes as a function of redshift. We derive some empirical formulae for the redshift-dependent event rate density for different types of transients. Based on the observed events, we derive the local specific event rate density, ρ0,L ∝ dρ0/dL for each type of transient, which represents its luminosity function. All the transients are consistent with having a single power law luminosity function, except the high luminosity long GRBs (HL-lGRBs), whose luminosity function can be well described by a broken power law. The total event rate density for a particular transient depends on the luminosity threshold, and we obtain the following values in units of Gpc-3 yr-1: 2.82^{+0.41}_{-0.36} for HL-lGRBs above 4×1049 erg s-1 218^{+130}_{-86} for low luminosity long GRBs above 6×1046 erg s-1 3.18^{+0.88}_{-0.70}, 2.87^{+0.80}_{-0.64}, and 6.25^{+1.73}_{-1.38} above 5×1049 erg s-1 for short GRBs with three different merger delay models (Gaussian, log-normal, and power law); 2.0^{+2.6}_{-1.3}×104 above 9×1043 erg s-1 for SBOs, 3.0^{+1.0}_{-0.8}×105 for normal TDEs above 1042 erg s-1 and 6.2^{+8.2}_{-4.0} above 3×1047 erg s-1for TDE jets as discovered by Swift. Intriguingly, the global specific event rate densities

  1. Temperature response functions introduce high uncertainty in modelled carbon stocks in cold temperature regimes

    NASA Astrophysics Data System (ADS)

    Portner, H.; Wolf, A.; Bugmann, H.

    2009-04-01

    function of Lloyd&Taylor therefore is an adequate choice to model the temperature dependency of soil organic matter decomposition. The Ticino catchment (300-2300m) in Southern Switzerland was used to study the sensitivity of long-term changes (100 years) in the prediction of carbon storage. The uncertainty in temperature response introduced into the model lead to high uncertainties in long-term soil carbon stocks. Interestingly, the uncertainty increased with decreasing temperature and increasing elevation. The carbon pools in lower elevations (mean annual temperature > 15 °C) turned over faster and little carbon accumulated in the soil. The carbon pools in higher elevations and hence in higher latitudes experiencing colder temperature (mean annual temperature < 15 °C) turned over slower and therefore accumulated more carbon over the simulation period. Therefore, the high elevation soils stored more carbon, but the prediction of the carbon pool size had a much higher uncertainty than the low elevation soils. We concluded that with our model, the predictions of the potential loss of soil carbon in cold temperature regimes is more uncertain than the carbon loss in warmer regions, both due to the higher soil carbon pools, but also due to the higher uncertainty found in our simulations.

  2. Functionalized magnetic mesoporous silica nanoparticles for U removal from low and high pH groundwater.

    PubMed

    Li, Dien; Egodawatte, Shani; Kaplan, Daniel I; Larsen, Sarah C; Serkiz, Steven M; Seaman, John C

    2016-11-01

    U(VI) species display limited adsorption onto sediment minerals and synthetic sorbents in pH <4 or pH >8 groundwater. In this work, magnetic mesoporous silica nanoparticles (MMSNs) with magnetite nanoparticle cores were functionalized with various organic molecules using post-synthetic methods. The functionalized MMSNs were characterized using N2 adsorption-desorption isotherms, thermogravimetric analysis (TGA), transmission electron microscopy (TEM), (13)C cross polarization and magic angle spinning (CPMAS) nuclear magnetic resonance (NMR) spectroscopy, and powder X-ray diffraction (XRD), which indicated that mesoporous silica (MCM-41) particles of 100-200nm formed around a core of magnetic iron oxide, and the functional groups were primarily grafted into the mesopores of ∼3.0nm in size. The functionalized MMSNs were effective for U removal from pH 3.5 and 9.6 artificial groundwater (AGW). Functionalized MMSNs removed U from the pH 3.5 AGW by as much as 6 orders of magnitude more than unfunctionalized nanoparticles or silica and had adsorption capacities as high as 38mg/g. They removed U from the pH 9.6 AGW as much as 4 orders of magnitude greater than silica and 2 orders of magnitude greater than the unfunctionalized nanoparticles with adsorption capacities as high as 133mg/g. These results provide an applied solution for treating U contamination that occurs at extreme pH environments and a scientific foundation for solving critical industrial issues related to environmental stewardship and nuclear power production.

  3. Functionalized magnetic mesoporous silica nanoparticles for U removal from low and high pH groundwater.

    PubMed

    Li, Dien; Egodawatte, Shani; Kaplan, Daniel I; Larsen, Sarah C; Serkiz, Steven M; Seaman, John C

    2016-11-01

    U(VI) species display limited adsorption onto sediment minerals and synthetic sorbents in pH <4 or pH >8 groundwater. In this work, magnetic mesoporous silica nanoparticles (MMSNs) with magnetite nanoparticle cores were functionalized with various organic molecules using post-synthetic methods. The functionalized MMSNs were characterized using N2 adsorption-desorption isotherms, thermogravimetric analysis (TGA), transmission electron microscopy (TEM), (13)C cross polarization and magic angle spinning (CPMAS) nuclear magnetic resonance (NMR) spectroscopy, and powder X-ray diffraction (XRD), which indicated that mesoporous silica (MCM-41) particles of 100-200nm formed around a core of magnetic iron oxide, and the functional groups were primarily grafted into the mesopores of ∼3.0nm in size. The functionalized MMSNs were effective for U removal from pH 3.5 and 9.6 artificial groundwater (AGW). Functionalized MMSNs removed U from the pH 3.5 AGW by as much as 6 orders of magnitude more than unfunctionalized nanoparticles or silica and had adsorption capacities as high as 38mg/g. They removed U from the pH 9.6 AGW as much as 4 orders of magnitude greater than silica and 2 orders of magnitude greater than the unfunctionalized nanoparticles with adsorption capacities as high as 133mg/g. These results provide an applied solution for treating U contamination that occurs at extreme pH environments and a scientific foundation for solving critical industrial issues related to environmental stewardship and nuclear power production. PMID:27341378

  4. Dengue virus-specific human CD4+ T-lymphocyte responses in a recipient of an experimental live-attenuated dengue virus type 1 vaccine: bulk culture proliferation, clonal analysis, and precursor frequency determination.

    PubMed Central

    Green, S; Kurane, I; Edelman, R; Tacket, C O; Eckels, K H; Vaughn, D W; Hoke, C H; Ennis, F A

    1993-01-01

    We analyzed the CD4+ T-lymphocyte responses to dengue, West Nile, and yellow fever viruses 4 months after immunization of a volunteer with an experimental live-attenuated dengue virus type 1 vaccine (DEN-1 45AZ5). We examined bulk culture proliferation to noninfectious antigens, determined the precursor frequency of specific CD4+ T cells by limiting dilution, and established and analyzed CD4+ T-cell clones. Bulk culture proliferation was predominantly dengue virus type 1 specific with a lesser degree of cross-reactive responses to other dengue virus serotypes, West Nile virus, and yellow fever virus. Precursor frequency determination by limiting dilution in the presence of noninfectious dengue virus antigens revealed a frequency of antigen-reactive cells of 1 in 1,686 peripheral blood mononuclear cells (PBMC) for dengue virus type 1, 1 in 9,870 PBMC for dengue virus type 3, 1 in 14,053 PBMC for dengue virus type 2, and 1 in 17,690 PBMC for dengue virus type 4. Seventeen CD4+ T-cell clones were then established by using infectious dengue virus type 1 as antigen. Two patterns of dengue virus specificity were found in these clones. Thirteen clones were dengue virus type 1 specific, and four clones recognized both dengue virus types 1 and 3. Analysis of human leukocyte antigen (HLA) restriction revealed that five clones are HLA-DRw52 restricted, one clone is HLA-DP3 restricted, and one clone is HLA-DP4 restricted. These results indicate that in this individual, the CD4+ T-lymphocyte responses to immunization with live-attenuated dengue virus type 1 vaccine are predominantly serotype specific and suggest that a multivalent vaccine may be necessary to elicit strong serotype-cross-reactive CD4+ T-lymphocyte responses in such individuals. PMID:8371350

  5. Reduced Volume of the Arcuate Fasciculus in Adults with High-Functioning Autism Spectrum Conditions

    PubMed Central

    Moseley, Rachel L.; Correia, Marta M.; Baron-Cohen, Simon; Shtyrov, Yury; Pulvermüller, Friedemann; Mohr, Bettina

    2016-01-01

    Atypical language is a fundamental feature of autism spectrum conditions (ASC), but few studies have examined the structural integrity of the arcuate fasciculus, the major white matter tract connecting frontal and temporal language regions, which is usually implicated as the main transfer route used in processing linguistic information by the brain. Abnormalities in the arcuate have been reported in young children with ASC, mostly in low-functioning or non-verbal individuals, but little is known regarding the structural properties of the arcuate in adults with ASC or, in particular, in individuals with ASC who have intact language, such as those with high-functioning autism or Asperger syndrome. We used probabilistic tractography of diffusion-weighted imaging to isolate and scrutinize the arcuate in a mixed-gender sample of 18 high-functioning adults with ASC (17 Asperger syndrome) and 14 age- and IQ-matched typically developing controls. Arcuate volume was significantly reduced bilaterally with clearest differences in the right hemisphere. This finding remained significant in an analysis of all male participants alone. Volumetric reduction in the arcuate was significantly correlated with the severity of autistic symptoms as measured by the Autism-Spectrum Quotient. These data reveal that structural differences are present even in high-functioning adults with ASC, who presented with no clinically manifest language deficits and had no reported developmental language delay. Arcuate structural integrity may be useful as an index of ASC severity and thus as a predictor and biomarker for ASC. Implications for future research are discussed. PMID:27242478

  6. Reduced Volume of the Arcuate Fasciculus in Adults with High-Functioning Autism Spectrum Conditions.

    PubMed

    Moseley, Rachel L; Correia, Marta M; Baron-Cohen, Simon; Shtyrov, Yury; Pulvermüller, Friedemann; Mohr, Bettina

    2016-01-01

    Atypical language is a fundamental feature of autism spectrum conditions (ASC), but few studies have examined the structural integrity of the arcuate fasciculus, the major white matter tract connecting frontal and temporal language regions, which is usually implicated as the main transfer route used in processing linguistic information by the brain. Abnormalities in the arcuate have been reported in young children with ASC, mostly in low-functioning or non-verbal individuals, but little is known regarding the structural properties of the arcuate in adults with ASC or, in particular, in individuals with ASC who have intact language, such as those with high-functioning autism or Asperger syndrome. We used probabilistic tractography of diffusion-weighted imaging to isolate and scrutinize the arcuate in a mixed-gender sample of 18 high-functioning adults with ASC (17 Asperger syndrome) and 14 age- and IQ-matched typically developing controls. Arcuate volume was significantly reduced bilaterally with clearest differences in the right hemisphere. This finding remained significant in an analysis of all male participants alone. Volumetric reduction in the arcuate was significantly correlated with the severity of autistic symptoms as measured by the Autism-Spectrum Quotient. These data reveal that structural differences are present even in high-functioning adults with ASC, who presented with no clinically manifest language deficits and had no reported developmental language delay. Arcuate structural integrity may be useful as an index of ASC severity and thus as a predictor and biomarker for ASC. Implications for future research are discussed. PMID:27242478

  7. Functionalized hollow siliceous spheres for VOCs removal with high efficiency and stability.

    PubMed

    Wang, Hongning; Tang, Mei; Zhang, Ke; Cai, Daofei; Huang, Weiqiu; Chen, Ruoyu; Yu, Chengzhong

    2014-03-15

    Functionalized hollow siliceous spheres (HSSs) have been prepared by surface modification with trimethylchlorosilane (TMCS) for the removal of volatile organic compounds (VOCs). The resultant HSSs-TMCS possesses a uniform and well-dispersed hollow spherical structure, high surface area, large total pore volume, high VOCs adsorption capacity, and small water vapor adsorption capacity. The adsorption and desorption performance of HSSs-TMCS under static (n-hexane and 93# gasoline) and dynamic (n-hexane) conditions was investigated. Compared with commercial silica gel (SG) and activated carbon (AC), HSSs-TMCS show higher capacity of adsorbing n-hexane and 93# gasoline with good stability and low water vapor adsorption capacity under static adsorption conditions, higher dynamic adsorption capacity and stable breakthrough time under dynamic adsorption conditions. The high efficiency and stability of functionalized HSSs are associated with their unique hollow morphology and structure parameters. The designed HSSs-TMCS with high VOCs removal capacity and recyclability are promising candidates for the treatment of air pollution. PMID:24486614

  8. Scalable Functionalized Graphene Nano-platelets as Tunable Cathodes for High-performance Lithium Rechargeable Batteries

    PubMed Central

    Kim, Haegyeom; Lim, Hee-Dae; Kim, Sung-Wook; Hong, Jihyun; Seo, Dong-Hwa; Kim, Dae-chul; Jeon, Seokwoo; Park, Sungjin; Kang, Kisuk

    2013-01-01

    High-performance and cost-effective rechargeable batteries are key to the success of electric vehicles and large-scale energy storage systems. Extensive research has focused on the development of (i) new high-energy electrodes that can store more lithium or (ii) high-power nano-structured electrodes hybridized with carbonaceous materials. However, the current status of lithium batteries based on redox reactions of heavy transition metals still remains far below the demands required for the proposed applications. Herein, we present a novel approach using tunable functional groups on graphene nano-platelets as redox centers. The electrode can deliver high capacity of ~250 mAh g−1, power of ~20 kW kg−1 in an acceptable cathode voltage range, and provide excellent cyclability up to thousands of repeated charge/discharge cycles. The simple, mass-scalable synthetic route for the functionalized graphene nano-platelets proposed in this work suggests that the graphene cathode can be a promising new class of electrode. PMID:23514953

  9. Associations among Symptoms of Autism, Symptoms of Depression and Executive Functions in Children with High-Functioning Autism: A 2 Year Follow-Up Study

    ERIC Educational Resources Information Center

    Andersen, Per Normann; Skogli, Erik Winther; Hovik, Kjell Tore; Egeland, Jens; Øie, Merete

    2015-01-01

    This study investigated the course of and association among changes in autism symptoms, depression symptoms and executive functions (EF) in children with high-functioning autism (HFA). Thirty-four children with HFA and 45 typically developing children (age 9-16) were assessed at baseline and after 2 years. Children with HFA had impaired scores on…

  10. Development and Pilot Testing of the Challenge Module: A Proposed Adjunct to the Gross Motor Function Measure for High-Functioning Children with Cerebral Palsy

    ERIC Educational Resources Information Center

    Wilson, Ashlea; Kavanaugh, Abi; Moher, Rosemarie; McInroy, Megan; Gupta, Neena; Salbach, Nancy M.; Wright, F. Virginia

    2011-01-01

    The aim was to develop a Challenge Module (CM) as a proposed adjunct to the Gross Motor Function Measure for children with cerebral palsy who have high-level motor function. Items were generated in a physiotherapist (PT) focus group. Item reduction was based on PTs' ratings of item importance and safety via online surveys. The proposed CM items…

  11. Impaired High-Density Lipoprotein Anti-Oxidant Function Predicts Poor Outcome in Critically Ill Patients

    PubMed Central

    Schrutka, Lore; Goliasch, Georg; Meyer, Brigitte; Wurm, Raphael; Koller, Lorenz; Kriechbaumer, Lukas; Heinz, Gottfried; Pacher, Richard; Lang, Irene M

    2016-01-01

    Introduction Oxidative stress affects clinical outcome in critically ill patients. Although high-density lipoprotein (HDL) particles generally possess anti-oxidant capacities, deleterious properties of HDL have been described in acutely ill patients. The impact of anti-oxidant HDL capacities on clinical outcome in critically ill patients is unknown. We therefore analyzed the predictive value of anti-oxidant HDL function on mortality in an unselected cohort of critically ill patients. Method We prospectively enrolled 270 consecutive patients admitted to a university-affiliated intensive care unit (ICU) and determined anti-oxidant HDL function using the HDL oxidant index (HOI). Based on their HOI, the study population was stratified into patients with impaired anti-oxidant HDL function and the residual study population. Results During a median follow-up time of 9.8 years (IQR: 9.2 to 10.0), 69% of patients died. Cox regression analysis revealed a significant and independent association between impaired anti-oxidant HDL function and short-term mortality with an adjusted HR of 1.65 (95% CI 1.22–2.24; p = 0.001) as well as 10-year mortality with an adj. HR of 1.19 (95% CI 1.02–1.40; p = 0.032) when compared to the residual study population. Anti-oxidant HDL function correlated with the amount of oxidative stress as determined by Cu/Zn superoxide dismutase (r = 0.38; p<0.001). Conclusion Impaired anti-oxidant HDL function represents a strong and independent predictor of 30-day mortality as well as long-term mortality in critically ill patients. PMID:26978526

  12. Does high-density lipoprotein protect vascular function in healthy pregnancy?

    PubMed

    Sulaiman, Wan N Wan; Caslake, Muriel J; Delles, Christian; Karlsson, Helen; Mulder, Monique T; Graham, Delyth; Freeman, Dilys J

    2016-04-01

    The maternal adaptation to pregnancy includes hyperlipidaemia, oxidative stress and chronic inflammation. In non-pregnant individuals, these processes are usually associated with poor vascular function. However, maternal vascular function is enhanced in pregnancy. It is not understood how this is achieved in the face of the adverse metabolic and inflammatory environment. Research into cardiovascular disease demonstrates that plasma HDL (high-density lipoprotein), by merit of its functionality rather than its plasma concentration, exerts protective effects on the vascular endothelium. HDL has vasodilatory, antioxidant, anti-thrombotic and anti-inflammatory effects, and can protect against endothelial cell damage. In pregnancy, the plasma HDL concentration starts to rise at 10 weeks of gestation, peaking at 20 weeks. The initial rise in plasma HDL occurs around the time of the establishment of the feto-placental circulation, a time when the trophoblast plugs in the maternal spiral arteries are released, generating oxidative stress. Thus there is the intriguing possibility that new HDL of improved function is synthesized around the time of the establishment of the feto-placental circulation. In obese pregnancy and, to a greater extent, in pre-eclampsia, plasma HDL levels are significantly decreased and maternal vascular function is reduced. Wire myography studies have shown an association between the plasma content of apolipoprotein AI, the major protein constituent of HDL, and blood vessel relaxation. These observations lead us to hypothesize that HDL concentration, and function, increases in pregnancy in order to protect the maternal vascular endothelium and that in pre-eclampsia this fails to occur.

  13. Multicatalytic colloids with highly scalable, adjustable, and stable functionalities in organic and aqueous media

    NASA Astrophysics Data System (ADS)

    Kim, Donghee; Cheong, Sanghyuk; Ahn, Yun Gyong; Ryu, Sook Won; Kim, Jai-Kyeong; Cho, Jinhan

    2016-03-01

    Despite a large number of developments of noble metal (or metal oxide) NP-based catalysts, it has been a great challenge to prepare high-performance recyclable catalysts with integrated functionalities that can be used in various solvent media. Here, we report on layer-by-layer (LbL) assembled multicatalysts with high catalytic performance, showing high dispersion and recycling stability in organic and aqueous media. The remarkable advantages of our approach are as follows. (i) Various metal or metal oxide NPs with desired catalytic performance can be easily incorporated into multilayered shells, forming densely packed arrays that allow one colloid to be used as a multicatalyst with highly integrated and controllable catalytic properties. (ii) Additionally, the dispersion stability of catalytic colloids in a desired solvent can be determined by the type of ultrathin outermost layer coating each colloid. (iii) Lastly, the covalent bonding between inorganic NPs and dendrimers within multilayer shells enhances the recycling stability of multicatalytic colloids. The resulting core-shell colloids including OA-Fe3O4 NPs, TOABr-Pd NPs, and OA-TiO2 NPs exhibited excellent performance in the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) and photocatalysis in aqueous media and in the Sonogashira coupling reaction (99% yield) in organic media. Given that the catalytic properties of recyclable colloids reported to date have entirely depended on the functionality of a single catalytic NP layer deposited onto colloids in selective solvent media, our approach provides a basis for the design and exploitation of high-performance recyclable colloids with integrated multicatalytic properties and high dispersion stability in a variety of solvents.Despite a large number of developments of noble metal (or metal oxide) NP-based catalysts, it has been a great challenge to prepare high-performance recyclable catalysts with integrated functionalities that can be used in various solvent

  14. High-Density Reconstitution of Functional Water Channels into Vesicular and Planar Block Copolymer Membranes

    PubMed Central

    2012-01-01

    The exquisite selectivity and unique transport properties of membrane proteins can be harnessed for a variety of engineering and biomedical applications if suitable membranes can be produced. Amphiphilic block copolymers (BCPs), developed as stable lipid analogs, form membranes that functionally incorporate membrane proteins and are ideal for such applications. While high protein density and planar membrane morphology are most desirable, BCP–membrane protein aggregates have so far been limited to low protein densities in either vesicular or bilayer morphologies. Here, we used dialysis to reproducibly form planar and vesicular BCP membranes with a high density of reconstituted aquaporin-0 (AQP0) water channels. We show that AQP0 retains its biological activity when incorporated at high density in BCP membranes, and that the morphology of the BCP–protein aggregates can be controlled by adjusting the amount of incorporated AQP0. We also show that BCPs can be used to form two-dimensional crystals of AQP0. PMID:23082933

  15. A numerical method for determining highly precise electron energy distribution functions from Langmuir probe characteristics

    SciTech Connect

    Bang, Jin-Young; Chung, Chin-Wook

    2010-12-15

    Electron energy distribution functions (EEDFs) were determined from probe characteristics using a numerical ac superimposed method with a distortion correction of high derivative terms by varying amplitude of a sinusoidal perturbation voltage superimposed onto the dc sweep voltage, depending on the related electron energy. Low amplitude perturbation applied around the plasma potential represented the low energy peak of the EEDF exactly, and high amplitude perturbation applied around the floating potential was effective to suppress noise or distortion of the probe characteristic, which is fatal to the tail electron distribution. When a small random noise was imposed over the stabilized prove characteristic, the numerical differentiation method was not suitable to determine the EEDF, while the numerical ac superimposed method was able to obtain a highly precise EEDF.

  16. A highly expressed miR-101 isomiR is a functional silencing small RNA

    PubMed Central

    2013-01-01

    Background MicroRNAs (miRNAs) are short non-coding regulatory RNAs that control gene expression usually producing translational repression and gene silencing. High-throughput sequencing technologies have revealed heterogeneity at length and sequence level for the majority of mature miRNAs (IsomiRs). Most isomiRs can be explained by variability in either Dicer1 or Drosha cleavage during miRNA biogenesis at 5’ or 3’ of the miRNA (trimming variants). Although isomiRs have been described in different tissues and organisms, their functional validation as modulators of gene expression remains elusive. Here we have characterized the expression and function of a highly abundant miR-101 5’-trimming variant (5’-isomiR-101). Results The analysis of small RNA sequencing data in several human tissues and cell lines indicates that 5’-isomiR-101 is ubiquitously detected and a highly abundant, especially in the brain. 5’-isomiR-101 was found in Ago-2 immunocomplexes and complementary approaches showed that 5’-isomiR-101 interacted with different members of the silencing (RISC) complex. In addition, 5’-isomiR-101 decreased the expression of five validated miR-101 targets, suggesting that it is a functional variant. Both the binding to RISC members and the degree of silencing were less efficient for 5’-isomiR-101 compared with miR-101. For some targets, both miR-101 and 5’-isomiR-101 significantly decreased protein expression with no changes in the respective mRNA levels. Although a high number of overlapping predicted targets suggest similar targeted biological pathways, a correlation analysis of the expression profiles of miR-101 variants and predicted mRNA targets in human brains at different ages, suggest specific functions for miR-101- and 5’-isomiR-101. Conclusions These results suggest that isomiRs are functional variants and further indicate that for a given miRNA, the different isomiRs may contribute to the overall effect as quantitative and

  17. Multicatalytic colloids with highly scalable, adjustable, and stable functionalities in organic and aqueous media.

    PubMed

    Kim, Donghee; Cheong, Sanghyuk; Ahn, Yun Gyong; Ryu, Sook Won; Kim, Jai-Kyeong; Cho, Jinhan

    2016-04-01

    Despite a large number of developments of noble metal (or metal oxide) NP-based catalysts, it has been a great challenge to prepare high-performance recyclable catalysts with integrated functionalities that can be used in various solvent media. Here, we report on layer-by-layer (LbL) assembled multicatalysts with high catalytic performance, showing high dispersion and recycling stability in organic and aqueous media. The remarkable advantages of our approach are as follows. (i) Various metal or metal oxide NPs with desired catalytic performance can be easily incorporated into multilayered shells, forming densely packed arrays that allow one colloid to be used as a multicatalyst with highly integrated and controllable catalytic properties. (ii) Additionally, the dispersion stability of catalytic colloids in a desired solvent can be determined by the type of ultrathin outermost layer coating each colloid. (iii) Lastly, the covalent bonding between inorganic NPs and dendrimers within multilayer shells enhances the recycling stability of multicatalytic colloids. The resulting core-shell colloids including OA-Fe3O4 NPs, TOABr-Pd NPs, and OA-TiO2 NPs exhibited excellent performance in the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) and photocatalysis in aqueous media and in the Sonogashira coupling reaction (99% yield) in organic media. Given that the catalytic properties of recyclable colloids reported to date have entirely depended on the functionality of a single catalytic NP layer deposited onto colloids in selective solvent media, our approach provides a basis for the design and exploitation of high-performance recyclable colloids with integrated multicatalytic properties and high dispersion stability in a variety of solvents.

  18. Functional coupling of renal K+ and Na+ handling causes high blood pressure in Na+ replete mice

    PubMed Central

    Vitzthum, Helga; Seniuk, Anika; Schulte, Laura Helene; Müller, Maxie Luise; Hetz, Hannah; Ehmke, Heimo

    2014-01-01

    A network of kinases, including WNKs, SPAK and Sgk1, is critical for the independent regulation of K+ and Na+ transport in the distal nephron. Angiotensin II is thought to act as a key hormone in orchestrating these kinases to switch from K+ secretion during hyperkalaemia to Na+ reabsorption during intravascular volume depletion, thus keeping disturbances in electrolyte and blood pressure homeostasis at a minimum. It remains unclear, however, how K+ and Na+ transport are regulated during a high Na+ intake, which is associated with suppressed angiotensin II levels and a high distal tubular Na+ load. We therefore investigated the integrated blood pressure, renal, hormonal and gene and protein expression responses to large changes of K+ intake in Na+ replete mice. Both low and high K+ intake increased blood pressure and caused Na+ retention. Low K+ intake was accompanied by an upregulation of the sodium-chloride cotransporter (NCC) and its activating kinase SPAK, and inhibition of NCC normalized blood pressure. Renal responses were unaffected by angiotensin AT1 receptor antagonism, indicating that low K+ intake activates the distal nephron by an angiotensin-independent mode of action. High K+ intake was associated with elevated plasma aldosterone concentrations and an upregulation of the epithelial sodium channel (ENaC) and its activating kinase Sgk1. Surprisingly, high K+ intake increased blood pressure even during ENaC or mineralocorticoid receptor antagonism, suggesting the contribution of aldosterone-independent mechanisms. These findings show that in a Na+ replete state, changes in K+ intake induce specific molecular and functional adaptations in the distal nephron that cause a functional coupling of renal K+ and Na+ handling, resulting in Na+ retention and high blood pressure when K+ intake is either restricted or excessively increased. PMID:24396058

  19. High content evaluation of shear dependent platelet function in a microfluidic flow assay.

    PubMed

    Hansen, Ryan R; Wufsus, Adam R; Barton, Steven T; Onasoga, Abimbola A; Johnson-Paben, Rebecca M; Neeves, Keith B

    2013-02-01

    The high blood volume requirements and low throughput of conventional flow assays for measuring platelet function are unsuitable for drug screening and clinical applications. In this study, we describe a microfluidic flow assay that uses 50 μL of whole blood to measure platelet function on ~300 micropatterned spots of collagen over a range of physiologic shear rates (50-920 s(-1)). Patterning of collagen thin films (CTF) was achieved using a novel hydrated microcontact stamping method. CTF spots of 20, 50, and 100 μm were defined on glass substrates and consisted of a dense mat of nanoscale collagen fibers (3.74 ± 0.75 nm). We found that a spot size of greater than 20 μm was necessary to support platelet adhesion under flow, suggesting a threshold injury size is necessary for stable platelet adhesion. Integrating 50 μm CTF microspots into a multishear microfluidic device yielded a high content assay from which we extracted platelet accumulation metrics (lag time, growth rate, total accumulation) on the spots using Hoffman modulation contrast microscopy. This method has potential broad application in identifying platelet function defects and screening, monitoring, and dosing antiplatelet agents. PMID:23001359

  20. Surface functionalization of solid state ultra-high molecular weight polyethylene through chemical grafting

    NASA Astrophysics Data System (ADS)

    Sherazi, Tauqir A.; Rehman, Tayyiba; Naqvi, Syed Ali Raza; Shaikh, Ahson Jabbar; Shahzad, Sohail Anjum; Abbas, Ghazanfar; Raza, Rizwan; Waseem, Amir

    2015-12-01

    The surface of ultra-high molecular weight polyethylene (UHMWPE) powder was functionalized with styrene using chemical grafting technique. The grafting process was initiated through radical generation on base polymer matrix in the solid state by sodium thiosulfate, while peroxides formed at radical sites during this process were dissociated by ceric ammonium nitrate. Various factors were optimized and reasonably high level of monomer grafting was achieved, i.e., 15.6%. The effect of different acids as additive and divinyl benzene (DVB) as a cross-linking agent was also studied. Post-grafting sulfonation was conducted to introduce the ionic moieties to the grafted polymer. Ion-exchange capacity (IEC) was measured experimentally and is found to be 1.04 meq g-1, which is in close agreement with the theoretical IEC values. The chemical structure of grafted and functionalized polymer was characterized by attenuated total reflection infrared spectroscopy (ATR-FTIR) and thermal properties were investigated by thermo gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Thermal analysis depicts that the presence of radicals on the polymer chain accelerates the thermal decomposition process. The results signify that the chemical grafting is an effective tool for substantial surface modification and subsequent functionalization of polyethylene.

  1. Low-rank separated representation surrogates of high-dimensional stochastic functions: Application in Bayesian inference

    SciTech Connect

    Validi, AbdoulAhad

    2014-03-01

    This study introduces a non-intrusive approach in the context of low-rank separated representation to construct a surrogate of high-dimensional stochastic functions, e.g., PDEs/ODEs, in order to decrease the computational cost of Markov Chain Monte Carlo simulations in Bayesian inference. The surrogate model is constructed via a regularized alternative least-square regression with Tikhonov regularization using a roughening matrix computing the gradient of the solution, in conjunction with a perturbation-based error indicator to detect optimal model complexities. The model approximates a vector of a continuous solution at discrete values of a physical variable. The required number of random realizations to achieve a successful approximation linearly depends on the function dimensionality. The computational cost of the model construction is quadratic in the number of random inputs, which potentially tackles the curse of dimensionality in high-dimensional stochastic functions. Furthermore, this vector-valued separated representation-based model, in comparison to the available scalar-valued case, leads to a significant reduction in the cost of approximation by an order of magnitude equal to the vector size. The performance of the method is studied through its application to three numerical examples including a 41-dimensional elliptic PDE and a 21-dimensional cavity flow.

  2. Analysis of the Radiative Transfer Equation with Highly Asymmetric Phase Function

    NASA Technical Reports Server (NTRS)

    Korkin, Sergey V.; Lyapustin, Alexei I.; Rozanov, Vladimir V.

    2011-01-01

    This paper considers a scalar radiative transfer problem with high scattering anisotropy, Two computational methods are presented based on decomposition of the diffuse light field into a regular and anisotropic part. The first algorithm (DOMAS) singles out the anisotropic radiance in the forward scattering peak using the Small-Angle Modification of RTE. The second algorithm (DOM2+) separates the single scattering radiance as an anisotropic part, which largely defines the fine detail of the total radiance in the backscattering directions. In both cases, the anisotropic part is represented analytically. With anisotropy subtraction, the regular part of the signal. which requires a numerical solution, is essentially smoothed as a function of angles. Further, the transport equation is obtained for the regular part that contains an additional source function from the anisotropic part of the signal. This equation is solved with the discrete ordinates method. A conducted numerical analysis of this work showed that algorithm DOMAS has a strong advantage as compared to the standard discrete ordinates method for simulation of the radiance transmission, and DOM2 + is the best of the three for the reflection computations. Both algorithms offer at least a factor of three acceleration of convergence of the azimuthal series for highly anisotropic phase functions.

  3. Multidentate polymeric ligands for long-term bioimaging using highly stable and functionalized quantum dots

    NASA Astrophysics Data System (ADS)

    Giovanelli, Emerson; Muro, Eleonora; Tasso, Mariana; Sitbon, Gary; Hanafi, Mohamed; Pons, Thomas; Dubertret, Benoît.; Lequeux, Nicolas

    2014-03-01

    Colloidal fluorescent semiconductor nanocrystals, named "quantum dots", possess unique features, such as a tunable peak wavelength (according to their composition and their size) or a large absorption cross-section, that make them very attractive for biomedical imaging. Nevertheless, typical syntheses provide nanoparticles capped with hydrophobic ligands. To be used in long-term bioexperiments, they have thus to be modified to exhibit essentially a high colloidal stability in aqueous conditions, but also a low non-specific adsorption, a small size and functionalization moities. As all of these properties are controlled by the layer of coating ligands, we designed a bidentate monozwitterionic ligand, to first address the need of small-sized and antibiofouling hydrophilic probes. But the corresponding quantum dots revealed to be unstable in highly diluted conditions and difficult to functionalize. To further increase the affinity between the nanoparticles and their surrounding ligands, we synthesized a multidentate polyzwitterionic ligand, issued from the copolymerization of a bidentate monomer and a monozwitterionic one. The nanocrystals passivated by this polymeric ligand showed an exceptional colloidal stability, regardless of the medium conditions (pH, salinity, dilution, and biological environment), and we demonstrated the affinity of the polymer exceeded by three orders of magnitude that of the bidentate ligand. The synthesis of the multidentate polyzwitterionic ligand proved also to be easily tunable and allowed the facile introduction of reacting moieties. Further functionalization of the corresponding quantum dots with biomolecules led to successful specific targeting, which could be confirmed, as an example, through FRET experiments.

  4. Development of combustion response functions in a subscale high-pressure transverse combustor

    NASA Astrophysics Data System (ADS)

    Wierman, M.; Pomeroy, B.; Anderson, W.

    2016-07-01

    Combustion response functions describe the magnitude and time lag behavior of a flame in response to unsteady pressure and velocity. By understanding the feedback between unsteady flowfields and heat release, the growth and decay of combustion instability can be better predicted. An automated data isolation and reduction method has been developed to generate meaningful graphical combustion response functions from a combination of pressure amplitude and various image analysis metrics. It was developed and tested using pressure measurements and high-speed imaging of combustion light taken from a single element at the midspan of an unstable high-pressure subscale transverse combustor. The code was used to isolate time slices of near stationary pressure amplitude and to process the corresponding images into combustion response approximated by aggregate intensity, intensity weighted spatial center, Proper Orthogonal Decomposition (POD), and Dynamic Mode Decomposition (DMD). Overall, the generated combustion response functions generally agreed with expected behavior of an element located at a first width (1W) velocity antinode and second width (2W) pressure antinode. Results from both POD and DMD successfully isolated the prominent spatial and temporal light emission behavior.

  5. High content evaluation of shear dependent platelet function in a microfluidic flow assay.

    PubMed

    Hansen, Ryan R; Wufsus, Adam R; Barton, Steven T; Onasoga, Abimbola A; Johnson-Paben, Rebecca M; Neeves, Keith B

    2013-02-01

    The high blood volume requirements and low throughput of conventional flow assays for measuring platelet function are unsuitable for drug screening and clinical applications. In this study, we describe a microfluidic flow assay that uses 50 μL of whole blood to measure platelet function on ~300 micropatterned spots of collagen over a range of physiologic shear rates (50-920 s(-1)). Patterning of collagen thin films (CTF) was achieved using a novel hydrated microcontact stamping method. CTF spots of 20, 50, and 100 μm were defined on glass substrates and consisted of a dense mat of nanoscale collagen fibers (3.74 ± 0.75 nm). We found that a spot size of greater than 20 μm was necessary to support platelet adhesion under flow, suggesting a threshold injury size is necessary for stable platelet adhesion. Integrating 50 μm CTF microspots into a multishear microfluidic device yielded a high content assay from which we extracted platelet accumulation metrics (lag time, growth rate, total accumulation) on the spots using Hoffman modulation contrast microscopy. This method has potential broad application in identifying platelet function defects and screening, monitoring, and dosing antiplatelet agents.

  6. High throughput functional genomics: identification of novel genes with tumor suppressor phenotypes.

    PubMed

    Koenig-Hoffmann, Kerstin; Bonin-Debs, Angelika L; Boche, Irene; Gawin, Beate; Gnirke, Andrea; Hergersberg, Christoph; Madeo, Frank; Kazinski, Michael; Klein, Matthias; Korherr, Christian; Link, Dieter; Röhrig, Sascha; Schäfer, Rolf; Brinkmann, Ulrich

    2005-01-20

    We have used a combination of high throughput functional genomics, computerized database mining and expression analyses to discover novel human tumor suppressor genes (TSGs). A genome-wide high throughput cDNA phenotype screen was established to identify genes that induce apoptosis or reduce cell viability. TSGs are expressed in normal tissue and frequently act by reduction of growth of transformed cells or induce apoptosis. In agreement with that and thus serving as platform validation, our pro-apoptotic hits included genes for which tumor suppressing activities were known, such as kangai1 and CD81 antigen. Additional genes that so far have been claimed as putative TSGs or associated with tumor inhibitory activities (prostate differentiation factor, hRAS-like suppressor 3, DPH2L1-like and the metastasis inhibitor Kiss1) were confirmed in their proposed TSG-like phenotype by functionally defining their growth inhibitory or pro-apoptotic function towards cancer cells. Finally, novel genes were identified for which neither association with cell growth nor with apoptosis were previously described. A subset of these genes show characteristics of TSGs because they (i) reduce the growth or induce apoptosis in tumor cells; (ii) show reduced expression in tumor vs. normal tissue; and (iii) are located on chromosomal (LOH-) loci for which cancer-associated deletions are described. The pro-apoptotic phenotype and differential expression of these genes in normal and malignant tissue make them promising target candidates for the diagnosis and therapy of various tumors.

  7. High-throughput monitoring of major cell functions by means of lensfree video microscopy

    NASA Astrophysics Data System (ADS)

    Kesavan, S. Vinjimore; Momey, F.; Cioni, O.; David-Watine, B.; Dubrulle, N.; Shorte, S.; Sulpice, E.; Freida, D.; Chalmond, B.; Dinten, J. M.; Gidrol, X.; Allier, C.

    2014-08-01

    Quantification of basic cell functions is a preliminary step to understand complex cellular mechanisms, for e.g., to test compatibility of biomaterials, to assess the effectiveness of drugs and siRNAs, and to control cell behavior. However, commonly used quantification methods are label-dependent, and end-point assays. As an alternative, using our lensfree video microscopy platform to perform high-throughput real-time monitoring of cell culture, we introduce specifically devised metrics that are capable of non-invasive quantification of cell functions such as cell-substrate adhesion, cell spreading, cell division, cell division orientation and cell death. Unlike existing methods, our platform and associated metrics embrace entire population of thousands of cells whilst monitoring the fate of every single cell within the population. This results in a high content description of cell functions that typically contains 25,000 - 900,000 measurements per experiment depending on cell density and period of observation. As proof of concept, we monitored cell-substrate adhesion and spreading kinetics of human Mesenchymal Stem Cells (hMSCs) and primary human fibroblasts, we determined the cell division orientation of hMSCs, and we observed the effect of transfection of siCellDeath (siRNA known to induce cell death) on hMSCs and human Osteo Sarcoma (U2OS) Cells.

  8. High-density EEG coherence analysis using functional units applied to mental fatigue.

    PubMed

    Ten Caat, Michael; Lorist, Monicque M; Bezdan, Eniko; Roerdink, Jos B T M; Maurits, Natasha M

    2008-06-30

    Electroencephalography (EEG) coherence provides a quantitative measure of functional brain connectivity which is calculated between pairs of signals as a function of frequency. Without hypotheses, traditional coherence analysis would be cumbersome for high-density EEG which employs a large number of electrodes. One problem is to find the most relevant regions and coherences between those regions in individuals and groups. Therefore, we previously developed a data-driven approach for individual as well as group analyses of high-density EEG coherence. Its data-driven regions of interest (ROIs) are referred to as functional units (FUs) and are defined as spatially connected sets of electrodes that record pairwise significantly coherent signals. Here, we apply our data-driven approach to a case study of mental fatigue. We show that our approach overcomes the severe limitations of conventional hypothesis-driven methods which depend on previous investigations and leads to a selection of coherences of interest taking full advantage of the recordings under investigation. The presented visualization of (group) FU maps provides a very economical data summary of extensive experimental results, which otherwise would be very difficult and time-consuming to assess. Our approach leads to an FU selection which may serve as a basis for subsequent conventional quantitative analysis; thus it complements rather than replaces the hypothesis-driven approach.

  9. Validation of GAITRite and PROMIS as High-Throughput Physical Function Outcome Measures Following ACL Reconstruction

    PubMed Central

    Papuga, M. Owen; Beck, Christopher A.; Kates, Stephen L.; Schwarz, Edward M.; Maloney, Michael D.

    2014-01-01

    New healthcare demands for quality measures of elective procedures, such as anterior cruciate ligament (ACL) reconstructive surgery, warrant the establishment of high through-put outcomes for high volume clinics. To this end we evaluated the PROMIS and GAITRite as physical function outcome measures to quantify early healing and post-operative complications in 106 patients at pre-op and 3, 10, 20 and 52 weeks post-ACL reconstruction with bone-tendon-bone autograft, and compared the results to the current IKDC validated outcome measure. The results showed that both PROMIS and GAITRite were significantly quicker to administer versus IKDC (p < 0.0001). Additional advantages were that PROMIS and GAITRite detected a significant decrease in physical function at 3 weeks post-op, and a significant improvement at 10 weeks post-op, versus pre-op (p<0.001), which were not detected with IKDC. GAITRite was limited by a low ceiling that could not detect improvement of physical function beyond 20 weeks, while both PROMIS and IKDC detected significant improvement out to 52 weeks postop (p<0.001). Linear regressions demonstrated a significant relationship between IKDC and PROMIS, with a combined correlation value of 0.8954 (p<.001) for all time points. Finally, ROC curve analysis demonstrated that PROMIS is a diagnostic test for poor outcomes. PMID:24532421

  10. A novel high yield method for dry functionalization of carbon nanotubes.

    PubMed

    Ansari, S G

    2011-04-01

    A novel and high yield (> 80%) dry method to functionalize (dry functionalization) carbon nanotubes (CNTs) using hydrothermal method, is reported here. The hydrothermal solution was prepared with HNO3, H2SO4 and H2O2 (1:3:2 vol. ratios) and reaction was carried out from 120 to 200 degrees C for 24 h. CNTs (multi wall) were kept in a way to avoid the direct contact with the solution. Treatment above 180 degrees C resulted in better functionalization of nanotubes as observed from Fourier transform infrared absorption spectroscopic (FTIR) measurements. Field emission scanning electron microscopic (FESEM) images showed that after functionalization, the nanotubes are seen with open ends, granular surface, twisted and are joined together. These clearly indicate the destruction of the graphite structure on the surface. This indicates that after treatment, CNTs reactivity has increased at the ends as well as at the side walls. X-ray Photoelectron Spectroscopic (XPS) studies show a shift in the C 1s peak position, increase in O 1s peak intensity and appearance of an N 1s peak. PMID:21776687

  11. Association between Exposure to Electromagnetic Fields from High Voltage Transmission Lines and Neurobehavioral Function in Children

    PubMed Central

    Huang, Jiongli; Tang, Tiantong; Hu, Guocheng; Zheng, Jing; Wang, Yuyu; Wang, Qiang; Su, Jing; Zou, Yunfeng; Peng, Xiaowu

    2013-01-01

    Background Evidence for a possible causal relationship between exposure to electromagnetic fields (EMF) emitted by high voltage transmission (HVT) lines and neurobehavioral dysfunction in children is insufficient. The present study aims to investigate the association between EMF exposure from HVT lines and neurobehavioral function in children. Methods Two primary schools were chosen based on monitoring data of ambient electromagnetic radiation. A cross-sectional study with 437 children (9 to 13 years old) was conducted. Exposure to EMF from HVT lines was monitored at each school. Information was collected on possible confounders and relevant exposure predictors using standardized questionnaires. Neurobehavioral function in children was evaluated using established computerized neurobehavioral tests. Data was analyzed using multivariable regression models adjusted for relevant confounders. Results After controlling for potential confounding factors, multivariable regression revealed that children attending a school near 500 kV HVT lines had poorer performance on the computerized neurobehavioral tests for Visual Retention and Pursuit Aiming compared to children attending a school that was not in close proximity to HVT lines. Conclusions The results suggest long-term low-level exposure to EMF from HVT lines might have a negative impact on neurobehavioral function in children. However, because of differences in results only for two of four tests achieved statistical significance and potential limitations, more studies are needed to explore the effects of exposure to extremely low frequency EMF on neurobehavioral function and development in children. PMID:23843999

  12. Change in Neuropsychological Functioning over One Year in Youth at Clinical High Risk for Psychosis

    PubMed Central

    Woodberry, Kristen A.; McFarlane, William R.; Giuliano, Anthony J.; Verdi, Mary B.; Cook, William L.; Faraone, Stephen V.; Seidman, Larry J.

    2013-01-01

    Schizophrenia and related psychotic disorders are associated with significant neuropsychological (NP) impairments. Yet the onset and developmental evolution of these impairments remains incompletely characterized. This study examined NP functioning over one year in a sample of youth at clinical high risk (CHR) for psychosis participating in a treatment study. We assessed functioning across six cognitive domains at two time points in a sample of 53 CHR and 32 healthy comparison (HC) subjects. Linear regression of HC one-year scores was used to predict one-year performance for CHR from baseline scores and relevant demographic variables. We used raw scores and MANOVAs of the standardized residuals to test for progressive impairment over time. NP functioning of CHR at one year fell significantly below predicted levels. Effects were largest and most consistent for a failure of normative improvement on tests of executive function. CHR who reached the highest positive symptom rating (6, severe and psychotic) on the Structured Interview of Prodromal Syndromes after the baseline assessment (n = 10/53) demonstrated a particularly large (d= −1.89), although non-significant, discrepancy between observed and predicted one-year verbal memory test performance. Findings suggest that, although much of the cognitive impairment associated with psychosis is present prior to the full expression of the psychotic syndrome, some progressive NP impairments may accompany risk for psychosis and be greatest for those who develop psychotic level symptoms. PMID:23434505

  13. REVIEW: High pressure NMR study of proteins - seeking roots for function, evolution, disease and food applications

    NASA Astrophysics Data System (ADS)

    Akasaka, Kazuyuki

    2010-12-01

    NMR experiments at variable pressure reveal a wide range of conformation of a globular protein spanning from within the folded ensemble to the fully unfolded ensemble, herewith collectively called "high-energy conformers". The observation of "high-energy conformers" in a wide variety of globular proteins has led to the "volume theorem": the partial molar volume of a protein decreases with the decrease in its conformational order. Since "high-energy conformers" are intrinsically more reactive than the basic folded conformer, they could play decisive roles in all phenomena of proteins, namely function, environmental adaptation and misfolding. Based on the information on high-energy conformers and the rules on their partial volume in its monomeric state and amyloidosis, one may have a general view on what is happening on proteins under pressure. Moreover, one may even choose a high-energy conformer of a protein with pressure as variable for a particular purpose. Bridging "high-energy conformers" to macroscopic pressure effects could be a key to success in pressure application to biology, medicine, food technology and industry in the near future.

  14. Adsorption of Ruthenium, Rhodium and Palladium from Simulated High-Level Liquid Waste by Highly Functional Xerogel - 13286

    SciTech Connect

    Onishi, Takashi; Koyama, Shin-ichi; Mimura, Hitoshi

    2013-07-01

    Fission products are generated by fission reactions in nuclear fuel. Platinum group (Pt-G) elements, such as palladium (Pd), rhodium (Rh) and ruthenium (Ru), are also produced. Generally, Pt-G elements play important roles in chemical and electrical industries. Highly functional xerogels have been developed for recovery of these useful Pt-G elements from high - level radioactive liquid waste (HLLW). An adsorption experiment from simulated HLLW was done by the column method to study the selective adsorption of Pt-G elements, and it was found that not only Pd, Rh and Ru, but also nickel, zirconium and tellurium were adsorbed. All other elements were not adsorbed. Adsorbed Pd was recovered by washing the xerogel-packed column with thiourea solution and thiourea - nitric acid mixed solution in an elution experiment. Thiourea can be a poison for automotive exhaust emission system catalysts, so it is necessary to consider its removal. Thermal decomposition and an acid digestion treatment were conducted to remove sulfur in the recovered Pd fraction. The relative content of sulfur to Pd was decreased from 858 to 0.02 after the treatment. These results will contribute to design of the Pt-G element separation system. (authors)

  15. High-Resolution Rotational Spectrum, Dunham Coefficients, and Potential Energy Function of NaCl

    PubMed Central

    Cabezas, C.; Cernicharo, J.; Quintana-Lacaci, G.; Peña, I.; Agundez, M.; Prieto, L. Velilla; Castro-Carrizo, A.; Zuñiga, J.; Bastida, A.; Alonso, J. L.; Requena, A.

    2016-01-01

    We report laboratory spectroscopy for the first time of the J = 1–0 and J = 2–1 lines of Na35Cl and Na37Cl in several vibrational states. The hyperfine structure has been resolved in both transitions for all vibrational levels, which permit us to predict with high accuracy the hyperfine splitting of the rotational transitions of the two isotopologues at higher frequencies. The new data have been merged with all previous works at microwave, millimeter, and infrared wavelengths and fitted to a series of mass-independent Dunham parameters and to a potential energy function. The obtained parameters have been used to compute a new dipole moment function, from which the dipole moment for infrared transitions up to Δv = 8 has been derived. Frequency and intensity predictions are provided for all rovibrational transitions up to J = 150 and v = 8, from which the ALMA data of evolved stars can be modeled and interpreted. PMID:27733778

  16. Highly functionalized tetrahydropyridines are cytotoxic and selective inhibitors of human puromycin sensitive aminopeptidase.

    PubMed

    Aeluri, Raghunath; Ganji, Roopa Jones; Marapaka, Anil Kumar; Pillalamarri, Vijaykumar; Alla, Manjula; Addlagatta, Anthony

    2015-12-01

    Efficient one-pot five-component synthetic protocols for highly functionalized tetrahydropyridines (THPs) and their biological evaluation have been illustrated. Synthesis of novel functionalized tetrahydropyridines containing differential substitutions at 2,6-positions has been achieved via a modified MCR. Cytotoxic studies of 23 synthesized compounds have been carried out against three different cell lines, namely A-549, HeLa and HepG2, wherein some compounds have displayed appreciable cytotoxicity. Further, investigation of enzyme inhibition by the synthesized THPs has been carried out against four members of M1 family aminopeptidases. Several compounds have selectively inhibited only one member of this enzyme family i.e., human puromycin sensitive aminopeptidase (hPSA). Among the compounds; 4b, 9b, 9e and 10a demonstrated best inhibition against hPSA.

  17. High-Intensity Ultrasound to Improve Physical and Functional Properties of Lipids.

    PubMed

    Wagh, Ashwini; Birkin, Peter; Martini, Silvana

    2016-01-01

    High-intensity ultrasound (HIU) has been used in recent years to change the crystallization behavior of edible lipids. This technique can be used in combination with other processing technologies to tailor lipids' functional properties and broaden their application for various food products. In general, sonication induces crystallization, increases crystallization rate, and generates a harder and more elastic crystalline network characterized by smaller crystals with a sharper melting profile. An important application of HIU is to improve the hardness and elasticity of shortenings that have a low content of saturated fatty acids and are free of trans-fats. This review summarizes recent research that used HIU to change the physical and functional properties of edible lipids and focuses on the importance of controlling processing variables such as sonication power level and duration and crystallization temperature.

  18. Performance of High School Adolescents on Functional Gait and Balance Measures

    PubMed Central

    Alsalaheen, Bara A.; Whitney, Susan L.; Marchetti, Gregory F.; Furman, Joseph M.; Kontos, Anthony P.; Collins, Michael W.; Sparto, Patrick J.

    2014-01-01

    Purpose To describe the performance of high school adolescents during common functional gait and balance measures used in vestibular physical therapy. Methods A cross-sectional study of 91 participants determined their performance on the Activities - specific Balance Confidence (ABC) scale, Dynamic Gait Index (DGI), Functional Gait Assessment (FGA), Timed “Up & Go” (TUG), Five Times Sit to Stand (FTSTS) test, tests of gait speed (GS) and the Balance Error Scoring System. In a subset of this sample, GS, TUG, and the FTSTS were repeated twice to examine test-retest reliability. Results The measures of GS, TUG, and FTSTS were normally distributed. The ABC, DGI, and FGA exhibited a ceiling effect. The timed measures exhibited moderate to good reliability. Conclusions These performance scores may provide end points for discharge from vestibular physical therapy. However, clinicians should be aware of the ceiling effect exhibited by some measures. PMID:24675118

  19. Chlorinated Indium Tin Oxide Electrodes with High Work Function for Organic Device Compatibility

    NASA Astrophysics Data System (ADS)

    Helander, M. G.; Wang, Z. B.; Qiu, J.; Greiner, M. T.; Puzzo, D. P.; Liu, Z. W.; Lu, Z. H.

    2011-05-01

    In organic light-emitting diodes (OLEDs), a stack of multiple organic layers facilitates charge flow from the low work function [~4.7 electron volts (eV)] of the transparent electrode (tin-doped indium oxide, ITO) to the deep energy levels (~6 eV) of the active light-emitting organic materials. We demonstrate a chlorinated ITO transparent electrode with a work function of >6.1 eV that provides a direct match to the energy levels of the active light-emitting materials in state-of-the art OLEDs. A highly simplified green OLED with a maximum external quantum efficiency (EQE) of 54% and power efficiency of 230 lumens per watt using outcoupling enhancement was demonstrated, as were EQE of 50% and power efficiency of 110 lumens per watt at 10,000 candelas per square meter.

  20. Functionalized graphene for high-performance two-dimensional spintronics devices.

    PubMed

    Li, Linze; Qin, Rui; Li, Hong; Yu, Lili; Liu, Qihang; Luo, Guangfu; Gao, Zhengxiang; Lu, Jing

    2011-04-26

    Using first-principles calculations, we explore the possibility of functionalized graphene as a high-performance two-dimensional spintronics device. Graphene functionalized with O on one side and H on the other side in the chair conformation is found to be a ferromagnetic metal with a spin-filter efficiency up to 54% at finite bias. The ground state of graphene semifunctionalized with F in the chair conformation is an antiferromagnetic semiconductor, and we construct a spin-valve device from it by introducing a magnetic field to stabilize its metallic ferromagnetic state. The resulting room-temperature magnetoresistance is up to 2200%, which is 1 order of magnitude larger than the available experimental values.