Characterization of a Proteasome and TAP-independent Presentation of Intracellular Epitopes by HLA-B27 Molecules*

PubMed Central

Magnacca, Adriana; Persiconi, Irene; Nurzia, Elisa; Caristi, Silvana; Meloni, Francesca; Barnaba, Vincenzo; Paladini, Fabiana; Raimondo, Domenico; Fiorillo, Maria Teresa; Sorrentino, Rosa

2012-01-01

Nascent HLA-class I molecules are stabilized by proteasome-derived peptides in the ER and the new complexes proceed to the cell surface through the post-ER vesicles. It has been shown, however, that less stable complexes can exchange peptides in the Trans Golgi Network (TGN). HLA-B27 are the most studied HLA-class I molecules due to their association with Ankylosing Spondylitis (AS). Chimeric proteins driven by TAT of HIV have been exploited by us to deliver viral epitopes, whose cross-presentation by the HLA-B27 molecules was proteasome and TAP-independent and not restricted to Antigen-Presenting Cells (APC). Here, using these chimeric proteins as epitope suppliers, we compared with each other and with the HLA-A2 molecules, the two HLA-B*2705 and B*2709 alleles differing at residue 116 (D116H) and differentially associated with AS. We found that the antigen presentation by the two HLA-B27 molecules was proteasome-, TAP-, and APC-independent whereas the presentation by the HLA-A2 molecules required proteasome, TAP and professional APC. Assuming that such difference could be due to the unpaired, highly reactive Cys-67 distinguishing the HLA-B27 molecules, C67S mutants in HLA-B*2705 and B*2709 and V67C mutant in HLA-A*0201 were also analyzed. The results showed that this mutation did not influence the HLA-A2-restricted antigen presentation while it drastically affected the HLA-B27-restricted presentation with, however, remarkable differences between B*2705 and B*2709. The data, together with the occurrence on the cell surface of unfolded molecules in the case of C67S-B*2705 mutant but not in that of C67S-B*2709 mutant, indicates that Cys-67 has a more critical role in stabilizing the B*2705 rather than the B*2709 complexes. PMID:22807446

A case-control study on association of proteasome subunit beta 8 (PSMB8) and transporter associated with antigen processing 1 (TAP1) polymorphisms and their transcript levels in vitiligo from Gujarat.

PubMed

Jadeja, Shahnawaz D; Mansuri, Mohmmad Shoab; Singh, Mala; Dwivedi, Mitesh; Laddha, Naresh C; Begum, Rasheedunnisa

2017-01-01

Autoimmunity has been implicated in the destruction of melanocytes from vitiligo skin. Major histocompatibility complex (MHC) class-II linked genes proteasome subunit beta 8 (PSMB8) and transporter associated with antigen processing 1 (TAP1), involved in antigen processing and presentation have been reported to be associated with several autoimmune diseases including vitiligo. To explore PSMB8 rs2071464 and TAP1 rs1135216 single nucleotide polymorphisms and to estimate the expression of PSMB8 and TAP1 in patients with vitiligo and unaffected controls from Gujarat. PSMB8 rs2071464 polymorphism was genotyped using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) and TAP1 rs1135216 polymorphism was genotyped by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in 378 patients with vitiligo and 509 controls. Transcript levels of PSMB8 and TAP1 were measured in the PBMCs of 91 patients and 96 controls by using qPCR. Protein levels of PSMB8 were also determined by Western blot analysis. The frequency of 'TT' genotype of PSMB8 polymorphism was significantly lowered in patients with generalized and active vitiligo (p = 0.019 and p = 0.005) as compared to controls suggesting its association with the activity of the disease. However, TAP1 polymorphism was not associated with vitiligo susceptibility. A significant decrease in expression of PSMB8 at both transcript level (p = 0.002) as well as protein level (p = 0.0460) was observed in vitiligo patients as compared to controls. No significant difference was observed between patients and controls for TAP1 transcripts (p = 0.553). Interestingly, individuals with the susceptible CC genotype of PSMB8 polymorphism showed significantly reduced PSMB8 transcript level as compared to that of CT and TT genotypes (p = 0.009 and p = 0.003 respectively). PSMB8 rs2071464 was associated with generalized and active vitiligo from Gujarat whereas TAP1 rs1135216 showed no association. The down-regulation of PSMB8 in patients with risk genotype 'CC' advocates the vital role of PSMB8 in the autoimmune basis of vitiligo.

What chickens would tell you about the evolution of antigen processing and presentation.

PubMed

Kaufman, Jim

2015-06-01

Outside of mammals, antigen processing and presentation have only been investigated in chickens. The chicken MHC is organized differently than mammals, allowing the co-evolution of polymorphic genes, with each MHC haplotype having a set of TAP1, TAP2 and tapasin alleles directed to high expression of a single classical class I molecule. However, the class I alleles vary in the size of peptide-binding repertoire, along with a suite of other properties. The salient features of the chicken MHC are found in many non-mammalian vertebrates, and are likely to have been set at the origin of the adaptive immune system of jawed vertebrates, with unrelated genes co-evolving to set up the original pathways. Half a billion years later, various features of presentation and resistance to disease still reflect this ancestral arrangement. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization of extrathymic CD8αβ T cells in the liver and intestine in TAP-1 deficient mice

PubMed Central

Tsukada, Chika; Miyaji, Chikako; Kawamura, Hiroki; Miyakawa, Ryoko; Yokoyama, Hisashi; Ishimoto, Yuiko; Miyazawa, Shinobu; Watanabe, Hisami; Abo, Toru

2003-01-01

TAP-1 deficient (−/−) mice cannot transport MHC class I antigens onto the cell surface, which results in failure of the generation of CD8+ T cells in the thymus. In a series of recent studies, it has been proposed that extrathymic T cells are generated in the liver and at other extrathymic sites (e.g. the intestine). It was therefore investigated whether CD8+ extrathymic T cells require an interaction with MHC class I antigens for their differentiation in TAP-1(−/−) mice. Although CD8+ thymically derived T cells were confirmed to be absent in the spleen as well as in the thymus, CD8αβ+ T cells were abundant in the livers and intestines of TAP-1(−/−) mice. These CD8+ T cells expanded in the liver as a function of age and were mainly confined to a NK1·1−CD3int population which is known to be truly of extrathymic origin. Hepatic lymphocytes, which contained CD8+ T cells and which were isolated from TAP-1(−/−) mice (H-2b), responded to neither mutated MHC class I antigens (bm1) nor allogeneic MHC class I antigens (H-2d) in in vitro mixed lymphocyte cultures. However, the results from repeated in vivo stimulations with alloantigens (H-2d) were interesting. Allogeneic cytotoxicity was induced in liver lymphocytes in TAP-1(−/−) mice, although the magnitude of cytotoxicity was lower than that of liver lymphocytes in immunized B6 mice. All allogeneic cytotoxicity disappeared with the elimination of CD8+ cells in TAP-1(−/−) mice. These results suggest that the generation and function of CD8+ extrathymic T cells are independent of the existence of the MHC class I antigens of the mouse but have a limited allorecognition ability. PMID:12807479

Altered Expression of TAP-1 and Major Histocompatibility Complex Class I in Laryngeal Papillomatosis: Correlation of TAP-1 with Disease

PubMed Central

Vambutas, Andrea; Bonagura, Vincent R.; Steinberg, Bettie M.

2000-01-01

Recurrent respiratory papillomatosis (RRP) is an insidious disease caused by human papillomavirus (HPV) infection. It is characterized by a variable clinical course that can include frequent disease recurrence, significant morbidity, and occasional mortality. The mechanisms responsible for the variability in the clinical course and the persistence of latent HPV infection remain unknown. Effective T-cell-mediated clearance of HPV-infected cells may be defective in patients with RRP, leading to recurrent disease and failure to suppress latent HPV reactivation. This study describes the down-regulation of the transporter associated with antigen presentation (TAP-1) and the major histocompatibility complex (MHC) class I protein expression in laryngeal papilloma tissue biopsies and cell culture of primary explants. There was a statistically significant correlation between reduction of TAP-1 expression in biopsy tissues and rapid recurrence of disease. Patients with RRP had less frequent recurrence if their papillomas expressed TAP-1 at levels close to that of normal tissue, compared with those with very low expression of TAP-1, who had frequent recurrence (32 versus 5 weeks to the next surgical intervention). These findings suggest that HPV may evade immune recognition by down-regulating class I MHC cell surface expression via decreased TAP-1 levels. Expression of TAP-1 could be used for prognostic evaluation of disease severity. Gamma interferon was able to restore class I MHC expression at the surfaces of laryngeal papilloma cells in culture. This up-regulation of class I MHC antigen at the cell surface potentially allows the infected cell to become a target for the immune system again. This finding provides some promise for nonsurgical treatment of laryngeal papillomas. PMID:10618282

A case-control study on association of proteasome subunit beta 8 (PSMB8) and transporter associated with antigen processing 1 (TAP1) polymorphisms and their transcript levels in vitiligo from Gujarat

PubMed Central

Jadeja, Shahnawaz D.; Mansuri, Mohmmad Shoab; Singh, Mala; Dwivedi, Mitesh; Laddha, Naresh C.

2017-01-01

Background Autoimmunity has been implicated in the destruction of melanocytes from vitiligo skin. Major histocompatibility complex (MHC) class-II linked genes proteasome subunit beta 8 (PSMB8) and transporter associated with antigen processing 1 (TAP1), involved in antigen processing and presentation have been reported to be associated with several autoimmune diseases including vitiligo. Objectives To explore PSMB8 rs2071464 and TAP1 rs1135216 single nucleotide polymorphisms and to estimate the expression of PSMB8 and TAP1 in patients with vitiligo and unaffected controls from Gujarat. Methods PSMB8 rs2071464 polymorphism was genotyped using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) and TAP1 rs1135216 polymorphism was genotyped by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in 378 patients with vitiligo and 509 controls. Transcript levels of PSMB8 and TAP1 were measured in the PBMCs of 91 patients and 96 controls by using qPCR. Protein levels of PSMB8 were also determined by Western blot analysis. Results The frequency of ‘TT’ genotype of PSMB8 polymorphism was significantly lowered in patients with generalized and active vitiligo (p = 0.019 and p = 0.005) as compared to controls suggesting its association with the activity of the disease. However, TAP1 polymorphism was not associated with vitiligo susceptibility. A significant decrease in expression of PSMB8 at both transcript level (p = 0.002) as well as protein level (p = 0.0460) was observed in vitiligo patients as compared to controls. No significant difference was observed between patients and controls for TAP1 transcripts (p = 0.553). Interestingly, individuals with the susceptible CC genotype of PSMB8 polymorphism showed significantly reduced PSMB8 transcript level as compared to that of CT and TT genotypes (p = 0.009 and p = 0.003 respectively). Conclusions PSMB8 rs2071464 was associated with generalized and active vitiligo from Gujarat whereas TAP1 rs1135216 showed no association. The down-regulation of PSMB8 in patients with risk genotype ‘CC’ advocates the vital role of PSMB8 in the autoimmune basis of vitiligo. PMID:28700671

Molecular mechanism and species specificity of TAP inhibition by herpes simplex virus ICP47.

PubMed Central

Ahn, K; Meyer, T H; Uebel, S; Sempé, P; Djaballah, H; Yang, Y; Peterson, P A; Früh, K; Tampé, R

1996-01-01

The immediate early protein ICP47 of herpes simplex virus (HSV) inhibits the transporter for antigen processing (TAP)-mediated translocation of antigen-derived peptides across the endoplasmic reticulum (ER) membrane. This interference prevents assembly of peptides with class I MHC molecules in the ER and ultimately recognition of HSV-infected cells by cytotoxic T-lymphocytes, potentially leading to immune evasion of the virus. Here, we demonstrate that recombinant, purified ICP47 containing a hexahistidine tag inhibits peptide import into microsomes of insect cells expressing human TAP, whereas inhibition of peptide transport by murine TAP was much less effective. This finding indicates an intrinsic species-specificity of ICP47 and suggests that no additional proteins interacting specifically with either ICP47 or TAP are required for inhibition of peptide transport. Since neither purified nor induced ICP47 inhibited photocrosslinking of 8-azido-ATP to TAP1 and TAP2 it seems that ICP47 does not prevent ATP from binding to TAP. By contrast, peptide binding was completely blocked by ICP47 as shown both by photoaffinity crosslinking of peptides to TAP and peptide binding to microsomes from TAP-transfected insect cells. Competition experiments indicated that ICP47 binds to human TAP with a higher affinity (50 nM) than peptides whereas the affinity to murine TAP was 100-fold lower. Our data suggest that ICP47 prevents peptides from being translocated by blocking their binding to the substrate-binding site of TAP. Images PMID:8670825

Human heat shock protein 70 enhances tumor antigen presentation through complex formation and intracellular antigen delivery without innate immune signaling.

PubMed

Bendz, Henriette; Ruhland, Sibylle C; Pandya, Maya J; Hainzl, Otmar; Riegelsberger, Stefan; Braüchle, Christoph; Mayer, Matthias P; Buchner, Johannes; Issels, Rolf D; Noessner, Elfriede

2007-10-26

Heat shock proteins (HSPs) have shown promise for the optimization of protein-based vaccines because they can transfer exogenous antigens to dendritic cells and at the same time induce their maturation. Great care must be exercised in interpretating HSP-driven studies, as by-products linked to the recombinant generation of these proteins have been shown to mediate immunological effects. We generated highly purified human recombinant Hsp70 and demonstrated that it strongly enhances the cross-presentation of exogenous antigens resulting in better antigen-specific T cell stimulation. Augmentation of T cell stimulation was a direct function of the degree of complex formation between Hsp70 and peptides and correlated with improved antigen delivery to endosomal compartments. The Hsp70 activity was independent of TAP proteins and was not inhibited by exotoxin A or endosomal acidification. Consequently, Hsp70 enhanced cross-presentation of various antigenic sequences, even when they required different post-uptake processing and trafficking, as exemplified by the tumor antigens tyrosinase and Melan-A/MART-1. Furthermore, Hsp70 enhanced cross-presentation by different antigen-presenting cells (APCs), including dendritic cells and B cells. Importantly, enhanced cross-presentation and antigen-specific T cell activation were observed in the absence of innate signals transmitted by Hsp70. As Hsp70 supports the cross-presentation of different antigens and APCs and is inert to APC function, it may show efficacy in various settings of immune modulation, including induction of antigen-specific immunity or tolerance.

Hypoxia and hypoxia-inducible factor (HIF) downregulate antigen-presenting MHC class I molecules limiting tumor cell recognition by T cells

PubMed Central

Nguyen, Thao; Hatfield, Stephen M.; Ohta, Akio; Sitkovsky, Michail V.

2017-01-01

Human cancers are known to downregulate Major Histocompatibility Complex (MHC) class I expression thereby escaping recognition and rejection by anti-tumor T cells. Here we report that oxygen tension in the tumor microenvironment (TME) serves as an extrinsic cue that regulates antigen presentation by MHC class I molecules. In support of this view, hypoxia is shown to negatively regulate MHC expression in a HIF-dependent manner as evidenced by (i) lower MHC expression in the hypoxic TME in vivo and in hypoxic 3-dimensional (3D) but not 2-dimensional (2D) tumor cell cultures in vitro; (ii) decreased MHC in human renal cell carcinomas with constitutive expression of HIF due to genetic loss of von Hippel-Lindau (VHL) function as compared with isogenically paired cells with restored VHL function, and iii) increased MHC in tumor cells with siRNA-mediated knockdown of HIF. In addition, hypoxia downregulated antigen presenting proteins like TAP 1/2 and LMP7 that are known to have a dominant role in surface display of peptide-MHC complexes. Corroborating oxygen-dependent regulation of MHC antigen presentation, hyperoxia (60% oxygen) transcriptionally upregulated MHC expression and increased levels of TAP2, LMP2 and 7. In conclusion, this study reveals a novel mechanism by which intra-tumoral hypoxia and HIF can potentiate immune escape. It also suggests the use of hyperoxia to improve tumor cell-based cancer vaccines and for mining novel immune epitopes. Furthermore, this study highlights the advantage of 3D cell cultures in reproducing hypoxia-dependent changes observed in the TME. PMID:29155844

Marker of cemento-periodontal ligament junction associated with periodontal regeneration.

PubMed

Hara, Ryohko; Wato, Masahiro; Tanaka, Akio

2005-06-01

The purpose of this study was to identify factors promoting formation of the cemento-periodontal ligament junction. Regeneration of the cemento-periodontal ligament junction is an important factor in recovery of the connective tissue attachment to the cementum and it is important to identify all specific substances that promote its formation. To clarify the substances involved in cemento-periodontal ligament junction formation, we produced a monoclonal antibody (mAb) to human cemento-periodontal ligament junction (designated as the anti-TAP mAb) and examined its immunostaining properties and reactive antigen. Hybridomas producing monoclonal antibody against human cemento-periodontal ligament junction antigens were established by fusing P3U1 mouse myeloma cells with spleen cells from BALB/c mice immunized with homogenized human cemento-periodontal ligament junction. The mAb, the anti-TAP mAb for cemento-periodontal ligament junction, was then isolated. The immunoglobulin class and light chain of the mAb were examined using an isotyping kit. Before immunostaining, antigen determination using an enzymatic method or heating was conducted. Human teeth, hard tissue-forming lesions, and animal tissues were immunostained by the anti-TAP mAb. The anti-TAP mAb was positive in human cemento-periodontal ligament junction and predentin but negative in all other human and animal tissues examined. In the cemento-osseous lesions, the anti-TAP mAb was positive in the peripheral area of the cementum and cementum-like hard tissues and not in the bone and bone-like tissues. The anti-TAP mAb showed IgM (kappa) and recognized phosphoprotein. The anti-TAP mAb is potentially useful for developing new agents promoting cementogenesis and periodontal regeneration.

A phase III, open-label, randomised multicentre study to evaluate the immunogenicity and safety of a booster dose of two different reduced antigen diphtheria-tetanus-acellular pertussis-polio vaccines, when co-administered with measles-mumps-rubella vaccine in 3 and 4-year-old healthy children in the UK.

PubMed

Marlow, Robin; Kuriyakose, Sherine; Mesaros, Narcisa; Han, Htay Htay; Tomlinson, Richard; Faust, Saul N; Snape, Matthew D; Pollard, Andrew J; Finn, Adam

2018-04-19

To evaluate the immunogenicity and safety of a reduced antigen diphtheria-tetanus-acellular pertussis-inactivated poliovirus (dTap-IPV B ) vaccine (Boostrix-IPV, GSK) as a pre-school booster in 3-4 year old children as compared to dTap-IPV R (Repevax, Sanofi Pasteur), when co-administered with mumps-measles-rubella vaccine (MMRV). This phase III, open label, randomised study was conducted in the UK between April 2011 and April 2012. Children due their pre-school dTap-IPV booster vaccination were randomised 2:1 to receive one of two different dTap-IPV vaccines (dTap-IPV B or dTap-IPV R ) with blood sample for immunogenicity assessment just prior and one month after vaccination. Immune responses to diphtheria, tetanus and polio antigens were compared between the study vaccines (inferential comparison). In the absence of an accepted pertussis correlate of protection, the immunogenicity of dTap-IPV B vaccine against pertussis was compared with historical pertussis efficacy data (inferential comparison). Safety and reactogenicity of both study vaccines were evaluated. 387 children were randomised and 385 vaccinated: 255 in the dTap-IPV B group and 130 in the dTap-IPV R group. Prior to vaccination, ≥76.8% of children had anti-diphtheria and ≥65.5% had anti-tetanus titres above the protection threshold; for pertussis, the pre-vaccination seropositivity rate ranged between 18.1 and 70.6%. Both vaccines were immunogenic with 99.2-100% of children achieving titres above the pre-specified seroprotection/seropositivity thresholds. One serious adverse event not considered as causally related to the study vaccination by the study investigator was reported in the dTap-IPV B group. Non-inferiority of dTap-IPV B to dTap-IPV R was demonstrated. Both vaccines had a clinically acceptable safety and reactogenicity profile when co-administered with MMRV to children 3-4 years old. NCT01245049 (ClinicalTrials.gov). Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

microRNA 125a Regulates MHC-I Expression on Esophageal Adenocarcinoma Cells, Associated With Suppression of Anti-tumor Immune Response and Poor Outcomes of Patients.

PubMed

Mari, Luigi; Hoefnagel, Sanne J M; Zito, Domenico; van de Meent, Marian; van Endert, Peter; Calpe, Silvia; Sancho Serra, Maria Del Carmen; Heemskerk, Mirjam H M; van Laarhoven, Hanneke W M; Hulshof, Maarten C C M; Gisbertz, Susanne S; Medema, Jan Paul; van Berge Henegouwen, Mark I; Meijer, Sybren L; Bergman, Jacques J G H M; Milano, Francesca; Krishnadath, Kausilia K

2018-06-07

Immune checkpoint inhibition may affect growth or progression of highly aggressive cancers, such as esophageal adenocarcinoma (EAC). We investigated the regulation of expression of major histocompatibility complex, class 1 (MHC-I) proteins (encoded by HLA-A, HLA-B, and HLA-C) and the immune response to EACs in patient samples. We performed quantitative PCR array analyses of OE33 cells and OE19 cells, which express different levels of the ATP binding cassette subfamily B member 1 (TAP1) and TAP2, required for antigen presentation by MHC-I, to identify microRNAs that regulate their expression. We performed luciferase assays to validate interactions between microRNAs and potential targets. We overexpressed candidate microRNAs in OE33, FLO-1, and OACP4 C cell lines and performed quantitative PCR, immunoblot, and flow cytometry analyses to identify changes in mRNA and protein expression; we studied the effects of cytotoxic T cells. We performed microRNA in situ hybridization, RNA-sequencing, and immunohistochemical analyses of tumor tissues from 51 untreated patients with EAC in the Netherlands. Clinical and survival data were collected for patients, and EACs subtypes were determined. We found OE19 cells to have increased levels of 7 microRNAs. Of these, we found binding sites for microRNA 125a (MIR125a)-5p in the 3'UTR of the TAP2 mRNA and binding sites for MIR148a-3p in 3'UTRs of HLA-A, HLA-B, and HLA-C mRNAs. Overexpression of these microRNAs reduced expression of TAP2 in OE33, FLO-1, and OACP4 C cells, and reduced cell-surface levels of MHC-I. OE33 cells that expressed the viral peptide BZLF1 were killed by cytotoxic T cells, whereas OE33 that overexpressed MIR125a-5p or MIR 148a along with BZLF1 were not. In EAC and non-tumor tissues, levels of MIR125a-5p correlated inversely with levels of TAP2 protein. High expression of TAP1 by EAC correlated with significantly shorter overall survival times of patients. EACs that expressed high levels of TAP1 and genes involved in antigen presentation also expressed high levels of genes that regulate the adaptive immune response, PD-L1, PD-L2, and IDO1; these EACs had a poor response to neo-adjuvant chemoradiotherapy and associated with shorter overall survival times of patients. In studies of EAC cell lines and tumor tissues, we found increased levels of MIR125a-5p and MIR148a-3p to reduce levels of TAP2 and MHC-I, required for antigen presentation. High expression of MHC-I molecules by EAC correlated with markers of an adaptive immune response and significantly shorter overall survival times of patients. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Molecular Pathways for Immune Recognition of Preproinsulin Signal Peptide in Type 1 Diabetes.

PubMed

Kronenberg-Versteeg, Deborah; Eichmann, Martin; Russell, Mark A; de Ru, Arnoud; Hehn, Beate; Yusuf, Norkhairin; van Veelen, Peter A; Richardson, Sarah J; Morgan, Noel G; Lemberg, Marius K; Peakman, Mark

2018-04-01

The signal peptide region of preproinsulin (PPI) contains epitopes targeted by HLA-A-restricted (HLA-A0201, A2402) cytotoxic T cells as part of the pathogenesis of β-cell destruction in type 1 diabetes. We extended the discovery of the PPI epitope to disease-associated HLA-B*1801 and HLA-B*3906 (risk) and HLA-A*1101 and HLA-B*3801 (protective) alleles, revealing that four of six alleles present epitopes derived from the signal peptide region. During cotranslational translocation of PPI, its signal peptide is cleaved and retained within the endoplasmic reticulum (ER) membrane, implying it is processed for immune recognition outside of the canonical proteasome-directed pathway. Using in vitro translocation assays with specific inhibitors and gene knockout in PPI-expressing target cells, we show that PPI signal peptide antigen processing requires signal peptide peptidase (SPP). The intramembrane protease SPP generates cytoplasm-proximal epitopes, which are transporter associated with antigen processing (TAP), ER-luminal epitopes, which are TAP independent, each presented by different HLA class I molecules and N-terminal trimmed by ER aminopeptidase 1 for optimal presentation. In vivo, TAP expression is significantly upregulated and correlated with HLA class I hyperexpression in insulin-containing islets of patients with type 1 diabetes. Thus, PPI signal peptide epitopes are processed by SPP and loaded for HLA-guided immune recognition via pathways that are enhanced during disease pathogenesis. © 2018 by the American Diabetes Association.

Efficient Capsid Antigen Presentation From Adeno-Associated Virus Empty Virions In Vivo.

PubMed

Pei, Xiaolei; Earley, Lauriel Freya; He, Yi; Chen, Xiaojing; Hall, Nikita Elexa; Samulski, Richard Jude; Li, Chengwen

2018-01-01

Adeno-associated virus (AAV) vectors have been successfully applied in clinical trials for hemophilic patients. Although promising, the clinical results suggest that the capsid-specific CD8+T cell response has a negative effect on therapeutic success. In an in vitro analysis using an engineered AAV virus carrying immune-dominant SIINFEKL peptide in the capsid backbone, we have previously demonstrated that capsid antigen presentation from full (genome containing) AAV capsids requires endosome escape and is proteasome dependent and that no capsid antigen presentation is induced from empty virions. In the present study, we examined capsid antigen presentation from administration of empty virions in animal models. In wild-type mice, similar to AAV full particles, capsid antigen presentation from AAV empty virion infection was dose dependent, and the kinetics studies showed that antigen presentation was detected from 2 to 40 days after AAV empty virion administration. In the transporter associated with antigen processing 1 deficient (TAP-/-) mice, capsid antigen presentation was inhibited from both AAV full and empty virions, but higher inhibition was achieved from AAV full particle administration than that from empty virions. This indicates that the pathway of capsid antigen presentation from AAV transduction is dependent on proteasome-mediated degradation of AAV capsids (mainly for full particles) and that the endosomal pathway may also play a role in antigen presentation from empty particles but not full virions. The capsid antigen presentation efficiency from AAV preparations was positively correlated with the amount of empty virions contaminated with full particles. Collectively, the results indicate that contamination of AAV empty virions induces efficient antigen presentation in vivo and the mechanism of capsid antigen presentation from empty virions involves both endosomal and proteasomal pathways. The elucidation of capsid antigen presentation from AAV empty virions may allow us to rationally design effective strategies to prevent elimination of AAV transduced target cells by capsid specific CD8+ T cells.

Antigen processing and presentation: evolution from a bird's eye view.

PubMed

Kaufman, Jim

2013-09-01

Most detailed knowledge of the MHC outside of mammals has come from studies of chickens, originally due to the economic importance of the poultry industry. We have used our discoveries about the chicken MHC to develop a framework for understanding the evolution of the MHC, based on the importance of genomic organisation for gene co-evolution. In humans, MHC class I molecules are polymorphic and determine the specificity of peptide presentation, while the molecules involved in antigen processing are functionally monomorphic. The genes for tapasin, transporters associated with antigen presentation (TAPs) and inducible proteasome components (LMPs) are located in and beyond the class II region, far away from the class I genes in the class I region. In contrast, chickens express only one class I locus at high levels, which can result in strong MHC associations with resistance to particular infectious pathogens. The chicken TAP and tapasin genes are located very close to the class I genes, and have high levels of allelic polymorphism and moderate sequence diversity, co-evolving their specificities to work optimally with the dominantly expressed class I molecule. The salient features of the chicken MHC are found in many if not most non-mammalian species examined, and are likely to represent the ancestral organisation of the MHC. Comparison with the MHC organisation of humans and typical mammals suggests that a large inversion brought the class III region into the middle of the MHC, separating the antigen processing genes from the class I gene, breaking the co-evolutionary relationships and allowing a multigene family of well-expressed class I genes. Such co-evolution in the primordial MHC was likely responsible for the appearance of the antigen presentation pathways and receptor-ligand interactions at the birth of the adaptive immune system. Of course, much further work is required to understand this evolutionary framework in more detail. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dynamics of major histocompatibility complex class I association with the human peptide-loading complex.

PubMed

Panter, Michaela S; Jain, Ankur; Leonhardt, Ralf M; Ha, Taekjip; Cresswell, Peter

2012-09-07

Although the human peptide-loading complex (PLC) is required for optimal major histocompatibility complex class I (MHC I) antigen presentation, its composition is still incompletely understood. The ratio of the transporter associated with antigen processing (TAP) and MHC I to tapasin, which is responsible for MHC I recruitment and peptide binding optimization, is particularly critical for modeling of the PLC. Here, we characterized the stoichiometry of the human PLC using both biophysical and biochemical approaches. By means of single-molecule pulldown (SiMPull), we determined a TAP/tapasin ratio of 1:2, consistent with previous studies of insect-cell microsomes, rat-human chimeric cells, and HeLa cells expressing truncated TAP subunits. We also report that the tapasin/MHC I ratio varies, with the PLC population comprising both 2:1 and 2:2 complexes, based on mutational and co-precipitation studies. The MHC I-saturated PLC may be particularly prevalent among peptide-selective alleles, such as HLA-C4. Additionally, MHC I association with the PLC increases when its peptide supply is reduced by inhibiting the proteasome or by blocking TAP-mediated peptide transport using viral inhibitors. Taken together, our results indicate that the composition of the human PLC varies under normal conditions and dynamically adapts to alterations in peptide supply that may arise during viral infection. These findings improve our understanding of the quality control of MHC I peptide loading and may aid the structural and functional modeling of the human PLC.

A Lipid Based Antigen Delivery System Efficiently Facilitates MHC Class-I Antigen Presentation in Dendritic Cells to Stimulate CD8+ T Cells

NASA Astrophysics Data System (ADS)

Maji, Mithun; Mazumder, Saumyabrata; Bhattacharya, Souparno; Choudhury, Somsubhra Thakur; Sabur, Abdus; Shadab, Md.; Bhattacharya, Pradyot; Ali, Nahid

2016-06-01

The most effective strategy for protection against intracellular infections such as Leishmania is vaccination with live parasites. Use of recombinant proteins avoids the risks associated with live vaccines. However, due to low immunogenicity, they fail to trigger T cell responses particularly of CD8+ cells requisite for persistent immunity. Previously we showed the importance of protein entrapment in cationic liposomes and MPL as adjuvant for elicitation of CD4+ and CD8+ T cell responses for long-term protection. In this study we investigated the role of cationic liposomes on maturation and antigen presentation capacity of dendritic cells (DCs). We observed that cationic liposomes were taken up very efficiently by DCs and transported to different cellular sites. DCs activated with liposomal rgp63 led to efficient presentation of antigen to specific CD4+ and CD8+ T cells. Furthermore, lymphoid CD8+ T cells from liposomal rgp63 immunized mice demonstrated better proliferative ability when co-cultured ex vivo with stimulated DCs. Addition of MPL to vaccine enhanced the antigen presentation by DCs and induced more efficient antigen specific CD8+ T cell responses when compared to free and liposomal antigen. These liposomal formulations presented to CD8+ T cells through TAP-dependent MHC-I pathway offer new possibilities for a safe subunit vaccine.

Crystal structure of a TAPBPR–MHC I complex reveals the mechanism of peptide editing in antigen presentation

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

Jiang, Jiansheng; Natarajan, Kannan; Boyd, Lisa F.

Central to CD8+ T cell–mediated immunity is the recognition of peptide–major histocompatibility complex class I (p–MHC I) proteins displayed by antigen-presenting cells. Chaperone-mediated loading of high-affinity peptides onto MHC I is a key step in the MHC I antigen presentation pathway. However, the structure of MHC I with a chaperone that facilitates peptide loading has not been determined. We report the crystal structure of MHC I in complex with the peptide editor TAPBPR (TAP-binding protein–related), a tapasin homolog. TAPBPR remodels the peptide-binding groove of MHC I, resulting in the release of low-affinity peptide. Changes include groove relaxation, modifications of keymore » binding pockets, and domain adjustments. This structure captures a peptide-receptive state of MHC I and provides insights into the mechanism of peptide editing by TAPBPR and, by analogy, tapasin.« less

Mechanistic determinants of the directionality and energetics of active export by a heterodimeric ABC transporter

DOE PAGES

Grossmann, Nina; Vakkasoglu, Ahmet S.; Hulpke, Sabine; ...

2014-11-07

The ATP-binding cassette (ABC) transporter associated with antigen processing (TAP) participates in immune surveillance by moving proteasomal products into the endoplasmic reticulum (ER) lumen for major histocompatibility complex class I loading and cell surface presentation to cytotoxic T cells. Here we delineate the mechanistic basis for antigen translocation. Notably, TAP works as a molecular diode, translocating peptide substrates against the gradient in a strict unidirectional way. We reveal the importance of the D-loop at the dimer interface of the two nucleotide-binding domains (NBDs) in coupling substrate translocation with ATP hydrolysis and defining transport vectoriality. Substitution of the converved aspartate, whichmore » coordinates the ATP-binding site, decreases NBD dimerization affinity and turns the unidirectional primary active pump into a passive bidirectional nucleotide-gated facilitator. Thus, ATP hydrolysis is not required for translocation per se, but is essential for both active and unidirectional transport. As a result, our data provide detailed mechanistic insight into how heterodimeric ABC exporters operate.« less

Modeling the MHC class I pathway by combining predictions of proteasomal cleavage, TAP transport and MHC class I binding.

PubMed

Tenzer, S; Peters, B; Bulik, S; Schoor, O; Lemmel, C; Schatz, M M; Kloetzel, P-M; Rammensee, H-G; Schild, H; Holzhütter, H-G

2005-05-01

Epitopes presented by major histocompatibility complex (MHC) class I molecules are selected by a multi-step process. Here we present the first computational prediction of this process based on in vitro experiments characterizing proteasomal cleavage, transport by the transporter associated with antigen processing (TAP) and MHC class I binding. Our novel prediction method for proteasomal cleavages outperforms existing methods when tested on in vitro cleavage data. The analysis of our predictions for a new dataset consisting of 390 endogenously processed MHC class I ligands from cells with known proteasome composition shows that the immunological advantage of switching from constitutive to immunoproteasomes is mainly to suppress the creation of peptides in the cytosol that TAP cannot transport. Furthermore, we show that proteasomes are unlikely to generate MHC class I ligands with a C-terminal lysine residue, suggesting processing of these ligands by a different protease that may be tripeptidyl-peptidase II (TPPII).

Glycan modification of antigen alters its intracellular routing in dendritic cells, promoting priming of T cells

PubMed Central

Streng-Ouwehand, Ingeborg; Ho, Nataschja I; Litjens, Manja; Kalay, Hakan; Boks, Martine Annemarie; Cornelissen, Lenneke AM; Kaur Singh, Satwinder; Saeland, Eirikur; Garcia-Vallejo, Juan J; Ossendorp, Ferry A; Unger, Wendy WJ; van Kooyk, Yvette

2016-01-01

Antigen uptake by dendritic cells and intracellular routing of antigens to specific compartments is regulated by C-type lectin receptors that recognize glycan structures. We show that the modification of Ovalbumin (OVA) with the glycan-structure LewisX (LeX) re-directs OVA to the C-type lectin receptor MGL1. LeX-modification of OVA favored Th1 skewing of CD4+ T cells and enhanced cross-priming of CD8+ T cells. While cross-presentation of native OVA requires high antigen dose and TLR stimuli, LeX modification reduces the required amount 100-fold and obviates its dependence on TLR signaling. The OVA-LeX-induced enhancement of T cell cross-priming is MGL1-dependent as shown by reduced CD8+ effector T cell frequencies in MGL1-deficient mice. Moreover, MGL1-mediated cross-presentation of OVA-LeX neither required TAP-transporters nor Cathepsin-S and was still observed after prolonged intracellular storage of antigen in Rab11+LAMP1+ compartments. We conclude that controlled neo-glycosylation of antigens can crucially influence intracellular routing of antigens, the nature and strength of immune responses and should be considered for optimizing current vaccination strategies. DOI: http://dx.doi.org/10.7554/eLife.11765.001 PMID:26999763

ABC transporters and immunity: mechanism of self-defense.

PubMed

Hinz, Andreas; Tampé, Robert

2012-06-26

The transporter associated with antigen processing (TAP) is a prototype of an asymmetric ATP-binding cassette (ABC) transporter, which uses ATP binding and hydrolysis to translocate peptides from the cytosol to the lumen of the endoplasmic reticulum (ER). Here, we review molecular details of peptide binding and ATP binding and hydrolysis as well as the resulting allosteric cross-talk between the nucleotide-binding domains and the transmembrane domains that drive translocation of the solute across the ER membrane. We also discuss the general molecular architecture of ABC transporters and demonstrate the importance of structural and functional studies for a better understanding of the role of the noncanonical site of asymmetric ABC transporters. Several aspects of peptide binding and specificity illustrate details of peptide translocation by TAP. Furthermore, this ABC transporter forms the central part of the major histocompatibility complex class I (MHC I) peptide-loading machinery. Hence, TAP is confronted with a number of viral factors, which prevent antigen translocation and MHC I loading in virally infected cells. We review how these viral factors have been used as molecular tools to decipher mechanistic aspects of solute translocation and discuss how they can help in the structural analysis of TAP.

HLA class I is most tightly linked to levels of tapasin compared with other antigen-processing proteins in glioblastoma.

PubMed

Thuring, Camilla; Follin, Elna; Geironson, Linda; Freyhult, Eva; Junghans, Victoria; Harndahl, Mikkel; Buus, Søren; Paulsson, Kajsa M

2015-09-15

Tumour cells can evade the immune system by dysregulation of human leukocyte antigens (HLA-I). Low quantity and/or altered quality of HLA-I cell surface expression is the result of either HLA-I alterations or dysregulations of proteins of the antigen-processing machinery (APM). Tapasin is an APM protein dedicated to the maturation of HLA-I and dysregulation of tapasin has been linked to higher malignancy in several different tumours. We studied the expression of APM components and HLA-I, as well as HLA-I tapasin-dependency profiles in glioblastoma tissues and corresponding cell lines. Tapasin displayed the strongest correlation to HLA-I heavy chain but also clustered with β2-microglobulin, transporter associated with antigen processing (TAP) and LMP. Moreover, tapasin also correlated to survival of glioblastoma patients. Some APM components, for example, TAP1/TAP2 and LMP2/LMP7, showed variable but coordinated expression, whereas ERAP1/ERAP2 displayed an imbalanced expression pattern. Furthermore, analysis of HLA-I profiles revealed variable tapasin dependence of HLA-I allomorphs in glioblastoma patients. Expression of APM proteins is highly variable between glioblastomas. Tapasin stands out as the APM component strongest correlated to HLA-I expression and we proved that HLA-I profiles in glioblastoma patients include tapasin-dependent allomorphs. The level of tapasin was also correlated with patient survival time. Our results support the need for individualisation of immunotherapy protocols.

Deficiency of activated STAT1 in head and neck cancer cells mediates TAP1-dependent escape from cytotoxic T lymphocytes

PubMed Central

Leibowitz, Michael S.; Filho, Pedro A. Andrade; Ferrone, Soldano; Ferris, Robert L.

2012-01-01

Squamous cell carcinoma of the head and neck (SCCHN) cells can escape recognition by tumor antigen (TA)-specific cytotoxic T lymphocytes (CTL) by downregulation of antigen processing machinery (APM) components, such as the transporter associated with antigen processing (TAP)-1/2 heterodimer. APM component upregulation by interferon gamma (IFN-γ) restores SCCHN cell recognition and susceptibility to lysis by CTL, but the mechanism underlying TAP1/2 downregulation in SCCHN cells is not known. Because IFN-γ activates signal transducer and activator of transcription (STAT)-1, we investigated phosphorylated (p)-STAT1 as a mediator of low basal TAP1/2 expression in SCCHN cells. SCCHN cells were found to express basal total STAT1 but low to undetectable levels of activated STAT1. The association of increased pSTAT1 levels and APM components likely reflects a cause–effect relationship, since STAT1 knockdown significantly reduced both IFN-γ-mediated APM component expression and TA-specific CTL recognition of IFN-γ-treated SCCHN cells. On the other hand, since oncogenic pSTAT3 is overexpressed in SCCHN cells and was found to heterodimerize with pSTAT1, we also tested whether pSTAT3 and pSTAT1:pSTAT3 heterodimers inhibited IFN-γ-induced STAT1 activation and APM component expression. First, STAT3 activation or depletion did not affect basal or IFN-γ-induced expression of pSTAT1 and APM components or recognition of SCCHN cells by TA-specific CTL. Second, pSTAT1:pSTAT3 heterodimers did not interfere with IFN-γ-induced STAT1 binding to the TAP1 promoter or APM protein expression. These findings demonstrate that APM component downregulation is regulated primarily by an IFN-γ-pSTAT1-mediated signaling pathway, independent of oncogenic STAT3 overexpression in SCCHN cells. PMID:21207025

Modified Vaccinia Virus Ankara-Infected Dendritic Cells Present CD4+ T-Cell Epitopes by Endogenous Major Histocompatibility Complex Class II Presentation Pathways

PubMed Central

Thiele, Frank; Tao, Sha; Zhang, Yi; Muschaweckh, Andreas; Zollmann, Tina; Protzer, Ulrike; Abele, Rubert

2014-01-01

ABSTRACT CD4+ T lymphocytes play a central role in the immune system and mediate their function after recognition of their respective antigens presented on major histocompatibility complex II (MHCII) molecules on antigen-presenting cells (APCs). Conventionally, phagocytosed antigens are loaded on MHCII for stimulation of CD4+ T cells. Certain epitopes, however, can be processed directly from intracellular antigens and are presented on MHCII (endogenous MHCII presentation). Here we characterized the MHCII antigen presentation pathways that are possibly involved in the immune response upon vaccination with modified vaccinia virus Ankara (MVA), a promising live viral vaccine vector. We established CD4+ T-cell lines specific for MVA-derived epitopes as tools for in vitro analysis of MHCII antigen processing and presentation in MVA-infected APCs. We provide evidence that infected APCs are able to directly transfer endogenous viral proteins into the MHCII pathway to efficiently activate CD4+ T cells. By using knockout mice and chemical inhibitory compounds, we further elucidated the molecular basis, showing that among the various subcellular pathways investigated, proteasomes and autophagy are key players in the endogenous MHCII presentation during MVA infection. Interestingly, although proteasomal processing plays an important role, neither TAP nor LAMP-2 was found to be involved in the peptide transport. Defining the molecular mechanism of MHCII presentation during MVA infection provides a basis for improving MVA-based vaccination strategies by aiming for enhanced CD4+ T-cell activation by directing antigens into the responsible pathways. IMPORTANCE This work contributes significantly to our understanding of the immunogenic properties of pathogens by deciphering antigen processing pathways contributing to efficient activation of antigen-specific CD4+ T cells. We identified autophagosome formation, proteasomal activity, and lysosomal integrity as being crucial for endogenous CD4+ T-cell activation. Since poxvirus vectors such as MVA are already used in clinical trials as recombinant vaccines, the data provide important information for the future design of optimized poxviral vaccines for the study of advanced immunotherapy options. PMID:25520512

Downregulation of peptide transporter genes in cell lines transformed with the highly oncogenic adenovirus 12

PubMed Central

1994-01-01

The expression of class I major histocompatibility complex antigens on the surface of cells transformed by adenovirus 12 (Ad12) is generally very low, and correlates with the high oncogenicity of this virus. In primary embryonal fibroblasts from transgenic mice that express both endogenous H-2 genes and a miniature swine class I gene (PD1), Ad12- mediated transformation results in suppression of cell surface expression of all class I antigens. Although class I mRNA levels of PD1 and H-2Db are similar to those in nonvirally transformed cells, recognition of newly synthesized class I molecules by a panel of monoclonal antibodies is impaired, presumably as a result of inefficient assembly and transport of the class I molecules. Class I expression can be partially induced by culturing cells at 26 degrees C, or by coculture of cells with class I binding peptides at 37 degrees C. Analysis of steady state mRNA levels of the TAP1 and TAP2 transporter genes for Ad12-transformed cell lines revealed that they both are significantly reduced, TAP2 by about 100-fold and TAP1 by 5-10-fold. Reconstitution of PD1 and H-2Db, but not H-2Kb, expression is achieved in an Ad12-transformed cell line by stable transfection with a TAP2, but not a TAP1, expression construct. From these data it may be concluded that suppressed expression of peptide transporter genes, especially TAP2, in Ad12-transformed cells inhibits cell surface expression of class I molecules. The failure to fully reconstitute H- 2Db and H-2Kb expression indicates that additional factors are involved in controlling class I gene expression in Ad12-transformed cells. Nevertheless, these results suggest that suppression of peptide transporter genes might be an important mechanism whereby virus- transformed cells escape immune recognition in vivo. PMID:7519239

Narrow Groove and Restricted Anchors of MHC Class I Molecule BF2*0401 Plus Peptide Transporter Restriction can Explain Disease Susceptibility of B4 Chickens

PubMed Central

Zhang, Jianhua; Chen, Yong; Qi, Jianxun; Gao, Feng; Liu, Yanjie; Liu, Jun; Zhou, Xuyu; Kaufman, Jim; Xia, Chun; Gao, George F.

2016-01-01

The major histocompatibility complex (MHC) has genetic associations with many diseases, often due to differences in presentation of antigenic peptides by polymorphic MHC molecules to T lymphocytes of the immune system. In chickens, only a single classical class I molecule in each MHC haplotype is expressed well due to co-evolution with the polymorphic transporters associated with antigen presentation (TAPs), which means that resistance and susceptibility to infectious pathogens are particularly easy to observe. Previously, structures of chicken MHC class I molecule BF2*2101 from B21 haplotype showed an unusually large peptide-binding groove that accommodates a broad spectrum of peptides to present as epitopes to cytotoxic T lymphocytes (CTL), explaining the MHC-determined resistance of B21 chickens to Marek's disease. Here, we report the crystal structure of BF2*0401 from the B4 (also known as B13) haplotype, showing a highly positively-charged surface hitherto unobserved in other MHC molecules, as well as a remarkably narrow groove due to the allele-specific residues with bulky side chains. Together, these properties limit the number of epitope peptides that can bind this class I molecule. However, peptide-binding assays show that in vitro BF2*0401 can bind a wider variety of peptides than are found on the surface of B4 cells. Thus, a combination of the specificities of the polymorphic TAP transporter and the MHC results in a very limited set of BF2*0401 peptides with negatively charged anchors to be presented to T lymphocytes. PMID:23041567

Genetic Variants in TAP Are Associated with High-Grade Cervical Neoplasia

PubMed Central

Einstein, Mark H.; Leanza, Suzanne; Chiu, Lydia G.; Schlecht, Nicolas F.; Goldberg, Gary L.; Steinberg, Bettie M.; Burk, Robert D.

2018-01-01

Purpose The transporter associated with antigen processing (TAP) is essential in assembling MHC-I proteins. Human papillomavirus (HPV) evades immune recognition by decreasing class I MHC cell surface expression through down-regulation of TAP1 levels. Consistent with heterogeneity in MHC expression is the individual variability in clearing detectable HPV infections. Genetic polymorphisms in TAP genes may affect protein structure, function, and the ability to clear HPV infection. Experimental Design Case-control study of women with cervical intraepithelial neoplasia (CIN) II or III (n = 114) and women without high-grade CIN (n = 366). Five nonsynonymous single nucleotide polymorphisms (SNP) in TAP1 and TAP2 were genotyped using DNA collected in cervicovaginal lavage samples using microsphere array technology (Luminex ×MAP). HPV typing was done using a PCR-based system with MY09/MY11 primers. TAP1 and TAP2 SNPs were validated by direct sequencing. Results Differences in allele distribution between women with high-grade cervical neoplasia and women without was seen for TAP1 I333V (P = 0.02) and TAP1 D637G (p = 0.01).The odds ratios (OR) for CIN III were significantly lower among carriers of the TAP1 I333V polymorphism (OR, 0.28; 95% confidence interval, 0.1-0.8), and TAP1 D637G polymorphism (OR, 0.27; 95% confidence interval, 0.1-0.7). These associations remained significant even after restricting the evaluation to women who were positive for high-risk HPV types. Conclusions In addition to the down-regulation of MHC-1 by oncogenic HPV, HPV pathogenesis might be facilitated by polymorphisms in the TAP proteins. Identifying TAP polymorphisms may potentially be used to identify women less susceptible to progression to high-grade CIN and cervical cancer. PMID:19188174

Assessment of cancer and virus antigens for cross-reactivity in human tissues.

PubMed

Jaravine, Victor; Raffegerst, Silke; Schendel, Dolores J; Frishman, Dmitrij

2017-01-01

Cross-reactivity (CR) or invocation of autoimmune side effects in various tissues has important safety implications in adoptive immunotherapy directed against selected antigens. The ability to predict CR (on-target and off-target toxicities) may help in the early selection of safer therapeutically relevant target antigens. We developed a methodology for the calculation of quantitative CR for any defined peptide epitope. Using this approach, we performed assessment of 4 groups of 283 currently known human MHC-class-I epitopes including differentiation antigens, overexpressed proteins, cancer-testis antigens and mutations displayed by tumor cells. In addition, 89 epitopes originating from viral sources were investigated. The natural occurrence of these epitopes in human tissues was assessed based on proteomics abundance data, while the probability of their presentation by MHC-class-I molecules was modelled by the method of Keşmir et al. which combines proteasomal cleavage, TAP affinity and MHC-binding predictions. The results of these analyses for many previously defined peptides are presented as CR indices and tissue profiles. The methodology thus allows for quantitative comparisons of epitopes and is suggested to be suited for the assessment of epitopes of candidate antigens in an early stage of development of adoptive immunotherapy. Our method is implemented as a Java program, with curated datasets stored in a MySQL database. It predicts all naturally possible self-antigens for a given sequence of a therapeutic antigen (or epitope) and after filtering for predicted immunogenicity outputs results as an index and profile of CR to the self-antigens in 22 human tissues. The program is implemented as part of the iCrossR webserver, which is publicly available at http://webclu.bio.wzw.tum.de/icrossr/ CONTACT: d.frishman@wzw.tum.deSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Schistosoma mansoni venom allergen-like protein 4 (SmVAL4) is a novel lipid-binding SCP/TAPS protein that lacks the prototypical CAP motifs

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

Kelleher, Alan; Darwiche, Rabih; Rezende, Wanderson C.

2014-08-01

The first structure of an S. mansoni venom allergen-like protein is presented. Schistosomiasis is a parasitic disease that affects over 200 million people. Vaccine candidates have been identified, including Schistosoma mansoni venom allergen-like proteins (SmVALs) from the SCP/TAPS (sperm-coating protein/Tpx/antigen 5/pathogenesis related-1/Sc7) superfamily. The first SmVAL structure, SmVAL4, was refined to a resolution limit of 2.16 Å. SmVAL4 has a unique structure that could not be predicted from homologous structures, with longer loops and an unusual C-terminal extension. SmVAL4 has the characteristic α/β-sandwich and central SCP/TAPS cavity. Furthermore, SmVAL4 has only one of the signature CAP cavity tetrad amino-acid residuesmore » and is missing the histidines that coordinate divalent cations such as Zn{sup 2+} in other SCP/TAPS proteins. SmVAL4 has a cavity between α-helices 1 and 4 that was observed to bind lipids in tablysin-15, suggesting the ability to bind lipids. Subsequently, SmVAL4 was shown to bind cholesterol in vitro. Additionally, SmVAL4 was shown to complement the in vivo sterol-export phenotype of yeast mutants lacking their endogenous CAP proteins. Expression of SmVAL4 in yeast cells lacking endogenous CAP function restores the block in sterol export. These studies suggest an evolutionarily conserved lipid-binding function shared by CAP proteins such as SmVAL4 and yeast CAP proteins such as Pry1.« less

Cellular Nuclear Export Factors TAP and Aly Are Required for HDAg-L-mediated Assembly of Hepatitis Delta Virus.

PubMed

Huang, Hsiu-Chen; Lee, Chung-Pei; Liu, Hui-Kang; Chang, Ming-Fu; Lai, Yu-Heng; Lee, Yu-Ching; Huang, Cheng

2016-12-09

Hepatitis delta virus (HDV) is a satellite virus of hepatitis B virus (HBV). HDV genome encodes two forms of hepatitis delta antigen (HDAg), small HDAg (HDAg-S), which is required for viral replication, and large HDAg (HDAg-L), which is essential for viral assembly. HDAg-L is identical to HDAg-S except that it bears a 19-amino acid extension at the C terminus. Both HDAgs contain a nuclear localization signal (NLS), but only HDAg-L contains a CRM1-independent nuclear export signal at its C terminus. The nuclear export activity of HDAg-L is important for HDV particle formation. However, the mechanisms of HDAg-L-mediated nuclear export of HDV ribonucleoprotein are not clear. In this study, the host cellular RNA export complex TAP-Aly was found to form a complex with HDAg-L, but not with an export-defective HDAg-L mutant, in which Pro 205 was replaced by Ala. HDAg-L was found to colocalize with TAP and Aly in the nucleus. The C-terminal domain of HDAg-L was shown to directly interact with the N terminus of TAP, whereas an HDAg-L mutant lacking the NLS failed to interact with full-length TAP. In addition, small hairpin RNA-mediated down-regulation of TAP or Aly reduced nuclear export of HDAg-L and assembly of HDV virions. Furthermore, a peptide, TAT-HDAg-L(198-210), containing the 10-amino acid TAT peptide and HDAg-L(198-210), inhibited the interaction between HDAg-L and TAP and blocked HDV virion assembly and secretion. These data demonstrate that formation and release of HDV particles are mediated by TAP and Aly. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Rational design based synthetic polyepitope DNA vaccine for eliciting HIV-specific CD8+ T cell responses.

PubMed

Bazhan, S I; Karpenko, L I; Ilyicheva, T N; Belavin, P A; Seregin, S V; Danilyuk, N K; Antonets, D V; Ilyichev, A A

2010-04-01

Advances in defining HIV-1 CD8+ T cell epitopes and understanding endogenous MHC class I antigen processing enable the rational design of polyepitope vaccines for eliciting broadly targeted CD8+ T cell responses to HIV-1. Here we describe the construction and comparison of experimental DNA vaccines consisting of ten selected HLA-A2 epitopes from the major HIV-1 antigens Env, Gag, Pol, Nef, and Vpr. The immunogenicity of designed gene constructs was assessed after double DNA prime, single vaccinia virus boost immunization of HLA-A2 transgenic mice. We compared a number of parameters including different strategies for fusing ubiquitin to the polyepitope and including spacer sequences between epitopes to optimize proteasome liberation and TAP transport. It was demonstrated that the vaccine construct that induced in vitro the largest number of [peptide-MHC class I] complexes was also the most immunogenic in the animal experiments. This most immunogenic vaccine construct contained the N-terminal ubiquitin for targeting the polyepitope to the proteasome and included both proteasome liberation and TAP transport optimized spacer sequences that flanked the epitopes within the polyepitope construct. The immunogenicity of determinants was strictly related to their affinities for HLA-A2. Our finding supports the concept of rational vaccine design based on detailed knowledge of antigen processing. Copyright 2010 Elsevier Ltd. All rights reserved.

Rhesus Cytomegalovirus Contains Functional Homologues of US2, US3, US6, and US11

PubMed Central

Pande, Nupur T.; Powers, Colin; Ahn, Kwangseog; Früh, Klaus

2005-01-01

Human cytomegalovirus (HCMV) is a paradigm for mechanisms subverting antigen presentation by major histocompatibility complex (MHC) molecules. Due to its limited host range, HCMV cannot be studied in animals. Thus, the in vivo importance of inhibiting antigen presentation for the establishment and maintenance of infection with HCMV is unknown. Rhesus cytomegalovirus (RhCMV) is an emerging animal model that shares many of the features of HCMV infection. The recent completion of the genomic sequence of RhCMV revealed a significant degree of homology to HCMV. Strikingly, RhCMV contains several genes with low homology to the HCMV US6 gene family of inhibitors of the MHC I antigen presentation pathway. Here, we examine whether the RhCMV US6 homologues (open reading frames Rh182, -184, -185, -186, -187, and -189) interfere with the MHC I antigen-processing pathway. We demonstrate that Rh182 and Rh189 function similarly to HCMV US2 and US11, respectively, mediating the proteasomal degradation of newly synthesized MHC I. The US3 homologue, Rh184, delayed MHC I maturation. Unlike US3, MHC I molecules eventually escaped retention by Rh184, so that steady-state surface levels of MHC I remained unchanged. Rh185 acted similarly to US6 and inhibited peptide transport by TAP and, consequently, peptide loading of MHC I molecules. Thus, despite relatively low sequence conservation, US6 family-related genes in RhCMV are functionally closely related to the conserved structural features of HCMV immunomodulators. The conservation of these mechanisms implies their importance for immune evasion in vivo, a question that can now be addressed experimentally. PMID:15827193

Buffer substitution in malaria rapid diagnostic tests causes false-positive results

PubMed Central

2010-01-01

Background Malaria rapid diagnostic tests (RDTs) are kits that generally include 20 to 25 test strips or cassettes, but only a single buffer vial. In field settings, laboratory staff occasionally uses saline, distilled water (liquids for parenteral drugs dilution) or tap water as substitutes for the RDT kit's buffer to compensate for the loss of a diluent bottle. The present study assessed the effect of buffer substitution on the RDT results. Methods Twenty-seven RDT brands were run with EDTA-blood samples of five malaria-free subjects, who were negative for rheumatoid factor and antinuclear antibodies. Saline, distilled water and tap water were used as substitute liquids. RDTs were also run with distilled water, without adding blood. Results were compared to those obtained with the RDT kit's buffer and Plasmodium positive samples. Results Only eight cassettes (in four RDT brands) showed no control line and were considered invalid. Visible test lines occurred for at least one malaria-free sample and one of the substitutes in 20/27 (74%) RDT brands (saline: n = 16; distilled water: n = 17; and tap water: n = 20), and in 15 RDTs which were run with distilled water only. They occurred for all Plasmodium antigens and RDT formats (two-, three- and four-band RDTs). Clearance of the background of the strip was excellent except for saline. The aspects (colour, intensity and crispness) of the control and the false-positive test lines were similar to those obtained with the RDT kits' buffer and Plasmodium positive samples. Conclusion Replacement of the RDT kit's dedicated buffer by saline, distilled water and tap water can cause false-positive test results. PMID:20650003

Quantitative modeling of peptide binding to TAP using support vector machine.

PubMed

Diez-Rivero, Carmen M; Chenlo, Bernardo; Zuluaga, Pilar; Reche, Pedro A

2010-01-01

The transport of peptides to the endoplasmic reticulum by the transporter associated with antigen processing (TAP) is a necessary step towards determining CD8 T cell epitopes. In this work, we have studied the predictive performance of support vector machine models trained on single residue positions and residue combinations drawn from a large dataset consisting of 613 nonamer peptides of known affinity to TAP. Predictive performance of these TAP affinity models was evaluated under 10-fold cross-validation experiments and measured using Pearson's correlation coefficients (R(p)). Our results show that every peptide position (P1-P9) contributes to TAP binding (minimum R(p) of 0.26 +/- 0.11 was achieved by a model trained on the P6 residue), although the largest contributions to binding correspond to the C-terminal end (R(p) = 0.68 +/- 0.06) and the P1 (R(p) = 0.51 +/- 0.09) and P2 (0.57 +/- 0.08) residues of the peptide. Training the models on additional peptide residues generally improved their predictive performance and a maximum correlation (R(p) = 0.89 +/- 0.03) was achieved by a model trained on the full-length sequences or a residue selection consisting of the first 5 N- and last 3 C-terminal residues of the peptides included in the training set. A system for predicting the binding affinity of peptides to TAP using the methods described here is readily available for free public use at http://imed.med.ucm.es/Tools/tapreg/. (c) 2009 Wiley-Liss, Inc.

The minor histocompatibility antigen HA-3 arises from differential proteasome-mediated cleavage of the lymphoid blast crisis (Lbc) oncoprotein.

PubMed

Spierings, Eric; Brickner, Anthony G; Caldwell, Jennifer A; Zegveld, Suzanne; Tatsis, Nia; Blokland, Els; Pool, Jos; Pierce, Richard A; Mollah, Sahana; Shabanowitz, Jeffrey; Eisenlohr, Laurence C; van Veelen, Peter; Ossendorp, Ferry; Hunt, Donald F; Goulmy, Els; Engelhard, Victor H

2003-07-15

Minor histocompatibility (H) antigens crucially affect the outcome of human leukocyte antigen (HLA)-identical allogeneic stem cell transplantation (SCT). To understand the basis of alloimmune responses against minor H antigens, identification of minor H peptides and their antigenicity-determining mechanisms is essential. Here we report the identification of HA-3 and its encoding gene. The HA-3 peptide, VTEPGTAQY (HA-3T), is encoded by the lymphoid blast crisis (Lbc) oncogene. We thus show for the first time that a leukemia-associated oncogene can give rise to immunogenic T-cell epitopes that may have participated in antihost and antileukemic alloimmune responses. Genotypic analysis of HA-3- individuals revealed the allelic counterpart VMEPGTAQY (HA-3M). Despite the lack of T-cell recognition of HA-3- cells, the Thr-->Met substitution had only a modest effect on peptide binding to HLA-A1 and a minimal impact on recognition by T cells when added exogenously to target cells. This substitution did not influence transporter associated with antigen processing (TAP) transport, but, in contrast to the HA-3T peptide, HA-3M is destroyed by proteasome-mediated digestion. Thus, the immunogenicity of minor H antigens can result from proteasome-mediated destruction of the negative allelic peptide.

Coevolution of MHC genes (LMP/TAP/class Ia; NKT-class Ib; NKp30-B7H6): Lessons from cold-blooded vertebrates

PubMed Central

Ohta, Yuko; Flajnik, Martin F.

2015-01-01

Summary Comparative immunology provides the long view of what is conserved across all vertebrate taxa versus what is specific to particular organisms or group of organisms. Regarding the major histocompatibility complex (MHC) and coevolution, three striking cases have been revealed in cold-blooded vertebrates: lineages of class Ia antigen-processing and -presenting genes, evolutionary conservation of NKT-class Ib recognition, and the ancient emergence of the natural cytotoxicity receptor NKp30 and its ligand B7H6. While coevolution of transporter associated with antigen processing (TAP) and class Ia has been documented in endothermic birds and two mammals, lineages of LMP7 are restricted to ectotherms. The unambiguous discovery of natural killer T (NKT) cells in Xenopus demonstrated that NKT cells are not restricted to mammals and are likely to have emerged at the same time in evolution as classical α/β and γ/δ T cells. NK cell receptors evolve at a rapid rate, and orthologues are nearly impossible to identify in different vertebrate classes. By contrast, we have detected NKp30 in all gnathostomes, except in species where it was lost. The recently discovered ligand of NKp30, B7H6, shows strong signs of coevolution with NKp30 throughout evolution, i.e. coincident loss or expansion of both genes in some species. NKp30 also offers an attractive IgSF candidate for the invasion of the RAG transposon, which is believed to have initiated T-cell receptor/immunoglobulin adaptive immunity. Besides reviewing these intriguing features of MHC evolution and coevolution, we offer suggestions for future studies and propose a model for the primordial or proto MHC. PMID:26284468

Epigenetic Silencing of TAP1 in Aldefluor+ Breast Cancer Stem Cells Contributes to Their Enhanced Immune Evasion.

PubMed

Sultan, Mohammad; Vidovic, Dejan; Paine, Arianne S; Huynh, Thomas T; Coyle, Krysta M; Thomas, Margaret L; Cruickshank, Brianne M; Dean, Cheryl A; Clements, Derek R; Kim, Youra; Lee, Kristen; Gujar, Shashi A; Weaver, Ian C G; Marcato, Paola

2018-05-01

Avoiding detection and destruction by immune cells is key for tumor initiation and progression. The important role of cancer stem cells (CSCs) in tumor initiation has been well established, yet their ability to evade immune detection and targeting is only partly understood. To investigate the ability of breast CSCs to evade immune detection, we identified a highly tumorigenic population in a spontaneous murine mammary tumor based on increased aldehyde dehydrogenase activity. We performed tumor growth studies in immunocompetent and immunocompromised mice. In immunocompetent mice, growth of the spontaneous mammary tumor was restricted; however, the Aldefluor + population was expanded, suggesting inherent resistance mechanisms. Gene expression analysis of the sorted tumor cells revealed that the Aldefluor + tumor cells has decreased expression of transporter associated with antigen processing (TAP) genes and co-stimulatory molecule CD80, which would decrease susceptibility to T cells. Similarly, the Aldefluor + population of patient tumors and 4T1 murine mammary cells had decreased expression of TAP and co-stimulatory molecule genes. In contrast, breast CSCs identified by CD44 + CD24 - do not have decreased expression of these genes, but do have increased expression of C-X-C chemokine receptor type 4. Decitabine treatment and bisulfite pyrosequencing suggests that DNA hypermethylation contributes to decreased TAP gene expression in Aldefluor + CSCs. TAP1 knockdown resulted in increased tumor growth of 4T1 cells in immunocompetent mice. Together, this suggests immune evasion mechanisms in breast CSCs are marker specific and epigenetic silencing of TAP1 in Aldefluor + breast CSCs contributes to their enhanced survival under immune pressure. Stem Cells 2018;36:641-654. © AlphaMed Press 2018.

Experimental Study on Environment Friendly Tap Hole Clay for Blast Furnace

NASA Astrophysics Data System (ADS)

Siva kumar, R.; Mohammed, Raffi; Srinivasa Rao, K.

2018-03-01

Blast furnace (BF) is the best possible route of iron production available. Blast furnace is a high pressure vessel where iron ore is melted and liquid iron is produced. The liquid iron is tapped through the hole in Blast Furnace called tap hole. The tapped liquid metal flowing through the tap hole is plugged using a clay called tap hole clay. Tap hole clay (THC) is a unshaped refractory used to plug the tap hole. The tap hole clay extruded through the tap hole using a gun. The tap hole clay is designed to expand and plug the tap hole. The tap hole filled with clay is drilled using drill bit and the hole made through the tap hole to tap the liquid metal accumulated inside the furnace. The number of plugging and drilling varies depending on the volume of the furnace. The tap hole clay need to have certain properties to avoid problems during plugging and drilling. In the present paper tap hole clay properties in industrial use was tested and studied. The problems were identified related to tap hole clay manufacturing. Experiments were conducted in lab scale to solve the identified problems. The present composition was modified with experimental results. The properties of the modified tap hole clay were found suitable and useful for blast furnace operation with lab scale experimental results.

HLA-F and MHC-I Open Conformers Cooperate in a MHC-I Antigen Cross-Presentation Pathway

PubMed Central

Goodridge, Jodie P.; Lee, Ni; Burian, Aura; Pyo, Chul-Woo; Tykodi, Scott S.; Warren, Edus H.; Yee, Cassian; Riddell, Stanley R.

2013-01-01

Peptides that are presented by MHC class I (MHC-I) are processed from two potential sources, as follows: newly synthesized endogenous proteins for direct presentation on the surface of most nucleated cells and exogenous proteins for cross-presentation typically by professional APCs. In this study, we present data that implicate the nonclassical HLA-F and open conformers of MHC-I expressed on activated cells in a pathway for the presentation of exogenous proteins by MHC-I. This pathway is distinguished from the conventional endogenous pathway by its independence from TAP and tapasin and its sensitivity to inhibitors of lysosomal enzymes, and further distinguished by its dependence on MHC-I allotype-specific epitope recognition for Ag uptake. Thus, our data from in vitro experiments collectively support a previously unrecognized model of Ag cross-presentation mediated by HLA-F and MHC-I open conformers on activated lymphocytes and monocytes, which may significantly contribute to the regulation of immune system functions and the immune defense. PMID:23851683

Booster Vaccination: The Role of Reduced Antigen Content Vaccines as a Preschool Booster

PubMed Central

Conversano, Michele; Zivelonghi, Giambattista; Zoppi, Giorgio

2014-01-01

The need for boosters for tetanus, diphtheria, pertussis, and polio, starting from preschool age, is related to the waning immune protection conferred by vaccination, the elimination/reduction of natural boosters due to large-scale immunization programs, and the possibility of reintroduction of wild agents from endemic areas. Taking into account the relevance of safety/tolerability in the compliance with vaccination among the population, it have been assessed whether today enough scientific evidences are available to support the use of dTap-IPV booster in preschool age. The review of the literature was conducted using the PubMed search engine. A total of 41 works has been selected; besides, the documentation produced by the World Health Organization, the European Centre for Disease Control, and the Italian Ministry of Health has been consulted. Many recent papers confirm the opportunity to use a low antigenic dose vaccine starting from 4 to 6 years of age. There is also evidence that 10 years after immunization the rate of seroprotected subjects against diphtheria does not differ significantly between those vaccinated with paediatric dose (DTaP) or reduced dose (dTaP or dTap) product. The dTpa vaccine is highly immunogenic for diphtheria toxoids regardless of prior vaccination history (2 + 1 and 3 + 1 schedules). PMID:24678509

Natural Polymorphisms in Tap2 Influence Negative Selection and CD4∶CD8 Lineage Commitment in the Rat

PubMed Central

Tuncel, Jonatan; Haag, Sabrina; Yau, Anthony C. Y.; Norin, Ulrika; Baud, Amelie; Lönnblom, Erik; Maratou, Klio; Ytterberg, A. Jimmy; Ekman, Diana; Thordardottir, Soley; Johannesson, Martina; Gillett, Alan; Stridh, Pernilla; Jagodic, Maja; Olsson, Tomas; Fernández-Teruel, Alberto; Zubarev, Roman A.; Mott, Richard; Aitman, Timothy J.; Flint, Jonathan; Holmdahl, Rikard

2014-01-01

Genetic variation in the major histocompatibility complex (MHC) affects CD4∶CD8 lineage commitment and MHC expression. However, the contribution of specific genes in this gene-dense region has not yet been resolved. Nor has it been established whether the same genes regulate MHC expression and T cell selection. Here, we assessed the impact of natural genetic variation on MHC expression and CD4∶CD8 lineage commitment using two genetic models in the rat. First, we mapped Quantitative Trait Loci (QTLs) associated with variation in MHC class I and II protein expression and the CD4∶CD8 T cell ratio in outbred Heterogeneous Stock rats. We identified 10 QTLs across the genome and found that QTLs for the individual traits colocalized within a region spanning the MHC. To identify the genes underlying these overlapping QTLs, we generated a large panel of MHC-recombinant congenic strains, and refined the QTLs to two adjacent intervals of ∼0.25 Mb in the MHC-I and II regions, respectively. An interaction between these intervals affected MHC class I expression as well as negative selection and lineage commitment of CD8 single-positive (SP) thymocytes. We mapped this effect to the transporter associated with antigen processing 2 (Tap2) in the MHC-II region and the classical MHC class I gene(s) (RT1-A) in the MHC-I region. This interaction was revealed by a recombination between RT1-A and Tap2, which occurred in 0.2% of the rats. Variants of Tap2 have previously been shown to influence the antigenicity of MHC class I molecules by altering the MHC class I ligandome. Our results show that a restricted peptide repertoire on MHC class I molecules leads to reduced negative selection of CD8SP cells. To our knowledge, this is the first study showing how a recombination between natural alleles of genes in the MHC influences lineage commitment of T cells. PMID:24586191

Vertical Finger Displacement Is Reduced in Index Finger Tapping During Repeated Bout Rate Enhancement.

PubMed

Mora-Jensen, Mark Holten; Madeleine, Pascal; Hansen, Ernst Albin

2017-10-01

The present study analyzed (a) whether a recently reported phenomenon of repeated bout rate enhancement in finger tapping (i.e., a cumulating increase in freely chosen finger tapping frequency following submaximal muscle activation in the form of externally unloaded voluntary tapping) could be replicated and (b) the hypotheses that the faster tapping was accompanied by changed vertical displacement of the fingertip and changed peak force during tapping. Right-handed, healthy, and recreationally active individuals (n = 24) performed two 3-min index finger tapping bouts at freely chosen tapping frequency, separated by 10-min rest. The recently reported phenomenon of repeated bout rate enhancement was replicated. The faster tapping (8.8 ± 18.7 taps/min, corresponding to 6.0 ± 11.0%, p = .033) was accompanied by reduced vertical displacement (1.6 ± 2.9 mm, corresponding to 6.3 ± 14.9%, p = .012) of the fingertip. Concurrently, peak force was unchanged. The present study points at separate control mechanisms governing kinematics and kinetics during finger tapping.

Eliciting Cervical Vestibular-Evoked Myogenic Potentials by Bone-Conducted Vibration via Various Tapping Sites.

PubMed

Tseng, Chia-Chen; Young, Yi-Ho

2016-01-01

This study compared bone-conducted vibration (BCV) cervical vestibular-evoked myogenic potentials (cVEMPs) via tapping at various skull sites in healthy subjects and patients with vestibular migraine (VM) to optimize stimulation conditions. Twenty healthy subjects underwent a series of cVEMP tests by BCV tapping via a minishaker at the Fz (forehead), Cz (vertex), and inion (occiput) sites in a randomized order of tapping sites. Another 20 VM patients were also enrolled in this study for comparison. All 20 healthy subjects had clear BCV cVEMPs when tapping at the inion (100%) or Cz (100%), but not at the Fz (75%). Mean p13 and n23 latencies from the Cz tapping were significantly longer than those from the Fz tapping, but not longer than those from the inion tapping. Unlike healthy subjects, tapping at the Cz (95%) elicited a significantly higher response rate of present cVEMPs than tapping at the inion (78%) in 20 VM patients (40 ears), because seven of nine VM ears with absent cVEMPs by inion tapping turned out to be present cVEMPs by Cz tapping. While both inion and Cz tapping elicited 100% response rate of cVEMPs for healthy individuals, Cz tapping had a higher response rate of cVEMPs than inion tapping for the VM group. In cases of total loss of saccular function, cVEMPs could not be activated by either inion or Cz tapping. However, if residual saccular function remains, Cz tapping may activate saccular afferents more efficiently than inion tapping.

Trefoil factor 2 (TFF2) deficiency in murine digestive tract influences the immune system.

PubMed

Baus-Loncar, Mirela; Schmid, Janinne; Lalani, El-Nasir; Rosewell, Ian; Goodlad, Robert A; Stamp, Gordon W H; Blin, Nikolaus; Kayademir, Tuncay

2005-01-01

The gastrointestinal trefoil factor family (TFF1, TFF2, TFF3) peptides are considered to play an important role in maintaining the integrity of the mucosa. The physiological role of TFF2 in the protection of the GI tract was investigated in TFF2 deficiency. TFF2-/- mice were generated and differential expression of various genes was assessed by using a mouse expression microarray, quantitative real time PCR, Northern blots or immunohistochemistry. On an mRNA level we found 128 differentially expressed genes. We observed modulation of a number of crucial genes involved in innate and adaptive immunity in the TFF2-/- mice. Expression of proteasomal subunits genes (LMP2, LMP7 and PSMB5) involved in the MHC class I presentation pathway were modulated indicating the formation of immunoproteasomes improving antigen presentation. Expression of one subunit of a transporter (TAP1) responsible for importing degraded antigens into ER was increased, similarly to the BAG2 gene that modulates chaperone activity in ER helping proper loading on MHC class I molecules. Several mouse defensin (cryptdin) genes coding important intestinal microbicidal proteins were up-regulated as a consequence of TFF2 deficiency. Normally moderate expression of TFF3 was highly increased in stomach. Copyright (c) 2005 S. Karger AG, Basel.

CD137 Stimulation Enhances Cetuximab-Induced Natural Killer: Dendritic Cell Priming of Antitumor T-Cell Immunity in Patients with Head and Neck Cancer.

PubMed

Srivastava, Raghvendra M; Trivedi, Sumita; Concha-Benavente, Fernando; Gibson, Sandra P; Reeder, Carly; Ferrone, Soldano; Ferris, Robert L

2017-02-01

Cetuximab, an EGFR-specific antibody (mAb), modestly improves clinical outcome in patients with head and neck cancer (HNC). Cetuximab mediates natural killer (NK) cell:dendritic cell (DC) cross-talk by cross-linking FcγRIIIa, which is important for inducing antitumor cellular immunity. Cetuximab-activated NK cells upregulate the costimulatory receptor CD137 (4-1BB), which, when triggered by agonistic mAb urelumab, might enhance NK-cell functions, to promote T-cell-based immunity. CD137 expression on tumor-infiltrating lymphocytes was evaluated in a prospective cetuximab neoadjuvant trial, and CD137 stimulation was evaluated in a phase Ib trial, in combining agonistic urelumab with cetuximab. Flow cytometry and cytokine release assays using NK cells and DC were used in vitro, testing the addition of urelumab to cetuximab-activated NK, DC, and cross presentation to T cells. CD137 agonist mAb urelumab enhanced cetuximab-activated NK-cell survival, DC maturation, and tumor antigen cross-presentation. Urelumab boosted DC maturation markers, CD86 and HLA DR, and antigen-processing machinery (APM) components TAP1/2, leading to increased tumor antigen cross-presentation. In neoadjuvant cetuximab-treated patients with HNC, upregulation of CD137 by intratumoral, cetuximab-activated NK cells correlated with FcγRIIIa V/F polymorphism and predicted clinical response. Moreover, immune biomarker modulation was observed in an open label, phase Ib clinical trial, of patients with HNC treated with cetuximab plus urelumab. These results suggest a beneficial effect of combination immunotherapy using cetuximab and CD137 agonist in HNC. Clin Cancer Res; 23(3); 707-16. ©2016 AACR. ©2016 American Association for Cancer Research.

Synchronized tapping facilitates learning sound sequences as indexed by the P300.

PubMed

Kamiyama, Keiko S; Okanoya, Kazuo

2014-01-01

The purpose of the present study was to determine whether and how single finger tapping in synchrony with sound sequences contributed to the auditory processing of them. The participants learned two unfamiliar sound sequences via different methods. In the tapping condition, they learned an auditory sequence while they tapped in synchrony with each sound onset. In the no tapping condition, they learned another sequence while they kept pressing a key until the sequence ended. After these learning sessions, we presented the two melodies again and recorded event-related potentials (ERPs). During the ERP recordings, 10% of the tones within each melody deviated from the original tones. An analysis of the grand average ERPs showed that deviant stimuli elicited a significant P300 in the tapping but not in the no-tapping condition. In addition, the significance of the P300 effect in the tapping condition increased as the participants showed highly synchronized tapping behavior during the learning sessions. These results indicated that single finger tapping promoted the conscious detection and evaluation of deviants within the learned sequences. The effect was related to individuals' musical ability to coordinate their finger movements along with external auditory events.

Synchronized tapping facilitates learning sound sequences as indexed by the P300

PubMed Central

Kamiyama, Keiko S.; Okanoya, Kazuo

2014-01-01

The purpose of the present study was to determine whether and how single finger tapping in synchrony with sound sequences contributed to the auditory processing of them. The participants learned two unfamiliar sound sequences via different methods. In the tapping condition, they learned an auditory sequence while they tapped in synchrony with each sound onset. In the no tapping condition, they learned another sequence while they kept pressing a key until the sequence ended. After these learning sessions, we presented the two melodies again and recorded event-related potentials (ERPs). During the ERP recordings, 10% of the tones within each melody deviated from the original tones. An analysis of the grand average ERPs showed that deviant stimuli elicited a significant P300 in the tapping but not in the no-tapping condition. In addition, the significance of the P300 effect in the tapping condition increased as the participants showed highly synchronized tapping behavior during the learning sessions. These results indicated that single finger tapping promoted the conscious detection and evaluation of deviants within the learned sequences. The effect was related to individuals’ musical ability to coordinate their finger movements along with external auditory events. PMID:25400564

NetCTLpan: pan-specific MHC class I pathway epitope predictions

PubMed Central

Larsen, Mette Voldby; Lundegaard, Claus; Nielsen, Morten

2010-01-01

Reliable predictions of immunogenic peptides are essential in rational vaccine design and can minimize the experimental effort needed to identify epitopes. In this work, we describe a pan-specific major histocompatibility complex (MHC) class I epitope predictor, NetCTLpan. The method integrates predictions of proteasomal cleavage, transporter associated with antigen processing (TAP) transport efficiency, and MHC class I binding affinity into a MHC class I pathway likelihood score and is an improved and extended version of NetCTL. The NetCTLpan method performs predictions for all MHC class I molecules with known protein sequence and allows predictions for 8-, 9-, 10-, and 11-mer peptides. In order to meet the need for a low false positive rate, the method is optimized to achieve high specificity. The method was trained and validated on large datasets of experimentally identified MHC class I ligands and cytotoxic T lymphocyte (CTL) epitopes. It has been reported that MHC molecules are differentially dependent on TAP transport and proteasomal cleavage. Here, we did not find any consistent signs of such MHC dependencies, and the NetCTLpan method is implemented with fixed weights for proteasomal cleavage and TAP transport for all MHC molecules. The predictive performance of the NetCTLpan method was shown to outperform other state-of-the-art CTL epitope prediction methods. Our results further confirm the importance of using full-type human leukocyte antigen restriction information when identifying MHC class I epitopes. Using the NetCTLpan method, the experimental effort to identify 90% of new epitopes can be reduced by 15% and 40%, respectively, when compared to the NetMHCpan and NetCTL methods. The method and benchmark datasets are available at http://www.cbs.dtu.dk/services/NetCTLpan/. Electronic supplementary material The online version of this article (doi:10.1007/s00251-010-0441-4) contains supplementary material, which is available to authorized users. PMID:20379710

Large-scale identification of c-MYC-associated proteins using a combined TAP/MudPIT approach.

PubMed

Koch, Heike B; Zhang, Ru; Verdoodt, Berlinda; Bailey, Aaron; Zhang, Chang-Dong; Yates, John R; Menssen, Antje; Hermeking, Heiko

2007-01-15

The c-MYC oncogene encodes a transcription factor, which is sufficient and necessary for the induction of cellular proliferation. However, the c-MYC protein is a relatively weak transactivator suggesting that it may have other functions. To identify protein interactors which may reveal new functions or represent regulators of c-MYC we systematically identified proteins associated with c-MYC in vivo using a proteomic approach. We combined tandem affinity purification (TAP) with the mass spectral multidimensional protein identification technology (MudPIT). Thereby, 221 c-MYC-associated proteins were identified. Among them were 17 previously known c-MYC-interactors. Selected new c-MYC-associated proteins (DBC-1, FBX29, KU70, MCM7, Mi2-beta/CHD4, RNA Pol II, RFC2, RFC3, SV40 Large T Antigen, TCP1alpha, U5-116kD, ZNF281) were confirmed independently. For association with MCM7, SV40 Large T Antigen and DBC-1 the functionally important MYC-box II region was required, whereas FBX29 and Mi2-beta interacted via MYC-box II and the BR-HLH-LZ motif. In addition, regulators of c-MYC activity were identified: ectopic expression of FBX29, an E3 ubiquitin ligase, decreased c-MYC protein levels and inhibited c-MYC transactivation, whereas knock-down of FBX29 elevated the concentration of c-MYC. Furthermore, sucrose gradient analysis demonstrated that c-MYC is present in numerous complexes with varying size and composition, which may accommodate the large number of new c-MYC-associated proteins identified here and mediate the diverse functions of c-MYC. Our results suggest that c-MYC, besides acting as a mitogenic transcription factor, regulates cellular proliferation by direct association with protein complexes involved in multiple synthetic processes required for cell division, as for example DNA-replication/repair and RNA-processing. Furthermore, this first comprehensive description of the c-MYC-associated sub-proteome will facilitate further studies aimed to elucidate the biology of c-MYC.

Reflex Augmentation of a Tap-Elicited Eyeblink: The Effects of Tone Frequency and Tap Intensity.

ERIC Educational Resources Information Center

Cohen, Michelle E.; And Others

1986-01-01

Describes two experiments that examined whether the amplitude of the human eyeblink by a mild tap between the eyebrows can be increased if a brief tone is presented simultaneously with the tap and how these effects change from newborn infants to adults. (HOD)

Effects of aging on control of timing and force of finger tapping.

PubMed

Sasaki, Hirokazu; Masumoto, Junya; Inui, Nobuyuki

2011-04-01

The present study examined whether the elderly produced a hastened or delayed tap with a negative or positive constant intertap interval error more frequently in self-paced tapping than in the stimulus-synchronized tapping for the 2 N target force at 2 or 4 Hz frequency. The analysis showed that, at both frequencies, the percentage of the delayed tap was larger in the self-paced tapping than in the stimulus-synchronized tapping, whereas the hastened tap showed the opposite result. At the 4 Hz frequency, all age groups had more variable intertap intervals during the self-paced tapping than during the stimulus-synchronized tapping, and the variability of the intertap intervals increased with age. Thus, although the increase in the frequency of delayed taps and variable intertap intervals in the self-paced tapping perhaps resulted from a dysfunction of movement timing in the basal ganglia with age, the decline in timing accuracy was somewhat improved by an auditory cue. The force variability of tapping at 4 Hz further increased with age, indicating an effect of aging on the control of force.

Yield modeling of acoustic charge transport transversal filters

NASA Technical Reports Server (NTRS)

Kenney, J. S.; May, G. S.; Hunt, W. D.

1995-01-01

This paper presents a yield model for acoustic charge transport transversal filters. This model differs from previous IC yield models in that it does not assume that individual failures of the nondestructive sensing taps necessarily cause a device failure. A redundancy in the number of taps included in the design is explained. Poisson statistics are used to describe the tap failures, weighted over a uniform defect density distribution. A representative design example is presented. The minimum number of taps needed to realize the filter is calculated, and tap weights for various numbers of redundant taps are calculated. The critical area for device failure is calculated for each level of redundancy. Yield is predicted for a range of defect densities and redundancies. To verify the model, a Monte Carlo simulation is performed on an equivalent circuit model of the device. The results of the yield model are then compared to the Monte Carlo simulation. Better than 95% agreement was obtained for the Poisson model with redundant taps ranging from 30% to 150% over the minimum.

[Application of PLA Method for Detection of p53/p63/p73 Complexes in Situ in Tumour Cells and Tumour Tissue].

PubMed

Hrabal, V; Nekulová, M; Nenutil, R; Holčaková, J; Coates, P J; Vojtěšek, B

2017-01-01

PLA (proximity ligation assay) can be used for detection of protein-protein interactions in situ directly in cells and tissues. Due to its high sensitivity and specificity it is useful for detection, localization and quantification of protein complexes with single molecule resolution. One of the mechanisms of mutated p53 gain of function is formation of proten-protein complexes with other members of p53 family - p63 and p73. These interactions influences chemosensitivity and invasivity of cancer cells and this is why these complexes are potential targets of anti-cancer therapy. The aim of this work is to detect p53/p63/p73 interactions in situ in tumour cells and tumour tissue using PLA method. Unique in-house antibodies for specific detection of p63 and p73 isoforms were developed and characterized. Potein complexes were detected using PLA in established cell lines SVK14, HCC1806 and FaDu and in paraffin sections of colorectal carcinoma tissue. Cell lines were also processed to paraffin blocks. p53/T-antigen and ΔNp63/T-antigen protein complexes were detected in SVK14 cells using PLA. Interactions of ΔNp63 and TAp73 isoforms were found in HCC1806 cell line with endogenous expression of these proteins. In FaDu cell line mut-p53/TAp73 complex was localized but not mut-p53/ΔNp63 complex. p53 tetramer was detected directly in colorectal cancer tissue. During development of PLA method for detection of protein complexes between p53 family members we detected interactions of p53 and p63 with T-antigen and mut-p53 and ΔNp63 with TAp73 tumour suppressor in tumour cell lines and p53 tetramers in paraffin sections of colorectal cancer tissue. PLA will be further used for detection of p53/p63, p53/p73 and p63/p73 interactions in tumour tissues and it could be also used for screening of compounds that can block formation of p53/p63/p73 protein complexes.Key words: p53 protein family - protein interaction mapping - immunofluorescence This work was supported by MEYS - NPS I - LO1413. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 13. 3. 2017Accepted: 26. 3. 2017.

Activation of antigen-specific cytotoxic T lymphocytes by beta 2-microglobulin or TAP1 gene disruption and the introduction of recipient-matched MHC class I gene in allogeneic embryonic stem cell-derived dendritic cells.

PubMed

Matsunaga, Yusuke; Fukuma, Daiki; Hirata, Shinya; Fukushima, Satoshi; Haruta, Miwa; Ikeda, Tokunori; Negishi, Izumi; Nishimura, Yasuharu; Senju, Satoru

2008-11-01

A method for the genetic modification of dendritic cells (DC) was previously established based on the in vitro differentiation of embryonic stem (ES) cells to DC (ES-DC). The unavailability of human ES cells genetically identical to the patients will be a problem in the future clinical application of this technology. This study attempted to establish a strategy to overcome this issue. The TAP1 or beta(2)-microglobulin (beta(2)m) gene was disrupted in 129 (H-2(b))-derived ES cells and then expression vectors for the H-2K(d) or beta(2)m-linked form of K(d) (beta2m-K(d)) were introduced, thus resulting in two types of genetically engineered ES-DC, TAP1(-/-)/K(d) ES-DC and beta(2)m(-/-)/beta(2)m-K(d) ES-DC. As intended, both of the transfectant ES-DC expressed K(d) but not the intrinsic H-2(b) haplotype-derived MHC class I. Beta(2)m(-/-)/beta(2)m-K(d) and TAP1(-/-)/K(d) ES-DC were not recognized by pre-activated H-2(b)-reactive CTL and did not prime H-2(b) reactive CTL in vitro or in vivo. Beta(2)m(-/-)/beta(2)m-K(d) ES-DC and TAP1(-/-)/K(d) ES-DC had a survival advantage in comparison to beta(2)m(+/-)/beta(2)m-K(d) ES-DC and TAP1(+/+)/K(d) ES-DC, when transferred into BALB/c mice. K(d)-restricted RSV-M2-derived peptide-loaded ES-DC could prime the epitope-specific CTL upon injection into the BALB/c mice, irrespective of the cell surface expression of intrinsic H-2(b) haplotype-encoded MHC class I. Beta(2)m(-/-)/beta(2)m-K(d) ES-DC were significantly more efficient in eliciting immunity against RSV M2 protein-expressing tumor cells than beta(2)m(+/-)/beta(2)m-K(d) ES-DC. The modification of the beta(2)m or TAP gene may therefore be an effective strategy to resolve the problem of HLA class I allele mismatch between human ES or induced pluripotent stem cells and the recipients to be treated.

Advanced analysis of finger-tapping performance: a preliminary study.

PubMed

Barut, Cağatay; Kızıltan, Erhan; Gelir, Ethem; Köktürk, Fürüzan

2013-06-01

The finger-tapping test is a commonly employed quantitative assessment tool used to measure motor performance in the upper extremities. This task is a complex motion that is affected by external stimuli, mood and health status. The complexity of this task is difficult to explain with a single average intertap-interval value (time difference between successive tappings) which only provides general information and neglects the temporal effects of the aforementioned factors. This study evaluated the time course of average intertap-interval values and the patterns of variation in both the right and left hands of right-handed subjects using a computer-based finger-tapping system. Cross sectional study. Thirty eight male individuals aged between 20 and 28 years (Mean±SD = 22.24±1.65) participated in the study. Participants were asked to perform single-finger-tapping test for 10 seconds of test period. Only the results of right-handed (RH) 35 participants were considered in this study. The test records the time of tapping and saves data as the time difference between successive tappings for further analysis. The average number of tappings and the temporal fluctuation patterns of the intertap-intervals were calculated and compared. The variations in the intertap-interval were evaluated with the best curve fit method. An average tapping speed or tapping rate can reliably be defined for a single-finger tapping test by analysing the graphically presented data of the number of tappings within the test period. However, a different presentation of the same data, namely the intertap-interval values, shows temporal variation as the number of tapping increases. Curve fitting applications indicate that the variation has a biphasic nature. The measures obtained in this study reflect the complex nature of the finger-tapping task and are suggested to provide reliable information regarding hand performance. Moreover, the equation reflects both the variations in and the general patterns associated with the task.

Cetuximab-activated natural killer (NK) and dendritic cells (DC) collaborate to trigger tumor antigen-specific T cell immunity in head and neck cancer patients

PubMed Central

Srivastava, Raghvendra M.; Lee, Steve C.; Filho, Pedro A. Andrade; Lord, Christopher A.; Jie, Hyun-bae; Davidson, H. Carter; López-Albaitero, Andrés; Gibson, Sandra P.; Gooding, William E.; Ferrone, Soldano; Ferris, Robert L.

2013-01-01

Purpose Tumor antigen (TA)-specific monoclonal antibodies (mAb) block oncogenic signaling and induce Fcγ receptor (FcγR)-mediated cytotoxicity. However, the role of CD8+ cytotoxic T lymphocyte (CTL) and FcγR in initiating innate and adaptive immune responses in mAb-treated human cancer patients is still emerging. Experimental Design FcγRIIIa codon 158 polymorphism was correlated with survival in 107 cetuximab-treated head and neck cancer (HNC) patients. Flow cytometry was performed to quantify EGFR-specific T cells in cetuximab-treated HNC patients. The effect of cetuximab on NK cell, dendritic cell (DC), and T cell activation was measured using IFN-γ release assays and flow cytometry. Results FcγR IIIa polymorphism did not predict clinical outcome in cetuximab-treated HNC patients, however elevated circulating EGFR -specific CD8+ 853-861 T cells were found in cetuximab-treated HNC patients (p<0.005). Cetuximab promoted EGFR-specific cellular immunity through the interaction of EGFR+ tumor cells and FcγRIIIa on NK cells, but not on the polymorphism per se. Cetuximab-activated NK cells induced IFN-γ dependent expression of DC maturation markers, antigen presentation machinery (APM) components such as TAP-1/2, and Th1 chemokines through NKG2D/MICA binding. Cetuximab initiated adaptive immune responses via NK-cell induced DC maturation, which enhanced cross-presentation to CTL specific for EGFR as well as another TA, MAGE-3. Conclusion Cetuximab-activated NK cells promote DC maturation and CD8+ T cell priming, leading to TA spreading and Th1 cytokine release through ‘NK-DC cross-talk.’ FcγRIIIa polymorphism did not predict clinical response to cetuximab, but was necessary for NK-DC interaction and mAb induced cross-presentation. EGFR-specific T cells in cetuximab treated HNC patients may contribute to clinical response. PMID:23444227

Human and Murine Clonal CD8+ T Cell Expansions Arise during Tuberculosis Because of TCR Selection

PubMed Central

Nunes-Alves, Cláudio; Booty, Matthew G.; Carpenter, Stephen M.; Rothchild, Alissa C.; Martin, Constance J.; Desjardins, Danielle; Steblenko, Katherine; Kløverpris, Henrik N.; Madansein, Rajhmun; Ramsuran, Duran; Leslie, Alasdair; Correia-Neves, Margarida; Behar, Samuel M.

2015-01-01

The immune system can recognize virtually any antigen, yet T cell responses against several pathogens, including Mycobacterium tuberculosis, are restricted to a limited number of immunodominant epitopes. The host factors that affect immunodominance are incompletely understood. Whether immunodominant epitopes elicit protective CD8+ T cell responses or instead act as decoys to subvert immunity and allow pathogens to establish chronic infection is unknown. Here we show that anatomically distinct human granulomas contain clonally expanded CD8+ T cells with overlapping T cell receptor (TCR) repertoires. Similarly, the murine CD8+ T cell response against M. tuberculosis is dominated by TB10.44-11-specific T cells with extreme TCRβ bias. Using a retrogenic model of TB10.44-11-specific CD8+ T cells, we show that TCR dominance can arise because of competition between clonotypes driven by differences in affinity. Finally, we demonstrate that TB10.4-specific CD8+ T cells mediate protection against tuberculosis, which requires interferon-γ production and TAP1-dependent antigen presentation in vivo. Our study of how immunodominance, biased TCR repertoires, and protection are inter-related, provides a new way to measure the quality of T cell immunity, which if applied to vaccine evaluation, could enhance our understanding of how to elicit protective T cell immunity. PMID:25945999

Human and Murine Clonal CD8+ T Cell Expansions Arise during Tuberculosis Because of TCR Selection.

PubMed

Nunes-Alves, Cláudio; Booty, Matthew G; Carpenter, Stephen M; Rothchild, Alissa C; Martin, Constance J; Desjardins, Danielle; Steblenko, Katherine; Kløverpris, Henrik N; Madansein, Rajhmun; Ramsuran, Duran; Leslie, Alasdair; Correia-Neves, Margarida; Behar, Samuel M

2015-05-01

The immune system can recognize virtually any antigen, yet T cell responses against several pathogens, including Mycobacterium tuberculosis, are restricted to a limited number of immunodominant epitopes. The host factors that affect immunodominance are incompletely understood. Whether immunodominant epitopes elicit protective CD8+ T cell responses or instead act as decoys to subvert immunity and allow pathogens to establish chronic infection is unknown. Here we show that anatomically distinct human granulomas contain clonally expanded CD8+ T cells with overlapping T cell receptor (TCR) repertoires. Similarly, the murine CD8+ T cell response against M. tuberculosis is dominated by TB10.44-11-specific T cells with extreme TCRβ bias. Using a retro genic model of TB10.44-11-specific CD8+ Tcells, we show that TCR dominance can arise because of competition between clonotypes driven by differences in affinity. Finally, we demonstrate that TB10.4-specific CD8+ T cells mediate protection against tuberculosis, which requires interferon-γ production and TAP1-dependent antigen presentation in vivo. Our study of how immunodominance, biased TCR repertoires, and protection are inter-related, provides a new way to measure the quality of T cell immunity, which if applied to vaccine evaluation, could enhance our understanding of how to elicit protective T cell immunity.

Interaction of TAPBPR, a tapasin homolog, with MHC-I molecules promotes peptide editing.

PubMed

Morozov, Giora I; Zhao, Huaying; Mage, Michael G; Boyd, Lisa F; Jiang, Jiansheng; Dolan, Michael A; Venna, Ramesh; Norcross, Michael A; McMurtrey, Curtis P; Hildebrand, William; Schuck, Peter; Natarajan, Kannan; Margulies, David H

2016-02-23

Peptide loading of major histocompatibility complex class I (MHC-I) molecules is central to antigen presentation, self-tolerance, and CD8(+) T-cell activation. TAP binding protein, related (TAPBPR), a widely expressed tapasin homolog, is not part of the classical MHC-I peptide-loading complex (PLC). Using recombinant MHC-I molecules, we show that TAPBPR binds HLA-A*02:01 and several other MHC-I molecules that are either peptide-free or loaded with low-affinity peptides. Fluorescence polarization experiments establish that TAPBPR augments peptide binding by MHC-I. The TAPBPR/MHC-I interaction is reversed by specific peptides, related to their affinity. Mutational and small-angle X-ray scattering (SAXS) studies confirm the structural similarities of TAPBPR with tapasin. These results support a role of TAPBPR in stabilizing peptide-receptive conformation(s) of MHC-I, permitting peptide editing.

Interaction of TAPBPR, a tapasin homolog, with MHC-I molecules promotes peptide editing

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

Morozov, Giora I.; Zhao, Huaying; Mage, Michael G.

Peptide loading of major histocompatibility complex class I (MHC-I) molecules is central to antigen presentation, self-tolerance, and CD8 + T-cell activation. TAP binding protein, related (TAPBPR), a widely expressed tapasin homolog, is not part of the classical MHC-I peptide-loading complex (PLC). Using recombinant MHC-I molecules, we show that TAPBPR binds HLA-A*02:01 and several other MHC-I molecules that are either peptide-free or loaded with low-affinity peptides. Fluorescence polarization experiments establish that TAPBPR augments peptide binding by MHC-I. The TAPBPR/MHC-I interaction is reversed by specific peptides, related to their affinity. Mutational and small-angle X-ray scattering (SAXS) studies confirm the structural similarities ofmore » TAPBPR with tapasin. These results support a role of TAPBPR in stabilizing peptide-receptive conformation(s) of MHC-I, permitting peptide editing.« less

Interaction of TAPBPR, a tapasin homolog, with MHC-I molecules promotes peptide editing

DOE PAGES

Morozov, Giora I.; Zhao, Huaying; Mage, Michael G.; ...

2016-02-11

Peptide loading of major histocompatibility complex class I (MHC-I) molecules is central to antigen presentation, self-tolerance, and CD8 + T-cell activation. TAP binding protein, related (TAPBPR), a widely expressed tapasin homolog, is not part of the classical MHC-I peptide-loading complex (PLC). Using recombinant MHC-I molecules, we show that TAPBPR binds HLA-A*02:01 and several other MHC-I molecules that are either peptide-free or loaded with low-affinity peptides. Fluorescence polarization experiments establish that TAPBPR augments peptide binding by MHC-I. The TAPBPR/MHC-I interaction is reversed by specific peptides, related to their affinity. Mutational and small-angle X-ray scattering (SAXS) studies confirm the structural similarities ofmore » TAPBPR with tapasin. These results support a role of TAPBPR in stabilizing peptide-receptive conformation(s) of MHC-I, permitting peptide editing.« less

Colostomy with Transversus Abdominis Plane Block

PubMed Central

Tekelioğlu, Ümit Yaşar; Demirhan, Abdullah; Şit, Mustafa; Kurt, Adem Deniz; Bilgi, Murat; Koçoğlu, Hasan

2015-01-01

Transversus abdominis plane (TAP) block is one of the abdominal field block. The TAP block is used for both anaesthetic management and post-operative pain therapy in lower abdominal surgery. TAP block is a procedure in which local anaesthetic agents are applied to the anatomic neurofacial space between the internal oblique and the transversus abdominis muscle. TAP block is a good method for post-operative pain control as well as allows for short operations involving the abdominal area. In this article, a case of colostomy under TAP block is presented. PMID:27366540

Tap Arduino: An Arduino microcontroller for low-latency auditory feedback in sensorimotor synchronization experiments.

PubMed

Schultz, Benjamin G; van Vugt, Floris T

2016-12-01

Timing abilities are often measured by having participants tap their finger along with a metronome and presenting tap-triggered auditory feedback. These experiments predominantly use electronic percussion pads combined with software (e.g., FTAP or Max/MSP) that records responses and delivers auditory feedback. However, these setups involve unknown latencies between tap onset and auditory feedback and can sometimes miss responses or record multiple, superfluous responses for a single tap. These issues may distort measurements of tapping performance or affect the performance of the individual. We present an alternative setup using an Arduino microcontroller that addresses these issues and delivers low-latency auditory feedback. We validated our setup by having participants (N = 6) tap on a force-sensitive resistor pad connected to the Arduino and on an electronic percussion pad with various levels of force and tempi. The Arduino delivered auditory feedback through a pulse-width modulation (PWM) pin connected to a headphone jack or a wave shield component. The Arduino's PWM (M = 0.6 ms, SD = 0.3) and wave shield (M = 2.6 ms, SD = 0.3) demonstrated significantly lower auditory feedback latencies than the percussion pad (M = 9.1 ms, SD = 2.0), FTAP (M = 14.6 ms, SD = 2.8), and Max/MSP (M = 15.8 ms, SD = 3.4). The PWM and wave shield latencies were also significantly less variable than those from FTAP and Max/MSP. The Arduino missed significantly fewer taps, and recorded fewer superfluous responses, than the percussion pad. The Arduino captured all responses, whereas at lower tapping forces, the percussion pad missed more taps. Regardless of tapping force, the Arduino outperformed the percussion pad. Overall, the Arduino is a high-precision, low-latency, portable, and affordable tool for auditory experiments.

RNA Seq analysis for transcriptome profiling in response to classical swine fever vaccination in indigenous and crossbred pigs.

PubMed

Pathak, Shalu Kumari; Kumar, Amit; Bhuwana, G; Sah, Vaishali; Upmanyu, Vikramadiya; Tiwari, A K; Sahoo, A P; Sahoo, A R; Wani, Sajjad A; Panigrahi, Manjit; Sahoo, N R; Kumar, Ravi

2017-09-01

In present investigation, differential expression of transcriptome after classical swine fever (CSF) vaccination has been explored at the cellular level in crossbred and indigenous (desi) piglets. RNA Sequencing by Expectation-Maximization (RSEM) package was used to quantify gene expression from RNA Sequencing data, and differentially expressed genes (DEGs) were identified using EBSeq, DESeq2, and edgeR softwares. After analysis, 5222, 6037, and 6210 common DEGs were identified in indigenous post-vaccinated verses pre-vaccinated, crossbred post-vaccinated verses pre-vaccinated, and post-vaccinated crossbred verses indigenous pigs, respectively. Functional annotation of these DEGs showed enrichment of antigen processing-cross presentation, B cell receptor signaling, T cell receptor signaling, NF-κB signaling, and TNF signaling pathways. The interaction network among the immune genes included more number of genes with greater connectivity in vaccinated crossbred than the indigenous piglets. Higher expression of IRF3, IL1β, TAP1, CSK, SLA2, SLADM, and NF-kB in crossbred piglets in comparison to indigenous explains the better humoral response observed in crossbred piglets. Here, we predicted that the processed CSFV antigen through the T cell receptor signaling cascade triggers the B cell receptor-signaling pathway to finally activate MAPK kinase and NF-κB signaling pathways in B cell. This activation results in expression of genes/transcription factors that lead to B cell ontogeny, auto immunity and immune response through antibody production. Further, immunologically important genes were validated by qRT-PCR.

Quantitative assessment of finger tapping characteristics in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease.

PubMed

Roalf, David R; Rupert, Petra; Mechanic-Hamilton, Dawn; Brennan, Laura; Duda, John E; Weintraub, Daniel; Trojanowski, John Q; Wolk, David; Moberg, Paul J

2018-06-01

Fine motor impairments are common in neurodegenerative disorders, yet standardized, quantitative measurements of motor abilities are uncommonly used in neurological practice. Thus, understanding and comparing fine motor abilities across disorders have been limited. The current study compared differences in finger tapping, inter-tap interval, and variability in Alzheimer's disease (AD), Parkinson's disease (PD), mild cognitive impairment (MCI), and healthy older adults (HOA). Finger tapping was measured using a highly sensitive light-diode finger tapper. Total number of finger taps, inter-tap interval, and intra-individual variability (IIV) of finger tapping was measured and compared in AD (n = 131), PD (n = 63), MCI (n = 46), and HOA (n = 62), controlling for age and sex. All patient groups had fine motor impairments relative to HOA. AD and MCI groups produced fewer taps with longer inter-tap interval and higher IIV compared to HOA. The PD group, however, produced more taps with shorter inter-tap interval and higher IIV compared to HOA. Disease-specific changes in fine motor function occur in the most common neurodegenerative diseases. The findings suggest that alterations in finger tapping patterns are common in AD, MCI, and PD. In addition, the present results underscore the importance of motor dysfunction even in neurodegenerative disorders without primary motor symptoms.

Using Math With Maple Sugaring.

ERIC Educational Resources Information Center

Christenson, Gary

1984-01-01

Suggest several math activities using the simple technique of tapping a sugar maple tree for sap. Information and activities presented are useful in tapping one or two trees on school property, helping students who tap trees at home, or leading a field trip to a nearby maple sugaring site. (ERB)

FPGA Based "Intelligent Tap" Device for Real-Time Ethernet Network Monitoring

NASA Astrophysics Data System (ADS)

Cupek, Rafał; Piękoś, Piotr; Poczobutt, Marcin; Ziębiński, Adam

This paper describes an "Intelligent Tap" - hardware device dedicated to support real-time Ethernet networks monitoring. Presented solution was created as a student project realized in Institute of Informatics, Silesian University of Technology with support from Softing A.G company. Authors provide description of realized FPGA based "Intelligent Tap" architecture dedicated for Real-Time Ethernet network monitoring systems. The practical device realization and feasibility study conclusions are presented also.

Vestibular evoked myogenic potentials in response to lateral skull taps are dependent on two different mechanisms.

PubMed

Brantberg, Krister; Westin, Magnus; Löfqvist, Lennart; Verrecchia, Luca; Tribukait, Arne

2009-05-01

To explore the mechanisms for skull tap induced vestibular evoked myogenic potentials (VEMP). The muscular responses were recorded over both sternocleidomastoid (SCM) muscles using skin electrodes. A skull tapper which provided a constant stimulus intensity was used to test cervical vestibular evoked myogenic potentials (VEMP) in response to lateral skull taps in healthy subjects (n=10) and in patients with severe unilateral loss of vestibular function (n=10). Skull taps applied approximately 2 cm above the outer ear canal caused highly reproducible VEMP. There were differences in VEMP in both normals and patients depending on side of tapping. In normals, there was a positive-negative ("normal") VEMP on the side contra-lateral to the skull tapping, but no significant VEMP ipsi-laterally. In patients, skull taps above the lesioned ear caused a contra-lateral positive-negative VEMP (as it did in the normals), in addition there was an ipsi-lateral negative-positive ("inverted") VEMP. When skull taps were presented above the healthy ear there was only a small contra-lateral positive-negative VEMP but, similar to the normals, no VEMP ipsi-laterally. The present data, in conjunction with earlier findings, support a theory that skull-tap VEMP responses are mediated by two different mechanisms. It is suggested that skull tapping causes both a purely ipsi-lateral stimulus side independent SCM response and a bilateral and of opposite polarity SCM response that is stimulus side dependent. Possibly, the skull tap induced VEMP responses are the sum of a stimulation of two species of vestibular receptors, one excited by vibration (which is rather stimulus site independent) and one excited by translation (which is more stimulus site dependent). Skull-tap VEMP probably have two different mechanisms. Separation of the two components might reveal the status of different labyrinthine functions.

Inhibition of serine-peptidase activity enhances the generation of a survivin-derived HLA-A2-presented CTL epitope in colon-carcinoma cells.

PubMed

Preta, G; Marescotti, D; Fortini, C; Carcoforo, P; Castelli, C; Masucci, M; Gavioli, R

2008-12-01

Cytotoxic T lymphocytes eliminate tumor cells expressing antigenic peptides in the context of MHC-I molecules. Peptides are generated during protein degradation by the proteasome and resulting products, surviving cytosolic amino-peptidases activity, may be presented by MHC-I molecules. The MHC-I processing pathway is altered in a large number of malignancies and modulation of antigen generation is one strategy employed by cells to evade immune control. In this study we analyzed the generation and presentation of a survivin-derived CTL epitope in HLA-A2-positive colon-carcinoma cells. Although all cell lines expressed the anti-apoptotic protein survivin, some tumors were poorly recognized by ELTLGEFLKL (ELT)-specific CTL cultures. The expression of MHC-I or TAP molecules was similar in all cell lines suggesting that tumors not recognized by CTLs may present defects in the generation of the ELT-epitope which could be due either to lack of generation or to subsequent degradation of the epitope. The cells were analyzed for the expression and the activity of extra-proteasomal peptidases. A significant overexpression and higher activity of TPPII was observed in colon-carcinoma cells which are not killed by ELT-specific CTLs, suggesting a possible role of TPPII in the degradation of the ELT-epitope. To confirm the role of TPPII in the degradation of the ELT-peptide, we showed that treatment of colon-carcinoma cells with a TPPII inhibitor resulted in a dose-dependent increased sensitivity to ELT-specific CTLs. These results suggest that TPPII is involved in degradation of the ELT-peptide, and its overexpression may contribute to the immune escape of colon-carcinoma cells.

The occurrence of antibiotic resistance genes in tap water - a review

NASA Astrophysics Data System (ADS)

Siedlecka, Agata

2018-02-01

The study presents a review of the occurrence of genetic determinants of antibiotic resistance in tap water. The aim of this study was also to compare the applied methods for antibiotic resistance genes (ARGs) investigations in tap water. As the concentration of ARGs in treated, drinking water is expected to be very low and may cause problems in a standard isolation procedure, the special emphasis is placed on the applied procedures of DNA extraction and their efficiency. The study presents the first attempts to obtain DNA directly from tap water. Further efforts must be put to determine the final amount of obtained DNA and the presence of chosen ARGs among the molecules.

Evaluation of primary stability of self-tapping and non-self-tapping dental implants. A 12-week clinical study.

PubMed

Marković, Aleksa; Calvo-Guirado, José Luís; Lazić, Zoran; Gómez-Moreno, Gerardo; Ćalasan, Dejan; Guardia, Javier; Čolic, Snježana; Aguilar-Salvatierra, Antonio; Gačić, Bojan; Delgado-Ruiz, Rafael; Janjić, Bojan; Mišić, Tijana

2013-06-01

The aim of this study was to investigate the relationship between surgical techniques and implant macro-design (self-tapping/non-self-tapping) for the optimization of implant stability in the low-density bone present in the posterior maxilla using resonance frequency analysis (RFA). A total of 102 implants were studied. Fifty-six self-tapping BlueSkyBredent® (Bredent GmbH&Co.Kg®, Senden, Germany) and 56 non-self-tapping Standard Plus Straumann® (Institut Straumann AG®, Waldenburg, Switzerland) were placed in the posterior segment of the maxilla. Implants of both types were placed in sites prepared with either lateral bone-condensing or with bone-drilling techniques. Implant stability measurements were performed using RFA immediately after implant placement and weekly during a 12-week follow-up period. Both types of implants placed after bone condensing achieved significantly higher stability immediately after surgery, as well as during the entire 12-week observation period compared with those placed following bone drilling. After bone condensation, there were no significant differences in primary stability or in implant stability after the first week between both implant types. From 2 to 12 postoperative weeks, significantly higher stability was shown by self-tapping implants. After bone drilling, self-tapping implants achieved significantly higher stability than non-self-tapping implants during the entire follow-up period. The outcomes of the present study indicate that bone drilling is not an effective technique for improving implant stability and, following this technique, the use of self-tapping implants is highly recommended. Implant stability optimization in the soft bone can be achieved by lateral bone-condensing technique, regardless of implant macro-design. © 2011 Wiley Periodicals, Inc.

What is the risk of infecting a cerebrospinal fluid-diverting shunt with percutaneous tapping?

PubMed

Spiegelman, Lindsey; Asija, Richa; Da Silva, Stephanie L; Krieger, Mark D; McComb, J Gordon

2014-10-01

Most CSF-diverting shunt systems have an access port that can be percutaneously tapped. Tapping the shunt can yield valuable information as to its function and whether an infection is present. The fear of causing a shunt infection by tapping may limit the physician's willingness to do so. The authors of this study investigate the risk of infecting a shunt secondary to percutaneous tapping. Following institutional review board approval, CSF specimens obtained from tapping an indwelling CSF-diverting shunt during the 2011 and 2012 calendar years were identified and matched with clinical information. A culture-positive CSF sample was defined as an infection. If results were equivocal, such as a broth-only-positive culture, a repeat CSF specimen was examined. The CSF was obtained by tapping the shunt access port with a 25-gauge butterfly needle after prepping the unshaven skin with chlorhexidine. During the study period, 266 children underwent 542 shunt taps. With 541 taps, no clinical evidence of a subsequent shunt infection was found. One child's CSF went from sterile to infected 11 days later; however, this patient had redness along the shunt tract at the time of the initial sterile tap. The risk of infection from tapping a shunt is remote if the procedure is done correctly.

Studies to overcome the manufacturing problems in blast furnace tap hole clay of Integrated Steel Plants: Experimental approach

NASA Astrophysics Data System (ADS)

Siva kumar, R.; Mohammed, Raffi; Srinivasa Rao, K.

2018-03-01

Integrated Steel Plants commonly uses Blast Furnace route for iron production which accounts for over 60 % of the world iron output. Blast Furnace runs for ten to twenty years without repairing hearth walls and Tap Hole (TH). Tap hole is an outlet for hot metal produced in a Blast Furnace and run from the shell of the furnace into the interior allowing access to the molten material. Tapping is the term used for drilling a hole through the tap hole which allows the molten iron and slag to flow out. In Iron making process, removal of liquid iron from furnace and sending it for steel making is known as cast house practice. For tapping liquid iron and operating the tap hole requires a special type of clay. Tap hole clay (THC) used to stop the flow of liquid iron and slag from the blast furnace. Present work deals with the study on manufacturing of THC at Visakhapatnam Steel Plant and problems related to manufacturing. Experiments were conducted to solve the identified problems and results are furnished in detail. The findings can improve the manufacturing process and improve the productivity of tap hole clay.

Getting the lead out: understanding risks in the distribution ...

EPA Pesticide Factsheets

This presentation discusses the importance of the water distribution system as a component of the source-to-tap continuum in public health protection. Issues covered include: understanding source water quality changes and their impacts throughout the system; use of mitigation measures such as filters); and holistic approaches and/or strategies that could be used to avoid unintended consequences of decisions from source to tap. Invited presentation on topics indicated as of interest. With exposure to lead as the context, this presentation discusses the importance of the water distribution system as a component of the source-to-tap continuum in public health protection. Issues covered include: understanding source water quality changes and their impacts throughout the system; use of mitigation measures such as filters); and holistic approaches and/or strategies that could be used to avoid unintended consequences of decisions from source to tap.

X-ray microtomography study of the compaction process of rods under tapping.

PubMed

Fu, Yang; Xi, Yan; Cao, Yixin; Wang, Yujie

2012-05-01

We present an x-ray microtomography study of the compaction process of cylindrical rods under tapping. The process is monitored by measuring the evolution of the orientational order parameter, local, and overall packing densities as a function of the tapping number for different tapping intensities. The slow relaxation dynamics of the orientational order parameter can be well fitted with a stretched-exponential law with stretching exponents ranging from 0.9 to 1.6. The corresponding relaxation time versus tapping intensity follows an Arrhenius behavior which is reminiscent of the slow dynamics in thermal glassy systems. We also investigated the boundary effect on the ordering process and found that boundary rods order faster than interior ones. In searching for the underlying mechanism of the slow dynamics, we estimated the initial random velocities of the rods under tapping and found that the ordering process is compatible with a diffusion mechanism. The average coordination number as a function of the tapping number at different tapping intensities has also been measured, which spans a range from 6 to 8.

APPLICATION OF EPANET TO UNDERSTAND LEAD ...

EPA Pesticide Factsheets

This presentation describes the factors affecting lead concentration in tap water using an EPANET hydraulic model for a simplified home model, a realistic home model, and EPA's experimental home plumbing system. This presentation describes the factors affecting lead concentration in tap water using an EPANET hydraulic model.

Tunable complex-valued multi-tap microwave photonic filter based on single silicon-on-insulator microring resonator.

PubMed

Lloret, Juan; Sancho, Juan; Pu, Minhao; Gasulla, Ivana; Yvind, Kresten; Sales, Salvador; Capmany, José

2011-06-20

A complex-valued multi-tap tunable microwave photonic filter based on single silicon-on-insulator microring resonator is presented. The degree of tunability of the approach involving two, three and four taps is theoretical and experimentally characterized, respectively. The constraints of exploiting the optical phase transfer function of a microring resonator aiming at implementing complex-valued multi-tap filtering schemes are also reported. The trade-off between the degree of tunability without changing the free spectral range and the number of taps is studied in-depth. Different window based scenarios are evaluated for improving the filter performance in terms of the side-lobe level.

Toxic effects of triazophos on rare minnow (Gobiocypris rarus) embryos and larvae.

PubMed

Zhu, Bin; Gong, Yu-Xin; Liu, Lei; Li, Dong-Liang; Wang, Yuan; Ling, Fei; Wang, Gao-Xue

2014-08-01

Triazophos (TAP) has been widely used in agriculture for controlling insect pests and is a known organophosphorus pesticide. Due to TAP characteristics, such as high chemical and photochemical stability, its potential toxicity to aquatic organisms has gained great interest. To explore the potential developmental toxicity of TAP, Gobiocypris rarus embryos and larvae were exposed to various concentrations of TAP (0.1-15 mg L(-1)) until 72 h. Results showed that values of 72 h LC50 and EC50 were 7.44 and 5.60 mg L(-1) for embryos, 2.52 and 1.37 mg L(-1) for larvae. Increased malformation, decreased heart rate and body length provide a gradual concentration-dependent pattern. Enzyme activities and mRNA levels were significantly changed even at low concentration (0.05 mg L(-1) for embryos and 0.01 mg L(-(1) for larvae). Overall, the present study points out that TAP is likely a risk to the early development of G. rarus. The information presented in this study will be helpful in better understanding the toxicity induced by TAP in fish embryos and larvae. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bi-harmonic cantilever design for improved measurement sensitivity in tapping-mode atomic force microscopy.

PubMed

Loganathan, Muthukumaran; Bristow, Douglas A

2014-04-01

This paper presents a method and cantilever design for improving the mechanical measurement sensitivity in the atomic force microscopy (AFM) tapping mode. The method uses two harmonics in the drive signal to generate a bi-harmonic tapping trajectory. Mathematical analysis demonstrates that the wide-valley bi-harmonic tapping trajectory is as much as 70% more sensitive to changes in the sample topography than the standard single-harmonic trajectory typically used. Although standard AFM cantilevers can be driven in the bi-harmonic tapping trajectory, they require large forcing at the second harmonic. A design is presented for a bi-harmonic cantilever that has a second resonant mode at twice its first resonant mode, thereby capable of generating bi-harmonic trajectories with small forcing signals. Bi-harmonic cantilevers are fabricated by milling a small cantilever on the interior of a standard cantilever probe using a focused ion beam. Bi-harmonic drive signals are derived for standard cantilevers and bi-harmonic cantilevers. Experimental results demonstrate better than 30% improvement in measurement sensitivity using the bi-harmonic cantilever. Images obtained through bi-harmonic tapping exhibit improved sharpness and surface tracking, especially at high scan speeds and low force fields.

Egocentric Temporal Action Proposals.

PubMed

Shao Huang; Weiqiang Wang; Shengfeng He; Lau, Rynson W H

2018-02-01

We present an approach to localize generic actions in egocentric videos, called temporal action proposals (TAPs), for accelerating the action recognition step. An egocentric TAP refers to a sequence of frames that may contain a generic action performed by the wearer of a head-mounted camera, e.g., taking a knife, spreading jam, pouring milk, or cutting carrots. Inspired by object proposals, this paper aims at generating a small number of TAPs, thereby replacing the popular sliding window strategy, for localizing all action events in the input video. To this end, we first propose to temporally segment the input video into action atoms, which are the smallest units that may contain an action. We then apply a hierarchical clustering algorithm with several egocentric cues to generate TAPs. Finally, we propose two actionness networks to score the likelihood of each TAP containing an action. The top ranked candidates are returned as output TAPs. Experimental results show that the proposed TAP detection framework performs significantly better than relevant approaches for egocentric action detection.

More than just tapping: index finger-tapping measures procedural learning in schizophrenia.

PubMed

Da Silva, Felipe N; Irani, Farzin; Richard, Jan; Brensinger, Colleen M; Bilker, Warren B; Gur, Raquel E; Gur, Ruben C

2012-05-01

Finger-tapping has been widely studied using behavioral and neuroimaging paradigms. Evidence supports the use of finger-tapping as an endophenotype in schizophrenia, but its relationship with motor procedural learning remains unexplored. To our knowledge, this study presents the first use of index finger-tapping to study procedural learning in individuals with schizophrenia or schizoaffective disorder (SCZ/SZA) as compared to healthy controls. A computerized index finger-tapping test was administered to 1169 SCZ/SZA patients (62% male, 88% right-handed), and 689 healthy controls (40% male, 93% right-handed). Number of taps per trial and learning slopes across trials for the dominant and non-dominant hands were examined for motor speed and procedural learning, respectively. Both healthy controls and SCZ/SZA patients demonstrated procedural learning for their dominant hand but not for their non-dominant hand. In addition, patients showed a greater capacity for procedural learning even though they demonstrated more variability in procedural learning compared to healthy controls. Left-handers of both groups performed better than right-handers and had less variability in mean number of taps between non-dominant and dominant hands. Males also had less variability in mean tap count between dominant and non-dominant hands than females. As expected, patients had a lower mean number of taps than healthy controls, males outperformed females and dominant-hand trials had more mean taps than non-dominant hand trials in both groups. The index finger-tapping test can measure both motor speed and procedural learning, and motor procedural learning may be intact in SCZ/SZA patients. Copyright © 2012 Elsevier B.V. All rights reserved.

The 3-Second Rule in Hereditary Pure Cerebellar Ataxia: A Synchronized Tapping Study

PubMed Central

Matsuda, Shunichi; Matsumoto, Hideyuki; Furubayashi, Toshiaki; Hanajima, Ritsuko; Tsuji, Shoji; Ugawa, Yoshikazu; Terao, Yasuo

2015-01-01

The ‘3-second rule’ has been proposed based on miscellaneous observations that a time period of around 3 seconds constitutes the fundamental unit of time related to the neuro-cognitive machinery in normal humans. The aim of paper was to investigate the temporal processing in patients with spinocerebellar ataxia type 6 (SCA6) and SCA31, pure cerebellar types of spinocerebellar degeneration, using a synchronized tapping task. Seventeen SCA patients (11 SCA6, 6 SCA31) and 17 normal age-matched volunteers participated. The task required subjects to tap a keyboard in synchrony with sequences of auditory stimuli presented at fixed interstimulus intervals (ISIs) between 200 and 4800 ms. In this task, the subjects required non-motor components to estimate the time of forthcoming tone in addition to motor components to tap. Normal subjects synchronized their taps to the presented tones at shorter ISIs, whereas as the ISI became longer, the normal subjects displayed greater latency between the tone and the tapping (transition zone). After the transition zone, normal subjects pressed the button delayed relative to the tone. On the other hand, SCA patients could not synchronize their tapping with the tone even at shorter ISIs, although they pressed the button delayed relative to the tone earlier than normal subjects did. The earliest time of delayed tapping appearance after the transition zone was 4800 ms in normal subjects but 1800 ms in SCA patients. The span of temporal integration in SCA patients is shortened compared to that in normal subjects. This could represent non-motor cerebellar dysfunction in SCA patients. PMID:25706752

Threading on ADI Cast Iron, Developing Tools and Conditions

NASA Astrophysics Data System (ADS)

Elósegui, I.; de Lacalle, L. N. López

2011-01-01

The present work is focussed on the improvement of the design and performance of the taps used for making threaded holes in ADI (Austempered Ductile Iron). It is divided in two steps: a) The development of a method valid to compare the taps wear without reaching the end of their life, measuring the required torque to make one threaded hole, after having made previously a significant number of threaded holes. The tap wear causes some teeth geometrical changes, that supposes an increase in the required torque and axial force. b) The taps wear comparison method is open to apply on different PVD coated taps, AlTiN, AlCrSiN, AlTiSiN, , and to different geometries.

Angiomodulin is required for cardiogenesis of embryonic stem cells and is maintained by a feedback loop network of p63 and Activin-A.

PubMed

Wolchinsky, Zohar; Shivtiel, Shoham; Kouwenhoven, Evelyn Nathalie; Putin, Daria; Sprecher, Eli; Zhou, Huiqing; Rouleau, Matthieu; Aberdam, Daniel

2014-01-01

The transcription factor p63, member of the p53 gene family, encodes for two main isoforms, TAp63 and ΔNp63 with distinct functions on epithelial homeostasis and cancer. Recently, we discovered that TAp63 is essential for in vitro cardiogenesis and heart development in vivo. TAp63 is expressed by embryonic endoderm and acts on cardiac progenitors by a cell-non-autonomous manner. In the present study, we search for cardiogenic secreted factors that could be regulated by TAp63 and, by ChIP-seq analysis, identified Angiomodulin (AGM), also named IGFBP7 or IGFBP-rP1. We demonstrate that AGM is necessary for cardiac commitment of embryonic stem cells (ESCs) and its regulation depends on TAp63 isoform. TAp63 directly activates both AGM and Activin-A during ESC cardiogenesis while these secreted factors modulate TAp63 gene expression by a feedback loop mechanism. The molecular circuitry controlled by TAp63 on AGM/Activin-A signaling pathway and thus on cardiogenesis emphasizes the importance of p63 during early cardiac development. © 2013.

Transversus abdominal plane (TAP) block for postoperative pain management: a review.

PubMed

Jakobsson, Jan; Wickerts, Liselott; Forsberg, Sune; Ledin, Gustaf

2015-01-01

Transversus abdominal plane (TAP) block has a long history and there is currently extensive clinical experience around TAP blocks. The aim of this review is to provide a summary of the present evidence on the effects of TAP block and to provide suggestions for further studies. There are several approaches to performing abdominal wall blocks, with the rapid implementation of ultrasound-guided technique facilitating a major difference in TAP block performance. During surgery, an abdominal wall block may also be applied by the surgeon from inside the abdominal cavity. Today, there are more than 11 meta-analyses providing a compiled evidence base around the effects of TAP block. These analyses include different procedures, different techniques of TAP block administration and, importantly, they compare the TAP block with a variety of alternative analgesic regimes. The effects of TAP block during laparoscopic cholecystectomy seem to be equivalent to local infiltration analgesia and also seem to be beneficial during laparoscopic colon resection. The effects of TAP are more pronounced when it is provided prior to surgery and these effects are local anaesthesia dose-dependent. TAP block seems an interesting alternative in patients with, for example, severe obesity where epidural or spinal anaesthesia/analgesia is technically difficult and/or poses a risk. There is an obvious need for further high-quality studies comparing TAP block prior to surgery with local infiltration analgesia, single-shot spinal analgesia, and epidural analgesia. These studies should be procedure-specific and the effects should be evaluated, both regarding short-term pain and analgesic requirement and also including the effects on postoperative nausea and vomiting, recovery of bowel function, ambulation, discharge, and protracted recovery outcomes (assessed by e.g., postoperative quality of recovery scale).

Mentoring community-based trainee assistant practitioners: a case study.

PubMed

Griggs, Chloe

2012-07-01

The healthcare workforce is changing, and the introduction of assistant practitioner roles in the community presents exciting opportunities for the unregistered workforce. Healthcare assistants wishing to become assistant practitioners are undertaking foundation degrees. During this period of study, they require support and supervision from a mentor to perform competencies; however, mentors are often poorly prepared for this role. This small-scale qualitative exploratory study sought to gain trainee assistant practitioner (TAP), mentor and management perspective on the level of support needed. Findings indicate that TAPs struggle for recognition and student/learner status; there was an assumption that mentors would be adequately equipped to mentor TAPs, and poor mentor preparation was linked to negative student experiences. This article considers the key factors, time and commitment, required to support TAP learners in the workplace. Further, it questions who is best placed to mentor TAPs. Recommendations include an increased level of preparation for mentors, a joint induction programme for TAPs and mentors, a raised profile of the assistant practitioner role within the wider healthcare team, recognition of the TAP as a learner, and allocated time for quality mentorship.

Variation in dual-task performance reveals late initiation of speech planning in turn-taking.

PubMed

Sjerps, Matthias J; Meyer, Antje S

2015-03-01

The smooth transitions between turns in natural conversation suggest that speakers often begin to plan their utterances while listening to their interlocutor. The presented study investigates whether this is indeed the case and, if so, when utterance planning begins. Two hypotheses were contrasted: that speakers begin to plan their turn as soon as possible (in our experiments less than a second after the onset of the interlocutor's turn), or that they do so close to the end of the interlocutor's turn. Turn-taking was combined with a finger tapping task to measure variations in cognitive load. We assumed that the onset of speech planning in addition to listening would be accompanied by deterioration in tapping performance. Two picture description experiments were conducted. In both experiments there were three conditions: (1) Tapping and Speaking, where participants tapped a complex pattern while taking over turns from a pre-recorded speaker, (2) Tapping and Listening, where participants carried out the tapping task while overhearing two pre-recorded speakers, and (3) Speaking Only, where participants took over turns as in the Tapping and Speaking condition but without tapping. The experiments differed in the amount of tapping training the participants received at the beginning of the session. In Experiment 2, the participants' eye-movements were recorded in addition to their speech and tapping. Analyses of the participants' tapping performance and eye movements showed that they initiated the cognitively demanding aspects of speech planning only shortly before the end of the turn of the preceding speaker. We argue that this is a smart planning strategy, which may be the speakers' default in many everyday situations. Copyright © 2014 Elsevier B.V. All rights reserved.

Identification and regulatory analysis of rainbow trout tapasin and tapasin-related genes

USGS Publications Warehouse

Landis, E.D.; Palti, Y.; Dekoning, J.; Drew, R.; Phillips, R.B.; Hansen, J.D.

2006-01-01

Tapasin (TAPBP) is a key member of MHC class Ia antigen-loading complexes, bridging the class Ia molecule to the transporter associated with antigen presentation (TAP). As part of an ongoing study of MHC genomics in rainbow trout, we have identified two rainbow trout TAPBP genes (Onmy-TAPBP.a and .b) and a similar but distinct TAPBP-related gene (Onmy-TAPBP-R) that had previously only been described in mammals. Physical and genetic mapping indicate that Onmy-TAPBP.a is on chromosome 18 in the MHC class Ia region and that Onmy-TAPBP.b resides on chromosome 14 in the MHC class Ib region. There are also at least two copies of TAPBP-R, Onmy-TAPBP-R.a and Onmy-TAPBP-R.b, located on chromosomes 2 and 3, respectively. Due to the central role of TAPBP expression during acute viral infection, we have characterized the transcriptional profile and regulatory regions for both Onmy-TAPBP and Onmy-TAPBP-R. Transcription of both genes increased during acute infection with infectious hematapoeitic necrosis virus (IHNV) in a fashion indicative of interferon-mediated regulation. Promoter-reporter assays in STE-137 cells demonstrate that the trout TAPBP and TAPBP-R promoters respond to interferon regulatory factors, Onmy-IRF1 and Onmy-IRF2. Overall, TAPBP is expressed at higher levels than TAPBP-R in nai??ve tissues and TAPBP transcription is more responsive to viral infection and IRF1 and 2 binding. ?? Springer-Verlag 2006.

A study of tapping by the unaffected finger of patients presenting with central and peripheral nerve damage.

PubMed

Zhang, Lingli; Han, Xiuying; Li, Peihong; Liu, Yang; Zhu, Yulian; Zou, Jun; Yu, Zhusheng

2015-01-01

Whether the unaffected function of the hand of patients presenting with nerve injury is affected remains inconclusive. We aimed to evaluate whether there are differences in finger tapping following central or peripheral nerve injury compared with the unaffected hand and the ipsilateral hand of a healthy subject. Thirty right brain stroke patients with hemiplegia, 30 left arm peripheral nerve injury cases, and 60 healthy people were selected. We tested finger tapping of the right hands, and each subject performed the test twice. Finger tapping following peripheral nerve injury as compared with the unaffected hand and the dominant hand of a healthy person was markedly higher than was found for central nerve injury (P < 0.05). Finger tapping of the male peripheral group's unaffected hand and the control group's dominant hand was significantly higher than the central group (P < 0.001). However, finger tapping of the female control group's dominant hand was significantly higher than the central group's unaffected hand (P < 0.01, P = 0.002), the peripheral group's unaffected hand (P < 0.05, P = 0.034). The unaffected function of the hand of patients with central and peripheral nerve injury was different as compared with the ipsilateral hand of healthy individuals. The rehabilitation therapist should intensify the practice of normal upper limb fine activities and coordination of the patient.

Primary stability and self-tapping blades: biomechanical assessment of dental implants in medium-density bone.

PubMed

Kim, Yung-Soo; Lim, Young-Jun

2011-10-01

The aim of this biomechanical study was to assess the influence of self-tapping blades in terms of primary implant stability between implants with self-tapping blades and implants without self-tapping blades using five different analytic methods, especially in medium-density bone. Two different types of dental implants (4 × 10 mm) were tested: self-tapping and non-self-tapping. The fixture design including thread profiles was exactly the same between the two groups; the only difference was the presence of cutting blades on one half of the apical portion of the implant body. Solid rigid polyurethane blocks with corresponding densities were selected to simulate medium-density bone. Five mechanical assessments (insertion torque, resonance frequency analysis [RFA], reverse torque, pull-out and push in test) were performed for primary stability. Implants without self-tapping blades showed significantly higher values (P<0.001) in four biomechanical assessments, except RFA (P=0.684). However, a statistically significant correlation could not be detected between insertion torque values with the four different outcome variables (P>0.05). The outcomes of the present study indicate that the implant body design without self-tapping blades has a good primary stability compared with that with self-tapping blades in medium-density bone. Considering the RFA, a distinct layer of cortical bone on marginal bone will yield implant stability quotient values similar to those in medium-bone density when implants have the same diameter. © 2011 John Wiley & Sons A/S.

Loss of retrovirus production in JB/RH melanoma cells transfected with H-2Kb and TAP-1 genes.

PubMed

Li, M; Xu, F; Muller, J; Huang, X; Hearing, V J; Gorelik, E

1999-01-20

JB/RH1 melanoma cells, as well as other melanomas of C57BL/6 mice (B16 and JB/MS), express a common melanoma-associated antigen (MAA) encoded by an ecotropic melanoma-associated retrovirus (MelARV). JB/RH1 cells do not express the H-2Kb molecules due to down-regulation of the H-2Kb and TAP-1 genes. When JB/RH1 cells were transfected with the H-2Kb and cotransfected with the TAP-1 gene, it resulted in the appearance of H-2Kb molecules and an increase in their immunogenicity, albeit they lost expression of retrovirus-encoded MAA recognized by MM2-9B6 mAb. Loss of MAA was found to result from a complete and stable elimination of ecotropic MelARV production in the H-2Kb/TAP-1-transfected JB/RH1 cells. Northern blot analysis showed no differences in ecotropic retroviral messages in MelARV-producing and -nonproducing melanoma cells, suggesting that loss of MelARV production was not due to down-regulation of MelARV transcription. Southern blot analysis revealed several rearrangements in the proviral DNA of H-2Kb-positive JB/RH1 melanoma cells. Sequence analysis of the ecotropic proviral DNA from these cells showed numerous nucleotide substitutions, some of which resulted in the appearance of a novel intraviral PstI restriction site and the loss of a HindIII restriction site in the pol region. PCR amplification of the proviral DNAs indicates that an ecotropic provirus found in the H-2Kb-positive cells is novel and does not preexist in the parental H-2Kb-negative melanoma cells. Conversely, the ecotropic provirus of the parental JB/RH1 cells was not amplifable from the H-2Kb-positive cells. Our data indicate that stable loss of retroviral production in the H-2Kb/TAP-1-transfected melanoma cells is probably due to the induction of recombination between a productive ecotropic MelARV and a defective nonecotropic provirus leading to the generation of a defective ecotropic provirus and the loss of MelARV production and expression of the retrovirus-encoded MAA. Copyright 1999 Academic Press.

Astronomy on Tap: science engagement in the pub

NASA Astrophysics Data System (ADS)

Livermore, Rachael C.; Silverman, Jeffrey Michael

2015-08-01

Astronomy on Tap is a series of free lectures by astronomers in the pub, aimed at disseminating the latest research to the public in an informal setting. Started in New York City in 2013, Astronomy on Tap has now expanded to seven cities across North and South America. Organized by local astronomers, each event features talks by astronomers from local institutions or visitors, or others whose professions or hobbies intersect with astronomy, along with games and opportunities for the public to interact with professional astronomers. The largest Astronomy on Tap events are in Austin, Texas, attracting over 150 people each month, which consists of populations outside of the self-selected groups that might be reached by more formal EPO activities. The organisers of Astronomy on Tap in Austin (AoTATX) will discuss the impact of and feedback from all of the locations, and present information on setting up new satellite locations.

The neural substrates of impaired finger tapping regularity after stroke.

PubMed

Calautti, Cinzia; Jones, P Simon; Guincestre, Jean-Yves; Naccarato, Marcello; Sharma, Nikhil; Day, Diana J; Carpenter, T Adrian; Warburton, Elizabeth A; Baron, Jean-Claude

2010-03-01

Not only finger tapping speed, but also tapping regularity can be impaired after stroke, contributing to reduced dexterity. The neural substrates of impaired tapping regularity after stroke are unknown. Previous work suggests damage to the dorsal premotor cortex (PMd) and prefrontal cortex (PFCx) affects externally-cued hand movement. We tested the hypothesis that these two areas are involved in impaired post-stroke tapping regularity. In 19 right-handed patients (15 men/4 women; age 45-80 years; purely subcortical in 16) partially to fully recovered from hemiparetic stroke, tri-axial accelerometric quantitative assessment of tapping regularity and BOLD fMRI were obtained during fixed-rate auditory-cued index-thumb tapping, in a single session 10-230 days after stroke. A strong random-effect correlation between tapping regularity index and fMRI signal was found in contralesional PMd such that the worse the regularity the stronger the activation. A significant correlation in the opposite direction was also present within contralesional PFCx. Both correlations were maintained if maximal index tapping speed, degree of paresis and time since stroke were added as potential confounds. Thus, the contralesional PMd and PFCx appear to be involved in the impaired ability of stroke patients to fingertap in pace with external cues. The findings for PMd are consistent with repetitive TMS investigations in stroke suggesting a role for this area in affected-hand movement timing. The inverse relationship with tapping regularity observed for the PFCx and the PMd suggests these two anatomically-connected areas negatively co-operate. These findings have implications for understanding the disruption and reorganization of the motor systems after stroke. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Chemotherapy Enhances Cross-Presentation of Nuclear Tumor Antigens

PubMed Central

Anyaegbu, Chidozie C.; Lake, Richard A.; Heel, Kathy; Robinson, Bruce W.; Fisher, Scott A.

2014-01-01

Cross-presentation of tumor antigen is essential for efficient priming of naïve CD8+ T lymphocytes and induction of effective anti-tumor immunity. We hypothesized that the subcellular location of a tumor antigen could affect the efficiency of cross-presentation, and hence the outcome of anti-tumor responses to that antigen. We compared cross-presentation of a nominal antigen expressed in the nuclear, secretory, or cytoplasmic compartments of B16 melanoma tumors. All tumors expressed similar levels of the antigen. The antigen was cross-presented from all compartments but when the concentration was low, nuclear antigen was less efficiently cross-presented than antigen from other cellular locations. The efficiency of cross-presentation of the nuclear antigen was improved following chemotherapy-induced tumor cell apoptosis and this correlated with an increase in the proportion of effector CTL. These data demonstrate that chemotherapy improves nuclear tumor antigen cross-presentation and could be important for anti-cancer immunotherapies that target nuclear antigens. PMID:25243472

Contingent negative variation (CNV) associated with sensorimotor timing error correction.

PubMed

Jang, Joonyong; Jones, Myles; Milne, Elizabeth; Wilson, Daniel; Lee, Kwang-Hyuk

2016-02-15

Detection and subsequent correction of sensorimotor timing errors are fundamental to adaptive behavior. Using scalp-recorded event-related potentials (ERPs), we sought to find ERP components that are predictive of error correction performance during rhythmic movements. Healthy right-handed participants were asked to synchronize their finger taps to a regular tone sequence (every 600 ms), while EEG data were continuously recorded. Data from 15 participants were analyzed. Occasional irregularities were built into stimulus presentation timing: 90 ms before (advances: negative shift) or after (delays: positive shift) the expected time point. A tapping condition alternated with a listening condition in which identical stimulus sequence was presented but participants did not tap. Behavioral error correction was observed immediately following a shift, with a degree of over-correction with positive shifts. Our stimulus-locked ERP data analysis revealed, 1) increased auditory N1 amplitude for the positive shift condition and decreased auditory N1 modulation for the negative shift condition; and 2) a second enhanced negativity (N2) in the tapping positive condition, compared with the tapping negative condition. In response-locked epochs, we observed a CNV (contingent negative variation)-like negativity with earlier latency in the tapping negative condition compared with the tapping positive condition. This CNV-like negativity peaked at around the onset of subsequent tapping, with the earlier the peak, the better the error correction performance with the negative shifts while the later the peak, the better the error correction performance with the positive shifts. This study showed that the CNV-like negativity was associated with the error correction performance during our sensorimotor synchronization study. Auditory N1 and N2 were differentially involved in negative vs. positive error correction. However, we did not find evidence for their involvement in behavioral error correction. Overall, our study provides the basis from which further research on the role of the CNV in perceptual and motor timing can be developed. Copyright © 2015 Elsevier Inc. All rights reserved.

Analysis of organophosphate hydraulic fluids in U.S. Air force base soils

PubMed

David; Seiber

1999-04-01

Tri-aryl and tri-alkyl organophosphates (TAPs) have been used extensively as flame-retardant hydraulic fluids and fluid additives in commercial and military aircraft. Up to 80% of the consumption of these fluids has been estimated to be lost to unrecovered leakage. Tri-aryl phosphate components of these fluids are resistant to volatilization and solubilization in water, thus, their primary environmental fate pathway is sorption to soils. Environmental audits of military air bases generally do not include quantification of these compounds in soils. We have determined the presence and extent of TAP contamination in soil samples from several U.S. Air Force bases. Soils were collected, extracted, and analyzed using GC/FPD and GC/MS. Tricresyl phosphate was the most frequently found TAP in soil, ranging from 0.02 to 130 ppm. Other TAPs in soils included triphenyl phosphate and isopropylated triphenyl phosphate. Observations are made regarding the distribution, typical concentrations, persistence, and need for further testing of TAPs in soils at military installations. Additionally, GC and mass spectral data for these TAPs are presented, along with methods for their extraction, sample clean-up, and quantification.

Abnormal maximal finger tapping in abstinent cannabis users.

PubMed

Flavel, Stanley C; White, Jason M; Todd, Gabrielle

2013-11-01

To investigate movement speed and rhythmicity in abstinent cannabis users, we hypothesized that abstinent cannabis users exhibit decreased maximal finger tapping frequency and increased variability of tapping compared with non-drug users. The study involved 10 healthy adult cannabis users and 10 age-matched and gender-matched controls with no history of illicit drug use. Subjects underwent a series of screening tests prior to participation. Subjects were then asked to tap a strain gauge as fast as possible with the index finger of their dominant hand (duration 5 s). The average intertap interval did not significantly differ between groups, but the coefficient of variation of the intertap interval was significantly greater in the cannabis group than in controls (p=0.011). The cannabis group also exhibited a slow tapping frequency at the beginning of the task. Rhythmicity of finger tapping is abnormal in individuals with a history of cannabis use. The abnormality appears to be long lasting and adds to the list of functional changes present in abstinent cannabis users. Copyright © 2013 John Wiley & Sons, Ltd.

Alteration of rhythmic unimanual tapping and anti-phase bimanual coordination in Alzheimer's disease: A sign of inter-hemispheric disconnection?

PubMed

Martin, Elodie; Blais, Mélody; Albaret, Jean-Michel; Pariente, Jérémie; Tallet, Jessica

2017-10-01

Little attention is paid to motor control in Alzheimer's disease (AD) although it is a relevant sign of central nervous system integrity and functioning. In particular, unimanual and bimanual tapping is a relevant paradigm because it requires intra- and inter-hemispheric transfer (IHT). Previous results indicate that both unimanual and anti-phase tapping requires more IHT than in-phase tapping, especially produced without external stimulation. The aim of the present study was to test the production of unimanual, bimanual in-phase and anti-phase tapping with a synchronization-continuation paradigm with and without visual stimulation in AD patients (N=9) and control participants (N=12). In accordance with our hypothesis, these results suggest that unimanual and anti-phase tapping is more altered in AD than in control participants. Moreover, performance is globally more variable in the AD group. These alterations are discussed in terms of possible IHT modulation, in line with functional and structural findings in AD, revealing changes in the connectivity of brain regions across hemispheres and white matter damage. Copyright © 2017 Elsevier B.V. All rights reserved.

Study of Designing BPF by Using LC Tap-Coupling Resonators

NASA Astrophysics Data System (ADS)

Yasuzumi, Takenori; Wada, Kouji; Nakajima, Naoko; Hashimoto, Osamu

The resonance characteristics of short-ended half-wavelength coplanar waveguide(CPW) LC tap-coupling resonators are examined theoretically and experimentally. The characteristics near the passband have been improved by applying the presented CPW resonator to a design of a bandpass filter(BPF). Moreover, the difference between the calculation and the measurement results is examined by using the equivalent circuit about the presented BPF.

Comparative Genome Analyses Reveal Distinct Structure in the Saltwater Crocodile MHC

PubMed Central

Jaratlerdsiri, Weerachai; Deakin, Janine; Godinez, Ricardo M.; Shan, Xueyan; Peterson, Daniel G.; Marthey, Sylvain; Lyons, Eric; McCarthy, Fiona M.; Isberg, Sally R.; Higgins, Damien P.; Chong, Amanda Y.; John, John St; Glenn, Travis C.; Ray, David A.; Gongora, Jaime

2014-01-01

The major histocompatibility complex (MHC) is a dynamic genome region with an essential role in the adaptive immunity of vertebrates, especially antigen presentation. The MHC is generally divided into subregions (classes I, II and III) containing genes of similar function across species, but with different gene number and organisation. Crocodylia (crocodilians) are widely distributed and represent an evolutionary distinct group among higher vertebrates, but the genomic organisation of MHC within this lineage has been largely unexplored. Here, we studied the MHC region of the saltwater crocodile (Crocodylus porosus) and compared it with that of other taxa. We characterised genomic clusters encompassing MHC class I and class II genes in the saltwater crocodile based on sequencing of bacterial artificial chromosomes. Six gene clusters spanning ∼452 kb were identified to contain nine MHC class I genes, six MHC class II genes, three TAP genes, and a TRIM gene. These MHC class I and class II genes were in separate scaffold regions and were greater in length (2–6 times longer) than their counterparts in well-studied fowl B loci, suggesting that the compaction of avian MHC occurred after the crocodilian-avian split. Comparative analyses between the saltwater crocodile MHC and that from the alligator and gharial showed large syntenic areas (>80% identity) with similar gene order. Comparisons with other vertebrates showed that the saltwater crocodile had MHC class I genes located along with TAP, consistent with birds studied. Linkage between MHC class I and TRIM39 observed in the saltwater crocodile resembled MHC in eutherians compared, but absent in avian MHC, suggesting that the saltwater crocodile MHC appears to have gene organisation intermediate between these two lineages. These observations suggest that the structure of the saltwater crocodile MHC, and other crocodilians, can help determine the MHC that was present in the ancestors of archosaurs. PMID:25503521

Divergence of stable isotopes in tap water across China

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

Zhao, Sihan; Hu, Hongchang; Tian, Fuqiang

Stable isotopes in water (e.g., δ2H and δ18O) are important indicators of hydrological and ecological patterns and processes. Tap water can reflect integrated features of regional hydrological processes and human activities. China is a large country with significant meteorological and geographical variations. This report presents the first national-scale survey of Stable Isotopes in Tap Water (SITW) across China. 780 tap water samples have been collected from 95 cities across China from December 2014 to December 2015. (1) Results yielded the Tap Water Line in China is δ2H = 7.72 δ18O + 6.57 (r2 = 0.95). (2) SITW spatial distribution presentsmore » typical "continental effect". (3) SITW seasonal variations indicate clearly regional patterns but no trends at the national level. (4) SITW can be correlated in some parts with geographic or meteorological factors. This work presents the first SITW map in China, which sets up a benchmark for further stable isotopes research across China. This is a critical step toward monitoring and investigating water resources in climate-sensitive regions, so the human-hydrological system. These findings could be used in the future to establish water management strategies at a national or regional scale. Title: Divergence of stable isotopes in tap water across China Authors: Zhao, SH; Hu, HC; Tian, FQ; Tie, Q; Wang, LX; Liu, YL; Shi, CX Source: SCIENTIFIC REPORTS, 7 10.1038/srep43653 MAR 2 2017« less

Viral Sequestration of Antigen Subverts Cross Presentation to CD8+ T Cells

PubMed Central

Tewalt, Eric F.; Grant, Jean M.; Granger, Erica L.; Palmer, Douglas C.; Heuss, Neal D.; Gregerson, Dale S.; Restifo, Nicholas P.; Norbury, Christopher C.

2009-01-01

Virus-specific CD8+ T cells (TCD8+) are initially triggered by peptide-MHC Class I complexes on the surface of professional antigen presenting cells (pAPC). Peptide-MHC complexes are produced by two spatially distinct pathways during virus infection. Endogenous antigens synthesized within virus-infected pAPC are presented via the direct-presentation pathway. Many viruses have developed strategies to subvert direct presentation. When direct presentation is blocked, the cross-presentation pathway, in which antigen is transferred from virus-infected cells to uninfected pAPC, is thought to compensate and allow the generation of effector TCD8+. Direct presentation of vaccinia virus (VACV) antigens driven by late promoters does not occur, as an abortive infection of pAPC prevents production of these late antigens. This lack of direct presentation results in a greatly diminished or ablated TCD8+ response to late antigens. We demonstrate that late poxvirus antigens do not enter the cross-presentation pathway, even when identical antigens driven by early promoters access this pathway efficiently. The mechanism mediating this novel means of viral modulation of antigen presentation involves the sequestration of late antigens within virus factories. Early antigens and cellular antigens are cross-presented from virus-infected cells, as are late antigens that are targeted to compartments outside of the virus factories. This virus-mediated blockade specifically targets the cross-presentation pathway, since late antigen that is not cross-presented efficiently enters the MHC Class II presentation pathway. These data are the first to describe an evasion mechanism employed by pathogens to prevent entry into the cross-presentation pathway. In the absence of direct presentation, this evasion mechanism leads to a complete ablation of the TCD8+ response and a potential replicative advantage for the virus. Such mechanisms of viral modulation of antigen presentation must also be taken into account during the rational design of antiviral vaccines. PMID:19478869

Nonclassical MHC Ib-restricted CD8+ T Cells Recognize Mycobacterium tuberculosis-Derived Protein Antigens and Contribute to Protection Against Infection

PubMed Central

Shang, Shaobin; Siddiqui, Sarah; Bian, Yao; Zhao, Jie; Wang, Chyung-Ru

2016-01-01

MHC Ib-restricted CD8+ T cells have been implicated in host defense against Mycobacterium tuberculosis (Mtb) infection. However, the relative contribution of various MHC Ib-restricted T cell populations to anti-mycobacterial immunity remains elusive. In this study, we used mice that lack MHC Ia (Kb-/-Db-/-), MHC Ia/H2-M3 (Kb-/-Db-/-M3-/-), or β2m (β2m-/-) to study the role of M3-restricted and other MHC Ib-restricted T cells in immunity against Mtb. Unlike their dominant role in Listeria infection, we found that M3-restricted CD8+ T cells only represented a small proportion of the CD8+ T cells responding to Mtb infection. Non-M3, MHC Ib-restricted CD8+ T cells expanded preferentially in the lungs of Mtb-infected Kb-/-Db-/-M3-/- mice, exhibited polyfunctional capacities and conferred protection against Mtb. These MHC Ib-restricted CD8+ T cells recognized several Mtb-derived protein antigens at a higher frequency than MHC Ia-restricted CD8+ T cells. The presentation of Mtb antigens to MHC Ib-restricted CD8+ T cells was mostly β2m-dependent but TAP-independent. Interestingly, a large proportion of Mtb-specific MHC Ib-restricted CD8+ T cells in Kb-/-Db-/-M3-/- mice were Qa-2-restricted while no considerable numbers of MR1 or CD1-restricted Mtb-specific CD8+ T cells were detected. Our findings indicate that nonclassical CD8+ T cells other than the known M3, CD1, and MR1-restricted CD8+ T cells contribute to host immune responses against Mtb infection. Targeting these MHC Ib-restricted CD8+ T cells would facilitate the design of better Mtb vaccines with broader coverage across MHC haplotypes due to the limited polymorphism of MHC class Ib molecules. PMID:27272249

Secondary anchor polymorphism in the HA-1 minor histocompatibility antigen critically affects MHC stability and TCR recognition

PubMed Central

Nicholls, Sarah; Piper, Karen P.; Mohammed, Fiyaz; Dafforn, Timothy R.; Tenzer, Stefan; Salim, Mahboob; Mahendra, Premini; Craddock, Charles; van Endert, Peter; Schild, Hansjörg; Cobbold, Mark; Engelhard, Victor H.; Moss, Paul A. H.; Willcox, Benjamin E.

2009-01-01

T cell recognition of minor histocompatibility antigens (mHags) underlies allogeneic immune responses that mediate graft-versus-host disease and the graft-versus-leukemia effect following stem cell transplantation. Many mHags derive from single amino acid polymorphisms in MHC-restricted epitopes, but our understanding of the molecular mechanisms governing mHag immunogenicity and recognition is incomplete. Here we examined antigenic presentation and T-cell recognition of HA-1, a prototypic autosomal mHag derived from single nucleotide dimorphism (HA-1H versus HA-1R) in the HMHA1 gene. The HA-1H peptide is restricted by HLA-A2 and is immunogenic in HA-1R/R into HA-1H transplants, while HA-1R has been suggested to be a “null allele” in terms of T cell reactivity. We found that proteasomal cleavage and TAP transport of the 2 peptides is similar and that both variants can bind to MHC. However, the His>Arg change substantially decreases the stability and affinity of HLA-A2 association, consistent with the reduced immunogenicity of the HA-1R variant. To understand these findings, we determined the structure of an HLA-A2-HA-1H complex to 1.3Å resolution. Whereas His-3 is accommodated comfortably in the D pocket, incorporation of the lengthy Arg-3 is predicted to require local conformational changes. Moreover, a soluble TCR generated from HA-1H-specific T-cells bound HA-1H peptide with moderate affinity but failed to bind HA-1R, indicating complete discrimination of HA-1 variants at the level of TCR/MHC interaction. Our results define the molecular mechanisms governing immunogenicity of HA-1, and highlight how single amino acid polymorphisms in mHags can critically affect both MHC association and TCR recognition. PMID:19234124

Super-Nyquist shaping and processing technologies for high-spectral-efficiency optical systems

NASA Astrophysics Data System (ADS)

Jia, Zhensheng; Chien, Hung-Chang; Zhang, Junwen; Dong, Ze; Cai, Yi; Yu, Jianjun

2013-12-01

The implementations of super-Nyquist pulse generation, both in a digital field using a digital-to-analog converter (DAC) or an optical filter at transmitter side, are introduced. Three corresponding signal processing algorithms at receiver are presented and compared for high spectral-efficiency (SE) optical systems employing the spectral prefiltering. Those algorithms are designed for the mitigation towards inter-symbol-interference (ISI) and inter-channel-interference (ICI) impairments by the bandwidth constraint, including 1-tap constant modulus algorithm (CMA) and 3-tap maximum likelihood sequence estimation (MLSE), regular CMA and digital filter with 2-tap MLSE, and constant multi-modulus algorithm (CMMA) with 2-tap MLSE. The principles and prefiltering tolerance are given through numerical and experimental results.

Comparison of TAPS Packages for Engineering

ERIC Educational Resources Information Center

Sidhu, S. Manjit

2008-01-01

Purpose: This paper aims to present the development of technology-assisted problem solving (TAPS) packages at University Tenaga Nasional (UNITEN). The project is the further work of the development of interactive multimedia based packages targeted for students having problems in understanding the subject of engineering mechanics dynamics.…

Automatic and Objective Assessment of Alternating Tapping Performance in Parkinson's Disease

PubMed Central

Memedi, Mevludin; Khan, Taha; Grenholm, Peter; Nyholm, Dag; Westin, Jerker

2013-01-01

This paper presents the development and evaluation of a method for enabling quantitative and automatic scoring of alternating tapping performance of patients with Parkinson's disease (PD). Ten healthy elderly subjects and 95 patients in different clinical stages of PD have utilized a touch-pad handheld computer to perform alternate tapping tests in their home environments. First, a neurologist used a web-based system to visually assess impairments in four tapping dimensions (‘speed’, ‘accuracy’, ‘fatigue’ and ‘arrhythmia’) and a global tapping severity (GTS). Second, tapping signals were processed with time series analysis and statistical methods to derive 24 quantitative parameters. Third, principal component analysis was used to reduce the dimensions of these parameters and to obtain scores for the four dimensions. Finally, a logistic regression classifier was trained using a 10-fold stratified cross-validation to map the reduced parameters to the corresponding visually assessed GTS scores. Results showed that the computed scores correlated well to visually assessed scores and were significantly different across Unified Parkinson's Disease Rating Scale scores of upper limb motor performance. In addition, they had good internal consistency, had good ability to discriminate between healthy elderly and patients in different disease stages, had good sensitivity to treatment interventions and could reflect the natural disease progression over time. In conclusion, the automatic method can be useful to objectively assess the tapping performance of PD patients and can be included in telemedicine tools for remote monitoring of tapping. PMID:24351667

Automatic and objective assessment of alternating tapping performance in Parkinson's disease.

PubMed

Memedi, Mevludin; Khan, Taha; Grenholm, Peter; Nyholm, Dag; Westin, Jerker

2013-12-09

This paper presents the development and evaluation of a method for enabling quantitative and automatic scoring of alternating tapping performance of patients with Parkinson's disease (PD). Ten healthy elderly subjects and 95 patients in different clinical stages of PD have utilized a touch-pad handheld computer to perform alternate tapping tests in their home environments. First, a neurologist used a web-based system to visually assess impairments in four tapping dimensions ('speed', 'accuracy', 'fatigue' and 'arrhythmia') and a global tapping severity (GTS). Second, tapping signals were processed with time series analysis and statistical methods to derive 24 quantitative parameters. Third, principal component analysis was used to reduce the dimensions of these parameters and to obtain scores for the four dimensions. Finally, a logistic regression classifier was trained using a 10-fold stratified cross-validation to map the reduced parameters to the corresponding visually assessed GTS scores. Results showed that the computed scores correlated well to visually assessed scores and were significantly different across Unified Parkinson's Disease Rating Scale scores of upper limb motor performance. In addition, they had good internal consistency, had good ability to discriminate between healthy elderly and patients in different disease stages, had good sensitivity to treatment interventions and could reflect the natural disease progression over time. In conclusion, the automatic method can be useful to objectively assess the tapping performance of PD patients and can be included in telemedicine tools for remote monitoring of tapping.

Tapping mode imaging with an interfacial force microscope

NASA Astrophysics Data System (ADS)

Warren, O. L.; Graham, J. F.; Norton, P. R.

1997-11-01

In their present embodiment, sensors used in interfacial force microscopy do not have the necessary mechanical bandwidth to be employed as free-running tapping mode devices. We describe an extremely stable method of obtaining tapping mode images using feedback on the sensor. Our method is immune to small dc drifts in the force signal, and the prospect of diminishing the risk of damaging fragile samples is realized. The feasibility of the technique is demonstrated by our imaging work on a Kevlar fiber-epoxy composite. We also present a model which accounts for the frequency dependence of the sensor in air when operating under closed loop control. A simplified force modulation model is investigated to explore the effect of contact on the closed loop response of the sensor.

Stable long-term cultures of self-renewing B cells and their applications.

PubMed

Kwakkenbos, Mark J; van Helden, Pauline M; Beaumont, Tim; Spits, Hergen

2016-03-01

Monoclonal antibodies are essential therapeutics and diagnostics in a large number of diseases. Moreover, they are essential tools in all sectors of life sciences. Although the great majority of monoclonal antibodies currently in use are of mouse origin, the use of human B cells to generate monoclonal antibodies is increasing as new techniques to tap the human B cell repertoire are rapidly emerging. Cloned lines of immortalized human B cells are ideal sources of monoclonal antibodies. In this review, we summarize our studies to the regulation of the replicative life span, differentiation, and maturation of B cells that led to the development of a platform that uses immortalization of human B cells by in vitro genetic modification for antibody development. We describe a number of human antibodies that were isolated using this platform and the application of the technique in other species. We also discuss the use of immortalized B cells as antigen-presenting cells for the discovery of tumor neoantigens. © 2016 The Authors. Immunological Reviews Published by John Wiley & Sons Ltd.

Sensorimotor Synchronization across the Life Span

ERIC Educational Resources Information Center

Drewing, Knut; Aschersleben, Gisa; Li, Shu-Chen

2006-01-01

The present study investigates the contribution of general processing resources as well as other more specific factors to the life-span development of sensorimotor synchronization and its component processes. Within a synchronization tapping paradigm, a group of 286 participants, 6 to 88 years of age, were asked to synchronize finger taps with…

Erie Community College. Report.

ERIC Educational Resources Information Center

Barber, Jerry

This document presents the findings of the Office of the State Comptroller of New York regarding the audit of the records and procedures used in administering the Tuition Assistance Program (TAP) and Supplemental Tuition Assistance Program (STAP) at Erie Community College. TAP is an entitlement program designed to provide tuition aid to eligible…

Analgesic efficacy of transversus abdominis plane block in neonates and early infants for colostomy and reversal of colostomy.

PubMed

Chen, Chee Kean; Teo, Shu Ching; Phui, Vui Eng; Saman, Mat Ariffin

2015-01-01

The application of ultrasound-guided transversus abdominis plane (TAP) block in paediatric population is gaining popularity among anaesthetists. We present a case series of ultrasound-guided TAP block in ten neonate and infants undergoing colostomy and reversal of stoma. Classical TAP as described by Hebbard was carried out and a maximum dosage of 1ml/kg of 0.25% levobupivacaine was injected. Pain score was assessed using Neonatal Infant Pain Scale for 24 hours. In all patients, the block was successful with minimal hemodynamic changes intraoperatively and no additional systemic analgesia was needed intraoperative and immediate postoperatively. Ultrasound-guided TAP block has an important role in providing safe and effective analgesia for colostomy creation and reversal of stoma surgeries in paediatric population.

Dynamical systems model and discrete element simulations of a tapped granular column

NASA Astrophysics Data System (ADS)

Rosato, A. D.; Blackmore, D.; Tricoche, X. M.; Urban, K.; Zuo, L.

2013-06-01

We present an approximate dynamical systems model for the mass center trajectory of a tapped column of N uniform, inelastic, spheres (diameter d), in which collisional energy loss is governed by the Walton-Braun linear loading-unloading soft interaction. Rigorous analysis of the model, akin to the equations for the motion of a single bouncing ball on a vibrating plate, reveals a parameter γ≔2aω2(1+e)/g that gauges the dynamical regimes and their transitions. In particular, we find bifurcations from periodic to chaotic dynamics that depend on frequency ω, amplitude a/d of the tap. Dynamics predicted by the model are also qualitatively observed in discrete element simulations carried out over a broad range of the tap parameters.

System efficiency of a tap transformer based grid connection topology applied on a direct driven generator for wind power.

PubMed

Apelfröjd, Senad; Eriksson, Sandra

2014-01-01

Results from experiments on a tap transformer based grid connection system for a variable speed vertical axis wind turbine are presented. The tap transformer based system topology consists of a passive diode rectifier, DC-link, IGBT inverter, LCL-filter, and tap transformer. Full range variable speed operation is enabled by using the different step-up ratios of a tap transformer. Simulations using MATLAB/Simulink have been performed in order to study the behavior of the system. A full experimental set up of the system has been used in the laboratory study, where a clone of the on-site generator was driven by an induction motor and the system was connected to a resistive load to better evaluate the performance. Furthermore, the system is run and evaluated for realistic wind speeds and variable speed operation. For a more complete picture of the system performance, a case study using real site Weibull parameters is done, comparing different tap selection options. The results show high system efficiency at nominal power and an increase in overall power output for full tap operation in comparison with the base case, a standard transformer. In addition, the loss distribution at different wind speeds is shown, which highlights the dominant losses at low and high wind speeds. Finally, means for further increasing the overall system efficiency are proposed.

System Efficiency of a Tap Transformer Based Grid Connection Topology Applied on a Direct Driven Generator for Wind Power

PubMed Central

2014-01-01

Results from experiments on a tap transformer based grid connection system for a variable speed vertical axis wind turbine are presented. The tap transformer based system topology consists of a passive diode rectifier, DC-link, IGBT inverter, LCL-filter, and tap transformer. Full range variable speed operation is enabled by using the different step-up ratios of a tap transformer. Simulations using MATLAB/Simulink have been performed in order to study the behavior of the system. A full experimental set up of the system has been used in the laboratory study, where a clone of the on-site generator was driven by an induction motor and the system was connected to a resistive load to better evaluate the performance. Furthermore, the system is run and evaluated for realistic wind speeds and variable speed operation. For a more complete picture of the system performance, a case study using real site Weibull parameters is done, comparing different tap selection options. The results show high system efficiency at nominal power and an increase in overall power output for full tap operation in comparison with the base case, a standard transformer. In addition, the loss distribution at different wind speeds is shown, which highlights the dominant losses at low and high wind speeds. Finally, means for further increasing the overall system efficiency are proposed. PMID:25258733

Efficient multichannel acoustic echo cancellation using constrained tap selection schemes in the subband domain

NASA Astrophysics Data System (ADS)

Desiraju, Naveen Kumar; Doclo, Simon; Wolff, Tobias

2017-12-01

Acoustic echo cancellation (AEC) is a key speech enhancement technology in speech communication and voice-enabled devices. AEC systems employ adaptive filters to estimate the acoustic echo paths between the loudspeakers and the microphone(s). In applications involving surround sound, the computational complexity of an AEC system may become demanding due to the multiple loudspeaker channels and the necessity of using long filters in reverberant environments. In order to reduce the computational complexity, the approach of partially updating the AEC filters is considered in this paper. In particular, we investigate tap selection schemes which exploit the sparsity present in the loudspeaker channels for partially updating subband AEC filters. The potential for exploiting signal sparsity across three dimensions, namely time, frequency, and channels, is analyzed. A thorough analysis of different state-of-the-art tap selection schemes is performed and insights about their limitations are gained. A novel tap selection scheme is proposed which overcomes these limitations by exploiting signal sparsity while not ignoring any filters for update in the different subbands and channels. Extensive simulation results using both artificial as well as real-world multichannel signals show that the proposed tap selection scheme outperforms state-of-the-art tap selection schemes in terms of echo cancellation performance. In addition, it yields almost identical echo cancellation performance as compared to updating all filter taps at a significantly reduced computational cost.

Antigen processing and remodeling of the endosomal pathway: requirements for antigen cross-presentation.

PubMed

Compeer, Ewoud Bernardus; Flinsenberg, Thijs Willem Hendrik; van der Grein, Susanna Geertje; Boes, Marianne

2012-01-01

Cross-presentation of endocytosed antigen as peptide/class I major histocompatibility complex complexes plays a central role in the elicitation of CD8(+) T cell clones that mediate anti-viral and anti-tumor immune responses. While it has been clear that there are specific subsets of professional antigen presenting cells capable of antigen cross-presentation, identification of mechanisms involved is still ongoing. Especially amongst dendritic cells (DC), there are specialized subsets that are highly proficient at antigen cross-presentation. We here present a focused survey on the cell biological processes in the endosomal pathway that support antigen cross-presentation. This review highlights DC-intrinsic mechanisms that facilitate the cross-presentation of endocytosed antigen, including receptor-mediated uptake, maturation-induced endosomal sorting of membrane proteins, dynamic remodeling of endosomal structures and cell surface-directed endosomal trafficking. We will conclude with the description of pathogen-induced deviation of endosomal processing, and discuss how immune evasion strategies pertaining endosomal trafficking may preclude antigen cross-presentation.

Characterization of MHC-II antigen presentation by B cells and monocytes from older individuals

PubMed Central

HL, Clark; R, Banks; L, Jones; TR, Hornick; PA, Higgins; CJ, Burant; DH, Canaday

2012-01-01

In this study we examine the effects of aging on antigen presentation of B cells and monocytes. We compared the antigen presentation function of peripheral blood B cells from young and old subjects using a system that specifically measures the B cell receptor (BCR)-mediated MHC-II antigen presentation. Monocytes were studied as well. Overall the mean magnitude of antigen presentation of soluble antigen and peptide was not different in older and younger subjects for both B cells and monocytes. Older subjects, however, showed increased heterogeneity of BCR-mediated antigen presentation by their B cells. The magnitude and variability of peptide presentation, which does not require uptake and processing, was the same between groups. Presentation by monocytes had similar variability between the older and younger subjects. These data suggest that poor B cell antigen processing, which results in diminished presentation in some older individuals may contribute to poor vaccine responses. PMID:22797466

Stable isotope ratios of tap water in the contiguous United States

NASA Astrophysics Data System (ADS)

Bowen, Gabriel J.; Ehleringer, James R.; Chesson, Lesley A.; Stange, Erik; Cerling, Thure E.

2007-03-01

Understanding links between water consumers and climatological (precipitation) sources is essential for developing strategies to ensure the long-term sustainability of water supplies. In pursing this understanding a need exists for tools to study and monitor complex human-hydrological systems that involve high levels of spatial connectivity and supply problems that are regional, rather than local, in nature. Here we report the first national-level survey of stable isotope ratios in tap water, including spatially and temporally explicit samples from a large number of cities and towns across the contiguous United States. We show that intra-annual ranges of tap water isotope ratios are relatively small (e.g., <10‰ for δ2H) at most sites. In contrast, spatial variation in tap water isotope ratios is very large, spanning ranges of 163‰ for δ2H and 23.6‰ for δ18O. The spatial distribution of tap water isotope ratios at the national level is similar to that of stable isotope ratios of precipitation. At the regional level, however, pervasive differences between tap water and precipitation isotope ratios can be attributed to hydrological factors in the water source to consumer chain. These patterns highlight the potential for monitoring of tap water isotope ratios to contribute to the study of regional water supply stability and provide warning signals for impending water resource changes. We present the first published maps of predicted tap water isotope ratios for the contiguous United States, which will be useful in guiding future research on human-hydrological systems and as a tool for applied forensics and traceability studies.

Tapping the Molecular Potential of Microalgae to Produce Biomass (JGI Seventh Annual User Meeting 2012: Genomics of Energy and Environment)

ScienceCinema

Sayre, Richard; Kyrpides, Nikos

2018-05-03

Richard Sayre, from Los Alamos National Laboratory, presents a talk titled "Tapping the Molecular Potential of Microalgae to Produce Biomass" at the JGI 7th Annual Users Meeting: Genomics of Energy & Environment Meeting on March 22, 2012 in Walnut Creek, California.

Teaching Problem Solving without Modeling through "Thinking Aloud Pair Problem Solving."

ERIC Educational Resources Information Center

Pestel, Beverly C.

1993-01-01

Reviews research relevant to the problem of unsatisfactory student problem-solving abilities and suggests a teaching strategy that addresses the issue. Author explains how she uses teaching aloud problem solving (TAPS) in college chemistry and presents evaluation data. Among the findings are that the TAPS class got fewer problems completely right,…

Gaining Momentum, Losing Ground. Progress Report, 2008

ERIC Educational Resources Information Center

Business Roundtable, 2008

2008-01-01

This report presents an update of the progress of Tapping America's Potential (TAP), a coalition of 15 of the nation's leading business organizations, and assesses three years' progress since 2005 in working towards the goal of doubling the number of students earning bachelor's degrees in science, technology, engineering and math (STEM) by 2015.…

Tapping the Molecular Potential of Microalgae to Produce Biomass (JGI Seventh Annual User Meeting 2012: Genomics of Energy and Environment)

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

Sayre, Richard; Kyrpides, Nikos

2012-03-22

Richard Sayre, from Los Alamos National Laboratory, presents a talk titled "Tapping the Molecular Potential of Microalgae to Produce Biomass" at the JGI 7th Annual Users Meeting: Genomics of Energy & Environment Meeting on March 22, 2012 in Walnut Creek, California.

Effect of oestradiol and pathogen-associated molecular patterns on class II-mediated antigen presentation and immunomodulatory molecule expression in the mouse female reproductive tract

PubMed Central

Ochiel, Daniel O; Rossoll, Richard M; Schaefer, Todd M; Wira, Charles R

2012-01-01

Cells of the female reproductive tract (FRT) can present antigen to naive and memory T cells. However, the effects of oestrogen, known to modulate immune responses, on antigen presentation in the FRT remain undefined. In the present study, DO11.10 T-cell antigen receptor transgenic mice specific for the class II MHC-restricted ovalbumin (OVA) 323–339 peptide were used to study the effects of oestradiol and pathogen-associated molecular patterns on antigen presentation in the FRT. We report here that oestradiol inhibited antigen presentation of OVA by uterine epithelial cells, uterine stromal cells and vaginal cells to OVA-specific memory T cells. When ovariectomized animals were treated with oestradiol for 1 or 3 days, antigen presentation was decreased by 20–80%. In contrast, incubation with PAMP increased antigen presentation by epithelial cells (Pam3Cys), stromal cells (peptidoglycan, Pam3Cys) and vaginal cells (Pam3Cys). In contrast, CpG inhibited both stromal and vaginal cell antigen presentation. Analysis of mRNA expression by reverse transcription PCR indicated that oestradiol inhibited CD40, CD80 and class II in the uterus and CD40, CD86 and class II in the vagina. Expression in isolated uterine and vaginal cells paralleled that seen in whole tissues. In contrast, oestradiol increased polymeric immunoglobulin receptor mRNA expression in the uterus and decreased it in the vagina. These results indicate that antigen-presenting cells in the uterus and vagina are responsive to oestradiol, which inhibits antigen presentation and co-stimulatory molecule expression. Further, these findings suggest that antigen-presenting cells in the uterus and vagina respond to selected Toll-like receptor agonists with altered antigen presentation. PMID:22043860

Efficient Capsid Antigen Presentation From Adeno-Associated Virus Empty Virions In Vivo

PubMed Central

Pei, Xiaolei; Earley, Lauriel Freya; He, Yi; Chen, Xiaojing; Hall, Nikita Elexa; Samulski, Richard Jude; Li, Chengwen

2018-01-01

Adeno-associated virus (AAV) vectors have been successfully applied in clinical trials for hemophilic patients. Although promising, the clinical results suggest that the capsid-specific CD8+T cell response has a negative effect on therapeutic success. In an in vitro analysis using an engineered AAV virus carrying immune-dominant SIINFEKL peptide in the capsid backbone, we have previously demonstrated that capsid antigen presentation from full (genome containing) AAV capsids requires endosome escape and is proteasome dependent and that no capsid antigen presentation is induced from empty virions. In the present study, we examined capsid antigen presentation from administration of empty virions in animal models. In wild-type mice, similar to AAV full particles, capsid antigen presentation from AAV empty virion infection was dose dependent, and the kinetics studies showed that antigen presentation was detected from 2 to 40 days after AAV empty virion administration. In the transporter associated with antigen processing 1 deficient (TAP−/−) mice, capsid antigen presentation was inhibited from both AAV full and empty virions, but higher inhibition was achieved from AAV full particle administration than that from empty virions. This indicates that the pathway of capsid antigen presentation from AAV transduction is dependent on proteasome-mediated degradation of AAV capsids (mainly for full particles) and that the endosomal pathway may also play a role in antigen presentation from empty particles but not full virions. The capsid antigen presentation efficiency from AAV preparations was positively correlated with the amount of empty virions contaminated with full particles. Collectively, the results indicate that contamination of AAV empty virions induces efficient antigen presentation in vivo and the mechanism of capsid antigen presentation from empty virions involves both endosomal and proteasomal pathways. The elucidation of capsid antigen presentation from AAV empty virions may allow us to rationally design effective strategies to prevent elimination of AAV transduced target cells by capsid specific CD8+ T cells. PMID:29725339

Financial and environmental modelling of water hardness--implications for utilising harvested rainwater in washing machines.

PubMed

Morales-Pinzón, Tito; Lurueña, Rodrigo; Gabarrell, Xavier; Gasol, Carles M; Rieradevall, Joan

2014-02-01

A study was conducted to determine the financial and environmental effects of water quality on rainwater harvesting systems. The potential for replacing tap water used in washing machines with rainwater was studied, and then analysis presented in this paper is valid for applications that include washing machines where tap water hardness may be important. A wide range of weather conditions, such as rainfall (284-1,794 mm/year); water hardness (14-315 mg/L CaCO3); tap water prices (0.85-2.65 Euros/m(3)) in different Spanish urban areas (from individual buildings to whole neighbourhoods); and other scenarios (including materials and water storage capacity) were analysed. Rainfall was essential for rainwater harvesting, but the tap water prices and the water hardness were the main factors for consideration in the financial and the environmental analyses, respectively. The local tap water hardness and prices can cause greater financial and environmental impacts than the type of material used for the water storage tank or the volume of the tank. The use of rainwater as a substitute for hard water in washing machines favours financial analysis. Although tap water hardness significantly affects the financial analysis, the greatest effect was found in the environmental analysis. When hard tap water needed to be replaced, it was found that a water price of 1 Euro/m(3) could render the use of rainwater financially feasible when using large-scale rainwater harvesting systems. When the water hardness was greater than 300 mg/L CaCO3, a financial analysis revealed that an net present value greater than 270 Euros/dwelling could be obtained at the neighbourhood scale, and there could be a reduction in the Global Warming Potential (100 years) ranging between 35 and 101 kg CO2 eq./dwelling/year. Copyright © 2013 Elsevier B.V. All rights reserved.

Two Axis Pointing System (TAPS) attitude acquisition, determination, and control

NASA Technical Reports Server (NTRS)

Azzolini, John D.; Mcglew, David E.

1990-01-01

The Two Axis Pointing System (TAPS) is a 2 axis gimbal system designed to provide fine pointing of Space Transportation System (STS) borne instruments. It features center-of-mass instrument mounting and will accommodate instruments of up to 1134 kg (2500 pounds) which fit within a 1.0 by 1.0 by 4.2 meter (40 by 40 by 166 inch) envelope. The TAPS system is controlled by a microcomputer based Control Electronics Assembly (CEA), a Power Distribution Unit (PDU), and a Servo Control Unit (SCU). A DRIRU-II inertial reference unit is used to provide incremental angles for attitude propagation. A Ball Brothers STRAP star tracker is used for attitude acquisition and update. The theory of the TAPS attitude determination and error computation for the Broad Band X-ray Telescope (BBXRT) are described. The attitude acquisition is based upon a 2 star geometric solution. The acquisition theory and quaternion algebra are presented. The attitude control combines classical position, integral and derivative (PID) control with techniques to compensate for coulomb friction (bias torque) and the cable harness crossing the gimbals (spring torque). Also presented is a technique for an adaptive bias torque compensation which adjusts to an ever changing frictional torque environment. The control stability margins are detailed, with the predicted pointing performance, based upon simulation studies. The TAPS user interface, which provides high level operations commands to facilitate science observations, is outlined.

The Beat Goes on: Rhythmic Modulation of Cortical Potentials by Imagined Tapping

ERIC Educational Resources Information Center

Osman, Allen; Albert, Robert; Ridderinkhof, K. Richard; Band, Guido; van der Molen, Maurits

2006-01-01

A frequency analysis was used to tag cortical activity from imagined rhythmic movements. Participants synchronized overt and imagined taps with brief visual stimuli presented at a constant rate, alternating between left and right index fingers. Brain potentials were recorded from across the scalp and topographic maps made of their power at the…

A Comparative Study of Analgesic Efficacy of Intrathecal Buprenorphine with Ultrasound-Guided Transversus Abdominis Plane Block for Postcesarean Delivery Analgesia.

PubMed

Marappa, Prakash; Chikkapillappa, Manjunath Abloodu; Chennappa, Nagaraj Mungasuvalli; Pujari, Vinayak Seenappa

2017-01-01

Women undergoing cesarean (CS) delivery present a unique set of challenges to the anesthetist in terms of postoperative pain management. This study was conducted to compare the analgesic efficacy of intrathecal buprenorphine (ITB) with ultrasound-guided transversus abdominis plane (TAP) block in post-CS delivery pain. A prospective randomized comparative study of sixty American Society of Anesthesiologists physical status I and II pregnant patients divided into two groups of thirty each as ITB group and TAP block group after satisfying the inclusion criteria. In the present study, demographic data were comparable between both groups. The time to first analgesic request was significantly longer in ITB group (389.67 ± 90.78 min) compared to TAP group (669.17 ± 140.65 min) and was statistically significant, P < 0.001. The mean paracetamol consumption in the first 24 h was higher in the TAP group (3.5 g) compared to the ITB group (1.13 g) and was statistically significant, P < 0.0001, and the mean tramadol consumed in first 24 h was higher in the TAP (46.66 mg) group as compared to the ITB group (16.66 mg) and was statistically significant, P < 0.001. The mean visual analog scale scores assessed at 4, 6, 12, and 24 h was higher in the TAP group and was statistically significant, P < 0.001. Our study showed that patients receiving ITB for post-CS pain management reported longer duration of analgesia, lower pain scores, and lower analgesic consumption during the first 24 h. The benefits of neuraxial opiates are significant and far outweigh the side effects.

Efficacy of transverse abdominis plane block in reduction of postoperation pain in laparoscopic cholecystectomy.

PubMed

Saliminia, Alireza; Azimaraghi, Omid; Babayipour, Shiva; Ardavan, Kamelia; Movafegh, Ali

2015-12-01

Transversus abdominis plane (TAP) block is a recently introduced regional anesthesia technique that is used for postoperative pain reduction in some abdominal surgeries. The present study evaluated the efficacy of the TAP block on the post laparoscopic cholecystectomy pain intensity and analgesic consumption. Fifty-four patients were enrolled in three groups: TAP block with normal saline (Group 1, n = 18); TAP block with bupivacaine (Group 2, n = 18); and TAP block with bupivacaine plus sufentanil (Group 3, n = 18). The time to the first fentanyl request, fentanyl consumption in the 24 hours following surgery, and postoperative pain intensity at 30 minutes, 1 hour, 6 hours, 12 hours, and 24 hours following discharge for recovery were measured and recorded. The total amount of 24-hour fentanyl consumption was higher in Group 1 (877.8 ± 338.8 μg) than either Group 2 (566.7 ± 367.8 μg) or Group 3 (555.5 ± 356.8 μg; p = 0.03). Postoperative pain score was higher in Group 1 than intervention groups (p = 0.006); however, there was no significant difference in intervention groups. The time to the first fentanyl request in Group 1 (79.44 ± 42.2) was significantly lower than Group 3 (206.38 ± 112.7; p = 0.001). The present study demonstrated that bilateral TAP block with 0.5% bupivacaine reduces post laparoscopic cholecystectomy pain intensity and fentanyl request and prolongs time to the first analgesic request. Adding sufentanil to the block solution reduced neither pain intensity nor fentanyl further consumption. Copyright © 2015. Published by Elsevier B.V.

Weber (slope) analyses of timing variability in tapping and drawing tasks.

PubMed

Spencer, Rebecca M C; Zelaznik, Howard N

2003-12-01

Timing variability in continuous drawing tasks has not been found to be correlated with timing variability in repetitive finger tapping in recent studies (S. D. Robertson et al., 1999; H. N. Zelaznik, R. M. C. Spencer, & R. B. Ivry, 2002). Furthermore, the central component of timing variability, as measured by the slope of the timing variance versus the square of the timed interval, differed for tapping and drawing tasks. On the basis of those results, the authors posited that timing in tapping is explicit and as such uses a central representation of the interval to be timed, whereas timing in drawing tasks is implicit, that is, the temporal component is an emergent property of the trajectory produced. The authors examined that hypothesis in the present study by determining the linear relationship between timing variance and squared duration for tapping, circle-drawing, and line-drawing tasks. Participants (N = 50) performed 1 of 5 tasks: finger tapping, line drawing in the x dimension, line drawing in the y dimension, continuous circle drawing timed in the x dimension, or continuous circle drawing timed in the y dimension. The slopes differed significantly between finger tapping, line drawing, and circle drawing, suggesting separable sources of timing variability. The slopes of the 2 circle-drawing tasks did not differ from one another, nor did the slopes of the 2 line-drawing tasks differ significantly, suggesting a shared timing process within those tasks. Those results are evidence of a high degree of specificity in timing processes.

A comparison of damage profiling of automated tap testers on aircraft CFRP panel

NASA Astrophysics Data System (ADS)

Mohd Aris, K. D.; Shariff, M. F.; Abd Latif, B. R.; Mohd Haris, M. Y.; Baidzawi, I. J.

2017-12-01

The use of composite materials nevertheless is getting more prominent. The combination of reinforcing fibers and matrices will produce the desired strength orientation, tailorability and not to mention the complex shape that is hard to form on metallic structure. The weight percentage of composite materials used in aerospace, civil, marine etc. has increased tremendously. Since composite are stacked together, the possibility of delamination and/disbond defects are highly present either in the monolithic or sandwich structures. Tap test is the cheapest form of nondestructive test to identify the presence of this damage. However, its inconsistency and wide area of coverage can reduce its effectivity since it is carried out manually. The indigenous automated tap tester known as KETOK was used to detect the damage due to trapped voids and air pockets. The mechanism of detection is through controlling the tapping on the surface automatically at a constant rate. Another manual tap tester RD-3 from Wichitech Industries Inc. was used as reference. The acquired data was translated into damage profiling and both results were compared. The results have shown that the indigenous automated tester can profile the damage better when compared with the existing tap tester. As a conclusion, the indigenous automated tap tester has a potential to be used as an IN-SITU damage detection tool to detect delamination and disbond damage on composite panel. However, more conclusive tests need to be done in order to make the unit available to conventional users.

Understanding the Biology of Antigen Cross-Presentation for the Design of Vaccines Against Cancer

PubMed Central

Fehres, Cynthia M.; Unger, Wendy W. J.; Garcia-Vallejo, Juan J.; van Kooyk, Yvette

2014-01-01

Antigen cross-presentation, the process in which exogenous antigens are presented on MHC class I molecules, is crucial for the generation of effector CD8+ T cell responses. Although multiple cell types are being described to be able to cross-present antigens, in vivo this task is mainly carried out by certain subsets of dendritic cells (DCs). Aspects such as the internalization route, the pathway of endocytic trafficking, and the simultaneous activation through pattern-recognition receptors have a determining influence in how antigens are handled for cross-presentation by DCs. In this review, we will summarize new insights in factors that affect antigen cross-presentation of human DC subsets, and we will discuss the possibilities to exploit antigen cross-presentation for immunotherapy against cancer. PMID:24782858

Benefit Estimates of Terminal Area Productivity Program Technologies

NASA Technical Reports Server (NTRS)

Hemm, Robert; Shapiro, Gerald; Lee, David; Gribko, Joana; Glaser, Bonnie

1999-01-01

This report documents benefit analyses for the NASA Terminal Area Technology (TAP) technology programs. Benefits are based on reductions in arrival delays at ten major airports over the 10 years from 2006 through 2015. Detailed analytic airport capacity and delay models were constructed to produce the estimates. The goal of TAP is enable good weather operations tempos in all weather conditions. The TAP program includes technologies to measure and predict runway occupancy times, reduce runway occupancy times in bad weather, accurately predict wake vortex hazards, and couple controller automation with aircraft flight management systems. The report presents and discusses the estimate results and describes the models. Three appendixes document the model algorithms and discuss the input parameters selected for the TAP technologies. The fourth appendix is the user's guide for the models. The results indicate that the combined benefits for all TAP technologies at all 10 airports range from $550 to $650 million per year (in constant 1997 dollars). Additional benefits will accrue from reductions in departure delays. Departure delay benefits are calculated by the current models.

Thrombin-activatable fluorescent peptide incorporated gold nanoparticles for dual optical/computed tomography thrombus imaging.

PubMed

Kwon, Sung-Pil; Jeon, Sangmin; Lee, Sung-Hoon; Yoon, Hong Yeol; Ryu, Ju Hee; Choi, Dayil; Kim, Jeong-Yeon; Kim, Jiwon; Park, Jae Hyung; Kim, Dong-Eog; Kwon, Ick Chan; Kim, Kwangmeyung; Ahn, Cheol-Hee

2018-01-01

Thrombosis is an important pathophysiologic phenomenon in various cardiovascular diseases, which can lead to oxygen deprivation and infarction of tissues by generation of a thrombus. Thus, direct thrombus imaging can provide beneficial in diagnosis and therapy of thrombosis. Herein, we developed thrombin-activatable fluorescent peptide (TAP) incorporated silica-coated gold nanoparticles (TAP-SiO 2 @AuNPs) for direct imaging of thrombus by dual near-infrared fluorescence (NIRF) and micro-computed tomography (micro-CT) imaging, wherein TAP molecules were used as targeted thrombin-activatable peptide probes for thrombin-specific NIRF imaging. The freshly prepared TAP-SiO 2 @AuNPs had an average diameter of 39.8 ± 2.55 nm and they showed the quenched NIRF signal in aqueous condition, due to the excellent quenching effect of TAP molecules on the silica-gold nanoparticle surface. However, 30.31-fold higher NIRF intensity was rapidly recovered in the presence of thrombin in vitro, due to the thrombin-specific cleavage of quenched TAP molecules on the gold particle surface. Furthermore, TAP-SiO 2 @AuNPs were successfully accumulated in thrombus by their particle size-dependent capturing property, and they presented a potential X-ray absorption property in a dose-dependent manner. Finally, thrombotic lesion was clearly distinguished from peripheral tissues by dual NIRF/micro-CT imaging after intravenous injection of TAP-SiO 2 @AuNPs in the in situ thrombotic mouse model, simultaneously. This study showed that thrombin-activatable fluorescent peptide incorporated silica-coated gold nanoparticles can be potentially used as a dual imaging probe for direct thrombus imaging and therapy in clinical applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Depletion of pro-oncogenic RUNX2 enhances gemcitabine (GEM) sensitivity of p53-mutated pancreatic cancer Panc-1 cells through the induction of pro-apoptotic TAp63.

PubMed

Ozaki, Toshinori; Nakamura, Mizuyo; Ogata, Takehiro; Sang, Meijie; Yoda, Hiroyuki; Hiraoka, Kiriko; Sang, Meixiang; Shimozato, Osamu

2016-11-01

Recently, we have described that siRNA-mediated silencing of runt-related transcription factor 2 (RUNX2) improves anti-cancer drug gemcitabine (GEM) sensitivity of p53-deficient human pancreatic cancer AsPC-1 cells through the augmentation of p53 family TAp63-dependent cell death pathway. In this manuscript, we have extended our study to p53-mutated human pancreatic cancer Panc-1 cells. According to our present results, knockdown of mutant p53 alone had a marginal effect on GEM-mediated cell death of Panc-1 cells. We then sought to deplete RUNX2 using siRNA in Panc-1 cells and examined its effect on GEM sensitivity. Under our experimental conditions, RUNX2 knockdown caused a significant enhancement of GEM sensitivity of Panc-1 cells. Notably, GEM-mediated induction of TAp63 but not of TAp73 was further stimulated in RUNX2-depleted Panc-1 cells, indicating that, like AsPC-1 cells, TAp63 might play a pivotal role in the regulation of GEM sensitivity of Panc-1 cells. Consistent with this notion, forced expression of TAp63α in Panc-1 cells promoted cell cycle arrest and/or cell death, and massively increased luciferase activities driven by TAp63-target gene promoters such as p21WAF1 and NOXA. In addition, immunoprecipitation experiments indicated that RUNX2 forms a complex with TAp63 in Panc-1 cells. Taken together, our current observations strongly suggest that depletion of RUNX2 enhances the cytotoxic effect of GEM on p53-mutated Panc-1 cells through the stimulation of TAp63-dependent cell death pathway even in the presence of a large amount of pro-oncogenic mutant p53, and might provide an attractive strategy to treat pancreatic cancer patients with p53 mutations.

Depletion of pro-oncogenic RUNX2 enhances gemcitabine (GEM) sensitivity of p53-mutated pancreatic cancer Panc-1 cells through the induction of pro-apoptotic TAp63

PubMed Central

Ozaki, Toshinori; Nakamura, Mizuyo; Ogata, Takehiro; Sang, Meijie; Yoda, Hiroyuki; Hiraoka, Kiriko; Sang, Meixiang; Shimozato, Osamu

2016-01-01

Recently, we have described that siRNA-mediated silencing of runt-related transcription factor 2 (RUNX2) improves anti-cancer drug gemcitabine (GEM) sensitivity of p53-deficient human pancreatic cancer AsPC-1 cells through the augmentation of p53 family TAp63-dependent cell death pathway. In this manuscript, we have extended our study to p53-mutated human pancreatic cancer Panc-1 cells. According to our present results, knockdown of mutant p53 alone had a marginal effect on GEM-mediated cell death of Panc-1 cells. We then sought to deplete RUNX2 using siRNA in Panc-1 cells and examined its effect on GEM sensitivity. Under our experimental conditions, RUNX2 knockdown caused a significant enhancement of GEM sensitivity of Panc-1 cells. Notably, GEM-mediated induction of TAp63 but not of TAp73 was further stimulated in RUNX2-depleted Panc-1 cells, indicating that, like AsPC-1 cells, TAp63 might play a pivotal role in the regulation of GEM sensitivity of Panc-1 cells. Consistent with this notion, forced expression of TAp63α in Panc-1 cells promoted cell cycle arrest and/or cell death, and massively increased luciferase activities driven by TAp63-target gene promoters such as p21WAF1 and NOXA. In addition, immunoprecipitation experiments indicated that RUNX2 forms a complex with TAp63 in Panc-1 cells. Taken together, our current observations strongly suggest that depletion of RUNX2 enhances the cytotoxic effect of GEM on p53-mutated Panc-1 cells through the stimulation of TAp63-dependent cell death pathway even in the presence of a large amount of pro-oncogenic mutant p53, and might provide an attractive strategy to treat pancreatic cancer patients with p53 mutations. PMID:27713122

Into hot water head first: distribution of intentional and unintentional immersion burns.

PubMed

Daria, Sonya; Sugar, Naomi F; Feldman, Kenneth W; Boos, Stephen C; Benton, Scott A; Ornstein, Amy

2004-05-01

Experience with several, previously unreported, intentional face-first immersion burns led us to evaluate the distribution of inflicted and unintentional immersion scald burns in a hospital series. (1) Authors' clinical and legal practices; (2) Burn center at regional Level 1 trauma hospital. : (1) Case series of face-first, inflicted immersion burn victims; (2) Consecutive hospitalized scald burn victims younger than 5 years old, 1/3/1996 to 3/25/2000. (1) Individual case reports; (2) Retrospective records review. Simple descriptive statistics, Fisher Exact test and t test. (1) Six cases of inflicted head and neck immersion injury are described. Four were tap water and 2 food/drink scalds. (2) 22/195 hospitalized victims had sustained immersion burns, 13 from tap water and 9 from other fluids. Six (46%) tap water immersions and no (0%) other immersions had inflicted injuries (P = 0.05). Two of the tap water immersions and one other source immersion included burning of the head and neck. Of these, one tap water immersion, but no other immersion, was inflicted. In no patients were head and neck injuries the sole or predominant site of scalding. In all, 9 children sustained inflicted scalds. Bilateral lower extremity tap water immersion scalds occurred in 100% (6/6) of abusive and 29% (2/7) of unintentional injuries (P = 0.02). Buttock and perineal injuries occurred in 67% (4/6) inflicted versus 29% (2/7) unintentional tap water immersion scalds (P = 0.28). Other fluids caused bilateral lower extremity immersion burns in 3/9 (33 %) unintentionally injured patients, but no abused children (NS). Craniofacial immersion injury, although seen by the authors in legal cases, is infrequent. It was present incidentally in one inflicted tap water burn in the consecutive hospital series. This series affirms the predominance of bilateral lower extremity burns in inflicted tap water immersions. Buttock/perineal immersions were more common with abuse than with unintentional injury.

Evaluation of transversus abdominis plane block for renal transplant recipients - A meta-analysis and trial sequential analysis of published studies.

PubMed

Singh, Preet Mohinder; Borle, Anuradha; Makkar, Jeetinder Kaur; Trisha, Aanjan; Sinha, Aashish

2018-01-01

Patients undergoing renal transplant (RT) have altered drug/opioid pharmacokinetics. Transversus abdominis plane (TAP) block in renal transplant recipients has been recently evaluated for analgesic and opioid-sparing potential by many trials. The studies comparing TAP-block to conventional analgesic regimens for RT were searched. Comparisons were made for total opioids consumed (as morphine-equivalents) during the first postoperative 24-h (primary objective), intraoperative, and immediate-postoperative period. Pain scores and postoperative nausea-vomiting (PONV) were also evaluated. Trial sequential analysis (TSA) was used to quantify the strength of analysis. Ten-trials with 258 and 237 patients in control and TAP-block group, respectively, were included. TAP-block decreased the 24-h (reported in 9-trials) opioid consumption by 14.61 ± 4.34 mg (reduction by 42.7%, random-effects, P < 0.001, I 2 = 97.82%). Sample size of the present analysis (472) was well past the required "information-size" variable (396) as per the TSA for a power of 85%. Intraoperative opioid consumption also decreased by 2.06 ± 0.63 mg (reduction of 27.8%) (random effects, P < 0.001, I 2 = 98.84%). Pain scores with TAP-block were significantly lower in both early and delayed postoperative phase. Odds ratio for PONV without TAP block was 1.99 ± 1.05 (Fixed-effects, P = 0.04, I 2 = 0%). Publication bias was likely (Egger's test, X-intercept=7.89, P < 0.05). TAP-block significantly lowers the intraoperative and cumulative postoperative 24-h opioid consumption in RT recipients. Persistent and better pain control is achieved when TAP-Block is used. Benefits of TAP block extend beyond the analgesic actions alone as it also decreases the 24-h incidence of postoperative nausea vomiting as well. The technique of the block needs standardization for RT recipients.

[One-time effects of drinking mineral water and tap water enriched with silver nanoparticles on the biochemical markers of liver condition and metabolic parameters in healthy rats].

PubMed

Efimenko, N V; Frolkov, V K; Kozlova, V V; Kaisinova, A S; Chalaya, E N

2017-12-05

 The objective of the present research was to study the influence of tap water enriched with silver nanoparticles (NP) as well as that of «Krasnoarmeysky» and «Essentuki №17» mineral waters after their single administration through the oral gavage to the rats on the metabolism of carbohydrates and lipids, the biochemical markers of the liver condition, and the endocrine profile in the healthy animals.  The laboratory animals (130 male Wistar rats) were allocated to thirteen groups comprised of 10 rats each as follows: 1st group (n=10) intact animals, 2nd group (5 minutes after the administration of silver NP (n=10), 3rd group (15 minutes after the of silver NP), 4th group (60 minutes after the administration of silver NP), 5th group (n=10) (5 minutes after the introduction of the «Krasnoarmeysky» mineral water), 6th group (n=10) (15 min after the introduction of the «Krasnoarmeysky» mineral water), 7th group (n=10), (60 minutes after the introduction of the «Krasnoarmeysky» mineral water) 8th group (n=10) (5 minutes after the introduction of the «Essentuki № 17» mineral water), 9th group (n=10) (15 min after the introduction of the «Essentuki № 7» mineral water) , 10th group (n=10) (60 minutes after the introduction of the «Essentuki №17» mineral water), 11th group (n=10) (5 minutes after administration of tap water (control),12th group (n=10) (15 minutes after administration of tap water (control), and 13th (n=10) group 60 minutes after administration of tap water (control).  The study has demonstrated that the tap water enriched with silver nanoparticles similar to the mineral waters caused stress reactions that are inferior to those induced by «Essentuki №17» mineral water in terms of the magnitude; however, the effect provoked by the tap water was of longer duration. Moreover, the tap water enriched with silver nanoparticles stimulates prooxidant reactions, and inhibit the activity of antioxidant protection. Silver nanoparticles appear to produce some destructive effect on the hepatocytes.  The silver nanoparticles present in the tap water have a significant biological potential of their own. Moreover, their one-time action is apt to alter the biological potential of the water into which they are administered. The single intake of the tap water enriched with silver nanoparticles by the healthy laboratory animals produces the response that resembles that of the drinking mineral water.

System for automatically switching transformer coupled lines

NASA Technical Reports Server (NTRS)

Dwinell, W. S. (Inventor)

1979-01-01

A system is presented for automatically controlling transformer coupled alternating current electric lines. The secondary winding of each transformer is provided with a center tap. A switching circuit is connected to the center taps of a pair of secondary windings and includes a switch controller. An impedance is connected between the center taps of the opposite pair of secondary windings. The switching circuit has continuity when the AC lines are continuous and discontinuity with any disconnect of the AC lines. Normally open switching means are provided in at least one AC line. The switch controller automatically opens the switching means when the AC lines become separated.

Nonlinear tapping dynamics of multi-walled carbon nanotube tipped atomic force microcantilevers

NASA Astrophysics Data System (ADS)

Lee, S. I.; Howell, S. W.; Raman, A.; Reifenberger, R.; Nguyen, C. V.; Meyyappan, M.

2004-05-01

The nonlinear dynamics of an atomic force microcantilever (AFM) with an attached multi-walled carbon nanotube (MWCNT) tip is investigated experimentally and theoretically. We present the experimental nonlinear frequency response of a MWCNT tipped microcantilever in the tapping mode. Several unusual features in the response distinguish it from those traditionally observed for conventional tips. The MWCNT tipped AFM probe is apparently immune to conventional imaging instabilities related to the coexistence of attractive and repulsive tapping regimes. A theoretical interaction model for the system using an Euler elastica MWCNT model is developed and found to predict several unusual features of the measured nonlinear response.

Systems Engineering Management Plan NASA Traffic Aware Planner Integration Into P-180 Airborne Test-Bed

NASA Technical Reports Server (NTRS)

Maris, John

2015-01-01

NASA's Traffic Aware Planner (TAP) is a cockpit decision support tool that provides aircrew with vertical and lateral flight-path optimizations with the intent of achieving significant fuel and time savings, while automatically avoiding traffic, weather, and restricted airspace conflicts. A key step towards the maturation and deployment of TAP concerned its operational evaluation in a representative flight environment. This Systems Engineering Management Plan (SEMP) addresses the test-vehicle design, systems integration, and flight-test planning for the first TAP operational flight evaluations, which were successfully completed in November 2013. The trial outcomes are documented in the Traffic Aware Planner (TAP) flight evaluation paper presented at the 14th AIAA Aviation Technology, Integration, and Operations Conference, Atlanta, GA. (AIAA-2014-2166, Maris, J. M., Haynes, M. A., Wing, D. J., Burke, K. A., Henderson, J., & Woods, S. E., 2014).

Secreted Immunodominant Mycobacterium tuberculosis Antigens Are Processed by the Cytosolic Pathway

PubMed Central

Grotzke, Jeff E.; Siler, Anne C.; Lewinsohn, Deborah A.; Lewinsohn, David M.

2010-01-01

Exposure to Mycobacterium tuberculosis can result in lifelong but asymptomatic infection in most individuals. Although CD8+ T cells are elicited at high frequencies over the course of infection in both humans and mice, how phagosomal M. tuberculosis Ags are processed and presented by MHC class I molecules is poorly understood. Broadly, both cytosolic and noncytosolic pathways have been described. We have previously characterized the presentation of three HLA-I epitopes from M. tuberculosis and shown that these Ags are processed in the cytosol, whereas others have demonstrated noncytosolic presentation of the 19-kDa lipoprotein as well as apoptotic bodies from M. tuberculosis-infected cells. In this paper, we now characterize the processing pathway in an additional six M. tuberculosis epitopes from four proteins in human dendritic cells. Addition of the endoplasmic reticulum-Golgi trafficking inhibitor, brefeldin A, resulted in complete abrogation of Ag processing consistent with cytosolic presentation. However, although addition of the proteasome inhibitor epoxomicin blocked the presentation of two epitopes, presentation of four epitopes was enhanced. To further examine the requirement for proteasomal processing of an epoxomicin-enhanced epitope, an in vitro proteasome digestion assay was established. We find that the proteasome does indeed generate the epitope and that epitope generation is enhanced in the presence of epoxomicin. To further confirm that both the epoxomicin-inhibited and epoxomicin-enhanced epitopes are processed cytosolically, we demonstrate that TAP transport and new protein synthesis are required for presentation. Taken together, these data demonstrate that immunodominant M. tuberculosis CD8+ Ags are processed and presented using a cytosolic pathway. PMID:20802151

Finger tapping and verbal fluency post-tap test improvement in INPH: its value in differential diagnosis and shunt-treatment outcomes prognosis.

PubMed

Liouta, Evangelia; Gatzonis, Stylianos; Kalamatianos, Theodosis; Kalyvas, Aristotelis; Koutsarnakis, Christos; Liakos, Faidon; Anagnostopoulos, Christos; Komaitis, Spyridon; Giakoumettis, Dimitris; Stranjalis, George

2017-12-01

Idiopathic normal pressure hydrocephalus (INPH) diagnosis is challenging as it can be mimicked by other neurological conditions, such as neurodegenerative dementia and motor syndromes. Additionally, outcomes after lumbar puncture (LP) tap test and shunt treatment may vary due to the lack of a common protocol in INPH assessment. The present study aimed to assess whether a post-LP test amelioration of frontal cognitive dysfunctions, characterizing this syndrome, can differentiate INPH from similar neurological conditions and whether this improvement can predict INPH post-shunt outcomes. Seventy-one consecutive patients referred for INPH suspicion and LP testing, were enrolled. According to the consensus guidelines criteria, 29 patients were diagnosed as INPH and 42 were assigned an alternative diagnosis (INPH-like group) after reviewing clinical, neuropsychological and imaging data, and before LP results. A comprehensive neuropsychological assessment for frontal executive, upper extremity fine motor functions, aphasias, apraxias, agnosias and gait evaluation were administered at baseline. Executive, fine motor functions and gait were re-examined post-LP test in all patients and post-shunt placement in INPH patients. Of the INPH patients, 86.2% showed cognitive amelioration in the post-LP test; in addition, all but one (97%) presented with neurocognitive and gait improvement post-shunt. Verbal phonological fluency and finger tapping task post-LP improvement predicted positive clinical outcome post-shunt. None of the INPH-like group presented with neurocognitive improvement post-LP. Post-LP amelioration of verbal fluency and finger tapping deficits can differentiate INPH from similar disorders and predict positive post-shunt clinical outcome in INPH. This becomes of great importance when gait assessment is difficult to perform in clinical practice.

Quality comparison of tap water vs. bottled water in the industrial city of Yanbu (Saudi Arabia).

PubMed

Ahmad, Maqbool; Bajahlan, Ahmad S

2009-12-01

This study was conducted to compare the quality of bottled water with potabilized desalinated tap water. Fourteen brands of local and imported bottled water samples were collected from the local market and analyzed for physicochemical parameters in the Royal Commission Environmental Laboratory. Results were compared with 5-year continuous monitoring data of tap water from different locations in Madinat Yanbu Al-Sinaiyah (MYAS) including storage tanks of desalination plant. Results show that there was no significant difference in the quality of tap water and bottled water. Bacteriological test was never found positive in the 5-year data in tap water. Similarly, physicochemical analysis shows the persistent quality of tap water. Based on hardness analysis, bottled and tap water are categorized as soft water. Trihalomethanes (THMs) study also indicates that traces of disinfection by products (DBPs) are present in both tap and bottled water and are much less than the World Health Organization and Environmental Protection Agency maximum permissible limits. It is also important to note that the tap water distribution network in MAYS is a high-pressure recirculation network and there is no chance to grow bacteria in stagnant water in pipe lines or houses. Recently, the Royal Commission has replaced the whole drinking water network, which was made of asbestos-cemented pipes with glass-reinforced plastic (GRP) pipes, to avoid any asbestos contaminations. Based on these results, it is concluded that drinking water distributed in the city is of very good and persistent quality, comparable with bottled water. Continuous monitoring also guarantees the safe drinking water to the community. Hence, it is the responsibility of the Royal Commission to encourage the peoples in the city to drink tap water as it is as good as bottled water even better than some of the brands and is monitored regularly. It is also much cheaper compared to bottled water and is available round the clock. Preference for tap water over bottled water will also reduce the production of bottled water that has flooded the market, the enormous strain on the environment, and the pollution due to used empty plastic bottles in the landfill area and will help to keep the city clean.

Adeno-associated virus capsid antigen presentation is dependent on endosomal escape

PubMed Central

Li, Chengwen; He, Yi; Nicolson, Sarah; Hirsch, Matt; Weinberg, Marc S.; Zhang, Ping; Kafri, Tal; Samulski, R. Jude

2013-01-01

Adeno-associated virus (AAV) vectors are attractive for gene delivery-based therapeutics, but data from recent clinical trials have indicated that AAV capsids induce a cytotoxic T lymphocyte (CTL) response that eliminates transduced cells. In this study, we used traditional pharmacological agents and AAV mutants to elucidate the pathway of capsid cross-presentation in AAV-permissive cells. Endosomal acidification inhibitors blocked AAV2 antigen presentation by over 90%, while proteasome inhibitors completely abrogated antigen presentation. Using mutant viruses that are defective for nuclear entry, we observed a 90% decrease in capsid antigen presentation. Different antigen presentation efficiencies were achieved by selectively mutating virion nuclear localization signals. Low antigen presentation was demonstrated with basic region 1 (BR1) mutants, despite relatively high transduction efficiency, whereas there was no difference in antigen presentation between BR2 and BR3 mutants defective for transduction, as compared with wild-type AAV2. These results suggest that effective AAV2 capsid antigen presentation is dependent on AAV virion escape from the endosome/lysosome for antigen degradation by proteasomes, but is independent of nuclear uncoating. These results should facilitate the design of effective strategies to evade capsid-specific CTL-mediated elimination of AAV-transduced target cells in future clinical trials. PMID:23454772

Four quadrant transversus abdominis plane block and continuous transversus abdominis plane analgesia: a 3-year prospective audit in 124 patients.

PubMed

Niraj, G; Kelkar, Aditi; Hart, Elaine; Kaushik, Vipul; Fleet, Danny; Jameson, John

2015-11-01

Transversus abdominis plane (TAP) blocks have been reported to be an effective method of providing analgesia after abdominal surgery. To perform a prospective audit on the effectiveness of a novel technique of providing continuous transversus abdominis plane (TAP) analgesia in patients undergoing emergency and elective abdominal surgery. Prospective single center audit over a 3-year period. University hospital. One hundred twenty-four American Society of Anesthesiologists I to IV adult patients presenting for elective as well as emergency abdominal surgery in whom epidural analgesia was contraindicated or refused. Four quadrant TAP blocks and continuous TAP analgesia. Numerical rating scale pain scores at rest and on coughing, nausea scores, satisfaction scores, complications, frequency of analgesia failure, therapeutic failure with continuous TAP analgesia and opioid consumption. One hundred twenty-four patients who received continuous TAP analgesia were audited. This included 34 patients for elective open surgery, 36 patients for emergency laparotomy, and 54 patients who underwent elective laparoscopic colorectal surgery. Surgical incision was within the dermatomal limit of the block in 70% of the patients (88/124). Therapeutic failure with the technique was 10%. Frequency of analgesic failure over the 48-hour period was none in 39% and below 5 episodes in 57%. Four quadrant transversus abdominis plane blocks and continuous TAP analgesia is an effective technique for providing postoperative analgesia after abdominal surgery. It has the potential to be used as a sole analgesic technique when the surgical incision is within its dermatomal limit. Copyright © 2015 Elsevier Inc. All rights reserved.

Neural correlates of cerebellar-mediated timing during finger tapping in children with fetal alcohol spectrum disorders.

PubMed

du Plessis, Lindie; Jacobson, Sandra W; Molteno, Christopher D; Robertson, Frances C; Peterson, Bradley S; Jacobson, Joseph L; Meintjes, Ernesta M

2015-01-01

Classical eyeblink conditioning (EBC), an elemental form of learning, is among the most sensitive indicators of fetal alcohol spectrum disorders. The cerebellum plays a key role in maintaining timed movements with millisecond accuracy required for EBC. Functional MRI (fMRI) was used to identify cerebellar regions that mediate timing in healthy controls and the degree to which these areas are also recruited in children with prenatal alcohol exposure. fMRI data were acquired during an auditory rhythmic/non-rhythmic finger tapping task. We present results for 17 children with fetal alcohol syndrome (FAS) or partial FAS, 17 heavily exposed (HE) nonsyndromal children and 16 non- or minimally exposed controls. Controls showed greater cerebellar blood oxygen level dependent (BOLD) activation in right crus I, vermis IV-VI, and right lobule VI during rhythmic than non-rhythmic finger tapping. The alcohol-exposed children showed smaller activation increases during rhythmic tapping in right crus I than the control children and the most severely affected children with either FAS or PFAS showed smaller increases in vermis IV-V. Higher levels of maternal alcohol intake per occasion during pregnancy were associated with reduced activation increases during rhythmic tapping in all four regions associated with rhythmic tapping in controls. The four cerebellar areas activated by the controls more during rhythmic than non-rhythmic tapping have been implicated in the production of timed responses in several previous studies. These data provide evidence linking binge-like drinking during pregnancy to poorer function in cerebellar regions involved in timing and somatosensory processing needed for complex tasks requiring precise timing.

Inhibition of CD1 antigen presentation by human cytomegalovirus.

PubMed

Raftery, Martin J; Hitzler, Manuel; Winau, Florian; Giese, Thomas; Plachter, Bodo; Kaufmann, Stefan H E; Schönrich, Günther

2008-05-01

The betaherpesvirus human cytomegalovirus (HCMV) encodes several molecules that block antigen presentation by the major histocompatibility complex (MHC) proteins. Humans also possess one other family of antigen-presenting molecules, the CD1 family; however, the effect of HCMV on CD1 expression is unknown. The majority of CD1 molecules are classified on the basis of homology as group 1 CD1 and are present almost exclusively on professional antigen-presenting cells such as dendritic cells, which are a major target for HCMV infection and latency. We have determined that HCMV encodes multiple blocking strategies targeting group 1 CD1 molecules. CD1 transcription is strongly inhibited by the HCMV interleukin-10 homologue cmvIL-10. HCMV also blocks CD1 antigen presentation posttranscriptionally by the inhibition of CD1 localization to the cell surface. This function is not performed by a known HCMV MHC class I-blocking molecule and is substantially stronger than the blockage induced by herpes simplex virus type 1. Antigen presentation by CD1 is important for the development of the antiviral immune response and the generation of mature antigen-presenting cells. HCMV present in antigen-presenting cells thus blunts the immune response by the blockage of CD1 molecules.

Fast, High Resolution, and Wide Modulus Range Nanomechanical Mapping with Bimodal Tapping Mode.

PubMed

Kocun, Marta; Labuda, Aleksander; Meinhold, Waiman; Revenko, Irène; Proksch, Roger

2017-10-24

Tapping mode atomic force microscopy (AFM), also known as amplitude modulated (AM) or AC mode, is a proven, reliable, and gentle imaging mode with widespread applications. Over the several decades that tapping mode has been in use, quantification of tip-sample mechanical properties such as stiffness has remained elusive. Bimodal tapping mode keeps the advantages of single-frequency tapping mode while extending the technique by driving and measuring an additional resonant mode of the cantilever. The simultaneously measured observables of this additional resonance provide the additional information necessary to extract quantitative nanomechanical information about the tip-sample mechanics. Specifically, driving the higher cantilever resonance in a frequency modulated (FM) mode allows direct measurement of the tip-sample interaction stiffness and, with appropriate modeling, the set point-independent local elastic modulus. Here we discuss the advantages of bimodal tapping, coined AM-FM imaging, for modulus mapping. Results are presented for samples over a wide modulus range, from a compliant gel (∼100 MPa) to stiff materials (∼100 GPa), with the same type of cantilever. We also show high-resolution (subnanometer) stiffness mapping of individual molecules in semicrystalline polymers and of DNA in fluid. Combined with the ability to remain quantitative even at line scan rates of nearly 40 Hz, the results demonstrate the versatility of AM-FM imaging for nanomechanical characterization in a wide range of applications.

Cellular Pathway(S) of Antigen Processing and Presentation in Fish APC: Endosomal Involvement and Cell-Free Antigen Presentation

PubMed Central

Vallejo, Abbe N.; Miller, Norman W.; Harvey, Nancy E.; Cuchens, Marvin A.; Warr, Gregory W.

1992-01-01

Studies were conducted to address further the role(s) of antigen processing and presentation in the induction of immune responses in a phylogenetically lower vertebrate, specifically a teleost, the channel catfish. In particular, studies were aimed at determining the subcellular compartments involved in antigen degradation by channel catfish antigen-presenting cells (APC) as well as ascertaining the reexpression of immunogenic peptides on the surfaces of APC. The results showed that exogenous protein antigens were actively endocytosed by APC as detected by flow cytometry. Use of radiolabeled antigen and subcellular fractionation protocols also showed that antigen localized in endosomes/lysosomes. Furthermore, there was an apparent redistribution of antigen between these organelles and the plasma membrane during the course of antigen pulsing. Functional assays for the induction of in vitro antigen-specific proliferation of immune catfish peripheral blood leukocytes (PBL) showed that membrane preparations from antigen-pulsed autologous APC were highly stimulatory. The magnitude of responses elicited with such membrane preparations was very similar to that of PBL cultures stimulated with native antigen-pulsed and fixed intact APC or prefixed intact APC incubated with a peptide fragment of the nominal antigen. Current data further corroborate our previous findings that steps akin to antigen processing and presentation are clearly important in the induction of immune responses in lower vertebrates like fish, in a manner similar to that seen in mammalian systems. Consequently, it would appear that many immune functions among the diverse taxa of vertebrates are remarkably conserved. PMID:1343103

Graves' disease: a host defense mechanism gone awry.

PubMed

Kohn, L D; Napolitano, G; Singer, D S; Molteni, M; Scorza, R; Shimojo, N; Kohno, Y; Mozes, E; Nakazato, M; Ulianich, L; Chung, H K; Matoba, H; Saunier, B; Suzuki, K; Schuppert, F; Saji, M

2000-01-01

In this report we summarize evidence to support a model for the development of Graves' disease. The model suggests that Graves' disease is initiated by an insult to the thyrocyte in an individual with a normal immune system. The insult, infectious or otherwise, causes double strand DNA or RNA to enter the cytoplasm of the cell. This causes abnormal expression of major histocompatibility (MHC) class I as a dominant feature, but also aberrant expression of MHC class II, as well as changes in genes or gene products needed for the thyrocyte to become an antigen presenting cell (APC). These include increased expression of proteasome processing proteins (LMP2), transporters of antigen peptides (TAP), invariant chain (Ii), HLA-DM, and the co-stimulatory molecule, B7, as well as STAT and NF-kappaB activation. A critical factor in these changes is the loss of normal negative regulation of MHC class I, class II, and thyrotropin receptor (TSHR) gene expression, which is necessary to maintain self-tolerance during the normal changes in gene expression involved in hormonally-increased growth and function of the cell. Self-tolerance to the TSHR is maintained in normals because there is a population of CD8- cells which normally suppresses a population of CD4+ cells that can interact with the TSHR if thyrocytes become APCs. This is a host self-defense mechanism that we hypothesize leads to autoimmune disease in persons, for example, with a specific viral infection, a genetic predisposition, or even, possibly, a TSHR polymorphism. The model is suggested to be important to explain the development of other autoimmune diseases including systemic lupus or diabetes.

Crucial role of gamma interferon-producing CD4+ Th1 cells but dispensable function of CD8+ T cell, B cell, Th2, and Th17 responses in the control of Brucella melitensis infection in mice.

PubMed

Vitry, Marie-Alice; De Trez, Carl; Goriely, Stanislas; Dumoutier, Laure; Akira, Shizuo; Ryffel, Bernhard; Carlier, Yves; Letesson, Jean-Jacques; Muraille, Eric

2012-12-01

Brucella spp. are facultative intracellular bacterial pathogens responsible for brucellosis, a worldwide zoonosis that causes abortion in domestic animals and chronic febrile disease associated with serious complications in humans. There is currently no approved vaccine against human brucellosis, and antibiotic therapy is long and costly. Development of a safe protective vaccine requires a better understanding of the roles played by components of adaptive immunity in the control of Brucella infection. The importance of lymphocyte subsets in the control of Brucella growth has been investigated separately by various research groups and remains unclear or controversial. Here, we used a large panel of genetically deficient mice to compare the importance of B cells, transporter associated with antigen processing (TAP-1), and major histocompatibility complex class II-dependent pathways of antigen presentation as well as T helper 1 (Th1), Th2, and Th17-mediated responses on the immune control of Brucella melitensis 16 M infection. We clearly confirmed the key function played by gamma interferon (IFN-γ)-producing Th1 CD4(+) T cells in the control of B. melitensis infection, whereas IFN-γ-producing CD8(+) T cells or B cell-mediated humoral immunity plays only a modest role in the clearance of bacteria during primary infection. In the presence of a Th1 response, Th2 or Th17 responses do not really develop or play a positive or negative role during the course of B. melitensis infection. On the whole, these results could improve our ability to develop protective vaccines or therapeutic treatments against brucellosis.

Efficient activation of human T cells of both CD4 and CD8 subsets by urease-deficient recombinant Mycobacterium bovis BCG that produced a heat shock protein 70-M. tuberculosis-derived major membrane protein II fusion protein.

PubMed

Mukai, Tetsu; Tsukamoto, Yumiko; Maeda, Yumi; Tamura, Toshiki; Makino, Masahiko

2014-01-01

For the purpose of obtaining Mycobacterium bovis bacillus Calmette-Guérin (BCG) capable of activating human naive T cells, urease-deficient BCG expressing a fusion protein composed of Mycobacterium tuberculosis-derived major membrane protein II (MMP-II) and heat shock protein 70 (HSP70) of BCG (BCG-DHTM) was produced. BCG-DHTM secreted the HSP70-MMP-II fusion protein and effectively activated human monocyte-derived dendritic cells (DCs) by inducing phenotypic changes and enhanced cytokine production. BCG-DHTM-infected DCs activated naive T cells of both CD4 and naive CD8 subsets, in an antigen (Ag)-dependent manner. The T cell activation induced by BCG-DHTM was inhibited by the pretreatment of DCs with chloroquine. The naive CD8(+) T cell activation was mediated by the transporter associated with antigen presentation (TAP) and the proteosome-dependent cytosolic cross-priming pathway. Memory CD8(+) T cells and perforin-producing effector CD8(+) T cells were efficiently produced from the naive T cell population by BCG-DHTM stimulation. Single primary infection with BCG-DHTM in C57BL/6 mice efficiently produced T cells responsive to in vitro secondary stimulation with HSP70, MMP-II, and M. tuberculosis-derived cytosolic protein and inhibited the multiplication of subsequently aerosol-challenged M. tuberculosis more efficiently than did vector control BCG. These results indicate that the introduction of MMP-II and HSP70 into urease-deficient BCG may be useful for improving BCG for control of tuberculosis.

A Glove for Tapping and Discrete 1D/2D Input

NASA Technical Reports Server (NTRS)

Miller, Sam A.; Smith, Andy; Bahram, Sina; SaintAmant, Robert

2012-01-01

This paper describes a glove with which users enter input by tapping fingertips with the thumb or by rubbing the thumb over the palmar surfaces of the middle and index fingers. The glove has been informally tested as the controller for two semi-autonomous robots in a a 3D simulation environment. A preliminary evaluation of the glove s performance is presented.

The National Rural Alcohol and Drug Abuse Network Awards for Excellence 2004: Submitted and Award-Winning Papers. Technical Assistance Publication Series (TAP) 28

ERIC Educational Resources Information Center

Substance Abuse and Mental Health Services Administration, 2006

2006-01-01

This TAP presents seven papers submitted to the 2004 National Rural Alcohol and Drug Abuse Network (NRADAN) Awards for Excellence. Each paper describes effective and innovative models of treatment and prevention services in rural populations. This publication seeks to promote and showcase research addressing the unique and special challenges of…

Co-evolution with chicken class I genes.

PubMed

Kaufman, Jim

2015-09-01

The concept of co-evolution (or co-adaptation) has a long history, but application at molecular levels (e.g., 'supergenes' in genetics) is more recent, with a consensus definition still developing. One interesting example is the chicken major histocompatibility complex (MHC). In contrast to typical mammals that have many class I and class I-like genes, only two classical class I genes, two CD1 genes and some non-classical Rfp-Y genes are known in chicken, and all are found on the microchromosome that bears the MHC. Rarity of recombination between the closely linked and polymorphic genes encoding classical class I and TAPs allows co-evolution, leading to a single dominantly expressed class I molecule in each MHC haplotype, with strong functional consequences in terms of resistance to infectious pathogens. Chicken tapasin is highly polymorphic, but co-evolution with TAP and class I genes remains unclear. T-cell receptors, natural killer (NK) cell receptors, and CD8 co-receptor genes are found on non-MHC chromosomes, with some evidence for co-evolution of surface residues and number of genes along the avian and mammalian lineages. Over even longer periods, co-evolution has been invoked to explain how the adaptive immune system of jawed vertebrates arose from closely linked receptor, ligand, and antigen-processing genes in the primordial MHC. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An improved push-pull voltage fed converter using a tapped output-filter inductor

NASA Technical Reports Server (NTRS)

Wester, G. W.

1983-01-01

A new concept of using a tapped output-filter inductor and an auxiliary commutating diode to reduce the likelihood of transformer core saturation in a push-pull, voltage-fed converter is presented. The linearized circuit model and transfer functions are derived with a hybrid approach using both state-space and circuit averaging. Operation of the new converter - including parasitic effects - is discussed, and a design equation for inductor tap ratio is established. It is predicted and experimentally confirmed that the new converter has more symmetrical transformer core operation, and the potential exits for lower transistor turnon current and reduced transistor voltage stress. These benefits reduce switching loss and enhance transistor reliability.

Molecular recognition of microbial lipid-based antigens by T cells.

PubMed

Gras, Stephanie; Van Rhijn, Ildiko; Shahine, Adam; Le Nours, Jérôme

2018-05-01

The immune system has evolved to protect hosts from pathogens. T cells represent a critical component of the immune system by their engagement in host defence mechanisms against microbial infections. Our knowledge of the molecular recognition by T cells of pathogen-derived peptidic antigens that are presented by the major histocompatibility complex glycoproteins is now well established. However, lipids represent an additional, distinct chemical class of molecules that when presented by the family of CD1 antigen-presenting molecules can serve as antigens, and be recognized by specialized subsets of T cells leading to antigen-specific activation. Over the past decades, numerous CD1-presented self- and bacterial lipid-based antigens have been isolated and characterized. However, our understanding at the molecular level of T cell immunity to CD1 molecules presenting microbial lipid-based antigens is still largely unexplored. Here, we review the insights and the molecular basis underpinning the recognition of microbial lipid-based antigens by T cells.

Abdominal tap

MedlinePlus

Peritoneal tap; Paracentesis; Ascites - abdominal tap; Cirrhosis - abdominal tap; Malignant ascites - abdominal tap ... abdominal cavity ( most often cancer of the ovaries ) Cirrhosis of the liver Damaged bowel Heart disease Infection ...

Presentation of lipid antigens to T cells.

PubMed

Mori, Lucia; De Libero, Gennaro

2008-04-15

T cells specific for lipid antigens participate in regulation of the immune response during infections, tumor immunosurveillance, allergy and autoimmune diseases. T cells recognize lipid antigens as complexes formed with CD1 antigen-presenting molecules, thus resembling recognition of MHC-peptide complexes. The biophysical properties of lipids impose unique mechanisms for their delivery, internalization into antigen-presenting cells, membrane trafficking, processing, and loading of CD1 molecules. Each of these steps is controlled at molecular and celular levels and determines lipid immunogenicity. Lipid antigens may derive from microbes and from the cellular metabolism, thus allowing the immune system to survey a large repertoire of immunogenic molecules. Recognition of lipid antigens facilitates the detection of infectious agents and the initiation of responses involved in immunoregulation and autoimmunity. This review focuses on the presentation mechanisms and specific recognition of self and bacterial lipid antigens and discusses the important open issues.

Preserved MHC-II antigen processing and presentation function in chronic HCV infection

PubMed Central

DH, Canaday; CJ, Burant; L, Jones; H, Aung; L, Woc-Colburn; DD, Anthony

2010-01-01

Individuals with chronic HCV infection have impaired response to vaccine, though the etiology remains to be elucidated. Dendritic cells (DC) and monocytes (MN) provide antigen uptake, processing, presentation, and costimulatory functions necessary to achieve optimal immune responses. The integrity of antigen processing and presentation function within these antigen presenting cells (APC) in the setting of HCV infection has been unclear. We used a novel T cell hybridoma system that specifically measures MHC-II antigen processing and presentation function of human APC. Results demonstrate MHC-II antigen processing and presentation function is preserved in both myeloid DC (mDC) and MN in the peripheral blood of chronically HCV-infected individuals, and indicates that an alteration in this function does not likely underlie the defective HCV-infected host response to vaccination. PMID:21055734

An estimation of finger-tapping rates and load capacities and the effects of various factors.

PubMed

Ekşioğlu, Mahmut; İşeri, Ali

2015-06-01

The aim of this study was to estimate the finger-tapping rates and finger load capacities of eight fingers (excluding thumbs) for a healthy adult population and investigate the effects of various factors on tapping rate. Finger-tapping rate, the total number of finger taps per unit of time, can be used as a design parameter of various products and also as a psychomotor test for evaluating patients with neurologic problems. A 1-min tapping task was performed by 148 participants with maximum volitional tempo for each of eight fingers. For each of the tapping tasks, the participant with the corresponding finger tapped the associated key in the standard position on the home row of a conventional keyboard for touch typing. The index and middle fingers were the fastest fingers for both hands, and little fingers the slowest. All dominant-hand fingers, except little finger, had higher tapping rates than the fastest finger of the nondominant hand. Tapping rate decreased with age and smokers tapped faster than nonsmokers. Tapping duration and exercise had also significant effect on tapping rate. Normative data of tapping rates and load capacities of eight fingers were estimated for the adult population. In designs of psychomotor tests that require the use of tapping rate or finger load capacity data, the effects of finger, age, smoking, and tapping duration need to be taken into account. The findings can be used for ergonomic designs requiring finger-tapping capacity and also as a reference in psychomotor tests. © 2015, Human Factors and Ergonomics Society.

Spontaneous eye blinks are entrained by finger tapping.

PubMed

Cong, D-K; Sharikadze, M; Staude, G; Deubel, H; Wolf, W

2010-02-01

We studied the mutual cross-talk between spontaneous eye blinks and continuous, self-paced unimanual and bimanual tapping. Both types of motor activities were analyzed with regard to their time-structure in synchronization-continuation tapping tasks which involved different task instructions, namely "standard" finger tapping (Experiment 1), "strong" tapping (Experiment 2) requiring more forceful finger movements, and "impulse-like" tapping (Experiment 3) where upward-downward finger movements had to be very fast. In a further control condition (Experiment 4), tapping was omitted altogether. The results revealed a prominent entrainment of spontaneous blink behavior by the manual tapping, with bimanual tapping being more effective than unimanual tapping, and with the "strong" and "impulse-like" tapping showing the largest effects on blink timing. Conversely, we found no significant effects of the tapping on the timing of the eye blinks across all experiments. The findings suggest a functional overlap of the motor control structures responsible for voluntary, rhythmic finger movements and eye blinking behavior.

Monkeys time their pauses of movement and not their movement-kinematics during a synchronization-continuation rhythmic task.

PubMed

Donnet, Sophie; Bartolo, Ramon; Fernandes, José Maria; Cunha, João Paulo Silva; Prado, Luis; Merchant, Hugo

2014-05-01

A critical question in tapping behavior is to understand whether the temporal control is exerted on the duration and trajectory of the downward-upward hand movement or on the pause between hand movements. In the present study, we determined the duration of both the movement execution and pauses of monkeys performing a synchronization-continuation task (SCT), using the speed profile of their tapping behavior. We found a linear increase in the variance of pause-duration as a function of interval, while the variance of the motor implementation was relatively constant across intervals. In fact, 96% of the variability of the duration of a complete tapping cycle (pause + movement) was due to the variability of the pause duration. In addition, we performed a Bayesian model selection to determine the effect of interval duration (450-1,000 ms), serial-order (1-6 produced intervals), task phase (sensory cued or internally driven), and marker modality (auditory or visual) on the duration of the movement-pause and tapping movement. The results showed that the most important parameter used to successfully perform the SCT was the control of the pause duration. We also found that the kinematics of the tapping movements was concordant with a stereotyped ballistic control of the hand pressing the push-button. The present findings support the idea that monkeys used an explicit timing strategy to perform the SCT, where a dedicated timing mechanism controlled the duration of the pauses of movement, while also triggered the execution of fixed movements across each interval of the rhythmic sequence. Copyright © 2014 the American Physiological Society.

Computerized measures of finger tapping: reliability, malingering and traumatic brain injury.

PubMed

Hubel, Kerry A; Yund, E William; Herron, Timothy J; Woods, David L

2013-01-01

We analyzed computerized finger tapping metrics in four experiments. Experiment 1 showed tapping-rate differences associated with hand dominance, digits, sex, and fatigue that replicated those seen in a previous, large-scale community sample. Experiment 2 revealed test-retest correlations (r = .91) that exceeded those reported in previous tapping studies. Experiment 3 investigated subjects simulating symptoms of traumatic brain injury (TBI); 62% of malingering subjects produced abnormally slow tapping rates. A tapping-rate malingering index, based on rate-independent tapping patterns, provided confirmatory evidence of malingering in 48% of the subjects with abnormal tapping rates. Experiment 4 compared tapping in 24 patients with mild TBI (mTBI) and a matched control group; mTBI patients showed slowed tapping without evidence of malingering. Computerized finger tapping measures are reliable measures of motor speed, useful in detecting subjects performing with suboptimal effort, and are sensitive to motor abnormalities following mTBI.

Evaluation of triple antibiotic paste removal by different irrigation procedures.

PubMed

Berkhoff, Julie A; Chen, Paul B; Teixeira, Fabricio B; Diogenes, Anibal

2014-08-01

Regenerative endodontics aims to re-establish a functional pulp-dentin complex. First, the root canal system is disinfected primarily by irrigants and medicaments. Triple antibiotic paste (TAP), a commonly used intracanal medicament, has been shown to be directly toxic to stem cells at concentrations greater than 0.1 g/mL. Thus, its complete removal is a crucial step in regenerative endodontic procedures. We hypothesized that currently used irrigation techniques do not completely remove TAP from root canal system. TAP was radiolabeled by the incorporation of I(125), and calcium hydroxide (Ultracal; Ultradent, South Jordan, UT) was radiolabeled with Ca(45). The intracanal medicaments were placed into standardized human root segments and incubated for 28 days at 37°C. Then, canals were irrigated with EndoActivator (Dentsply, Tulsa, OK), passive ultrasonic irrigation, EndoVac (SybronEndo, Coppell, TX), or a syringe/Max-i-Probe needle (Dentsply Rinn, Elgin, IL) using a standardized irrigation protocol in a closed system. Radioactivity levels (counts per minute values) were measured for each tooth before and after the irrigation protocols. Furthermore, the canals were sequentially enlarged and dentin samples collected and evaluated for radioactivity. Data were analyzed with analysis of variance and Bonferroni post hoc testing (P < .05). Approximately 88% of the TAP was retained in the root canal system regardless of the irrigation technique used (no difference among groups). Furthermore, approximately 50% of the radiolabeled TAP was present circumferentially up to 350 μm within the dentin. Conversely, up to 98% of the radiolabeled intracanal calcium hydroxide was removed, and most residual medicament was found present in the initial 50 μm of dentin. Current irrigation techniques do not effectively remove TAP from root canal systems, possibly because of its penetration and binding into dentin. However, calcium hydroxide is effectively removed with significant less residual presence. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Keratin 5/14‑mediated cell differentiation and transformation are regulated by TAp63 and Notch‑1 in oral squamous cell carcinoma‑derived cells.

PubMed

Srivastava, Saumya S; Alam, Hunain; Patil, Sonam J; Shrinivasan, Rashmi; Raikundalia, Sweta; Chaudhari, Pratik Rajeev; Vaidya, Milind M

2018-05-01

Keratins 5/14 (K5/14) are intermediate filament proteins expressed in the basal layer of stratified epithelial cells and are known targets of p63. Previous research in our laboratory showed that upon K5/14 downregulation in oral squamous cell carcinoma (OSCC)‑derived cells, there was an increase in intracellular Notch‑1 levels and differentiation markers such as involucrin, keratin 1 and a decrease in tumorigenic potential in vivo. However, the molecules involved in the K14 regulated cell differentiation and transformation are not known to date. In order to understand the possible role of TAp63, we downregulated TAp63 in a K14‑knockdown background. We observed that there was a decrease in the expression of Notch‑1. Expression levels of differentiation markers such as involucrin, K1, loricrin and filaggrin were also decreased. Furthermore, TAp63 downregulation led to an increase in invasion, migration and in vivo tumorigenic potential of these cells. We observed a decrease in β‑catenin signaling in K14‑downregulated cells. Notably, when TAp63 was downregulated in K14‑knockdown cells, there was increase in non‑phospho β‑catenin levels. Hence, this study indicates that TAp63 plays an important role in K14‑downregulated cells possibly by regulating the Notch‑1 expression. K14 regulates the expression of TAp63 which in turn regulates expression of Notch‑1. The present study is a step forward in our quest to understand the functional significance of molecules that regulate the process of differentiation and tumorigenesis in stratified epithelial cells.

Ultrasound-guided transversus abdominis plane block for postoperative analgesia in living liver donors: A prospective, randomized, double-blinded clinical trial.

PubMed

Kıtlık, Arzu; Erdogan, Mehmet Ali; Ozgul, Ulku; Aydogan, Mustafa Said; Ucar, Muharrem; Toprak, Huseyin Ilksen; Colak, Cemil; Durmus, Mahmut

2017-02-01

Transversus abdominis plane (TAP) block is a peripheral nerve block that reduces postoperative pain, nausea, vomiting and the need for postoperative opioids following various types of abdominal surgery. The primary aim of the present study was to evaluate the effects of TAP block on postoperative analgesia and opioid consumption in living liver donors in whom a right "J" abdominal incision was used. This prospective, double-blinded, randomized controlled study was conducted with 50 living liver donors, aged 18-65years, who were scheduled to undergo right hepatectomy. Patients who received ultrasonography-guided subcostal TAP block were allocated into Group 1, and patients who did not receive TAP block were allocated into Group 2. The TAP blocks were performed bilaterally at the conclusion of surgery using 1.5mg∗kg -1 bupivacaine diluted with saline to reach a total volume of 40mL. For each patient, morphine consumption, pain scores at rest and movement, sedation scores, nausea, vomiting and the need for antiemetic medication were assessed at 0, 2, 4, 6, 12 and 24h postoperatively by researchers who were blinded to the study groups. Morphine consumption was significantly lower in Group 1 than in Group 2 at the 2nd, 6th and 24th hours (P<0.05). The mean total morphine consumption values after 24h were 40mg and 65mg in Groups 1 and 2, respectively. The TAP block significantly reduced postoperative visual analog scale pain scores both at rest and during movement at 0, 2, 4, 6, and 24h postoperatively (P<0.05). The TAP block reduced 24-h postoperative morphine consumption and contributed to analgesia in living liver donors who underwent upper abdominal wall incisions. Copyright © 2016 Elsevier Inc. All rights reserved.

Evidence for repetitive load in the trapezius muscle during a tapping task.

PubMed

Tomatis, L; Müller, C; Nakaseko, M; Läubli, T

2012-08-01

Many studies describe the trapezius muscle activation pattern during repetitive key-tapping focusing on continuous activation. The objectives of this study were to determine whether the upper trapezius is phasically active during supported key tapping, whether this activity is cross-correlated with forearm muscle activity, and whether trapezius activity depends on key characteristic. Thirteen subjects (29.7 ± 11.4 years) were tested. Surface EMG of the finger's extensor and flexor and of the trapezius muscles, as well as the key on-off signal was recorded while the subject performed a 2-min session of key tapping at 4 Hz. The linear envelopes obtained were cut into single tapping cycles extending from one onset to the next onset signal and subsequently time-normalized. Effect size between mean range and maximal standard deviation was calculated to determine as to whether a burst of trapezius muscle activation was present. Cross-correlation was used to determine the time-lag of the activity bursts between forearm and trapezius muscles. For each person the mean and standard deviation of the cross-correlations coefficient between forearm muscles and trapezius were determined. Results showed a burst of activation in the trapezius muscle during most of the tapping cycles. The calculated effect size was ≥0.5 in 67% of the cases. Cross-correlation factors between forearm and trapezius muscle activity were between 0.75 and 0.98 for both extensor and flexor muscles. The cross-correlated phasic trapezius activity did not depend on key characteristics. Trapezius muscle was dynamically active during key tapping; its activity was clearly correlated with forearm muscles' activity.

A role for mitochondria in antigen processing and presentation

PubMed Central

Bonifaz, Laura C; Cervantes-Silva, Mariana P; Ontiveros-Dotor, Elizabeth; López-Villegas, Edgar O; Sánchez-García, F Javier

2015-01-01

Immune synapse formation is critical for T-lymphocyte activation, and mitochondria have a role in this process, by localizing close to the immune synapse, regulating intracellular calcium concentration, and providing locally required ATP. The interaction between antigen-presenting cells (APCs) and T lymphocytes is a two-way signalling process. However, the role of mitochondria in APCs during this process remains unknown. For APCs to be able to activate T lymphocytes, they must first engage in an antigen-uptake, -processing and -presentation process. Here we show that hen egg white lysozyme (HEL) -loaded B lymphocytes, as a type of APC, undergo a small but significant mitochondrial depolarization by 1–2 hr following antigen exposure, suggesting an increase in their metabolic demands. Inhibition of ATP synthase (oligomycin) or mitochondrial Ca2+ uniporter (MCU) (Ruthenium red) had no effect on antigen uptake. Therefore, antigen processing and antigen presentation were further analysed. Oligomycin treatment reduced the amount of specific MHC–peptide complexes but not total MHC II on the cell membrane of B lymphocytes, which correlated with a decrease in antigen presentation. However, oligomycin also reduced antigen presentation by B lymphocytes, which endogenously express HEL and by B lymphocytes loaded with the HEL48–62 peptide, although to a lesser extent. ATP synthase inhibition and MCU inhibition had a clear inhibitory effect on antigen processing (DQ-OVA). Taken together these results suggest that ATP synthase and MCU are relevant for antigen processing and presentation. Finally, APC mitochondria were found to re-organize towards the APC–T immune synapse. PMID:25251370

Persistence of antibiotic resistance genes and bacterial community changes in drinking water treatment system: From drinking water source to tap water.

PubMed

Su, Hao-Chang; Liu, You-Sheng; Pan, Chang-Gui; Chen, Jun; He, Liang-Ying; Ying, Guang-Guo

2018-03-01

As emerging contaminants, antibiotic resistance genes (ARGs) have become a public concern. This study aimed to investigate the occurrence and diversity of ARGs, and variation in the composition of bacterial communities in source water, drinking water treatment plants, and tap water in the Pearl River Delta region, South China. Various ARGs were present in the different types of water. Among the 27 target ARGs, floR and sul1 dominated in source water from three large rivers in the region. Pearson correlation analysis suggested that sul1, sul2, floR, and cmlA could be potential indicators for ARGs in water samples. The total abundance of the detected ARGs in tap water was much lower than that in source water. Sand filtration and sedimentation in drinking water treatment plants could effectively remove ARGs; in contrast, granular activated carbon filtration increased the abundance of ARGs. It was found that Pseudomonas may be involved in the proliferation and dissemination of ARGs in the studied drinking water treatment system. Bacteria and ARGs were still present in tap water after treatment, though they were significantly reduced. More research is needed to optimize the water treatment process for ARG removal. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative evaluation of insertion torque and mechanical stability for self-tapping and self-drilling orthodontic miniscrews - an in vitro study.

PubMed

Tepedino, Michele; Masedu, Francesco; Chimenti, Claudio

2017-05-30

The aim of the present study was to evaluate the relationship between insertion torque and stability of miniscrews in terms of resistance against dislocation, then comparing a self-tapping screw with a self-drilling one. Insertion torque was measured during placement of 30 self-drilling and 31 self-tapping stainless steel miniscrews (Leone SpA, Sesto Fiorentino, Italy) in synthetic bone blocks. Then, an increasing pulling force was applied at an angle of 90° and 45°, and the displacement of the miniscrews was recorded. The statistical analysis showed a statistically significant difference between the mean Maximum Insertion Torque (MIT) observed in the two groups and showed that force angulation and MIT have a statistically significant effect on miniscrews stability. For both the miniscrews, an angle of 90° between miniscrew and loading force is preferable in terms of stability. The tested self-drilling orthodontic miniscrews showed higher MIT and greater resistance against dislocation than the self-tapping ones.

Study of tapping process of carbon fiber reinforced plastic composites/AA7075 stacks

NASA Astrophysics Data System (ADS)

D'Orazio, Alessio; Mehtedi, Mohamad El; Forcellese, Archimede; Nardinocchi, Alessia; Simoncini, Michela

2018-05-01

The present investigation aims at studying the tapping process of a three-layer stack constituted by two CFRP layers and a core plate in AA7075 aluminum alloy. The CFRP laminates were obtained by a pre-impregnated woven sample made up of T700 carbon fibers and a thermoset epoxy matrix. Tapping experiments were performed on a 5-axis machining center instrumented with a dynamometer to measure thrust force generated during process. A high-speed steel tool, coated with nanocomposite TiAlN, was used. According to the tool manufacturer recommendations, rotational speed and feed rate were 800 rpm and 1000 mm/min, respectively. Similar thrust force time history responses were obtained by tapping different holes, even though the vertical force increases with number of threaded holes. Furthermore, a quantitative evaluation of delamination at the periphery of entry holes was carried out. The delamination at the entry hole strongly increases with number of threaded holes.

BIOMECHANICAL EVALUATION OF THE INFLUENCE OF CERVICAL SCREWS TAPPING AND DESIGN.

PubMed

Silva, Patricia; Rosa, Rodrigo César; Shimano, Antonio Carlos; Albuquerque de Paula, Francisco José; Volpon, José Batista; Aparecido Defino, Helton Luiz

2009-01-01

To assess if the screw design (self-drilling/self-tapping) and the pilot hole tapping could affect the insertion torque and screw pullout strength of the screw used in anterior fixation of the cervical spine. Forty self-tapping screws and 20 self-drilling screws were inserted into 10 models of artificial bone and 10 cervical vertebrae of sheep. The studied parameters were the insertion torque and pullout strength. The following groups were created: Group I-self-tapping screw insertion after pilot hole drilling and tapping; Group II-self-tapping screw insertion after pilot hole drilling without tapping; Group III-self-drilling screw insertion without drilling and tapping. In Groups I and II, the pilot hole had 14.0 mm in depth and was made with a 3mmn drill, while tapping was made with a 4mm tap. The insertion torque was measured and the pullout test was performed. The comparison between groups was made considering the mean insertion torque and the maximum mean pullout strength with the variance analysis (ANOVA; p≤ 0.05). Previous drilling and tapping of pilot hole significantly decreased the insertion torque and the pullout strength. The insertion torque and pullout strength of self-drilling screws were significantly higher when compared to self-tapping screws inserted after pilot hole tapping.

Presentation of antigen to T lymphocytes by non-immune B-cell hybridoma clones: evidence for specific and non-specific presentation

NASA Technical Reports Server (NTRS)

Cohly, H. H.; Morrison, D. R.; Zouhair Atassi, M. Z.

1989-01-01

Non-immune SJL (H-2s) spleen cells were fused with non-secreting, non-antigen presenting (H-2d) Balb/c 653-myeloma cells and the hybridomas were cloned by two limiting dilutions. The resulting hybrid B-cell clones were tested for their antigen presentation capability to SJL T-cell lines that were specific for either lysozyme or myoglobin. In proliferative assays, 53% of the antigen presenting B-cell clones presented both myoglobin and lysozyme (general presenters) while the other 47% presented specifically either myoglobin or lysozyme (specific presenters). The ability to selectively present either myoglobin or lysozyme indicates that antigen presentation at the clonal level can be specific or non-specific depending on the particular B-cell clone.

Antigen-B Cell Receptor Complexes Associate with Intracellular major histocompatibility complex (MHC) Class II Molecules*

PubMed Central

Barroso, Margarida; Tucker, Heidi; Drake, Lisa; Nichol, Kathleen; Drake, James R.

2015-01-01

Antigen processing and MHC class II-restricted antigen presentation by antigen-presenting cells such as dendritic cells and B cells allows the activation of naïve CD4+ T cells and cognate interactions between B cells and effector CD4+ T cells, respectively. B cells are unique among class II-restricted antigen-presenting cells in that they have a clonally restricted antigen-specific receptor, the B cell receptor (BCR), which allows the cell to recognize and respond to trace amounts of foreign antigen present in a sea of self-antigens. Moreover, engagement of peptide-class II complexes formed via BCR-mediated processing of cognate antigen has been shown to result in a unique pattern of B cell activation. Using a combined biochemical and imaging/FRET approach, we establish that internalized antigen-BCR complexes associate with intracellular class II molecules. We demonstrate that the M1-paired MHC class II conformer, shown previously to be critical for CD4 T cell activation, is incorporated selectively into these complexes and loaded selectively with peptide derived from BCR-internalized cognate antigen. These results demonstrate that, in B cells, internalized antigen-BCR complexes associate with intracellular MHC class II molecules, potentially defining a site of class II peptide acquisition, and reveal a selective role for the M1-paired class II conformer in the presentation of cognate antigen. These findings provide key insights into the molecular mechanisms used by B cells to control the source of peptides charged onto class II molecules, allowing the immune system to mount an antibody response focused on BCR-reactive cognate antigen. PMID:26400081

Interleukin 10 (IL-10)-mediated Immunosuppression

PubMed Central

Mittal, Sharad K.; Cho, Kyung-Jin; Ishido, Satoshi; Roche, Paul A.

2015-01-01

Efficient immune responses require regulated antigen presentation to CD4 T cells. IL-10 inhibits the ability of dendritic cells (DCs) and macrophages to stimulate antigen-specific CD4 T cells; however, the mechanisms by which IL-10 suppresses antigen presentation remain poorly understood. We now report that IL-10 stimulates expression of the E3 ubiquitin ligase March-I in activated macrophages, thereby down-regulating MHC-II, CD86, and antigen presentation to CD4 T cells. By contrast, IL-10 does not stimulate March-I expression in DCs, does not suppress MHC-II or CD86 expression on either resting or activated DCs, and does not affect antigen presentation by activated DCs. IL-10 does, however, inhibit the process of DC activation itself, thereby reducing the efficiency of antigen presentation in a March-I-independent manner. Thus, IL-10 suppression of antigen presenting cell function in macrophages is March-I-dependent, whereas in DCs, suppression is March- I-independent. PMID:26408197

The consequences of the intracellular retention of pathogen-derived T-cell-independent antigens on protein presentation to T cells.

PubMed

Leyva-Cobián, F; Outschoorn, I M; Carrasco-Marín, E; Alvarez-Domínguez, C

1997-10-01

Intracellular pathogens can be considered as particulate antigens chemically composed of a complex mixture of T-cell-dependent antigens (TD) (peptides and proteins) and T-cell-independent antigens (TI) (glycolipids and complex polysaccharides). A large range of saccharides (from oligosaccharides to complex polysaccharides) derived from pathogenic microorganisms are being isolated and characterized. They are currently implicated in signaling systems and concomitant host-parasite relationships. However, there are not many structure-function relationships described for these pathogens. This is particularly true of polysaccharides. In this report we have reviewed the role of defined TI antigens in the processing and presentation of defined TD antigens to specific T cells by antigen-presenting cells (APC). We also considered the importance of some of the chemical characteristics shared by different carbohydrates implicated in the inhibition of antigen presentation. These findings are discussed in relation to the clear immunopathological consequences of long retention periods of complex carbohydrate molecules derived from intracellular parasites inside certain APC and the absence of antigen presentation impairment in physiological situations such as the removal of senescent or damaged red blood cells by splenic macrophages or intracellular accumulation of carbohydrates in colostrum and milk macrophages during lactation.

Central Tolerance to Tissue-specific Antigens Mediated by Direct and Indirect Antigen Presentation

PubMed Central

Gallegos, Alena M.; Bevan, Michael J.

2004-01-01

Intrathymic expression of tissue-specific antigens (TSAs) by medullary thymic epithelial cells (Mtecs) leads to deletion of autoreactive T cells. However, because Mtecs are known to be poor antigen-presenting cells (APCs) for tolerance to ubiquitous antigens, and very few Mtecs express a given TSA, it was unclear if central tolerance to TSA was induced directly by Mtec antigen presentation or indirectly by thymic bone marrow (BM)-derived cells via cross-presentation. We show that professional BM-derived APCs acquire TSAs from Mtecs and delete autoreactive CD8 and CD4 T cells. Although direct antigen presentation by Mtecs did not delete the CD4 T cell population tested in this study, Mtec presentation efficiently deleted both monoclonal and polyclonal populations of CD8 T cells. For developing CD8 T cells, deletion by BM-derived APC and by Mtec presentation occurred abruptly at the transitional, CD4high CD8low TCRintermediate stage, presumably as the cells transit from the cortex to the medulla. These studies reveal a cooperative relationship between Mtecs and BM-derived cells in thymic elimination of autoreactive T cells. Although Mtecs synthesize TSAs and delete a subset of autoreactive T cells, BM-derived cells extend the range of clonal deletion by cross-presenting antigen captured from Mtecs. PMID:15492126

Differential protein expression, DNA binding and interaction with SV40 large tumour antigen implicate the p63-family of proteins in replicative senescence.

PubMed

Djelloul, Siham; Tarunina, Marina; Barnouin, Karin; Mackay, Alan; Jat, Parmjit S

2002-02-07

P53 activity plays a key role in mammalian cells when they undergo replicative senescence at their Hayflick limit. To determine whether p63 proteins, members of the family of p53-related genes, are also involved in this process, we examined their expression in serially passaged rat embryo fibroblasts. Upon senescence, two truncated DeltaNp63 proteins decreased in abundance whereas two TAp63 isoforms accumulated. 2-D gel analysis showed that the DeltaNp63 proteins underwent post-translational modifications in both proliferating and senescent cells. Direct binding of DeltaNp63 proteins to a p53 consensus motif was greater in proliferating cells than senescent cells. In contrast p63alpha isoforms bound to DNA in a p53 dependent manner and this was higher in senescent cells than proliferating cells. An interaction of p63alpha proteins with SV40 large tumour antigen was also detected and ectopic expression of DeltaNp63alpha can extend the lifespan of rat embryo fibroblasts. Taken together the results indicate that p63 proteins may play a role in replicative senescence either by competition for p53 DNA binding sites or by direct interaction with p53 protein bound to DNA.

Covalent binding of C3b to tetanus toxin: influence on uptake/internalization of antigen by antigen-specific and non-specific B cells.

PubMed Central

Villiers, M B; Villiers, C L; Jacquier-Sarlin, M R; Gabert, F M; Journet, A M; Colomb, M G

1996-01-01

Antigen opsonization by the C3b fragment of complement is a significant event in the modulation of cell-mediated immune response, but its mechanism is still largely unknown. The structural characteristics of C3b allow it to act as a bifunctional ligand between antigen and cells via their membrane C3b receptors. It was thus of interest to study the influence of the covalent link between C3b and antigen on the fixation and internalization of this antigen by antigen-presenting cells. Tetanus toxin (TT) was used as antigen, either free or covalently linked to C3b (TT-C3b). The antigen-presenting cells were TT-specific (4.2) or non-specific (BL15) Epstein-Barr virus (EBV)-transformed B cells. C3b was found to play an important role in antigen fixation and internalization by both antigen-specific and antigen non-specific cells. Covalent binding of C3b on TT (1) permitted fixation and internalization of this antigen by non-specific cells via their complement receptors; (2) enhanced antigen fixation and resulted in cross-linking between membrane immunoglobulins and complement receptors on antigen-specific cells. The consequences of covalent C3b binding to TT were analysed using antigen-specific and antigen-nonspecific cells. In both cases, a net increase in antigen fixation was observed. At the intracellular level, covalent C3b binding to TT resulted in a large TT incorporation in endosomes of nonspecific cells, similar to that observed in antigen-specific cells. Thus, C3b covalently linked to antigen enlarges the array of B-cell types capable of presenting antigen, including non-specific cells. Images Figure 2 PMID:8958046

Extraction of Cell-Wall Polysaccharide Antigen from Streptococci

PubMed Central

Slade, Hutton D.

1965-01-01

Slade, Hutton D. (Northwestern University Medical School, Chicago, Ill., and Max-Planck Institut für Immunbiologie, Freiburg, Germany). Extraction of cell-wall polysaccharide antigen from streptococci. J. Bacteriol. 90:667–672. 1965.—The carbohydrate grouping antigens in the cell walls of streptococci belonging to groups A, E, G, L, and T were extracted with 5% trichloroacetic acid at 90 C. The antigens were removed also from dry whole cells by extraction with trichloroacetic acid followed by treatment with phenol-water. Details of the methods are presented. The antigens obtained by use of either of these procedures were suitable for studies on immunological specificity and chemical structure. Quantitative enzymatic and chemical analyses of two group E antigens and one group T preparation showed the presence of l-rhamnose (22 to 44%), d-glucose (7 to 22%), d-galactose (T antigen only, 26%), glucosamine (2 to 16%), and galactosamine (T antigen only, 3%). In addition, analyses of A and G antigen preparations are presented. The protein and phosphate content of the A and E antigens were about 1% each. Quantitative precipitin curves of these antigens are presented. PMID:16562065

Cationic liposomes promote antigen cross-presentation in dendritic cells by alkalizing the lysosomal pH and limiting the degradation of antigens

PubMed Central

Gao, Jie; Ochyl, Lukasz J; Yang, Ellen; Moon, James J

2017-01-01

Cationic liposomes (CLs) have been widely examined as vaccine delivery nanoparticles since they can form complexes with biomacromolecules, promote delivery of antigens and adjuvant molecules to antigen-presenting cells (APCs), and mediate cellular uptake of vaccine components. CLs are also known to trigger antigen cross-presentation – the process by which APCs internalize extracellular protein antigens, degrade them into minimal CD8+ T-cell epitopes, and present them in the context of major histocompatibility complex-I (MHC-I). However, the precise mechanisms behind CL-mediated induction of cross-presentation and cross-priming of CD8+ T-cells remain to be elucidated. In this study, we have developed two distinct CL systems and examined their impact on the lysosomal pH in dendritic cells (DCs), antigen degradation, and presentation of peptide:MHC-I complexes to antigen-specific CD8+ T-cells. To achieve this, we have used 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as the prototypical components of CLs with tertiary amine groups and compared the effect of CLs and anionic liposomes on lysosomal pH, antigen degradation, and cross-presentation by DCs. Our results showed that CLs, but not anionic liposomes, elevated the lysosomal pH in DCs and reduced antigen degradation, thereby promoting cross-presentation and cross-priming of CD8+ T-cell responses. These studies shed new light on CL-mediated cross-presentation and suggest that intracellular fate of vaccine components and subsequent immunological responses can be controlled by rational design of nanomaterials. PMID:28243087

Estimation method of finger tapping dynamics using simple magnetic detection system

NASA Astrophysics Data System (ADS)

Kandori, Akihiko; Sano, Yuko; Miyashita, Tsuyoshi; Okada, Yoshihisa; Irokawa, Masataka; Shima, Keisuke; Tsuji, Toshio; Yokoe, Masaru; Sakoda, Saburo

2010-05-01

We have developed the simple estimation method of a finger tapping dynamics model for investigating muscle resistance and stiffness during tapping movement in normal subjects. We measured finger tapping movements of 207 normal subjects using a magnetic finger tapping detection system. Each subject tapped two fingers in time with a metronome at 1, 2, 3, 4, and 5 Hz. The velocity and acceleration values for both the closing and opening tapping data were used to estimate a finger tapping dynamics model. Using the frequency response of the ratio of acceleration to velocity of the mechanical impedance parameters, we estimated the resistance (friction coefficient) and compliance (stiffness). We found two dynamics models for the maximum open position and tap position. In the maximum open position, the extensor muscle resistance was twice as high as the flexor muscle resistance and males had a higher spring constant. In the tap position, the flexor muscle resistance was much higher than the extensor muscle resistance. This indicates that the tapping dynamics in the maximum open position are controlled by the balance of extensor and flexor muscle friction resistances and the flexor stiffness, and the flexor friction resistance is the main component in the tap position. It can be concluded that our estimation method makes it possible to understand the tapping dynamics.

Estimation method of finger tapping dynamics using simple magnetic detection system.

PubMed

Kandori, Akihiko; Sano, Yuko; Miyashita, Tsuyoshi; Okada, Yoshihisa; Irokawa, Masataka; Shima, Keisuke; Tsuji, Toshio; Yokoe, Masaru; Sakoda, Saburo

2010-05-01

We have developed the simple estimation method of a finger tapping dynamics model for investigating muscle resistance and stiffness during tapping movement in normal subjects. We measured finger tapping movements of 207 normal subjects using a magnetic finger tapping detection system. Each subject tapped two fingers in time with a metronome at 1, 2, 3, 4, and 5 Hz. The velocity and acceleration values for both the closing and opening tapping data were used to estimate a finger tapping dynamics model. Using the frequency response of the ratio of acceleration to velocity of the mechanical impedance parameters, we estimated the resistance (friction coefficient) and compliance (stiffness). We found two dynamics models for the maximum open position and tap position. In the maximum open position, the extensor muscle resistance was twice as high as the flexor muscle resistance and males had a higher spring constant. In the tap position, the flexor muscle resistance was much higher than the extensor muscle resistance. This indicates that the tapping dynamics in the maximum open position are controlled by the balance of extensor and flexor muscle friction resistances and the flexor stiffness, and the flexor friction resistance is the main component in the tap position. It can be concluded that our estimation method makes it possible to understand the tapping dynamics.

Bacterial community of iron tubercles from a drinking water distribution system and its occurrence in stagnant tap water.

PubMed

Chen, Lu; Jia, Rui-Bao; Li, Li

2013-07-01

Bacteria in drinking water distribution systems can cause deterioration of the water quality, and the microbial quality of tap water is closely related to consumer health. In the present study, the potential effects of bacteria attached to cast iron pipes on tap water in a distribution system were investigated. Comparison of the bacterial community composition of pipe tubercles with that of stagnant tap water samples based on a denaturing gradient gel electrophoresis analysis of the 16S rRNA gene revealed that the communities were related. Specifically, the main bacterial members were identical to each other. The bacterial community was found to be dominated by Firmicutes, Actinobacteria, and Proteobacteria, which included Rhizobium, Pseudomonas, Lactococcus, Brevundimonas, Rheinheimera, Arthrobacter, Bacillus, and Herbaspirillum. Heterotrophic bacteria proliferation was observed during the period of stagnation, followed by a decrease of assimilable organic carbon and a slight increase of microbially available phosphorus. These findings indicated that the regrowth of bacteria might be boosted by the release of nutrients such as phosphorus from the pipe walls, as well as the decline of residual chlorine during stagnation. Inorganic contaminants at low levels, including Al, Mn, Zn, Pb, Cr, Cu, and Ni, were detected in tubercles and were concentrated in particulates from tap water following the release of iron during stagnation.

Motion tracking and electromyography-assisted identification of mirror hand contributions to functional near-infrared spectroscopy images acquired during a finger-tapping task performed by children with cerebral palsy.

PubMed

Hervey, Nathan; Khan, Bilal; Shagman, Laura; Tian, Fenghua; Delgado, Mauricio R; Tulchin-Francis, Kirsten; Shierk, Angela; Roberts, Heather; Smith, Linsley; Reid, Dahlia; Clegg, Nancy J; Liu, Hanli; MacFarlane, Duncan; Alexandrakis, George

2014-10-01

Recent studies have demonstrated functional near-infrared spectroscopy (fNIRS) to be a viable and sensitive method for imaging sensorimotor cortex activity in children with cerebral palsy (CP). However, during unilateral finger tapping, children with CP often exhibit unintended motions in the nontapping hand, known as mirror motions, which confuse the interpretation of resulting fNIRS images. This work presents a method for separating some of the mirror motion contributions to fNIRS images and demonstrates its application to fNIRS data from four children with CP performing a finger-tapping task with mirror motions. Finger motion and arm muscle activity were measured simultaneously with fNIRS signals using motion tracking and electromyography (EMG), respectively. Subsequently, subject-specific regressors were created from the motion capture or EMG data and independent component analysis was combined with a general linear model to create an fNIRS image representing activation due to the tapping hand and one image representing activation due to the mirror hand. The proposed method can provide information on how mirror motions contribute to fNIRS images, and in some cases, it helps remove mirror motion contamination from the tapping hand activation images.

Motion tracking and electromyography-assisted identification of mirror hand contributions to functional near-infrared spectroscopy images acquired during a finger-tapping task performed by children with cerebral palsy

PubMed Central

Hervey, Nathan; Khan, Bilal; Shagman, Laura; Tian, Fenghua; Delgado, Mauricio R.; Tulchin-Francis, Kirsten; Shierk, Angela; Roberts, Heather; Smith, Linsley; Reid, Dahlia; Clegg, Nancy J.; Liu, Hanli; MacFarlane, Duncan; Alexandrakis, George

2014-01-01

Abstract. Recent studies have demonstrated functional near-infrared spectroscopy (fNIRS) to be a viable and sensitive method for imaging sensorimotor cortex activity in children with cerebral palsy (CP). However, during unilateral finger tapping, children with CP often exhibit unintended motions in the nontapping hand, known as mirror motions, which confuse the interpretation of resulting fNIRS images. This work presents a method for separating some of the mirror motion contributions to fNIRS images and demonstrates its application to fNIRS data from four children with CP performing a finger-tapping task with mirror motions. Finger motion and arm muscle activity were measured simultaneously with fNIRS signals using motion tracking and electromyography (EMG), respectively. Subsequently, subject-specific regressors were created from the motion capture or EMG data and independent component analysis was combined with a general linear model to create an fNIRS image representing activation due to the tapping hand and one image representing activation due to the mirror hand. The proposed method can provide information on how mirror motions contribute to fNIRS images, and in some cases, it helps remove mirror motion contamination from the tapping hand activation images. PMID:26157980

Prolonged expression of MHC class I - peptide expression in bone marrow derived retrovirus transfected matured dendritic cells by continuous centrifugation in the presence of IL-4.

PubMed

Hettihewa, L M

2011-11-01

Dendritic cells (DCs) are potent antigen presenting cells which proceed from immature to a mature stage during their differentiation. There are several methods of obtaining long lasting mature antigen expressing DCs and different methods show different levels of antigen expressions. We investigated bone marrow derived DCs for the degree of maturation and genetically engineered antigen presentation in the presence of interleukin-4 (IL-4) as a maturity enhancer. DCs and transfected retrovirus were cultured together in the presence of granulocyte-macrophage colony stimulating factor (GMCSF)-IL4, GMCSF +IL4, lipopolysaccharide (LPS). B 7.1, B7.2 and CD11c were measured by the degree of immune fluorescence using enhanced green fluorescent protein (EGFP) shuttled retrovirus transfected antigen. Degree of MHC class I molecule with antigen presentation of antigen was also evaluated by fluorescence activated cell sorting. The antigen presenting capacity of transfected DCs was investigated. Bone marrow DCs were generated in the presence of GMCSF and IL-4 in vitro. Dividing bone marrow cells were infected with EGFP shuttled retrovirus expressing SSP2 by prolonged centrifugation for three consecutive days from day 5, 6 and 7 and continued to culture in the presence of GMSCF and IL-4 until day 8. IL-4 as a cytokine increased the maturation of retrovirus transfected DCs by high expression of B 7-1 and B 7-2. Also, IL-4 induced DC enhanced by the prolonged centrifugation and it was shown by increased antigen presentation of these dendric cells as antigen presenting cell (APC). Cytolytic effects were significantly higher in cytotoxic T cell response (CTLs) mixed with transfected DCs than CTLs mixed with pulsed DCs. There was an enhanced antigen presentation by prolonged expression of antigen loaded MHC class I receptors in DCs in the presence of IL-4 by prolonged centrifugation.

The translocon protein Sec61 mediates antigen transport from endosomes in the cytosol for cross-presentation to CD8(+) T cells.

PubMed

Zehner, Matthias; Marschall, Andrea L; Bos, Erik; Schloetel, Jan-Gero; Kreer, Christoph; Fehrenschild, Dagmar; Limmer, Andreas; Ossendorp, Ferry; Lang, Thorsten; Koster, Abraham J; Dübel, Stefan; Burgdorf, Sven

2015-05-19

The molecular mechanisms regulating antigen translocation into the cytosol for cross-presentation are under controversial debate, mainly because direct data is lacking. Here, we have provided direct evidence that the activity of the endoplasmic reticulum (ER) translocon protein Sec61 is essential for endosome-to-cytosol translocation. We generated a Sec61-specific intrabody, a crucial tool that trapped Sec61 in the ER and prevented its recruitment into endosomes without influencing Sec61 activity and antigen presentation in the ER. Expression of this ER intrabody inhibited antigen translocation and cross-presentation, demonstrating that endosomal Sec61 indeed mediates antigen transport across endosomal membranes. Moreover, we showed that the recruitment of Sec61 toward endosomes, and hence antigen translocation and cross-presentation, is dependent on dendritic cell activation by Toll-like receptor (TLR) ligands. These data shed light on a long-lasting question regarding antigen cross-presentation and point out a role of the ER-associated degradation machinery in compartments distinct from the ER. Copyright © 2015 Elsevier Inc. All rights reserved.

Age-related changes in the bimanual advantage and in brain oscillatory activity during tapping movements suggest a decline in processing sensory reafference.

PubMed

Sallard, Etienne; Spierer, Lucas; Ludwig, Catherine; Deiber, Marie-Pierre; Barral, Jérôme

2014-02-01

Deficits in the processing of sensory reafferences have been suggested as accounting for age-related decline in motor coordination. Whether sensory reafferences are accurately processed can be assessed based on the bimanual advantage in tapping: because of tapping with an additional hand increases kinesthetic reafferences, bimanual tapping is characterized by a reduced inter-tap interval variability than unimanual tapping. A suppression of the bimanual advantage would thus indicate a deficit in sensory reafference. We tested whether elderly indeed show a reduced bimanual advantage by measuring unimanual (UM) and bimanual (BM) self-paced tapping performance in groups of young (n = 29) and old (n = 27) healthy adults. Electroencephalogram was recorded to assess the underlying patterns of oscillatory activity, a neurophysiological mechanism advanced to support the integration of sensory reafferences. Behaviorally, there was a significant interaction between the factors tapping condition and age group at the level of the inter-tap interval variability, driven by a lower variability in BM than UM tapping in the young, but not in the elderly group. This result indicates that in self-paced tapping, the bimanual advantage is absent in elderly. Electrophysiological results revealed an interaction between tapping condition and age group on low beta band (14-20 Hz) activity. Beta activity varied depending on the tapping condition in the elderly but not in the young group. Source estimations localized this effect within left superior parietal and left occipital areas. We interpret our results in terms of engagement of different mechanisms in the elderly depending on the tapping mode: a 'kinesthetic' mechanism for UM and a 'visual imagery' mechanism for BM tapping movement.

Acanthamoeba keratitis: the role of domestic tap water contamination in the United Kingdom.

PubMed

Kilvington, Simon; Gray, Trevor; Dart, John; Morlet, Nigel; Beeching, John R; Frazer, David G; Matheson, Melville

2004-01-01

The incidence of acanthamoeba keratitis (AK) in the UK is some 15 times that in the United States and seven times that in Holland. To investigate reasons for this higher frequency, a study of the role of domestic tap water as a potential source of AK was undertaken. Tap outlets from the homes of 27 patients with culture-proven AK were sampled and cultured for free-living amoebae (FLA). For all Acanthamoeba isolates, mitochondrial DNA (mtDNA) restriction fragment length polymorphisms (RFLPs) and cytochrome oxidase (cox 1/2) sequence typing was performed to determine the similarity between corneal and tap water isolates. FLA, including Acanthamoeba, were isolated from 24 (89%) of 27 homes, and the presence within the homes varied significantly with tap water temperature and location: 19 (76%) of 25 bathroom sink cold taps sampled compared with 6 (24%) of 25 hot and 9 (47%) of 19 kitchen cold taps compared with 3 (16%) of 19 of hot kitchen taps. Acanthamoeba were isolated from 8 (30%) of 27 homes (five bathroom sink cold taps, one cloakroom cold tap, one bath, and one bedroom sink mixer [hot/cold] taps). In six cases, identical Acanthamoeba mtDNA profiles were found for the clinical and home tap water isolates. In keeping with UK plumbing practice, 24 of 27 homes had internal roof water storage tanks to supply domestic taps, but the mains fed the kitchen cold tap. Water storage tanks promote colonization of domestic water with FLA, including Acanthamoeba, and hence increase the risk of AK. This accounts for the significantly greater incidence of AK in the UK and supports advice to avoid using tap water in contact lens care routines.

The Effect of Superparamagnetic Iron Oxide Nanoparticle Surface Charge on Antigen Cross-Presentation.

PubMed

Mou, Yongbin; Xing, Yun; Ren, Hongyan; Cui, Zhihua; Zhang, Yu; Yu, Guangjie; Urba, Walter J; Hu, Qingang; Hu, Hongming

2017-12-01

Magnetic nanoparticles (NPs) of superparamagnetic iron oxide (SPIO) have been explored for different kinds of applications in biomedicine, mechanics, and information. Here, we explored the synthetic SPIO NPs as an adjuvant on antigen cross-presentation ability by enhancing the intracellular delivery of antigens into antigen presenting cells (APCs). Particles with different chemical modifications and surface charges were used to study the mechanism of action of antigen delivery. Specifically, two types of magnetic NPs, γFe 2 O 3 /APTS (3-aminopropyltrimethoxysilane) NPs and γFe 2 O 3 /DMSA (meso-2, 3-Dimercaptosuccinic acid) NPs, with the same crystal structure, magnetic properties, and size distribution were prepared. Then, the promotion of T-cell activation via dendritic cells (DCs) was compared among different charged antigen coated NPs. Moreover, the activation of the autophagy, cytosolic delivery of the antigens, and antigen degradation mediated by the proteasome and lysosome were measured. Our results indicated that positive charged γFe 2 O 3 /APTS NPs, but not negative charged γFe 2 O 3 /DMSA NPs, enhanced the cross-presentation ability of DCs. Increased cross-presentation ability induced by γFe 2 O 3 /APTS NPs was associated with increased cytosolic antigen delivery. On the contrary, γFe 2 O 3 /DMSA NPs was associated with rapid autophagy. Overall, our results suggest that antigen delivered in cytoplasm induced by positive charged particles is beneficial for antigen cross-presentation and T-cell activation. NPs modified with different chemistries exhibit diverse biological properties and differ greatly in their adjuvant potentials. Thus, it should be carefully considered many different effects of NPs to design effective and safe adjuvants.

The Effect of Superparamagnetic Iron Oxide Nanoparticle Surface Charge on Antigen Cross-Presentation

NASA Astrophysics Data System (ADS)

Mou, Yongbin; Xing, Yun; Ren, Hongyan; Cui, Zhihua; Zhang, Yu; Yu, Guangjie; Urba, Walter J.; Hu, Qingang; Hu, Hongming

2017-01-01

Magnetic nanoparticles (NPs) of superparamagnetic iron oxide (SPIO) have been explored for different kinds of applications in biomedicine, mechanics, and information. Here, we explored the synthetic SPIO NPs as an adjuvant on antigen cross-presentation ability by enhancing the intracellular delivery of antigens into antigen presenting cells (APCs). Particles with different chemical modifications and surface charges were used to study the mechanism of action of antigen delivery. Specifically, two types of magnetic NPs, γFe2O3/APTS (3-aminopropyltrimethoxysilane) NPs and γFe2O3/DMSA (meso-2, 3-Dimercaptosuccinic acid) NPs, with the same crystal structure, magnetic properties, and size distribution were prepared. Then, the promotion of T-cell activation via dendritic cells (DCs) was compared among different charged antigen coated NPs. Moreover, the activation of the autophagy, cytosolic delivery of the antigens, and antigen degradation mediated by the proteasome and lysosome were measured. Our results indicated that positive charged γFe2O3/APTS NPs, but not negative charged γFe2O3/DMSA NPs, enhanced the cross-presentation ability of DCs. Increased cross-presentation ability induced by γFe2O3/APTS NPs was associated with increased cytosolic antigen delivery. On the contrary, γFe2O3/DMSA NPs was associated with rapid autophagy. Overall, our results suggest that antigen delivered in cytoplasm induced by positive charged particles is beneficial for antigen cross-presentation and T-cell activation. NPs modified with different chemistries exhibit diverse biological properties and differ greatly in their adjuvant potentials. Thus, it should be carefully considered many different effects of NPs to design effective and safe adjuvants.

Tumor-Derived Microvesicles Modulate Antigen Cross-Processing via Reactive Oxygen Species-Mediated Alkalinization of Phagosomal Compartment in Dendritic Cells.

PubMed

Battisti, Federico; Napoletano, Chiara; Rahimi Koshkaki, Hassan; Belleudi, Francesca; Zizzari, Ilaria Grazia; Ruscito, Ilary; Palchetti, Sara; Bellati, Filippo; Benedetti Panici, Pierluigi; Torrisi, Maria Rosaria; Caracciolo, Giulio; Altieri, Fabio; Nuti, Marianna; Rughetti, Aurelia

2017-01-01

Dendritic cells (DCs) are the only antigen-presenting cells able to prime naïve T cells and cross-prime antigen-specific CD8 + T cells. Their functionality is a requirement for the induction and maintenance of long-lasting cancer immunity. Albeit intensively investigated, the in vivo mechanisms underlying efficient antigen cross-processing and presentation are not fully understood. Several pieces of evidence indicate that antigen transfer to DCs mediated by microvesicles (MVs) enhances antigen immunogenicity. This mechanism is also relevant for cross-presentation of those tumor-associated glycoproteins such as MUC1 that are blocked in HLA class II compartment when internalized by DCs as soluble molecules. Here, we present pieces of evidence that the internalization of tumor-derived MVs modulates antigen-processing machinery of DCs. Employing MVs derived from ovarian cancer ascites fluid and established tumor cell lines, we show that MV uptake modifies DC phagosomal microenvironment, triggering reactive oxygen species (ROS) accumulation and early alkalinization. Indeed, tumor MVs carry radical species and the MV uptake by DCs counteracts the chemically mediated acidification of the phagosomal compartment. Further pieces of evidence suggest that efficacious antigen cross-priming of the MUC1 antigen carried by the tumor MVs results from the early signaling induced by MV internalization and the function of the antigen-processing machinery of DCs. These results strongly support the hypothesis that tumor-derived MVs impact antigen immunogenicity by tuning the antigen-processing machinery of DCs, besides being carrier of tumor antigens. Furthermore, these findings have important implications for the exploitation of MVs as antigenic cell-free immunogen for DC-based therapeutic strategies.

Enhanced Direct Major Histocompatibility Complex Class I Self-Antigen Presentation Induced by Chlamydia Infection

PubMed Central

Cram, Erik D.; Simmons, Ryan S.; Palmer, Amy L.; Hildebrand, William H.; Rockey, Daniel D.

2015-01-01

The direct major histocompatibility complex (MHC) class I antigen presentation pathway ensures intracellular peptides are displayed at the cellular surface for recognition of infected or transformed cells by CD8+ cytotoxic T lymphocytes. Chlamydia spp. are obligate intracellular bacteria and, as such, should be targeted by CD8+ T cells. It is likely that Chlamydia spp. have evolved mechanisms to avoid the CD8+ killer T cell responses by interfering with MHC class I antigen presentation. Using a model system of self-peptide presentation which allows for posttranslational control of the model protein's stability, we tested the ability of various Chlamydia species to alter direct MHC class I antigen presentation. Infection of the JY lymphoblastoid cell line limited the accumulation of a model host protein and increased presentation of the model-protein-derived peptides. Enhanced self-peptide presentation was detected only when presentation was restricted to defective ribosomal products, or DRiPs, and total MHC class I levels remained unaltered. Skewed antigen presentation was dependent on a bacterial synthesized component, as evidenced by reversal of the observed phenotype upon preventing bacterial transcription, translation, and the inhibition of bacterial lipooligosaccharide synthesis. These data suggest that Chlamydia spp. have evolved to alter the host antigen presentation machinery to favor presentation of defective and rapidly degraded forms of self-antigen, possibly as a mechanism to diminish the presentation of peptides derived from bacterial proteins. PMID:26597986

Are perfluoroalkyl acids in waste water treatment plant effluents the result of primary emissions from the technosphere or of environmental recirculation?

PubMed

Filipovic, Marko; Berger, Urs

2015-06-01

Wastewater treatment plants (WWTP) have been suggested to be one of the major pathways of perfluoroalkyl acids (PFAAs) from the technosphere to the aquatic environment. The origin of PFAAs in WWTP influents is either from current primary emissions or a result of recirculation of PFAAs that have been residing and transported in the environment for several years or decades. Environmental recirculation can then occur when PFAAs from the environment enter the wastewater stream in, e.g., tap water. In this study 13 PFAAs and perfluorooctane sulfonamide were analyzed in tap water as well as WWTP influent, effluent and sludge from three Swedish cities: Bromma (in the metropolitan area of Stockholm), Bollebygd and Umeå. A mass balance of the WWTPs was assembled for each PFAA. Positive mass balances were observed for PFHxA and PFOA in all WWTPs, indicating the presence of precursor compounds in the technosphere. With regard to environmental recirculation, tap water was an important source of PFAAs to the Bromma WWTP influent, contributing >40% for each quantified sulfonic acid and up to 30% for the carboxylic acids. The PFAAs in tap water from Bollebygd and Umeå did not contribute significantly to the PFAA load in the WWTP influents. Our results show that in order to estimate current primary emissions from the technosphere, it may be necessary to correct the PFAA emission rates in WWTP effluents for PFAAs present in tap water, especially in the case of elevated levels in tap water. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of Transversus Abdominis Plane Block on Postoperative Pain after Colorectal Surgery: A Meta-Analysis of Randomized Controlled Trials.

PubMed

Liu, Lin; Xie, Yan-Hu; Zhang, Wei; Chai, Xiao-Qing

2018-01-01

To assess the analgesic efficacy of transversus abdominis plane (TAP) block in patients undergoing colorectal surgery (CRS). The databases of PubMed, ISI Web of Science, and Embase were searched, and randomized controlled studies (RCTs) that compared TAP block to control for relief of postoperative pain in patients who underwent CRS were included. Outcomes, including postoperative pain at rest and with movement, morphine use, postoperative nausea and vomiting, and the length of hospital stay, were analyzed using STATA software. The weighted mean differences (WMDs) with 95% confidence intervals (95% CIs) or relative risk with 95% CI were used to present the strength of associations. A total of 7 RCTs with 511 patients were included. The results of this study suggested that TAP block significantly relieved postoperative pain during postanesthetic recovery after CRS at rest and during movement (WMDs were -0.98 [95% CI -1.57 to -0.38] and -0.68 [-1.07 to -0.30], respectively), and also decreased pain intensity during movement 24 h after CRS (WMD: -0.57 [95% CI -1.06 to -0.08]). TAP block significantly reduced opioid consumption within 24 h when compared to controls, with a WMD of 15.66 (95% CI -23.93 to -7.39). However, TAP block did not shorten the length of hospital stay. TAP block was an effective approach for relief of postoperative pain and reduced postoperative consumption of morphine. More RCTs with large sample sizes are required to confirm these findings. © 2018 The Author(s) Published by S. Karger AG, Basel.

Uncovering beat deafness: detecting rhythm disorders with synchronized finger tapping and perceptual timing tasks.

PubMed

Dalla Bella, Simone; Sowiński, Jakub

2015-03-16

A set of behavioral tasks for assessing perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) is presented here with the goal of uncovering rhythm disorders, such as beat deafness. Beat deafness is characterized by poor performance in perceiving durations in auditory rhythmic patterns or poor synchronization of movement with auditory rhythms (e.g., with musical beats). These tasks include the synchronization of finger tapping to the beat of simple and complex auditory stimuli and the detection of rhythmic irregularities (anisochrony detection task) embedded in the same stimuli. These tests, which are easy to administer, include an assessment of both perceptual and sensorimotor timing abilities under different conditions (e.g., beat rates and types of auditory material) and are based on the same auditory stimuli, ranging from a simple metronome to a complex musical excerpt. The analysis of synchronized tapping data is performed with circular statistics, which provide reliable measures of synchronization accuracy (e.g., the difference between the timing of the taps and the timing of the pacing stimuli) and consistency. Circular statistics on tapping data are particularly well-suited for detecting individual differences in the general population. Synchronized tapping and anisochrony detection are sensitive measures for identifying profiles of rhythm disorders and have been used with success to uncover cases of poor synchronization with spared perceptual timing. This systematic assessment of perceptual and sensorimotor timing can be extended to populations of patients with brain damage, neurodegenerative diseases (e.g., Parkinson's disease), and developmental disorders (e.g., Attention Deficit Hyperactivity Disorder).

Bimanual tapping of a syncopated rhythm reveals hemispheric preferences for relative movement frequencies.

PubMed

Pflug, Anja; Gompf, Florian; Kell, Christian Alexander

2017-08-01

In bimanual multifrequency tapping, right-handers commonly use the right hand to tap the relatively higher rate and the left hand to tap the relatively lower rate. This could be due to hemispheric specializations for the processing of relative frequencies. An extension of the double-filtering-by-frequency theory to motor control proposes a left hemispheric specialization for the control of relatively high and a right hemispheric specialization for the control of relatively low tapping rates. We investigated timing variability and rhythmic accentuation in right handers tapping mono- and multifrequent bimanual rhythms to test the predictions of the double-filtering-by-frequency theory. Yet, hemispheric specializations for the processing of relative tapping rates could be masked by a left hemispheric dominance for the control of known sequences. Tapping was thus either performed in an overlearned quadruple meter (tap of the slow rhythm on the first auditory beat) or in a syncopated quadruple meter (tap of the slow rhythm on the fourth auditory beat). Independent of syncopation, the right hand outperformed the left hand in timing accuracy for fast tapping. A left hand timing benefit for slow tapping rates as predicted by the double-filtering-by-frequency theory was only found in the syncopated tapping group. This suggests a right hemisphere preference for the control of slow tapping rates when rhythms are not overlearned. Error rates indicate that overlearned rhythms represent hierarchically structured meters that are controlled by a single timer that could potentially reside in the left hemisphere. Copyright © 2017 Elsevier B.V. All rights reserved.

40 CFR 63.544 - Standards for process fugitive sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Smelting furnace and dryer charging hoppers, chutes, and skip hoists; (2) Smelting furnace lead taps, and molds during tapping; (3) Smelting furnace slag taps, and molds during tapping; (4) Refining kettles; (5) Dryer transition pieces; and (6) Agglomerating furnace product taps. (b) Process fugitive emission...

Types of diaphragmatic motion during hepatic angiography.

PubMed

Katsuda, T; Kuroda, C; Fujita, M

1997-01-01

To determine the types and causes of diaphragmatic motion during hepatic angiography, the authors used transarterial cut-film portography (TAP) to study movement of the diaphragm during breath-holding. Thirty-three TAP sequences were studied, and the patients' diaphragmatic motions were classified into four categories according to the distance their diaphragms moved. Results showed that the diaphragm was stationary in 33% of the TAP studies, while perpetual motion occurred in 15% of the studies, early-phase motion occurred in 12% and late-phase motion occurred in 40%. Ten sequences showed diaphragmatic motion of more than 10 mm, with eight sequences showing caudal motion and two showing cranial motion. This article discusses the cause of diaphragmatic motion during breath-holding for hepatic angiography and presents suggestions to reduce motion artifacts during the exam.

Melodic cues for metre.

PubMed

Vos, P G; van Dijk, A; Schomaker, L

1994-01-01

A method of time-series analysis and a time-beating experiment were used to test the structural and perceptual validity of notated metre. Autocorrelation applied to the flow of melodic intervals between notes from thirty fragments of compositions for solo instruments by J S Bach strongly supported the validity of bar length specifications. Time-beating data, obtained with four stimuli from the same set, played in an expressionless mode, and presented under categorically distinct tempos to different subgroups of musically trained subjects, were rather inconsistent with respect to tapped bar lengths. However, taps were most frequently given to the events in the stimuli that corresponded with the first beats according to the score notations. No significant effects of tempo on tapping patterns were observed. The findings are discussed in comparison with other examinations of metre inference from musical compositions.

Antigen Cross-Presentation of Immune Complexes

PubMed Central

Platzer, Barbara; Stout, Madeleine; Fiebiger, Edda

2014-01-01

The ability of dendritic cells (DCs) to cross-present tumor antigens has long been a focus of interest to physicians, as well as basic scientists, that aim to establish efficient cell-based cancer immune therapy. A prerequisite for exploiting this pathway for therapeutic purposes is a better understanding of the mechanisms that underlie the induction of tumor-specific cytotoxic T-lymphocyte (CTL) responses when initiated by DCs via cross-presentation. The ability of humans DC to perform cross-presentation is of utmost interest, as this cell type is a main target for cell-based immunotherapy in humans. The outcome of a cross-presentation event is guided by the nature of the antigen, the form of antigen uptake, and the subpopulation of DCs that performs presentation. Generally, CD8α+ DCs are considered to be the most potent cross-presenting DCs. This paradigm, however, only applies to soluble antigens. During adaptive immune responses, immune complexes form when antibodies interact with their specific epitopes on soluble antigens. Immunoglobulin G (IgG) immune complexes target Fc-gamma receptors on DCs to shuttle exogenous antigens efficiently into the cross-presentation pathway. This receptor-mediated cross-presentation pathway is a well-described route for the induction of strong CD8+ T cell responses. IgG-mediated cross-presentation is intriguing because it permits the CD8− DCs, which are commonly considered to be weak cross-presenters, to efficiently cross-present. Engaging multiple DC subtypes for cross-presentation might be a superior strategy to boost CTL responses in vivo. We here summarize our current understanding of how DCs use IgG-complexed antigens for the efficient induction of CTL responses. Because of its importance for human cell therapy, we also review the recent advances in the characterization of cross-presentation properties of human DC subsets. PMID:24744762

Computerized measures of finger tapping: effects of hand dominance, age, and sex.

PubMed

Hubel, Kerry A; Reed, Bruce; Yund, E William; Herron, Timothy J; Woods, David L

2013-06-01

Computerized measures of digit tapping rate were obtained over 3 successive, 10-sec. periods in the right and left index fingers, from a community sample of 1,519 participants (ages 18 to 65 years; 607 men, 912 women). Differences between the dominant and non-dominant hands were found for tapping rate, movement initiation, and button down times, and the decline in tapping rate over the successive, 10-sec. periods. Declines were found in tapping rate in older participants in association with increased intertap variability. Men had higher tapping rates than women in all age ranges. The computerized finger tapping test is an efficient and precise measure of tapping speed and kinetics of potential utility in research and clinical studies of motor performance.

Brain activity during bilateral rapid alternate finger tapping measured with magnetoencephalography

NASA Astrophysics Data System (ADS)

Fukuda, Hiroshi; Odagaki, Masato; Hiwaki, Osamu; Kodabashi, Atsushi; Fujimoto, Toshiro

2009-04-01

Using magnetoencephalography (MEG), brain regions involved in an alternate bimanual tapping task by index fingers triggered with spontaneous timing were investigated. The tapping mode in which both index fingers moved simultaneously was interlaced during the task. The groups of the alternate tapping (AL mode) and the simultaneous tapping (SI mode) were extracted from the successive alternating taps with a histogram of intervals between the right and left index fingers. MEG signals in each mode were averaged separately before and after the tapping initiation of the dominant index finger. The activities of the contralateral sensorimotor cortex before and after the tapping initiation in the AL mode were larger than that in the SI mode. The result indicates that the activity of the contralateral sensorimotor cortex depends on the degree of achievement in the difficult motor task such as the voluntary alternate tapping movements.

Freely Chosen Index Finger Tapping Frequency Is Increased in Repeated Bouts of Tapping.

PubMed

Hansen, Ernst Albin; Ebbesen, Brian Duborg; Dalsgaard, Ane; Mora-Jensen, Mark Holten; Rasmussen, Jakob

2015-01-01

Healthy individuals (n = 40) performed index finger tapping at freely chosen frequency during repeated bouts and before and after near-maximal muscle action consisting of 3 intense flexions of the index finger metacarpal phalangeal joint. One experiment showed, unexpectedly, that a bout of tapping increased the tapping frequency in the subsequent bout. Thus, a cumulating increase of 8.2 ± 5.4% (p < .001) occurred across 4 bouts, which were all separated by 10 min rest periods. Follow-up experiments revealed that tapping frequency was still increased in consecutive bouts when rest periods were extended to 20 min. Besides, near-maximal muscle activation, followed by 5 min rest, did not affect the tapping frequency. In conclusion, freely chosen tapping frequency was increased in repeated bouts of tapping, which were separated by 10-20 min rest periods. The observed phenomenon is suggested to be termed repeated bout rate enhancement.

Assessment of leg muscle activity using toe tapping in patients with Parkinson's disease: comparison of two types of toe tapping.

PubMed

Taniguchi, Seira; Peper, Ferdinand; Shimokawa, Tetsuya

2018-05-01

[Purpose] This study investigates two types of toe tapping, i.e., "closed," with both feet on the floor, and "open," in which the foot does not touch the ground, and evaluates their usefulness in combination with monitoring of muscle activity during toe tapping. [Subjects and Methods] The study enrolled 11 patients with Parkinson's disease (PD) and 9 controls (Controls). The tibialis anterior (TA) and gastrocnemius (GS) muscle activity during toe tapping was measured using surface electromyography. [Results] In closed tapping, the minima in GS activation with the first tap was significantly higher in patients with PD than in Controls. In open tapping, the coefficient of variation (CV) of local maxima in TA activation was significantly higher in patients with PD than in Controls. In both types of tapping, the CV of extrema in GS activities increased with disease duration, but this may be due to the long-term administration of Levodopa, which itself tends to cause excessive GS activities. [Conclusion] Closed tapping is suitable for the assessment of GS activity and can detect excessive activities, which is observed as visible movement. Open tapping, on the other hand, is suitable for assessment of TA activity.

Nonclassical T Cells and Their Antigens in Tuberculosis

PubMed Central

De Libero, Gennaro; Singhal, Amit; Lepore, Marco; Mori, Lucia

2014-01-01

T cells that recognize nonpeptidic antigens, and thereby are identified as nonclassical, represent important yet poorly characterized effectors of the immune response. They are present in large numbers in circulating blood and tissues and are as abundant as T cells recognizing peptide antigens. Nonclassical T cells exert multiple functions including immunoregulation, tumor control, and protection against infections. They recognize complexes of nonpeptidic antigens such as lipid and glycolipid molecules, vitamin B2 precursors, and phosphorylated metabolites of the mevalonate pathway. Each of these antigens is presented by antigen-presenting molecules other than major histocompatibility complex (MHC), including CD1, MHC class I–related molecule 1 (MR1), and butyrophilin 3A1 (BTN3A1) molecules. Here, we discuss how nonclassical T cells participate in the recognition of mycobacterial antigens and in the mycobacterial-specific immune response. PMID:25059739

Visual mental image generation does not overlap with visual short-term memory: a dual-task interference study.

PubMed

Borst, Gregoire; Niven, Elaine; Logie, Robert H

2012-04-01

Visual mental imagery and working memory are often assumed to play similar roles in high-order functions, but little is known of their functional relationship. In this study, we investigated whether similar cognitive processes are involved in the generation of visual mental images, in short-term retention of those mental images, and in short-term retention of visual information. Participants encoded and recalled visually or aurally presented sequences of letters under two interference conditions: spatial tapping or irrelevant visual input (IVI). In Experiment 1, spatial tapping selectively interfered with the retention of sequences of letters when participants generated visual mental images from aural presentation of the letter names and when the letters were presented visually. In Experiment 2, encoding of the sequences was disrupted by both interference tasks. However, in Experiment 3, IVI interfered with the generation of the mental images, but not with their retention, whereas spatial tapping was more disruptive during retention than during encoding. Results suggest that the temporary retention of visual mental images and of visual information may be supported by the same visual short-term memory store but that this store is not involved in image generation.

Overexpression of the PP2A regulatory subunit Tap46 leads to enhanced plant growth through stimulation of the TOR signalling pathway

PubMed Central

Ahn, Chang Sook; Ahn, Hee-Kyung; Pai, Hyun-Sook

2015-01-01

Tap46, a regulatory subunit of protein phosphatase 2A (PP2A), plays an essential role in plant growth and development through a functional link with the Target of Rapamycin (TOR) signalling pathway. Here, we have characterized the molecular mechanisms behind a gain-of-function phenotype of Tap46 and its relationship with TOR to gain further insights into Tap46 function in plants. Constitutive overexpression of Tap46 in Arabidopsis resulted in overall growth stimulation with enlarged organs, such as leaves and siliques. Kinematic analysis of leaf growth revealed that increased cell size was mainly responsible for the leaf enlargement. Tap46 overexpression also enhanced seed size and viability under accelerated ageing conditions. Enhanced plant growth was also observed in dexamethasone (DEX)-inducible Tap46 overexpression Arabidopsis lines, accompanied by increased cellular activities of nitrate-assimilating enzymes. DEX-induced Tap46 overexpression and Tap46 RNAi resulted in increased and decreased phosphorylation of S6 kinase (S6K), respectively, which is a sensitive indicator of endogenous TOR activity, and Tap46 interacted with S6K in planta based on bimolecular fluorescence complementation and co-immunoprecipitation. Furthermore, inactivation of TOR by estradiol-inducible RNAi or rapamycin treatment decreased Tap46 protein levels, but increased PP2A catalytic subunit levels. Real-time quantitative PCR analysis revealed that Tap46 overexpression induced transcriptional modulation of genes involved in nitrogen metabolism, ribosome biogenesis, and lignin biosynthesis. These findings suggest that Tap46 modulates plant growth as a positive effector of the TOR signalling pathway and Tap46/PP2Ac protein abundance is regulated by TOR activity. PMID:25399018

Indirect presentation in the thymus limits naive and regulatory T-cell differentiation by promoting deletion of self-reactive thymocytes.

PubMed

Yap, Jin Yan; Wirasinha, Rushika C; Chan, Anna; Howard, Debbie R; Goodnow, Christopher C; Daley, Stephen R

2018-02-07

Acquisition of T-cell central tolerance involves distinct pathways of self-antigen presentation to thymocytes. One pathway termed indirect presentation requires a self-antigen transfer step from thymic epithelial cells (TECs) to bone marrow-derived cells before the self-antigen is presented to thymocytes. The role of indirect presentation in central tolerance is context-dependent, potentially due to variation in self-antigen expression, processing and presentation in the thymus. Here, we report experiments in mice in which TECs expressed a membrane-bound transgenic self-antigen, hen egg lysozyme (HEL), from either the insulin (insHEL) or thyroglobulin (thyroHEL) promoter. Intrathymic HEL expression was less abundant and more confined to the medulla in insHEL mice compared with thyroHEL mice. When indirect presentation was impaired by generating mice lacking MHC class II expression in bone marrow-derived antigen-presenting cells, insHEL-mediated thymocyte deletion was abolished, whereas thyroHEL-mediated deletion occurred at a later stage of thymocyte development and Foxp3 + regulatory T-cell differentiation increased. Indirect presentation increased the strength of T-cell receptor signalling that both self-antigens induced in thymocytes, as assessed by Helios expression. Hence, indirect presentation limits the differentiation of naive and regulatory T cells by promoting deletion of self-reactive thymocytes. © 2018 John Wiley & Sons Ltd.

Complement opsonization of HIV-1 results in a different intracellular processing pattern and enhanced MHC class I presentation by dendritic cells

PubMed Central

Tjomsland, Veronica; Ellegård, Rada; Burgener, Adam; Mogk, Kenzie; Che, Karlhans F; Westmacott, Garrett; Hinkula, Jorma; Lifson, Jeffrey D; Larsson, Marie

2013-01-01

Induction of optimal HIV-1-specific T-cell responses, which can contribute to controlling viral infection in vivo, depends on antigen processing and presentation processes occurring in DCs. Opsonization can influence the routing of antigen processing and pathways used for presentation. We studied antigen proteolysis and the role of endocytic receptors in MHC class I (MHCI) and II (MHCII) presentation of antigens derived from HIV-1 in human monocyte-derived immature DCs (IDCs) and mature DCs, comparing free and complement opsonized HIV-1 particles. Opsonization of virions promoted MHCI presentation by DCs, indicating that complement opsonization routes more virions toward the MHCI presentation pathway. Blockade of macrophage mannose receptor (MMR) and β7-integrin enhanced MHCI and MHCII presentation by IDCs and mature DCs, whereas the block of complement receptor 3 decreased MHCI and MHCII presentation. In addition, we found that IDC and MDC proteolytic activities were modulated by HIV-1 exposure; complement-opsonized HIV-1 induced an increased proteasome activity in IDCs. Taken together, these findings indicate that endocytic receptors such as MMR, complement receptor 3, and β7-integrin can promote or disfavor antigen presentation probably by routing HIV-1 into different endosomal compartments with distinct efficiencies for degradation of viral antigens and MHCI and MHCII presentation, and that HIV-1 affects the antigen-processing machinery. PMID:23526630

Synergistic cooperation of MDM2 and E2F1 contributes to TAp73 transcriptional activity

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

Kasim, Vivi, E-mail: vivikasim78@gmail.com; Huang, Can; Zhang, Jing

2014-07-04

Highlights: • MDM2 is a novel positive regulator of TAp73 transcriptional activity. • MDM2 colocalizes together and physically interacts with E2F1. • Synergistic cooperation of MDM2 and E2F1 is crucial for TAp73 transcription. • MDM2 regulates TAp73 transcriptional activity in a p53-independent manner. - Abstract: TAp73, a structural homologue of p53, plays an important role in tumorigenesis. E2F1 had been reported as a transcriptional regulator of TAp73, however, the detailed mechanism remains to be elucidated. Here we reported that MDM2-silencing reduced the activities of the TAp73 promoters and the endogenous TAp73 expression level significantly; while MDM2 overexpression upregulated them. Wemore » further revealed that the regulation of TAp73 transcriptional activity occurs as a synergistic effect of MDM2 and E2F1, most probably through their physical interaction in the nuclei. Furthermore, we also suggested that MDM2 might be involved in DNA damage-induced TAp73 transcriptional activity. Finally, we elucidated that MDM2-silencing reduced the proliferation rate of colon carcinoma cells regardless of the p53 status. Our data show a synergistic effect of MDM2 and E2F1 on TAp73 transcriptional activity, suggesting a novel regulation pathway of TAp73.« less

A randomized trial comparing surgeon-administered intraoperative transversus abdominis plane block with anesthesiologist-administered transcutaneous block.

PubMed

Narasimhulu, D M; Scharfman, L; Minkoff, H; George, B; Homel, P; Tyagaraj, K

2018-04-27

Injection of local anesthetic into the transversus abdominis plane (TAP block) decreases systemic morphine requirements after abdominal surgery. We compared intraoperative surgeon-administered TAP block (surgical TAP) to anesthesiologist-administered transcutaneous ultrasound-guided TAP block (conventional TAP) for post-cesarean analgesia. We hypothesized that surgical TAP blocks would take less time to perform than conventional TAP blocks. We performed a randomized trial, recruiting 41 women undergoing cesarean delivery under neuraxial anesthesia, assigning them to either surgical TAP block (n=20) or conventional TAP block (n=21). Time taken to perform the block was the primary outcome, while postoperative pain scores and 24-hour opioid requirements were secondary outcomes. Student's t-test was used to compare block time and Kruskal-Wallis test opioid consumption and pain-scores. Time taken to perform the block (2.4 vs 12.1 min, P <0.001), and time spent in the operating room after delivery (55.3 vs 77.9 min, P <0.001) were significantly less for surgical TAP. The 24 h morphine consumption (P=0.17) and postoperative pain scores at 4, 8, 24 and 48 h were not significantly different between the groups. Surgical TAP blocks are feasible and less time consuming than conventional TAP blocks, while providing comparable analgesia after cesarean delivery. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Cutaneous Rabbit Revisited

ERIC Educational Resources Information Center

Flach, Rudiger; Haggard, Patrick

2006-01-01

In the cutaneous rabbit effect (CRE), a tactile event (so-called attractee tap) is mislocalized toward an adjacent attractor tap. The effect depends on the time interval between the taps. The authors delivered sequences of taps to the forearm and asked participants to report the location of one of the taps. The authors replicated the original CRE…

Sensitivity, specificity and predictive values of anterior chamber tap in cases of bacterial endophthalmitis.

PubMed

Sjoholm-Gomez de Liano, Carl; Soberon-Ventura, Vidal F; Salcedo-Villanueva, Guillermo; Santos-Palacios, Abril; Guerrero-Naranjo, Jose Luis; Fromow-Guerra, Jans; García-Aguirre, Gerardo; Morales-Canton, Virgilio; Velez-Montoya, Raul

2017-01-01

To assess the sensitivity, specificity, positive predictive value and negative predictive value of anterior chamber tap for the diagnosis of bacterial endophthalmitis on a population with high prevalence. Retrospective, single centre, case series study. We reviewed all medical records with clinical diagnosis of bacterial endophthalmitis in our hospital from January 1st, 2000 to December 31st 2014. From each record, we documented general demographic data, best corrected visual acuity and vitreous and aqueous tap microbiological results. All cases were further divided according to the endophthalmitis aetiology to perform individual calculations of sensitivity, specificity, positive predictive value, negative predictive value, accuracy and prevalence. We used the results of the vitreous tap as the gold standard for diagnosis of bacterial endophthalmitis. We excluded those records in which the aqueous and vitreous samples were not taken simultaneously or had an incomplete microbiological report. Significance were assessed with chi squared statistics, with an alpha value of 0.05 for statistical significance. A total of 190 cases fulfilled the inclusion/exclusion criteria. Positive culture rate from vitreous samples was 64.74%. Positive culture rate from aqueous sample was 32.11%. Bacteria isolated from aqueous samples matched those isolated from vitreous samples 78.68% of the time. The overall sensitivity was 38.21%, specificity: 75.51%, positive predictive value: 79.66%, negative predictive value: 32.74% ( p  = 0.08). Subgroup analysis showed that anterior chamber taps in cases of post-surgical endophthalmitis had a moderate to low sensitivity (37.73%), high specificity (93%) and high positive predictive value (95%) ( p  < 0.04). The sensitivity and specificity of anterior chamber tap are low and should not be used for critical therapeutic decisions in patients with suspected bacterial endophthalmitis. In cases of post-surgical endophthalmitis, the result of an anterior chamber tap could be used for therapeutic guidance, but only in conjunction with clinical presentation and in the absence of a better method for diagnosis.

Plasma-activation of tap water using DBD for agronomy applications: Identification and quantification of long lifetime chemical species and production/consumption mechanisms.

PubMed

Judée, F; Simon, S; Bailly, C; Dufour, T

2018-04-15

Cold atmospheric plasmas are weakly ionized gases that can be generated in ambient air. They produce energetic species (e.g. electrons, metastables) as well as reactive oxygen species, reactive nitrogen species, UV radiations and local electric field. Their interaction with a liquid such as tap water can hence change its chemical composition. The resulting "plasma-activated liquid" can meet many applications, including medicine and agriculture. Consequently, a complete experimental set of analytical techniques dedicated to the characterization of long lifetime chemical species has been implemented to characterize tap water treated using cold atmospheric plasma process and intended to agronomy applications. For that purpose, colorimetry and acid titrations are performed, considering acid-base equilibria, pH and temperature variations induced during plasma activation. 16 species are quantified and monitored: hydroxide and hydronium ions, ammonia and ammonium ions, orthophosphates, carbonate ions, nitrite and nitrate ions and hydrogen peroxide. The related consumption/production mechanisms are discussed. In parallel, a chemical model of electrical conductivity based on Kohlrausch's law has been developed to simulate the electrical conductivity of the plasma-activated tap water (PATW). Comparing its predictions with experimental measurements leads to a narrow fitting, hence supporting the self-sufficiency of the experimental set, I.e. the fact that all long lifetime radicals of interest present in PATW are characterized. Finally, to evaluate the potential of cold atmospheric plasmas for agriculture applications, tap water has been daily plasma-treated to irrigate lentils seeds. Then, seedlings lengths have been measured and compared with untreated tap water, showing an increase as high as 34.0% and 128.4% after 3 days and 6 days of activation respectively. The interaction mechanisms between plasma and tap water are discussed as well as their positive synergy on agronomic results. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influenza A Virus Infection of Human Primary Dendritic Cells Impairs Their Ability to Cross-Present Antigen to CD8 T Cells

PubMed Central

Smed-Sörensen, Anna; Chalouni, Cécile; Chatterjee, Bithi; Cohn, Lillian; Blattmann, Peter; Nakamura, Norihiro; Delamarre, Lélia; Mellman, Ira

2012-01-01

Influenza A virus (IAV) infection is normally controlled by adaptive immune responses initiated by dendritic cells (DCs). We investigated the consequences of IAV infection of human primary DCs on their ability to function as antigen-presenting cells. IAV was internalized by both myeloid DCs (mDCs) and plasmacytoid DCs but only mDCs supported viral replication. Although infected mDCs efficiently presented endogenous IAV antigens on MHC class II, this was not the case for presentation on MHC class I. Indeed, cross-presentation by uninfected cells of minute amounts of endocytosed, exogenous IAV was ∼300-fold more efficient than presentation of IAV antigens synthesized by infected cells and resulted in a statistically significant increase in expansion of IAV-specific CD8 T cells. Furthermore, IAV infection also impaired cross-presentation of other exogenous antigens, indicating that IAV infection broadly attenuates presentation on MHC class I molecules. Our results suggest that cross-presentation by uninfected mDCs is a preferred mechanism of antigen-presentation for the activation and expansion of CD8 T cells during IAV infection. PMID:22412374

The influence of the insertion technique on the pullout force of pedicle screws: an experimental study.

PubMed

Chatzistergos, Panagiotis E; Sapkas, George; Kourkoulis, Stavros K

2010-04-20

The pullout strength of a typical pedicle screw was evaluated experimentally for different screw insertion techniques. OBJECTIVE.: To conclude whether the self-tapping insertion technique is indeed the optimum one for self-tapping screws, with respect to the pullout strength. It is reported in the literature that the size of the pilot-hole significantly influences the pullout strength of a self-tapping screw. In addition it is accepted that an optimum value of the diameter of the pilot-hole exists. For non self-tapping screw insertion it is reported that undertapping of the pilot-hole can increase its pullout strength. Finally it is known that in some cases orthopedic surgeons open the threaded holes, using another screw instead of a tap. A typical commercial self-tapping pedicle screw was inserted into blocks of Solid Rigid Polyurethane Foam (simulating osteoporotic cancellous bone), following different insertion techniques. The pullout force was measured according to the ASTM-F543-02 standard. The screw was inserted into previously prepared holes of different sizes, either threaded or cylindrical, to conclude whether an optimum size of the pilot-hole exists and whether tapping can increase the pullout strength. The case where the tapping is performed using another screw was also studied. For screw insertion with tapping, decreasing the outer radius of the threaded hole from 1.00 to 0.87 of the screw's outer radius increased the pullout force 9%. For insertion without tapping, decreasing the pilot-hole's diameter from 0.87 to 0.47 of the screw's outer diameter increased its pullout force 75%. Finally, tapping using another screw instead of a tap, gave results similar to those of conventional tapping. Undertapping of a pilot-hole either using a tap or another screw can increase the pullout strength of self-tapping pedicle screws.

Analysis of UV filters in tap water and other clean waters in Spain.

PubMed

Díaz-Cruz, M Silvia; Gago-Ferrero, Pablo; Llorca, Marta; Barceló, Damià

2012-03-01

The present paper describes the development of a method for the simultaneous determination of five hormonally active UV filters namely benzophenone-3 (BP3), 3-(4-methylbenzylidene) camphor (4MBC), 2-ethylhexyl 4-(dimethylamino) benzoate (OD-PABA), 2-ethylhexyl 4-methoxycinnamate (EHMC) and octocrylene (OC) by means of solid-phase extraction and gas chromatography-electron impact ionization-mass spectrometry. Under optimized conditions, this methodology achieved low method limits of detection (needed for clean waters, especially drinking water analysis), between 0.02 and 8.42 ng/L, and quantitative recovery rates higher than 73% in all cases. Inter- and intraday precision for all compounds were lower than 7% and 11%, respectively. The optimized methodology was applied to perform the first survey of UV absorbing compounds in tap water from the metropolitan area and the city of Barcelona (Catalonia, Spain). In addition, other types of clean water matrices (mineral bottled water, well water and tap water treated with an ion-exchange resin) were investigated as well. Results evidenced that all the UV filters investigated were detected in the water samples analyzed. The compounds most frequently found were EHMC and OC. Maximum concentrations reached in tap water were 290 (BP3), 35 (4MBC), 110 (OD-PABA), 260 (EHMC), and 170 ng/L (OC). This study constitutes the first evidence of the presence of UV filter residues in tap water in Europe.

A tapping device for recording and quantitative characterization of rhythmic/auditory sequences.

PubMed

Piazza, Caterina; Cesareo, Ambra; Caccia, Martina; Reni, Gianluigi; Lorusso, Maria L

2017-07-01

The processing of auditory stimuli is essential for the correct perception of language and deficits in this ability are often related to the presence or development of language disorders. The motor imitation (e.g. tapping or beating) of rhythmic sequences can be a very sensitive correlate of deficits in auditory processing. Thus, the study of the tapping performance, with the investigation of both temporal and intensity information, might be very useful. The present work is aimed at the development and preliminary testing of a tapping device to be used for the imitation and/or the production of rhythmic sequences, allowing the recording of both tapping duration and intensity. The device is essentially made up of a Force Sensing Resistor and an Arduino UNO board. It was validated using different sampling frequencies (f s ) in a group of 10 young healthy adults investigating its efficacy in terms of touch and intensity detection by means of two testing procedures. Results demonstrated a good performance of the device when programmed with fs equal to 50 and 100Hz. Moreover, both temporal and intensity parameters were extracted, thus supporting the potential use of the device for the analysis of the imitation or production of rhythmic sequences. This work represents a first step for the development of a useful, low cost tool to support the diagnosis, training and rehabilitation of language disorders.

Temporal prediction abilities are mediated by motor effector and rhythmic expertise.

PubMed

Manning, Fiona C; Harris, Jennifer; Schutz, Michael

2017-03-01

Motor synchronization is a critical part of musical performance and listening. Recently, motor control research has described how movements that contain more available degrees of freedom are more accurately timed. Previously, we demonstrated that stick tapping improves perception in a timing detection task, where percussionists greatly outperformed non-percussionists only when tapping along. Since most synchronization studies implement finger tapping to examine simple motor synchronization, here we completed a similar task where percussionists and non-percussionists synchronized using finger tapping; movement with fewer degrees of freedom than stick tapping. Percussionists and non-percussionists listened to an isochronous beat sequence and identified the timing of a probe tone. On half of the trials, they tapped along with their index finger, and on the other half of the trials, they listened without moving prior to making timing judgments. We found that both groups benefited from tapping overall. Interestingly, percussionists performed only marginally better than did non-percussionists when finger tapping and no different when listening alone, differing from past studies reporting highly superior timing abilities in percussionists. Additionally, we found that percussionist finger tapping was less variable and less asynchronous than was non-percussionist tapping. Moreover, in both groups finger tapping was more variable and more asynchronous than stick tapping in our previous study. This study demonstrates that the motor effector implemented in tapping studies affects not only synchronization abilities, but also subsequent prediction abilities. We discuss these findings in light of effector-specific training and degrees of freedom in motor timing, both of which impact timing abilities to different extents.

HIV-1 vaccine strategies utilizing viral vectors including antigen- displayed inoviral vectors.

PubMed

Hassapis, Kyriakos A; Kostrikis, Leondios G

2013-12-01

Antigen-presenting viral vectors have been extensively used as vehicles for the presentation of antigens to the immune system in numerous vaccine strategies. Particularly in HIV vaccine development efforts, two main viral vectors have been used as antigen carriers: (a) live attenuated vectors and (b) virus-like particles (VLPs); the former, although highly effective in animal studies, cannot be clinically tested in humans due to safety concerns and the latter have failed to induce broadly neutralizing anti-HIV antibodies. For more than two decades, Inoviruses (non-lytic bacterial phages) have also been utilized as antigen carriers in several vaccine studies. Inoviral vectors are important antigen-carriers in vaccine development due to their ability to present an antigen on their outer architecture in many copies and to their natural high immunogenicity. Numerous fundamental studies have been conducted, which have established the unique properties of antigen-displayed inoviral vectors in HIV vaccine efforts. The recent isolation of new, potent anti-HIV broadly neutralizing monoclonal antibodies provides a new momentum in this emerging technology.

PREDICTIVE MODELING OF ACOUSTIC SIGNALS FROM THERMOACOUSTIC POWER SENSORS (TAPS)

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

Dumm, Christopher M.; Vipperman, Jeffrey S.

2016-06-30

Thermoacoustic Power Sensor (TAPS) technology offers the potential for self-powered, wireless measurement of nuclear reactor core operating conditions. TAPS are based on thermoacoustic engines, which harness thermal energy from fission reactions to generate acoustic waves by virtue of gas motion through a porous stack of thermally nonconductive material. TAPS can be placed in the core, where they generate acoustic waves whose frequency and amplitude are proportional to the local temperature and radiation flux, respectively. TAPS acoustic signals are not measured directly at the TAPS; rather, they propagate wirelessly from an individual TAPS through the reactor, and ultimately to a low-powermore » receiver network on the vessel’s exterior. In order to rely on TAPS as primary instrumentation, reactor-specific models which account for geometric/acoustic complexities in the signal propagation environment must be used to predict the amplitude and frequency of TAPS signals at receiver locations. The reactor state may then be derived by comparing receiver signals to the reference levels established by predictive modeling. In this paper, we develop and experimentally benchmark a methodology for predictive modeling of the signals generated by a TAPS system, with the intent of subsequently extending these efforts to modeling of TAPS in a liquid sodium environmen« less

Finding the right fit: studying the biomechanics of under-tapping with varying thread depths and pitches.

PubMed

Jazini, Ehsan; Petraglia, Carmen; Moldavsky, Mark; Tannous, Oliver; Weir, Tristan; Saifi, Comron; Elkassabany, Omar; Cai, Yiwei; Bucklen, Brandon; O'Brien, Joseph; Ludwig, Steven C

2017-04-01

Compromise of pedicle screw purchase is a concern in maintaining rigid spinal fixation, especially with osteoporosis. Little consistency exists among various tapping techniques. Pedicle screws are often prepared with taps of a smaller diameter, which can further exacerbate inconsistency. The objective of this study was to determine whether a mismatch between tap thread depth (D) and thread pitch (P) and screw D and P affects fixation when under-tapping in osteoporotic bone. This study is a polyurethane foam block biomechanical analysis. A foam block osteoporotic bone model was used to compare pullout strength of pedicle screws with a 5.3 nominal diameter tap of varying D's and P's. Blocks were sorted into seven groups: (1) probe only; (2) 0.5-mm D, 1.5-mm P tap; (3) 0.5-mm D, 2.0-mm P tap; (4) 0.75-mm D, 2.0-mm P tap; (5) 0.75-mm D, 2.5-mm P tap; (6) 0.75-mm D, 3.0-mm P tap; and (7) 1.0-mm D, 2.5-mm P tap. A pedicle screw, 6.5 mm in diameter and 40 mm in length, was inserted to a depth of 40 mm. Axial pullout testing was performed at a rate of 5 mm/min on 10 blocks from each group. No significant difference was noted between groups under axial pullout testing. The mode of failure in the probe-only group was block fracture, occurring in 50% of cases. Among the other six groups, only one screw failed because of block fracture. The other 59 failed because of screw pullout. In an osteoporotic bone model, changing the D or P of the tap has no statistically significant effect on axial pullout. Osteoporotic bone might render tap features marginal. Our findings indicate that changing the characteristics of the tap D and P does not help with pullout strength in an osteoporotic model. The high rate of fracture in the probe-only group might imply the potential benefit of tapping to prevent catastrophic failure of bone. Copyright © 2016 Elsevier Inc. All rights reserved.

Polymer blend particles with defined compositions for targeting antigen to both class I and II antigen presentation pathways

PubMed Central

Tran, Kenny K.; Zhan, Xi; Shen, Hong

2013-01-01

Defense against many persistent and difficult-to-treat diseases requires a combination of humoral, CD4+ and CD8+ T cell responses, which necessitates targeting antigens to both class I and II antigen presentation pathways. In this study, we developed polymer blend particles by mixing two functionally unique polymers, poly(lactide-co-glycolide) (PLGA) and a pH-responsive polymer, poly(dimethylaminoethyl methacrylate-co-propylacrylic acid-co-butyl methacrylate) (DMAEMA-co-PAA-co-BMA). We showed polymer blend particles enabled the delivery of antigens into both class I and II antigen presentation pathways in vitro. Increasing the ratio of the pH-responsive polymer in blend particles increased the degree of class I antigen presentation, while maintaining high levels of class II antigen presentation. In a mouse model, we demonstrated that a significantly higher and sustained level of CD4+ and CD8+ T cell responses, and comparable antibody responses, were elicited with polymer blend particles than PLGA particles and a conventional vaccine, Alum. The polymer blend particles offer a potential vaccine delivery platform to generate a combination of humoral and cell-mediated immune responses that insure robust and long-lasting immunity against many infectious diseases and cancers. PMID:24124123

Control system for a wound-rotor motor

DOEpatents

Ellis, James N.

1983-01-01

A load switching circuit for switching two or more transformer taps under load carrying conditions includes first and second parallel connected bridge rectifier circuits which control the selective connection of a direct current load to taps of a transformer. The first bridge circuit is normally conducting so that the load is connected to a first tap through the first bridge circuit. To transfer the load to the second tap, a switch is operable to connect the second bridge circuit to a second tap, and when the second bridge circuit begins to conduct, the first bridge circuit ceases conduction because the potential at the second tap is higher than the potential at the first tap, and the load is thus connected to the second tap through the second bridge circuit. The load switching circuit is applicable in a motor speed controller for a wound-rotor motor for effecting tap switching as a function of motor speed while providing a stepless motor speed control characteristic.

Effects of age, task, and frequency on variability of finger tapping.

PubMed

Sommervoll, Yngve; Ettema, Gertjan; Vereijken, Beatrix

2011-10-01

The goal was to assess whether prior studies might have overestimated performance variability in older adults in dual task conditions by relying on primary motor tasks that are not constant with aging. 30 younger and 31 older adults performed a bimanual tapping task at four different frequencies in isolation or concurrently with a secondary task. Results showed that performance of younger and older adults was not significantly different in performing the tapping task at all frequencies and with either secondary task, as indicated by mean tapping performance and low number of errors in the secondary tasks. Both groups showed increased variability as tapping frequency increased and with the presence of a secondary task. Tapping concurrently while reading words increased tapping variability more than tapping concurrently while naming colours. Although older participants' performances were overall more variable, no interaction effects with age were found and at the highest frequencies of tapping, younger and older participants did not differ in performance.

Cancer Immunotherapy Utilized Bubble Liposomes and Ultrasound as Antigen Delivery System

NASA Astrophysics Data System (ADS)

Oda, Yusuke; Otake, Shota; Suzuki, Ryo; Otake, Shota; Nishiie, Norihito; Hirata, Keiichi; Taira, Yuichiro; Utoguchi, Naoki; Maruyama, Kazuo

2010-03-01

In dendritic cells (DCs)-based cancer immunotherapy, it is important to present the epitope peptide derived from tumor associated antigens (TAAs) on MHC class I in order to induce tumor specific cytotoxic T lymphocytes (CTLs). However, MHC class I molecules generally present the epitope peptides derived from endogenous antigens for DCs but not exogenous ones such as TAAs. Recently, we developed the novel liposomal bubbles (Bubble liposomes) encapsulating perfluoropropane nanobubbles. In this study, we attempted to establish the novel antigen delivery system to induce MHC class I presentation using the combination of ultrasound and Bubble liposomes. Using ovalbumin (OVA) as model antigen, the combination of Bubble liposomes and ultrasound exposure for the DC could induce MHC class I presentation. In addition, the viability of DCs was more than 80%. These results suggest that Bubble liposomes might be a novel ultrasound enhanced antigen delivery tool in DC-based cancer immunotherapy.

Killer artificial antigen-presenting cells: the synthetic embodiment of a ‘guided missile’

PubMed Central

Schütz, Christian; Oelke, Mathias; Schneck, Jonathan P; Mackensen, Andreas; Fleck, Martin

2010-01-01

At present, the treatment of T-cell-dependent autoimmune diseases relies exclusively on strategies leading to nonspecific suppression of the immune systems causing a substantial reduced ability to control concomitant infections or malignancies. Furthermore, long-term treatment with most drugs is accompanied by several serious adverse effects and does not consequently result in cure of the primary immunological malfunction. By contrast, antigen-specific immunotherapy offers the potential to achieve the highest therapeutic efficiency in accordance with minimal adverse effects. Therefore, several studies have been performed utilizing antigen-presenting cells specifically engineered to deplete allo- or antigen-specific T cells (‘guided missiles’). Many of these strategies take advantage of the Fas/Fas ligand signaling pathway to efficiently induce antigen-presenting cell-mediated apoptosis in targeted T cells. In this article, we discuss the advantages and shortcomings of a novel non-cell-based ‘killer artificial antigen-presenting cell’ strategy, developed to overcome obstacles related to current cell-based approaches for the treatment of T-cell-mediated autoimmunity. PMID:20636007

Pathogen-Sensing and Regulatory T Cells: Integrated Regulators of Immune Responses

PubMed Central

Grossman, Zvi; Paul, William E.

2014-01-01

We present the concept that pathogen-sensing and Tregs mutually regulate immune responses to conventional and tumor antigens through countervailing effects on dendritic cells. Normally, conventional CD4 T cells recognizing their cognate antigen-presented by a dendritic cell will respond only if the dendritic cell also receives a signal through its pathogen-sensing/ danger / adjuvant recognition systems (the pathogen-sensing triad). However, if Tregs capable of interacting with the same DC are absent, dendritic cells are competent to present antigens, both foreign and self, even without the stimulation provided by the pathogen-sensing triad. Tregs recognizing an antigen presented by the DC that is also presenting antigen to a conventional CD4 T cell will prevent such responses but a signal delivered by a member of the pathogen-sensing traid will overcome the Tregs’inhibitory action and will allow responses to go forward. These considerations take on special meaning for responses to “weak antigens” such as many of the antigens displayed by spontaneous human tumors. PMID:24894087

Modulation of Phosphorylation of Tocopherol and Phosphatidylinositol by hTAP1/SEC14L2-Mediated Lipid Exchange

PubMed Central

Zingg, Jean-Marc; Libinaki, Roksan; Meydani, Mohsen; Azzi, Angelo

2014-01-01

The vitamin E derivative, alpha-tocopheryl phosphate (αTP), is detectable in cultured cells, plasma and tissues in small amounts, suggesting the existence of enzyme(s) with α-tocopherol (αT) kinase activity. Here, we characterize the production of αTP from αT and [γ-32P]-ATP in primary human coronary artery smooth muscle cells (HCA-SMC) using separation by thin layer chromatography (TLC) and subsequent analysis by Ultra Performance Liquid Chromatography (UPLC). In addition to αT, although to a lower amount, also γT is phosphorylated. In THP-1 monocytes, γTP inhibits cell proliferation and reduces CD36 scavenger receptor expression more potently than αTP. Both αTP and γTP activate the promoter of the human vascular endothelial growth factor (VEGF) gene with similar potency, whereas αT and γT had no significant effect. The recombinant human tocopherol associated protein 1 (hTAP1, hSEC14L2) binds both αT and αTP and stimulates phosphorylation of αT possibly by facilitating its transport and presentation to a putative αT kinase. Recombinant hTAP1 reduces the in vitro activity of the phosphatidylinositol-3-kinase gamma (PI3Kγ) indicating the formation of a stalled/inactive hTAP1/PI3Kγ heterodimer. The addition of αT, βT, γT, δT or αTP differentially stimulates PI3Kγ, suggesting facilitated egress of sequestered PI from hTAP1 to the enzyme. It is suggested that the continuous competitive exchange of different lipophilic ligands in hTAPs with cell enzymes and membranes may be a way to make these lipophiles more accessible as substrates for enzymes and as components of specific membrane domains. PMID:24983950

Simultaneous determination and assessment of 4-nonylphenol, bisphenol A and triclosan in tap water, bottled water and baby bottles.

PubMed

Li, Xu; Ying, Guang-Guo; Su, Hao-Chang; Yang, Xiao-Bing; Wang, Li

2010-08-01

This study investigated the levels of 4-nonylphenol (4-NP), bisphenol A (BPA) and triclosan (TCS) in bottled water and tap water in Guangzhou and release of these chemicals from baby bottles using gas chromatography-mass spectrometry with negative chemical ionization. Results show that 4-NP was present in all the bottled water while 17 out of 21 contained BPA and 18 out of 21 contained TCS. Their concentrations in bottled water ranged from 108 to 298 ng/L, 17.6 to 324 ng/L and 0.6 to 9.7 ng/L, respectively. Five of the tap water samples from six drinking water plants were found to contain 4-NP and BPA both in June and December, while TCS was detected in the same five plants only in June. The highest concentrations in tap water for 4-NP, BPA and TCS were 1987, 317 and 14.5ng/L, respectively. Daily intakes of 4-NP, BPA and TCS of adults by drinking 2L of tap water were estimated to be 1410, 148 and 10 ng/day, respectively. BPA was found to be released within 24h from four brands of baby bottles at room temperature (24 degrees C), 40 degrees C and 100 degrees C. Increased temperature led to higher release of BPA from the baby bottles. Estimated daily intakes of 4-NP, BPA and TCS for infants were 705, 1340 and 5 ng/day, respectively, by drinking 1L of tap water from a baby bottle at 40 degrees C. This study showed that the exposure to the three compounds from drinking water is unlikely to pose a health risk. Copyright 2010 Elsevier Ltd. All rights reserved.

[Volatile organic compounds of the tap water in the Watarase, Tone and Edo River system].

PubMed

Ohmichi, Kimihide; Ohmichi, Masayoshi; Machida, Kazuhiko

2004-01-01

The chlorination of river water in purification plants is known to produce carcinogens such as trihalomethanes (THMs). We studied the river system of the Watarase, Tone, and Edo Rivers in regard to the formation of THMs. This river system starts from the base of the Ashio copper mine and ends at Tokyo Bay. Along the rivers, there are 14 local municipalities in Gunma, Saitama, Ibaragi and Chiba Prefectures, as well as Tokyo. This area is the center of the Kanto plain and includes the main sources of water pollution from human activities. We also analyzed various chemicals in river water and tap water to clarify the status of the water environment, and we outline the problems of the water environment in the research area (Fig. 1). Water samples were taken from 18 river sites and 42 water faucets at public facilities in 14 local municipalities. We analyzed samples for volatile organic compounds such as THMs, by gas chromatography mass spectrometry (GC-MS), and evaluations of chemical oxygen demand (COD) were made with reference to Japanese drinking water quality standards. Concentrations of THMs in the downstream tap water samples were higher than those in the samples from the upperstream. This tendency was similar to the COD of the river water samples, but no correlation between the concentration of THMs in tap water and the COD in tap water sources was found. In tap water of local government C, trichloroethylene was detected. The current findings suggest that the present water filtration plant procedures are not sufficient to remove some hazardous chemicals from the source water. Moreover, it was confirmed that the water filtration produced THMs. Also, trichloroethylene was detected from the water environment in the research area, suggesting that pollution of the water environment continues.

Template-Independent Enzymatic Oligonucleotide Synthesis (TiEOS): Its History, Prospects, and Challenges.

PubMed

Jensen, Michael A; Davis, Ronald W

2018-03-27

There is a growing demand for sustainable methods in research and development, where instead of hazardous chemicals, an aqueous medium is chosen to perform biological reactions. In this Perspective, we examine the history and current methodology of using enzymes to generate artificial single-stranded DNA. By using traditional solid-phase phosphoramidite chemistry as a metric, we also explore criteria for the method of template-independent enzymatic oligonucleotide synthesis (TiEOS). As its key component, we delve into the biology of one of the most enigmatic enzymes, terminal deoxynucleotidyl transferase (TdT). As TdT is found to exponentially increase antigen receptor diversity in the vertebrate immune system by adding nucleotides in a template-free manner, researchers have exploited this function as an alternative to the phosphoramidite synthesis method. Though TdT is currently the preferred enzyme for TiEOS, its random nucleotide incorporation presents a barrier in synthesis automation. Taking a closer look at the TiEOS cycle, particularly the coupling step, we find it is comprised of additions > n+1 and deletions. By tapping into the physical and biochemical properties of TdT, we strive to further elucidate its mercurial behavior and offer ways to better optimize TiEOS for production-grade oligonucleotide synthesis.

Cytotoxic T Lymphocyte Epitopes of HIV-1 Nef

PubMed Central

Lucchiari-Hartz, Maria; van Endert, Peter M.; Lauvau, Grégoire; Maier, Reinhard; Meyerhans, Andreas; Mann, Derek; Eichmann, Klaus; Niedermann, Gabriele

2000-01-01

Although a pivotal role of proteasomes in the proteolytic generation of epitopes for major histocompatibility complex (MHC) class I presentation is undisputed, their precise function is currently the subject of an active debate: do proteasomes generate many epitopes in definitive form, or do they merely generate the COOH termini, whereas the definitive NH2 termini are cleaved by aminopeptidases? We determined five naturally processed MHC class I ligands derived from HIV-1 Nef. Unexpectedly, the five ligands correspond to only three cytotoxic T lymphocyte (CTL) epitopes, two of which occur in two COOH-terminal length variants. Parallel analyses of proteasomal digests of a Nef fragment encompassing the epitopes revealed that all five ligands are direct products of proteasomes. Moreover, in four of the five ligands, the NH2 termini correspond to major proteasome cleavage sites, and putative NH2-terminally extended precursor fragments were detected for only one of the five ligands. All ligands are transported by the transporter associated with antigen processing (TAP). The combined results from these five ligands provide strong evidence that many definitive MHC class I ligands are precisely cleaved at both ends by proteasomes. Additional evidence supporting this conclusion is discussed, along with contrasting results of others who propose a strong role for NH2-terminal trimming with direct proteasomal epitope generation being a rare event. PMID:10637269

Disinfection potential of electrolyzed solutions containing sodium chloride at low concentrations.

PubMed

Morita, C; Sano, K; Morimatsu, S; Kiura, H; Goto, T; Kohno, T; Hong, W U; Miyoshi, H; Iwasawa, A; Nakamura, Y; Tagawa, M; Yokosuka, O; Saisho, H; Maeda, T; Katsuoka, Y

2000-03-01

Electrolyzed products of sodium chloride solution were examined for their disinfection potential against hepatitis B virus (HBV) and human immunodeficiency virus (HIV) in vitro. Electrolysis of 0.05% NaCl in tap water was carried out for 45 min at room temperature using a 3 A electric current in separate wells installed with positive and negative electrodes. The electrolyzed products were obtained from the positive well. The oxidation reduction potential (ORP), pH and free chlorine content of the product were 1053 mV, pH 2.34 and 4.20 ppm, respectively. The products modified the antigenicity of the surface protein of HBV as well as the infectivity of HIV in time- and concentration-dependent manner. Although the inactivating potential was decreased by the addition of contaminating protein, recycling of the product or continuous addition of fresh product may restore the complete disinfection against bloodborne pathogens.

Antibody-Antigen-Adjuvant Conjugates Enable Co-Delivery of Antigen and Adjuvant to Dendritic Cells in Cis but Only Have Partial Targeting Specificity

PubMed Central

Abuknesha, Ram; Uematsu, Satoshi; Akira, Shizuo; Nestle, Frank O.; Diebold, Sandra S.

2012-01-01

Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC) by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is paramount. However, co-administration of unlinked adjuvant cannot ensure that all cells targeted by the antibody conjugates are appropriately activated. Furthermore, antigen-presenting cells (APC) that do not present the desired antigen are equally strongly activated and could prime undesired responses against self-antigens. We, therefore, were interested in exploring targeted co-delivery of antigen and adjuvant in cis in form of antibody-antigen-adjuvant conjugates for the induction of anti-tumour immunity. In this study, we report on the assembly and characterization of conjugates consisting of DEC205-specific antibody, the model antigen ovalbumin (OVA) and CpG oligodeoxynucleotides (ODN). We show that such conjugates are more potent at inducing cytotoxic T lymphocyte (CTL) responses than control conjugates mixed with soluble CpG. However, our study also reveals that the nucleic acid moiety of such antibody-antigen-adjuvant conjugates alters their binding and uptake and allows delivery of the antigen and the adjuvant to cells partially independently of DEC205. Nevertheless, antibody-antigen-adjuvant conjugates are superior to antibody-free antigen-adjuvant conjugates in priming CTL responses and efficiently induce anti-tumour immunity in the murine B16 pseudo-metastasis model. A better understanding of the role of the antibody moiety is required to inform future conjugate vaccination strategies for efficient induction of anti-tumour responses. PMID:22808118

AntigenMap 3D: an online antigenic cartography resource.

PubMed

Barnett, J Lamar; Yang, Jialiang; Cai, Zhipeng; Zhang, Tong; Wan, Xiu-Feng

2012-05-01

Antigenic cartography is a useful technique to visualize and minimize errors in immunological data by projecting antigens to 2D or 3D cartography. However, a 2D cartography may not be sufficient to capture the antigenic relationship from high-dimensional immunological data. AntigenMap 3D presents an online, interactive, and robust 3D antigenic cartography construction and visualization resource. AntigenMap 3D can be applied to identify antigenic variants and vaccine strain candidates for pathogens with rapid antigenic variations, such as influenza A virus. http://sysbio.cvm.msstate.edu/AntigenMap3D

Inhibiting DNA methylation activates cancer testis antigens and expression of the antigen processing and presentation machinery in colon and ovarian cancer cells.

PubMed

Siebenkäs, Cornelia; Chiappinelli, Katherine B; Guzzetta, Angela A; Sharma, Anup; Jeschke, Jana; Vatapalli, Rajita; Baylin, Stephen B; Ahuja, Nita

2017-01-01

Innovative therapies for solid tumors are urgently needed. Recently, therapies that harness the host immune system to fight cancer cells have successfully treated a subset of patients with solid tumors. These responses have been strong and durable but observed in subsets of patients. Work from our group and others has shown that epigenetic therapy, specifically inhibiting the silencing DNA methylation mark, activates immune signaling in tumor cells and can sensitize to immune therapy in murine models. Here we show that colon and ovarian cancer cell lines exhibit lower expression of transcripts involved in antigen processing and presentation to immune cells compared to normal tissues. In addition, treatment with clinically relevant low doses of DNMT inhibitors (that remove DNA methylation) increases expression of both antigen processing and presentation and Cancer Testis Antigens in these cell lines. We confirm that treatment with DNMT inhibitors upregulates expression of the antigen processing and presentation molecules B2M, CALR, CD58, PSMB8, PSMB9 at the RNA and protein level in a wider range of colon and ovarian cancer cell lines and treatment time points than had been described previously. In addition, we show that DNMTi treatment upregulates many Cancer Testis Antigens common to both colon and ovarian cancer. This increase of both antigens and antigen presentation by epigenetic therapy may be one mechanism to sensitize patients to immune therapies.

Hypokinesia without decrement distinguishes progressive supranuclear palsy from Parkinson's disease

PubMed Central

Massey, Luke A.; Lees, Andrew J.; Brown, Peter; Day, Brian L.

2012-01-01

Repetitive finger tapping is commonly used to assess bradykinesia in Parkinson's disease. The Queen Square Brain Bank diagnostic criterion of Parkinson's disease defines bradykinesia as ‘slowness of initiation with progressive reduction in speed and amplitude of repetitive action’. Although progressive supranuclear palsy is considered an atypical parkinsonian syndrome, it is not known whether patients with progressive supranuclear palsy have criteria-defined bradykinesia. This study objectively assessed repetitive finger tap performance and handwriting in patients with Parkinson's disease (n = 15), progressive supranuclear palsy (n = 9) and healthy age- and gender-matched controls (n = 16). The motion of the hand and digits was recorded in 3D during 15-s repetitive index finger-to-thumb tapping trials. The main finding was hypokinesia without decrement in patients with progressive supranuclear palsy, which differed from the finger tap pattern in Parkinson's disease. Average finger separation amplitude in progressive supranuclear palsy was less than half of that in controls and Parkinson's disease (P < 0.001 in both cases). Change in tap amplitude over consecutive taps was computed by linear regression. The average amplitude slope in progressive supranuclear palsy was nearly zero (0.01°/cycle) indicating a lack of decrement, which differed from the negative slope in patients with Parkinson's disease OFF levodopa (−0.20°/cycle, P = 0.002). ‘Hypokinesia’, defined as <50% of control group's mean amplitude, combined with ‘absence of decrement’, defined as mean positive amplitude slope, were identified in 87% of finger tap trials in the progressive supranuclear palsy group and only 12% in the Parkinson's disease OFF levodopa group. In progressive supranuclear palsy, the mean amplitude was not correlated with disease duration or other clinimetric scores. In Parkinson's disease, finger tap pattern was compatible with criteria-defined bradykinesia, characterized by slowness with progressive reduction in amplitude and speed and increased variability in speed throughout the tap trial. In Parkinson's disease, smaller amplitude, slower speed and greater speed variability were all associated with a more severe Unified Parkinson's Disease Rating Scale motor score. Analyses of handwriting showed that micrographia, defined as smaller than 50% of the control group's mean script size, was present in 75% of patients with progressive supranuclear palsy and 15% of patients with Parkinson's disease (P = 0.022). Most scripts performed by patients with progressive supranuclear palsy did not exhibit decrements in script size. In conclusion, patients with progressive supranuclear palsy have a specific finger tap pattern of ‘hypokinesia without decrement’ and they do not have criteria-defined limb bradykinesia. Similarly, ‘micrographia’ and ‘lack of decrement in script size’ are also more common in progressive supranuclear palsy than in Parkinson's disease. PMID:22396397

[Post-operative pain after ultrasound transversus abdominis plane block versus trocar site infiltration in laparoscopic nephrectomy: a prospective study].

PubMed

Araújo, Ana M; Guimarães, Joana; Nunes, Catarina S; Couto, Paula S; Amadeu, Eduarda

Transversus abdominis plane (TAP) block is useful in reducing post-operative pain in laparoscopic nephrectomy compared to placebo. The purpose of this work is to compare post-operative pain and recovery after TAP block or trocar site infiltration (TSI) in this surgery. A prospective, single blinded study on patients scheduled for laparoscopic nephrectomy. Patients were assigned to two groups: TSI Group: trocar site infiltration at the end of surgery; TAP Group: unilateral ultrasound-guided TAP block after induction. Sevoflurane and remifentanil, in a target controlled infusion mode, were used for maintenance of general anesthesia. Before the end of surgery paracetamol, tramadol and morphine were administered. Visual analogue scale (VAS 0-100mm) at rest and with cough was applied in three moments: in recovery room (T1 at admission and T2 before discharge) and 24h after surgery (T3). Pain scores with incentive spirometer were also evaluated at T3. In recovery, morphine was administered as a rescue drug whenever VAS>30mm. Time to oral intake, chair sitting, ambulation and length of hospital stay were evaluated 24h after surgery. Student's t-test and Chi-square test, and linear regression models. A p-value<0.05 was considered significant. Data are presented as mean (SD). Forty patients were enrolled in the study. The primary outcome variable, VAS pain scores did not show a statistical significant difference between groups (p>0.05). VAS at rest (TAP vs. TSI groups) was: T1=33±29 vs. 39±32, T2=10±9 vs. 17±18 and T3=7±12 vs. 10±18. VAS with cough (TAP vs. TSI groups) was: T1=51±34 vs. 45±32, T2=24±24 vs. 33±23 and T3=20±23 vs. 23±23. VAS with incentive spirometer (TAP vs. TSI groups) was: T3=21±27 vs. 21±25. Intraoperative remifentanil consumption was similar between TAP (0.16±0.07mcg.kg -1 .min -1 ) and TSI (0.18±0.9mcg.kg -1 .min -1 ) groups. There were no differences in opioid consumption between TAP (4.4±3.49mg) and TSI (6.87±4.83mg) groups during recovery. Functional recovery parameters were not statistically different between groups. Multimodal analgesia with TAP block did not show a significant clinical benefit compared with trocar site infiltration in laparoscopic nephrectomies. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Synthesis, characterization, and nonlinear optical properties of graphene oxide functionalized with tetra-amino porphyrin

NASA Astrophysics Data System (ADS)

Yamuna, R.; Ramakrishnan, S.; Dhara, Keerthy; Devi, R.; Kothurkar, Nikhil K.; Kirubha, E.; Palanisamy, P. K.

2013-01-01

The synthesis of a porphyrin-graphene oxide hybrid (GO-TAP) was carried out by covalently functionalizing graphene oxide (GO) with 5,10,15,20 mesotetra (4-aminophenyl) porphyrin (TAP) through an amide linkage. The GO-TAP hybrid has been characterized by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and UV-visible spectroscopy. The peak intensity of the Soret band of the material was suppressed compared to neat TAP. This indicates a strong interaction between the electronic energy level of TAP and GO in the GO-TAP hybrid. The functionalization of GO with TAP significantly improved its solubility and dispersion stability in organic solvents. Scanning electron micrographs reveal that the hybrid was found to be similar to the unmodified GO but slightly more wrinkled. Transmission electron micrographs also demonstrate that GO sheet in the hybrid is more wrinkled with some dark spot due to functionalization. Atomic force microscopy results also reveal that the TAP functionalization increases the thickness of GO sheet to 2.0-3.0 nm from 1.2 to 1.8 nm. We observed improved nonlinear optical and optical limiting properties for the hybrid compared to both graphene oxide and porphyrin. GO-TAP shows fluorescence quenching compared with porphyrin, indicating excellent electron and/or energy transfer to GO from TAP. Thermogravimetric analysis confirms that the GO-TAP hybrid has outstanding thermal stability.

Conventional CD4+ T cells present bacterial antigens to induce cytotoxic and memory CD8+ T cell responses.

PubMed

Cruz-Adalia, Aránzazu; Ramirez-Santiago, Guillermo; Osuna-Pérez, Jesús; Torres-Torresano, Mónica; Zorita, Virgina; Martínez-Riaño, Ana; Boccasavia, Viola; Borroto, Aldo; Martínez Del Hoyo, Gloria; González-Granado, José María; Alarcón, Balbino; Sánchez-Madrid, Francisco; Veiga, Esteban

2017-11-17

Bacterial phagocytosis and antigen cross-presentation to activate CD8 + T cells are principal functions of professional antigen presenting cells. However, conventional CD4 + T cells also capture and kill bacteria from infected dendritic cells in a process termed transphagocytosis (also known as transinfection). Here, we show that transphagocytic T cells present bacterial antigens to naive CD8 + T cells, which proliferate and become cytotoxic in response. CD4 + T-cell-mediated antigen presentation also occurs in vivo in the course of infection, and induces the generation of central memory CD8 + T cells with low PD-1 expression. Moreover, transphagocytic CD4 + T cells induce protective anti-tumour immune responses by priming CD8 + T cells, highlighting the potential of CD4 + T cells as a tool for cancer immunotherapy.

The processing and presentation of lipids and glycolipids to the immune system

PubMed Central

Vartabedian, Vincent F.; Savage, Paul B.; Teyton, Luc

2016-01-01

Summary The recognition of CD1-lipid complexes by T cells was discovered twenty years ago and has since been an emerging and expanding field of investigation. Unlike protein antigens, which are presented on MHC class I and II molecules, lipids can only be presented by CD1 molecules, a unique family of MHC-like proteins whose singularity is a hydrophobic antigen binding groove. The processing and loading of lipid antigens inside this groove of CD1 molecules require localization to late endosomal and lysosomal subcellular compartments and their acidic pHs. This particular environment provides the necessary glycolytic enzymes and lipases that process lipid and glycolipid antigens, as well as a set of lipid transfer proteins that load the final version of the antigen inside the groove of CD1. The overall sequence of events needed for efficient presentation of lipid antigens is now understood and presented in this review. However, a large number of important details have been elusive. This elusiveness is linked to the inherent technical difficulties of studying lipids and the lipid-protein interface in vitro and in vivo. Here, we will expose some of those limitations and describe new approaches to address them during the characterization of lipids and glycolipids antigen presentation. PMID:27319346

Presentation of antigen to T lymphocytes by non-immune B-cell hybridoma clones: evidence for specific and non-specific presentation

NASA Technical Reports Server (NTRS)

Cohly, H. H.; Morrison, D. R.; Atassi, M. Z.

1988-01-01

Non-immune SJL (H-2s) spleen cells were fused with (H-2d) Balb/c 653-myeloma cells and the hybridomas were cloned by two limiting dilutions. The resulting hybrid B- cell clones were tested for their antigen presentation capability to SJL T-cell lines that were specific for either lysozyme or myoglobin. In proliferative assays, 53% of the antigen presenting B-cell clones were able to present both myoglobin and lysozyme (general presenters) while the other 47% presented specifically either myoglobin or lysozyme (specific presenters). The ability to selectively present either myoglobin or lysozyme indicates that antigen presentation at the clonal level can be specific or non-specific depending on the particular B-cell clone.

Motor Synchronization in Patients With Schizophrenia: Preserved Time Representation With Abnormalities in Predictive Timing.

PubMed

Wilquin, Hélène; Delevoye-Turrell, Yvonne; Dione, Mariama; Giersch, Anne

2018-01-01

Objective: Basic temporal dysfunctions have been described in patients with schizophrenia, which may impact their ability to connect and synchronize with the outer world. The present study was conducted with the aim to distinguish between interval timing and synchronization difficulties and more generally the spatial-temporal organization disturbances for voluntary actions. A new sensorimotor synchronization task was developed to test these abilities. Method: Twenty-four chronic schizophrenia patients matched with 27 controls performed a spatial-tapping task in which finger taps were to be produced in synchrony with a regular metronome to six visual targets presented around a virtual circle on a tactile screen. Isochronous (time intervals of 500 ms) and non-isochronous auditory sequences (alternated time intervals of 300/600 ms) were presented. The capacity to produce time intervals accurately versus the ability to synchronize own actions (tap) with external events (tone) were measured. Results: Patients with schizophrenia were able to produce the tapping patterns of both isochronous and non-isochronous auditory sequences as accurately as controls producing inter-response intervals close to the expected interval of 500 and 900 ms, respectively. However, the synchronization performances revealed significantly more positive asynchrony means (but similar variances) in the patient group than in the control group for both types of auditory sequences. Conclusion: The patterns of results suggest that patients with schizophrenia are able to perceive and produce both simple and complex sequences of time intervals but are impaired in the ability to synchronize their actions with external events. These findings suggest a specific deficit in predictive timing, which may be at the core of early symptoms previously described in schizophrenia.

End-threaded intramedullary positive profile screw ended self-tapping pin (Admit pin) - A cost-effective novel implant for fixing canine long bone fractures.

PubMed

Chanana, Mitin; Kumar, Adarsh; Tyagi, Som Prakash; Singla, Amit Kumar; Sharma, Arvind; Farooq, Uiase Bin

2018-02-01

The current study was undertaken to evaluate the clinical efficacy of end-threaded intramedullary pinning for management of various long bone fractures in canines. This study was conducted in two phases, managing 25 client-owned dogs presented with different fractures. The technique of application of end-threaded intramedullary pinning in long bone fractures was initially standardized in 6 clinical patients presented with long bone fractures. In this phase, end-threaded pins of different profiles, i.e., positive and negative, were used as the internal fixation technique. On the basis of results obtained from standardization phase, 19 client-owned dogs clinically presented with different fractures were implanted with end-threaded intramedullary positive profile screw ended self-tapping pin in the clinical application phase. The patients, allocated randomly in two groups, when evaluated postoperatively revealed slight pin migration in Group-I (negative profile), which resulted in disruption of callus site causing delayed union in one case and large callus formation in other two cases whereas no pin migration was observed in Group-II (positive profile). Other observations in Group-I was reduced muscle girth and delayed healing time as compared to Group-II. In clinical application, phase 21 st and 42 nd day post-operative radiographic follow-up revealed no pin migration in any of the cases, and there was no bone shortening or fragment collapse in end-threaded intramedullary positive profile screw ended self-tapping pin. The end-threaded intramedullary positive profile screw ended self-tapping pin used for fixation of long bone fractures in canines can resist pin migration, pin breakage, and all loads acting on the bone, i.e., compression, tension, bending, rotation, and shearing to an extent with no post-operative complications.

Spatial separation of the processing and MHC class I loading compartments for cross-presentation of the tumor-associated antigen HER2/neu by human dendritic cells

PubMed Central

Baleeiro, Renato B; Rietscher, René; Diedrich, Andrea; Czaplewska, Justyna A; Lehr, Claus-Michael; Scherließ, Regina; Hanefeld, Andrea; Gottschaldt, Michael; Walden, Peter

2015-01-01

Cross-presentation is the process by which professional antigen presenting cells (APCs) (B cells, dendritic cells (DCs) and macrophages) present endocytosed antigens (Ags) via MHC-I to CD8+ T cells. This process is crucial for induction of adaptive immune responses against tumors and infected cells. The pathways and cellular compartments involved in cross-presentation are unresolved and controversial. Among the cells with cross-presenting capacity, DCs are the most efficient, which was proposed to depend on prevention of endosomal acidification to block degradation of the epitopes. Contrary to this view, we show in this report that some cargoes induce strong endosomal acidification following uptake by human DCs, while others not. Moreover, processing of the tumor-associated antigen HER2/neu delivered in nanoparticles (NP) for cross-presentation of the epitope HER2/neu369–377 on HLA-A2 depended on endosomal acidification and cathepsin activity as well as proteasomes, and newly synthesized HLA class I. However, the HLA-A*0201/HER2/neu369–377 complexes were not found in the endoplasmic reticulum (ER) nor in endolysosomes but in hitherto not described vesicles. The data thus indicate spatial separation of antigen processing and loading of MHC-I for cross-presentation: antigen processing occurs in the uptake compartment and the cytosol whereas MHC-I loading with peptide takes place in a distinct subcellular compartment. The findings further elucidate the cellular pathways involved in the cross-presentation of a full-length, clinically relevant tumor-associated antigen by human DCs, and the impact of the vaccine formulation on antigen processing and CD8+ T cell induction. PMID:26985398

Microbiological tap water profile of a medium-sized building and effect of water stagnation.

PubMed

Lipphaus, Patrick; Hammes, Frederik; Kötzsch, Stefan; Green, James; Gillespie, Simon; Nocker, Andreas

2014-01-01

Whereas microbiological quality of drinking water in water distribution systems is routinely monitored for reasons of legal compliance, microbial numbers in tap water are grossly understudied. Motivated by gross differences in water from private households, we applied in this study flow cytometry as a rapid analytical method to quantify microbial concentrations in water sampled at diverse taps in a medium size research building receiving chlorinated water. Taps differed considerably in frequency of usage and were located in laboratories, bathrooms, and a coffee kitchen. Substantial differences were observed between taps with concentrations (per mL) in the range from 6.29 x 10(3) to 7.74 x 10(5) for total cells and from 1.66 x 10(3) to 4.31 x 10(5) for intact cells. The percentage of intact cells varied between 7% and 96%. Water from taps with very infrequent use showed the highest bacterial numbers and the highest proportions of intact cells. Stagnation tended to increase microbial numbers in water from those taps which were otherwise frequently used. Microbial numbers in other taps that were rarely opened were not affected by stagnation as their water is probably mostly stagnant. For cold water taps, microbial numbers and the percentage of intact cells tended to decline with flushing with the greatest decline for taps used least frequently whereas microbial concentrations in water from hot water taps tended to be somewhat more stable. We conclude that microbiological water quality is mainly determined by building-specific parameters. Tap water profiling can provide valuable insight into plumbing system hygiene and maintenance.

Epstein–Barr virus nuclear antigen 3C interact with p73: Interplay between a viral oncoprotein and cellular tumor suppressor

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

Sahu, Sushil Kumar; Mohanty, Suchitra; Kumar, Amit

The p73 protein has structural and functional homology with the tumor suppressor p53, which plays an important role in cell cycle regulation, apoptosis, and DNA repair. The p73 locus encodes both a tumor suppressor (TAp73) and a putative oncogene (ΔNp73). p73 May play a significant role in p53-deficient lymphomas infected with Epstein–Barr virus (EBV). EBV produces an asymptomatic infection in the majority of the global population, but it is associated with several human B-cell malignancies. The EBV-encoded Epstein–Barr virus nuclear antigen 3C (EBNA3C) is thought to disrupt the cell cycle checkpoint by interacting directly with p53 family proteins. Doxorubicin, amore » commonly used chemotherapeutic agent, induces apoptosis through p53 and p73 signaling such that the lowΔNp73 level promotes the p73-mediated intrinsic pathway of apoptosis. In this report, we investigated the mechanism by which EBV infection counters p73α-induced apoptosis through EBNA3C. - Highlights: • EBV-encoded EBNA3C suppresses doxorubicin-induced apoptosis in B-cell lymphomas. • EBNA3C binds to p73 to suppress its apoptotic effect. • EBNA3C maintains latency by regulating downstream mitochondrial pathways.« less

A cell-based MHC stabilization assay for the detection of peptide binding to the canine classical class I molecule, DLA-88.

PubMed

Ross, Peter; Holmes, Jennifer C; Gojanovich, Gregory S; Hess, Paul R

2012-12-15

Identifying immunodominant CTL epitopes is essential for studying CD8+ T-cell responses in populations, but remains difficult, as peptides within antigens typically are too numerous for all to be synthesized and screened. Instead, to facilitate discovery, in silico scanning of proteins for sequences that match the motif, or binding preferences, of the restricting MHC class I allele - the largest determinant of immunodominance - can be used to predict likely candidates. The high false positive rate with this analysis ideally requires binding confirmation, which is obtained routinely by an assay using cell lines such as RMA-S that have defective transporter associated with antigen processing (TAP) machinery, and consequently, few surface class I molecules. The stabilization and resultant increased life-span of peptide-MHC complexes on the cell surface by the addition of true binders validates their identity. To determine whether a similar assay could be developed for dogs, we transfected a prevalent class I allele, DLA-88*50801, into RMA-S. In the BARC3 clone, the recombinant heavy chain was associated with murine β2-microglobulin, and importantly, could differentiate motif-matched and -mismatched peptides by surface MHC stabilization. This work demonstrates the potential to use RMA-S cells transfected with canine alleles as a tool for CTL epitope discovery in this species. Copyright © 2012 Elsevier B.V. All rights reserved.

Towards Preserving the Immunogenicity of Protein Antigens Carried by Nanoparticles While Avoiding the Cold Chain

PubMed Central

Sloat, Brian R.; Sandoval, Michael A.; Cui, Zhengrong

2010-01-01

Nanoparticles are an attractive vaccine carrier with potent adjuvant activity. Data from our previous studies showed that immunization of mice with lecithin/glyceryl monostearate-based nanoparticles with protein antigens conjugated onto their surface induced a strong, quick, and long-lasting antigen-specific immune response. In the present study, we evaluated the feasibility of preserving the immunogenicity of protein antigens carried by nanoparticles without refrigeration using these antigen-conjugated nanoparticles as a model. The nanoparticles were lyophilized, and the immunogenicity of the antigens was evaluated in a mouse model using bovine serum albumin or the Bacillus anthracis protective antigen protein as model antigens. With proper excipients, the nanoparticles can be lyophilized while maintaining the immunogenicity of the antigens. Moreover, the immunogenicity of the model antigen conjugated onto the nanoparticles was undamaged after a relatively extended period of storage at room temperature or under accelerated conditions (37°C) when the nanoparticles were lyophilized with 5% mannitol plus 1% polyvinylpyrrolidone. To our knowledge, the present study represents an early attempt to preserve the immunogenicity of the protein antigens carried by nanoparticles without refrigeration. PMID:20416366

Antibody to the rheumatoid arthritis nuclear antigen. Its relationship to in vivo Epstein-Barr virus infection.

PubMed

Catalano, M A; Carson, D A; Niederman, J C; Feorino, P; Vaughan, J H

1980-05-01

Most patients with seropositive rheumatoid arthritis, and a variable but lesser percentage of normal subjects, have precipitating antibodies to a nuclear antigen, rheumatoid arthritis nuclear antigen, present in Epstein-Barr virus-infected human B lymphoblastoid cells. We have used a sensitive indirect immunofluorescence assay for antibody to rheumatoid arthritis nuclear antigen in a study of patients with infectious mononucleosis and healthy control subjects. Of 110 sera from normal, college-age cadets, 58 were from individuals without prior Epstein-Barr virus infection, as indicated by the lack of antibody to viral capsid antigen. All of these also lacked activity to rheumatoid arthritis nuclear antigen. 52 sera were positive for antibody to viral capsid antigen, and antibody to rheumatoid arthritis nuclear antigen was present in 26 (50%) of these. In 67 sequential sera from 11 college-age students with infectious mononucleosis who became positive for antibody to rheumatoid arthritis nuclear antigen, only 2 were positive during the 1 mo. Thereafter the incidence and titers increased progressively through the 1st yr after infection. This time-course resembled that for the development of antibody to Epstein-Barr nuclear antigen, another transformation antigen in Epstein-Barr virus-infected B lymphocytes. The development of positivity for both was much later than that of antibody to the structural viral capsid antigen, which in the current study was always positive by 1 wk. Thus, antibody to rheumatoid arthritis nuclear antigen is present in a large proportion of normal individuals and can now be clearly ascribed, from both in vivo and in vitro studies, to prior infection with Epstein-Barr virus.

Inhibitory effects of thymus-independent type 2 antigens on MHC class II-restricted antigen presentation: comparative analysis of carbohydrate structures and the antigen presenting cell.

PubMed

González-Fernández, M; Carrasco-Marín, E; Alvarez-Domínguez, C; Outschoorn, I M; Leyva-Cobián, F

1997-02-25

The role of thymus-independent type 2 (TI-2) antigens (polysaccharides) on the MHC-II-restricted processing of protein antigens was studied in vitro. In general, antigen presentation is inhibited when both peritoneal and splenic macrophages (M phi) as well as Küpffer cells (KC) are preincubated with acidic polysaccharides or branched dextrans. However, the inhibitory effect of neutral polysaccharides was minimal when KC were used as antigen presenting cells (APC). Morphological evaluation of the uptake of fluoresceinated polysaccharides clearly correlates with this selective and differential interference. Polysaccharides do not block MHC-I-restricted antigen presentation. Some chemical characteristics shared by different saccharides seem to be specially related to their potential inhibitory abilities: (i) those where two anomeric carbon atoms of two interlinked sugars and (ii) those containing several sulfate groups per disaccharide repeating unit. No polysaccharide being inhibitory in M phi abrogated antigen processing in other APC: lipopolysaccharide-activated B cells, B lymphoma cells, or dendritic cells (DC). Using radiolabeled polysaccharides it was observed that DC and B cells incorporated less radioactivity as a function of time than M phi. Morphological evaluation of these different APC incubated for extended periods of time with inhibitory concentrations of polysaccharides revealed intense cytoplasmic vacuolization in M phi but not in B cells or DC. The large majority of M phi lysosomes containing polysaccharides fail to fuse with incoming endocytic vesicles and delivery of fluid-phase tracers was reduced, suggesting that indigestible carbohydrates reduced the fusion of these loaded lysosomes with endosomes containing recently internalized tracers. It is suggested that the main causes of this antigen presentation blockade are (i) the chemical characteristics of certain carbohydrates and whether the specific enzymatic machinery for their intracellular degradation exists; and (ii) the different phagocytic abilities of distinct APC populations, fluid-phase pinocytosis and receptor-mediated saccharide uptake, and existence of a differential antigen-processing pathway in M phi and DC or B cells, which could be based on a polysaccharide-inhibited step present in M phi but unaffected or irrelevant in both B cells and DC.

A Novel Method Linking Antigen Presentation by Human Monocyte-Derived Macrophages to CD8+ T Cell Polyfunctionality

PubMed Central

Short, Kirsty R.; Grant, Emma J.; Vissers, Marloes; Reading, Patrick C.; Diavatopoulos, Dimitri A.; Kedzierska, Katherine

2013-01-01

To understand the interactions between innate and adaptive immunity, and specifically how virally infected macrophages impact T cell function, novel assays examining the ability of macrophages to present antigen to CD8+ T cells are needed. In the present study, we have developed a robust in vitro assay to measure how antigen presentation by human monocyte-derived macrophages (MDMs) affects the functional capacity of autologous CD8+ T cells. The assay is based on the polyfunctional characteristics of antigen-specific CD8+ T cells, and is thus called a Mac-CD8 Polyfunctionality Assay. Following purification of monocytes and their maturation to MDMs, MDMs were pulsed with an antigenic peptide to be presented to CD8+ T cells. Peptide-pulsed MDMs were then incubated with antigen-specific CD8+ T cells in order to assess the efficacy of antigen presentation to T cells. CD8+ T cell polyfunctionality was assessed by staining with mAbs to IFN-γ, TNF-α, and CD107a in a multi-color intracellular cytokine staining assay. To highlight the utility of the Mac-CD8 Polyfunctionality Assay, we assessed the effects of influenza infection on the ability of human macrophages to present antigen to CD8+ T cells. We found that influenza infection of human MDMs can alter the effector efficacy of MDMs to activate more CD8+ T cells with cytotoxic capacity. This has important implications for understanding how the virus-infected macrophages affect adaptive immunity at the site of infection. PMID:24312096

TAP polymorphism in patients with Behçet's disease.

PubMed Central

González-Escribano, M F; Morales, J; García-Lozano, J R; Castillo, M J; Sánchez-Román, J; Núñez-Roldán, A; Sánchez, B

1995-01-01

OBJECTIVE--To determine if susceptibility to Behçet's disease (BD) is associated with polymorphism of HLA-DRB1, HLA-DQB1, DQB1, and TAP1 and TAP2 genes. METHODS--Fifty eight Spanish BD patients and 116 ethnically matched unrelated healthy subjects were typed at the HLA-DRB1 and HLA-DQB1 loci using polymerase chain reaction/sequence specific oligotyping (PCR/SSO). TAP1 and TAP2 alleles were assigned using amplification refractory mutation system-PCR. RESULTS--TAP1C was absent in BD patients, but was found in 12.1% of control subjects (pcorr < 0.05; relative risk = 0.06). Additionally, a linkage disequilibrium between HLA-DQB1*0501 and TAP2B was observed in BD patients (delta = 0.095, pcorr < 0.02), but not in the control group (delta = -0.0031, p > 0.05). CONCLUSIONS--The complete absence of TAP1C alleles in BD patients may indicate that TAP1 polymorphism is not without some significance in the development of BD. Furthermore, the existence of a linkage disequilibrium between HLA-DQB1*0501 and TAP2B in our patients suggests that the gene conferring susceptibility for BD is inherited as an extended haplotype in the population studied. PMID:7794046

On-line tool breakage monitoring of vibration tapping using spindle motor current

NASA Astrophysics Data System (ADS)

Li, Guangjun; Lu, Huimin; Liu, Gang

2008-10-01

Input current of driving motor has been employed successfully as monitoring the cutting state in manufacturing processes for more than a decade. In vibration tapping, however, the method of on-line monitoring motor electric current has not been reported. In this paper, a tap failure prediction method is proposed to monitor the vibration tapping process using the electrical current signal of the spindle motor. The process of vibration tapping is firstly described. Then the relationship between the torque of vibration tapping and the electric current of motor is investigated by theoretic deducing and experimental measurement. According to those results, a monitoring method of tool's breakage is proposed through monitoring the ratio of the current amplitudes during adjacent vibration tapping periods. Finally, a low frequency vibration tapping system with motor current monitoring is built up using a servo motor B-106B and its driver CR06. The proposed method has been demonstrated with experiment data of vibration tapping in titanic alloys. The result of experiments shows that the method, which can avoid the tool breakage and giving a few error alarms when the threshold of amplitude ratio is 1.2 and there is at least 2 times overrun among 50 adjacent periods, is feasible for tool breakage monitoring in the process of vibration tapping small thread holes.

A statistical characterization of the finger tapping test: modeling, estimation, and applications.

PubMed

Austin, Daniel; McNames, James; Klein, Krystal; Jimison, Holly; Pavel, Misha

2015-03-01

Sensory-motor performance is indicative of both cognitive and physical function. The Halstead-Reitan finger tapping test is a measure of sensory-motor speed commonly used to assess function as part of a neuropsychological evaluation. Despite the widespread use of this test, the underlying motor and cognitive processes driving tapping behavior during the test are not well characterized or understood. This lack of understanding may make clinical inferences from test results about health or disease state less accurate because important aspects of the task such as variability or fatigue are unmeasured. To overcome these limitations, we enhanced the tapper with a sensor that enables us to more fully characterize all the aspects of tapping. This modification enabled us to decompose the tapping performance into six component phases and represent each phase with a set of parameters having clear functional interpretation. This results in a set of 29 total parameters for each trial, including change in tapping over time, and trial-to-trial and tap-to-tap variability. These parameters can be used to more precisely link different aspects of cognition or motor function to tapping behavior. We demonstrate the benefits of this new instrument with a simple hypothesis-driven trial comparing single and dual-task tapping.

Comparison of bone-conducted vibration for eliciting ocular vestibular-evoked myogenic potentials: forehead versus mastoid tapping.

PubMed

Tseng, Chia-Chen; Wang, Shou-Jen; Young, Yi-Ho

2012-02-01

This study compared bone-conducted vibration (BCV) stimuli at forehead (Fz) and mastoid sites for eliciting ocular vestibular-evoked myogenic potentials (oVEMPs). Prospective study. University hospital. Twenty healthy subjects underwent oVEMP testing via BCV stimuli at Fz and mastoid sites. Another 50 patients with unilateral Meniere's disease also underwent oVEMP testing. All healthy subjects showed clear oVEMPs via BCV stimulation regardless of the tapping sites. The right oVEMPs stimulated by tapping at the right mastoid had earlier nI and pI latencies and a larger nI-pI amplitude compared with those stimulated by tapping at the Fz and left mastoid. Similar trends were also observed in left oVEMPs. However, the asymmetry ratio did not differ significantly between the ipsilateral mastoid and Fz sites. Clinically, tapping at the Fz revealed absent oVEMPs in 28% of Meniere's ears, which decreased to 16% when tapping at the ipsilesional (hydropic) mastoid site, exhibiting a significant difference. Tapping at the ipsilateral mastoid site elicits earlier oVEMP latencies and larger oVEMP amplitudes when compared with tapping at the Fz site. Thus, tapping at the Fz site is suggested to screen for the otolithic function, whereas tapping at the ipsilesional mastoid site is suitable for evaluating residual otolithic function.

Perfluoroalkyl acids (PFAAs) in the Pra and Kakum River basins and associated tap water in Ghana.

PubMed

Essumang, David K; Eshun, Albert; Hogarh, Jonathan N; Bentum, John K; Adjei, Joseph K; Negishi, Junya; Nakamichi, Shihori; Habibullah-Al-Mamun, Md; Masunaga, Shigeki

2017-02-01

Perfluoroalkyl acids (PFAAs) are persistent environmental pollutants that have been detected in various media including human serum. Due to concerns regarding their bioaccumulation and possible negative health effects, an understanding of routes of human exposure is necessary. PFAAs are recalcitrant in many water treatment processes, making drinking water a potential source of human exposure. This study presents the first report on contamination from PFAAs in river and drinking water in Ghana. The targeted PFAAs were perfluoroalkyl carboxylic acids (PFCAs) with C 4-14 carbon chain and perfluoroalkane sulphonic acids (PFSAs) with C 6, 8, 10 . Five PFAA congeners - PFOA, PFOS, PFHxA, PFDA and PFPeA - were commonly detected in river and tap water. The mean concentrations of ∑PFAAs in the Kakum and Pra Rivers were 281 and 398ng/L, while tap water (supplied from the treatment of water from those rivers) contained concentrations of 197 and 200ng/L, respectively. PFOA and PFOS constituted about 99% of the ∑PFAAs. The risk quotient (RQ) attributed to drinking of tap water was estimated at 1.01 and 1.74 for PFOA and PFOS, respectively. For a country that has not produced these compounds, the RQs were unexpectedly high, raising concerns particularly about contamination from such emerging pollutants in local water sources. The study revealed limitations of local tap water treatment in getting rid of these emerging pollutants. Copyright © 2016 Elsevier B.V. All rights reserved.

Likability’s Effect on Interpersonal Motor Coordination: Exploring Natural Gaze Direction

PubMed Central

Zhao, Zhong; Salesse, Robin N.; Marin, Ludovic; Gueugnon, Mathieu; Bardy, Benoît G.

2017-01-01

Although existing studies indicate a positive effect of interpersonal motor coordination (IMC) on likability, no consensus has been reached as for the effect of likability back onto IMC. The present study specifically investigated the causal effect of likability on IMC and explored, by tracking the natural gaze direction, the possible underlying mechanisms. Twenty-two participants were engaged in an interpersonal finger-tapping task with a confederate in three likability conditions (baseline, likable, and unlikable), while wearing an eye tracker. They had to perform finger tapping at their comfort tempo with the confederate who tapped at the same or 1.5 times of the participant’s preferred frequency. Results showed that when tapping at the same frequency, the effect of likability on IMC varied with time. Participants coordinated at a higher level in the baseline condition at the beginning of the coordination task, and a facilitative effect of likability on IMC was revealed in the last session. As a novelty, our results evidenced a positive correlation between IMC and the amount of gaze onto the coordination partner’s movement only in the likable condition. No effect of likability was found when the confederate was tapping at 1.5 times of the participant’s preferred frequency. Our research suggests that the psychosocial property of the coordinating partner should be taken into consideration when investigating the performance of IMC and that IMC is a parameter that is sensitive to multiple factors. PMID:29123495

Quantitative immunophenotypic analysis of antigen-presenting cells involved in ectromelia virus antigen presentation in BALB/c and C57BL/6 mice.

PubMed

Szulc-Dąbrowska, Lidia; Gieryńska, Małgorzata; Boratyńska-Jasińska, Anna; Martyniszyn, Lech; Winnicka, Anna; Niemiałtowski, Marek G

2013-08-01

During mousepox in resistant (C57BL/6) or susceptible (BALB/c) strains of mice, stimulation of Th1 or Th2 cytokine immune response, respectively, is observed. Because mechanisms of different polarization of T cells remain elusive, in this study, we quantitatively assessed the phenotype of antigen-presenting cells (APCs) involved in ectromelia virus (ECTV) antigen presentation and cluster formation with effector cells in secondary lymphoid organs of BALB/c and C57BL/6 mice. We showed that both strains of mice display similar dynamics and kinetics of viral antigen presentation by CD11c(+) , CD11b(+) , and CD19(+) cells. CD11c(+) and CD11b(+) cells highly participated in viral antigen presentation during all stages of mousepox, whereas CD19(+) cells presented viral peptides later in infection. The main population of dendritic cells (DCs) engaged in ECTV antigen presentation and cell junction formation with effector cells was a population of myeloid CD11b(+) DCs (mDCs). We suggest that, on the one hand, ECTV may differentially affect the functions of APCs depending on the strain of mice. On the other hand, we suggest that some types of APCs, such as mDCs or other DCs subsets, have different abilities to direct the shape of immune response depending on the host resistance to mousepox. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

T cell activation is determined by the number of presented antigens.

PubMed

Deeg, Janosch; Axmann, Markus; Matic, Jovana; Liapis, Anastasia; Depoil, David; Afrose, Jehan; Curado, Silvia; Dustin, Michael L; Spatz, Joachim P

2013-01-01

Antigen recognition is a key event during T cell activation. Here, we introduce nanopatterned antigen arrays that mimic the antigen presenting cell surface during T cell activation. The assessment of activation related events revealed the requirement of a minimal density of 90-140 stimulating major histocompatibility complex class II proteins (pMHC) molecules per μm(2). We demonstrate that these substrates induce T cell responses in a pMHC dose-dependent manner and that the number of presented pMHCs dominates over local pMHC density.

T Cell Activation is Determined by the Number of Presented Antigens

PubMed Central

2013-01-01

Antigen recognition is a key event during T cell activation. Here, we introduce nanopatterned antigen arrays that mimic the antigen presenting cell surface during T cell activation. The assessment of activation related events revealed the requirement of a minimal density of 90–140 stimulating major histocompatibility complex class II proteins (pMHC) molecules per μm2. We demonstrate that these substrates induce T cell responses in a pMHC dose-dependent manner and that the number of presented pMHCs dominates over local pMHC density. PMID:24117051

The Relationship of Perceptions of Tap Water Safety with Intake of Sugar Sweetened Beverages and Plain Water among U.S. Adults

PubMed Central

Onufrak, Stephen J; Park, Sohyun; Sharkey, Joseph R; Sherry, Bettylou

2015-01-01

Objective Research is limited on whether mistrust of tap water discourages plain water intake and leads to greater intake of sugar-sweetened beverages (SSB). The objective of this study is to examine demographic differences in perceptions of tap water safety and determine if these perceptions are associated with intake of SSB and plain water Design The study examined perceptions of tap water safety and their cross-sectional association with intake of SSB and plain water. Racial/ethnic differences in the associations of tap water perceptions with SSB and plain water intake were also examined. Setting Nationally weighted data from 2010 HealthStyles Survey (n=4184) Subjects United States adults ≥18 years Results Overall, 13.0% of participants disagreed that their local tap water was safe to drink and 26.4% of participants agreed that bottled water was safer than tap water. Both mistrust of tap water safety and favoring bottled water differed by region, age, race/ethnicity, income, and education. The associations of tap water mistrust on intake of SSB and plain water were modified by race/ethnicity (p<0.05). Non-white racial/ethnic groups who disagreed that their local tap water was safe to drink were more likely to report low intake of plain water. The odds of consuming ≥1 SSB/day among Hispanics who mistrusted their local tap water was twice that of Hispanics who did not (OR = 2.0; 95% CI: 1.2, 3.3). Conclusions Public health efforts to promote healthy beverages should recognize the potential impact of tap water perceptions on water and SSB intake among minority populations. PMID:23098620

The CD1 family: serving lipid antigens to T cells since the Mesozoic era.

PubMed

Zajonc, Dirk M

2016-08-01

Class I-like CD1 molecules are in a family of antigen-presenting molecules that bind lipids and lipopeptides, rather than peptides for immune surveillance by T cells. Since CD1 lacks the high degree of polymorphism found in their major histocompatibility complex (MHC) class I molecules, different species express different numbers of CD1 isotypes, likely to be able to present structurally diverse classes of lipid antigens. In this review, we will present a historical overview of the structures of the different human CD1 isotypes and also discuss species-specific adaptations of the lipid-binding groove. We will discuss how single amino acid changes alter the shape and volume of the CD1 binding groove, how these minor changes can give rise to different numbers of binding pockets, and how these pockets affect the lipid repertoire that can be presented by any given CD1 protein. We will compare the structures of various lipid antigens and finally, we will discuss recognition of CD1-presented lipid antigens by antigen receptors on T cells (TCRs).

The CD1 family: serving lipid antigens to T cells since the Mesozoic era

PubMed Central

Zajonc, Dirk M.

2016-01-01

Class I-like CD1 molecules are in a family of antigen-presenting molecules that bind lipids and lipopeptides, rather than peptides for immune surveillance by T cells. Since CD1 lacks the high degree of polymorphism found in their major histocompatibility complex (MHC) class I molecules, different species express different numbers of CD1 isotypes, likely to be able to present structurally diverse classes of lipid antigens. In this review, we will present a historical overview of the structures of the different human CD1 isotypes and also discuss species-specific adaptations of the lipid-binding groove. We will discuss how single amino acid changes alter the shape and volume of the CD1 binding groove, how these minor changes can give rise to different numbers of binding pockets, and how these pockets affect the lipid repertoire that can be presented by any given CD1 protein. We will compare the structures of various lipid antigens and finally, we will discuss recognition of CD1-presented lipid antigens by antigen receptors on T cells (TCRs). PMID:27368414

Cost of Maple Sap Production for Various Size Tubing Operations

Treesearch

Niel K. Huyler

2000-01-01

Reports sap production costs for small (500 to 1,000 taps), medium (1,000 to 5,000), and large (5,000 to 15,000) maple syrup operations that use plastic tubing with vacuum pumping. The average annual operating cost per tap ranged from $4.64 for a 500-tap sugarbush operation to $1.84 for a sugarbush with 10,000 taps. The weighted average was $2.87 per tap or $11.48 per...

The gene for a lectin-like protein is transcriptionally activated during sexual development, but is not essential for fruiting body formation in the filamentous fungus Sordaria macrospora

PubMed Central

Nowrousian, Minou; Cebula, Patricia

2005-01-01

Background The filamentous fungus Sordaria macrospora forms complex three-dimensional fruiting bodies called perithecia that protect the developing ascospores and ensure their proper discharge. In previous microarray analyses, several genes have been identified that are downregulated in sterile mutants compared to the wild type. Among these genes was tap1 (transcript associated with perithecial development), a gene encoding a putative lectin homolog. Results Analysis of tap1 transcript levels in the wild type under conditions allowing only vegetative growth compared to conditions that lead to fruiting body development showed that tap1 is not only downregulated in developmental mutants but is also upregulated in the wild type during fruiting body development. We have cloned and sequenced a 3.2 kb fragment of genomic DNA containing the tap1 open reading frame and adjoining sequences. The genomic region comprising tap1 is syntenic to its homologous region in the closely related filamentous fungus Neurospora crassa. To determine whether tap1 is involved in fruiting body development in S. macrospora, a knockout construct was generated in which the tap1 open reading frame was replaced by the hygromycin B resistance gene hph under the control of fungal regulatory regions. Transformation of the S. macrospora wild type with this construct resulted in a tap1 deletion strain where tap1 had been replaced by the hph cassette. The knockout strain displayed no phenotypic differences under conditions of vegetative growth and sexual development when compared to the wild type. Double mutants carrying the Δtap1 allele in several developmental mutant backgrounds were phenotypically similar to the corresponding developmental mutant strains. Conclusion The tap1 transcript is strongly upregulated during sexual development in S. macrospora; however, analysis of a tap1 knockout strain shows that tap1 is not essential for fruiting body formation in S. macrospora. PMID:16266439

Clinical outcome in neonates with twin anemia-polycythemia sequence.

PubMed

Lopriore, Enrico; Slaghekke, Femke; Oepkes, Dick; Middeldorp, Johanna M; Vandenbussche, Frank P; Walther, Frans J

2010-07-01

The purpose of this study was to evaluate neonatal outcome of monochorionic twin pregnancies complicated by twin anemia-polycythemia sequence (TAPS). A cohort of consecutive monochorionic twins with TAPS with double survivors was included in the study. Each twin pair with TAPS was compared with 2 monochorionic twin pairs who were unaffected by TAPS or twin-to-twin transfusion syndrome and who were matched for gestational age at birth. Neonatal death, severe morbidity, and cerebral injury were studied. We included 19 twin pairs in the TAPS group and 38 control twin pairs. The incidence of neonatal death and severe neonatal morbidity was similar in the TAPS group and control group (3% [1/38] vs 1% [1/76] and 24% [9/38] vs 28% [21/76], respectively). Severe cerebral injury was detected in 1 infant (5%) in the TAPS group and 1 infant (2%) in the control group. Neonatal mortality and morbidity rates in a select population of TAPS neonates are similar to control neonatal rates. Copyright (c) 2010 Mosby, Inc. All rights reserved.

TAp63 is a master transcriptional regulator of lipid and glucose metabolism

PubMed Central

Su, Xiaohua; Gi, Young Jin; Chakravarti, Deepavali; Chan, Io Long; Zhang, Aijun; Xia, Xuefeng; Tsai, Kenneth Y.; Flores, Elsa R.

2012-01-01

SUMMARY TAp63 prevents premature aging suggesting a link to genes that regulate longevity. Further characterization of TAp63−/− mice revealed that these mice develop obesity, insulin resistance, and glucose intolerance, similar to those seen in mice lacking two key metabolic regulators, Silent information regulator T1 (Sirt1) and AMPK. While the roles of Sirt1 and AMPK in metabolism have been well studied, their upstream regulators are not well understood. We found that TAp63 is important in regulating energy metabolism by accumulating in response to metabolic stress and transcriptionally activating Sirt1, AMPKα2, and LKB1 resulting in increased fatty acid synthesis and decreased fatty acid oxidation. Moreover, we found that TAp63 lowers blood glucose levels in response to metformin. Restoration of Sirt1, AMPKα2, and LKB1 in TAp63−/− mice rescued some of the metabolic defects of the TAp63−/− mice. Our study defines a role for TAp63 in metabolism and weight control. PMID:23040072

HLA class I antigen processing machinery (APM) component expression and PD-1:PD-L1 pathway activation in HIV-infected head and neck cancers.

PubMed

Pai, Sara I; Jack Lee, J; Carey, Thomas E; Westra, William H; Ferrone, Soldano; Moore, Charles; Mosunjac, Marina B; Shin, Dong M; Ferris, Robert L

2018-02-01

Human immunodeficiency virus (HIV)-infected individuals are at increased risk for developing several non-AIDS related malignancies and are often excluded from cancer immunotherapy regimens. To evaluate the immune competence of this cancer patient population, we evaluated HLA class I antigen presenting machinery (APM) component expression and PD-1:PD-L1 pathway upregulation in HIV(+) and HIV(-) head and neck cancers (HNCs). Sixty-two HIV(+) and 44 matched HIV(-) controls diagnosed with HNC between 1991 and 2011 from five tertiary care referral centers in the United States were identified. HLA class I APM component, PD-1, and PD-L1 expression were analyzed by immunohistochemical staining with monoclonal antibodies (mAbs). Clinical data was abstracted from the medical records. There was no significant difference between the cases and controls in LMP2, TAP1, HLA-A and HLA-B/C, as well as PD-1 and PD-L1 expression. Overall, 62% of all subjects had high PD-1 expression and 82% of the subjects expressed PD-L1 within the tumor microenvironment. LMP2, HLA-A and HLA-B/C expression were significantly associated with moderate to high PD-1 expression in the HIV(+) HNC cases (p = .004, p = .026, and p = .006, respectively) but not in the HIV(-) controls. In addition, HLA-A expression was significantly associated with PD-L1 expression in the HIV(+) HNC cases only (p = .029). HIV-infected individuals diagnosed with HNC do not have any detectable defects in HLA class I APM component expression and in PD-1:PD-L1 pathway activation. Given the current successes of HAART therapy in maintaining immune cell counts, HIV(+) patients diagnosed with cancer may benefit from the recently FDA-approved immune checkpoint blockade therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clean Energy Policies Analysis: The Role of Policy in Clean Energy Market Transformation (Presentation)

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

Doris, E.

2010-11-01

This presentation was written and presented by Elizabeth Doris (NREL) at the November 17 TAP Webinar to provide background detail about how state policies are transforming the clean energy market in different regions of the country.

Increasing HIV testing among pregnant women in Nigeria: evaluating the traditional birth attendant and primary health center integration (TAP-In) model.

PubMed

Chizoba, Amara Frances; Pharr, Jennifer R; Oodo, Gina; Ezeobi, Edith; Ilozumb, Jude; Egharevba, Johnbull; Ezeanolue, Echezona E; Nwandu, Anthea

2017-09-01

Engaging Traditional Birth Attendants (TBAs) may be critical to preventing mother-to-child transmission of HIV (PMTCT) in Nigeria. We integrated TBAs into Primary Health Centers (PHCs) and provided the TBAs with HIV counseling and testing (HCT) training for PMTCT (TAP-In). The purpose of this study was to evaluate the impact of TAP-In on HCT uptake among pregnant women. A quasi-experimental design was used for this study. Twenty PHCs were assigned to the intervention group that integrated TAP-In and 20 were assigned to the control group. Data were collected six months prior to the initiation of TAP-In and six months post, using antenatal clinic registries. Intervention PHCs more than doubled the number of pregnant women who received HCT in their catchment area post TAP-In while control PHCs had no significant change. After initiating TAP-In, intervention PHCs provided almost three times more HCT than the control PHCs (p < 0.01) with TBA provided over half of the HCT post TAP-In. The TAP-In model was effective for increasing HCT among pregnant women.

The time course of phase correction: A kinematic investigation of motor adjustment to timing perturbations during sensorimotor synchronization

PubMed Central

Hove, Michael J.; Balasubramaniam, Ramesh; Keller, Peter E.

2014-01-01

Synchronizing movements with a beat requires rapid compensation for timing errors. The phase-correction response (PCR) has been studied extensively in finger tapping by shifting a metronome onset and measuring the adjustment of the following tap time. How the response unfolds during the subsequent tap cycle remains unknown. Using motion capture, we examined finger kinematics during the PCR. Participants tapped with a metronome containing phase perturbations. They tapped in ‘legato’ and ‘staccato’ style at various tempi, which altered the timing of the constituent movement stages (dwell at the surface, extension, flexion). After a phase perturbation, tapping kinematics changed compared to baseline, and the PCR was distributed differently across movement stages. In staccato tapping, the PCR trajectory changed primarily during finger extension across tempi. In legato tapping, at fast tempi the PCR occurred primarily during extension, whereas at slow tempi most phase correction was already completed during dwell. Across conditions, timing adjustments occurred primarily 100-250 ms into the following tap cycle. The change in movement around 100 ms represents the time to integrate information into an already planned movement and the rapidity suggests a subcortical route. PMID:25151103

Water use and time analysis in ablution from taps

NASA Astrophysics Data System (ADS)

Zaied, Roubi A.

2017-09-01

There is a lack of water resources and an extreme use of potable water in our Arab region. Ablution from taps was studied since it is a repeated daily activity that consumes more water. Five different tap types are investigated for water consumption fashions including traditional mixing tap and automatic tap. Analyzing 100 experimental observations revealed that 22.7-28.8 % of ablution water is used for washing of feet and the largest water waste occurs during washing of face portions. Moreover, 30-47 % amount of water consumed in ablution from taps is wasted which can be saved if tap releases water only at moments of need. The push-type tap is being spread recently especially in airports. If it is intended for use in ablution facilities, batch duration and volume must be tuned. When each batch is 0.25 L of water and lasts for 3 s, 3 L are sufficient for one complete ablution in average which means considerable saving. A cost-benefit model is proposed for using different tap types and an economic feasibility study is performed on a case study. This analysis can help us to design better ablution systems.

Self-Advancing Step-Tap Drills

NASA Technical Reports Server (NTRS)

Pettit, Donald R.; Camarda, Charles J.; Penner, Ronald K.; Franklin, Larry D.

2007-01-01

Self-advancing tool bits that are hybrids of drills and stepped taps make it possible to form threaded holes wider than about 1/2 in. (about 13 mm) without applying any more axial force than is necessary for forming narrower pilot holes. These self-advancing stepped-tap drills were invented for use by space-suited astronauts performing repairs on reinforced carbon/carbon space-shuttle leading edges during space walks, in which the ability to apply axial drilling forces is severely limited. Self-advancing stepped-tap drills could also be used on Earth for making wide holes without applying large axial forces. A self-advancing stepped-tap drill (see figure) includes several sections having progressively larger diameters, typically in increments between 0.030 and 0.060 in. (between about 0.8 and about 1.5 mm). The tip section, which is the narrowest, is a pilot drill bit that typically has a diameter between 1/8 and 3/16 in. (between about 3.2 and about 4.8 mm). The length of the pilot-drill section is chosen, according to the thickness of the object to be drilled and tapped, so that the pilot hole is completed before engagement of the first tap section. Provided that the cutting-edge geometry of the drill bit is optimized for the material to be drilled, only a relatively small axial force [typically of the order of a few pounds (of the order of 10 newtons)] must be applied during drilling of the pilot hole. Once the first tap section engages the pilot hole, it is no longer necessary for the drill operator to apply axial force: the thread engagement between the tap and the workpiece provides the axial force to advance the tool bit. Like the pilot-drill section, each tap section must be long enough to complete its hole before engagement of the next, slightly wider tap section. The precise values of the increments in diameter, the thread pitch, the rake angle of the tap cutting edge, and other geometric parameters of the tap sections must be chosen, in consideration of the workpiece material and thickness, to prevent stripping of threads during the drilling/tapping operation. A stop-lip or shoulder at the shank end of the widest tap section prevents further passage of the tool bit through the hole.

Immunoglobulins drive terminal maturation of splenic dendritic cells

PubMed Central

Ziętara, Natalia; Łyszkiewicz, Marcin; Puchałka, Jacek; Pei, Gang; Gutierrez, Maximiliano Gabriel; Lienenklaus, Stefan; Hobeika, Elias; Reth, Michael; Martins dos Santos, Vitor A. P.; Krueger, Andreas; Weiss, Siegfried

2013-01-01

Nature and physiological status of antigen-presenting cells, such as dendritic cells DCs, are decisive for the immune reactions elicited. Multiple factors and cell interactions have been described that affect maturation of DCs. Here, we show that DCs arising in the absence of immunoglobulins (Ig) in vivo are impaired in cross-presentation of soluble antigen. This deficiency was due to aberrant cellular targeting of antigen to lysosomes and its rapid degradation. Function of DCs could be restored by transfer of Ig irrespective of antigen specificity and isotype. Modulation of cross-presentation by Ig was inhibited by coapplication of mannan and, thus, likely to be mediated by C-type lectin receptors. This unexpected dependency of splenic DCs on Ig to cross-present antigen provides insights into the interplay between cellular and humoral immunity and the immunomodulatory capacity of Ig. PMID:23345431

EVIR: chimeric receptors that enhance dendritic cell cross-dressing with tumor antigens.

PubMed

Squadrito, Mario Leonardo; Cianciaruso, Chiara; Hansen, Sarah K; De Palma, Michele

2018-03-01

We describe a lentivirus-encoded chimeric receptor, termed extracellular vesicle (EV)-internalizing receptor (EVIR), which enables the selective uptake of cancer-cell-derived EVs by dendritic cells (DCs). The EVIR enhances DC presentation of EV-associated tumor antigens to CD8 + T cells primarily through MHCI recycling and cross-dressing. EVIRs should facilitate exploring the mechanisms and implications of horizontal transfer of tumor antigens to antigen-presenting cells.

Introducing Improvisational Skills Through Rhythm Tap: Whether Used in a Dance Class or in a Physical Education Dance Unit, These Simple Exercises Will Overcome Students' Inhibitions and Encourage Their Creative Abilities

ERIC Educational Resources Information Center

West, Colleen N.

2005-01-01

Rhythm tap is sweeping the nation as an outlet for self-expression. Also known as "jazz tap" or "percussive tap," this art form's dominant focus is musicality, improvisation, simple-to-complex rhythms, and new styles. It reaches beyond technique and serves as an outlet for self-expression, independence, and spontaneity. Rhythm tap incorporates an…

Levels of major and trace elements, including rare earth elements, and ²³⁸U in Croatian tap waters.

PubMed

Fiket, Željka; Rožmarić, Martina; Krmpotić, Matea; Benedik, Ljudmila

2015-05-01

Concentrations of 46 elements, including major, trace, and rare earth elements, and (238)U in Croatian tap waters were investigated. Selected sampling locations include tap waters from various hydrogeological regions, i.e., different types of aquifers, providing insight into the range of concentrations of studied elements and (238)U activity concentrations in Croatian tap waters. Obtained concentrations were compared with the Croatian maximum contaminant levels for trace elements in water intended for human consumption, as well as WHO and EPA drinking water standards. Concentrations in all analyzed tap waters were found in accordance with Croatian regulations, except tap water from Šibenik in which manganese in concentration above maximum permissible concentration (MPC) was measured. Furthermore, in tap water from Osijek, levels of arsenic exceeded the WHO guidelines and EPA regulations. In general, investigated tap waters were found to vary considerably in concentrations of studied elements, including (238)U activity concentrations. Causes of variability were further explored using statistical methods. Composition of studied tap waters was found to be predominately influenced by hydrogeological characteristics of the aquifer, at regional and local level, the existing redox conditions, and the household plumbing system. Rare earth element data, including abundances and fractionation patterns, complemented the characterization and facilitated the interpretation of factors affecting the composition of the analyzed tap waters.

Functional Macroautophagy Induction by Influenza A Virus without a Contribution to Major Histocompatibility Complex Class II-Restricted Presentation▿†

PubMed Central

Comber, Joseph D.; Robinson, Tara M.; Siciliano, Nicholas A.; Snook, Adam E.; Eisenlohr, Laurence C.

2011-01-01

Major histocompatibility complex (MHC) class II-presented peptides can be derived from both exogenous (extracellular) and endogenous (biosynthesized) sources of antigen. Although several endogenous antigen-processing pathways have been reported, little is known about their relative contributions to global CD4+ T cell responses against complex antigens. Using influenza virus for this purpose, we assessed the role of macroautophagy, a process in which cytosolic proteins are delivered to the lysosome by de novo vesicle formation and membrane fusion. Influenza infection triggered productive macroautophagy, and autophagy-dependent presentation was readily observed with model antigens that naturally traffic to the autophagosome. Furthermore, treatments that enhance or inhibit macroautophagy modulated the level of presentation from these model antigens. However, validated enzyme-linked immunospot (ELISpot) assays of influenza-specific CD4+ T cells from infected mice using a variety of antigen-presenting cells, including primary dendritic cells, revealed no detectable macroautophagy-dependent component. In contrast, the contribution of proteasome-dependent endogenous antigen processing to the global influenza CD4+ response was readily appreciated. The contribution of macroautophagy to the MHC class II-restricted response may vary depending upon the pathogen. PMID:21525345

Towards preserving the immunogenicity of protein antigens carried by nanoparticles while avoiding the cold chain.

PubMed

Sloat, Brian R; Sandoval, Michael A; Cui, Zhengrong

2010-06-30

Nanoparticles are an attractive vaccine carrier with potent adjuvant activity. Data from our previous studies showed that immunization of mice with lecithin/glyceryl monostearate-based nanoparticles with protein antigens conjugated onto their surface induced a strong, quick, and long-lasting antigen-specific immune response. In the present study, we evaluated the feasibility of preserving the immunogenicity of protein antigens carried by nanoparticles without refrigeration using these antigen-conjugated nanoparticles as a model. The nanoparticles were lyophilized, and the immunogenicity of the antigens was evaluated in a mouse model using bovine serum albumin or the Bacillus anthracis protective antigen protein as model antigens. With proper excipients, the nanoparticles can be lyophilized while maintaining the immunogenicity of the antigens. Moreover, the immunogenicity of the model antigen conjugated onto the nanoparticles was undamaged after a relatively extended period of storage at room temperature or under accelerated conditions (37 degrees C) when the nanoparticles were lyophilized with 5% mannitol plus 1% polyvinylpyrrolidone. To our knowledge, the present study represents an early attempt to preserve the immunogenicity of the protein antigens carried by nanoparticles without refrigeration. 2010 Elsevier B.V. All rights reserved.

Serum and urine concentrations of trypsinogen-activation peptide as markers for acute pancreatitis in cats

PubMed Central

Allen, Heidi S.; Steiner, Jörg; Broussard, John; Mansfield, Caroline; Williams, David A.; Jones, Boyd

2006-01-01

The purpose of this study was to compare the clinical utility of the serum concentration of feline trypsin-like immunoreactivity (fTLI), the plasma and urine concentrations of trypsinogen-activation peptide (TAP), and the ratio of the urine TAP and creatinine concentrations (TAP:Cr) in the diagnosis of feline acute pancreatitis. We used 13 healthy cats and 10 cats with a diagnosis of acute pancreatitis. The mean serum fTLI and plasma TAP concentrations were significantly higher in the cats with acute pancreatitis than in the healthy cats (P < 0.05); the mean urine TAP concentrations and the median urine TAP:Cr ratios were not significantly different. Among the cats examined in this study, there was no benefit of plasma TAP over serum fTLI in the evaluation of suspected acute pancreatitis. PMID:17042387

Ventricular shunt tap as a predictor of proximal shunt malfunction in children: a prospective study.

PubMed

Rocque, Brandon G; Lapsiwala, Samir; Iskandar, Bermans J

2008-06-01

The clinical diagnosis of cerebrospinal fluid (CSF) shunt malfunction can be challenging. In this prospective study, the authors evaluated a common method of interrogating shunts: the shunt tap; specifically, its ability to predict proximal malfunction. The authors performed standardized shunt taps in a consecutive series of cases involving children with suspected or proven shunt malfunction, assessing flow and, when possible, opening pressure. Data were collected prospectively, and results analyzed in light of surgical findings. A shunt tap was performed prior to 68 operative explorations in 51 patients. Of the 68 taps, 28 yielded poor or no CSF flow on aspiration. After 26 of these 28 procedures, proximal catheter obstruction was identified. After 28 taps with good CSF return and normal or low opening pressure, 18 shunts were found to have a proximal obstruction, 8 had no obstruction, and 2 had a distal obstruction. Another 12 taps with good CSF flow had high opening pressure; subsequent surgery showed distal obstruction in 11 of the shunts, and proximal obstruction in 1. The positive predictive value of poor flow was 93%, while good flow on shunt tap predicted adequate proximal catheter function in only 55% of cases. Poor flow of CSF on shunt tap is highly predictive of obstruction of the proximal catheter. Because not all patients with good flow on shunt tap underwent surgical shunt exploration, the specificity of this test cannot be determined. Nonetheless, a shunt tap that reveals good flow with a normal opening pressure can be misleading, and management of such cases should be based on clinical judgment.

Frankincense tapping reduces the carbohydrate storage of Boswellia trees.

PubMed

Mengistu, Tefera; Sterck, Frank J; Fetene, Masresha; Bongers, Frans

2013-06-01

Carbohydrates fixed by photosynthesis are stored in plant organs in the form of starch or sugars. Starch and sugars sum to the total non-structural carbohydrate pool (TNC) and may serve as intermediate pools between assimilation and utilization. We examined the impact of tapping on TNC concentrations in stem-wood, bark and root tissues of the frankincense tree (Boswellia papyrifera (Del.) Hochst) in two natural woodlands of Ethiopia. Two tapping treatments, one without tapping (control) and the other with tapping at 12 incisions, are applied on experimental trees. Trees are tapped in the leafless dry period, diminishing their carbon storage pools. If storage pools are not refilled by assimilation during the wet season, when crowns are in full leaf, tapping may deplete the carbon pool and weaken Boswellia trees. The highest soluble sugar concentrations were in the bark and the highest starch concentrations in the stem-wood. The stem-wood contains 12 times higher starch than soluble sugar concentrations. Hence, the highest TNC concentrations occurred in the stem-wood. Moreover, wood volume was larger than root or bark volumes and, as a result, more TNC was stored in the stem-wood. As predicted, tapping reduced the TNC concentrations and pool sizes in frankincense trees during the dry season. During the wet season, these carbon pools were gradually filled in tapped trees, but never to the size of non-tapped trees. We conclude that TNC is dynamic on a seasonal time scale and offers resilience against stress, highlighting its importance for tree carbon balance. But current resin tapping practices are intensive and may weaken Boswellia populations, jeopardizing future frankincense production.

A novel role of HLA class I in the pathology of medulloblastoma.

PubMed

Smith, Courtney; Santi, Mariarita; Rajan, Bhargavi; Rushing, Elisabeth J; Choi, Mi Rim; Rood, Brian R; Cornelison, Robert; MacDonald, Tobey J; Vukmanovic, Stanislav

2009-07-12

MHC class I expression by cancer cells enables specific antigen recognition by the immune system and protection of the host. However, in some cancer types MHC class I expression is associated with an unfavorable outcome. We explored the basis of MHC class I association with unfavorable prognostic marker expression in the case of medulloblastoma. We investigated expression of four essential components of MHC class I (heavy chain, beta2m, TAP1 and TAP2) in 10 medulloblastoma mRNA samples, a tissue microarray containing 139 medulloblastoma tissues and 3 medulloblastoma cell lines. Further, in medulloblastoma cell lines we evaluated the effects of HLA class I engagement on activation of ERK1/2 and migration in vitro. The majority of specimens displayed undetectable or low levels of the heavy chains. Medulloblastomas expressing high levels of HLA class I displayed significantly higher levels of anaplasia and c-myc expression, markers of poor prognosis. Binding of beta2m or a specific antibody to open forms of HLA class I promoted phosphorylation of ERK1/2 in medulloblastoma cell line with high levels, but not in the cell line with low levels of HLA heavy chain. This treatment also promoted ERK1/2 activation dependent migration of medulloblastoma cells. MHC class I expression in medulloblastoma is associated with anaplasia and c-myc expression, markers of poor prognosis. Peptide- and/or beta2m-free forms of MHC class I may contribute to a more malignant phenotype of medulloblastoma by modulating activation of signaling molecules such as ERK1/2 that stimulates cell mobility.

A novel role of HLA class I in the pathology of medulloblastoma

PubMed Central

Smith, Courtney; Santi, Mariarita; Rajan, Bhargavi; Rushing, Elisabeth J; Choi, Mi Rim; Rood, Brian R; Cornelison, Robert; MacDonald, Tobey J; Vukmanovic, Stanislav

2009-01-01

Background MHC class I expression by cancer cells enables specific antigen recognition by the immune system and protection of the host. However, in some cancer types MHC class I expression is associated with an unfavorable outcome. We explored the basis of MHC class I association with unfavorable prognostic marker expression in the case of medulloblastoma. Methods We investigated expression of four essential components of MHC class I (heavy chain, β2m, TAP1 and TAP2) in 10 medulloblastoma mRNA samples, a tissue microarray containing 139 medulloblastoma tissues and 3 medulloblastoma cell lines. Further, in medulloblastoma cell lines we evaluated the effects of HLA class I engagement on activation of ERK1/2 and migration in vitro. Results The majority of specimens displayed undetectable or low levels of the heavy chains. Medulloblastomas expressing high levels of HLA class I displayed significantly higher levels of anaplasia and c-myc expression, markers of poor prognosis. Binding of β2m or a specific antibody to open forms of HLA class I promoted phosphorylation of ERK1/2 in medulloblastoma cell line with high levels, but not in the cell line with low levels of HLA heavy chain. This treatment also promoted ERK1/2 activation dependent migration of medulloblastoma cells. Conclusion MHC class I expression in medulloblastoma is associated with anaplasia and c-myc expression, markers of poor prognosis. Peptide- and/or β2m-free forms of MHC class I may contribute to a more malignant phenotype of medulloblastoma by modulating activation of signaling molecules such as ERK1/2 that stimulates cell mobility. PMID:19594892

76 FR 12418 - Recruitment Notice for the Taxpayer Advocacy Panel

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-07

... for Recruitment of IRS Taxpayer Advocacy Panel (TAP) Members. DATES: March 14, 2011 through April 29... Advocacy Panel (TAP). The mission of the TAP is to listen to taxpayers, identify issues that affect taxpayers, and make suggestions for improving IRS service and customer satisfaction. The TAP serves as an...

33 CFR 165.1710 - Port Valdez and Valdez Narrows, Valdez, Alaska-security zones.

Code of Federal Regulations, 2010 CFR

2010-07-01

... following areas are security zones: (1) Trans-Alaska Pipeline (TAPS) Valdez Terminal complex (Terminal), Valdez, Alaska and TAPS tank vessels. All waters enclosed within a line beginning on the southern... TAPS tank vessel maneuvering to approach, moor, unmoor or depart the TAPS Terminal or transiting...

77 FR 13390 - Recruitment Notice for the Taxpayer Advocacy Panel

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-06

... for Recruitment of IRS Taxpayer Advocacy Panel (TAP) Members. DATES: March 19, 2012 through April 27... Advocacy Panel (TAP). The mission of the TAP is to listen to taxpayers, identify issues that affect taxpayers, and make suggestions for improving IRS service and customer satisfaction. The TAP serves as an...

75 FR 40033 - Proposed Collection; Comment Request for Taxpayer Advocacy Panel (TAP) Tax Check Waiver

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-13

... Taxpayer Advocacy Panel (TAP) Tax Check Waiver AGENCY: Internal Revenue Service (IRS), Treasury. ACTION... comments concerning Taxpayer Advocacy Panel (TAP) Tax Check Waiver. DATES: Written comments should [email protected] . SUPPLEMENTARY INFORMATION: Title: Taxpayer Advocacy Panel (TAP) Tax Check Waiver. OMB...

40 CFR 60.265 - Monitoring of operations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... quantity, by weight. (3) Time and duration of each tapping period and the identification of material tapped... only the volumetric flow rate through the capture system for control of emissions from the tapping... performance test. If emissions due to tapping are captured and ducted separately from emissions of the...

75 FR 9028 - Recruitment Notice for the Taxpayer Advocacy Panel

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-26

... for Recruitment of IRS Taxpayer Advocacy Panel (TAP) Members. DATES: March 15, 2010 through April 30... Advocacy Panel (TAP). The mission of the TAP is to listen to taxpayers, identify issues that affect taxpayers, and make suggestions for improving IRS service and customer satisfaction. The TAP serves as an...

49 CFR 192.151 - Tapping.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 3 2010-10-01 2010-10-01 false Tapping. 192.151 Section 192.151 Transportation... BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Design of Pipeline Components § 192.151 Tapping. (a) Each mechanical fitting used to make a hot tap must be designed for at least the operating pressure of...

The overlooked "nonclassical" functions of major histocompatibility complex (MHC) class II antigens in immune and nonimmune cells.

PubMed

Altomonte, M; Pucillo, C; Maio, M

1999-06-01

Besides their "classical" antigenic peptide-presenting activity, major histocompatibility complex (MHC) class II antigens can activate different cellular functions in immune and nonimmune cells. However, this "nonclassical" role and its functional consequences are still substantially overlooked. In this review, we will focus on these alternative functional properties of MHC class II antigens, to reawaken attention to their present and foreseeable immunobiologic and pathogenetic implications. The main issues that will be addressed concern 1) the role of MHC class II molecules as basic components of exchangeable oligomeric protein complexes with intracellular signaling ability; 2) the nonclassical functions of MHC class II antigens in immune cells; 3) the pathogenetic role of MHC class II antigens in inflammatory/autoimmune and infectious disease; and 4) the functional role of MHC class II antigens in solid malignancies.

Enhancement of MHC-I antigen presentation via architectural control of pH-responsive, endosomolytic polymer nanoparticles.

PubMed

Wilson, John T; Postma, Almar; Keller, Salka; Convertine, Anthony J; Moad, Graeme; Rizzardo, Ezio; Meagher, Laurence; Chiefari, John; Stayton, Patrick S

2015-03-01

Protein-based vaccines offer a number of important advantages over organism-based vaccines but generally elicit poor CD8(+) T cell responses. We have previously demonstrated that pH-responsive, endosomolytic polymers can enhance protein antigen delivery to major histocompatibility complex class I (MHC-I) antigen presentation pathways thereby augmenting CD8(+) T cell responses following immunization. Here, we describe a new family of nanocarriers for protein antigen delivery assembled using architecturally distinct pH-responsive polymers. Reversible addition-fragmentation chain transfer (RAFT) polymerization was used to synthesize linear, hyperbranched, and core-crosslinked copolymers of 2-(N,N-diethylamino)ethyl methacrylate (DEAEMA) and butyl methacrylate (BMA) that were subsequently chain extended with a hydrophilic N,N-dimethylacrylamide (DMA) segment copolymerized with thiol-reactive pyridyl disulfide (PDS) groups. In aqueous solution, polymer chains assembled into 25 nm micellar nanoparticles and enabled efficient and reducible conjugation of a thiolated protein antigen, ovalbumin. Polymers demonstrated pH-dependent membrane-destabilizing activity in an erythrocyte lysis assay, with the hyperbranched and cross-linked polymer architectures exhibiting significantly higher hemolysis at pH ≤ 7.0 than the linear diblock. Antigen delivery with the hyperbranched and cross-linked polymer architecture enhanced in vitro MHC-I antigen presentation relative to free antigen, whereas the linear construct did not have a discernible effect. The hyperbranched system elicited a four- to fivefold increase in MHC-I presentation relative to the cross-linked architecture, demonstrating the superior capacity of the hyperbranched architecture in enhancing MHC-I presentation. This work demonstrates that the architecture of pH-responsive, endosomolytic polymers can have dramatic effects on intracellular antigen delivery, and offers a promising strategy for enhancing CD8(+) T cell responses to protein-based vaccines.

Effective antigen presentation to helper T cells by human eosinophils.

PubMed

Farhan, Ruhaifah K; Vickers, Mark A; Ghaemmaghami, Amir M; Hall, Andrew M; Barker, Robert N; Walsh, Garry M

2016-12-01

Although eosinophils are inflammatory cells, there is increasing attention on their immunomodulatory roles. For example, murine eosinophils can present antigen to CD4 + T helper (Th) cells, but it remains unclear whether human eosinophils also have this ability. This study determined whether human eosinophils present a range of antigens, including allergens, to activate Th cells, and characterized their expression of MHC class II and co-stimulatory molecules required for effective presentation. Human peripheral blood eosinophils purified from non-allergic donors were pulsed with the antigens house dust mite extract (HDM), Timothy Grass extract (TG) or Mycobacterium tuberculosis purified protein derivative (PPD), before co-culture with autologous CD4 + Th cells. Proliferative and cytokine responses were measured, with eosinophil expression of HLA-DR/DP/DQ and the co-stimulatory molecules CD40, CD80 and CD86 determined by flow cytometry. Eosinophils pulsed with HDM, TG or PPD drove Th cell proliferation, with the response strength dependent on antigen concentration. The cytokine responses varied with donor and antigen, and were not biased towards any particular Th subset, often including combinations of pro- and anti-inflammatory cytokines. Eosinophils up-regulated surface expression of HLA-DR/DP/DQ, CD80, CD86 and CD40 in culture, increases that were sustained over 5 days when incubated with antigens, including HDM, or the major allergens it contains, Der p I or Der p II. Human eosinophils can, therefore, act as effective antigen-presenting cells to stimulate varied Th cell responses against a panel of antigens including HDM, TG or PPD, an ability that may help to determine the development of allergic disease. © 2016 John Wiley & Sons Ltd.

Astronomy on Tap as a Professional Development Tool

NASA Astrophysics Data System (ADS)

Rice, Emily; Burtnyk, Kimberly; Silverman, Jeffrey; Popinchalk, Mark; Constellation of Astronomy On Tap Host Stars

2018-01-01

We lured scientists, educators, and other astronomy enthusiasts into bars around the world with promises of fun public outreach, but we secretly provided them with networking opportunities and taught them how to be better communicators! Astronomy on Tap (AoT) events began in New York City in 2013, and since then nearly 400 events (featuring 1-6 presenters each) have been organized by over 100 people in over 30 locations across the U.S. and around the world. Implicit in the design of typical AoT events are opportunities for professional development in several areas, most prominently in networking and science communication. We surveyed organizers and presenters to assess the extent to which they have benefited from these opportunities. We report results from that survey and present plans for codifying professional development aspects of AoT events for future implementation.

Lateralized dual task interference in left-handers: initial value differences do not affect the outcome.

PubMed

McBride, D M; Cherry, B J; Kee, D W; Neale, P L

1995-07-01

The study was conducted to clarify factors involved in dual-task finger-tapping interference. Left-handers, as assessed by hand-writing preference and left-hand baseline tapping advantage, tapped both alone and while solving anagrams. Even though the left-hand baseline tapping advantage was experimentally removed on some (adjusted) trials, greater left- than right-hand tapping interference was observed during concurrent task performance. This result coupled with previous findings for right-handed subjects [Kee and Cherry, Neuropsychologia, Vol. 28, pp. 313-316, 1990] indicates that lateralized interference effects are not merely due to initial baseline tapping differences as proposed by Willis and Goodwin [Neuropsychologia, Vol. 25, pp. 719-724, 1987].

Why do proteases mess up with antigen presentation by re-shuffling antigen sequences?

PubMed

Liepe, Juliane; Ovaa, Huib; Mishto, Michele

2018-04-30

The sequence of a large number of MHC-presented epitopes is not present as such in the original antigen because it has been re-shuffled by the proteasome or other proteases. Why do proteases throw a spanner in the works of our model of antigen tagging and immune recognition? We describe in this review what we know about the immunological relevance of post-translationally spliced epitopes and why proteases seem to have a second (dark) personality, which is keen to create new peptide bonds. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Elimination of current spikes in buck power converters

NASA Technical Reports Server (NTRS)

Mclyman, W. T. (Inventor)

1981-01-01

Current spikes in a buck power converter due to commutating diode turn-off time are eliminated by using a tapped inductor in the converter with the tap connected to the switching transistor. The commutating diode is not in the usual place, but is instead connected to conduct current from one end of the tapped inductor remote from the load during the interval in which the transistor is not conducting. In the case of a converter having a center-tapped (primary and secondary) transformer between two switching power transistors operated in a push-pull mode and two rectifying diodes in the secondary circuit, current spikes due to transformer saturation are also eliminated by using a tapped inductor in the converter with the tap connected to the rectifying diodes and a diode connected to conduct current from one end of the tapped inductor remote from the load during the interval in which the transistors are not conducting.

Demographic factors associated with perceptions about water safety and tap water consumption among adults in Santa Clara County, California, 2011.

PubMed

van Erp, Brianna; Webber, Whitney L; Stoddard, Pamela; Shah, Roshni; Martin, Lori; Broderick, Bonnie; Induni, Marta

2014-06-12

The objective of this study was to examine differences in tap water consumption and perceptions of bottle versus tap water safety for Hispanics and non-Hispanic whites, as well as associations with other demographic characteristics. Data are from the Santa Clara County, California, Dietary Practices Survey (2011; N = 306). We used logistic regression to examine associations between demographic characteristics and 1) perceptions that bottled water is safer than tap and 2) primarily consuming tap water. Hispanics were less likely than non-Hispanic whites to primarily drink tap water (OR = 0.33; 95% CI, 0.11-0.99), although there was no significant difference in perceptions that bottled water is safer between these groups (OR = 0.50; 95% CI, 0.11-2.27). Hispanics may be an important population for interventions promoting tap water consumption.

Neural Entrainment in Drum Rhythms with Silent Breaks: Evidence from Steady-state Evoked and Event-related Potentials.

PubMed

Stupacher, Jan; Witte, Matthias; Hove, Michael J; Wood, Guilherme

2016-12-01

The fusion of rhythm, beat perception, and movement is often summarized under the term "entrainment" and becomes obvious when we effortlessly tap our feet or snap our fingers to the pulse of music. Entrainment to music involves a large network of brain structures, and neural oscillations at beat-related frequencies can help elucidate how this network is connected. Here, we used EEG to investigate steady-state evoked potentials (SSEPs) and event-related potentials (ERPs) during listening and tapping to drum clips with different rhythmic structures that were interrupted by silent breaks of 2-6 sec. This design allowed us to address the question of whether neural entrainment processes persist after the physical presence of musical rhythms and to link neural oscillations and event-related neural responses. During stimulus presentation, SSEPs were elicited in both tasks (listening and tapping). During silent breaks, SSEPs were only present in the tapping task. Notably, the amplitude of the N1 ERP component was more negative after longer silent breaks, and both N1 and SSEP results indicate that neural entrainment was increased when listening to drum rhythms compared with an isochronous metronome. Taken together, this suggests that neural entrainment to music is not solely driven by the physical input but involves endogenous timing processes. Our findings break ground for a tighter linkage between steady-state and transient evoked neural responses in rhythm processing. Beyond music perception, they further support the crucial role of entrained oscillatory activity in shaping sensory, motor, and cognitive processes in general.

Case study of complaints on drinking water quality: relationship to copper content?

PubMed

Pizarro, Fernando; Araya, Magdalena; Vásquez, Marcela; Lagos, Gustavo; Olivares, Manuel; Méndez, Marco A; Leyton, Bárbara; Reyes, Arturo; Letelier, Victoria; Uauy, Ricardo

2007-05-01

Several families of Talca city, Chile complained to health authorities for what they attributed to consumption of copper (Cu)-contaminated drinking water. We assessed the situation 6-12 mo after the initiation of complaints by characterizing the symptoms reported, the chemistry of drinking water, and the Cu concentration in stagnant drinking water. After completing a census, 1778 households accepted participation and were categorized as follows: category 1, Cu plumbing for tap water and dwellers reporting health complaints (HC); category 2, Cu plumbing for tap water and dwellers reporting no HC; category 3, plastic plumbing for tap water and dwellers reporting no HC. Questionnaires recorded characteristics of households and symptoms presented by each member of the family in the last 3 mo. The Cu concentration in drinking water was measured in a subsample of 80 homes with Cu pipes. In category 1, participants presented significantly more abdominal pain, diarrhea, and/or vomiting (gastrointestinal [GI] symptoms) in comparison to category 3 and to categories 2 plus 3. The stagnant Cu concentrations measured in drinking water in all houses studied were below the US Environmental Protection Agency guideline value (<1.3 mg Cu/L). In summary, data obtained by interviews suggested that individuals in some areas of Talca city were suffering more GI symptoms potentially related to Cu excess, but measurement of Cu concentration in stagnant tap waters ruled out the association between Cu exposure and GI symptom reports at the time of this study. The dose-response curves for GI symptoms and Cu exposure now available were crucial in the analyses of results.

Dendritic cells cross-present HIV antigens from live as well as apoptotic infected CD4+ T lymphocytes

NASA Astrophysics Data System (ADS)

Marañón, Concepción; Desoutter, Jean-François; Hoeffel, Guillaume; Cohen, William; Hanau, Daniel; Hosmalin, Anne

2004-04-01

A better understanding of the antigen presentation pathways that lead to CD8+ T cell recognition of HIV epitopes in vivo is needed to achieve better immune control of HIV replication. Here, we show that cross-presentation of very small amounts of HIV proteins from apoptotic infected CD4+ T lymphocytes by dendritic cells to CD8+ T cells is much more efficient than other known HIV presentation pathways, i.e., direct presentation of infectious virus or cross-presentation of defective virus. Unexpectedly, dendritic cells also take up actively antigens into endosomes from live infected CD4+ T lymphocytes and cross-present them as efficiently as antigens derived from apoptotic infected cells. Moreover, live infected CD4+ T cells costimulate cross-presenting dendritic cells in the process. Therefore, dendritic cells can present very small amounts of viral proteins from infected T cells either after apoptosis, which is frequent during HIV infection, or not. Thus, if HIV expression is transiently induced while costimulation is enhanced (for instance after IL-2 and IFN immune therapy), this HIV antigen presentation pathway could be exploited to eradicate latently infected reservoirs, which are poorly recognized by patients' immune systems.

Solanaceae plant malformation in Chongqing City, China, reveals a pollution threat to the Yangtze River.

PubMed

Zhang, Hongbo; Liu, Guanshan; Timko, Michael P; Li, Jiana; Wang, Wenjing; Ma, Haoran

2014-10-21

Water quality is under increasing threat from industrial and natural sources of pollutants. Here, we present our findings about a pollution incident involving the tap water of Chongqing City in China. In recent years, Solanaceae plants grown in greenhouses in this city have displayed symptoms of cupped, strappy leaves. These symptoms resembled those caused by chlorinated auxinic herbicides. We have determined that these symptoms were caused by the tap water used for irrigation. Using a bioactivity-guided fractionation method, we isolated a substance with corresponding auxinic activity from the tap water. The substance was named "solanicide" because of its strong bioactivity against Solanaceae plants. Further investigation revealed that the solanicide in the water system of Chongqing City is derived from the Jialing River, a major tributary of the Yangtze River. Therefore, it is also present in the Yangtze River downstream of Chongqing after the inflow of the Jialing River. Biological analyses indicated that solanicide is functionally similar to, but distinct from, other known chlorinated auxinic herbicides. Chemical assays further showed that solanicide structurally differs from those compounds. This study has highlighted a water pollution threat to the Yangtze River and its floodplain ecosystem.

SERS as an analytical tool in environmental science: The detection of sulfamethoxazole in the nanomolar range by applying a microfluidic cartridge setup.

PubMed

Patze, Sophie; Huebner, Uwe; Liebold, Falk; Weber, Karina; Cialla-May, Dana; Popp, Juergen

2017-01-01

Sulfamethoxazole (SMX) is a commonly applied antibiotic for treating urinary tract infections; however, allergic reactions and skin eczema are known side effects that are observed for all sulfonamides. Today, this molecule is present in drinking and surface water sources. The allowed concentration in tap water is 2·10 -7  mol L -1 . SMX could unintentionally be ingested by healthy people when drinking contaminated tap water, representing unnecessary drug intake. To assess the quality of tap water, fast, specific and sensitive detection methods are required, in which consequence measures for improving the purification of water might be initiated in the short term. Herein, the quantitative detection of SMX down to environmentally and physiologically relevant concentrations in the nanomolar range by employing surface-enhanced Raman spectroscopy (SERS) and a microfluidic cartridge system is presented. By applying surface-water samples as matrices, the detection of SMX down to 2.2·10 -9  mol L -1 is achieved, which illustrates the great potential of our proposed method in environmental science. Copyright © 2016 Elsevier B.V. All rights reserved.

Haitian Tap-Taps

ERIC Educational Resources Information Center

Sterling, Joan

2011-01-01

In the small island country of Haiti, colorful taxis transport the natives to the market. Although the taxis may be crowded with people, goods, and even livestock, it is considered a luxury to ride rather than go on foot. The children's picture book, "Tap-Tap," is a wonderful introduction to the culture of this land. The name…

Gaining Momentum, Losing Ground. Tapping America's Potential (TAP) Progress Report, 2008. Executive Summary

ERIC Educational Resources Information Center

Tapping America's Potential, 2008

2008-01-01

In July 2005, Business Roundtable and fifteen of America's most prominent business organizations--Tapping America's Potential, the TAP coalition--issued a report stating that "one of the pillars of American economic prosperity--U.S. scientific and technological superiority--is beginning to atrophy even as other nations are developing their own…

43 CFR 29.7 - Imposition of strict liability.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Pipeline and ports under the jurisdiction of the United States, and is carrying TAPS oil, the Owner and... discharge of TAPS oil from such vessel. Strict liability under this section shall cease when the TAPS oil... State law. (2) The Fund shall establish uniform procedures to determine whether claims from a TAPS oil...

The Ability to Tap to a Beat Relates to Cognitive, Linguistic, and Perceptual Skills

ERIC Educational Resources Information Center

Tierney, Adam T.; Kraus, Nina

2013-01-01

Reading-impaired children have difficulty tapping to a beat. Here we tested whether this relationship between reading ability and synchronized tapping holds in typically-developing adolescents. We also hypothesized that tapping relates to two other abilities. First, since auditory-motor synchronization requires monitoring of the relationship…

75 FR 82145 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-29

... Advocacy Panel (TAP) Tax Check Waiver. Abstract: Taxpayer Advocacy Panel (TAP) members must be compliant with their tax obligations and must undergo and pass a tax check in order to be selected as a TAP... otherwise confidential, to the Director of TAP to help in determining the suitability of the applicant for...

49 CFR 192.627 - Tapping pipelines under pressure.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 3 2010-10-01 2010-10-01 false Tapping pipelines under pressure. 192.627 Section... NATURAL AND OTHER GAS BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Operations § 192.627 Tapping pipelines under pressure. Each tap made on a pipeline under pressure must be performed by a crew qualified to make...

Lower extremity kinetics in tap dance.

PubMed

Mayers, Lester; Bronner, Shaw; Agraharasamakulam, Sujani; Ojofeitimi, Sheyi

2010-01-01

Tap dance is a unique performing art utilizing the lower extremities as percussion instruments. In a previous study these authors reported decreased injury prevalence among tap dancers compared to other dance and sports participants. No biomechanical analyses of tap dance exist to explain this finding. The purpose of the current pilot study was to provide a preliminary overview of normative peak kinetic and kinematic data, based on the hypothesis that tap dance generates relatively low ground reaction forces and joint forces and moments. Six professional tap dancers performed four common tap dance sequences that produced data captured by the use of a force platform and a five-camera motion analysis system. The mean vertical ground reaction force for all sequences was found to be 2.06+/-0.55 BW. Mean peak sagittal, frontal, and transverse plane joint moments (hip, knee, and ankle) ranged from 0.07 to 2.62 N.m/kg. These small ground reaction forces and joint forces and moments support our hypothesis, and may explain the relatively low injury incidence in tap dancers. Nevertheless, the analysis is highly complex, and other factors remain to be studied and clarified.

Effectiveness of Modal Decomposition for Tapping Atomic Force Microscopy Microcantilevers in Liquid Environment.

PubMed

Kim, Il Kwang; Lee, Soo Il

2016-05-01

The modal decomposition of tapping mode atomic force microscopy microcantilevers in liquid environments was studied experimentally. Microcantilevers with different lengths and stiffnesses and two sample surfaces with different elastic moduli were used in the experiment. The response modes of the microcantilevers were extracted as proper orthogonal modes through proper orthogonal decomposition. Smooth orthogonal decomposition was used to estimate the resonance frequency directly. The effects of the tapping setpoint and the elastic modulus of the sample under test were examined in terms of their multi-mode responses with proper orthogonal modes, proper orthogonal values, smooth orthogonal modes and smooth orthogonal values. Regardless of the stiffness of the microcantilever under test, the first mode was dominant in tapping mode atomic force microscopy under normal operating conditions. However, at lower tapping setpoints, the flexible microcantilever showed modal distortion and noise near the tip when tapping on a hard sample. The stiff microcantilever had a higher mode effect on a soft sample at lower tapping setpoints. Modal decomposition for tapping mode atomic force microscopy can thus be used to estimate the characteristics of samples in liquid environments.

Antigen discovery and delivery of subunit vaccines by nonliving bacterial ghost vectors.

PubMed

Walcher, Petra; Mayr, Ulrike B; Azimpour-Tabrizi, Chakameh; Eko, Francis O; Jechlinger, Wolfgang; Mayrhofer, Peter; Alefantis, Tim; Mujer, Cesar V; DelVecchio, Vito G; Lubitz, Werner

2004-12-01

The bacterial ghost (BG) platform system is a novel vaccine delivery system endowed with intrinsic adjuvant properties. BGs are nonliving Gram-negative bacterial cell envelopes which are devoid of their cytoplasmic contents, yet maintain their cellular morphology and antigenic structures, including bioadhesive properties. The main advantages of BGs as carriers of subunit vaccines include their ability to stimulate a high immune response and to target the carrier itself to primary antigen-presenting cells. The intrinsic adjuvant properties of BGs enhance the immune response to target antigens, including T-cell activation and mucosal immunity. Since native and foreign antigens can be carried in the envelope complex of BGs, combination vaccines with multiple antigens of diverse origin can be presented to the immune system simultaneously. Beside the capacity of BGs to function as carriers of protein antigens, they also have a high loading capacity for DNA. Thus, loading BGs with recombinant DNA takes advantage of the excellent bioavailability for DNA-based vaccines and the high expression rates of the DNA-encoded antigens in target cell types such as macrophages and dendritic cells. There are many spaces within BGs including the inner and outer membranes, the periplasmic space and the internal lumen which can carry antigens, DNA or mediators of the immune response. All can be used for subunit antigen to design new vaccine candidates with particle presentation technology. In addition, the fact that BGs can also carry piggyback large-size foreign antigen particles, increases the technologic usefulness of BGs as combination vaccines against viral and bacterial pathogens. Furthermore, the BG antigen carriers can be stored as freeze-dried preparations at room temperature for extended periods without loss of efficacy. The potency, safety and relatively low production cost of BGs offer a significant technical advantage over currently utilized vaccine technologies.

Clinical safety and effectiveness of transversus abdominis plane (TAP) block in post-operative analgesia: a systematic review and meta-analysis.

PubMed

Ma, Ning; Duncan, Joanna K; Scarfe, Anje J; Schuhmann, Susanne; Cameron, Alun L

2017-06-01

Transversus abdominis plane (TAP) blocks can provide analgesia postoperatively for a range of surgeries. Abundant clinical trials have assessed TAP block showing positive analgesic effects. This systematic review assesses safety and effectiveness outcomes of TAP block in all clinical settings, comparing with both active (standard care) and inactive (placebo) comparators. PubMed, EMBASE, The Cochrane Library and the University of York CRD databases were searched. RCTs were screened for their eligibility and assessed for risk of bias. Meta-analyses were performed on available data. TAP block showed an equivalent safety profile to all comparators in the incidence of nausea (OR = 1.07) and vomiting (OR = 0.81). TAP block was more effective in reducing morphine consumption [MD = 13.05, 95% CI (8.33, 51.23)] and in delaying time to first analgesic request [MD = 123.49, 95% CI (48.59, 198.39)]. Postoperative pain within 24 h was reduced or at least equivalent in TAP block compared to its comparators. Therefore, TAP block is a safe and effective procedure compared to standard care, placebo and other analgesic techniques. Further research is warranted to investigate whether the TAP block technique can be improved by optimizing dose and technique-related factors.

Evolution of transversus abdominis plane infiltration techniques for postsurgical analgesia following abdominal surgeries.

PubMed

Gadsden, Jeffrey; Ayad, Sabry; Gonzales, Jeffrey J; Mehta, Jaideep; Boublik, Jan; Hutchins, Jacob

2015-01-01

Transversus abdominis plane (TAP) infiltration is a regional anesthesia technique that has been demonstrated to be effective for management of postsurgical pain after abdominal surgery. There are several different clinical variations in the approaches used for achieving analgesia via TAP infiltration, and methods for identification of the TAP have evolved considerably since the landmark-guided technique was first described in 2001. There are many factors that impact the analgesic outcomes following TAP infiltration, and the various nuances of this technique have led to debate regarding procedural classification of TAP infiltration. Based on our current understanding of fascial and neuronal anatomy of the anterior abdominal wall, as well as available evidence from studies assessing local anesthetic spread and cutaneous sensory block following TAP infiltration, it is clear that TAP infiltration techniques are appropriately classified as field blocks. While the objective of peripheral nerve block and TAP infiltration are similar in that both approaches block sensory response in order to achieve analgesia, the technical components of the two procedures are different. Unlike peripheral nerve block, which involves identification or stimulation of a specific nerve or nerve plexus, followed by administration of a local anesthetic in close proximity, TAP infiltration involves administration and spread of local anesthetic within an anatomical plane of the surgical site.

Quantifying Parkinson's disease finger-tapping severity by extracting and synthesizing finger motion properties.

PubMed

Sano, Yuko; Kandori, Akihiko; Shima, Keisuke; Yamaguchi, Yuki; Tsuji, Toshio; Noda, Masafumi; Higashikawa, Fumiko; Yokoe, Masaru; Sakoda, Saburo

2016-06-01

We propose a novel index of Parkinson's disease (PD) finger-tapping severity, called "PDFTsi," for quantifying the severity of symptoms related to the finger tapping of PD patients with high accuracy. To validate the efficacy of PDFTsi, the finger-tapping movements of normal controls and PD patients were measured by using magnetic sensors, and 21 characteristics were extracted from the finger-tapping waveforms. To distinguish motor deterioration due to PD from that due to aging, the aging effect on finger tapping was removed from these characteristics. Principal component analysis (PCA) was applied to the age-normalized characteristics, and principal components that represented the motion properties of finger tapping were calculated. Multiple linear regression (MLR) with stepwise variable selection was applied to the principal components, and PDFTsi was calculated. The calculated PDFTsi indicates that PDFTsi has a high estimation ability, namely a mean square error of 0.45. The estimation ability of PDFTsi is higher than that of the alternative method, MLR with stepwise regression selection without PCA, namely a mean square error of 1.30. This result suggests that PDFTsi can quantify PD finger-tapping severity accurately. Furthermore, the result of interpreting a model for calculating PDFTsi indicated that motion wideness and rhythm disorder are important for estimating PD finger-tapping severity.

Persistent suppression of subthalamic beta-band activity during rhythmic finger tapping in Parkinson's disease.

PubMed

Joundi, Raed A; Brittain, John-Stuart; Green, Alex L; Aziz, Tipu Z; Brown, Peter; Jenkinson, Ned

2013-03-01

The function of synchronous oscillatory activity at beta band (15-30Hz) frequencies within the basal ganglia is unclear. Here we sought support for the hypothesis that beta activity has a global function within the basal ganglia and is not directly involved in the coding of specific biomechanical parameters of movement. We recorded local field potential activity from the subthalamic nuclei of 11 patients with Parkinson's disease during a synchronized tapping task at three different externally cued rates. Beta activity was suppressed during tapping, reaching a minimum that differed little across the different tapping rates despite an increase in velocity of finger movements. Thus beta power suppression was independent of specific motor parameters. Moreover, although beta oscillations remained suppressed during all tapping rates, periods of resynchronization between taps were markedly attenuated during high rate tapping. As such, a beta rebound above baseline between taps at the lower rates was absent at the high rate. Our results demonstrate that beta desynchronization in the region of the subthalamic nucleus is independent of motor parameters and that the beta resynchronization is differentially modulated by rate of finger tapping, These findings implicate consistent beta suppression in the facilitation of continuous movement sequences. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Impact analysis of tap switch out of step for converter transformer

NASA Astrophysics Data System (ADS)

Hong-yue, ZHANG; Zhen-hua, ZHANG; Zhang-xue, XIONG; Gao-wang, YU

2017-06-01

AC transformer load regulation is mainly used to adjust the load side voltage level, improve the quality of power supply, the voltage range is relatively narrow. In DC system, converter transformer is the core equipment of AC and DC power converter and inverter. converter transformer tap adjustment can maintain the normal operation of the converter in small angle range control, the absorption of reactive power, economic operation, valve less stress, valve damping circuit loss, AC / DC harmonic component is also smaller. In this way, the tap switch action is more frequent, and a large range of the tap switch adjustment is required. Converter transformer with a more load voltage regulation switch, the voltage regulation range of the switch is generally 20~30%, the adjustment of each file is 1%~2%. Recently it is often found that the tap switch of Converter Transformers is out of step in Converter station. In this paper, it is analyzed in detail the impact of tap switch out of step for differential protection, overexcitation protection and zero sequence over current protection. Analysis results show that: the tap switch out of step has no effect on the differential protection and the overexcitation protection including the tap switch. But the tap switch out of step has effect on zero sequence overcurrent protection of out of step star-angle converter transformer. The zero sequence overcurrent protection will trip when the tap switch out of step is greater than 3 for out of step star-angle converter transformer.

Finger tapping ability in healthy elderly and young adults.

PubMed

Aoki, Tomoko; Fukuoka, Yoshiyuki

2010-03-01

The maximum isometric force production capacity of the fingers decreases with age. However, little information is available on age-related changes in dynamic motor capacity of individual fingers. The purpose of this study was to compare the dynamic motor function of individual fingers between elderly and young adults using rapid single-finger and double-finger tapping. Fourteen elderly and 14 young adults performed maximum frequency tapping by the index, middle, ring, or little finger (single-finger tapping) and with alternate movements of the index-middle, middle-ring, or ring-little finger-pair (double-finger tapping). The maximum pinch force between the thumb and each finger, tactile sensitivity of each fingertip, and time taken to complete a pegboard test were also measured. Compared with young subjects, the older subjects had significantly slower tapping rates in all fingers and finger-pairs in the tapping tasks. The age-related decline was also observed in the tactile sensitivities of all fingers and in the pegboard test. However, there was no group difference in the pinch force of any finger. The tapping rate of each finger did not correlate with the pinch force or tactile sensitivity for the corresponding finger in the elderly subjects. Maximum rate of finger tapping was lower in the elderly adults compared with the young adults. The decline of finger tapping ability in elderly adults seems to be less affected by their maximum force production capacities of the fingers as well as tactile sensitivities at the tips of the fingers.

"Transversus Abdominis Plane Blocks in Microsurgical Breast Reconstruction: Analysis of Pain, Narcotic Consumption, Length of Stay and Cost."

PubMed

Salibian, Ara A; Frey, Jordan D; Thanik, Vishal D; Karp, Nolan S; Choi, Mihye

2018-06-02

Transversus abdominis plane (TAP) blocks are increasingly being utilized in microvascular breast reconstruction. The implications of TAP blocks on specific reconstructive, patient and institutional outcomes remain to be fully elucidated. Patients undergoing abdominally-based microvascular breast reconstruction from 2015-2017 were reviewed. Length of stay, complications, narcotic consumption, donor-site pain and hospital expenses were compared between patients that did and those that did not receive TAP blocks with liposomal bupivacaine. Outcomes were subsequently compared in patients with elevated body mass index (BMI). Fifty patients (43.9%) received TAP blocks (27 [54.0%] under ultrasound guidance) and 64 patients (56.1%) did not. Patients with TAP blocks had significantly decreased oral and total narcotic consumption (p=0.0001 and p<0.0001, respectively) as well as significantly less donor-site pain (3.3 versus 4.3, p<0.0001). There was no significant difference in hospital expenses between the two cohorts ($21,531.53 versus $22,050.15 per patient, p=0.5659). Patients with BMI≥25 who received TAP blocks had a significantly decreased length of stay (3.8 versus 4.4 days, p=0.0345) as well as decreased narcotic consumption and postoperative pain compared to patients without TAP blocks. Patients with BMI<25 did not have a significant difference in postoperative pain, narcotic consumption or length of stay between the TAP versus no TAP block groups. TAP blocks with liposomal bupivacaine significantly reduce oral and total postoperative narcotic consumption as well as donor-site pain in all patients after abdominally-based microvascular breast reconstruction without increasing hospital expenses. TAP blocks additionally significantly decrease length of stay in patients with BMI≥25.

Determination of physicochemical properties and degradation kinetics of triamcinolone acetonide palmitate in vitro.

PubMed

Peng, Cuilian; Liu, Cong; Tang, Xing

2010-12-01

Triamcinolone acetonide palmitate (TAP) is a lipophilic prodrug of triamcinolone acetonide (TAA) to improve the insoluble TAA physicochemical properties for the preparation of emulsions. This investigation has focused on the preformulation study of TAP, including its physicochemical properties and hydrolysis kinetics in vitro. The solubility of TAP in medium-chain triglyceride is about twice greater than that in soybean oil (long-chain triglyceride) (19.17 versus 9.55 mg/g) at 25°C, and in all investigated cases, lecithin (80, 160, and 240 mg/g) as solubilizer provided increased solubility of drugs in medium-chain triglyceride and long-chain triglyceride, whereas the maximum water solubility of TAP was 0.10 μg/mL. The partition coefficient (log P) of TAP was 5.79 irrespective of the pH conditions. The hydrolysis of TAP followed pseudo-first-order kinetics in aqueous solutions, and the stable pH range was from pH 5.0 to 9.0. The in vitro enzymolysis kinetics of TAP in rat plasma and liver homogenate was evaluated by measuring the decrease of TAP as well as the increase of TAA at 37°C for 96 hours. The results demonstrated that the TAP may be hydrolyzed mainly by rat plasma esterase and, to a minor extent, by liver esterase, and the hydrolysis half-life of TAP in 100% rat plasma was 17.53 ± 6.85 hours at pH 7.4. All these results indicated that TAP had successfully obtained higher lipid-soluble property for the preparation of intravenous emulsion and may be an effective prodrug for sustained release of TAA in vivo.

Placental share and hemoglobin level in relation to birth weight in twin anemia-polycythemia sequence.

PubMed

Zhao, D; Slaghekke, F; Middeldorp, J M; Duan, T; Oepkes, D; Lopriore, E

2014-12-01

Twin anemia-polycythemia sequence (TAPS) is a newly described form of chronic twin transfusion. Previous observational studies noted a discordance between birth weight and individual placental share in TAPS. The purpose of this study was to investigate if fetal growth in monochorionic (MC) twins with TAPS is determined by placental share or by the net inter-twin blood transfusion. All consecutive MC twin placentas of live-born twin pairs with and without TAPS examined at our center between June 2002 and February 2014 were included in this study. Hemoglobin (Hb) levels and individual placental share were evaluated at birth and correlated with birth weight share. We excluded MC twin pregnancies with twin-twin transfusion syndrome. A total of 270 MC twin pregnancies (TAPS group, n = 20; control group without TAPS, n = 250) were included in this study. Donors with TAPS had a lower birth weight than recipients in 90% (18/20) of cases, but a larger placental share in 65% (13/20) of cases. In the TAPS group, birth weight share was positively correlated with Hb share at birth (P < 0.01) but not with placental share (P = 0.54). In the control group without TAPS, birth weight share was strongly correlated with placental share (P < 0.01) but not with Hb share (P = 0.14). A relatively larger placental share may enable the survival of the anemic twin in TAPS. In contrast with uncomplicated MC twins, fetal growth in MC twins with TAPS is determined primarily by the net inter-twin blood transfusion instead of placental share. Copyright © 2014 Elsevier Ltd. All rights reserved.

The gene for a lectin-like protein is transcriptionally activated during sexual development, but is not essential for fruiting body formation in the filamentous fungus Sordaria macrospora.

PubMed

Nowrousian, Minou; Cebula, Patricia

2005-11-03

The filamentous fungus Sordaria macrospora forms complex three-dimensional fruiting bodies called perithecia that protect the developing ascospores and ensure their proper discharge. In previous microarray analyses, several genes have been identified that are downregulated in sterile mutants compared to the wild type. Among these genes was tap1 (transcript associated with perithecial development), a gene encoding a putative lectin homolog. Analysis of tap1 transcript levels in the wild type under conditions allowing only vegetative growth compared to conditions that lead to fruiting body development showed that tap1 is not only downregulated in developmental mutants but is also upregulated in the wild type during fruiting body development. We have cloned and sequenced a 3.2 kb fragment of genomic DNA containing the tap1 open reading frame and adjoining sequences. The genomic region comprising tap1 is syntenic to its homologous region in the closely related filamentous fungus Neurospora crassa. To determine whether tap1 is involved in fruiting body development in S. macrospora, a knockout construct was generated in which the tap1 open reading frame was replaced by the hygromycin B resistance gene hph under the control of fungal regulatory regions. Transformation of the S. macrospora wild type with this construct resulted in a tap1 deletion strain where tap1 had been replaced by the hph cassette. The knockout strain displayed no phenotypic differences under conditions of vegetative growth and sexual development when compared to the wild type. Double mutants carrying the Deltatap1 allele in several developmental mutant backgrounds were phenotypically similar to the corresponding developmental mutant strains. The tap1 transcript is strongly upregulated during sexual development in S. macrospora; however, analysis of a tap1 knockout strain shows that tap1 is not essential for fruiting body formation in S. macrospora.

P32/TAP, a cellular protein that interacts with EBNA-1 of Epstein-Barr virus.

PubMed

Wang, Y; Finan, J E; Middeldorp, J M; Hayward, S D

1997-09-15

The Epstein-Barr virus (EBV) EBNA-1 protein has a central role in the maintenance of a latent EBV infection and is the only virus-encoded protein expressed in all EBV-associated tumors. EBNA-1 is required for replication of the episomal form of the latent viral genome and transactivates the latency C and LMP-1 promoters. The mechanisms by which EBNA-1 performs these functions are not known. Here we describe the cloning, expression, and characterization of a cellular protein, P32/TAP, which strongly interacts with EBNA-1. We show that P32/TAP is expressed at high levels in Raji cells and is synthesized as a proprotein of 282 amino acids (aa) that is posttranslationally processed by a two-step cleavage process to yield a mature protein of 209 aa. It has been previously reported that P32/TAP is expressed on the cell surface. Our transient expression assays detected full-length P32/TAP (1-282 aa) in the cytoplasm while mature P32/TAP protein localized to the nucleus. Three lines of evidence support P32/TAP interaction with EBNA-1. First, in the yeast two-hybrid system we mapped two interactive N-terminal regions of EBNA-1, aa 40-60 and aa 325-376, each of which contains arginine-glycine repeats. These regions interact with the C-terminal half of P32/TAP. Second, the full-length cytoplasmic P32/TAP protein can translocate nuclear EBNA-1 into the cytoplasm. Third, P32/TAP co-immunoprecipitated with EBNA-1. We have confirmed that a Gal4 fusion protein containing the C-terminal region of P32/TAP (aa 244-282) transactivates expression from a reporter containing upstream Gal4-binding sites. Deletion of the P32/TAP interactive regions of EBNA-1 severely diminished EBNA-1 transactivation of FRTKCAT in transient expression assays. Our data suggest that interaction with P32/TAP may contribute to EBNA-1-mediated transactivation. Copyright 1997 Academic Press.

A Single Subset of Dendritic Cells Controls the Cytokine Bias of Natural Killer T Cell Responses to Diverse Glycolipid Antigens

PubMed Central

Arora, Pooja; Baena, Andres; Yu, Karl O.A.; Saini, Neeraj K.; Kharkwal, Shalu S.; Goldberg, Michael F.; Kunnath-Velayudhan, Shajo; Carreño, Leandro J.; Venkataswamy, Manjunatha M.; Kim, John; Lazar-Molnar, Eszter; Lauvau, Gregoire; Chang, Young-tae; Liu, Zheng; Bittman, Robert; Al-Shamkhani, Aymen; Cox, Liam R.; Jervis, Peter J.; Veerapen, Natacha; Besra, Gurdyal S.; Porcelli, Steven A.

2014-01-01

Summary Many hematopoietic cell types express CD1d and are capable of presenting glycolipid antigens to invariant natural killer T cells (iNKT cells). However, the question of which cells are the principal presenters of glycolipid antigens in vivo remains controversial, and it has been suggested that this might vary depending on the structure of a particular glycolipid antigen. Here we have shown that a single type of cell, the CD8α+ DEC-205+ dendritic cell, was mainly responsible for capturing and presenting a variety of different glycolipid antigens, including multiple forms of α-galactosylceramide that stimulate widely divergent cytokine responses. After glycolipid presentation, these dendritic cells rapidly altered their expression of various costimulatory and coinhibitory molecules in a manner that was dependent on the structure of the antigen. These findings show flexibility in the outcome of two-way communication between CD8α+ dendritic cells and iNKT cells, providing a mechanism for biasing toward either proinflammatory or anti-inflammatory responses. PMID:24412610

Understanding MHC Class I Presentation of Viral Antigens by Human Dendritic Cells as a Basis for Rational Design of Therapeutic Vaccines

PubMed Central

van Montfoort, Nadine; van der Aa, Evelyn; Woltman, Andrea M.

2014-01-01

Effective viral clearance requires the induction of virus-specific CD8+ cytotoxic T lymphocytes (CTL). Since dendritic cells (DC) have a central role in initiating and shaping virus-specific CTL responses, it is important to understand how DC initiate virus-specific CTL responses. Some viruses can directly infect DC, which theoretically allow direct presentation of viral antigens to CTL, but many viruses target other cells than DC and thus the host depends on the cross-presentation of viral antigens by DC to activate virus-specific CTL. Research in mouse models has highly enhanced our understanding of the mechanisms underlying cross-presentation and the dendritic cells (DC) subsets involved, however, these results cannot be readily translated toward the role of human DC in MHC class I-antigen presentation of human viruses. Here, we summarize the insights gained in the past 20 years on MHC class I presentation of viral antigen by human DC and add to the current debate on the capacities of different human DC subsets herein. Furthermore, possible sources of viral antigens and essential DC characteristics for effective induction of virus-specific CTL are evaluated. We conclude that cross-presentation is not only an efficient mechanism exploited by DC to initiate immunity to viruses that do not infect DC but also to viruses that do infect DC, because cross-presentation has many conceptual advantages and bypasses direct immune modulatory effects of the virus on its infected target cells. Since knowledge on the mechanism of viral antigen presentation and the preferred DC subsets is crucial for rational vaccine design, the obtained insights are very instrumental for the development of effective anti-viral immunotherapy. PMID:24795724

Effector CD4+ T cells recognize intravascular antigen presented by patrolling monocytes.

PubMed

Westhorpe, Clare L V; Norman, M Ursula; Hall, Pam; Snelgrove, Sarah L; Finsterbusch, Michaela; Li, Anqi; Lo, Camden; Tan, Zhe Hao; Li, Songhui; Nilsson, Susan K; Kitching, A Richard; Hickey, Michael J

2018-02-21

Although effector CD4 + T cells readily respond to antigen outside the vasculature, how they respond to intravascular antigens is unknown. Here we show the process of intravascular antigen recognition using intravital multiphoton microscopy of glomeruli. CD4 + T cells undergo intravascular migration within uninflamed glomeruli. Similarly, while MHCII is not expressed by intrinsic glomerular cells, intravascular MHCII-expressing immune cells patrol glomerular capillaries, interacting with CD4 + T cells. Following intravascular deposition of antigen in glomeruli, effector CD4 + T-cell responses, including NFAT1 nuclear translocation and decreased migration, are consistent with antigen recognition. Of the MHCII + immune cells adherent in glomerular capillaries, only monocytes are retained for prolonged durations. These cells can also induce T-cell proliferation in vitro. Moreover, monocyte depletion reduces CD4 + T-cell-dependent glomerular inflammation. These findings indicate that MHCII + monocytes patrolling the glomerular microvasculature can present intravascular antigen to CD4 + T cells within glomerular capillaries, leading to antigen-dependent inflammation.

Polymer nanoparticles for cross-presentation of exogenous antigens and enhanced cytotoxic T-lymphocyte immune response

PubMed Central

Song, Chanyoung; Noh, Young-Woock; Lim, Yong Taik

2016-01-01

Effective induction of an antigen-specific cytotoxic T lymphocyte (CTL) immune response is one of the key goals of cancer immunotherapy. We report the design and fabrication of polyethylenimine (PEI)-coated polymer nanoparticles (NPs) as efficient antigen-delivery carriers that can induce antigen cross-presentation and a strong CTL response. After synthesis of poly(d,l-lactide-co-glycolide) (PLGA) NPs containing ovalbumin (OVA) by the double-emulsion solvent-evaporation method, cationic-charged PLGA NPs were generated by coating them with PEI. In a methyl tetrazolium salt assay, no discernible cytotoxic effect of PEI-coated PLGA (OVA) NPs was observed. The capacity and mechanism of PEI-coated PLGA (OVA) NPs for antigen delivery and cross-presentation on dendritic cells (DCs) were determined by fluorescence microscopy and flow cytometry. PEI-coated PLGA (OVA) NPs were internalized efficiently via phagocytosis or macropinocytosis in DCs and induced efficient cross-presentation of the antigen on MHC class I molecules via both endosome escape and a lysosomal processing mechanism. The DCs treated with PEI-coated PLGA (OVA) NPs induced a release of IL-2 cytokine from OVA-specific CD8-OVA1.3 T cells more efficiently than DCs treated with PLGA (OVA) NPs. Therefore, the PEI-coated PLGA (OVA) NPs can induce antigen cross-presentation and are expected to be used for induction of a strong CTL immune response and for efficient anticancer immunotherapy. PMID:27540289

IMMUNOGLOBULIN ISOANTIGENS (ALLOTYPES) IN THE MOUSE

PubMed Central

Herzenberg, Leonard A.; Warner, Noel L.; Herzenberg, Leonore A.

1965-01-01

Eight antigens of 7S γ2-immunoglobulins controlled by alleles at a single locus Ig-1, have been identified in mice. This locus has previously been shown to determine antigenic specificities on the F fragments of 7S γ2a-globulins. The reactions of these antigens with various isoantisera have shown that the antigens all cross react with one another. New methods for the analysis of antigenic specificities of soluble proteins are presented in detail. A sensitive method for detecting in the order of 0.01 µg of these isoantigens has been developed, based on the quantitative inhibition of precipitation of I125-labeled antigen. Cross-reactions of the antigens were analysed in inhibition assays and the data is compatible with the existence of a minimum of eight antigenic specificities. Each of the antigens is composed of different combinations of these specificities, with only one antigen having a specificity not present in any other. Sixty-eight mouse strains have been tested with specific isoantisera, and on the basis of the results, have been placed into the eight allele groups. Evidence for close genetic linkage of the Ig-1 locus and 11 chromosome markers has been sought and not found. PMID:14270242

Crown discoloration promoted by materials used in regenerative endodontic procedures and effect of dental bleaching: spectrophotometric analysis.

PubMed

Santos, Luciane Geanini Pena Dos; Felippe, Wilson Tadeu; Souza, Beatriz Dulcineia Mendes de; Konrath, Andrea Cristina; Cordeiro, Mabel Mariela Rodríguez; Felippe, Mara Cristina Santos

2017-01-01

To assess tooth crown's color after intracanal treatment with triple antibiotic paste (TAP) or calcium hydroxide (CH); cervical sealing with glass ionomer cement (GIC) or mineral trioxide aggregate (MTA); and bleaching with carbamide peroxide. After pulp removal and color spectrophotometer measurement, 50 bovine incisors were divided into 4 experimental groups and one control (untreated). Experiments were performed in phases (Ph). Ph1: TAP (ciprofloxacin, metronidazole, minocycline), TAPM (ciprofloxacin, metronidazole, amoxicillin), DAP (ciprofloxacin, metronidazole), or CH treatment groups. After 1 and 3 days (d); 1, 2, 3 weeks (w); and 1, 2, 3 and 4 months (m), color was measured and medications were removed. Ph2: GIC or MTA cervical sealing, each using half of the specimens from each group. Color was assessed after 1d, 3d; 1w, 2w, 3w; 1m and 2m. Ph3: Two bleaching sessions, each followed by color measurement. Data were analyzed with ANOVA and post-hoc Holm-Sidak method. Ph1: Specimens of TAP group presented higher color alteration (ΔE) mean than those of TAPM group. No significant difference was found among TAP or TAPM and CH, DAP or Control groups. Ph2: cervical sealing materials showed no influence on color alteration. Ph3: Different ΔE means (from different groups), prior to bleaching, became equivalent after one bleaching session. TAP induces higher color alteration than TAPM; color alteration increases over time; cervical sealing material has no influence on color alteration; and, dental bleaching was able to recover, at least partially, the tooth crown's color.

High quality-factor quartz tuning fork glass probe used in tapping mode atomic force microscopy for surface profile measurement

NASA Astrophysics Data System (ADS)

Chen, Yuan-Liu; Xu, Yanhao; Shimizu, Yuki; Matsukuma, Hiraku; Gao, Wei

2018-06-01

This paper presents a high quality-factor (Q-factor) quartz tuning fork (QTF) with a glass probe attached, used in frequency modulation tapping mode atomic force microscopy (AFM) for the surface profile metrology of micro and nanostructures. Unlike conventionally used QTFs, which have tungsten or platinum probes for tapping mode AFM, and suffer from a low Q-factor influenced by the relatively large mass of the probe, the glass probe, which has a lower density, increases the Q-factor of the QTF probe unit allowing it to obtain better measurement sensitivity. In addition, the process of attaching the probe to the QTF with epoxy resin, which is necessary for tapping mode AFM, is also optimized to further improve the Q-factor of the QTF glass probe. The Q-factor of the optimized QTF glass probe unit is demonstrated to be very close to that of a bare QTF without a probe attached. To verify the effectiveness and the advantages of the optimized QTF glass probe unit, the probe unit is integrated into a home-built tapping mode AFM for conducting surface profile measurements of micro and nanostructures. A blazed grating with fine tool marks of 100 nm, a microprism sheet with a vertical amplitude of 25 µm and a Fresnel lens with a steep slope of 90 degrees are used as measurement specimens. From the measurement results, it is demonstrated that the optimized QTF glass probe unit can achieve higher sensitivity as well as better stability than conventional probes in the measurement of micro and nanostructures.

Interdisciplinary development of manual and automated product usability assessments for older adults with dementia: lessons learned.

PubMed

Boger, Jennifer; Taati, Babak; Mihailidis, Alex

2016-10-01

The changes in cognitive abilities that accompany dementia can make it difficult to use everyday products that are required to complete activities of daily living. Products that are inherently more usable for people with dementia could facilitate independent activity completion, thus reducing the need for caregiver assistance. The objectives of this research were to: (1) gain an understanding of how water tap design impacted tap usability and (2) create an automated computerized tool that could assess tap usability. 27 older adults, who ranged from cognitively intact to advanced dementia, completed 1309 trials on five tap designs. Data were manually analyzed to investigate tap usability as well as used to develop an automated usability analysis tool. Researchers collaborated to modify existing techniques and to create novel ones to accomplish both goals. This paper presents lessons learned through the course of this research, which could be applicable in the development of other usability studies, automated vision-based assessments and the development of assistive technologies for cognitively impaired older adults. Collaborative interdisciplinary teamwork, which included older adult with dementia participants, was key to enabling innovative advances that achieved the projects' research goals. Implications for Rehabilitation Products that are implicitly familiar and usable by older adults could foster independent activity completion, potentially reducing reliance on a caregiver. The computer-based automated tool can significantly reduce the time and effort required to perform product usability analysis, making this type of analysis more feasible. Interdisciplinary collaboration can result in a more holistic understanding of assistive technology research challenges and enable innovative solutions.

Molecular cloning and in-silico characterization of high temperature stress responsive pAPX gene isolated from heat tolerant Indian wheat cv. Raj 3765.

PubMed

Padaria, Jasdeep Chatrath; Vishwakarma, Harinder; Biswas, Koushik; Jasrotia, Rahul Singh; Singh, Gyanendra Pratap

2014-10-10

Heat stress leads to accelerated production of reactive oxygen species (ROS) which causes a huge amount of oxidative damage to the cellular components of plants. A large number of heat stress related genes as HSPs, catalases, peroxidases are overexpressed at the time of stress. A potent stress responsive gene peroxisomal ascorbate peroxidase (TapAPX) obtained from heat stress (42 °C) responsive subtractive cDNA library from a thermo tolerant wheat cv. Raj3765 at anthesis stage was cloned, characterized and its role was validated under heat stress by proteomics and in-silico studies. In the present study we report the characterization at molecular and in-silico level of peroxisomal TapAPX gene isolated from heat tolerant wheat cultivar of India. qPCR studies of TapAPX gene displayed up to 203 fold level of expression at 42 °C heat stress exposure. A full length cDNA of 876 bp obtained by RACE deduced a protein of 292 amino acid residues which gives a complete 3D structure of pAPX by homology modeling. TapAPX cDNA was cloned in expression vector pET28 (a+) and the recombinant protein over-expressed in E. coli BL21 showed highest homology with APX protein as deduced by peptide mass fingerprinting. TapAPX gene from wheat cv Raj3765 has a distinct role in conferring thermo tolerance to the plants and thus can be used in crop improvement programmes for development of crops tolerant to high temperature.

Exploiting the pliability and lateral mobility of Pickering emulsion for enhanced vaccination

NASA Astrophysics Data System (ADS)

Xia, Yufei; Wu, Jie; Wei, Wei; Du, Yiqun; Wan, Tao; Ma, Xiaowei; An, Wenqi; Guo, Aiying; Miao, Chunyu; Yue, Hua; Li, Shuoguo; Cao, Xuetao; Su, Zhiguo; Ma, Guanghui

2018-02-01

A major challenge in vaccine formulations is the stimulation of both the humoral and cellular immune response for well-defined antigens with high efficacy and safety. Adjuvant research has focused on developing particulate carriers to model the sizes, shapes and compositions of microbes or diseased cells, but not antigen fluidity and pliability. Here, we develop Pickering emulsions--that is, particle-stabilized emulsions that retain the force-dependent deformability and lateral mobility of presented antigens while displaying high biosafety and antigen-loading capabilities. Compared with solid particles and conventional surfactant-stabilized emulsions, the optimized Pickering emulsions enhance the recruitment, antigen uptake and activation of antigen-presenting cells, potently stimulating both humoral and cellular adaptive responses, and thus increasing the survival of mice upon lethal challenge. The pliability and lateral mobility of antigen-loaded Pickering emulsions may provide a facile, effective, safe and broadly applicable strategy to enhance adaptive immunity against infections and diseases.

Collective Genetic Interaction Effects and the Role of Antigen Presenting Cells in Autoimmune Diseases

DTIC Science & Technology

2017-01-12

RESEARCH ARTICLE Collective Genetic Interaction Effects and the Role of Antigen-Presenting Cells in Autoimmune Diseases Hyung Jun Woo*, Chenggang Yu...autoimmunity. Genetic predispositions center around the major histocompatibility complex (MHC) class II loci involved in antigen presentation, the key...helper and regulatory T cells showing strong dis- ease-associated interactions with B cells. Our results provide direct genetic evidence point- ing to

Interaction of Perceptual Grouping and Crossmodal Temporal Capture in Tactile Apparent-Motion

PubMed Central

Chen, Lihan; Shi, Zhuanghua; Müller, Hermann J.

2011-01-01

Previous studies have shown that in tasks requiring participants to report the direction of apparent motion, task-irrelevant mono-beeps can “capture” visual motion perception when the beeps occur temporally close to the visual stimuli. However, the contributions of the relative timing of multimodal events and the event structure, modulating uni- and/or crossmodal perceptual grouping, remain unclear. To examine this question and extend the investigation to the tactile modality, the current experiments presented tactile two-tap apparent-motion streams, with an SOA of 400 ms between successive, left-/right-hand middle-finger taps, accompanied by task-irrelevant, non-spatial auditory stimuli. The streams were shown for 90 seconds, and participants' task was to continuously report the perceived (left- or rightward) direction of tactile motion. In Experiment 1, each tactile stimulus was paired with an auditory beep, though odd-numbered taps were paired with an asynchronous beep, with audiotactile SOAs ranging from −75 ms to 75 ms. Perceived direction of tactile motion varied systematically with audiotactile SOA, indicative of a temporal-capture effect. In Experiment 2, two audiotactile SOAs—one short (75 ms), one long (325 ms)—were compared. The long-SOA condition preserved the crossmodal event structure (so the temporal-capture dynamics should have been similar to that in Experiment 1), but both beeps now occurred temporally close to the taps on one side (even-numbered taps). The two SOAs were found to produce opposite modulations of apparent motion, indicative of an influence of crossmodal grouping. In Experiment 3, only odd-numbered, but not even-numbered, taps were paired with auditory beeps. This abolished the temporal-capture effect and, instead, a dominant percept of apparent motion from the audiotactile side to the tactile-only side was observed independently of the SOA variation. These findings suggest that asymmetric crossmodal grouping leads to an attentional modulation of apparent motion, which inhibits crossmodal temporal-capture effects. PMID:21383834

Observation Data Model Core Components, its Implementation in the Table Access Protocol Version 1.1

NASA Astrophysics Data System (ADS)

Louys, Mireille; Tody, Doug; Dowler, Patrick; Durand, Daniel; Michel, Laurent; Bonnarel, Francos; Micol, Alberto; IVOA DataModel Working Group; Louys, Mireille; Tody, Doug; Dowler, Patrick; Durand, Daniel

2017-05-01

This document defines the core components of the Observation data model that are necessary to perform data discovery when querying data centers for astronomical observations of interest. It exposes use-cases to be carried out, explains the model and provides guidelines for its implementation as a data access service based on the Table Access Protocol (TAP). It aims at providing a simple model easy to understand and to implement by data providers that wish to publish their data into the Virtual Observatory. This interface integrates data modeling and data access aspects in a single service and is named ObsTAP. It will be referenced as such in the IVOA registries. In this document, the Observation Data Model Core Components (ObsCoreDM) defines the core components of queryable metadata required for global discovery of observational data. It is meant to allow a single query to be posed to TAP services at multiple sites to perform global data discovery without having to understand the details of the services present at each site. It defines a minimal set of basic metadata and thus allows for a reasonable cost of implementation by data providers. The combination of the ObsCoreDM with TAP is referred to as an ObsTAP service. As with most of the VO Data Models, ObsCoreDM makes use of STC, Utypes, Units and UCDs. The ObsCoreDM can be serialized as a VOTable. ObsCoreDM can make reference to more complete data models such as Characterisation DM, Spectrum DM or Simple Spectral Line Data Model (SSLDM). ObsCore shares a large set of common concepts with DataSet Metadata Data Model (Cresitello-Dittmar et al. 2016) which binds together most of the data model concepts from the above models in a comprehensive and more general frame work. This current specification on the contrary provides guidelines for implementing these concepts using the TAP protocol and answering ADQL queries. It is dedicated to global discovery.

Self-modulation of primary motor cortex activity with motor and motor imagery tasks using real-time fMRI-based neurofeedback

PubMed Central

Berman, Brian D.; Horovitz, Silvina G.; Venkataraman, Gaurav; Hallett, Mark

2011-01-01

Advances in fMRI data acquisition and processing have made it possible to analyze brain activity as rapidly as the images are acquired allowing this information to be fed back to subjects in the scanner. The ability of subjects to learn to volitionally control localized brain activity within motor cortex using such real-time fMRI-based neurofeedback (NF) is actively being investigated as it may have clinical implications for motor rehabilitation after central nervous system injury and brain-computer interfaces. We investigated the ability of fifteen healthy volunteers to use NF to modulate brain activity within the primary motor cortex (M1) during a finger tapping and tapping imagery task. The M1 hand area ROI (ROIm) was functionally localized during finger tapping and a visual representation of BOLD signal changes within the ROIm fed back to the subject in the scanner. Surface EMG was used to assess motor output during tapping and ensure no motor activity was present during motor imagery task. Subjects quickly learned to modulate brain activity within their ROIm during the finger-tapping task, which could be dissociated from the magnitude of the tapping, but did not show a significant increase within the ROIm during the hand motor imagery task at the group level despite strongly activating a network consistent with the performance of motor imagery. The inability of subjects to modulate M1 proper with motor imagery may reflect an inherent difficulty in activating synapses in this area, with or without NF, since such activation may lead to M1 neuronal output and obligatory muscle activity. Future real-time fMRI-based NF investigations involving motor cortex may benefit from focusing attention on cortical regions other than M1 for feedback training or alternative feedback strategies such as measures of functional connectivity within the motor system. PMID:21803163

Allogeneic substitution for nominal antigen-specific T-cell clone reactivity in schistosomiasis.

PubMed Central

Linette, G P; Lammie, P J; Phillips, S M

1986-01-01

The present studies have established the nature of a T-cell clone which demonstrates dual reactivity directed against Schistosoma mansoni antigen presented by syngeneic antigen presenting cells and against allogeneic cells. Clone G4, when stimulated by either antigen (SEA) or allogeneic cells (PL/J), exhibits similar functional and phenotypic characteristics. A subclone of G4, G4A.1, which has been maintained in continuous mixed lymphocyte culture for 12 months (in the absence of SEA), retains comparable reactivity with respect to proliferation and ability to produce lymphokines, transfer delayed-type hypersensitivity, and produce in vitro granulomas in response to SEA. Normal antigenic stimulation is highly contingent upon I-Ab compatibility while antibody blocking experiments map allo-reactivity to I-Eu. The failure of B10.PL spleen cells to stimulate G4, however, suggests that alloreactivity may be directed against the recently described Mls X locus. Both allogeneic and nominal antigen induced T-cell activation are blocked by antibody directed against L3T4A, confirming Class II MHC restriction for both types of stimulation. These studies suggest that stimulation of T cells by either alloantigen or nominal antigen elicits qualitatively similar functional profiles, and further suggest the feasibility of producing large numbers of nominal antigen reactive cloned T cells in the absence of nominal antigen under mixed lymphocyte culture conditions. PMID:2420707

49 CFR 179.200-9 - Compartment tanks.

Code of Federal Regulations, 2010 CFR

2010-10-01

... must be provided with at least one tapped drain hole at their lowest point, and a tapped hole at the... between heads of tanks joined together to form a compartment tank shall be provided with a tapped drain hole at their lowest point and a tapped hole at top of tank. The top hole shall be closed and the...

Oropharyngeal Tularemia Outbreak Associated with Drinking Contaminated Tap Water, Turkey, July-September 2013.

PubMed

Aktas, Dilber; Celebi, Bekir; Isik, Mehmet Emirhan; Tutus, Celal; Ozturk, Huseyin; Temel, Fehminaz; Kizilaslan, Mecit; Zhu, Bao-Ping

2015-12-01

In 2013, an oropharyngeal tularemia outbreak in Turkey affected 55 persons. Drinking tap water during the likely exposure period was significantly associated with illness (attack rate 27% vs. 11% among non-tap water drinkers). Findings showed the tap water source had been contaminated by surface water, and the chlorination device malfunctioned.

NASA/UK TAP

NASA Technical Reports Server (NTRS)

1987-01-01

The purpose of the Technology Applications Program (TAP) is to provide problem solving information and assistance to both the public and private sectors in the Commonwealth of Kentucky, with emphasis primarily in the public sector. The TAP accesses over 1200 online computer databases, including files from the U.S., Canada, Europe, and Australia. During the 1985 to 1986 contract period, TAP responded to 645 inquiries which resulted in an increase of 16 percent over the 1984 to 1985 contract period. The activities of TAP for the 1985 to 1986 contract period are summarized.

The Role of FcRn in Antigen Presentation

PubMed Central

Baker, Kristi; Rath, Timo; Pyzik, Michal; Blumberg, Richard S.

2014-01-01

Immunoglobulins are unique molecules capable of simultaneously recognizing a diverse array of antigens and themselves being recognized by a broad array of receptors. The abundance specifically of the IgG subclass and the variety of signaling receptors to which it binds render this an important immunomodulatory molecule. In addition to the classical Fcγ receptors that bind IgG at the cell surface, the neonatal Fc receptor (FcRn) is a lifelong resident of the endolysosomal system of most hematopoietic cells where it determines the intracellular fate of both IgG and IgG-containing immune complexes (IgG IC). Cross-linking of FcRn by multivalent IgG IC within antigen presenting cells such as dendritic cells initiates specific mechanisms that result in trafficking of the antigen-bearing IgG IC into compartments from which the antigen can successfully be processed into peptide epitopes compatible with loading onto both major histocompatibility complex class I and II molecules. In turn, this enables the synchronous activation of both CD4+ and CD8+ T cell responses against the cognate antigen, thereby bridging the gap between the humoral and cellular branches of the adaptive immune response. Critically, FcRn-driven T cell priming is efficient at very low doses of antigen due to the exquisite sensitivity of the IgG-mediated antigen delivery system through which it operates. FcRn-mediated antigen presentation has important consequences in tissue compartments replete with IgG and serves not only to determine homeostatic immune activation at a variety of sites but also to induce inflammatory responses upon exposure to antigens perceived as foreign. Therapeutically targeting the pathway by which FcRn enables T cell activation in response to IgG IC is thus a highly attractive prospect not only for the treatment of diseases that are driven by immune complexes but also for manipulating local immune responses against defined antigens such as those present during infections and cancer. PMID:25221553

Two-Dimensional Neutronic and Fuel Cycle Analysis of the Transatomic Power Molten Salt Reactor

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

Betzler, Benjamin R.; Powers, Jeffrey J.; Worrall, Andrew

2017-01-15

This status report presents the results from the first phase of the collaboration between Transatomic Power Corporation (TAP) and Oak Ridge National Laboratory (ORNL) to provide neutronic and fuel cycle analysis of the TAP core design through the Department of Energy Gateway for Accelerated Innovation in Nuclear, Nuclear Energy Voucher program. The TAP design is a molten salt reactor using movable moderator rods to shift the neutron spectrum in the core from mostly epithermal at beginning of life to thermal at end of life. Additional developments in the ChemTriton modeling and simulation tool provide the critical moderator-to-fuel ratio searches andmore » time-dependent parameters necessary to simulate the continuously changing physics in this complex system. Results from simulations with these tools show agreement with TAP-calculated performance metrics for core lifetime, discharge burnup, and salt volume fraction, verifying the viability of reducing actinide waste production with this design. Additional analyses of time step sizes, mass feed rates and enrichments, and isotopic removals provide additional information to make informed design decisions. This work further demonstrates capabilities of ORNL modeling and simulation tools for analysis of molten salt reactor designs and strongly positions this effort for the upcoming three-dimensional core analysis.« less

Microbial quality of drinking water from microfiltered water dispensers.

PubMed

Sacchetti, R; De Luca, G; Dormi, A; Guberti, E; Zanetti, F

2014-03-01

A comparison was made between the microbial quality of drinking water obtained from Microfiltered Water Dispensers (MWDs) and that of municipal tap water. A total of 233 water samples were analyzed. Escherichia coli (EC), enterococci (ENT), total coliforms (TC), Staphylococcus aureus, Pseudomonas aeruginosa and heterotrophic plate count (HPC) at 22 °C and 37 °C were enumerated. In addition, information was collected about the principal structural and functional characteristics of each MWD in order to study the various factors that might influence the microbial quality of the water. EC and ENT were not detected in any of the samples. TC were never detected in the tap water but were found in 5 samples taken from 5 different MWDs. S. aureus was found in a single sample of microfiltered water. P. aeruginosa was found more frequently and at higher concentrations in the samples collected from MWDs. The mean HPCs at 22 °C and 37 °C were significantly higher in microfiltered water samples compared to those of the tap water. In conclusion, the use of MWDs may increase the number of bacteria originally present in tap water. It is therefore important to monitor the quality of the dispensed water over time, especially if it is destined for vulnerable users. Copyright © 2013 Elsevier GmbH. All rights reserved.

Dichorionic triamniotic triplet pregnancy complicated by twin anemia polycythemia sequence: the place of fetal therapy.

PubMed

Griersmith, Thérèse H; Fung, Alison M; Walker, Susan P

2014-12-01

Monochorionic twins as part of a high order multiple pregnancy can be an unintended consequence of the increasingly common practice of blastocyst transfer for couples requiring in vitro fertilisation (IVF) for infertility. Dichorionic triamniotic (DCTA) triplets is the most common presentation, and these pregnancies are particularly high risk because of the additional risks associated with monochorionicity. Surveillance for twin-to-twin transfusion syndrome, including twin anemia polycythemia sequence, may be more difficult, and any intervention to treat the monochorionic pair needs to balance the proposed benefits against the risks posed to the unaffected singleton. Counseling of families with DCTA triplets is therefore complex. Here, we report a case of DCTA triplets, where the pregnancy was complicated by threatened preterm labour, and twin anemia polycythemia sequence (TAPS) was later diagnosed at 28 weeks. The TAPS was managed with a single intraperitoneal transfusion, enabling safe prolongation of the pregnancy for over 2 weeks until recurrence of TAPS and preterm labour supervened. Postnatal TAPS was confirmed, and all three infants were later discharged home at term corrected age, and were normal at follow-up. This case highlights that in utero therapy has an important role in multiple pregnancies of mixed chorionicity, and can achieve safe prolongation of pregnancy at critical gestations.

Efficient induction of CD25- iTreg by co-immunization requires strongly antigenic epitopes for T cells.

PubMed

Geng, Shuang; Yu, Yang; Kang, Youmin; Pavlakis, George; Jin, Huali; Li, Jinyao; Hu, Yanxin; Hu, Weibin; Wang, Shuang; Wang, Bin

2011-05-05

We previously showed that co-immunization with a protein antigen and a DNA vaccine coding for the same antigen induces CD40 low IL-10 high tolerogenic DCs, which in turn stimulates the expansion of antigen-specific CD4+CD25-Foxp3+ regulatory T cells (CD25- iTreg). However, it was unclear how to choose the antigen sequence to maximize tolerogenic antigen presentation and, consequently, CD25- iTreg induction. In the present study, we demonstrated the requirement of highly antigenic epitopes for CD25- iTreg induction. Firstly, we showed that the induction of CD25- iTreg by tolerogenic DC can be blocked by anti-MHC-II antibody. Next, both the number and the suppressive activity of CD25- iTreg correlated positively with the overt antigenicity of an epitope to activate T cells. Finally, in a mouse model of dermatitis, highly antigenic epitopes derived from a flea allergen not only induced more CD25- iTreg, but also more effectively prevented allergenic reaction to the allergen than did weakly antigenic epitopes. Our data thus indicate that efficient induction of CD25- iTreg requires highly antigenic peptide epitopes. This finding suggests that highly antigenic epitopes should be used for efficient induction of CD25- iTreg for clinical applications such as flea allergic dermatitis.

The biology and underlying mechanisms of cross-presentation of exogenous antigens on MHC I molecules

PubMed Central

Cruz, Freidrich M.; Colbert, Jeff D.; Merino, Elena; Kriegsman, Barry A.; Rock, Kenneth L.

2017-01-01

To monitor the health of cells, the immune system tasks antigen presenting cells with gathering antigens from other cells and reporting them to CD8 T cells in the form of peptides bound to MHC I molecules. Most cells would be unable to perform this function because they use their MHC I molecules to exclusively present peptides derived from the cell’s own proteins. However, the immune system evolved mechanisms for dendritic cells and some other phagocytes to sample and present antigens from the extracellular milieu on MHC I through a process called cross-presentation (XPT). How this important task is accomplished, its role in health and disease and its potential for exploitation are the subject of this review. PMID:28125356

Alternative Bio-Derived JP-8 Class Fuel and JP-8 Fuel: Flame Tube Combustor Test Results Compared using a GE TAPS Injector Configuration

NASA Technical Reports Server (NTRS)

Hicks, Yolanda R.; Anderson, Robert; Tedder, Sarah

2016-01-01

This paper presents results from tests in a NASA Glenn Research Center (GRC) flame tube facility, where a bio-derived alternate fuel was compared with JP-8 for emissions and general combustion performance. A research version of General Electric Aviation (GE) TAPS injector was used for the tests. Results include 2D, planar laser-based imaging as well as basic flow visualization of the flame. Four conditions were selected that simulate various engine power conditions relevant to NASA Fundamental Aeronautics Supersonics and Environmentally Responsible Aviation Projects were tested.

Analgesic Effect Of Bilateral Subcostal Tap Block After Laparoscopic Cholecystectomy.

PubMed

Khan, Karima Karam; Khan, Robyna Irshad

2018-01-01

Pain after laparoscopic cholecystectomy is mild to moderate in intensity. Several modalities are employed for achieving safe and effective postoperative analgesia, the benefits of which adds to the early recovery of the patients. As a part of multimodal analgesia, various approaches of Transversus abdominis plane (TAP) block has been used for management of parietal and incisional components of pain after laparoscopic cholecystectomy. This study was designed to compare the analgesic efficacy of two different approaches of ultrasound guided TAP block, i.e., Subcostal-TAP block technique with ultrasound guided Posterior-TAP block for postoperative pain management in patients undergoing laparoscopic cholecystectomy under general anaesthesia. In this double blinded randomized controlled study, consecutive nonprobability sampling was done and a total of 126 patients admitted for elective laparoscopic cholecystectomy fulfilling the inclusion criteria were selected. After induction of general anaesthesia, patients were randomized through draw method and received either ultrasound guided posterior TAP block with 0.375% bupivacaine (20ml volume) on each side of the abdomen or subcostal TAP block bilaterally with the same. Up to 24 hours postoperatively, static and dynamic numeric rating pain scores were assessed. We found statistically significant difference in mean static pain scores over 24 hours postoperatively in subcostal TAP group, suggesting improved analgesia. However, mean dynamic postoperative pain scores were comparable between the two groups. Whereas, patients in both groups were satisfied with pain management. Ultrasound guided subcostal TAP block provides better postoperative analgesia as compared to the Posterior TAP block in laparoscopic cholecystectomy. Otherwise both of the approaches improve patient outcomes towards early recovery and discharge from hospital.

Factors associated with drinking and being satisfied with tap water in Indigenous communities in Saskatchewan, Canada

PubMed Central

Bharadwaj, Lalita; Waldner, Cheryl L.

2018-01-01

ABSTRACT Previous studies have described concerns regarding tap water in Indigenous communities, yet there is little information on participants who report drinking their tap water and being satisfied with its quality. This study undertaken with members of 8 Indigenous communities in Saskatchewan, Canada, and identified factors associated with both the decision to drink tap water at home and being satisfied with its quality. We examined the importance of factors such as individual attributes, experiences, attitudes, household and community-based variables. Less than one-quarter of participants (23.4%) drank tap water and were satisfied with its quality. Individuals who did not boil tap water (odds ratio [OR] = 5.76, 95% confidence interval [CI] = 1.68–19.8), those who did not experience tap water odour (OR = 2.38, 95% CI = 1.26–4.50) and participants living in communities away from urban centres (OR = 2.74, 95% CI = 1.63–4.51) were more likely to drink and be satisfied with their tap water. Concerns about the environment had the most impact on community members aged 55+ years. Those not reporting concerns about environmental problems affecting water (OR = 11.4, 95% CI = 3.10–42.2) were much more likely to drink and be satisfied with their tap water. Programmes to improve water quality, reduce the need for boil water advisories and increase community confidence in the environment could improve tap water satisfaction and consumption. PMID:29697009

Stereotypes for lever-tap operation.

PubMed

Chan, Alan H S; Tsang, Steve N H; Hoffmann, Errol R

2016-04-15

Lever-operated taps have become more popular and are commonly used in operating theatres, food preparation areas and where users have poor strength; however, there is very little data available for user expectations on tap operation. Thus, an experiment on dual lever-operated water tap (faucets) was conducted with the aim of for providing information for improved design. This study aims to compare different lever-tap designs and their stereotypes adopted by the end-user to operate them also to verify the stereotypes for increasing or decreasing the water flow. 240 participants were requested to rotate the lever tap to indicate direction for increasing and decreasing water flow with simulated hardware, using actual taps placed at the top of a simulated washbasin. Nine initial positions of the lever were used for increasing and decreasing flows, ranging from the ends of both levers facing outward from the bowl center to the ends of both levers facing inward. All levers operated in the horizontal plane. Strong stereotypes (greater than 80%) for several initial lever orientations were found for increasing water flow, especially when the initial lever end positions were facing outwards. However, for different initial positions at which participants were told that the water was flowing and the flow was to be decreased, no strong stereotypes existed. The stereotypes for increasing water flow of dual-lever taps were strong, whereas those for decreasing water flow were weak and hence the stereotype reversibility was also weak. In terms of user expectations, lever taps do not show any great advantage over cross-taps in terms of operator expectations for increasing and decreasing water flow.

Biomechanical loading on the upper extremity increases from single key tapping to directional tapping.

PubMed

Qin, Jin; Trudeau, Matthieu; Katz, Jeffrey N; Buchholz, Bryan; Dennerlein, Jack T

2011-08-01

Musculoskeletal disorders associated with computer use span the joints of the upper extremity. Computing typically involves tapping in multiple directions. Thus, we sought to describe the loading on the finger, wrist, elbow and shoulder joints in terms of kinematic and kinetic difference across single key switch tapping to directional tapping on multiple keys. An experiment with repeated measures design was conducted. Six subjects tapped with their right index finger on a stand-alone number keypad placed horizontally in three conditions: (1) on single key switch (the number key 5); (2) left and right on number key 4 and 6; (3) top and bottom on number key 8 and 2. A force-torque transducer underneath the keypad measured the fingertip force. An active-marker infrared motion analysis system measured the kinematics of the fingertip, hand, forearm, upper arm and torso. Joint moments for the metacarpophalangeal, wrist, elbow, and shoulder joints were estimated using inverse dynamics. Tapping in the top-bottom orientation introduced the largest biomechanical loading on the upper extremity especially for the proximal joint, followed by tapping in the left-right orientation, and the lowest loading was observed during single key switch tapping. Directional tapping on average increased the fingertip force, joint excursion, and peak-to-peak joint torque by 45%, 190% and 55%, respectively. Identifying the biomechanical loading patterns associated with these fundamental movements of keying improves the understanding of the risks of upper extremity musculoskeletal disorders for computer keyboard users. Copyright © 2010 Elsevier Ltd. All rights reserved.

Hematological characteristics in neonates with twin anemia-polycythemia sequence (TAPS).

PubMed

Lopriore, E; Slaghekke, F; Oepkes, D; Middeldorp, J M; Vandenbussche, F P H A; Walther, F J

2010-03-01

To evaluate the neonatal hematological features of monochorionic twins with twin anemia-polycythemia sequence (TAPS) and to determine the additional diagnostic value of reticulocyte count measurement. A cohort of consecutive monochorionic twins with TAPS (n = 19) was included in the study and each twin pair was compared with two monochorionic twin pairs (n = 38) unaffected by TAPS or twin-twin transfusion syndrome (TTTS), matched for gestational age at birth. We measured full blood counts on day 1 and determined the incidence of anemia, polycythemia, reticulocytosis and thrombocytopenia. Median inter-twin hemoglobin (Hb) difference in monochorionic twins with and without TAPS was 13.7 g/dL and 2.4 g/dL, respectively (p < 0.01). Median inter-twin reticulocyte count ratio in twins with and without TAPS was 3.1 and 1.0, respectively (p < 0.01). Thrombocytopenia (platelet count < 150 x 10(9)/L) occurred more often in the TAPS group than in the control group, 45% (17/38) versus 11% (11/38), respectively (p < 0.01). In the TAPS group, mean platelet count was significantly lower in recipients than in donors, 133 x 10(9)/L versus 218 x 10(9)/L, respectively (p < 0.01). TAPS twins have a large inter-twin Hb difference in combination with a large inter-twin reticulocyte count ratio. Recipients are more often thrombocytopenic than donors, probably due to polycythemia. Copyright (c) 2010 John Wiley & Sons, Ltd.

Finger tapping and pre-attentive sensorimotor timing in adults with ADHD.

PubMed

Hove, Michael J; Gravel, Nickolas; Spencer, Rebecca M C; Valera, Eve M

2017-12-01

Sensorimotor timing deficits are considered central to attention-deficit/hyperactivity disorder (ADHD). However, the tasks establishing timing impairments often involve interconnected processes, including low-level sensorimotor timing and higher level executive processes such as attention. Thus, the source of timing deficits in ADHD remains unclear. Low-level sensorimotor timing can be isolated from higher level processes in a finger-tapping task that examines the motor response to unexpected shifts of metronome onsets. In this study, adults with ADHD and ADHD-like symptoms (n = 25) and controls (n = 26) performed two finger-tapping tasks. The first assessed tapping variability in a standard tapping task (metronome-paced and unpaced). In the other task, participants tapped along with a metronome that contained unexpected shifts (±15, 50 ms); the timing adjustment on the tap following the shift captures pre-attentive sensorimotor timing (i.e., phase correction) and thus should be free of potential higher order confounds (e.g., attention). In the standard tapping task, as expected, the ADHD group had higher timing variability in both paced and unpaced tappings. However, in the pre-attentive task, performance did not differ between the ADHD and control groups. Together, results suggest that low-level sensorimotor timing and phase correction are largely preserved in ADHD and that some timing impairments observed in ADHD may stem from higher level factors (such as sustained attention).

Finger-tapping motion analysis in cervical myelopathy by magnetic-sensor tapping device.

PubMed

Miwa, Toshitada; Hosono, Noboru; Mukai, Yoshihiro; Makino, Takahiro; Kandori, Akihiko; Fuji, Takeshi

2013-08-01

Case-control study. The purpose of this study is to determine finger motion of patients with cervical myelopathy during finger-tapping cycles. A major symptom of patients with compressive cervical myelopathy is finger clumsiness. Therefore, understanding finger motion is prerequisite in assessing the severity of myelopathy. The popular grip-and-release test evaluates only the number of motion cycles, which is insufficient to fully describe complex finger motion. Forty-three patients with cervical myelopathy and 41 healthy controls tapped their index fingers against their thumbs as rapidly as possible for 30 seconds and the motion was recorded by a magnetic-sensor coil attached to the nail surface. Output signals were stored in a computer, which automatically calculated tapping frequency, distance moved, ratio of opening/closing velocity and the SD of the tapping interval. The SD of the tapping interval was significantly greater and all other measures were significantly smaller in patients with cervical myelopathy, than in healthy controls. All indices significantly improved after surgical decompression of the cervical spine. Distance moved (Pearson correlation coefficient: r=0.590, P<0.001) and the SD of the tapping interval (r=-0.451; P=0.002) were significantly correlated with the Japanese Orthopedic Association score (neurological scale). The quantitative evaluation of finger paralysis was performed by this tapping device. Speed and regularity in repetitive motion of fingers were correlated with the severity of cervical myelopathy.

Enhanced activation of human T cell clones specific for virus-like particles expressing the HIV V3 loop in the presence of HIV V3 loop-specific polyclonal antibodies

PubMed Central

Peifang, S.; Pira, G. L.; Fenoglio, D.; Harris, S.; Costa, M. G.; Venturino, V.; Dessì, V.; Layton, G.; Laman, J.; Huisman, J. G.; Manca, F.

1994-01-01

Recombinant virus-like particles (VLP), formed by the yeast Ty p1 protein, carrying the HIV gp120 V3 loop on their surface (V3-VLP) have been tested in vitro for immunogenicity and antigenicity by using VLP p1-specific human CD4+ T cell lines and clones. VLP-specific human T cell lines and clones were generated from normal individuals, indicating that VLP-specific precursor cells present in the peripheral lymphocyte pool can be induced to expand clonally upon antigen challenge in vitro, in the absence of previous immunization. It was also shown that V3-specific polyclonal antibodies enhance V3-VLP-induced activation of VLP-specific T cell clones. Antibody-dependent potentiation has been shown previously in other antigen systems, and it depends on enhanced uptake of complexed antigen by Fc receptor-positive antigen-presenting cells. Since in this case antigen is internalized by presenting cells as a complex, it can be inferred that a similar event of antibody-mediated antigen uptake can take place with V3-specific B cells, resulting in presentation by the B cells of T helper epitopes derived from processing of the VLP p1 moiety. This suggests that T helper cells specific for the carrier VLP p1 protein can be activated to provide help to V3-specific B cells in the presence of the appropriate antigen construct. PMID:7915974

Drinking of tap water is smart, but how do it better? - A tap water quality research

NASA Astrophysics Data System (ADS)

Mika, Anna; Sekuła, Klaudia; Dendys, Marta; Ptaszek, Weronika; Postawa, Adam

2018-02-01

Drinking tap water has recently become popular. It is a way to fight with the tons of garbage (disposable, plastic bottles). However, many people are afraid of water quality. The research was performed in December 2015 in Krakow, during one week. 56 samples were collected. The samples were taken in different times of the day and in the two types of building (old one with installation from the 80s and new one with installation built in past few years). Samples were taken by two qualified operators. The first sample was collected at the morning at 6 a.m., before anyone uses the tap. The second one after the tap was flushed and then the third one after 30 minutes stagnation. At the evening was taken one sample (after using the tap all day).The aim of the research was to check the quality of drinking water in the end-user. The results show that quality of tap water in Krakow is good, also in the end-user, but the concentration of chemical elements are changing during the flushing and using of the tap.

Brain activity associated with memory and cognitive function during jaw-tapping movement in healthy subjects using functional magnetic resonance imaging.

PubMed

Cho, Seung-Yeon; Shin, Ae-Sook; Na, Byung-Jo; Jahng, Geon-Ho; Park, Seong-Uk; Jung, Woo-Sang; Moon, Sang-Kwan; Park, Jung-Mi

2013-06-01

To determine whether jaw-tapping movement, a classically described as an indication of personal well-being and mental health, stimulates the memory and the cognitive regions of the brain and is associated with improved brain performance. Twelve healthy right-handed female subjects completed the study. Each patient performed a jaw-tapping task and an n-back task during functional magnetic resonance imaging (fMRI). The subjects were trained to carry out the jaw-tapping movement at home twice a day for 4 weeks. The fMRI was repeated when they returned. During the first and second jaw-tapping session, both sides of precentral gyrus and the right middle frontal gyrus (BA 6) were activated. And during the second session of the jaw-tapping task, parts of frontal lobe and temporal lobe related to memory function were more activated. In addition, the total percent task accuracy in n-back task significantly increased after 4 weeks of jawtapping movement. After jaw-tapping training for 4 weeks, brain areas related to memory showed significantly increased blood oxygen level dependent signals. Jaw-tapping movement might be a useful exercise for stimulating the memory and cognitive regions of the brain.

Commercializing Defense Technologies and Helping Defense Firms Succeed in Commercial Markets: A Report on the Objectives, Activities, and Accomplishments of the TAP-IN Program

NASA Technical Reports Server (NTRS)

1997-01-01

Technology Access for Product Innovation (TAP-IN), the largest technology deployment project funded by TRP, was competitively selected through a national solicitation for proposals. TAP-IN was created to help companies access and apply defense technologies and help defense-dependent companies enter new commercial markets. Defense technologies included technologies developed by DoD, DOE, NASA, and their contractors. TAP-IN was structured to provide region-based technology access services that were able to draw on technology resources nationwide. TAP-IN provided expert assistance in all stages of the commercialization process from concept through prototype design to capital sourcing and marketing strategy. TAP-IN helped companies locate new technology, identify business partners, secure financing, develop ideas for new products, identify new markets, license technology, solve technical problems, and develop company-specific applications of federal technology. TAP-IN leveraged NASA's existing commercial technology network to create an integrated national network of organizations that assisted companies in every state. In addition to NASA's six regional technology transfer centers (RTTCs), TAP-IN included business and technology development organizations in every state, the Industrial Designers Society of America, and the Federal Laboratory Consortium (FLC).

MHC structure and function − antigen presentation. Part 2

PubMed Central

Goldberg, Anna Carla; Rizzo, Luiz Vicente

2015-01-01

The second part of this review deals with the molecules and processes involved in the processing and presentation of the antigenic fragments to the T-cell receptor. Though the nature of the antigens presented varies, the most significant class of antigens is proteins, processed within the cell to be then recognized in the form of peptides, a mechanism that confers an extraordinary degree of precision to this mode of immune response. The efficiency and accuracy of this system is also the result of the myriad of mechanisms involved in the processing of proteins and production of peptides, in addition to the capture and recycling of alternative sources aiming to generate further diversity in the presentation to T-cells. PMID:25807243

Arginine methylation of REF/ALY promotes efficient handover of mRNA to TAP/NXF1

PubMed Central

Hung, Ming-Lung; Hautbergue, Guillaume M.; Snijders, Ambrosius P. L.; Dickman, Mark J.; Wilson, Stuart A.

2010-01-01

The REF/ALY mRNA export adaptor binds TAP/NXF1 via an arginine-rich region, which overlaps with its RNA-binding domain. When TAP binds a REF:RNA complex, it triggers transfer of the RNA from REF to TAP. Here, we have examined the effects of arginine methylation on the activities of the REF protein in mRNA export. We have mapped the arginine methylation sites of REF using mass spectrometry and find that several arginines within the TAP and RNA binding domains are methylated in vivo. However, arginine methylation has no effect on the REF:TAP interaction. Instead, arginine methylation reduces the RNA-binding activity of REF in vitro and in vivo. The reduced RNA-binding activity of REF in its methylated state is essential for efficient displacement of RNA from REF by TAP in vivo. Therefore, arginine methylation fine-tunes the RNA-binding activity of REF such that the RNA–protein interaction can be readily disrupted by export factors further down the pathway. PMID:20129943

Biofilm formation in an experimental water distribution system: the contamination of non-touch sensor taps and the implication for healthcare.

PubMed

Moore, Ginny; Stevenson, David; Thompson, Katy-Anne; Parks, Simon; Ngabo, Didier; Bennett, Allan M; Walker, Jimmy T

2015-01-01

Hospital tap water is a recognised source of Pseudomonas aeruginosa. U.K. guidance documents recommend measures to control/minimise the risk of P. aeruginosa in augmented care units but these are based on limited scientific evidence. An experimental water distribution system was designed to investigate colonisation of hospital tap components. P. aeruginosa was injected into 27 individual tap 'assemblies'. Taps were subsequently flushed twice daily and contamination levels monitored over two years. Tap assemblies were systematically dismantled and assessed microbiologically and the effect of removing potentially contaminated components was determined. P. aeruginosa was repeatedly recovered from the tap water at levels above the augmented care alert level. The organism was recovered from all dismantled solenoid valves with colonisation of the ethylene propylene diene monomer (EPDM) diaphragm confirmed by microscopy. Removing the solenoid valves reduced P. aeruginosa counts in the water to below detectable levels. This effect was immediate and sustained, implicating the solenoid diaphragm as the primary contamination source.

Quantification of Finger-Tapping Angle Based on Wearable Sensors

PubMed Central

Djurić-Jovičić, Milica; Jovičić, Nenad S.; Roby-Brami, Agnes; Popović, Mirjana B.; Kostić, Vladimir S.; Djordjević, Antonije R.

2017-01-01

We propose a novel simple method for quantitative and qualitative finger-tapping assessment based on miniature inertial sensors (3D gyroscopes) placed on the thumb and index-finger. We propose a simplified description of the finger tapping by using a single angle, describing rotation around a dominant axis. The method was verified on twelve subjects, who performed various tapping tasks, mimicking impaired patterns. The obtained tapping angles were compared with results of a motion capture camera system, demonstrating excellent accuracy. The root-mean-square (RMS) error between the two sets of data is, on average, below 4°, and the intraclass correlation coefficient is, on average, greater than 0.972. Data obtained by the proposed method may be used together with scores from clinical tests to enable a better diagnostic. Along with hardware simplicity, this makes the proposed method a promising candidate for use in clinical practice. Furthermore, our definition of the tapping angle can be applied to all tapping assessment systems. PMID:28125051

Quantification of Finger-Tapping Angle Based on Wearable Sensors.

PubMed

Djurić-Jovičić, Milica; Jovičić, Nenad S; Roby-Brami, Agnes; Popović, Mirjana B; Kostić, Vladimir S; Djordjević, Antonije R

2017-01-25

We propose a novel simple method for quantitative and qualitative finger-tapping assessment based on miniature inertial sensors (3D gyroscopes) placed on the thumb and index-finger. We propose a simplified description of the finger tapping by using a single angle, describing rotation around a dominant axis. The method was verified on twelve subjects, who performed various tapping tasks, mimicking impaired patterns. The obtained tapping angles were compared with results of a motion capture camera system, demonstrating excellent accuracy. The root-mean-square (RMS) error between the two sets of data is, on average, below 4°, and the intraclass correlation coefficient is, on average, greater than 0.972. Data obtained by the proposed method may be used together with scores from clinical tests to enable a better diagnostic. Along with hardware simplicity, this makes the proposed method a promising candidate for use in clinical practice. Furthermore, our definition of the tapping angle can be applied to all tapping assessment systems.

The ability to tap to a beat relates to cognitive, linguistic, and perceptual skills

PubMed Central

Tierney, Adam T.; Kraus, Nina

2013-01-01

Reading-impaired children have difficulty tapping to a beat. Here we tested whether this relationship between reading ability and synchronized tapping holds in typically-developing adolescents. We also hypothesized that tapping relates to two other abilities. First, since auditory-motor synchronization requires monitoring of the relationship between motor output and auditory input, we predicted that subjects better able to tap to the beat would perform better on attention tests. Second, since auditory-motor synchronization requires fine temporal precision within the auditory system for the extraction of a sound’s onset time, we predicted that subjects better able to tap to the beat would be less affected by backward masking, a measure of temporal precision within the auditory system. As predicted, tapping performance related to reading, attention, and backward masking. These results motivate future research investigating whether beat synchronization training can improve not only reading ability, but potentially executive function and basic auditory processing as well. PMID:23400117

Encryption of agonistic motifs for TLR4 into artificial antigens augmented the maturation of antigen-presenting cells.

PubMed

Ito, Masaki; Hayashi, Kazumi; Minamisawa, Tamiko; Homma, Sadamu; Koido, Shigeo; Shiba, Kiyotaka

2017-01-01

Adjuvants are indispensable for achieving a sufficient immune response from vaccinations. From a functional viewpoint, adjuvants are classified into two categories: "physical adjuvants" increase the efficacy of antigen presentation by antigen-presenting cells (APC) and "signal adjuvants" induce the maturation of APC. Our previous study has demonstrated that a physical adjuvant can be encrypted into proteinous antigens by creating artificial proteins from combinatorial assemblages of epitope peptides and those peptide sequences having propensities to form certain protein structures (motif programming). However, the artificial antigens still require a signal adjuvant to maturate the APC; for example, co-administration of the Toll-like receptor 4 (TLR4) agonist monophosphoryl lipid A (MPLA) was required to induce an in vivo immunoreaction. In this study, we further modified the previous artificial antigens by appending the peptide motifs, which have been reported to have agonistic activity for TLR4, to create "adjuvant-free" antigens. The created antigens with triple TLR4 agonistic motifs in their C-terminus have activated NF-κB signaling pathways through TLR4. These proteins also induced the production of the inflammatory cytokine TNF-α, and the expression of the co-stimulatory molecule CD40 in APC, supporting the maturation of APC in vitro. Unexpectedly, these signal adjuvant-encrypted proteins have lost their ability to be physical adjuvants because they did not induce cytotoxic T lymphocytes (CTL) in vivo, while the parental proteins induced CTL. These results confirmed that the manifestation of a motif's function is context-dependent and simple addition does not always work for motif-programing. Further optimization of the molecular context of the TLR4 agonistic motifs in antigens should be required to create adjuvant-free antigens.

Encryption of agonistic motifs for TLR4 into artificial antigens augmented the maturation of antigen-presenting cells

PubMed Central

Hayashi, Kazumi; Minamisawa, Tamiko; Homma, Sadamu; Koido, Shigeo; Shiba, Kiyotaka

2017-01-01

Adjuvants are indispensable for achieving a sufficient immune response from vaccinations. From a functional viewpoint, adjuvants are classified into two categories: “physical adjuvants” increase the efficacy of antigen presentation by antigen-presenting cells (APC) and “signal adjuvants” induce the maturation of APC. Our previous study has demonstrated that a physical adjuvant can be encrypted into proteinous antigens by creating artificial proteins from combinatorial assemblages of epitope peptides and those peptide sequences having propensities to form certain protein structures (motif programming). However, the artificial antigens still require a signal adjuvant to maturate the APC; for example, co-administration of the Toll-like receptor 4 (TLR4) agonist monophosphoryl lipid A (MPLA) was required to induce an in vivo immunoreaction. In this study, we further modified the previous artificial antigens by appending the peptide motifs, which have been reported to have agonistic activity for TLR4, to create “adjuvant-free” antigens. The created antigens with triple TLR4 agonistic motifs in their C-terminus have activated NF-κB signaling pathways through TLR4. These proteins also induced the production of the inflammatory cytokine TNF-α, and the expression of the co-stimulatory molecule CD40 in APC, supporting the maturation of APC in vitro. Unexpectedly, these signal adjuvant-encrypted proteins have lost their ability to be physical adjuvants because they did not induce cytotoxic T lymphocytes (CTL) in vivo, while the parental proteins induced CTL. These results confirmed that the manifestation of a motif’s function is context-dependent and simple addition does not always work for motif-programing. Further optimization of the molecular context of the TLR4 agonistic motifs in antigens should be required to create adjuvant-free antigens. PMID:29190754

Cationic liposomes as vaccine adjuvants.

PubMed

Christensen, Dennis; Korsholm, Karen S; Rosenkrands, Ida; Lindenstrøm, Thomas; Andersen, Peter; Agger, Else Marie

2007-10-01

Cationic liposomes are lipid-bilayer vesicles with a positive surface charge that have re-emerged as a promising new adjuvant technology. Although there is some evidence that cationic liposomes themselves can improve the immune response against coadministered vaccine antigens, their main functions are to protect the antigens from clearance in the body and deliver the antigens to professional antigen-presenting cells. In addition, cationic liposomes can be used to introduce immunomodulators to enhance and modulate the immune response in a desirable direction and, thereby, represent an efficient tool when designing tailor-made adjuvants for specific disease targets. In this article we review the recent progress on cationic liposomes as vehicles, enhancing the effect of immunomodulators and the presentation of vaccine antigens.

MyD88/CD40 Genetic Adjuvant Function in Cutaneous Atypical Antigen-Presenting Cells Contributes to DNA Vaccine Immunogenicity

PubMed Central

Slawin, Kevin M.; Levitt, Jonathan M.; Spencer, David M.

2016-01-01

Therapeutic DNA-based vaccines aim to prime an adaptive host immune response against tumor-associated antigens, eliminating cancer cells primarily through CD8+ cytotoxic T cell-mediated destruction. To be optimally effective, immunological adjuvants are required for the activation of tumor-specific CD8+ T cells responses by DNA vaccination. Here, we describe enhanced anti-tumor efficacy of an in vivo electroporation-delivered DNA vaccine by inclusion of a genetically encoded chimeric MyD88/CD40 (MC) adjuvant, which integrates both innate and adaptive immune signaling pathways. When incorporated into a DNA vaccine, signaling by the MC adjuvant increased antigen-specific CD8+ T cells and promoted elimination of pre-established tumors. Interestingly, MC-enhanced vaccine efficacy did not require direct-expression of either antigen or adjuvant by local antigen-presenting cells, but rather our data supports a key role for MC function in “atypical” antigen-presenting cells of skin. In particular, MC adjuvant-modified keratinocytes increased inflammatory cytokine secretion, upregulated surface MHC class I, and were able to increase in vitro and in vivo priming of antigen-specific CD8+ T cells. Furthermore, in the absence of critical CD8α+/CD103+ cross-priming dendritic cells, MC was still able to promote immune priming in vivo, albeit at a reduced level. Altogether, our data support a mechanism by which MC signaling activates an inflammatory phenotype in atypical antigen-presenting cells within the cutaneous vaccination site, leading to an enhanced CD8+ T cell response against DNA vaccine-encoded antigens, through both CD8α+/CD103+ dendritic cell-dependent and independent pathways. PMID:27741278

IL-10 down-regulates T cell activation by antigen-presenting liver sinusoidal endothelial cells through decreased antigen uptake via the mannose receptor and lowered surface expression of accessory molecules.

PubMed

Knolle, P A; Uhrig, A; Hegenbarth, S; Löser, E; Schmitt, E; Gerken, G; Lohse, A W

1998-12-01

Our study demonstrates that antigen-presenting liver sinusoidal endothelial cells (LSEC) induce production of interferon-gamma (IFN-gamma) from cloned Th1 CD4+ T cells. We show that LSEC used the mannose receptor for antigen uptake, which further strengthened the role of LSEC as antigen-presenting cell (APC) population in the liver. The ability of LSEC to activate cloned CD4+ T cells antigen-specifically was down-regulated by exogenous prostaglandin E2 (PGE2) and by IL-10. We identify two separate mechanisms by which IL-10 down-regulated T cell activation through LSEC. IL-10 decreased the constitutive surface expression of MHC class II as well as of the accessory molecules CD80 and CD86 on LSEC. Furthermore, IL-10 diminished mannose receptor activity in LSEC. Decreased antigen uptake via the mannose receptor and decreased expression of accessory molecules may explain the down-regulation of T cell activation through IL-10. Importantly, the expression of low numbers of antigen on MHC II in the absence of accessory signals on LSEC may lead to induction of anergy in T cells. Because PGE2 and IL-10 are released from LSEC or Kupffer cells (KC) in response to those concentrations of endotoxin found physiologically in portal venous blood, it is possible that the continuous presence of these mediators and their negative effect on the local APC may explain the inability of the liver to induce T cell activation and to clear chronic infections. Our results support the notion that antigen presentation by LSEC in the hepatic microenvironment contributes to the observed inability to mount an effective cell-mediated immune response in the liver.

Serological purification of polysaccharide antigens from Streptococcus mutans serotypes a and d: characterization of multiple antigenic determinants.

PubMed

Linzer, R; Mukasa, H; Slade, H D

1975-10-01

The polysaccharide antigen preparations from serotype a and serotype d strains of Streptococcus mutans contained both a serotype-specific antigenic determinant and a common a-d antigenic determinant, as demonstrated by agar gel diffusion studies and a quantitative cross-precipitin assay. The chromatographically purified antigens were isolated by a method which depended on their serological specificity to determine if these two antigenic determinants were located on the same molecule. The a and d polysaccharides were recovered from specific antigen-antibody complexes and characterized with respect to their immunological specificity and chemical composition. Agar gel diffusion tests demonstrated that, in both the a and d preparations, the serotype-specific antigenic determinant and the common a-d antigenic determinant were present in one molecule.

NLRC5/MHC class I transactivator is a target for immune evasion in cancer.

PubMed

Yoshihama, Sayuri; Roszik, Jason; Downs, Isaac; Meissner, Torsten B; Vijayan, Saptha; Chapuy, Bjoern; Sidiq, Tabasum; Shipp, Margaret A; Lizee, Gregory A; Kobayashi, Koichi S

2016-05-24

Cancer cells develop under immune surveillance, thus necessitating immune escape for successful growth. Loss of MHC class I expression provides a key immune evasion strategy in many cancers, although the molecular mechanisms remain elusive. MHC class I transactivator (CITA), known as "NLRC5" [NOD-like receptor (NLR) family, caspase recruitment (CARD) domain containing 5], has recently been identified as a critical transcriptional coactivator of MHC class I gene expression. Here we show that the MHC class I transactivation pathway mediated by CITA/NLRC5 constitutes a target for cancer immune evasion. In all the 21 tumor types we examined, NLRC5 expression was highly correlated with the expression of MHC class I, with cytotoxic T-cell markers, and with genes in the MHC class I antigen-presentation pathway, including LMP2/LMP7, TAP1, and β2-microglobulin. Epigenetic and genetic alterations in cancers, including promoter methylation, copy number loss, and somatic mutations, were most prevalent in NLRC5 among all MHC class I-related genes and were associated with the impaired expression of components of the MHC class I pathway. Strikingly, NLRC5 expression was significantly associated with the activation of CD8(+) cytotoxic T cells and patient survival in multiple cancer types. Thus, NLRC5 constitutes a novel prognostic biomarker and potential therapeutic target of cancers.

NLRC5/MHC class I transactivator is a target for immune evasion in cancer

PubMed Central

Yoshihama, Sayuri; Roszik, Jason; Downs, Isaac; Meissner, Torsten B.; Vijayan, Saptha; Chapuy, Bjoern; Sidiq, Tabasum; Shipp, Margaret A.; Lizee, Gregory A.; Kobayashi, Koichi S.

2016-01-01

Cancer cells develop under immune surveillance, thus necessitating immune escape for successful growth. Loss of MHC class I expression provides a key immune evasion strategy in many cancers, although the molecular mechanisms remain elusive. MHC class I transactivator (CITA), known as “NLRC5” [NOD-like receptor (NLR) family, caspase recruitment (CARD) domain containing 5], has recently been identified as a critical transcriptional coactivator of MHC class I gene expression. Here we show that the MHC class I transactivation pathway mediated by CITA/NLRC5 constitutes a target for cancer immune evasion. In all the 21 tumor types we examined, NLRC5 expression was highly correlated with the expression of MHC class I, with cytotoxic T-cell markers, and with genes in the MHC class I antigen-presentation pathway, including LMP2/LMP7, TAP1, and β2-microglobulin. Epigenetic and genetic alterations in cancers, including promoter methylation, copy number loss, and somatic mutations, were most prevalent in NLRC5 among all MHC class I-related genes and were associated with the impaired expression of components of the MHC class I pathway. Strikingly, NLRC5 expression was significantly associated with the activation of CD8+ cytotoxic T cells and patient survival in multiple cancer types. Thus, NLRC5 constitutes a novel prognostic biomarker and potential therapeutic target of cancers. PMID:27162338

Vaccinia virus decreases major histocompatibility complex (MHC) class II antigen presentation, T-cell priming, and peptide association with MHC class II

PubMed Central

Rehm, Kristina E; Connor, Ramsey F; Jones, Gwendolyn J B; Yimbu, Kenneth; Mannie, Mark D; Roper, Rachel L

2009-01-01

Vaccinia virus (VACV) is the current live virus vaccine used to protect humans against smallpox and monkeypox, but its use is contraindicated in several populations because of its virulence. It is therefore important to elucidate the immune evasion mechanisms of VACV. We found that VACV infection of antigen-presenting cells (APCs) significantly decreased major histocompatibility complex (MHC) II antigen presentation and decreased synthesis of 13 chemokines and cytokines, suggesting a potent viral mechanism for immune evasion. In these model systems, responding T cells were not directly affected by virus, indicating that VACV directly affects the APC. VACV significantly decreased nitric oxide production by peritoneal exudate cells and the RAW macrophage cell line in response to lipopolysaccharide (LPS) and interferon (IFN)-γ, decreased class II MHC expression on APCs, and induced apoptosis in macrophages and dendritic cells. However, VACV decreased antigen presentation by 1153 B cells without apparent apoptosis induction, indicating that VACV differentially affects B lymphocytes and other APCs. We show that the key mechanism of VACV inhibition of antigen presentation may be its reduction of antigenic peptide loaded into the cleft of MHC class II molecules. These data indicate that VACV evades the host immune response by impairing critical functions of the APC. PMID:20067538

A piezoelectric film-based intrasplint detection method for bruxism.

PubMed

Takeuchi, H; Ikeda, T; Clark, G T

2001-08-01

An accurate, easy-to-use, long-term method other than EMG is needed to monitor bruxism. This article presents pilot data on the reproducibility, validity, and utility of an intrasplint piezoelectric film method. Simulated bruxism behaviors (steady-state and rhythmic clenching, grinding, and tapping) in 5 subjects were recorded with the use of both masseter EMG and an intrasplint piezoelectric film method. Correlation coefficients calculated for simulated bruxism event duration with the use of a masseter EMG or an intrasplint piezoelectric film method were 0.99 for tapping and steady-state clenching, 0.96 for rhythmic clenching, and 0.79 for grinding. Piezoelectric film has its limitations and does not faithfully capture sustained force magnitudes. However, for the target behaviors associated with bruxism (tooth grinding, clenching, and tapping), it appears to faithfully reproduce above-baseline events with durations statistically indistinguishable from those recorded with masseter EMG. Masseter EMG was poorest at detecting a simulated side-to-side grinding behavior.

Ethanol fermentation characteristics of recycled water by Saccharomyces cerevisiae in an integrated ethanol-methane fermentation process.

PubMed

Yang, Xinchao; Wang, Ke; Wang, Huijun; Zhang, Jianhua; Mao, Zhonggui

2016-11-01

An process of integrated ethanol-methane fermentation with improved economics has been studied extensively in recent years, where the process water used for a subsequent fermentation of carbohydrate biomass is recycled. This paper presents a systematic study of the ethanol fermentation characteristics of recycled process water. Compared with tap water, fermentation time was shortened by 40% when mixed water was employed. However, while the maximal ethanol production rate increased from 1.07g/L/h to 2.01g/L/h, ethanol production was not enhanced. Cell number rose from 0.6×10(8) per mL in tap water to 1.6×10(8) per mL in mixed water but although biomass increased, cell morphology was not affected. Furthermore, the use of mixed water increased the glycerol yield but decreased that of acetic acid, and the final pH with mixed water was higher than when using tap water. Copyright © 2016 Elsevier Ltd. All rights reserved.

Erosion of aluminum 6061-T6 under cavitation attack in mineral oil and water

NASA Technical Reports Server (NTRS)

Rao, B. C. S.; Buckley, D. H.

1985-01-01

Studies of the erosion of aluminum 6061-T6 under cavitation attack in distilled water, ordinary tap water and a viscous mineral oil are presented. The mean depth of penetration for the mineral oil was about 40 percent of that for water at the end of a 40 min test. The mean depth of penetration and its rate did not differ significantly for distilled and tap water. The mean depth of penetration rate for both distilled and tap water increased to a maximum and then decreased with test duration, while that for mineral oil had a maximum during the initial period. The ratio h/2a of the pit depth h to the pit diameter 2a varied from 0.04 to 0.13 in water and from 0.06 to 0.20 in mineral oil. Scanning electron microscopy indicates that the pits are initially formed over the grain boundaries and precipitates while the surface grains are deformed under cavitation attack.

Femtosecond laser inscription of asymmetric directional couplers for in-fiber optical taps and fiber cladding photonics.

PubMed

Grenier, Jason R; Fernandes, Luís A; Herman, Peter R

2015-06-29

Precise alignment of femtosecond laser tracks in standard single mode optical fiber is shown to enable controllable optical tapping of the fiber core waveguide light with fiber cladding photonic circuits. Asymmetric directional couplers are presented with tunable coupling ratios up to 62% and bandwidths up to 300 nm at telecommunication wavelengths. Real-time fiber monitoring during laser writing permitted a means of controlling the coupler length to compensate for micron-scale alignment errors and to facilitate tailored design of coupling ratio, spectral bandwidth and polarization properties. Laser induced waveguide birefringence was harnessed for polarization dependent coupling that led to the formation of in-fiber polarization-selective taps with 32 dB extinction ratio. This technology enables the interconnection of light propagating in pre-existing waveguides with laser-formed devices, thereby opening a new practical direction for the three-dimensional integration of optical devices in the cladding of optical fibers and planar lightwave circuits.

CK2 phosphorylates and inhibits TAp73 tumor suppressor function to promote expression of cancer stem cell genes and phenotype in head and neck cancer.

PubMed

Lu, Hai; Yan, Carol; Quan, Xin Xin; Yang, Xinping; Zhang, Jialing; Bian, Yansong; Chen, Zhong; Van Waes, Carter

2014-10-01

Cancer stem cells (CSC) and genes have been linked to cancer development and therapeutic resistance, but the signaling mechanisms regulating CSC genes and phenotype are incompletely understood. CK2 has emerged as a key signal serine/threonine kinase that modulates diverse signal cascades regulating cell fate and growth. We previously showed that CK2 is often aberrantly expressed and activated in head and neck squamous cell carcinomas (HNSCC), concomitantly with mutant (mt) tumor suppressor TP53, and inactivation of its family member, TAp73. Unexpectedly, we observed that classical stem cell genes Nanog, Sox2, and Oct4, are overexpressed in HNSCC with inactivated TAp73 and mtTP53. However, the potential relationship between CK2, TAp73 inactivation, and CSC phenotype is unknown. We reveal that inhibition of CK2 by pharmacologic inhibitors or siRNA inhibits the expression of CSC genes and side population (SP), while enhancing TAp73 mRNA and protein expression. Conversely, CK2 inhibitor attenuation of CSC protein expression and the SP by was abrogated by TAp73 siRNA. Bioinformatic analysis uncovered a single predicted CK2 threonine phosphorylation site (T27) within the N-terminal transactivation domain of TAp73. Nuclear CK2 and TAp73 interaction, confirmed by co-immunoprecipitation, was attenuated by CK2 inhibitor, or a T27A point-mutation of this predicted CK2 threonine phospho-acceptor site of TAp73. Further, T27A mutation attenuated phosphorylation, while enhancing TAp73 function in repressing CSC gene expression and SP cells. A new CK2 inhibitor, CX-4945, inhibited CSC related SP cells, clonogenic survival, and spheroid formation. Our study unveils a novel regulatory mechanism whereby aberrant CK2 signaling inhibits TAp73 to promote the expression of CSC genes and phenotype.

Microfluidic squeezing for intracellular antigen loading in polyclonal B-cells as cellular vaccines

NASA Astrophysics Data System (ADS)

Lee Szeto, Gregory; van Egeren, Debra; Worku, Hermoon; Sharei, Armon; Alejandro, Brian; Park, Clara; Frew, Kirubel; Brefo, Mavis; Mao, Shirley; Heimann, Megan; Langer, Robert; Jensen, Klavs; Irvine, Darrell J.

2015-05-01

B-cells are promising candidate autologous antigen-presenting cells (APCs) to prime antigen-specific T-cells both in vitro and in vivo. However to date, a significant barrier to utilizing B-cells as APCs is their low capacity for non-specific antigen uptake compared to “professional” APCs such as dendritic cells. Here we utilize a microfluidic device that employs many parallel channels to pass single cells through narrow constrictions in high throughput. This microscale “cell squeezing” process creates transient pores in the plasma membrane, enabling intracellular delivery of whole proteins from the surrounding medium into B-cells via mechano-poration. We demonstrate that both resting and activated B-cells process and present antigens delivered via mechano-poration exclusively to antigen-specific CD8+T-cells, and not CD4+T-cells. Squeezed B-cells primed and expanded large numbers of effector CD8+T-cells in vitro that produced effector cytokines critical to cytolytic function, including granzyme B and interferon-γ. Finally, antigen-loaded B-cells were also able to prime antigen-specific CD8+T-cells in vivo when adoptively transferred into mice. Altogether, these data demonstrate crucial proof-of-concept for mechano-poration as an enabling technology for B-cell antigen loading, priming of antigen-specific CD8+T-cells, and decoupling of antigen uptake from B-cell activation.

Bottled, filtered, and tap water use in Latino and non-Latino children.

PubMed

Hobson, Wendy L; Knochel, Miguel L; Byington, Carrie L; Young, Paul C; Hoff, Charles J; Buchi, Karen F

2007-05-01

To describe bottled, filtered, and tap water consumption and fluoride use among pediatric patients; to analyze differences between ethnic and socioeconomic groups; and to describe the frequency of physician-parent discussions regarding water consumption. Convenience sample survey. An urban public health clinic. Parents attending a public health clinic. The primary outcome measure was the prevalence of tap, filtered, and bottled water use. The secondary outcome measures were supplemental fluoride use and the percentage of patients reporting discussions of water consumption with their physician. A total of 216 parents (80.5% Latino and 19.5% non-Latino) completed the survey. Of the parents, 30.1% never drank tap water and 41.2% never gave it to their children. Latino parents were less likely than non-Latino parents to drink tap water (odds ratio, 0.26; 95% confidence interval, 0.10-0.67) and less likely to give tap water to their children (odds ratio, 0.32; 95% confidence interval, 0.15-0.70). More Latinos believed that tap water would make them sick (odds ratio, 5.63; 95% confidence interval, 2.17-14.54). Approximately 40% of children who never drank tap water were not receiving fluoride supplements. Of the lowest-income families (

Identifying Safer Anti-Wear Triaryl Phosphate Additives for Jet Engine Lubricants

PubMed Central

Baker, Paul E.; Cole, Toby B.; Cartwright, Megan; Suzuki, Stephanie M.; Thummel, Kenneth E.; Lin, Yvonne S.; Co, Aila L.; Rettie, Allan E.; Kim, Jerry H.; Furlong, Clement E.

2013-01-01

Individuals aboard jet aircraft may be exposed to potentially toxic triaryl organophosphate anti-wear lubricant additives (TAPs) that are converted by cytochromes P450 into toxic metabolites. Consequences of exposure could be reduced by using less toxic TAPs. Our goal was to determine whether an in vitro assay for inhibition of butyrylcholinesterase (BChE) by bioactivated TAPs would be predictive of inhibition of serine active-site enzymes in vivo. The in vitro assay involved TAP bioactivation with liver microsomes and NADPH, followed by incubation with human BChE and measurement of BChE activity. Of 19 TAPs tested, tert-butylated isomers produced the least BChE inhibition. To determine the relevance of these results in vivo, mice were exposed to Durad 125 (D125; a commercial mixture of TAP esters) or to TAPs demonstrating low or no BChE inhibition when assayed in vitro. Inhibition of BChE by bioactivated TAPs in vitro correlated well with inhibition of other serine active-site enzymes in vivo, with the exception of brain acetylcholinesterase and neuropathy target esterase (NTE), which were not inhibited by any TAP tested following single exposures. A recombinant catalytic domain of NTE (rNEST) exhibited classical kinetic properties of NTE. The metabolite of tri-(o-cresyl) phosphate (ToCP), 2-(o-cresyl)-4H-1,3,2-benzodioxaphosphoran-2-one (CBDP), inhibited rNEST in vitro, but with an IC50 value almost 6-times higher than for inhibition of BChE. Physiologically-relevant concentrations of the flavonoid, naringenin, dramatically reduced D125 bioconversion in vitro. The in vitro assay should provide a valuable tool for prescreening candidate TAP anti-wear additives, identifying safer additives and reducing the number of animals required for in vivo toxicity testing. PMID:23085349

Identifying safer anti-wear triaryl phosphate additives for jet engine lubricants.

PubMed

Baker, Paul E; Cole, Toby B; Cartwright, Megan; Suzuki, Stephanie M; Thummel, Kenneth E; Lin, Yvonne S; Co, Aila L; Rettie, Allan E; Kim, Jerry H; Furlong, Clement E

2013-03-25

Individuals aboard jet aircraft may be exposed to potentially toxic triaryl organophosphate anti-wear lubricant additives (TAPs) that are converted by cytochromes P450 into toxic metabolites. Consequences of exposure could be reduced by using less toxic TAPs. Our goal was to determine whether an in vitro assay for inhibition of butyrylcholinesterase (BChE) by bioactivated TAPs would be predictive of inhibition of serine active-site enzymes in vivo. The in vitro assay involved TAP bioactivation with liver microsomes and NADPH, followed by incubation with human BChE and measurement of BChE activity. Of 19 TAPs tested, tert-butylated isomers produced the least BChE inhibition. To determine the relevance of these results in vivo, mice were exposed to Durad 125 (D125; a commercial mixture of TAP esters) or to TAPs demonstrating low or no BChE inhibition when assayed in vitro. Inhibition of BChE by bioactivated TAPs in vitro correlated well with inhibition of other serine active-site enzymes in vivo, with the exception of brain acetylcholinesterase and neuropathy target esterase (NTE), which were not inhibited by any TAP tested following single exposures. A recombinant catalytic domain of NTE (rNEST) exhibited classical kinetic properties of NTE. The metabolite of tri-(o-cresyl) phosphate (ToCP), 2-(o-cresyl)-4H-1,3,2-benzodioxaphosphoran-2-one (CBDP), inhibited rNEST in vitro, but with an IC(50) value almost 6-times higher than for inhibition of BChE. Physiologically-relevant concentrations of the flavonoid naringenin dramatically reduced D125 bioconversion in vitro. The in vitro assay should provide a valuable tool for prescreening candidate TAP anti-wear additives, identifying safer additives and reducing the number of animals required for in vivo toxicity testing. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Traffic Aware Planner (TAP) Flight Evaluation

NASA Technical Reports Server (NTRS)

Maris, John M.; Haynes, Mark A.; Wing, David J.; Burke, Kelly A.; Henderson, Jeff; Woods, Sharon E.

2014-01-01

NASA's Traffic Aware Planner (TAP) is a cockpit decision support tool that has the potential to achieve significant fuel and time savings when it is embedded in the data-rich Next Generation Air Transportation System (NextGen) airspace. To address a key step towards the operational deployment of TAP and the NASA concept of Traffic Aware Strategic Aircrew Requests (TASAR), a system evaluation was conducted in a representative flight environment in November, 2013. Numerous challenges were overcome to achieve this goal, including the porting of the foundational Autonomous Operations Planner (AOP) software from its original simulation-based, avionics-embedded environment to an Electronic Flight Bag (EFB) platform. A flight-test aircraft was modified to host the EFB, the TAP application, an Automatic Dependent Surveillance Broadcast (ADS-B) processor, and a satellite broadband datalink. Nine Evaluation Pilots conducted 26 hours of TAP assessments using four route profiles in the complex eastern and north-eastern United States airspace. Extensive avionics and video data were collected, supplemented by comprehensive inflight and post-flight questionnaires. TAP was verified to function properly in the live avionics and ADS-B environment, characterized by recorded data dropouts, latency, and ADS-B message fluctuations. Twelve TAP-generated optimization requests were submitted to ATC, of which nine were approved, and all of which resulted in fuel and/or time savings. Analysis of subjective workload data indicated that pilot interaction with TAP during flight operations did not induce additional cognitive loading. Additionally, analyses of post-flight questionnaire data showed that the pilots perceived TAP to be useful, understandable, intuitive, and easy to use. All program objectives were met, and the next phase of TAP development and evaluations with partner airlines is in planning for 2015.

A comparison among tapentadol tamper-resistant formulations (TRF) and OxyContin® (non-TRF) in prescription opioid abusers

PubMed Central

Vosburg, Suzanne K.; Jones, Jermaine D.; Manubay, Jeanne M.; Ashworth, Judy B.; Shapiro, Douglas Y.; Comer, Sandra D.

2013-01-01

Aims To examine whether tamper-resistant formulations (TRFs) of tapentadol hydrochloride ER 50 mg (TAP50) and tapentadol hydrochloride 250 mg (TAP250) could be converted into forms amenable to intranasal (Study 1) or intravenous abuse (Study 2). Design Randomized, repeated-measures study designs were employed. A non-TRF of OxyContin® 40 mg (OXY40) served as a positive control. No drug was taken in either study. Setting The studies took place in an outpatient setting in New York, NY. Participants 25 experienced, healthy extended-release oxycodone abusers participated in each study. Measurements The primary outcome for Study 1 was percentage of participants who indicated they would snort the tampered tablets, while the primary outcome for Study 2 was percent yield of active drug in solution. Other descriptive variables such as time spent manipulating the tablets were also examined to better characterize tampering behaviors. Findings Tampered TRF tablets were less desirable than the tampered OXY40 tablets. Few individuals were willing to snort the TRF particles (TAP50: 24%, TAP250: 16%; OXY40: 100% p<.001). There was less drug extracted from the TAP50 tablet than from the OXY40 tablet (3.5% vs. 37.0%, p=.008), and no samples from the TAP250 tablets contained analyzable solutions of the drug. It took participants longer to tamper with the TAPs (Study 1: TAP50 vs. OXY40, p<.01; TAP250 vs. OXY40, p<.01; Study 2: TAP250 vs. OXY40, p<05). Conclusions Taptentadol TRF tablets were not well-liked by individuals who regularly tampered with extended-release oxycodone tablets. Employing tamper resistant technology may be a promising approach towards reducing the abuse potential of tapentadol ER. PMID:23316699

Combined visual illusion effects on the perceived index of difficulty and movement outcomes in discrete and continuous fitts' tapping.

PubMed

Alphonsa, Sushma; Dai, Boyi; Benham-Deal, Tami; Zhu, Qin

2016-01-01

The speed-accuracy trade-off is a fundamental movement problem that has been extensively investigated. It has been established that the speed at which one can move to tap targets depends on how large the targets are and how far they are apart. These spatial properties of the targets can be quantified by the index of difficulty (ID). Two visual illusions are known to affect the perception of target size and movement amplitude: the Ebbinghaus illusion and Muller-Lyer illusion. We created visual images that combined these two visual illusions to manipulate the perceived ID, and then examined people's visual perception of the targets in illusory context as well as their performance in tapping those targets in both discrete and continuous manners. The findings revealed that the combined visual illusions affected the perceived ID similarly in both discrete and continuous judgment conditions. However, the movement outcomes were affected by the combined visual illusions according to the tapping mode. In discrete tapping, the combined visual illusions affected both movement accuracy and movement amplitude such that the effective ID resembled the perceived ID. In continuous tapping, none of the movement outcomes were affected by the combined visual illusions. Participants tapped the targets with higher speed and accuracy in all visual conditions. Based on these findings, we concluded that distinct visual-motor control mechanisms were responsible for execution of discrete and continuous Fitts' tapping. Although discrete tapping relies on allocentric information (object-centered) to plan for action, continuous tapping relies on egocentric information (self-centered) to control for action. The planning-control model for rapid aiming movements is supported.

Motor facilitation during real-time movement imitation in Parkinson's disease: a virtual reality study.

PubMed

Robles-García, Verónica; Arias, Pablo; Sanmartín, Gabriel; Espinosa, Nelson; Flores, Julian; Grieve, Kenneth L; Cudeiro, Javier

2013-12-01

Impaired temporal stability and poor motor unit recruitment are key impairments in Parkinsonian motor control during a whole spectrum of rhythmic movements, from simple finger tapping to gait. Therapies based on imitation can be designed for patients with motor impairments and virtual-reality (VR) offers a new perspective. Motor actions are known to depend upon the dopaminergic system, whose involvement in imitation is unknown. We sought to understand this role and the underlying possibilities for motor rehabilitation, by observing the execution of different motor-patterns during imitation in a VR environment in subjects with and without dopaminergic deficits. 10 OFF-dose idiopathic Parkinson's Disease patients (PD), 9 age-matched and 9 young-subjects participated. Subjects performed finger-tapping at their "comfort" and "slow-comfort" rates, while immersed in VR presenting their "avatar" in 1st person perspective. Imitation was evaluated by asking subjects to replicate finger-tapping patterns different to their natural one. The finger-pattern presented matched their comfort and comfort-slow rates, but without a pause on the table (continuously moving). Patients were able to adapt their finger-tapping correctly, showing that in comparison with the control groups, the dopaminergic deficiency of PD did not impair imitation. During imitation the magnitude of EMG increased and the temporal variability of movement decreased. PD-patients have unaltered ability to imitate instructed motor-patterns, suggesting that a fully-functional dopaminergic system is not essential for such imitation. It should be further investigated if imitation training over a period of time induces positive off-line motor adaptations with transfer to non-imitation tasks. Copyright © 2013 Elsevier Ltd. All rights reserved.

Virtual Reality as a Tool for Evaluation of Repetitive Rhythmic Movements in the Elderly and Parkinson's Disease Patients

PubMed Central

Arias, Pablo; Robles-García, Verónica; Sanmartín, Gabriel; Flores, Julian; Cudeiro, Javier

2012-01-01

This work presents an immersive Virtual Reality (VR) system to evaluate, and potentially treat, the alterations in rhythmic hand movements seen in Parkinson's disease (PD) and the elderly (EC), by comparison with healthy young controls (YC). The system integrates the subjects into a VR environment by means of a Head Mounted Display, such that subjects perceive themselves in a virtual world consisting of a table within a room. In this experiment, subjects are presented in 1st person perspective, so that the avatar reproduces finger tapping movements performed by the subjects. The task, known as the finger tapping test (FT), was performed by all three subject groups, PD, EC and YC. FT was carried out by each subject on two different days (sessions), one week apart. In each FT session all subjects performed FT in the real world (FTREAL) and in the VR (FTVR); each mode was repeated three times in randomized order. During FT both the tapping frequency and the coefficient of variation of inter-tap interval were registered. FTVR was a valid test to detect differences in rhythm formation between the three groups. Intra-class correlation coefficients (ICC) and mean difference between days for FTVR (for each group) showed reliable results. Finally, the analysis of ICC and mean difference between FTVR vs FTREAL, for each variable and group, also showed high reliability. This shows that FT evaluation in VR environments is valid as real world alternative, as VR evaluation did not distort movement execution and detects alteration in rhythm formation. These results support the use of VR as a promising tool to study alterations and the control of movement in different subject groups in unusual environments, such as during fMRI or other imaging studies. PMID:22279559

Did I see your hand moving? The effect of movement-related information on the Corsi block tapping task.

PubMed

Brunetti, Riccardo; Del Gatto, Claudia; Cavallina, Clarissa; Farina, Benedetto; Delogu, Franco

2018-05-01

The Corsi Block Tapping Task is a widespread test used to assess spatial working memory. Previous research hypothesized that the discrepancy found in some cases between the traditional and the digital (touchscreen) version of the Corsi block tapping task may be due to a direct motor resonance between the experimenter's and the participant's hand movements. However, we hypothesize that this discrepancy might be due to extra movement-related information included in the traditional version, lacking in the digital one. We investigated the effects of such task-irrelevant information using eCorsi, a touchscreen version of the task. In Experiment 1, we manipulate timing in sequence presentation, creating three conditions. In the Congruent condition, the inter-stimulus intervals reflected the physical distance in which the stimuli were spatially placed: The longer the spatial distance, the longer the temporal interval. In the Incongruent condition the timing changed randomly. Finally, in the Isochronous condition every stimulus appeared after a fixed interval, independently from its spatial position. The results showed a performance enhancement in the Congruent condition, suggesting an incidental spatio-temporal binding. In Experiment 2, we added straight lines between each location in the sequences: In the Trajectories condition participants saw trajectories from one spatial position to the other during sequence presentation, while a condition without such trajectories served as control. Results showed better performances in the Trajectories condition. We suggest that the timing and trajectories information play a significant role in the discrepancies found between the traditional and the touchscreen version of the Corsi Block Tapping Task, without the necessity of explanations involving direct motor resonance (e.g. seeing an actual hand moving) as a causal factor.

Can we remove iodine-131 from tap water in Japan by boiling? - Experimental testing in response to the Fukushima Daiichi Nuclear Power Plant accident.

PubMed

Tagami, K; Uchida, S

2011-08-01

Iodine-131 concentrations in tap water higher than 100 BqL(-1) were reported by several local governments in Japan following the Fukushima Daiichi Nuclear Power Plant accident. Some individuals in the emergency-response community recommended the boiling of tap water to remove iodine-131. However, the tap water boiling tests in this study showed no iodine-131 loss from the tap water with either short-term boiling (1-10 min) or prolonged boiling (up to 30 min) resulting in up to 3-fold volume reductions. In this situation, boiling was shown to be not effective in removing iodine-131 from tap water; indeed even higher concentrations may result from the liquid-volume reduction accompanying this process. Copyright © 2011 Elsevier Ltd. All rights reserved.

Rhythmic motor entrainment in children with speech and language impairments: tapping to the beat.

PubMed

Corriveau, Kathleen H; Goswami, Usha

2009-01-01

In prior work (Corriveau et al., 2007), we showed that children with speech and language impairments (SLI) were significantly less sensitive than controls to two auditory cues to rhythmic timing, amplitude envelope rise time and duration. Here we explore whether rhythmic problems extend to rhythmic motor entrainment. Tapping in synchrony with a beat has been described as the simplest rhythmic act that humans perform. We explored whether tapping to a beat would be impaired in children for whom auditory rhythmic timing is impaired. Children with SLI were indeed found to be impaired in a range of measures of paced rhythmic tapping, but were not equally impaired in tapping in an unpaced control condition requiring an internally-generated rhythm. The severity of impairment in paced tapping was linked to language and literacy outcomes.

Association between finger tapping, attention, memory, and cognitive diagnosis in elderly patients.

PubMed

Rabinowitz, Israel; Lavner, Yizhar

2014-08-01

This study examined the association between spontaneous finger tapping and cognitive function, with a detailed analysis of the two main phases of finger tapping, the touch-phase and the off-phase. 170 elderly patients (83 men, 87 women; M age = 82.1 yr., SD = 6.2) underwent cognitive assessment including the Mini-Mental State Examination, a forward digit span test, and 15 sec. of finger tapping. Results indicated a significant increase in the length and variability of the finger-touch phase among participants with mild cognitive impairment or dementia compared to participants with no cognitive impairment, suggesting a relationship between finger tapping and attention, short-term memory, and cognitive diagnosis. Pattern classification analyses on the finger tapping parameters indicated a specificity of 0.91 and sensitivity of 0.52 for ruling out cognitive impairment.

Antigen Presentation by Individually Transferred HLA Class I Genes in HLA-A, HLA-B, HLA-C Null Human Cell Line Generated Using the Multiplex CRISPR-Cas9 System.

PubMed

Hong, Cheol-Hwa; Sohn, Hyun-Jung; Lee, Hyun-Joo; Cho, Hyun-Il; Kim, Tai-Gyu

Human leukocyte antigens (HLAs) are essential immune molecules that affect transplantation and adoptive immunotherapy. When hematopoietic stem cells or organs are transplanted with HLA-mismatched recipients, graft-versus-host disease or graft rejection can be induced by allogeneic immune responses. The function of each HLA allele has been studied using HLA-deficient cells generated from mutant cell lines or by RNA interference, zinc finger nuclease, and the CRISPR/Cas9 system. To improve HLA gene editing, we attempted to generate an HLA class I null cell line using the multiplex CRISPR/Cas9 system by targeting exons 2 and 3 of HLA-A, HLA-B, and HLA-C genes simultaneously. Multiplex HLA editing could induce the complete elimination of HLA class I genes by bi-allelic gene disruption on target sites which was defined by flow cytometry and target-specific polymerase chain reaction. Furthermore, artificial antigen-presenting cells were generated by transfer of a single HLA class I allele and co-stimulatory molecules into this novel HLA class I null cell line. Artificial antigen-presenting cells showed HLA-restricted antigen presentation following antigen processing and were successfully used for the efficient generation of tumor antigen-specific cytotoxic T cells in vitro. The efficient editing of HLA genes may provide a basis for universal cellular therapies and transplantation.

Role of Plastid Protein Phosphatase TAP38 in LHCII Dephosphorylation and Thylakoid Electron Flow

PubMed Central

Pribil, Mathias; Pesaresi, Paolo; Hertle, Alexander; Barbato, Roberto; Leister, Dario

2010-01-01

Short-term changes in illumination elicit alterations in thylakoid protein phosphorylation and reorganization of the photosynthetic machinery. Phosphorylation of LHCII, the light-harvesting complex of photosystem II, facilitates its relocation to photosystem I and permits excitation energy redistribution between the photosystems (state transitions). The protein kinase STN7 is required for LHCII phosphorylation and state transitions in the flowering plant Arabidopsis thaliana. LHCII phosphorylation is reversible, but extensive efforts to identify the protein phosphatase(s) that dephosphorylate LHCII have been unsuccessful. Here, we show that the thylakoid-associated phosphatase TAP38 is required for LHCII dephosphorylation and for the transition from state 2 to state 1 in A. thaliana. In tap38 mutants, thylakoid electron flow is enhanced, resulting in more rapid growth under constant low-light regimes. TAP38 gene overexpression markedly decreases LHCII phosphorylation and inhibits state 1→2 transition, thus mimicking the stn7 phenotype. Furthermore, the recombinant TAP38 protein is able, in an in vitro assay, to directly dephosphorylate LHCII. The dependence of LHCII dephosphorylation upon TAP38 dosage, together with the in vitro TAP38-mediated dephosphorylation of LHCII, suggests that TAP38 directly acts on LHCII. Although reversible phosphorylation of LHCII and state transitions are crucial for plant fitness under natural light conditions, LHCII hyperphosphorylation associated with an arrest of photosynthesis in state 2 due to inactivation of TAP38 improves photosynthetic performance and plant growth under state 2-favoring light conditions. PMID:20126264

Functional Analysis of the Accessory Protein TapA in Bacillus subtilis Amyloid Fiber Assembly

PubMed Central

Romero, Diego; Vlamakis, Hera; Losick, Richard

2014-01-01

Bacillus subtilis biofilm formation relies on the assembly of a fibrous scaffold formed by the protein TasA. TasA polymerizes into highly stable fibers with biochemical and morphological features of functional amyloids. Previously, we showed that assembly of TasA fibers requires the auxiliary protein TapA. In this study, we investigated the roles of TapA sequences from the C-terminal and N-terminal ends and TapA cysteine residues in its ability to promote the assembly of TasA amyloid-like fibers. We found that the cysteine residues are not essential for the formation of TasA fibers, as their replacement by alanine residues resulted in only minor defects in biofilm formation. Mutating sequences in the C-terminal half had no effect on biofilm formation. However, we identified a sequence of 8 amino acids in the N terminus that is key for TasA fiber formation. Strains expressing TapA lacking these 8 residues were completely defective in biofilm formation. In addition, this TapA mutant protein exhibited a dominant negative effect on TasA fiber formation. Even in the presence of wild-type TapA, the mutant protein inhibited fiber assembly in vitro and delayed biofilm formation in vivo. We propose that this 8-residue sequence is crucial for the formation of amyloid-like fibers on the cell surface, perhaps by mediating the interaction between TapA or TapA and TasA molecules. PMID:24488317

Functional analysis of the accessory protein TapA in Bacillus subtilis amyloid fiber assembly.

PubMed

Romero, Diego; Vlamakis, Hera; Losick, Richard; Kolter, Roberto

2014-04-01

Bacillus subtilis biofilm formation relies on the assembly of a fibrous scaffold formed by the protein TasA. TasA polymerizes into highly stable fibers with biochemical and morphological features of functional amyloids. Previously, we showed that assembly of TasA fibers requires the auxiliary protein TapA. In this study, we investigated the roles of TapA sequences from the C-terminal and N-terminal ends and TapA cysteine residues in its ability to promote the assembly of TasA amyloid-like fibers. We found that the cysteine residues are not essential for the formation of TasA fibers, as their replacement by alanine residues resulted in only minor defects in biofilm formation. Mutating sequences in the C-terminal half had no effect on biofilm formation. However, we identified a sequence of 8 amino acids in the N terminus that is key for TasA fiber formation. Strains expressing TapA lacking these 8 residues were completely defective in biofilm formation. In addition, this TapA mutant protein exhibited a dominant negative effect on TasA fiber formation. Even in the presence of wild-type TapA, the mutant protein inhibited fiber assembly in vitro and delayed biofilm formation in vivo. We propose that this 8-residue sequence is crucial for the formation of amyloid-like fibers on the cell surface, perhaps by mediating the interaction between TapA or TapA and TasA molecules.

Tapping insertional torque allows prediction for better pedicle screw fixation and optimal screw size selection.

PubMed

Helgeson, Melvin D; Kang, Daniel G; Lehman, Ronald A; Dmitriev, Anton E; Luhmann, Scott J

2013-08-01

There is currently no reliable technique for intraoperative assessment of pedicle screw fixation strength and optimal screw size. Several studies have evaluated pedicle screw insertional torque (IT) and its direct correlation with pullout strength. However, there is limited clinical application with pedicle screw IT as it must be measured during screw placement and rarely causes the spine surgeon to change screw size. To date, no study has evaluated tapping IT, which precedes screw insertion, and its ability to predict pedicle screw pullout strength. The objective of this study was to investigate tapping IT and its ability to predict pedicle screw pullout strength and optimal screw size. In vitro human cadaveric biomechanical analysis. Twenty fresh-frozen human cadaveric thoracic vertebral levels were prepared and dual-energy radiographic absorptiometry scanned for bone mineral density (BMD). All specimens were osteoporotic with a mean BMD of 0.60 ± 0.07 g/cm(2). Five specimens (n=10) were used to perform a pilot study, as there were no previously established values for optimal tapping IT. Each pedicle during the pilot study was measured using a digital caliper as well as computed tomography measurements, and the optimal screw size was determined to be equal to or the first size smaller than the pedicle diameter. The optimal tap size was then selected as the tap diameter 1 mm smaller than the optimal screw size. During optimal tap size insertion, all peak tapping IT values were found to be between 2 in-lbs and 3 in-lbs. Therefore, the threshold tapping IT value for optimal pedicle screw and tap size was determined to be 2.5 in-lbs, and a comparison tapping IT value of 1.5 in-lbs was selected. Next, 15 test specimens (n=30) were measured with digital calipers, probed, tapped, and instrumented using a paired comparison between the two threshold tapping IT values (Group 1: 1.5 in-lbs; Group 2: 2.5 in-lbs), randomly assigned to the left or right pedicle on each specimen. Each pedicle was incrementally tapped to increasing size (3.75, 4.00, 4.50, and 5.50 mm) until the threshold value was reached based on the assigned group. Pedicle screw size was determined by adding 1 mm to the tap size that crossed the threshold torque value. Torque measurements were recorded with each revolution during tap and pedicle screw insertion. Each specimen was then individually potted and pedicle screws pulled out "in-line" with the screw axis at a rate of 0.25 mm/sec. Peak pullout strength (POS) was measured in Newtons (N). The peak tapping IT was significantly increased (50%) in Group 2 (3.23 ± 0.65 in-lbs) compared with Group 1 (2.15 ± 0.56 in-lbs) (p=.0005). The peak screw IT was also significantly increased (19%) in Group 2 (8.99 ± 2.27 in-lbs) compared with Group 1 (7.52 ± 2.96 in-lbs) (p=.02). The pedicle screw pullout strength was also significantly increased (23%) in Group 2 (877.9 ± 235.2 N) compared with Group 1 (712.3 ± 223.1 N) (p=.017). The mean pedicle screw diameter was significantly increased in Group 2 (5.70 ± 1.05 mm) compared with Group 1 (5.00 ± 0.80 mm) (p=.0002). There was also an increased rate of optimal pedicle screw size selection in Group 2 with 9 of 15 (60%) pedicle screws compared with Group 1 with 4 of 15 (26.7%) pedicle screws within 1 mm of the measured pedicle width. There was a moderate correlation for tapping IT with both screw IT (r=0.54; p=.002) and pedicle screw POS (r=0.55; p=.002). Our findings suggest that tapping IT directly correlates with pedicle screw IT, pedicle screw pullout strength, and optimal pedicle screw size. Therefore, tapping IT may be used during thoracic pedicle screw instrumentation as an adjunct to preoperative imaging and clinical experience to maximize fixation strength and optimize pedicle "fit and fill" with the largest screw possible. However, further prospective, in vivo studies are necessary to evaluate the intraoperative use of tapping IT to predict screw loosening/complications. Published by Elsevier Inc.

Antigen recognition by H-2-restricted T cells. I. Cell-free antigen processing

PubMed Central

1983-01-01

We examined the ability of a set of cloned chicken ovalbumin (cOVA)- specific, Id-restricted, T cell hybridomas to produce interleukin-2 in response to cOVA presented by the Ia+ B cell lymphoma line, A20-2J. Although viable A20-2J cells presented native, denatured, and fragmented cOVA more or less equally well, A20-2J cells that were glutaraldehyde-fixed could present only enzymatically or chemically fragmented cOVA. These results suggest that antigen fragmentation may be both necessary and sufficient to define accessory cell processing of soluble antigens so that they may be recognized in association with I- region molecules by T cells. PMID:6193218

Deploying a Route Optimization EFB Application for Commercial Airline Operational Trials

NASA Technical Reports Server (NTRS)

Roscoe, David A.; Vivona, Robert A.; Woods, Sharon E.; Karr, David A.; Wing, David J.

2016-01-01

The Traffic Aware Planner (TAP), developed for NASA Langley Research Center to support the Traffic Aware Strategic Aircrew Requests (TASAR) project, is a flight-efficiency software application developed for an Electronic Flight Bag (EFB). Tested in two flight trials and planned for operational testing by two commercial airlines, TAP is a real-time trajectory optimization application that leverages connectivity with onboard avionics and broadband Internet sources to compute and recommend route modifications to flight crews to improve fuel and time performance. The application utilizes a wide range of data, including Automatic Dependent Surveillance Broadcast (ADS-B) traffic, Flight Management System (FMS) guidance and intent, on-board sensors, published winds and weather, and Special Use Airspace (SUA) schedules. This paper discusses the challenges of developing and deploying TAP to various EFB platforms, our solutions to some of these challenges, and lessons learned, to assist commercial software developers and hardware manufacturers in their efforts to implement and extend TAP functionality in their environments. EFB applications (such as TAP) typically access avionics data via an ARINC 834 Simple Text Avionics Protocol (STAP) server hosted by an Aircraft Interface Device (AID) or other installed hardware. While the protocol is standardized, the data sources, content, and transmission rates can vary from aircraft to aircraft. Additionally, the method of communicating with the AID may vary depending on EFB hardware and/or the availability of onboard networking services, such as Ethernet, WIFI, Bluetooth, or other mechanisms. EFBs with portable and installed components can be implemented using a variety of operating systems, and cockpits are increasingly incorporating tablet-based technologies, further expanding the number of platforms the application may need to support. Supporting multiple EFB platforms, AIDs, avionics datasets, and user interfaces presents a challenge for software developers and the management of their code baselines. Maintaining multiple baselines to support all deployment targets can be extremely cumbersome and expensive. Certification also needs to be considered when developing the application. Regardless of whether the software is itself destined to be certified, data requirements in support of the application and user interface elements may introduce certification requirements for EFB manufacturers and the airlines. The example of TAP, the challenges faced, solutions implemented, and lessons learned will give EFB application and hardware developers insight into future potential requirements in deploying TAP or similar flight-deck EFB applications.

Exploration of graphene oxide as an intelligent platform for cancer vaccines

NASA Astrophysics Data System (ADS)

Yue, Hua; Wei, Wei; Gu, Zonglin; Ni, Dezhi; Luo, Nana; Yang, Zaixing; Zhao, Lin; Garate, Jose Antonio; Zhou, Ruhong; Su, Zhiguo; Ma, Guanghui

2015-11-01

We explored an intelligent vaccine system via facile approaches using both experimental and theoretical techniques based on the two-dimensional graphene oxide (GO). Without extra addition of bio/chemical stimulators, the microsized GO imparted various immune activation tactics to improve the antigen immunogenicity. A high antigen adsorption was acquired, and the mechanism was revealed to be a combination of electrostatic, hydrophobic, and π-π stacking interactions. The ``folding GO'' acted as a cytokine self-producer and antigen reservoir and showed a particular autophagy, which efficiently promoted the activation of antigen presenting cells (APCs) and subsequent antigen cross-presentation. Such a ``One but All'' modality thus induced a high level of anti-tumor responses in a programmable way and resulted in efficient tumor regression in vivo. This work may shed light on the potential use of a new dimensional nano-platform in the development of high-performance cancer vaccines.We explored an intelligent vaccine system via facile approaches using both experimental and theoretical techniques based on the two-dimensional graphene oxide (GO). Without extra addition of bio/chemical stimulators, the microsized GO imparted various immune activation tactics to improve the antigen immunogenicity. A high antigen adsorption was acquired, and the mechanism was revealed to be a combination of electrostatic, hydrophobic, and π-π stacking interactions. The ``folding GO'' acted as a cytokine self-producer and antigen reservoir and showed a particular autophagy, which efficiently promoted the activation of antigen presenting cells (APCs) and subsequent antigen cross-presentation. Such a ``One but All'' modality thus induced a high level of anti-tumor responses in a programmable way and resulted in efficient tumor regression in vivo. This work may shed light on the potential use of a new dimensional nano-platform in the development of high-performance cancer vaccines. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04986e

Podocytes Are Nonhematopoietic Professional Antigen-Presenting Cells

PubMed Central

Burkard, Miriam; Ölke, Martha; Daniel, Christoph; Amann, Kerstin; Hugo, Christian; Kurts, Christian; Steinkasserer, Alexander; Gessner, André

2013-01-01

Podocytes are essential to the structure and function of the glomerular filtration barrier; however, they also exhibit increased expression of MHC class II molecules under inflammatory conditions, and they remove Ig and immune complexes from the glomerular basement membrane (GBM). This finding suggests that podocytes may act as antigen-presenting cells, taking up and processing antigens to initiate specific T cell responses, similar to professional hematopoietic cells such as dendritic cells or macrophages. Here, MHC–antigen complexes expressed exclusively on podocytes of transgenic mice were sufficient to activate CD8+ T cells in vivo. In addition, deleting MHC class II exclusively on podocytes prevented the induction of experimental anti-GBM nephritis. Podocytes ingested soluble and particulate antigens, activated CD4+ T cells, and crosspresented exogenous antigen on MHC class I molecules to CD8+ T cells. In conclusion, podocytes participate in the antigen-specific activation of adaptive immune responses, providing a potential target for immunotherapies of inflammatory kidney diseases and transplant rejection. PMID:23539760

Toxoplasma gondii Recombinant Antigens as Tools for Serodiagnosis of Human Toxoplasmosis: Current Status of Studies

PubMed Central

2013-01-01

Toxoplasma gondii is a parasitic protozoan which is the cause of toxoplasmosis. Although human toxoplasmosis in healthy adults is usually asymptomatic, serious disease can occur in the case of congenital infections and immunocompromised individuals. Furthermore, despite the exact recognition of its etiology, it still presents a diagnostic problem. Diagnosis of toxoplasmosis is mainly based on the results of serological tests detecting anti-T. gondii-specific antibodies in the patient's serum sample. The specificities and sensitivities of serology tests depend mostly on the diagnostic antigen(s) used. Most of the commercial serological kits currently available are based on Toxoplasma lysate antigens (TLAs). In recent years, many studies showed that recombinant antigenic proteins of T. gondii may be an alternative source of antigens which are very useful for the serodiagnosis of toxoplasmosis. This article presents a review of current studies on the application and usefulness of different T. gondii recombinant antigens in serological tests for the diagnosis of human toxoplasmosis. PMID:23784855

The Effect of Spinal Tap Test on Different Sensory Modalities of Postural Stability in Idiopathic Normal Pressure Hydrocephalus.

PubMed

Abram, Katrin; Bohne, Silvia; Bublak, Peter; Karvouniari, Panagiota; Klingner, Carsten M; Witte, Otto W; Guntinas-Lichius, Orlando; Axer, Hubertus

2016-01-01

Postural instability in patients with normal pressure hydrocephalus (NPH) is a most crucial symptom leading to falls with secondary complications. The aim of the current study was to evaluate the therapeutic effect of spinal tap on postural stability in these patients. Seventeen patients with clinical symptoms of NPH were examined using gait scale, computerized dynamic posturography (CDP), and neuropsychological assessment. Examinations were done before and after spinal tap test. The gait score showed a significant improvement 24 h after spinal tap test in all subtests and in the sum score (p < 0.003), while neuropsychological assessment did not reveal significant differences 72 h after spinal tap test. CDP showed significant improvements after spinal tap test in the Sensory Organization Tests 2 (p = 0.017), 4 (p = 0.001), and 5 (p = 0.009) and the composite score (p = 0.01). Patients showed best performance in somatosensory and worst performance in vestibular dominated tests. Vestibular dominated tests did not improve significantly after spinal tap test, while somatosensory and visual dominated tests did. Postural stability in NPH is predominantly affected by deficient vestibular functions, which did not improve after spinal tap test. Conditions which improved best were mainly independent from visual control and are based on proprioceptive functions.

Long-period gratings in photonic crystal fibers operating near the phase-matching turning point for evanescent chemical and biochemical sensing

NASA Astrophysics Data System (ADS)

Kanka, Jiri

2012-06-01

Fiber-optic long-period grating (LPG) operating near the dispersion turning point in its phase matching curve (PMC), referred to as a Turn Around Point (TAP) LPG, is known to be extremely sensitive to external parameters. Moreover, in a TAP LPG the phase matching condition can be almost satisfied over large spectral range, yielding a broadband LPG operation. TAP LPGs have been investigated, namely for use as broadband mode convertors and biosensors. So far TAP LPGs have been realized in specially designed or post-processed conventional fibers, not yet in PCFs, which allow a great degree of freedom in engineering the fiber's dispersion properties through the control of the PCF structural parameters. We have developed the design optimization technique for TAP PCF LPGs employing the finite element method for PCF modal analysis in a combination with the Nelder-Mead simplex method for minimizing the objective function based on target-specific PCF properties. Using this tool we have designed TAP PCF LPGs for specified wavelength ranges and refractive indices of medium in the air holes. Possible TAP PCF-LPG operational regimes - dual-resonance, broadband mode conversion and transmitted intensity-based operation - will be demonstrated numerically. Potential and limitations of TAP PCF-LPGs for evanescent chemical and biochemical sensing will be assessed.

Target of rapamycin complex 1 and Tap42-associated phosphatases are required for sensing changes in nitrogen conditions in the yeast Saccharomyces cerevisiae.

PubMed

Li, Jinmei; Yan, Gonghong; Liu, Sichi; Jiang, Tong; Zhong, Mingming; Yuan, Wenjie; Chen, Shaoxian; Zheng, Yin; Jiang, Yong; Jiang, Yu

2017-12-01

In yeast target of rapamycin complex 1 (TORC1) and Tap42-associated phosphatases regulate expression of genes involved in nitrogen limitation response and the nitrogen discrimination pathway. However, it remains unclear whether TORC1 and the phosphatases are required for sensing nitrogen conditions. Utilizing temperature sensitive mutants of tor2 and tap42, we examined the role of TORC1 and Tap42 in nuclear entry of Gln3, a key transcription factor in yeast nitrogen metabolism, in response to changes in nitrogen conditions. Our data show that TORC1 is essential for Gln3 nuclear entry upon nitrogen limitation and downshift in nitrogen quality. However, Tap42-associated phosphatases are required only under nitrogen limitation condition. In cells grown in poor nitrogen medium, the nitrogen permease reactivator kinase (Npr1) inhibits TORC1 activity and alters its association with Tap42, rendering Tap42-associated phosphatases unresponsive to nitrogen limitation. These findings demonstrate a direct role for TORC1 and Tap42-associated phosphatases in sensing nitrogen conditions and unveil an Npr1-dependent mechanism that controls TORC1 and the phosphatases in response to changes in nitrogen quality. © 2017 John Wiley & Sons Ltd.

Indoor Heating Drives Water Bacterial Growth and Community Metabolic Profile Changes in Building Tap Pipes during the Winter Season

PubMed Central

Zhang, Hai-Han; Chen, Sheng-Nan; Huang, Ting-Lin; Shang, Pan-Lu; Yang, Xiao; Ma, Wei-Xing

2015-01-01

The growth of the bacterial community harbored in indoor drinking water taps is regulated by external environmental factors, such as indoor temperature. However, the effect of indoor heating on bacterial regrowth associated with indoor drinking water taps is poorly understood. In the present work, flow cytometry and community-level sole-carbon-source utilization techniques were combined to explore the effects of indoor heating on water bacterial cell concentrations and community carbon metabolic profiles in building tap pipes during the winter season. The results showed that the temperature of water stagnated overnight (“before”) in the indoor water pipes was 15–17 °C, and the water temperature decreased to 4–6 °C after flushing for 10 min (“flushed”). The highest bacterial cell number was observed in water stagnated overnight, and was 5–11 times higher than that of flushed water. Meanwhile, a significantly higher bacterial community metabolic activity (AWCD590nm) was also found in overnight stagnation water samples. The significant “flushed” and “taps” values indicated that the AWCD590nm, and bacterial cell number varied among the taps within the flushed group (p < 0.01). Heatmap fingerprints and principle component analyses (PCA) revealed a significant discrimination bacterial community functional metabolic profiles in the water stagnated overnight and flushed water. Serine, threonine, glucose-phosphate, ketobutyric acid, phenylethylamine, glycerol, putrescine were significantly used by “before” water samples. The results suggested that water stagnated at higher temperature should be treated before drinking because of bacterial regrowth. The data from this work provides useful information on reasonable utilization of drinking water after stagnation in indoor pipes during indoor heating periods. PMID:26516885

Use of targeted transversus abdominus plane blocks in pediatric patients with anterior cutaneous nerve entrapment syndrome.

PubMed

Nizamuddin, Sarah L; Koury, Katharine M; Lau, Mary E; Watt, Lisa D; Gulur, Padma

2014-01-01

Anterior cutaneous nerve entrapment syndrome (ACNES) is a commonly overlooked source of chronic abdominal wall pain. A diagnosis of ACNES should be considered in cases of severe, localized abdominal pain that is accentuated by physical activity. Providers should consider diagnosing ACNES once a patient has both a positive result from a Carnett's test and precise localization of pain. We describe the use of transversus abdominus plane (TAP) blocks to treat ACNES in the pediatric patient population. TAP blocks are a treatment modality which have been described less frequently in the management of this syndrome, with rectus sheath blocks being used more commonly. TAP blocks can be used effectively for ACNES by targeting the site of maximal tenderness, which was identified using ultrasound guidance. Moreover, TAP blocks are an attractive procedure option for ACNES as they are less invasive than other commonly used techniques. We present 3 case series reports of pediatric patients evaluated at our institution for severe abdominal pain to describe the clinical manifestations, sequelae, and outcome of ACNES. Though the exact incidence of ACNES in the pediatric population is unknown, this condition has significant implications from chronic pain. Chronic pain can lead to significant emotional and social impacts on these pediatric patients, as well as their on their families. Further, the extensive utilization of health care resources is impacted when children with undiagnosed ACNES undergo invasive treatments when ACNES is not in the early differential. The purpose of this case series report is to prompt better recognition of the condition ACNES, and to highlight the efficacy of TAP blocks as a management strategy.

Exposure to Tobacco Advertising and Promotion among School Children Aged 13-15 in Vietnam - an Overview from GYTS 2014.

PubMed

Long, Tran Khanh; Son, Phung Xuan; Giang, Kim Bao; Hai, Phan Thi; Huyen, Doan Thi Thu; Khue, Luong Ngoc; Nga, Pham Thi Quynh; Lam, Nguyen Tuan; Minh, Hoang Van; Huong, Le Thi Thanh

2016-01-01

Evidence shows that tobacco advertising and promotion activities may increase tobacco consumption and usage, especially in youth. Despite the regulation on prohibiting advertisement of any tobacco product, tobacco advertisement and promotion activities are still common in Vietnam. This article presents current exposure to tobacco advertising and promotion (TAP) among school children aged 13 to 15 years in Vietnam in 2014 and potential influencing factors. Data from the Global Youth Tobacco Survey 2014 in Vietnam covering 3,430 school aged children were used. Both descriptive and analytical statistics were carried out with Stata 13 statistical software. Binary logistic regression was applied to explain the exposure to TAP among youth and examine relationships with individual factors. A significance level of p<0.05 and sampling weights were used in all of the computations. In the past 30 days, 48.6% of the students experienced exposure to at least 1 type of tobacco advertising or promotion. Wearing or otherwise using products related to tobacco was the most exposure TAP type reported by students (22.3%). The internet (22.1), points of sales (19.2) and social events (11.5) were three places that students aged 13-15 frequently were exposed to TAP. Binary logistic results showed that gender (female vs male) (OR = 0.61, 95%CI: 0.52 - 0.71), susceptibility to smoking (OR = 2.12, 95%CI: 1.53 - 2.92), closest friends' smoked (OR = 1.43, 95%CI: 1.2 - 1.7) and parents smoking status (OR = 2.83, 95%CI: 1.6 - 5.01) were significantly associated with TAP exposure among school-aged children. The research findings should contribute to effective implementation of measures for preventing and controlling tobacco use among students aged 13-15 in Viet Nam.

Twin anemia polycythemia sequence: a single center experience and literature review.

PubMed

Moaddab, Amirhossein; Nassr, Ahmed A; Espinoza, Jimmy; Ruano, Rodrigo; Bateni, Zhoobin H; Shamshirsaz, Amir A; Mandy, George T; Welty, Stephen E; Erfani, Hadi; Popek, Edwina J; Belfort, Michael A; Shamshirsaz, Alireza A

2016-10-01

Twin anemia polycythemia sequence (TAPS) is defined by significant intertwin hemoglobin discordance without the amniotic fluid discordance that characterizes twin-twin-transfusion syndrome (TTTS) in monochorionic twin pregnancies. TAPS is an uncommon condition which can either occur spontaneously, or following fetoscopic laser ablation for TTTS. This complication is thought to result from chronic transfusion through very small placental anastomoses; however, the pathogenesis of TAPS remains unknown. Consequently, there is no consensus in the management of TAPS. In this article, three cases of TAPS are described and we review the literature on this uncommon pregnancy complication. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The neural basis of audiomotor entrainment: an ALE meta-analysis

PubMed Central

Chauvigné, Léa A. S.; Gitau, Kevin M.; Brown, Steven

2014-01-01

Synchronization of body movement to an acoustic rhythm is a major form of entrainment, such as occurs in dance. This is exemplified in experimental studies of finger tapping. Entrainment to a beat is contrasted with movement that is internally driven and is therefore self-paced. In order to examine brain areas important for entrainment to an acoustic beat, we meta-analyzed the functional neuroimaging literature on finger tapping (43 studies) using activation likelihood estimation (ALE) meta-analysis with a focus on the contrast between externally-paced and self-paced tapping. The results demonstrated a dissociation between two subcortical systems involved in timing, namely the cerebellum and the basal ganglia. Externally-paced tapping highlighted the importance of the spinocerebellum, most especially the vermis, which was not activated at all by self-paced tapping. In contrast, the basal ganglia, including the putamen and globus pallidus, were active during both types of tapping, but preferentially during self-paced tapping. These results suggest a central role for the spinocerebellum in audiomotor entrainment. We conclude with a theoretical discussion about the various forms of entrainment in humans and other animals. PMID:25324765

Equine infectious anemia virus-infected dendritic cells retain antigen presentation capability

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

Rivera, Julie A.; McGuire, Travis C.

2005-05-10

To determine if equine monocyte-derived dendritic cells (DC) were susceptible to equine infectious anemia virus (EIAV) infection, ex vivo-generated DC were infected with virus in vitro. EIAV antigen was detected by immunofluorescence 3 days post-infection with maximum antigen being detected on day 4, whereas there was no antigen detected in DC incubated with the same amount of heat-inactivated EIAV. No cytolytic activity was observed after EIAV{sub WSU5} infection of DC. These monocyte-derived DC were more effective than macrophages and B cells in stimulating allogenic T lymphocytes. Both infected macrophages and DC stimulated similar levels of memory CTL responses in mixturesmore » of CD8+ and CD4+ cells as detected with {sup 51}Cr-release assays indicating that EIAV infection of DC did not alter antigen presentation. However, EIAV-infected DC were more effective than infected macrophages when used to stimulate memory CTL in isolated CD8+ cells. The maintenance of antigen processing and presenting function by EIAV-infected DC in vitro suggests that this function is maintained during in vivo infection.« less

Antibodies to Coprococcus comes in sera of patients with Crohn's disease. Isolation and purification of the agglutinating antigen tested with an ELISA technique.

PubMed

Hazenberg, M P; van de Merwe, J P; Peña, A S; Pennock-Schröder, A M; van Lieshout, L M

1987-07-01

Previous studies showed that agglutinating antibodies to Coprococcus comes, an anaerobic Gram-positive coccoid rod isolated from the faecal flora of patients with Crohn's disease, are more frequently found in sera of Crohn patients than in ulcerative colitis patients and healthy subjects. Isolation of the antigen may be useful in developing a more sensitive and specific diagnostic test. The present study describes first a method to improve the presentation of the relevant agglutinating antigen by the bacterium and second, the purification by column chromatography of a relatively crude antigen extract of C. comes described previously by Hazenberg et al. (1). Comparative results with the agglutination reactions and ELISA technique of extensive series of patients with Crohn's disease and healthy subjects have shown that the agglutinating antigen of C. comes has been isolated. Although the present ELISA technique cannot replace the simple and reliable agglutination reaction for screening purposes, the purified antigen will allow further immunological studies and it is to be hoped that a deeper insight into pathogenesis of the disease will be gained.

Therapeutic use of Aldara in chronic myeloid leukemia.

PubMed

Marleau, Annette M; Lipton, Jeffrey H; Riordan, Neil H; Ichim, Thomas E

2007-01-25

The potent clinical responses seen in patients with chronic myeloid leukemia (CML) after administration of donor-specific lymphocytes, as well as the correlation between the presence of antigen specific T cells and prolonged remission in these patients, suggests a role for the immunological control of CML. Here we propose Aldara, a clinically used formulation of imiquimod, as an agent for augmenting immune responses to CML antigens. Our proposition is based upon 3 tenets: 1) Endogenous dendritic cells (DC) of CML patients, which are known to be derived from the malignant clone, express and present various leukemic antigens; 2) CML-antigen reactive T cell clones exist in the patient but in many situations are ineffectively stimulated to cause significant hematological responses; and 3) Antigen presentation by mature, activated DC, which endogenously express CML-antigens may endow the pre-existing ineffective T cell responses with ability to control CML progression. The practical use of Aldara as a localized activator of DC in the context of present day leukemic therapeutics, as well as various properties of this unique immune modulator will be discussed.

Pros and Cons of Antigen-Presenting Cell Targeted Tumor Vaccines.

PubMed

Goyvaerts, Cleo; Breckpot, Karine

2015-01-01

In therapeutic antitumor vaccination, dendritic cells play the leading role since they decide if, how, when, and where a potent antitumor immune response will take place. Since the disentanglement of the complexity and merit of different antigen-presenting cell subtypes, antitumor immunotherapeutic research started to investigate the potential benefit of targeting these subtypes in situ. This review will discuss which antigen-presenting cell subtypes are at play and how they have been targeted and finally question the true meaning of targeting antitumor-based vaccines.

PLGA particulate delivery systems for subunit vaccines: Linking particle properties to immunogenicity.

PubMed

Silva, A L; Soema, P C; Slütter, B; Ossendorp, F; Jiskoot, W

2016-04-02

Among the emerging subunit vaccines are recombinant protein- and synthetic peptide-based vaccine formulations. However, proteins and peptides have a low intrinsic immunogenicity. A common strategy to overcome this is to co-deliver (an) antigen(s) with (an) immune modulator(s) by co-encapsulating them in a particulate delivery system, such as poly(lactic-co-glycolic acid) (PLGA) particles. Particulate PLGA formulations offer many advantages for antigen delivery as they are biocompatible and biodegradable; can protect the antigens from degradation and clearance; allow for co-encapsulation of antigens and immune modulators; can be targeted to antigen presenting cells; and their particulate nature can increase uptake and cross-presentation by mimicking the size and shape of an invading pathogen. In this review we discuss the pros and cons of using PLGA particulate formulations for subunit vaccine delivery and provide an overview of formulation parameters that influence their adjuvanticity and the ensuing immune response.

Transportation Air Pollution Studies (TAPS) System

DOT National Transportation Integrated Search

1974-03-01

This report describes the Transportation Air Pollution Studies (TAPS) Data Base and the Software System which has been developed in association with it. : The TAPS Data Base will be used to store the transportation air pollution data (including emiss...

Word-initial rhotic clusters in Spanish-speaking preschoolers in Chile and Granada, Spain.

PubMed

Perez, Denisse; Vivar, Pilar; Bernhardt, Barbara May; Mendoza, Elvira; Ávila, Carmen; Carballo, Gloria; Fresneda, Dolores; Muñoz, Juana; Vergara, Patricio

2018-01-01

The current paper describes Spanish acquisition of rhotic onset clusters. Data are also provided on related singleton taps/trills and /l/ as a singleton and in clusters. Participants included 9 typically developing (TD) toddlers and 30 TD preschoolers in Chile, and 30 TD preschoolers and 29 with protracted phonological development (PPD) in Granada, Spain. Results showed age and developmental group effects. Preservation of cluster timing units preceded segmental accuracy, especially in stressed syllables. Tap clusters versus singleton trills were variable in order of mastery, some children mastering clusters first, and others, the trill. Rhotics were acquired later than /l/. In early development, mismatches (errors) involved primarily deletion of taps; where substitutions occurred, [j] frequently replaced tap. In later development, [l] more frequently replaced tap; where taps did occur, vowel epenthesis sometimes occurred. The data serve as a criterion reference database for onset cluster acquisition in Chilean and Granada Spanish.

Astronomy on Tap: Public Outreach Events in Bars

NASA Astrophysics Data System (ADS)

Rice, E. L.; Levine, B. W.

2016-12-01

Astronomy on Tap public outreach events are as easy to organise or as elaborate as you would like them to be. In addition to communicating cutting-edge research and fundamental concepts to the public, Astronomy on Tap events showcase the passion, creativity and diversity of scientists, facilitate personal and meaningful interactions between scientists and the general public, and offer networking and professional development opportunities for scientists. Astronomy on Tap organisers provide a growing cadre of resources for starting similar events, which have so far taken place in twenty locations around the world, mainly in the United States but also in Canada, Chile, and Taiwan, reaching a total of almost 15 000 people. Through this reflection on the Astronomy on Tap project we invite you to consider whether you could adopt aspects of the Astronomy on Tap model for existing outreach programmes, or even organise a new satellite event in your location.

Tapping but not massage enhances vasodilation and improves venous palpation of cutaneous veins.

PubMed

Ichimura, Mika; Sasaki, Shinsuke; Mori, Masaharu; Ogino, Tetsuya

2015-01-01

This paper investigated whether tapping on the median cubital vein or massaging the forearm was more effective in obtaining better venous palpation for venipuncture. Forty healthy volunteers in their twenties were subjected to tapping (10 times in 5 sec) or massage (10 strokes in 20 sec from the wrist to the cubital fossa) under tourniquet inflation on the upper arm. Venous palpation was assessed using the venous palpation score (0-6, with 0 being impalpable). Three venous factors-venous depth, cross-sectional area, and elevation-were also measured using ultrasonography. The venous palpation score increased significantly by tapping but not by massage. Moreover, all 3 venous measurements changed significantly by tapping, while only the depth decreased significantly by massage. The three venous measurements correlated significantly with the venous palpation score, indicating that they are useful objective indicators for evaluating vasodilation. We suggest that tapping is an effective vasodilation technique.

Disruption of HLA class II antigen presentation in Burkitt lymphoma: implication of a 47 000 MW acid labile protein in CD4+ T-cell recognition

PubMed Central

God, Jason M; Zhao, Dan; Cameron, Christine A; Amria, Shereen; Bethard, Jennifer R; Haque, Azizul

2014-01-01

While Burkitt lymphoma (BL) has a well-known defect in HLA class I-mediated antigen presentation, the exact role of BL-associated HLA class II in generating a poor CD4+ T-cell response remains unresolved. Here, we found that BL cells are deficient in their ability to optimally stimulate CD4+ T cells via the HLA class II pathway. This defect in CD4+ T-cell recognition was not associated with low levels of co-stimulatory molecules on BL cells, as addition of external co-stimulation failed to elicit CD4+ T-cell activation by BL. Further, the defect was not caused by faulty antigen/class II interaction, because antigenic peptides bound with measurable affinity to BL-associated class II molecules. Interestingly, functional class II–peptide complexes were formed at acidic pH 5·5, which restored immune recognition. Acidic buffer (pH 5·5) eluate from BL cells contained molecules that impaired class II-mediated antigen presentation and CD4+ T-cell recognition. Biochemical analysis showed that these molecules were greater than 30 000 molecular weight in size, and proteinaceous in nature. In addition, BL was found to have decreased expression of a 47 000 molecular weight enolase-like molecule that enhances class II-mediated antigen presentation in B cells, macrophages and dendritic cells, but not in BL cells. These findings demonstrate that BL likely has multiple defects in HLA class II-mediated antigen presentation and immune recognition, which may be exploited for future immunotherapies. PMID:24628049

Effects of low temperature plasmas and plasma activated waters on Arabidopsis thaliana germination and growth

PubMed Central

Martinez, Yves; Merbahi, Nofel; Eichwald, Olivier; Dunand, Christophe

2018-01-01

Two plasma devices at atmospheric pressure (air dielectric barrier discharge and helium plasma jet) have been used to study the early germination of Arabidopsis thaliana seeds during the first days. Then, plasma activated waters are used during the later stage of plant development and growth until 42 days. The effects on both testa and endospserm ruptures during the germination stage are significant in the case of air plasma due to its higher energy and efficiency of producing reactive oxygen species than the case of helium plasma. The latter has shown distinct effects only for testa rupture. Analysis of germination stimulations are based on specific stainings for reactive oxygen species production, peroxidase activity and also membrane permeability tests. Furthermore, scanning electron microscopy (SEM) has shown a smoother seed surface for air plasma treated seeds that can explain the plasma induced-germination. During the growth stage, plants were watered using 4 kinds of water (tap and deionized waters activated or not by the low temperature plasma jet). With regards to other water kinds, the characterization of the tap water has shown a larger conductivity, acidity and concentration of reactive nitrogen and oxygen species. Only the tap water activated by the plasma jet has shown a significant effect on the plant growth. This effect could be correlated to reactive nitrogen species such as nitrite/nitrate species present in plasma activated tap water. PMID:29630641

Occurrence of bisphenol A in surface water, drinking water and plasma from Malaysia with exposure assessment from consumption of drinking water.

PubMed

Santhi, V A; Sakai, N; Ahmad, E D; Mustafa, A M

2012-06-15

This study investigated the level of bisphenol A (BPA) in surface water used as potable water, drinking water (tap and bottled mineral water) and human plasma in the Langat River basin, Malaysia. BPA was present in 93% of the surface water samples at levels ranging from below limit of quantification (LOQ; 1.3 ng/L) to 215 ng/L while six fold higher levels were detected in samples collected near industrial and municipal sewage treatment plant outlets. Low levels of BPA were detected in most of the drinking water samples. BPA in tap water ranged from 3.5 to 59.8 ng/L with the highest levels detected in samples collected from taps connected to PVC pipes and water filter devices. Bottled mineral water had lower levels of BPA (3.3±2.6 ng/L) although samples stored in poor storage condition had significantly higher levels (11.3±5.3 ng/L). Meanwhile, only 17% of the plasma samples had detectable levels of BPA ranging from 0.81 to 3.65 ng/mL. The study shows that BPA is a ubiquitous contaminant in surface, tap and bottled mineral water. However, exposure to BPA from drinking water is very low and is less than 0.01% of the tolerable daily intake (TDI). Copyright © 2012 Elsevier B.V. All rights reserved.

Interactive effects in transfer-appropriate processing for event-based prospective memory: the roles of effort, ongoing task, and PM cue properties.

PubMed

Abney, Drew H; McBride, Dawn M; Petrella, Samantha N

2013-10-01

Past studies (e.g., Marsh, Hicks, & Cook Journal of Experimental Psychology: Learning, Memory, and Cognition 31:68-75, 2005; Meiser & Schult European Journal of Cognitive Psychology 20:290-311, 2008) have shown that transfer-appropriate processing (TAP) effects in event-based prospective memory (PM) depend on the effort directed toward the ongoing task. In the present study, we addressed mixed findings from these studies and examined monitoring in TAP and transfer-inappropriate processing (TIP) conditions. In two experiments, a semantic or orthographic ongoing task was paired with a PM cue that either was matched in processing (TAP) or did not match in processing (TIP). Within each condition, effort was varied across trials. The results indicated that PM accuracy was higher in TAP than in TIP conditions, regardless of effort condition, supporting the findings reported by Meiser and Schult. Ex-Gaussian functions were fit to the mean reaction times (cf. Brewer Journal of Psychology 219:117-124, 2011) in order to examine monitoring across conditions. The analysis of distributional skew (τ parameter) showed sensitivity to ongoing task instructions and properties of the PM cues. These results support Meiser and Schult's suggestion that TIP conditions require more attentional processing, and they also afford novel discussion on the interactive effects of ongoing task condition, PM cue properties, and manipulations of effort.

On the nature of phase attraction in sensorimotor synchronization with interleaved auditory sequences.

PubMed

Repp, Bruno H

2004-10-01

In a task that requires in-phase synchronization of finger taps with an isochronous sequence of target tones that is interleaved with a sequence of distractor tones at various fixed phase relationships, the taps tend to be attracted to the distractor tones, especially when the distractor tones closely precede the target tones [Repp, B. H. (2003a). Phase attraction in sensorimotor synchronization with auditory sequences: Effects of single and periodic distractors on synchronization accuracy. Journal of Experimental Psychology: Human Perception and Performance, 29, 290-309]. The present research addressed two related questions about this distractor effect: (1) Is it a function of the absolute temporal separation or of the relative phase of the two stimulus sequences? (2) Is it the result of perceptual grouping (integration) of target and distractor tones or of simultaneous attraction to two independent sequences? In three experiments, distractor effects were compared across two different sequence rates. The results suggest that absolute temporal separation, not relative phase, is the critical variable. Experiment 3 also included an anti-phase tapping task that addressed the second question directly. The results suggest that the attraction of taps to distractor tones is caused mainly by temporal integration of target and distractor tones within a fixed window of 100-150 ms duration, with the earlier-occurring tone being weighted more strongly than the later-occurring one.

Development of Team Action Projects in Surgery (TAPS): a multilevel team-based approach to teaching quality improvement.

PubMed

Waits, Seth A; Reames, Bradley N; Krell, Robert W; Bryner, Benjamin; Shih, Terry; Obi, Andrea T; Henke, Peter K; Minter, Rebecca M; Englesbe, Michael J; Wong, Sandra L

2014-01-01

To meet the Accreditation Council for Graduate Medical Education core competency in Practice-Based Learning and Improvement, educational curricula need to address training in quality improvement (QI). We sought to establish a program to train residents in the principles of QI and to provide practical experiences in developing and implementing improvement projects. We present a novel approach for engaging students, residents, and faculty in QI efforts-Team Action Projects in Surgery (TAPS). Large academic medical center and health system. Multiple teams consisting of undergraduate students, medical students, surgery residents, and surgery faculty were assembled and QI projects developed. Using "managing to learn" Lean principles, these multilevel groups approached each project with robust data collection, development of an A3, and implementation of QI activities. A total of 5 resident led QI projects were developed during the TAPS pilot phase. These included a living kidney donor enhanced recovery protocol, consult improvement process, venous thromboembolism prophylaxis optimization, Clostridium difficile treatment standardization, and understanding variation in operative duration of laparoscopic cholecystectomy. Qualitative and quantitative assessment showed significant value for both the learner and stakeholders of QI related projects. Through the development of TAPS, we demonstrate a novel approach to addressing the increasing focus on QI within graduate medical education. Efforts to expand this multilevel team based approach would have value for teachers and learners alike. Copyright © 2014. Published by Elsevier Inc.

Assessment of the Neutronic and Fuel Cycle Performance of the Transatomic Power Molten Salt Reactor Design

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

Robertson, Sean; Dewan, Leslie; Massie, Mark

This report presents results from a collaboration between Transatomic Power Corporation (TAP) and Oak Ridge National Laboratory (ORNL) to provide neutronic and fuel cycle analysis of the TAP core design through the Department of Energy Gateway for Accelerated Innovation in Nuclear (GAIN) Nuclear Energy Voucher program. The TAP concept is a molten salt reactor using configurable zirconium hydride moderator rod assemblies to shift the neutron spectrum in the core from mostly epithermal at beginning of life to thermal at end of life. Additional developments in the ChemTriton modeling and simulation tool provide the critical moderator-to-fuel ratio searches and time-dependent parametersmore » necessary to simulate the continuously changing physics in this complex system. The implementation of continuous-energy Monte Carlo transport and depletion tools in ChemTriton provide for full-core three-dimensional modeling and simulation. Results from simulations with these tools show agreement with TAP-calculated performance metrics for core lifetime, discharge burnup, and salt volume fraction, verifying the viability of reducing actinide waste production with this concept. Additional analyses of mass feed rates and enrichments, isotopic removals, tritium generation, core power distribution, core vessel helium generation, moderator rod heat deposition, and reactivity coeffcients provide additional information to make informed design decisions. This work demonstrates capabilities of ORNL modeling and simulation tools for neutronic and fuel cycle analysis of molten salt reactor concepts.« less

Nanoparticle based tailoring of adjuvant function: the role in vaccine development.

PubMed

Prashant, Chandravilas Keshvan; Kumar, Manoj; Dinda, Amit Kumar

2014-09-01

Vaccination is one of the most powerful therapeutic tools for prevention and management of various infective and non-infective diseases including malignancy. Mass vaccination is a great strategy for eradicating major infectious diseases throughout the world like small pox. Application of nanotechnology for antigen delivery is a unique area of research and development which can change the vaccination strategy and policy in future. Nanocarriers can enhance antigen presentation including modulation of antigen processing pathways according to the specific need. The current review explores the pros and cons of application of different nanomaterials for antigen presentation and vaccine development.

Dendritic cells in oral tolerance in the gut.

PubMed

Rescigno, Maria

2011-09-01

Oral tolerance is a process that allows generation of systemic unresponsiveness to food antigens. Hence if the same antigen is introduced systemically even under immunogenic conditions it does not induce immune responsiveness. Dendritic cells (DCs) have been identified as essential players in this process. DCs in the gut are located in a strategic position as they can interact directly with luminal antigens or indirectly after their transcytosis across epithelial cells. DCs can then migrate to associated lymphoid tissues to induce tolerance. Antigen presenting cells in the gut are specialized in function and have divided their labour so that there are cells capable to migrate to the draining mesenteric lymph node for induction of T regulatory cells, while other subsets are resident and are required to enforce tolerance locally in the gut after food antigen exposure. In this review, I shall summarize the characteristics of antigen presenting cells in the gut and their involvement in oral tolerance induction. In addition, I will also emphasize that tolerance to food allergens may be contributed by plasmacytoid DCs in the liver that participate to the elimination or anergy of allergen-specific CD8 T cells. Hence specialized functions are associated to different subsets of antigen presenting cells and different organs. © 2011 Blackwell Publishing Ltd.

Exposure to sequestered self-antigens in vivo is not sufficient for the induction of autoimmune diabetes

PubMed Central

Chan, Olivia; Hall, Håkan; Elford, Alisha R.; Yen, Patty; Calzascia, Thomas; Spencer, David M.; Ohashi, Pamela S.

2017-01-01

Although the role of T cells in autoimmunity has been explored for many years, the mechanisms leading to the initial priming of an autoimmune T cell response remain enigmatic. The ‘hit and run’ model suggests that self-antigens released upon cell death can provide the initial signal for a self-sustaining autoimmune response. Using a novel transgenic mouse model where we could induce the release of self-antigens via caspase-dependent apoptosis. We tracked the fate of CD8+ T cells specific for the self-antigen. Our studies demonstrated that antigens released from apoptotic cells were cross-presented by CD11c+ cells in the draining lymph node. This cross-presentation led to proliferation of self-antigen specific T cells, followed by a transient ability to produce IFN-γ, but did not lead to the development of autoimmune diabetes. Using this model we examined the consequences on T cell immunity when apoptosis was combined with dendritic cell maturation signals, an autoimmune susceptible genetic background, and the deletion of Tregs. The results of our study demonstrate that autoimmune diabetes cannot be initiated by the presentation of antigens released from apoptotic cells in vivo even in the presence of factors known to promote autoimmunity. PMID:28257518

Perioperative transversus abdominis plane (TAP) blocks for analgesia after abdominal surgery.

PubMed

Charlton, Shona; Cyna, Allan M; Middleton, Philippa; Griffiths, James D

2010-12-08

The transversus abdominis plane (TAP) block is a peripheral nerve block which anaesthetises the abdominal wall. The increasing use of TAP block, as a form of pain relief after abdominal surgery warrants evaluation of its effectiveness as an adjunctive technique to routine care and, when compared with other analgesic techniques. To assess effects of TAP blocks (and variants) on postoperative analgesia requirements after abdominal surgery. We searched specialised registers of Cochrane Anaesthesia and Cochrane Pain, Palliative and Supportive Care Review Groups, CENTRAL, MEDLINE, EMBASE and CINAHL to June 2010. We included randomised controlled trials (RCTs) comparing TAP block or rectus sheath block with: no TAP or rectus sheath block; placebo; systemic, epidural or any other analgesia. At least two review authors assessed study eligibility and risk of bias, and extracted data. We included eight studies (358 participants), five assessing TAP blocks, three assessing rectus sheath blocks; with moderate risk of bias overall. All studies had a background of general anaesthesia in both arms in most cases.Compared with no TAP block or saline placebo, TAP block resulted in significantly less postoperative requirement for morphine at 24 hours (mean difference (MD) -21.95 mg, 95% confidence interval (CI) -37.91 to 5.96; five studies, 236 participants) and 48 hours (MD -28.50, 95% CI -38.92 to -18.08; one study of 50 participants) but not at two hours (all random-effects analyses). Pain at rest was significantly reduced in two studies, but not a third.Only one of three included studies of rectus sheath blocks found a reduction in postoperative analgesic requirements in participants receiving blocks. One study, assessing number of participants who were pain-free after their surgery, found more participants who received a rectus sheath block to be pain-free for up to 10 hours postoperatively. As with TAP blocks, rectus sheath blocks made no apparent impact on nausea and vomiting or sedation scores. No studies have compared TAP block with other analgesics such as epidural analgesia or local anaesthetic infiltration into the abdominal wound. There is only limited evidence to suggest use of perioperative TAP block reduces opioid consumption and pain scores after abdominal surgery when compared with no intervention or placebo. There is no apparent reduction in postoperative nausea and vomiting or sedation from the small numbers of studies to date. Many relevant studies are currently underway or awaiting publication.

B-cell acquisition of antigen: Sensing the surface.

PubMed

Knight, Andrew M

2015-06-01

B-cell antigen receptor (BCR) recognition and acquisition of antigen by B cells is the essential first step in the generation of effective antibody responses. As B-cell-mediated antigen presentation is also believed to play a significant role in the activation of CD4(+) Th-cell responses, considerable effort has focused on clarifying the nature of antigen/BCR interactions. Following earlier descriptions of interactions of soluble antigens with the BCR, it is now clear that B cells also recognize, physically extract and present antigens that are tethered to, or integral components of, the surfaces or extracellular matrix of other cells. In this issue of the European Journal of Immunology, Zeng et al. [Eur. J. Immunol. 2015. 45: XXXX-XXXX] examine how the physical property or "stiffness" of the surface displaying antigens to B cells influences the B-cell response. This commentary reports that antigen tethered on "less stiff" surfaces induces increased B-cell activation and antibody responses. I then infer how "sensing the surface" by B cells may represent a new component of the immune system's ability to detect "damage," and how this understanding may influence approaches to clinical therapies where immune activity is either unwanted or desired. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Dendritic cell-based therapeutic cancer vaccines].

PubMed

Rizzo, Manglio; Alaniz, Laura; Mazzolini, Guillermo D

In recent years immunotherapy has revolutionized the treatment of patients with advanced cancer. The increased knowledge in the tumor immune-biology has allowed developing rational treatments by manipulation of the immune system with significant clinical impact. This rapid development has significantly changed the prognosis of many tumors without treatment options up to date. Other strategies have explored the use of therapeutic vaccines based on dendritic cells (DC) by inducing antitumor immunity. DC are cells of hematopoietic origin, constitutively expressing molecules capable to present antigens, that are functionally the most potent inducers of the activation and proliferation of antigen specific T lymphocytes. The CD8+ T cells proliferate and acquire cytotoxic capacity after recognizing their specific antigen presented on the surface of DC, although only some types of DC can present antigens internalized from outside the cell to precursors of cytotoxic T lymphocytes (this function is called cross-presentation) requiring translocation mechanisms of complex antigens. The induction of an effective adaptive immune response is considered a good option given its specificity, and prolonged duration of response. The DC, thanks to its particular ability of antigen presentation and lymphocyte stimulation, are able to reverse the poor antitumor immune response experienced by patients with cancer. The DC can be obtained from various sources, using different protocols to generate differentiation and maturation, and are administered by various routes such as subcutaneous, intravenous or intranodal. The wide variety of protocols resulted in heterogeneous clinical responses.

Impact of aging on antigen presentation cell function of dendritic cells.

PubMed

Wong, Christine; Goldstein, Daniel R

2013-08-01

Older people exhibit increased mortality to infections and cancer as compared to younger people, indicating that aging impairs immunity. Dendritic cells (DCs) are key for bridging the innate and adaptive arms of the immune system by priming antigen specific T cells. Discerning how aging impacts DC function to initiate adaptive immune responses is of great biomedical importance as this could lead to the development of novel therapeutics to enhance immunity with aging. This review details reports indicating that aging impairs the antigen presenting function of DCs but highlights other studies indicating preserved DC function with aging. How aging impacts antigen presentation by DCs is complex and without a clear unifying biological underpinning. Copyright © 2013 Elsevier Ltd. All rights reserved.

Langerhans cells utilize CD1a and langerin to efficiently present nonpeptide antigens to T cells

PubMed Central

Hunger, Robert E.; Sieling, Peter A.; Ochoa, Maria Teresa; Sugaya, Makoto; Burdick, Anne E.; Rea, Thomas H.; Brennan, Patrick J.; Belisle, John T.; Blauvelt, Andrew; Porcelli, Steven A.; Modlin, Robert L.

2004-01-01

Langerhans cells (LCs) constitute a subset of DCs that initiate immune responses in skin. Using leprosy as a model, we investigated whether expression of CD1a and langerin, an LC-specific C-type lectin, imparts a specific functional role to LCs. LC-like DCs and freshly isolated epidermal LCs presented nonpeptide antigens of Mycobacterium leprae to T cell clones derived from a leprosy patient in a CD1a-restricted and langerin-dependent manner. LC-like DCs were more efficient at CD1a-restricted antigen presentation than monocyte-derived DCs. LCs in leprosy lesions coexpress CD1a and langerin, placing LCs in position to efficiently present a subset of antigens to T cells as part of the host response to human infectious disease. PMID:14991068

Tapping into the "Hidden" Home and Community Resources of Students

ERIC Educational Resources Information Center

Moll, Luis C.

2015-01-01

The author provides an overview of a "funds of knowledge" approach and presents three different adaptations of the approach with a common theme of expanding teachers' and students' resources for learning.

APPLICATION OF EPANET TO UNDERSTAND LEAD RELEASE IN PREMISE PLUMBING

EPA Science Inventory

This presentation describes the factors affecting lead concentration in tap water using an EPANET hydraulic model for a simplified home model, a realistic home model, and EPA's experimental home plumbing system.

TAP 2: A finite element program for thermal analysis of convectively cooled structures

NASA Technical Reports Server (NTRS)

Thornton, E. A.

1980-01-01

A finite element computer program (TAP 2) for steady-state and transient thermal analyses of convectively cooled structures is presented. The program has a finite element library of six elements: two conduction/convection elements to model heat transfer in a solid, two convection elements to model heat transfer in a fluid, and two integrated conduction/convection elements to represent combined heat transfer in tubular and plate/fin fluid passages. Nonlinear thermal analysis due to temperature-dependent thermal parameters is performed using the Newton-Raphson iteration method. Transient analyses are performed using an implicit Crank-Nicolson time integration scheme with consistent or lumped capacitance matrices as an option. Program output includes nodal temperatures and element heat fluxes. Pressure drops in fluid passages may be computed as an option. User instructions and sample problems are presented in appendixes.

Surgical strategies to improve fixation in the osteoporotic spine: the effects of tapping, cement augmentation, and screw trajectory.

PubMed

Kuhns, Craig A; Reiter, Michael; Pfeiffer, Ferris; Choma, Theodore J

2014-02-01

Study Design Biomechanical study of pedicle screw fixation in osteoporotic bone. Objective To investigate whether it is better to tap or not tap osteoporotic bone prior to placing a cement-augmented pedicle screw. Methods Initially, we evaluated load to failure of screws placed in cancellous bone blocks with or without prior tapping as well as after varying the depths of tapping prior to screw insertion. Then we evaluated load to failure of screws placed in bone block models with a straight-ahead screw trajectory as well as with screws having a 23-degree cephalad trajectory (toward the end plate). These techniques were tested with nonaugmented (NA) screws as well as with bioactive cement (BioC) augmentation prior to screw insertion. Results In the NA group, pretapping decreased fixation strength in a dose-dependent fashion. In the BioC group, the tapped screws had significantly greater loads to failure (p < 0.01). Comparing only the screw orientation, the screws oriented at 23 degrees cephalad had a significantly higher failure force than their respective counterparts at 0 degrees (p < 0.01). Conclusions Standard pedicle screw fixation is often inadequate in the osteoporotic spine, but this study suggests tapping prior to cement augmentation will substantially improve fixation when compared with not tapping. Angulating screws more cephalad also seems to enhance aging spine fixation.

Tapping linked to function and structure in premanifest and symptomatic Huntington disease(e–Pub ahead of print)

PubMed Central

Bechtel, N.; Scahill, R.I.; Rosas, H.D.; Acharya, T.; van den Bogaard, S.J.A.; Jauffret, C.; Say, M.J.; Sturrock, A.; Johnson, H.; Onorato, C.E.; Salat, D.H.; Durr, A.; Leavitt, B.R.; Roos, R.A.C.; Landwehrmeyer, G.B.; Langbehn, D.R.; Stout, J.C.; Tabrizi, S.J.; Reilmann, R.

2010-01-01

Objective: Motor signs are functionally disabling features of Huntington disease. Characteristic motor signs define disease manifestation. Their severity and onset are assessed by the Total Motor Score of the Unified Huntington's Disease Rating Scale, a categorical scale limited by interrater variability and insensitivity in premanifest subjects. More objective, reliable, and precise measures are needed which permit clinical trials in premanifest populations. We hypothesized that motor deficits can be objectively quantified by force-transducer-based tapping and correlate with disease burden and brain atrophy. Methods: A total of 123 controls, 120 premanifest, and 123 early symptomatic gene carriers performed a speeded and a metronome tapping task in the multicenter study TRACK-HD. Total Motor Score, CAG repeat length, and MRIs were obtained. The premanifest group was subdivided into A and B, based on the proximity to estimated disease onset, the manifest group into stages 1 and 2, according to their Total Functional Capacity scores. Analyses were performed centrally and blinded. Results: Tapping variability distinguished between all groups and subgroups in both tasks and correlated with 1) disease burden, 2) clinical motor phenotype, 3) gray and white matter atrophy, and 4) cortical thinning. Speeded tapping was more sensitive to the detection of early changes. Conclusion: Tapping deficits are evident throughout manifest and premanifest stages. Deficits are more pronounced in later stages and correlate with clinical scores as well as regional brain atrophy, which implies a link between structure and function. The ability to track motor phenotype progression with force-transducer-based tapping measures will be tested prospectively in the TRACK-HD study. GLOSSARY CoV = coefficient of variation; DBS = disease burden score; Freq = frequency; HD = Huntington disease; ICV = intracranial volume; IOI = interonset interval; ΔIOI = deviation from interonset interval; IPI = interpeak interval; ΔIPI = deviation from interpeak interval; ITI = intertap interval; log = logarithmic; MT = metronome tapping; ΔMTI = deviation from midtap interval; preHD = premanifest Huntington disease; RT = reaction time; ST = speeded tapping; TD = tap duration; TF = tapping force; TFC = Total Functional Capacity; UHDRS = Unified Huntington's Disease Rating Scale; UHDRS-TMS = Unified Huntington's Disease Rating Scale-Total Motor Score; VBM = voxel-based morphometry. PMID:21068430

Comparison of Transversus Abdominis Plane Infiltration with Liposomal Bupivacaine versus Continuous Epidural Analgesia versus Intravenous Opioid Analgesia.

PubMed

Ayad, Sabry; Babazade, Rovnat; Elsharkawy, Hesham; Nadar, Vinayak; Lokhande, Chetan; Makarova, Natalya; Khanna, Rashi; Sessler, Daniel I; Turan, Alparslan

2016-01-01

Epidural analgesia is considered the standard of care but cannot be provided to all patients Liposomal bupivacaine has been approved for field blocks such as transversus abdominis plane (TAP) blocks but has not been clinically compared against other modalities. In this retrospective propensity matched cohort study we thus tested the primary hypothesis that TAP infiltration are noninferior (not worse) to continuous epidural analgesia and superior (better) to intravenous opioid analgesia in patients recovering from major lower abdominal surgery. 318 patients were propensity matched on 18 potential factors among three groups (106 per group): 1) TAP infiltration with bupivacaine liposome; 2) continuous Epidural analgesia with plain bupivacaine; and; 3) intravenous patient-controlled analgesia (IV PCA). We claimed TAP noninferior (not worse) over Epidural if TAP was noninferior (not worse) on total morphine-equivalent opioid and time-weighted average pain score (10-point scale) within first 72 hours after surgery with noninferiority deltas of 1 (10-point scale) for pain and an increase less of 20% in the mean morphine equivalent opioid consumption. We claimed TAP or Epidural groups superior (better) over IV PCA if TAP or Epidural was superior on opioid consumption and at least noninferior on pain outcome. Multivariable linear regressions within the propensity-matched cohorts were used to model total morphine-equivalent opioid dose and time-weighted average pain score within first 72 hours after surgery; joint hypothesis framework was used for formal testing. TAP infiltration were noninferior to Epidural on both primary outcomes (p<0.001). TAP infiltration were noninferior to IV PCA on pain scores (p = 0.001) but we did not find superiority on opioid consumption (p = 0.37). We did not find noninferiority of Epidural over IV PCA on pain scores (P = 0.13) and nor did we find superiority on opioid consumption (P = 0.98). TAP infiltration with liposomal bupivacaine and continuous epidural analgesia were similar in terms of pain and opioid consumption, and not worse in pain compared with IV PCA. TAP infiltrations might be a reasonable alternative to epidural analgesia in abdominal surgical patients. A large randomized trial comparing these techniques is justified.

A computer vision framework for finger-tapping evaluation in Parkinson's disease.

PubMed

Khan, Taha; Nyholm, Dag; Westin, Jerker; Dougherty, Mark

2014-01-01

The rapid finger-tapping test (RFT) is an important method for clinical evaluation of movement disorders, including Parkinson's disease (PD). In clinical practice, the naked-eye evaluation of RFT results in a coarse judgment of symptom scores. We introduce a novel computer-vision (CV) method for quantification of tapping symptoms through motion analysis of index-fingers. The method is unique as it utilizes facial features to calibrate tapping amplitude for normalization of distance variation between the camera and subject. The study involved 387 video footages of RFT recorded from 13 patients diagnosed with advanced PD. Tapping performance in these videos was rated by two clinicians between the symptom severity levels ('0: normal' to '3: severe') using the unified Parkinson's disease rating scale motor examination of finger-tapping (UPDRS-FT). Another set of recordings in this study consisted of 84 videos of RFT recorded from 6 healthy controls. These videos were processed by a CV algorithm that tracks the index-finger motion between the video-frames to produce a tapping time-series. Different features were computed from this time series to estimate speed, amplitude, rhythm and fatigue in tapping. The features were trained in a support vector machine (1) to categorize the patient group between UPDRS-FT symptom severity levels, and (2) to discriminate between PD patients and healthy controls. A new representative feature of tapping rhythm, 'cross-correlation between the normalized peaks' showed strong Guttman correlation (μ2=-0.80) with the clinical ratings. The classification of tapping features using the support vector machine classifier and 10-fold cross validation categorized the patient samples between UPDRS-FT levels with an accuracy of 88%. The same classification scheme discriminated between RFT samples of healthy controls and PD patients with an accuracy of 95%. The work supports the feasibility of the approach, which is presumed suitable for PD monitoring in the home environment. The system offers advantages over other technologies (e.g. magnetic sensors, accelerometers, etc.) previously developed for objective assessment of tapping symptoms. Copyright © 2013 Elsevier B.V. All rights reserved.

PLGA nano/micro particles encapsulated with pertussis toxoid (PTd) enhances Th1/Th17 immune response in a murine model.

PubMed

Li, Pan; Asokanathan, Catpagavalli; Liu, Fang; Khaing, Kyi Kyi; Kmiec, Dorota; Wei, Xiaoqing; Song, Bing; Xing, Dorothy; Kong, Deling

2016-11-20

Poly(lactic-co-glycolic acid) (PLGA) based nano/micro particles were investigated as a potential vaccine platform for pertussis antigen. Presentation of pertussis toxoid as nano/micro particles (NP/MP) gave similar antigen-specific IgG responses in mice compared to soluble antigen. Notably, in cell line based assays, it was found that PLGA based nano/micro particles enhanced the phagocytosis of fluorescent antigen-nano/micro particles by J774.2 murine monocyte/macrophage cells compared to soluble antigen. More importantly, when mice were immunised with the antigen-nano/micro particles they significantly increased antigen-specific Th1 cytokines INF-γ and IL-17 secretion in splenocytes after in vitro re-stimulation with heat killed Bordetalla pertussis, indicating the induction of a Th1/Th17 response. Also, presentation of pertussis antigen in a NP/MP formulation is able to provide protection against respiratory infection in a murine model. Thus, the NP/MP formulation may provide an alternative to conventional acellular vaccines to achieve a more balanced Th1/Th2 immune response. Copyright © 2016 Elsevier B.V. All rights reserved.

20 CFR 1001.151 - Other funding criteria.

Code of Federal Regulations, 2010 CFR

2010-04-01

... allocation will be available for distribution based on Transition Assistance Program (TAP) workload and other exigencies. (b) Funding for TAP workshops will be allocated on a per workshop basis. Funding to the States... for TAP workshops, will be allocated based on need. ...

Post-earthquake outbreak of rotavirus gastroenteritis in Kashmir (India): an epidemiological analysis.

PubMed

Karmakar, Somenath; Rathore, Abhilakh Singh; Kadri, Syed Manzoor; Dutt, Som; Khare, Shashi; Lal, Shiv

2008-10-01

An earthquake struck Kashmir on 8 October 2005. A central team of public health specialists was sent to Kashmir to assess the public health measures required following the earthquake, and to assist in institution of public health measures. Epidemiological and environmental investigation in Tangdar block (Kupwara district) and Uri Tehsil (Baramula district). Visits to villages affected by the earthquake, rehabilitation camps and health care, examination of cases with acute diarrhoeal disease (ADD), environmental observations, collection of clinical samples from ADD cases and environmental samples from drinking water sources, and laboratory methods. In total, 1783 cases of ADD were reported between 14 October and 17 December 2005 in Tangdar (population 65000). The overall attack rate was 20% in children under 4 years of age. Twelve cases of ADD with loose motions without blood were studied, and 11 rectal swabs and one stool sample were processed. No bacterial enteropathogens could be isolated, but three of the 12 samples yielded rotavirus antigen on enzyme-linked immunosorbent assay. Twelve of 13 (92.3%) water samples, collected from various stream or tap water (source: spring/stream) sources, were unsatisfactory (P=0.001) using the H(2)S strip method compared with other sources (well/mineral water). All eight water sources in Tangdar block were unsatisfactory, indicated by blackening of H(2)S filter paper strips. Following the earthquake, drinking stream water or tap water without boiling or chlorination may have led to a common source water-borne outbreak of rotavirus gastroenteritis. Other contributing factors were: overcrowding; poor sanitation; open-air defaecation; poor hygiene; and living in makeshift camps near streams. Person-to-person transmission may also have contributed to perpetuation of the outbreak. Following the establishment of medical camps and information, education and communication regarding the need to drink boiled water and follow safer hygienic practices, the outbreak was brought under control. The earthquake in Kashmir in 2005 led to widespread contamination of drinking water sources such as stream and tap water (source: stream or spring). This appears to have led to a common source outbreak of rotavirus between October and December 2005, leading to ADD, amongst infants and small children, transmitted by the faecal-oral route and perpetuated by person-to-person transmission.

Carbohydrates and T cells: A sweet twosome

PubMed Central

Avci, Fikri Y.; Li, Xiangming; Tsuji, Moriya; Kasper, Dennis L.

2013-01-01

Carbohydrates as T cell-activating antigens have been generating significant interest. For many years, carbohydrates were thought of as T-independent antigens, however, more recent research had demonstrated that mono- or oligosaccharides glycosidically-linked to peptides can be recognized by T cells. T cell recognition of these glycopeptides depends on the structure of both peptide and glycan portions of the antigen. Subsequently, it was discovered that natural killer T cells recognized glycolipids when presented by the antigen presenting molecule CD1d. A transformative insight into glycan-recognition by T cells occurred when zwitterionic polysaccharides were discovered to bind to and be presented by MHCII to CD4+ T cells. Based on this latter observation, the role that carbohydrate epitopes generated from glycoconjugate vaccines had in activating helper T cells was explored and it was found that these epitopes are presented to specific carbohydrate recognizing T cells through a unique mechanism. Here we review the key interactions between carbohydrate antigens and the adaptive immune system at the molecular, cellular and systems levels exploring the significant biological implications in health and disease. PMID:23757291

Adaptor protein-3 is required in dendritic cells for optimal Toll-like receptor signaling from phagosomes and antigen presentation to CD4+ T cells

PubMed Central

Mantegazza, Adriana R.; Guttentag, Susan H.; El-Benna, Jamel; Sasai, Miwa; Iwasaki, Akiko; Shen, Hao; Laufer, Terri M.; Marks, Michael S.

2012-01-01

SUMMARY Effective major histocompatibility complex-II (MHC-II) antigen presentation from phagocytosed particles requires phagosome-intrinsic toll-like receptor (TLR) signaling, but the molecular mechanisms underlying TLR delivery to phagosomes and how signaling regulates antigen presentation are incompletely understood. We show a requirement in dendritic cells (DCs) for adaptor protein-3 (AP-3) in efficient TLR recruitment to phagosomes and MHC-II presentation of antigens internalized by phagocytosis but not receptor-mediated endocytosis. DCs from AP-3-deficient pearl mice elicited impaired CD4+ T cell activation and Th1 effector function to particulate antigen in vitro and to recombinant Listeria monocytogenes infection in vivo. Whereas phagolysosome maturation and peptide:MHC-II complex assembly proceeded normally in pearl DCs, peptide:MHC-II export to the cell surface was impeded. This correlated with reduced TLR4 recruitment and proinflammatory signaling from phagosomes by particulate TLR ligands. We propose that AP-3-dependent TLR delivery from endosomes to phagosomes and subsequent signaling mobilize peptide:MHC-II export from intracellular stores. PMID:22560444

Potentiation of pH-sensitive polymer-modified liposomes with cationic lipid inclusion as antigen delivery carriers for cancer immunotherapy.

PubMed

Yoshizaki, Yuta; Yuba, Eiji; Sakaguchi, Naoki; Koiwai, Kazunori; Harada, Atsushi; Kono, Kenji

2014-09-01

Cationic lipid-incorporated liposomes modified with pH-sensitive polymers were prepared by introducing 3, 5-didodecyloxybenzamidine as a cationic lipid to egg yolk phosphatidylcholine liposomes modified with 3-methylglutarylated hyperbranched poly(glycidol) (MGlu-HPG) as a pH-sensitive polymer. These liposomes were stable at neutral pH, but were destabilized below pH 6.0 because MGlu-HPG changed its characteristics from hydrophilic to hydrophobic in response to the pH decrease. Cationic lipid inclusion improved their pH sensitivity at weakly acidic pH and association of liposomes with murine dendritic cell (DC) lines. Cationic lipid-incorporated liposomes delivered entrapped ovalbumin (OVA) molecules not only to cytosol but also to endosome/lysosome. Treatment with cationic lipid-incorporated liposomes induced up-regulation of antigen presentation-involved molecules on DCs, the promotion of cytokine production, and antigen presentation via both major histocompatibility complex (MHC) class I and II molecules. Especially, antigen presentation via MHC class II was promoted by cationic lipid inclusion, which might correspond to efficient endosome/lysosome delivery of OVA. Subcutaneous administration of OVA-loaded cationic lipid-incorporated liposomes induced antigen-specific antibody production in serum and Th1-dominant immune responses in the spleen. Furthermore, administration of the cationic lipid-incorporated liposomes to mice bearing E.G7-OVA tumor more significantly reduced the tumor volume than liposomes without cationic lipids. Therefore, cationic lipid inclusion into pH-sensitive polymer-modified liposomes, which can achieve both efficient antigen intracellular delivery and activation of antigen presenting cell, is an effective approach to develop antigen carriers for efficient cancer immunotherapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bacteriological quality of bottled drinking water versus municipal tap water in Dharan municipality, Nepal.

PubMed

Pant, Narayan Dutt; Poudyal, Nimesh; Bhattacharya, Shyamal Kumar

2016-06-07

Water-related diseases are of great concern in developing countries like Nepal. Every year, there are countless morbidity and mortality due to the consumption of unsafe drinking water. Recently, there have been increased uses of bottled drinking water in an assumption that the bottled water is safer than the tap water and its use will help to protect from water-related diseases. So, the main objective of this study was to analyze the bacteriological quality of bottled drinking water and that of municipal tap water. A total of 100 samples (76 tap water and 24 bottled water) were analyzed for bacteriological quality and pH. The methods used were spread plate method for total plate count (TPC) and membrane filter method for total coliform count (TCC), fecal coliform count (FCC), and fecal streptococcal count (FSC). pH meter was used for measuring pH. One hundred percent of the tap water samples and 87.5 % of the bottled water samples were found to be contaminated with heterotrophic bacteria. Of the tap water samples, 55.3 % were positive for total coliforms, compared with 25 % of the bottled water. No bottled water samples were positive for fecal coliforms and fecal streptococci, in contrast to 21.1 % and 14.5 % of the tap water samples being contaminated with fecal coliforms and fecal streptococci, respectively. One hundred percent of the tap water samples and 54.2 % of the bottled water samples had pH in the acceptable range. All of the municipal tap water samples and most of the bottled drinking water samples distributed in Dharan municipality were found to be contaminated with one or more than one type of indicator organisms. On the basis of our findings, we may conclude that comparatively, the bottled drinking water may have been safer (than tap water) to drink.

Microbiological evaluation of water during the 2011 flood crisis in Thailand.

PubMed

Chaturongkasumrit, Yuphakhun; Techaruvichit, Punnida; Takahashi, Hajime; Kimura, Bon; Keeratipibul, Suwimon

2013-10-01

In 2011, a severe flood occurred in Thailand, covering nearly half the country in water for several months. The contamination of floodwater and subsequent contamination of water for human consumption could have potentially led to a widespread health crisis. However, to date, no study has been conducted to determine the safety of the waters used for human consumption in Thailand during the severe flood. Therefore, we conducted microbiological analysis of 4 kinds of water (floodwater, river water, tap water, and filtered tap water) collected from industrial and residential areas that were damaged due to flooding. Higher net levels of bacteria were found in water with a higher turbidity. No clear trend was observed in the pH value of all 4 water samples. The level of total bacterial contamination in the water samples was estimated by real-time quantitative polymerase chain reaction (PCR). Eleven of the 12 tap water samples and all of the filtered tap water samples had a total bacterial load that exceeded the Thai water quality standards. One of the tap water samples and one of the filtered tap water samples were found to be positive for Shigella sp., although none of the floodwater samples showed detectable levels of this pathogen as determined by PCR analysis. One of the samples of floodwater was also found to be positive for Leptospira sp., but none of the tap water or filtered tap water samples were positive. Most of the tap water samples and all filtered tap water samples were found to be contaminated with Vibrio cholerae. Bacterial contamination in water samples was also analyzed by denaturing gradient gel electrophoresis (DGGE) analysis. These results revealed that several microorganisms were transferred via floodwater to different areas in the central part of Thailand and cross-contaminated between floodwater and water for human consumption. © 2013.

Multimedia Exposures to Arsenic and Lead for Children Near an Inactive Mine Tailings and Smelter Site

PubMed Central

Loh, Miranda M.; Sugeng, Anastasia; Lothrop, Nathan; Klimecki, Walter; Cox, Melissa; Wilkinson, Sarah T.; Lu, Zhenqiang; Beamer, Paloma I.

2016-01-01

Children living near contaminated mining waste areas may have high exposures to metals from the environment. This study investigates whether exposure to arsenic and lead is higher in children in a community near a legacy mine and smelter site in Arizona compared to children in other parts of the United States and the relationship of that exposure to the site. Arsenic and lead were measured in residential soil, house dust, tap water, urine, and toenail samples from 70 children in 34 households up to 7 miles from the site. Soil and house dust were sieved, digested, and analyzed via ICP-MS. Tap water and urine were analyzed without digestion, while toenails were washed, digested and analyzed. Blood lead was analyzed by an independent, certified laboratory. Spearman correlation coefficients were calculated between each environmental media and urine and toenails for arsenic and lead. Geometric mean arsenic (standard deviation) concentrations for each matrix were: 22.1 (2.59) ppm and 12.4 (2.27) ppm for soil and house dust (<63 μm), 5.71 (6.55) ppb for tap water, 14.0 (2.01) μg/L for specific gravity-corrected total urinary arsenic, 0.543 (3.22) ppm for toenails. Soil and vacuumed dust lead concentrations were 16.9 (2.03) ppm and 21.6 (1.90) ppm. The majority of blood lead levels were below the limit of quantification. Arsenic and lead concentrations in soil and house dust decreased with distance from the site. Concentrations in soil, house dust, tap water, along with floor dust loading were significantly associated with toenail and urinary arsenic but not lead. Mixed models showed that soil and tap water best predicted urinary arsenic. In our study, despite being present in mine tailings at similar levels, internal lead exposure was not high, but arsenic exposure was of concern, particularly from soil and tap water. Naturally occurring sources may be an additional important contributor to exposures in certain legacy mining areas. PMID:26803211

Detection of Escherichia coli, Salmonella species, and Vibrio cholerae in tap water and bottled drinking water in Isfahan, Iran.

PubMed

Momtaz, Hassan; Dehkordi, Farhad Safarpoor; Rahimi, Ebrahim; Asgarifar, Amin

2013-06-07

The quality of drinking water has an important role in human infection and disease. This study was aimed at comparing polymerase chain reaction and culture in detecting Escherichia coli, Salmonella species and Vibrio cholera in tape water and bottled drinking water in various seasons in Isfahan province, Iran. A total of 448 water samples from tap water and bottled mineral water were taken over 6 months, from July 2010 to December 2010, and after filtration, samples were examined by culture and polymerase chain reaction methods for detection of Escherichia coli, Salmonella species, and Vibrio cholerae. The culture method showed that 34 (7.58%), 4 (0.89%) and 3 (0.66%) of all 448 water samples were positive for Escherichia coli, Salmonella species, and Vibrio cholera, respectively. The uidA gene from Escherichia coli, IpaB gene from Salmonella species, and epsM gene from Vibrio cholera were detected in 38 (26.38%), 5 (3.47%), and 3 (2.08%) of 144 tap-water samples, respectively. Escherichia coli was detected in 8 (2.63%) of 304 samples of bottled drinking water from 5 companies. The water of southern part of Isfahan and company 5 had the highest prevalence of bacteria. The Escherichia coli water contamination was significantly higher (P < 0.05) in the hot seasons (July-August) than cold (November-December) seasons and in company 5 than other companies. There were significant differences (P < 0.05) for the prevalence of bacteria between the tap waters of southern part and tap waters of central part of Isfahan. This study showed that the polymerase chain reaction assays can be an extremely accurate, fast, safe, sensitive and specific approach to monitor drinking water quality from purification facilities and bottled water companies. Also, our study confirmed the presence of Escherichia coli, Salmonella species, and Vibrio cholerae as water-borne pathogens in tap water and bottled drinking water of Isfahan, Iran. The present study showed the important public health problem in Isfahan, Iran.

Detection of Escherichia coli, Salmonella species, and Vibrio cholerae in tap water and bottled drinking water in Isfahan, Iran

PubMed Central

2013-01-01

Background The quality of drinking water has an important role in human infection and disease. This study was aimed at comparing polymerase chain reaction and culture in detecting Escherichia coli, Salmonella species and Vibrio cholera in tape water and bottled drinking water in various seasons in Isfahan province, Iran. Methods A total of 448 water samples from tap water and bottled mineral water were taken over 6 months, from July 2010 to December 2010, and after filtration, samples were examined by culture and polymerase chain reaction methods for detection of Escherichia coli, Salmonella species, and Vibrio cholerae. Results The culture method showed that 34 (7.58%), 4 (0.89%) and 3 (0.66%) of all 448 water samples were positive for Escherichia coli, Salmonella species, and Vibrio cholera, respectively. The uidA gene from Escherichia coli, IpaB gene from Salmonella species, and epsM gene from Vibrio cholera were detected in 38 (26.38%), 5 (3.47%), and 3 (2.08%) of 144 tap-water samples, respectively. Escherichia coli was detected in 8 (2.63%) of 304 samples of bottled drinking water from 5 companies. The water of southern part of Isfahan and company 5 had the highest prevalence of bacteria. The Escherichia coli water contamination was significantly higher (P < 0.05) in the hot seasons (July-August) than cold (November-December) seasons and in company 5 than other companies. There were significant differences (P < 0.05) for the prevalence of bacteria between the tap waters of southern part and tap waters of central part of Isfahan. Conclusions This study showed that the polymerase chain reaction assays can be an extremely accurate, fast, safe, sensitive and specific approach to monitor drinking water quality from purification facilities and bottled water companies. Also, our study confirmed the presence of Escherichia coli, Salmonella species, and Vibrio cholerae as water-borne pathogens in tap water and bottled drinking water of Isfahan, Iran. The present study showed the important public health problem in Isfahan, Iran. PMID:23742181

Processing of urushiol (poison ivy) hapten by both endogenous and exogenous pathways for presentation to T cells in vitro.

PubMed

Kalish, R S; Wood, J A; LaPorte, A

1994-05-01

The antigen processing requirements for urushiol, the immunogen of poison ivy (Toxicodendron radicans), were tested by presentation of urushiol to cultured human urushiol-responsive T cells. Urushiol was added to antigen-presenting cells (APC) either before or after fixation with paraformaldehyde. Three distinct routes of antigen processing were detected. CD8+ and CD4+ T cells, which were dependent upon processing, proliferated if urushiol was added to APC before fixation, but did not proliferate when urushiol was added to APC after fixation. Processing of urushiol for presentation to CD8+ T cells was inhibited by azide, monensin, and brefeldin A. This suggests that urushiol was processed by the endogenous pathway. In contrast, presentation of urushiol to CD4+ T cells was inhibited by monensin but not by brefeldin A. This was compatible with antigen processing by the endosomal (exogenous) pathway. Finally, certain CD8+ T cells recognized urushiol in the absence of processing. These cells proliferated in response to APC incubated with urushiol after fixation. Classification of contact allergens by antigen processing pathway may predict the relative roles of CD4+ and CD8+ cells in the immunopathogensis of allergic contact dermatitis.

Processing of urushiol (poison ivy) hapten by both endogenous and exogenous pathways for presentation to T cells in vitro.

PubMed Central

Kalish, R S; Wood, J A; LaPorte, A

1994-01-01

The antigen processing requirements for urushiol, the immunogen of poison ivy (Toxicodendron radicans), were tested by presentation of urushiol to cultured human urushiol-responsive T cells. Urushiol was added to antigen-presenting cells (APC) either before or after fixation with paraformaldehyde. Three distinct routes of antigen processing were detected. CD8+ and CD4+ T cells, which were dependent upon processing, proliferated if urushiol was added to APC before fixation, but did not proliferate when urushiol was added to APC after fixation. Processing of urushiol for presentation to CD8+ T cells was inhibited by azide, monensin, and brefeldin A. This suggests that urushiol was processed by the endogenous pathway. In contrast, presentation of urushiol to CD4+ T cells was inhibited by monensin but not by brefeldin A. This was compatible with antigen processing by the endosomal (exogenous) pathway. Finally, certain CD8+ T cells recognized urushiol in the absence of processing. These cells proliferated in response to APC incubated with urushiol after fixation. Classification of contact allergens by antigen processing pathway may predict the relative roles of CD4+ and CD8+ cells in the immunopathogensis of allergic contact dermatitis. Images PMID:7910172

Does Melody Assist in the Reproduction of Novel Rhythm Patterns?

ERIC Educational Resources Information Center

Kinney, Daryl W.; Forsythe, Jere L.

2013-01-01

We examined music education majors' ability to reproduce rhythmic stimuli presented in melody and rhythm only conditions. Participants reproduced rhythms of two-measure music examples by immediately echo-performing through a method of their choosing (e.g., clapping, tapping, vocalizing). Forty examples were presented in melody and rhythm only…

CELL SEPARATION ON ANTIGEN-COATED COLUMNS

PubMed Central

Wigzell, Hans; Andersson, Birger

1969-01-01

Glass and plastic bead columns coated with antigenic protein molecules were used as an immunological filter for cell populations containing immune cells of relevant specificity. A selective elimination of these immune cells from the passing cell suspension was regularly noted and it approached, in some experiments, complete abolition of the specific immune reactivity of the filtered cell population. This specific retention of immune cells by antigenic columns could be selectively blocked by the presence of free antigen molecules in the medium during filtration. The results obtained support the concept of a cell-associated antigen-specific receptor being present on the outer surface of immune cells, displaying the same antigen-binding specificity as the potential product of the cell, the humoral antibody. Using the present bead column system, results were obtained indicating that this receptor was an active product of the immune cells and not any passively adsorbed, cytophilic antibody. Antigenic bead columns may very well constitute a tool for the production in vitro of cell populations being specifically deprived of immune reactivity and allow detailed analysis of the characteristics of the cell-associated antibody of immune cells. PMID:5782770

Immunization Route Dictates Cross-Priming Efficiency and Impacts the Optimal Timing of Adjuvant Delivery

PubMed Central

Bouvier, Isabelle; Jusforgues-Saklani, Hélène; Lim, Annick; Lemaître, Fabrice; Lemercier, Brigitte; Auriau, Charlotte; Nicola, Marie-Anne; Leroy, Sandrine; Law, Helen K.; Bandeira, Antonio; Moon, James J.; Bousso, Philippe; Albert, Matthew L.

2011-01-01

Delivery of cell-associated antigen represents an important strategy for vaccination. While many experimental models have been developed in order to define the critical parameters for efficient cross-priming, few have utilized quantitative methods that permit the study of the endogenous repertoire. Comparing different strategies of immunization, we report that local delivery of cell-associated antigen results in delayed T cell cross-priming due to the increased time required for antigen capture and presentation. In comparison, delivery of disseminated antigen resulted in rapid T cell priming. Surprisingly, local injection of cell-associated antigen, while slower, resulted in the differentiation of a more robust, polyfunctional, effector response. We also evaluated the combination of cell-associated antigen with poly I:C delivery and observed an immunization route-specific effect regarding the optimal timing of innate immune stimulation. These studies highlight the importance of considering the timing and persistence of antigen presentation, and suggest that intradermal injection with delayed adjuvant delivery is the optimal strategy for achieving CD8+ T cell cross-priming. PMID:22566860

20 CFR 1001.150 - Method of calculating State basic grant awards.

Code of Federal Regulations, 2010 CFR

2010-04-01

... will be retained separately from the funds retained for TAP workload and other exigencies, as... funding for TAP workload and other exigencies, a compelling reason to recalculate would exist. In that... is available for TAP workload and other exigencies. ...

Fixture For Drilling And Tapping A Curved Workpiece

NASA Technical Reports Server (NTRS)

Espinosa, P. S.; Lockyer, R. T.

1992-01-01

Simple fixture guides drilling and tapping of holes in prescribed locations and orientations on workpiece having curved surface. Tool conceived for use in reworking complexly curved helicopter blades made of composite materials. Fixture is block of rigid foam with epoxy filler, custom-fitted to surface contour, containing bushings and sleeves at drilling and tapping sites. Bushings changed, so taps and drills of various sizes accommodated. In use, fixture secured to surface by hold-down bolts extending through sleeves and into threads in substrate.

Intersection of autophagy with pathways of antigen presentation.

PubMed

Patterson, Natalie L; Mintern, Justine D

2012-12-01

Traditionally, macroautophagy (autophagy) is viewed as a pathway of cell survival. Autophagy ensures the elimination of damaged or unwanted cytosolic components and provides a source of cellular nutrients during periods of stress. Interestingly, autophagy can also directly intersect with, and impact, other major pathways of cellular function. Here, we will review the contribution of autophagy to pathways of antigen presentation. The autophagy machinery acts to modulate both MHCI and MHCII antigen presentation. As such autophagy is an important participant in pathways that elicit host cell immunity and the elimination of infectious pathogens.

Ambulatory circadian monitoring (ACM) based on thermometry, motor activity and body position (TAP): a comparison with polysomnography.

PubMed

Ortiz-Tudela, Elisabet; Martinez-Nicolas, Antonio; Albares, Javier; Segarra, Francesc; Campos, Manuel; Estivill, Eduard; Rol, Maria Angeles; Madrid, Juan Antonio

2014-03-14

An integrated variable based on the combination of wrist Temperature, motor Activity and body Position (TAP) was previously developed at our laboratory to evaluate the functioning of the circadian system and sleep-wake rhythm under ambulatory conditions. However, the reliability of TAP needed to be validated with polysomnography (PSG). 22 subjects suffering from sleep disorders were monitored for one night with a temperature sensor (iButton), an actimeter (HOBO) and exploratory PSG. Mean waveforms, sensitivity (SE), specificity (SP), agreement rates (AR) and comparisons between TAP and sleep stages were studied. The TAP variable was optimized for SE, SP and AR with respect to each individual variable (SE: 92%; SP: 78%; AR: 86%). These results improved upon estimates previously published for actigraphy. Furthermore, TAP values tended to decrease as sleep depth increased, reaching the lowest point at phase 3. Finally, TAP estimates for sleep latency (SL: 37±9 min), total sleep time (TST: 367±13 min), sleep efficiency (SE: 86.8±1.9%) and number of awakenings (NA>5 min: 3.3±.4) were not significantly different from those obtained with PSG (SL: 29±4 min; SE: 89.9±1.8%; NA>5 min: 2.3±.4), despite the heterogeneity of the sleep pathologies monitored. The TAP variable is a novel measurement for evaluating circadian system status and sleep-wake rhythms with a level of reliability better to that of actigraphy. Furthermore, it allows the evaluation of a patient's sleep-wake rhythm in his/her normal home environment, and at a much lower cost than PSG. Future studies in specific pathologies would verify the relevance of TAP in those conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

Drinking water management: health risk perceptions and choices in First Nations and non-First Nations communities in Canada.

PubMed

Dupont, Diane; Waldner, Cheryl; Bharadwaj, Lalita; Plummer, Ryan; Carter, Blair; Cave, Kate; Zagozewski, Rebecca

2014-05-30

The relationship between tap water and health has been a topic of public concern and calls for better management in Canada since well-publicized contamination events in two provinces (Ontario and Saskatchewan) in 2000-2001. This study reports the perspectives on health risks from tap water and corresponding use of, and spending on, bottled water in a number of different communities in Canada. In 2009-2010, four First Nations communities (three from Ontario and one from Saskatchewan) and a geographically diverse sample of non-First Nations Canadians were surveyed about their beliefs concerning health risks from tap water and their spending practices for bottled water as a substitute. Responses to five identical questions were examined, revealing that survey respondents from Ontario First Nations communities were more likely than non-First Nations Canadians to believe bottled water is safer than tap water (OR 1.6); more likely to report someone became ill from tap water (OR 3.6); more likely to express water and health concerns related to tap water consumption (OR 2.4); and more likely to spend more on bottled water (OR 4.9). On the other hand, participants from one Saskatchewan First Nations community were less likely than non-First Nations Canadians to believe that someone had become ill from drinking tap water (OR 3.8), less likely to believe bottled water is safer than tap (OR 2.0), and less likely to have health concerns with tap water (OR 1.5). These differences, however, did not translate into differences in the likelihood of high bottled water expenditures or being a 100% bottled water consumer. The paper discusses how the differences observed may be related to water supply and regulation, trust, perceived control, cultural background, location, and past experience.

Comparison of the Mineral Content of Tap Water and Bottled Waters

PubMed Central

Azoulay, Arik; Garzon, Philippe; Eisenberg, Mark J

2001-01-01

OBJECTIVES Because of growing concern that constituents of drinking water may have adverse health effects, consumption of tap water in North America has decreased and consumption of bottled water has increased. Our objectives were to 1) determine whether North American tap water contains clinically important levels of calcium (Ca2+), magnesium (Mg2+), and sodium (Na+) and 2) determine whether differences in mineral content of tap water and commercially available bottled waters are clinically important. DESIGN We obtained mineral analysis reports from municipal water authorities of 21 major North American cities. Mineral content of tap water was compared with published data regarding commercially available bottled waters and with dietary reference intakes (DRIs). MEASUREMENTS AND MAIN RESULTS Mineral levels varied among tap water sources in North America and among bottled waters. European bottled waters generally contained higher mineral levels than North American tap water sources and North American bottled waters. For half of the tap water sources we examined, adults may fulfill between 8% and 16% of their Ca2+ DRI and between 6% and 31% of their Mg2+ DRI by drinking 2 liters per day. One liter of most moderate mineralization European bottled waters contained between 20% and 58% of the Ca2+ DRI and between 16% and 41% of the Mg2+ DRI in adults. High mineralization bottled waters often contained up to half of the maximum recommended daily intake of Na+. CONCLUSION Drinking water sources available to North Americans may contain high levels of Ca2+, Mg2+, and Na+ and may provide clinically important portions of the recommended dietary intake of these minerals. Physicians should encourage patients to check the mineral content of their drinking water, whether tap or bottled, and choose water most appropriate for their needs. PMID:11318912

Association of tobacco advertising, promotion and sponsorship (TAPS) exposure and cigarette use among Nigerian adolescents: implications for current practices, products and policies.

PubMed

Chido-Amajuoyi, Onyema G; Mantey, Dale S; Clendennen, Stephanie L; Pérez, Adriana

2017-01-01

This study investigates the association between exposure to tobacco advertising, promotion and sponsorship (TAPS) and cigarette use behaviours among adolescents in five Nigerian regions. This is imperative given a 2015 WHO report on the global tobacco epidemic, revealing Nigeria has not met any of the MPOWER TAPS ban indicators instituted since 2008. Secondary data analysis of the 2008 Global Youth Tobacco Survey for Nigeria. Participants were 1399 adolescents, representative of 5 Nigerian regions. Weighted multivariable logistic regression models were used to assess the relationship between TAPS exposure and (1) past 30-day (current) cigarette use, (2) ever cigarette use and (3) susceptibility to use cigarettes among never cigarette users. Sensitivity analysis via complete case analysis and multiple imputation were conducted. Ninety-five per cent of Nigerian adolescents reported exposure to TAPS. Among adolescents who had never smoked, 15% were susceptible to use cigarettes. Cumulative TAPS exposure was significantly associated with both an increased odds of current cigarette use (AOR: 1.73; 95% CI 1.09 to2.99) and ever cigarette use (AOR: 1.29; 95% CI 1.15 to1.45); as well as increased susceptibility to cigarette smoking (AOR: 1.18; 95% CI 1.03 to 1.34), among non-smokers. Given study results, the emergence of new tobacco products and novel platforms for TAPS globally, implementation of existing policies and enhancement of efforts to attain comprehensive bans on all forms of direct and indirect TAPS in line with article 13 of the WHO Framework Convention on Tobacco Control are needed to reduce TAPS exposure and curtail tobacco use in Nigeria.

Association of tobacco advertising, promotion and sponsorship (TAPS) exposure and cigarette use among Nigerian adolescents: implications for current practices, products and policies

PubMed Central

Mantey, Dale S; Clendennen, Stephanie L; Pérez, Adriana

2017-01-01

Background This study investigates the association between exposure to tobacco advertising, promotion and sponsorship (TAPS) and cigarette use behaviours among adolescents in five Nigerian regions. This is imperative given a 2015 WHO report on the global tobacco epidemic, revealing Nigeria has not met any of the MPOWER TAPS ban indicators instituted since 2008. Methods Secondary data analysis of the 2008 Global Youth Tobacco Survey for Nigeria. Participants were 1399 adolescents, representative of 5 Nigerian regions. Weighted multivariable logistic regression models were used to assess the relationship between TAPS exposure and (1) past 30-day (current) cigarette use, (2) ever cigarette use and (3) susceptibility to use cigarettes among never cigarette users. Sensitivity analysis via complete case analysis and multiple imputation were conducted. Results Ninety-five per cent of Nigerian adolescents reported exposure to TAPS. Among adolescents who had never smoked, 15% were susceptible to use cigarettes. Cumulative TAPS exposure was significantly associated with both an increased odds of current cigarette use (AOR: 1.73; 95% CI 1.09 to2.99) and ever cigarette use (AOR: 1.29; 95% CI 1.15 to1.45); as well as increased susceptibility to cigarette smoking (AOR: 1.18; 95% CI 1.03 to 1.34), among non-smokers. Conclusion Given study results, the emergence of new tobacco products and novel platforms for TAPS globally, implementation of existing policies and enhancement of efforts to attain comprehensive bans on all forms of direct and indirect TAPS in line with article 13 of the WHO Framework Convention on Tobacco Control are needed to reduce TAPS exposure and curtail tobacco use in Nigeria. PMID:29082014

Metabolic effect of TAp63α: enhanced glycolysis and pentose phosphate pathway, resulting in increased antioxidant defense

PubMed Central

D'Alessandro, Angelo; Amelio, Ivano; Berkers, Celia R.; Antonov, Alexey; Vousden, Karen H.; Melino, Gerry; Zolla, Lello

2014-01-01

TAp63α is a member of the p53 family, which plays a central role in epithelial cancers. Recently, a role has emerged for p53 family members in cancer metabolic modulation. In order to assess whether TAp63α plays a role in cancer metabolism, we exploited p53-null osteosarcoma Tet-On Saos-2 cells, in which the expression of TAp63α was dependent on doxycycline supplementation to the medium. Metabolomics labeling experiments were performed by incubating the cells in 13C-glucose or 13C15N-glutamine-labeled culture media, as to monitor metabolic fluxes upon induced expression of TAp63α. Induced expression of TAp63α resulted in cell cycle arrest at the G1 phase. From a metabolic standpoint, expression of Tap63α promoted glycolysis and the pentose phosphate pathway, which was uncoupled from nucleotide biosynthesis, albeit prevented oxidative stress in the form of oxidized glutathione. Double 13C-glucose and 13C15N-glutamine metabolic labeling confirmed that induced expression of TAp63α corresponded to a decreased flux of pyruvate to the Krebs cycle and decreased utilization of glutamine for catabolic purposes in the TCA cycle. Results were not conclusive in relation to anabolic utilization of labeled glutamine, since it is unclear to what extent the observed minor TAp63α-dependent increases of glutamine-derived labeling in palmitate could be tied to increased rates of reductive carboxylation and de novo synthesis of fatty acids. Finally, bioinformatics elaborations highlighted a link between patient survival rates and the co-expression of p63 and rate limiting enzymes of the pentose phosphate pathway, G6PD and PGD. PMID:25229745

Transversus abdominis plane block vs. wound infiltration in Caesarean section: a randomised controlled trial.

PubMed

Telnes, A; Skogvoll, E; Lonnée, H

2015-04-01

Multiple studies suggest that transversus abdominis plane (TAP) block (without intrathecal morphine) after Caesarean section (CS) reduces post-operative morphine consumption. In our study, we wanted to compare the analgesic effect of TAP block with infiltration of the wound after CS. We included 60 pregnant women scheduled for elective CS under spinal anaesthesia in a randomised, single-centre, double-blind study. Thirty patients received ultrasound-guided TAP block using 20 ml bupivacaine 0.25% with adrenaline 5 μg/ml bilaterally and 20 ml normal saline as wound infiltration (TAP group). The other 30 patients (the control group) received normal saline 20 ml bilaterally in the TAP, and 20 ml bupivacaine 0.25% with adrenaline 5 μg/ml as wound infiltration. The main outcome was cumulative morphine consumption at 48 h after surgery. In addition, continuous morphine consumption, pain scores and side effects were registered. Fifty-seven patients completed the study. Cumulative morphine consumption at 48 h (mean±standard deviation) was 41±34 mg in the TAP group and 38±27 mg in the control group (P=0.7); a difference of 3 mg (95% confidence interval -13 to 19 mg). Morphine consumption at any time up to 48 h was virtually identical in both groups. Side effects were similar, except for a higher degree of sedation in the TAP group (P=0.04). Compared with wound infiltration with local anaesthetics, TAP block did not reduce cumulative morphine consumption following CS. The TAP block was associated with more pronounced sedation. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Transversus abdominis plane (TAP) block in laparoscopic colorectal surgery improves postoperative pain management: a meta-analysis.

PubMed

Hain, E; Maggiori, L; Prost À la Denise, J; Panis, Y

2018-04-01

Transversus abdominis plane (TAP) block is a locoregional anaesthesia technique of growing interest in abdominal surgery. However, its efficacy following laparoscopic colorectal surgery is still debated. This meta-analysis aimed to assess the efficacy of TAP block after laparoscopic colorectal surgery. All comparative studies focusing on TAP block after laparoscopic colorectal surgery have been systematically identified through the MEDLINE database, reviewed and included. Meta-analysis was performed according to the Mantel-Haenszel method for random effects. End-points included postoperative opioid consumption, morbidity, time to first bowel movement and length of hospital stay. A total of 13 studies, including 7 randomized controlled trials, were included, comprising a total of 600 patients who underwent laparoscopic colorectal surgery with TAP block, compared with 762 patients without TAP block. Meta-analysis of these studies showed that TAP block was associated with a significantly reduced postoperative opioid consumption on the first day after surgery [weighted mean difference (WMD) -14.54 (-25.14; -3.94); P = 0.007] and a significantly shorter time to first bowel movement [WMD -0.53 (-0.61; -0.44); P < 0.001] but failed to show any impact on length of hospital stay [WMD -0.32 (-0.83; 0.20); P = 0.23] although no study considered length of stay as its primary outcome. Finally, TAP block was not associated with a significant increase in the postoperative overall complication rate [OR = 0.84 (0.62-1.14); P = 0.27]. Transversus abdominis plane (TAP) block in laparoscopic colorectal surgery improves postoperative opioid consumption and recovery of postoperative digestive function without any significant drawback. Colorectal Disease © 2018 The Association of Coloproctology of Great Britain and Ireland.

Anatomically ordered tapping interferes more with one-digit addition than two-digit addition: a dual-task fMRI study.

PubMed

Soylu, Firat; Newman, Sharlene D

2016-02-01

Fingers are used as canonical representations for numbers across cultures. In previous imaging studies, it was shown that arithmetic processing activates neural resources that are known to participate in finger movements. Additionally, in one dual-task study, it was shown that anatomically ordered finger tapping disrupts addition and subtraction more than multiplication, possibly due to a long-lasting effect of early finger counting experiences on the neural correlates and organization of addition and subtraction processes. How arithmetic task difficulty and tapping complexity affect the concurrent performance is still unclear. If early finger counting experiences have bearing on the neural correlates of arithmetic in adults, then one would expect anatomically and non-anatomically ordered tapping to have different interference effects, given that finger counting is usually anatomically ordered. To unravel these issues, we studied how (1) arithmetic task difficulty and (2) the complexity of the finger tapping sequence (anatomical vs. non-anatomical ordering) affect concurrent performance and use of key neural circuits using a mixed block/event-related dual-task fMRI design with adult participants. The results suggest that complexity of the tapping sequence modulates interference on addition, and that one-digit addition (fact retrieval), compared to two-digit addition (calculation), is more affected from anatomically ordered tapping. The region-of-interest analysis showed higher left angular gyrus BOLD response for one-digit compared to two-digit addition, and in no-tapping conditions than dual tapping conditions. The results support a specific association between addition fact retrieval and anatomically ordered finger movements in adults, possibly due to finger counting strategies that deploy anatomically ordered finger movements early in the development.