Peripheral blood TIM-3 positive NK and CD8+ T cells throughout pregnancy: TIM-3/galectin-9 interaction and its possible role during pregnancy.

PubMed

Meggyes, Matyas; Miko, Eva; Polgar, Beata; Bogar, Barbara; Farkas, Balint; Illes, Zsolt; Szereday, Laszlo

2014-01-01

The T-cell immunoglobulin and mucin domain (TIM) family is a relatively newly described group of molecules with a conserved structure and important immunological functions. Identification of Galectin-9 as a ligand for TIM-3 has established the Galectin-9/TIM-3 pathway as an important negative regulator of Th1 immunity and tolerance induction. Data about the TIM-3/Gal-9 pathway in the pathogenesis of human diseases is emerging, but their possible role during human pregnancy is not precisely known. The aim of our study was to investigate the number, phenotype and functional activity of TIM-3+ peripheral blood mononuclear cells during healthy human pregnancy. 57 healthy pregnant women [first trimester (n = 16); second trimester (n = 19); third trimester (n = 22)] and 30 non-pregnant controls were enrolled in the study. We measured the surface expression of TIM-3 by cytotoxic T cells, NK cells and NK cell subsets as well as Galectin-9 expression by regulatory T cells by flow cytometry. We analyzed the cytokine production and cytotoxicity of TIM3+ and TIM3- CD8 T and NK cells obtained from non-pregnant and healthy pregnant women at different stages of pregnancy by flow cytometry. Serum Galectin-9 levels were measured by ELISA. Our results show that the numbers of peripheral NK and cytotoxic T cells and their TIM-3 expression do not change between the first, second and third trimesters of pregnancy. Compared to non-pregnant individuals, regulatory T cells show higher level of Galectin-9 expression as pregnancy proceeds, which is in line with the level of Galectin-9 in the patients sera. Cytotoxic T cells, NK cells and NK cell subsets expressing TIM-3 molecule show altered cytokine production and cytotoxicity during pregnancy compared to non-pregnant individuals. Our results indicate that Galectin-9 expressing regulatory T cells, TIM-3+ cytotoxic T cells and NK cells could play an important role in the maintenance of healthy pregnancy.

Role of the Phosphatidylserine Receptor TIM-1 in Enveloped-Virus Entry

PubMed Central

Moller-Tank, Sven; Kondratowicz, Andrew S.; Davey, Robert A.; Rennert, Paul D.

2013-01-01

The cell surface receptor T cell immunoglobulin mucin domain 1 (TIM-1) dramatically enhances filovirus infection of epithelial cells. Here, we showed that key phosphatidylserine (PtdSer) binding residues of the TIM-1 IgV domain are critical for Ebola virus (EBOV) entry through direct interaction with PtdSer on the viral envelope. PtdSer liposomes but not phosphatidylcholine liposomes competed with TIM-1 for EBOV pseudovirion binding and transduction. Further, annexin V (AnxV) substituted for the TIM-1 IgV domain, supporting a PtdSer-dependent mechanism. Our findings suggest that TIM-1-dependent uptake of EBOV occurs by apoptotic mimicry. Additionally, TIM-1 enhanced infection of a wide range of enveloped viruses, including alphaviruses and a baculovirus. As further evidence of the critical role of enveloped-virion-associated PtdSer in TIM-1-mediated uptake, TIM-1 enhanced internalization of pseudovirions and virus-like proteins (VLPs) lacking a glycoprotein, providing evidence that TIM-1 and PtdSer-binding receptors can mediate virus uptake independent of a glycoprotein. These results provide evidence for a broad role of TIM-1 as a PtdSer-binding receptor that mediates enveloped-virus uptake. Utilization of PtdSer-binding receptors may explain the wide tropism of many of these viruses and provide new avenues for controlling their virulence. PMID:23698310

TIM1 (HAVCR1) Is Not Essential for Cellular Entry of Either Quasi-enveloped or Naked Hepatitis A Virions.

PubMed

Das, Anshuman; Hirai-Yuki, Asuka; González-López, Olga; Rhein, Bethany; Moller-Tank, Sven; Brouillette, Rachel; Hensley, Lucinda; Misumi, Ichiro; Lovell, William; Cullen, John M; Whitmire, Jason K; Maury, Wendy; Lemon, Stanley M

2017-09-05

2 decades ago to be an essential cellular receptor for hepatitis A virus (HAV), a picornavirus in the Hepatovirus genus, resulting in its designation as "hepatitis A virus cellular receptor 1" (HAVCR1) by the Human Genome Organization Gene Nomenclature Committee. However, recent studies have shown that HAV exists in nature as both naked, nonenveloped (HAV) virions and membrane-cloaked, quasi-enveloped infectious virus (eHAV), prompting us to revisit the role of TIM1 in viral entry. We show here that TIM1 (HAVCR1) is not an essential cellular receptor for HAV entry into cultured cells or required for viral replication and pathogenesis in permissive strains of mice, although it may facilitate early stages of infection by binding phosphatidylserine on the eHAV surface. This work thus corrects the published record and sets the stage for future efforts to identify specific hepatovirus entry factors. Copyright © 2017 Das et al.

Circulating and tumor-infiltrating Tim-3 in patients with colorectal cancer

PubMed Central

Gao, Quanli; Yuan, Peng; Zhao, Peng; Yuan, Huijuan; Fan, Huijie; Li, Tiepeng; Qin, Peng; Han, Lu; Fang, Weijia; Suo, Zhenhe

2015-01-01

T-cell exhaustion represents a progressive loss of T-cell function. The inhibitory receptor PD-1 is known to negatively regulate CD8+ T cell responses directed against tumor antigen, but the blockades of PD-1 pathway didn't show the objective responses in patients with colorectal cancer (CRC). Thus, further exploring the molecular mechanism responsible for inducing T-cell dysfunction in CRC patients may reveal effective strategies for immune therapy. This study aims to characterize co-inhibitory receptors on T cells in CRC patients to identify novel targets for immunotherapy. In this study, peripheral blood samples from 20 healthy controls and 54 consented CRC patients, and tumor and matched paraneoplastic tissues from 7 patients with advanced CRC, subjected to multicolor flow cytometric analysis of the expression of PD-1 and Tim-3 receptors on CD8+ T cells. It was found that CRC patients presented with significantly higher levels of circulating Tim-3+PD-1+CD8+ T cells compared to the healthy controls (medians of 3.12% and 1.99%, respectively, p = 0.0403). A similar increase of Tim-3+PD-1+CD8+ T cells was also observed in the tumor tissues compared to paraneoplastic tussues. Tim-3+PD-1+CD8+ T cells in tumor tissues produced even less cytokine than that in paraneoplastic tissues. Functional ex vivo experiments showed that Tim-3+PD-1+CD8+ T cells produced significantly less IFN-γ than Tim-3−PD-1−CD8+ T cells, followed by Tim-3+PD-1−CD8+ T cells, and Tim-3−PD-1+CD8+ T cells, indicating a stronger inhibition of IFN-γ production of Tim-3+CD8+ T cells. It is also found in this study that Tim-3+PD-1+CD8+ T cell increase in circulation was correlated with clinical cancer stage but not histologic grade and serum concentrations of cancer biomarker CEA. Our results indicate that upregulation of the inhibitory receptor Tim-3 may restrict T cell responses in CRC patients, and therefore blockage of Tim-3 and thus restoring T cell responses may be a potential

Tim2 is expressed in mouse fetal hepatocytes and regulates their differentiation.

PubMed

Watanabe, Natsumi; Tanaka, Minoru; Suzuki, Kaori; Kumanogoh, Atsushi; Kikutani, Hitoshi; Miyajima, Atsushi

2007-05-01

Liver development is regulated by various extracellular molecules such as cytokines and cell surface proteins. Although several such regulators have been identified, additional molecules are likely to be involved in liver development. To identify such molecules, we employed the signal sequence trap (SST) method to screen cDNAs encoding a secreted or membrane protein from fetal liver and obtained a number of clones. Among them, we found that T cell immunoglobulin and mucin domain 2 (Tim2) was expressed specifically on immature hepatocytes in the fetal liver. Tim2 has been shown to regulate immune responses, but its role in liver development had not been studied. We have examined the possible role of Tim2 in hepatocyte differentiation. At first, we prepared a soluble Tim2 fusion protein consisting of its extracellular domain and the Fc domain of human IgG (Tim2-hFc) and found that it bound to fetal and adult hepatocytes, suggesting that there are Tim2-binding molecules on hepatocytes. Second, Tim2-hFc inhibited the differentiation of hepatocytes in fetal liver primary culture, i.e., the expression of mature hepatic enzymes and accumulation of glycogen were severely reduced. Third, Tim2-hFc also inhibited proliferation of fetal hepatocytes. Fourth, down-regulation of Tim2 expression by small interfering RNA (siRNA) enhanced the expression of liver differentiation marker genes. It is strongly suggested that Tim2 is involved in the differentiation of fetal hepatocytes.

TIM-1 Mediates Dystroglycan-Independent Entry of Lassa Virus.

PubMed

Brouillette, Rachel B; Phillips, Elisabeth K; Patel, Radhika; Mahauad-Fernandez, Wadie; Moller-Tank, Sven; Rogers, Kai J; Dillard, Jacob A; Cooney, Ashley L; Martinez-Sobrido, Luis; Okeoma, Chioma; Maury, Wendy

2018-06-06

Lassa virus (LASV) is an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year. LASV entry into a variety of cell types is mediated by interactions with glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor, α-dystroglycan (αDG). Yet, cells lacking αDG are permissive to LASV infection, suggesting that alternative receptors exist. Previous studies demonstrate that phosphatidylserine (PtdSer)-binding receptors, Axl and Tyro3 along with C-type lectin receptors, mediate αDG-independent entry. Here, we demonstrate that another PtdSer receptor, TIM-1, mediates LASV glycoprotein (GP) pseudotyped virions entry into αDG knocked out HEK 293T and wild-type (WT) Vero which express αDG lacking appropriate glycosylation. To investigate the mechanism by which TIM-1 mediates enhancement of entry, we demonstrate that mutagenesis of the TIM-1 IgV domain PtdSer-binding pocket abrogated transduction. Further, the human TIM-1 IgV domain binding monoclonal antibody, ARD5, blocked transduction of pseudovirions bearing LASV GP in a dose-dependent manner. Finally, as we showed previously for other viruses that use TIM-1 for entry, a chimeric TIM-1 protein that substitutes the proline rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor. These studies provide evidence that, in the absence of a functional αDG, TIM-1 mediates entry of LASV pseudoviral particles through interactions of virions with the IgV PtdSer binding pocket of TIM-1. Importance PtdSer receptors, such as TIM-1, are emerging as critical entry factors for many enveloped viruses. Most recently, Hepatitis C virus and Zika virus have been added to a growing list. PtdSer receptors engage with enveloped viruses through binding of PtdSer embedded in the viral envelope, defining them as GP-independent receptors. This GP-independent entry mechanism should effectively mediate entry of all

Taming dendritic cells with TIM-3: Another immunosuppressive strategy by tumors

PubMed Central

Patel, Jaina; Bozeman, Erica N.; Selvaraj, Periasamy

2013-01-01

The identification of TIM-3 expression on tumor associated dendritic cells (TADCs) provides insight into another aspect of tumor-mediated immunosuppression. The role of TIM-3 has been well characterized on tumor-infiltrating T cells, however its role on TADCs was not previously known. The current paper demonstrated that TIM-3 was predominantly expressed by TADCs and its interaction with the nuclear protein HMGB1 suppressed nucleic acid mediated activation of an effective antitumor immune response. The authors were able to show that TIM-3 interaction with HMGB1 prevented the localization of nucleic acids into endosomal vesicles. Furthermore, chemotherapy was found to be more effective in anti-TIM-3 mAb treated mice or mice depleted of all DCs which indicated that significant role played by TADCs inhibiting tumor regression. Taken together, these findings identify TIM-3 as a potential target for inducing antitumor immunity in conjunction with DNA vaccines and/or immunogenic chemotherapy in clinical settings. PMID:23240746

HST PSF simulation using Tiny Tim

NASA Technical Reports Server (NTRS)

Krist, J. E.

1992-01-01

Tiny Tim is a program which simulates Hubble Space Telescope imaging camera PSF's. It is portable (written and distributed in C) and is reasonably fast. It can model the WFPC, WFPC 2, FOC, and COSTAR corrected FOC cameras. In addition to aberrations such as defocus and spherical, it also includes WFPC obscuration shifting, mirror zonal error maps, and jitter. The program has been used at a number of sites for deconvolving HST images. Tiny Tim is available via anonymous ftp on stsci.edu in the directory software/tinytim.

Distinct forms of mitochondrial TOM-TIM supercomplexes define signal-dependent states of preprotein sorting.

PubMed

Chacinska, Agnieszka; van der Laan, Martin; Mehnert, Carola S; Guiard, Bernard; Mick, David U; Hutu, Dana P; Truscott, Kaye N; Wiedemann, Nils; Meisinger, Chris; Pfanner, Nikolaus; Rehling, Peter

2010-01-01

Mitochondrial import of cleavable preproteins occurs at translocation contact sites, where the translocase of the outer membrane (TOM) associates with the presequence translocase of the inner membrane (TIM23) in a supercomplex. Different views exist on the mechanism of how TIM23 mediates preprotein sorting to either the matrix or inner membrane. On the one hand, two TIM23 forms were proposed, a matrix transport form containing the presequence translocase-associated motor (PAM; TIM23-PAM) and a sorting form containing Tim21 (TIM23(SORT)). On the other hand, it was reported that TIM23 and PAM are permanently associated in a single-entity translocase. We have accumulated distinct transport intermediates of preproteins to analyze the translocases in their active, preprotein-carrying state. We identified two different forms of active TOM-TIM23 supercomplexes, TOM-TIM23(SORT) and TOM-TIM23-PAM. These two supercomplexes do not represent separate pathways but are in dynamic exchange during preprotein translocation and sorting. Depending on the signals of the preproteins, switches between the different forms of supercomplex and TIM23 are required for the completion of preprotein import.

Disruption of T-cell immunoglobulin and mucin domain molecule (TIM)-1/TIM4 interaction as a therapeutic strategy in a dendritic cell-induced peanut allergy model.

PubMed

Feng, Bai-Sui; Chen, Xiao; He, Shao-Heng; Zheng, Peng-Yuan; Foster, Jane; Xing, Zhou; Bienenstock, John; Yang, Ping-Chang

2008-07-01

Recent reports indicate that dendritic cell (DC)-derived T-cell immunoglobulin and mucin domain molecule (TIM)-4 plays an important role in the initiation of T(H)2 polarization. This study aims to elucidate the mechanisms of peanut allergy mediated by microbial products and DCs and the relationship between peanut allergy and TIM4. Mouse bone marrow-derived DCs (BMDCs) were generated and exposed to cholera toxin (CT) or/and peanut extract (PE) for 24 hours and then adoptively transferred to naive mice. After re-exposure to specific antigen PE, the mice were killed; intestinal allergic status was determined. Increased expression of TIM4 and costimulatory molecules was detected in BMDCs after concurrent exposure to CT and PE. Adoptively transferred CT/PE-conditioned BMDCs resulted in the increases in serum PE-specific IgE and skewed T(H)2 polarization in the intestine. Oral challenge with specific antigen PE induced mast cell activation in the intestine. Treating with Toll-like receptor 4 small interfering RNA abolished increased expression of TIM4 and costimulatory molecules by BMDCs. Pretreatment with anti-TIM1 or anti-TIM4 antibody abolished PE-specific T(H)2 polarization and allergy in the intestine. Concurrent exposure to microbial product CT and food antigen PE increases TIM4 expression in DCs and promotes DC maturation, which plays an important role in the initiation of PE-specific T(H)2 polarization and allergy in the intestine. Modulation of TIM4 production in DCs represents a novel therapeutic approach for the treatment of peanut allergy.

Cooperation of TOM and TIM23 complexes during translocation of proteins into mitochondria.

PubMed

Waegemann, Karin; Popov-Čeleketić, Dušan; Neupert, Walter; Azem, Abdussalam; Mokranjac, Dejana

2015-03-13

Translocation of the majority of mitochondrial proteins from the cytosol into mitochondria requires the cooperation of TOM and TIM23 complexes in the outer and inner mitochondrial membranes. The molecular mechanisms underlying this cooperation remain largely unknown. Here, we present biochemical and genetic evidence that at least two contacts from the side of the TIM23 complex play an important role in TOM-TIM23 cooperation in vivo. Tim50, likely through its very C-terminal segment, interacts with Tom22. This interaction is stimulated by translocating proteins and is independent of any other TOM-TIM23 contact known so far. Furthermore, the exposure of Tim23 on the mitochondrial surface depends not only on its interaction with Tim50 but also on the dynamics of the TOM complex. Destabilization of the individual contacts reduces the efficiency of import of proteins into mitochondria and destabilization of both contacts simultaneously is not tolerated by yeast cells. We conclude that an intricate and coordinated network of protein-protein interactions involving primarily Tim50 and also Tim23 is required for efficient translocation of proteins across both mitochondrial membranes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Taming dendritic cells with TIM-3: another immunosuppressive strategy used by tumors.

PubMed

Patel, Jaina; Bozeman, Erica N; Selvaraj, Periasamy

2012-12-01

Evaluation of: Chiba S, Baghdadi M, Akiba H et al. Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat. Immunol. 13, 832-842 (2012). The identification of TIM-3 expression on tumor-associated dendritic cells (TADCs) provides insight into another aspect of tumor-mediated immunosuppression. The role of TIM-3 has been well characterized on tumor-infiltrating T cells; however, its role on TADCs was not previously known. The current paper demonstrated that TIM-3 was predominantly expressed by TADCs and its interaction with the nuclear protein HMGB1 suppressed nucleic acid-mediated activation of an effective antitumor immune response. The authors were able to show that TIM-3 interaction with HMGB1 prevented the localization of nucleic acids into endosomal vesicles. Furthermore, chemotherapy was found to be more effective in anti-TIM-3 monoclonal antibody-treated mice or mice depleted of all DCs, which indicated that a significant role is played by TADCs in inhibiting tumor regression. Taken together, these findings identify TIM-3 as a potential target for inducing antitumor immunity in conjunction with DNA vaccines and/or immunogenic chemotherapy in clinical settings.

The TIM and TAM families of phosphatidylserine receptors mediate dengue virus entry.

PubMed

Meertens, Laurent; Carnec, Xavier; Lecoin, Manuel Perera; Ramdasi, Rasika; Guivel-Benhassine, Florence; Lew, Erin; Lemke, Greg; Schwartz, Olivier; Amara, Ali

2012-10-18

Dengue viruses (DVs) are responsible for the most medically relevant arboviral diseases. However, the molecular interactions mediating DV entry are poorly understood. We determined that TIM and TAM proteins, two receptor families that mediate the phosphatidylserine (PtdSer)-dependent phagocytic removal of apoptotic cells, serve as DV entry factors. Cells poorly susceptible to DV are robustly infected after ectopic expression of TIM or TAM receptors. Conversely, DV infection of susceptible cells is inhibited by anti-TIM or anti-TAM antibodies or knockdown of TIM and TAM expression. TIM receptors facilitate DV entry by directly interacting with virion-associated PtdSer. TAM-mediated infection relies on indirect DV recognition, in which the TAM ligand Gas6 acts as a bridging molecule by binding to PtdSer within the virion. This dual mode of virus recognition by TIM and TAM receptors reveals how DVs usurp the apoptotic cell clearance pathway for infectious entry. Copyright © 2012 Elsevier Inc. All rights reserved.

TIM Version 3.0 beta - Technical Description and User's Guidance

EPA Pesticide Factsheets

Provides technical information on version 3.0 of the Terrestrial Investigation Model (TIM v.3.0). Describes how TIM derives joint distributions of exposure and toxicity to calculate the risk of mortality to birds.

Tim-3 Up-regulation in Patients with Gastric Cancer and Peptic Ulcer Disease

PubMed Central

Naghavi-Alhosseini, Mahdieh; Tehrani, Mohsen; Ajami, Abolghasem; Rafiei, Alireza; Taghvaei, Tarang; Vahedi-Larijani, Laleh; Hossein-Nataj, Hadi; Asgarian-Omran, Hossein

2017-01-01

Background: T-cell immunoglobulin and mucin domain protein-3 (Tim-3), an inhibitory immunoregulatory receptor, has been recently implicated in tumor biology and tumor-associated immune suppression. In the present study, expression of Tim-3 was evaluated in gastric cancer (GC) and peptic ulcer disease (PUD) at both mRNA and protein levels. Methods: A total of 133 gastric tissue biopsies, comprising 43 from GC cases, 48 from PUD and 42 from non-ulcer dyspepsia (NUD) serving as controls were collected. Additionally, non-neoplastic adjacent tissue biopsies were also obtained from 6 patients with GC. Infection with Helicobacter pylori was determined by the rapid urease test for all participants and H&E staining was conducted for GC and PUD patients. Tim-3 relative mRNA expression was determined by SYBR Green based Real-Time PCR using β-actin as a reference gene. Tim-3 protein expression was also studied by immunohistochemistry in 7 GC, 7 PUD and 10 NUD tissue samples. Results: Tim-3 was expressed at higher levels in GC (p=0.030) and PUD (p=0.022) cases compared to he NUD group. Among paired samples obtained from gastric cancer patients, tumor tissues showed elevated Tim-3 expression (p=0.019) in comparison with adjacent non-neoplastic biopsies. Tim-3 mRNA findings were supported by detection of more Tim-3 protein in cancerous (p=0.002) and ulcerative (p=0.01) tissues than in controls. Tim-3 was similarly expressed in H. pylori positive and negative cases. Conclusion: Higher Tim-3 expression in patients with gastric cancer and peptic ulcer implies that it might be involved in immune regulation and establishment of these gastrointestinal diseases. Targeted immunotherapy by blocking of inhibitory receptors like Tim-3 could be a promising approach for gastric cancer treatment. PMID:28441784

Tim-3 directly enhances CD8 T cell responses to acute Listeria monocytogenes infection

PubMed Central

Gorman, Jacob V.; Starbeck-Miller, Gabriel; Pham, Nhat-Long L.; Traver, Geri L.; Rothman, Paul B.; Harty, John T.; Colgan, John D.

2014-01-01

Tim-3 is a surface molecule expressed throughout the immune system that can mediate both stimulatory and inhibitory effects. Previous studies have provided evidence that Tim-3 functions to enforce CD8 T cell exhaustion, a dysfunctional state associated with chronic stimulation. In contrast, the role of Tim-3 in the regulation of CD8 T cell responses to acute and transient stimulation remains undefined. To address this knowledge gap, we examined how Tim-3 affects CD8 T cell responses to acute Listeria monocytogenes (LM) infection. Analysis of wild-type (WT) mice infected with LM revealed that Tim-3 was transiently expressed by activated CD8 T cells and was associated primarily with acquisition of an effector phenotype. Comparison of responses to LM by WT and Tim-3 KO mice showed that the absence of Tim-3 significantly reduced the magnitudes of both primary and secondary CD8 T cell responses, which correlated with decreased IFN-γ production and degranulation by Tim-3 KO cells stimulated with peptide antigen ex vivo. To address the T cell-intrinsic role of Tim-3, we analyzed responses to LM infection by WT and Tim-3 KO TCR-transgenic CD8 T cells following adoptive transfer into a shared WT host. In this setting, the accumulation of CD8 T cells and the generation of cytokine-producing cells were significantly reduced by the lack of Tim-3, demonstrating that this molecule has a direct effect on CD8 T cell function. Combined, our results suggest that Tim-3 can mediate a stimulatory effect on CD8 T cell responses to an acute infection. PMID:24567532

Interaction of divalent metal ions with human translocase of inner membrane of mitochondria Tim23.

PubMed

Feng, Wei; Zhang, Yongqiang; Deng, Honghua; Li, Shu Jie

2016-06-17

The preprotein translocase of the inner membrane of mitochondria (TIM23 complex) is the main entry gate for proteins of the matrix and the inner membrane. Tim23p, the core component of TIM23 complex, forms the import pore across the inner membrane and exerts a key function in the protein import. However, the interaction of divalent metal ions with Tim23p and the contribution in the interaction of presequence peptide with Tim23p are still unknown. Herein, we investigated the interaction of divalent metal ions with the intermembrane space domain of Tim23p (Tim23IMS) and the interaction of presequence peptides with Tim23IMS in presence of Ca(2+) ion by fluorescence spectroscopy in vitro. The static fluorescence quenching indicates the existence of strong binding between divalent metal ions and Tim23IMS. The order of the binding strength is Ca(2+), Mg(2+), Cu(2+), Mn(2+), and Co(2+) (from strong to weak). Moreover, the interaction of presequence peptides with Tim23IMS is weakened in presence of Ca(2+) ion, which implicates that Ca(2+) ion may play an important role in the protein import by TIM23 complex. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysis of TIMS performance subjected to simulated wind blast

NASA Technical Reports Server (NTRS)

Jaggi, S.; Kuo, S.

1992-01-01

The results of the performance of the Thermal Infrared Multispectral Scanner (TIMS) when it is subjected to various wind conditions in the laboratory are described. Various wind conditions were simulated using a 24 inch fan or combinations of air jet streams blowing toward either or both of the blackbody surfaces. The fan was used to simulate a large volume of air flow at moderate speeds (up to 30 mph). The small diameter air jets were used to probe TIMS system response in reaction to localized wind perturbations. The maximum nozzle speed of the air jet was 60 mph. A range of wind directions and speeds were set up in the laboratory during the test. The majority of the wind tests were conducted under ambient conditions with the room temperature fluctuating no more than 2 C. The temperature of the high speed air jet was determined to be within 1 C of the room temperature. TIMS response was recorded on analog tape. Additional thermistor readouts of the blackbody temperatures and thermocouple readout of the ambient temperature were recorded manually to be compared with the housekeeping data recorded on the tape. Additional tests were conducted under conditions of elevated and cooled room temperatures. The room temperature was varied between 19.5 to 25.5 C in these tests. The calibration parameters needed for quantitative analysis of TIMS data were first plotted on a scanline-by-scanline basis. These parameters are the low and high blackbody temperature readings as recorded by the TIMS and their corresponding digitized count values. Using these values, the system transfer equations were calculated. This equation allows us to compute the flux for any video count by computing the slope and intercept of the straight line that relates the flux to the digital count. The actual video of the target (the lab floor in this case) was then compared with a simulated target. This simulated target was assumed to be a blackbody at emissivity of .95 degrees and the temperature was

Architecture of the TIM23 inner mitochondrial translocon and interactions with the matrix import motor.

PubMed

Ting, See-Yeun; Schilke, Brenda A; Hayashi, Masaya; Craig, Elizabeth A

2014-10-10

Translocation of proteins from the cytosol across the mitochondrial inner membrane is driven by action of the matrix-localized multi-subunit import motor, which is associated with the TIM23 translocon. The architecture of the import apparatus is not well understood. Here, we report results of site-specific in vivo photocross-linking along with genetic and coimmunoprecipitation analyses dissecting interactions between import motor subunits and the translocon. The translocon is composed of the two integral membrane proteins Tim23 and Tim17, each containing four membrane-spanning segments. We found that Tim23 having a photoactivatable cross-linker in the matrix exposed loop between transmembrane domains 1 and 2 (loop 1) cross-linked to Tim44. Alterations in this loop destabilized interaction of Tim44 with the translocon. Analogously, Tim17 having a photoactivatable cross-linker in the matrix exposed loop between transmembrane segments 1 and 2 (loop 1) cross-linked to Pam17. Alterations in this loop caused destabilization of the interaction of Pam17 with the translocon. Substitution of individual photoactivatable residues in Tim44 and Pam17 in regions we previously identified as important for translocon association resulted in cross-linking to Tim23 and Tim17, respectively. Our results are consistent with a model in which motor association is achieved via interaction of Tim23 with Tim44, which serves as a scaffold for association of other motor components, and of Tim17 with Pam17. As both Tim44 and Pam17 have been implicated as regulatory subunits of the motor, this positioning is conducive for responding to conformational changes in the translocon upon a translocating polypeptide entering the channel. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

User's manual for The TIM benefit-cost (TIM-BC) Tool (Version: 1.0.0)

DOT National Transportation Integrated Search

2015-07-04

This document serves as a users manual for the Traffic Incident Management Benefit-Cost Tool (TIM-BC) Version 1.0.0 - Safety Service Patrol Benefit-Cost (SSP-BC) Tool, which is used to assist State and local engineers and decisionmakers with evalu...

Lithologic mapping of silicate rocks using TIMS

NASA Technical Reports Server (NTRS)

Gillespie, A. R.

1986-01-01

Common rock-forming minerals have thermal infrared spectral features that are measured in the laboratory to infer composition. An airborne Daedalus scanner (TIMS) that collects six channels of thermal infrared radiance data (8 to 12 microns), may be used to measure these same features for rock identification. Previously, false-color composite pictures made from channels 1, 3, and 5 and emittance spectra for small areas on these images were used to make lithologic maps. Central wavelength, standard deviation, and amplitude of normal curves regressed on the emittance spectra are related to compositional information for crystalline igneous silicate rocks. As expected, the central wavelength varies systematically with silica content and with modal quartz content. Standard deviation is less sensitive to compositional changes, but large values may result from mixed admixture of vegetation. Compression of the six TIMS channels to three image channels made from the regressed parameters may be effective in improving geologic mapping from TIMS data, and these synthetic images may form a basis for the remote assessment of rock composition.

TIM Barrel Protein Structure Classification Using Alignment Approach and Best Hit Strategy

NASA Astrophysics Data System (ADS)

Chu, Jia-Han; Lin, Chun Yuan; Chang, Cheng-Wen; Lee, Chihan; Yang, Yuh-Shyong; Tang, Chuan Yi

2007-11-01

The classification of protein structures is essential for their function determination in bioinformatics. It has been estimated that around 10% of all known enzymes have TIM barrel domains from the Structural Classification of Proteins (SCOP) database. With its high sequence variation and diverse functionalities, TIM barrel protein becomes to be an attractive target for protein engineering and for the evolution study. Hence, in this paper, an alignment approach with the best hit strategy is proposed to classify the TIM barrel protein structure in terms of superfamily and family levels in the SCOP. This work is also used to do the classification for class level in the Enzyme nomenclature (ENZYME) database. Two testing data sets, TIM40D and TIM95D, both are used to evaluate this approach. The resulting classification has an overall prediction accuracy rate of 90.3% for the superfamily level in the SCOP, 89.5% for the family level in the SCOP and 70.1% for the class level in the ENZYME. These results demonstrate that the alignment approach with the best hit strategy is a simple and viable method for the TIM barrel protein structure classification, even only has the amino acid sequences information.

Tim18, a component of the mitochondrial translocator, mediates yeast cell death induced by arsenic.

PubMed

Du, Li; Yu, Yong; Li, Zidong; Chen, Jingsi; Liu, Yan; Xia, Yongjing; Liu, Xiangjun

2007-08-01

Evidence is presented that Tim18, a mitochondria translocase, plays a role in the previously described apoptosis induced by arsenite in Saccharomyces cerevisiae. Tim18 deletion mutant exhibited resistance to arsenite. After arsenite treatment, both the wild type and Tim18-deficient cells showed reactive oxygen species (ROS) production. Arsenite induced the higher expression of tim18 in wild type yeast cells. We found that the tim18 deletion mutant also exhibited resistance to other apoptotic stresses such as acetic acid, H2O2, and hyperosmotic stress. These results suggest that Tim18 is important for yeast cell death induced by arsenic, and it may act downstream of ROS production.

The TIM Barrel Architecture Facilitated the Early Evolution of Protein-Mediated Metabolism.

PubMed

Goldman, Aaron David; Beatty, Joshua T; Landweber, Laura F

2016-01-01

The triosephosphate isomerase (TIM) barrel protein fold is a structurally repetitive architecture that is present in approximately 10% of all enzymes. It is generally assumed that this ubiquity in modern proteomes reflects an essential historical role in early protein-mediated metabolism. Here, we provide quantitative and comparative analyses to support several hypotheses about the early importance of the TIM barrel architecture. An information theoretical analysis of protein structures supports the hypothesis that the TIM barrel architecture could arise more easily by duplication and recombination compared to other mixed α/β structures. We show that TIM barrel enzymes corresponding to the most taxonomically broad superfamilies also have the broadest range of functions, often aided by metal and nucleotide-derived cofactors that are thought to reflect an earlier stage of metabolic evolution. By comparison to other putatively ancient protein architectures, we find that the functional diversity of TIM barrel proteins cannot be explained simply by their antiquity. Instead, the breadth of TIM barrel functions can be explained, in part, by the incorporation of a broad range of cofactors, a trend that does not appear to be shared by proteins in general. These results support the hypothesis that the simple and functionally general TIM barrel architecture may have arisen early in the evolution of protein biosynthesis and provided an ideal scaffold to facilitate the metabolic transition from ribozymes, peptides, and geochemical catalysts to modern protein enzymes.

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

PubMed

Feng, Xuemei; Feng, Juan

2016-12-01

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

Role of Tim50 in the Transfer of Precursor Proteins from the Outer to the Inner Membrane of Mitochondria

PubMed Central

Sichting, Martin; Popov-Čeleketić, Dušan; Mapa, Koyeli; Gevorkyan-Airapetov, Lada; Zohary, Keren; Hell, Kai; Azem, Abdussalam

2009-01-01

Transport of essentially all matrix and a number of inner membrane proteins is governed, entirely or in part, by N-terminal presequences and requires a coordinated action of the translocases of outer and inner mitochondrial membranes (TOM and TIM23 complexes). Here, we have analyzed Tim50, a subunit of the TIM23 complex that is implicated in transfer of precursors from TOM to TIM23. Tim50 is recruited to the TIM23 complex via Tim23 in an interaction that is essentially independent of the rest of the translocase. We find Tim50 in close proximity to the intermembrane space side of the TOM complex where it recognizes both types of TIM23 substrates, those that are to be transported into the matrix and those destined to the inner membrane, suggesting that Tim50 recognizes presequences. This function of Tim50 depends on its association with TIM23. We conclude that the efficient transfer of precursors between TOM and TIM23 complexes requires the concerted action of Tim50 with Tim23. PMID:19144822

Role of Tim50 in the transfer of precursor proteins from the outer to the inner membrane of mitochondria.

PubMed

Mokranjac, Dejana; Sichting, Martin; Popov-Celeketić, Dusan; Mapa, Koyeli; Gevorkyan-Airapetov, Lada; Zohary, Keren; Hell, Kai; Azem, Abdussalam; Neupert, Walter

2009-03-01

Transport of essentially all matrix and a number of inner membrane proteins is governed, entirely or in part, by N-terminal presequences and requires a coordinated action of the translocases of outer and inner mitochondrial membranes (TOM and TIM23 complexes). Here, we have analyzed Tim50, a subunit of the TIM23 complex that is implicated in transfer of precursors from TOM to TIM23. Tim50 is recruited to the TIM23 complex via Tim23 in an interaction that is essentially independent of the rest of the translocase. We find Tim50 in close proximity to the intermembrane space side of the TOM complex where it recognizes both types of TIM23 substrates, those that are to be transported into the matrix and those destined to the inner membrane, suggesting that Tim50 recognizes presequences. This function of Tim50 depends on its association with TIM23. We conclude that the efficient transfer of precursors between TOM and TIM23 complexes requires the concerted action of Tim50 with Tim23.

Ebola Virus Binding to Tim-1 on T Lymphocytes Induces a Cytokine Storm.

PubMed

Younan, Patrick; Iampietro, Mathieu; Nishida, Andrew; Ramanathan, Palaniappan; Santos, Rodrigo I; Dutta, Mukta; Lubaki, Ndongala Michel; Koup, Richard A; Katze, Michael G; Bukreyev, Alexander

2017-09-26

Ebola virus (EBOV) disease (EVD) results from an exacerbated immunological response that is highlighted by a burst in the production of inflammatory mediators known as a "cytokine storm." Previous reports have suggested that nonspecific activation of T lymphocytes may play a central role in this phenomenon. T-cell immunoglobulin and mucin domain-containing protein 1 (Tim-1) has recently been shown to interact with virion-associated phosphatidylserine to promote infection. Here, we demonstrate the central role of Tim-1 in EBOV pathogenesis, as Tim-1 -/- mice exhibited increased survival rates and reduced disease severity; surprisingly, only a limited decrease in viremia was detected. Tim-1 -/- mice exhibited a modified inflammatory response as evidenced by changes in serum cytokines and activation of T helper subsets. A series of in vitro assays based on the Tim-1 expression profile on T cells demonstrated that despite the apparent absence of detectable viral replication in T lymphocytes, EBOV directly binds to isolated T lymphocytes in a phosphatidylserine-Tim-1-dependent manner. Exposure to EBOV resulted in the rapid development of a CD4 Hi CD3 Low population, non-antigen-specific activation, and cytokine production. Transcriptome and Western blot analysis of EBOV-stimulated CD4 + T cells confirmed the induction of the Tim-1 signaling pathway. Furthermore, comparative analysis of transcriptome data and cytokine/chemokine analysis of supernatants highlight the similarities associated with EBOV-stimulated T cells and the onset of a cytokine storm. Flow cytometry revealed virtually exclusive binding and activation of central memory CD4 + T cells. These findings provide evidence for the role of Tim-1 in the induction of a cytokine storm phenomenon and the pathogenesis of EVD. IMPORTANCE Ebola virus infection is characterized by a massive release of inflammatory mediators, which has come to be known as a cytokine storm. The severity of the cytokine storm is

The intermembrane space domain of Tim23 is intrinsically disordered with a distinct binding region for presequences

PubMed Central

de la Cruz, Laura; Bajaj, Rakhi; Becker, Stefan; Zweckstetter, Markus

2010-01-01

Proteins targeted to the mitochondrial matrix are translocated through the outer and the inner mitochondrial membranes by two protein complexes, the translocase of the outer membrane (TOM) and one of the translocases of the inner membrane (TIM23). The protein Tim23, the core component of TIM23, consists of an N-terminal, soluble domain in the intermembrane space (IMS) and a C-terminal domain that forms the import pore across the inner membrane. Before translocation proceeds, precursor proteins are recognized by the N-terminal domain of Tim23, Tim23N (residues 1–96). By using NMR spectroscopy, we show that Tim23N is a monomeric protein belonging to the family of intrinsically disordered proteins. Titrations of Tim23N with two presequences revealed a distinct binding region of Tim23N formed by residues 71–84. In a charge-hydropathy plot containing all soluble domains of TOM and TIM23, Tim23N was found to be the only domain with more than 40 residues in the IMS that is predicted to be intrinsically disordered, suggesting that Tim23N might function as hub in the mitochondrial import machinery protein network. PMID:20718036

Combined blockade of Tim-3 and MEK inhibitor enhances the efficacy against melanoma

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

Liu, Yang; Cai, Pengcheng; Wang, Ning

Insights into the role of the mitogen-activated protein kinase (MAPK) pathway and immune checkpoints have led combined targeted therapy and immunotherapy to be a promising regimen. Trametinib, as a mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor, has demonstrated effectiveness in patients with advanced melanoma. T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3), an immune checkpoint molecule, participates in multiple negative regulation of antitumor immunity. We for the first time to our knowledge reported the combination of trametinib and anti-Tim-3 monoclonal antibody (mAb) in treating B16-F10 melanoma mice. We discovered that trametinib remarkably promoted apoptosis and inhibited cell proliferation while inhibition of MEKmore » improved the expression of Tim-3 and caused the decrease of CD8{sup +} T cells; to the contrary, anti-Tim-3 mAb enhanced antitumor immunity by stimulating CD8{sup +} T cells, thus the combined therapy produced potent antitumor effect cooperatively. Taken together, our study provides compelling evidence for combining trametinib and anti-Tim-3 mAb as a potential valuable regimen in treating melanoma. - Highlights: • The potent antitumor efficacy of combined trametinib and anti-Tim-3 mAb. • MEK inhibitor involves in up-regulation of Tim-3. • The combined medication provides new insights into melanoma treatment.« less

Decreased TIM-3 mRNA expression in peripheral blood mononuclear cells from nephropathy patients.

PubMed

Cai, X Z; Liu, N; Qiao, Y; Du, S Y; Chen, Y; Chen, D; Yu, S; Jiang, Y

2015-06-12

Increasing evidence shows that TIM-1 and TIM-3 in-fluence chronic autoimmune diseases, and their expression levels in immune cells from nephritic patients are still unknown. Real-time transcription-polymerase chain reaction analysis was used to deter-mine expression levels of TIM-1 and TIM-3 mRNA in peripheral blood mononuclear cells (PBMCs) from 36 patients with minimal change glo-merulopathy (MCG), 65 patients with lupus nephritis (LN), 78 patients with IgA nephropathy (IgAN), 55 patients with membranous nephropa-thy (MN), 22 patients with crescentic glomerulonephritis (CGN), 26 patients with anaphylactoid purpura nephritis (APN), and 63 healthy controls. TIM-3 mRNA expression significantly decreased in PBMCs from nephritic patients (LN, P < 0.0001; MCG, P < 0.0001; MN, P = 0.0031; CGN, P = 0.0464; IgAN, P = 0.0002; APN, P = 0.0392) com-pared with healthy controls. In contrast, there was no significant differ-ence in TIM-1 mRNA expression between the patients and the healthy controls. Our results suggest that insufficient expression of TIM-3 mRNA may be involved in the pathogenesis of nephropathy.

BOREAS Level-0 TIMS Imagery: Digital Counts in BIL Format

NASA Technical Reports Server (NTRS)

Newcomer, Jeffrey A.; Dominquez, Roseanne; Hall, Forrest G. (Editor)

2000-01-01

For BOREAS, the TIMS imagery, along with the other remotely sensed images, was collected to provide spatially extensive information over the primary study areas. The level-0 TIMS images cover the time periods of 16-Apr-1994 to 20-Apr-1994 and 06-Sep-1994 to 17-Sep-1994. The images are available in their original uncalibrated format.

Analysis and production of the traffic incident management state self-assessments (TIM SA) national report.

DOT National Transportation Integrated Search

2008-09-29

The Traffic Incident Management Self-Assessment (TIM SA) provides a means for evaluating progress in achievement of individual TIM program components and overall TIM program success in three areas: Program and Institutional Issues; Operational Issues...

Application of split window technique to TIMS data

NASA Technical Reports Server (NTRS)

Matsunaga, Tsuneo; Rokugawa, Shuichi; Ishii, Yoshinori

1992-01-01

Absorptions by the atmosphere in thermal infrared region are mainly due to water vapor, carbon dioxide, and ozone. As the content of water vapor in the atmosphere greatly changes according to weather conditions, it is important to know its amount between the sensor and the ground for atmospheric corrections of thermal Infrared Multispectral Scanner (TIMS) data (i.e. radiosonde). On the other hand, various atmospheric correction techniques were already developed for sea surface temperature estimations from satellites. Among such techniques, Split Window technique, now widely used for AVHRR (Advanced Very High Resolution Radiometer), uses no radiosonde or any kind of supplementary data but a difference between observed brightness temperatures in two channels for estimating atmospheric effects. Applications of Split Window technique to TIMS data are discussed because availability of atmospheric profile data is not clear when ASTER operates. After these theoretical discussions, the technique is experimentally applied to TIMS data at three ground targets and results are compared with atmospherically corrected data using LOWTRAN 7 with radiosonde data.

PD-1 and Tim-3 Pathways Regulate CD8+ T Cells Function in Atherosclerosis.

PubMed

Qiu, Ming-Ke; Wang, Song-Cun; Dai, Yu-Xin; Wang, Shu-Qing; Ou, Jing-Min; Quan, Zhi-Wei

2015-01-01

T cell-mediated immunity plays a significant role in the development of atherosclerosis (AS). There is increasing evidence that CD8+ T cells are also involved in AS but their exact roles remain unclear. The inhibitory receptors programmed cell death-1 (PD-1) and T cell immunoglobulin and mucin domain 3 (Tim-3) are well known inhibitory molecules that play a crucial role in regulating CD8+ T cell activation or tolerance. Here, we demonstrate that the co-expression of PD-1 and Tim-3 on CD8+ T cells is up-regulated in AS patients. PD-1+ Tim-3+ CD8+ T cells are enriched for within the central T (TCM) cell subset, with high proliferative activity and CD127 expression. Co-expression of PD-1 and Tim-3 on CD8+ T cells is associated with increased anti-atherogenic cytokine production as well as decreased pro-atherogenic cytokine production. Blockade of PD-1 and Tim-3 results in a decrease of anti-atherogenic cytokine production by PD-1+ Tim-3+ CD8+ T cells and in an augmentation of TNF-α and IFN-γ production. These findings highlight the important role of the PD-1 and Tim-3 pathways in regulating CD8+ T cells function in human AS.

PD-1 and Tim-3 Pathways Regulate CD8+ T Cells Function in Atherosclerosis

PubMed Central

Qiu, Ming-Ke; Wang, Song-Cun; Dai, Yu-Xin; Wang, Shu-Qing; Ou, Jing-Min; Quan, Zhi-Wei

2015-01-01

T cell-mediated immunity plays a significant role in the development of atherosclerosis (AS). There is increasing evidence that CD8+ T cells are also involved in AS but their exact roles remain unclear. The inhibitory receptors programmed cell death-1 (PD-1) and T cell immunoglobulin and mucin domain 3 (Tim-3) are well known inhibitory molecules that play a crucial role in regulating CD8+ T cell activation or tolerance. Here, we demonstrate that the co-expression of PD-1 and Tim-3 on CD8+ T cells is up-regulated in AS patients. PD-1+ Tim-3+ CD8+ T cells are enriched for within the central T (TCM) cell subset, with high proliferative activity and CD127 expression. Co-expression of PD-1 and Tim-3 on CD8+ T cells is associated with increased anti-atherogenic cytokine production as well as decreased pro-atherogenic cytokine production. Blockade of PD-1 and Tim-3 results in a decrease of anti-atherogenic cytokine production by PD-1+ Tim-3+ CD8+ T cells and in an augmentation of TNF-α and IFN-γ production. These findings highlight the important role of the PD-1 and Tim-3 pathways in regulating CD8+ T cells function in human AS. PMID:26035207

Ebola Virus Binding to Tim-1 on T Lymphocytes Induces a Cytokine Storm

PubMed Central

Younan, Patrick; Iampietro, Mathieu; Nishida, Andrew; Ramanathan, Palaniappan; Santos, Rodrigo I.; Dutta, Mukta; Lubaki, Ndongala Michel; Koup, Richard A.; Katze, Michael G.

2017-01-01

ABSTRACT Ebola virus (EBOV) disease (EVD) results from an exacerbated immunological response that is highlighted by a burst in the production of inflammatory mediators known as a “cytokine storm.” Previous reports have suggested that nonspecific activation of T lymphocytes may play a central role in this phenomenon. T-cell immunoglobulin and mucin domain-containing protein 1 (Tim-1) has recently been shown to interact with virion-associated phosphatidylserine to promote infection. Here, we demonstrate the central role of Tim-1 in EBOV pathogenesis, as Tim-1−/− mice exhibited increased survival rates and reduced disease severity; surprisingly, only a limited decrease in viremia was detected. Tim-1−/− mice exhibited a modified inflammatory response as evidenced by changes in serum cytokines and activation of T helper subsets. A series of in vitro assays based on the Tim-1 expression profile on T cells demonstrated that despite the apparent absence of detectable viral replication in T lymphocytes, EBOV directly binds to isolated T lymphocytes in a phosphatidylserine–Tim-1-dependent manner. Exposure to EBOV resulted in the rapid development of a CD4Hi CD3Low population, non-antigen-specific activation, and cytokine production. Transcriptome and Western blot analysis of EBOV-stimulated CD4+ T cells confirmed the induction of the Tim-1 signaling pathway. Furthermore, comparative analysis of transcriptome data and cytokine/chemokine analysis of supernatants highlight the similarities associated with EBOV-stimulated T cells and the onset of a cytokine storm. Flow cytometry revealed virtually exclusive binding and activation of central memory CD4+ T cells. These findings provide evidence for the role of Tim-1 in the induction of a cytokine storm phenomenon and the pathogenesis of EVD. PMID:28951472

Drosophila TIM binds importin α1, and acts as an adapter to transport PER to the nucleus.

PubMed

Jang, A Reum; Moravcevic, Katarina; Saez, Lino; Young, Michael W; Sehgal, Amita

2015-02-01

Regulated nuclear entry of clock proteins is a conserved feature of eukaryotic circadian clocks and serves to separate the phase of mRNA activation from mRNA repression in the molecular feedback loop. In Drosophila, nuclear entry of the clock proteins, PERIOD (PER) and TIMELESS (TIM), is tightly controlled, and impairments of this process produce profound behavioral phenotypes. We report here that nuclear entry of PER-TIM in clock cells, and consequently behavioral rhythms, require a specific member of a classic nuclear import pathway, Importin α1 (IMPα1). In addition to IMPα1, rhythmic behavior and nuclear expression of PER-TIM require a specific nuclear pore protein, Nup153, and Ran-GTPase. IMPα1 can also drive rapid and efficient nuclear expression of TIM and PER in cultured cells, although the effect on PER is mediated by TIM. Mapping of interaction domains between IMPα1 and TIM/PER suggests that TIM is the primary cargo for the importin machinery. This is supported by attenuated interaction of IMPα1 with TIM carrying a mutation previously shown to prevent nuclear entry of TIM and PER. TIM is detected at the nuclear envelope, and computational modeling suggests that it contains HEAT-ARM repeats typically found in karyopherins, consistent with its role as a co-transporter for PER. These findings suggest that although PER is the major timekeeper of the clock, TIM is the primary target of nuclear import mechanisms. Thus, the circadian clock uses specific components of the importin pathway with a novel twist in that TIM serves a karyopherin-like role for PER.

De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy

PubMed Central

Parmeggiani, Fabio; Velasco, D. Alejandro Fernandez; Höcker, Birte; Baker, David

2015-01-01

Despite efforts for over 25 years, de novo protein design has not succeeded in achieving the TIM-barrel fold. Here we describe the computational design of 4-fold symmetrical (β/α)8-barrels guided by geometrical and chemical principles. Experimental characterization of 33 designs revealed the importance of sidechain-backbone hydrogen bonding for defining the strand register between repeat units. The X-ray crystal structure of a designed thermostable 184-residue protein is nearly identical with the designed TIM-barrel model. PSI-BLAST searches do not identify sequence similarities to known TIM-barrel proteins, and sensitive profile-profile searches indicate that the design sequence is distant from other naturally occurring TIM-barrel superfamilies, suggesting that Nature has only sampled a subset of the sequence space available to the TIM-barrel fold. The ability to de novo design TIM-barrels opens new possibilities for custom-made enzymes. PMID:26595462

Corner Office: EBSCO's Tim Collins

ERIC Educational Resources Information Center

Fialkoff, Francine; Oder, Norman

2008-01-01

This article presents an interview with Tim Collins, president of EBSCO Publishing. The amiable Collins put EBSCO Publishing (EP) on the map through a combination of first-rate search and user-friendly interfaces, a long list of strategic acquisitions, and a dedicated, stable staff. Now, the company Collins has nurtured for over two decades ranks…

Influence of the redox active ligand on the reactivity and electronic structure of a series of Fe(TIM) complexes.

PubMed

Hess, Corinna R; Weyhermüller, Thomas; Bill, Eckhard; Wieghardt, Karl

2010-06-21

The redox properties of Fe and Zn complexes coordinated by an alpha-diimine based N(4)-macrocyclic ligand (TIM) have been examined using spectroscopic methods and density functional theory (DFT) computational analysis. DFT results on the redox series of [Zn(TIM*)](n) and [Fe(TIM*)](n) molecules indicate the preferential reduction of the alpha-diimine ligand moiety. In addition to the previously reported [Fe(TIM*)](2) dimer, we have now synthesized and characterized a further series of monomeric and dimeric complexes coordinated by the TIM ligand. This includes the five-coordinate monomeric [Fe(TIM*)I], the neutral and cationic forms of a monomeric phosphite adduct, [Fe(TIM*)(P(OPh)(3))] and [Fe(TIM*)(P(OPh)(3))](PF(6)), as well as a binuclear hydroxy-bridged complex, [{Fe(TIM*)}(2)(mu-OH)](PF(6)). Experimental and computational data for these synthetic compounds denote the presence of ferrous and ferric species, suggesting that the alpha-diimine based macrocycles do not readily support the formation of formally low-valent (M(0) or M(I)) metal complexes as previously speculated. Magnetochemical, Mossbauer, electron paramagnetic resonance (EPR), and electronic spectral data have been employed to experimentally determine the oxidation state of the central metal ion and of the macrocyclic ligand (TIM*) in each compound. The series of compounds is described as follows: [Fe(II)(TIM(0))(CH(3)CN(2))](2+), S(Fe) = S(T) = 0; [Fe(2.5)(TIM(2.5-))](2), S(T) = 1; [{Fe(III)(TIM(2-))}(2)(mu-OH)](+), S(Fe) = 3/2, S(T) = 0; [Fe(III)(TIM(2-))I], S(Fe) = 3/2, S(T) = 1/2; [Fe(II)(TIM(2-))(P(OPh(3)))], S(Fe) = S(T) = 0; and [Fe(II)(TIM(1-))(P(OPh(3)))](1+)/[Fe(I)(TIM(0))(P(OPh(3)))](1+), S(T) = 1/2. The results have been corroborated by DFT calculations.

Drosophila TIM Binds Importin α1, and Acts as an Adapter to Transport PER to the Nucleus

PubMed Central

Jang, A. Reum; Moravcevic, Katarina; Saez, Lino; Young, Michael W.; Sehgal, Amita

2015-01-01

Regulated nuclear entry of clock proteins is a conserved feature of eukaryotic circadian clocks and serves to separate the phase of mRNA activation from mRNA repression in the molecular feedback loop. In Drosophila, nuclear entry of the clock proteins, PERIOD (PER) and TIMELESS (TIM), is tightly controlled, and impairments of this process produce profound behavioral phenotypes. We report here that nuclear entry of PER-TIM in clock cells, and consequently behavioral rhythms, require a specific member of a classic nuclear import pathway, Importin α1 (IMPα1). In addition to IMPα1, rhythmic behavior and nuclear expression of PER-TIM require a specific nuclear pore protein, Nup153, and Ran-GTPase. IMPα1 can also drive rapid and efficient nuclear expression of TIM and PER in cultured cells, although the effect on PER is mediated by TIM. Mapping of interaction domains between IMPα1 and TIM/PER suggests that TIM is the primary cargo for the importin machinery. This is supported by attenuated interaction of IMPα1 with TIM carrying a mutation previously shown to prevent nuclear entry of TIM and PER. TIM is detected at the nuclear envelope, and computational modeling suggests that it contains HEAT-ARM repeats typically found in karyopherins, consistent with its role as a co-transporter for PER. These findings suggest that although PER is the major timekeeper of the clock, TIM is the primary target of nuclear import mechanisms. Thus, the circadian clock uses specific components of the importin pathway with a novel twist in that TIM serves a karyopherin-like role for PER. PMID:25674790

Mitochondrial protein import: Mia40 facilitates Tim22 translocation into the inner membrane of mitochondria.

PubMed

Wrobel, Lidia; Trojanowska, Agata; Sztolsztener, Malgorzata E; Chacinska, Agnieszka

2013-03-01

The mitochondrial intermembrane space assembly (MIA) pathway is generally considered to be dedicated to the redox-dependent import and biogenesis of proteins localized to the intermembrane space of mitochondria. The oxidoreductase Mia40 is a central component of the pathway responsible for the transfer of disulfide bonds to intermembrane space precursor proteins, causing their oxidative folding. Here we present the first evidence that the function of Mia40 is not restricted to the transport and oxidative folding of intermembrane space proteins. We identify Tim22, a multispanning membrane protein and core component of the TIM22 translocase of inner membrane, as a protein with cysteine residues undergoing oxidation during Tim22 biogenesis. We show that Mia40 is involved in the biogenesis and complex assembly of Tim22. Tim22 forms a disulfide-bonded intermediate with Mia40 upon import into mitochondria. Of interest, Mia40 binds the Tim22 precursor also via noncovalent interactions. We propose that Mia40 not only is responsible for disulfide bond formation, but also assists the Tim22 protein in its integration into the inner membrane of mitochondria.

TIM, a ray-tracing program for METATOY research and its dissemination

NASA Astrophysics Data System (ADS)

Lambert, Dean; Hamilton, Alasdair C.; Constable, George; Snehanshu, Harsh; Talati, Sharvil; Courtial, Johannes

2012-03-01

TIM (The Interactive METATOY) is a ray-tracing program specifically tailored towards our research in METATOYs, which are optical components that appear to be able to create wave-optically forbidden light-ray fields. For this reason, TIM possesses features not found in other ray-tracing programs. TIM can either be used interactively or by modifying the openly available source code; in both cases, it can easily be run as an applet embedded in a web page. Here we describe the basic structure of TIM's source code and how to extend it, and we give examples of how we have used TIM in our own research. Program summaryProgram title: TIM Catalogue identifier: AEKY_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEKY_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public License No. of lines in distributed program, including test data, etc.: 124 478 No. of bytes in distributed program, including test data, etc.: 4 120 052 Distribution format: tar.gz Programming language: Java Computer: Any computer capable of running the Java Virtual Machine (JVM) 1.6 Operating system: Any; developed under Mac OS X Version 10.6 RAM: Typically 145 MB (interactive version running under Mac OS X Version 10.6) Classification: 14, 18 External routines: JAMA [1] (source code included) Nature of problem: Visualisation of scenes that include scene objects that create wave-optically forbidden light-ray fields. Solution method: Ray tracing. Unusual features: Specifically designed to visualise wave-optically forbidden light-ray fields; can visualise ray trajectories; can visualise geometric optic transformations; can create anaglyphs (for viewing with coloured "3D glasses") and random-dot autostereograms of the scene; integrable into web pages. Running time: Problem-dependent; typically seconds for a simple scene.

A polymorphism of the TIM-1 IgV domain: implications for the susceptibility to filovirus infection.

PubMed

Kuroda, Makoto; Fujikura, Daisuke; Noyori, Osamu; Kajihara, Masahiro; Maruyama, Junki; Miyamoto, Hiroko; Yoshida, Reiko; Takada, Ayato

2014-12-12

Filoviruses, including Ebola and Marburg viruses, cause severe hemorrhagic fever in humans and nonhuman primates with mortality rates of up to 90%. Human T-cell immunoglobulin and mucin domain 1 (TIM-1) is one of the host proteins that have been shown to promote filovirus entry into cells. In this study, we cloned TIM-1 genes from three different African green monkey kidney cell lines (Vero E6, COS-1, and BSC-1) and found that TIM-1 of Vero E6 had a 23-amino acid deletion and 6 amino acid substitutions compared with those of COS-1 and BSC-1. Interestingly, Vero E6 TIM-1 had a greater ability to promote the infectivity of vesicular stomatitis viruses pseudotyped with filovirus glycoproteins than COS-1-derived TIM-1. We further found that the increased ability of Vero E6 TIM-1 to promote virus infectivity was most likely due to a single amino acid difference between these TIM-1s. These results suggest that a polymorphism of the TIM-1 molecules is one of the factors that influence cell susceptibility to filovirus infection, providing a new insight into the molecular basis for the filovirus host range. Copyright © 2014 Elsevier Inc. All rights reserved.

Airborne Thermal Infrared Multispectral Scanner (TIMS) images over disseminated gold deposits, Osgood Mountains, Humboldt County, Nevada

NASA Technical Reports Server (NTRS)

Krohn, M. Dennis

1986-01-01

The U.S. Geological Survey (USGS) acquired airborne Thermal Infrared Multispectral Scanner (TIMS) images over several disseminated gold deposits in northern Nevada in 1983. The aerial surveys were flown to determine whether TIMS data could depict jasperoids (siliceous replacement bodies) associated with the gold deposits. The TIMS data were collected over the Pinson and Getchell Mines in the Osgood Mountains, the Carlin, Maggie Creek, Bootstrap, and other mines in the Tuscarora Mountains, and the Jerritt Canyon Mine in the Independence Mountains. The TIMS data seem to be a useful supplement to conventional geochemical exploration for disseminated gold deposits in the western United States. Siliceous outcrops are readily separable in the TIMS image from other types of host rocks. Different forms of silicification are not readily separable, yet, due to limitations of spatial resolution and spectral dynamic range. Features associated with the disseminated gold deposits, such as the large intrusive bodies and fault structures, are also resolvable on TIMS data. Inclusion of high-resolution thermal inertia data would be a useful supplement to the TIMS data.

Traditional Indian medicine (TIM) and traditional Korean medicine (TKM): aconstitutional-based concept and comparison.

PubMed

Kang, Young Min; Komakech, Richard; Karigar, Chandrakant Shivappa; Saqib, Asma

2017-06-01

Traditional and complementary medicine (T&CM) plays an integral role in providing health care worldwide. It is based on sound fundamental principles and centuries of practices. This study compared traditional Indian medicine (TIM) and traditional Korean medicine (TKM) basing on data obtained from peer reviewed articles, respective government institutional reports and World Health Organization reports. Despite the fact that TIM and TKM have individual qualities that are unique from each other including different histories of origin, they share a lot in common. Apart from Homeopathy in TIM, both systems are hinged on similar principle of body constitutional-based concept and similar disease diagnosis methods of mainly auscultation, palpation, visual inspection, and interrogation. Similarly, the treatment methods of TIM and TKM follow similar patterns involving use of medicinal herbs, moxibustion, acupuncture, cupping, and manual therapy. Both T&CM are majorly practiced in well-established hospitals by T&CM doctors who have undergone an average of 6-7 years of specialized trainings. However, unlike TIM which has less insurance coverage, the popularity of TKM is majorly due to its wide national insurance coverage. These two medical traditions occupy increasingly greater portion of the global market. However, TIM especially Ayurveda has gained more global recognition than TKM although the emergence of Sasang Constitutional Medicine in TKM is beginning to become more popular. This comparative analysis between TIM and TKM may provide vital and insightful contribution towards constitutional-based concept for further development and future studies in T&CM.

Meet EPA Scientist Tim Shafer, Ph.D.

EPA Pesticide Factsheets

Tim Shafer earned his bachelor’s degree in biology and chemistry from Hope College in Holland, MI, in 1986 and his Ph.D. in pharmacology and environmental toxicology from Michigan State University in 1991.

Increased Tim-3 expression alleviates liver injury by regulating macrophage activation in MCD-induced NASH mice.

PubMed

Du, Xianhong; Wu, Zhuanchang; Xu, Yong; Liu, Yuan; Liu, Wen; Wang, Tixiao; Li, Chunyang; Zhang, Cuijuan; Yi, Fan; Gao, Lifen; Liang, Xiaohong; Ma, Chunhong

2018-05-07

As an immune checkpoint, Tim-3 plays roles in the regulation of both adaptive and innate immune cells including macrophages and is greatly involved in chronic liver diseases. However, the precise roles of Tim-3 in nonalcoholic steatohepatitis (NASH) remain unstated. In the current study, we analyzed Tim-3 expression on different subpopulations of liver macrophages and further investigated the potential roles of Tim-3 on hepatic macrophages in methionine and choline-deficient diet (MCD)-induced NASH mice. The results of flow cytometry demonstrated the significantly increased expression of Tim-3 on all detected liver macrophage subsets in MCD mice, including F4/80 + CD11b + , F4/80 + CD68 + , and F4/80 + CD169 + macrophages. Remarkably, Tim-3 knockout (KO) significantly accelerated MCD-induced liver steatosis, displaying higher serum ALT, larger hepatic vacuolation, more liver lipid deposition, and more severe liver fibrosis. Moreover, compared with wild-type C57BL/6 mice, Tim-3 KO MCD mice demonstrated an enhanced expression of NOX2, NLRP3, and caspase-1 p20 together with increased generation of IL-1β and IL-18 in livers. In vitro studies demonstrated that Tim-3 negatively regulated the production of reactive oxygen species (ROS) and related downstream pro-inflammatory cytokine secretion of IL-1β and IL-18 in macrophages. Exogenous administration of N-Acetyl-L-cysteine (NAC), a small molecular inhibitor of ROS, remarkably suppressed caspase-1 p20 expression and IL-1β and IL-18 production in livers of Tim-3 KO mice, thus significantly reducing the severity of steatohepatitis induced by MCD. In conclusion, Tim-3 is a promising protector in MCD-induced steatohepatitis by controlling ROS and the associated pro-inflammatory cytokine production in macrophages.

Combination Therapy with Anti-PD-1, Anti-TIM-3, and Focal Radiation Results in Regression of Murine Gliomas.

PubMed

Kim, Jennifer E; Patel, Mira A; Mangraviti, Antonella; Kim, Eileen S; Theodros, Debebe; Velarde, Esteban; Liu, Ann; Sankey, Eric W; Tam, Ada; Xu, Haiying; Mathios, Dimitrios; Jackson, Christopher M; Harris-Bookman, Sarah; Garzon-Muvdi, Tomas; Sheu, Mary; Martin, Allison M; Tyler, Betty M; Tran, Phuoc T; Ye, Xiaobu; Olivi, Alessandro; Taube, Janis M; Burger, Peter C; Drake, Charles G; Brem, Henry; Pardoll, Drew M; Lim, Michael

2017-01-01

Checkpoint molecules like programmed death-1 (PD-1) and T-cell immunoglobulin mucin-3 (TIM-3) are negative immune regulators that may be upregulated in the setting of glioblastoma multiforme. Combined PD-1 blockade and stereotactic radiosurgery (SRS) have been shown to improve antitumor immunity and produce long-term survivors in a murine glioma model. However, tumor-infiltrating lymphocytes (TIL) can express multiple checkpoints, and expression of ≥2 checkpoints corresponds to a more exhausted T-cell phenotype. We investigate TIM-3 expression in a glioma model and the antitumor efficacy of TIM-3 blockade alone and in combination with anti-PD-1 and SRS. C57BL/6 mice were implanted with murine glioma cell line GL261-luc2 and randomized into 8 treatment arms: (i) control, (ii) SRS, (iii) anti-PD-1 antibody, (iv) anti-TIM-3 antibody, (v) anti-PD-1 + SRS, (vi) anti-TIM-3 + SRS, (vii) anti-PD-1 + anti-TIM-3, and (viii) anti-PD-1 + anti-TIM-3 + SRS. Survival and immune activation were assessed. Dual therapy with anti-TIM-3 antibody + SRS or anti-TIM-3 + anti-PD-1 improved survival compared with anti-TIM-3 antibody alone. Triple therapy resulted in 100% overall survival (P < 0.05), a significant improvement compared with other arms. Long-term survivors demonstrated increased immune cell infiltration and activity and immune memory. Finally, positive staining for TIM-3 was detected in 7 of 8 human GBM samples. This is the first preclinical investigation on the effects of dual PD-1 and TIM-3 blockade with radiation. We also demonstrate the presence of TIM-3 in human glioblastoma multiforme and provide preclinical evidence for a novel treatment combination that can potentially result in long-term glioma survival and constitutes a novel immunotherapeutic strategy for the treatment of glioblastoma multiforme. Clin Cancer Res; 23(1); 124-36. ©2016 AACR. ©2016 American Association for Cancer Research.

Isotopic Ratios of Samarium by TIMS for Nuclear Forensic Application

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

Louis Jean, James; Inglis, Jeremy David

The isotopic ratio of Nd, Sm, and Gd can provide important information regarding fissile material (nuclear devices, reactors), neutron environment, and device yield. These studies require precise measurement of Sm isotope ratios, by either TIMS or MC-ICP-MS. There has been an increasing trend to measure smaller and smaller quantities of Sm bearing samples. In nuclear forensics 10-100 ng of Sm are needed for precise measurement. To measure sub-ng Sm samples using TIMS for nuclear forensic analysis.

BOREAS Level-1B TIMS Imagery: At-sensor Radiance in BSQ Format

NASA Technical Reports Server (NTRS)

Hall, Forrest G. (Editor); Nickeson, Jaime (Editor); Strub, Richard; Newcomer, Jeffrey A.; Chernobieff, Sonia

2000-01-01

The Boreal Ecosystem-Atmospheric Study (BOREAS) Staff Science Aircraft Data Acquisition Program focused on providing the research teams with the remotely sensed satellite data products they needed to compare and spatially extend point results. For BOREAS, the Thermal Infrared Multispectral Scanner (TIMS) imagery, along with other aircraft images, was collected to provide spatially extensive information over the primary study areas. The Level-1b TIMS images cover the time periods of 16 to 20 Apr 1994 and 06 to 17 Sep 1994. The system calibrated images are stored in binary image format files. The TIMS images are available from the Earth Observing System Data and Information System (EOSDIS) Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC).

Novel effector phenotype of Tim-3+ regulatory T cells leads to enhanced suppressive function in head and neck cancer patients.

PubMed

Liu, Zhuqing; McMichael, Elizabeth L; Shayan, Gulidanna; Li, Jing; Chen, Kevin; Srivastava, Raghvendra M; Kane, Lawrence P; Lu, Binfeng; Ferris, Robert L

2018-04-30

Regulatory T (Treg) cells are important suppressive cells among tumor infiltrating lymphocytes (TIL). Treg express the well-known immune checkpoint receptor PD-1, which is reported to mark "exhausted" Treg with lower suppressive function. T cell immunoglobulin mucin (Tim)-3, a negative regulator of Th1 immunity, is expressed by a sizeable fraction of TIL Tregs, but the functional status of Tim-3+ Tregs remains unclear. CD4+CTLA-4+CD25high Treg were sorted from freshly excised head and neck squamous cell carcinoma (HNSCC) TIL based on Tim-3 expression. Functional and phenotypic features of these Tim-3+ and Tim-3- TIL Tregs were tested by in vitro suppression assays and multi-color flow cytometry. Gene expression profiling and NanoString analysis of Tim-3+ TIL Treg were performed. A murine HNSCC tumor model was used to test the effect of anti-PD-1 immunotherapy on Tim-3+ Treg.  Results: Despite high PD-1 expression, Tim-3+ TIL Treg displayed a greater capacity to inhibit naïve T cell proliferation than Tim-3- Treg. Tim-3+ Treg from human HNSCC TIL also displayed an effector-like phenotype, with more robust expression of CTLA-4, PD-1, CD39 and IFN-γ receptor. Exogenous IFN-γ treatment could partially reverse the suppressive function of Tim-3+ TIL Treg. Anti-PD-1 immunotherapy downregulated Tim-3 expression on Tregs isolated from murine HNSCC tumors, and this treatment reversed the suppressive function of HNSCC TIL Tregs. Tim-3+ Treg are functionally and phenotypically distinct in HNSCC TIL, and are highly effective at inhibiting T cell proliferation despite high PD-1 expression.  IFN-γ induced by anti-PD-1 immunotherapy may be beneficial by reversing Tim-3+ Treg suppression. Copyright ©2018, American Association for Cancer Research.

Towards Discovery and Targeted Peptide Biomarker Detection Using nanoESI-TIMS-TOF MS

NASA Astrophysics Data System (ADS)

Garabedian, Alyssa; Benigni, Paolo; Ramirez, Cesar E.; Baker, Erin S.; Liu, Tao; Smith, Richard D.; Fernandez-Lima, Francisco

2018-05-01

In the present work, the potential of trapped ion mobility spectrometry coupled to TOF mass spectrometry (TIMS-TOF MS) for discovery and targeted monitoring of peptide biomarkers from human-in-mouse xenograft tumor tissue was evaluated. In particular, a TIMS-MS workflow was developed for the detection and quantification of peptide biomarkers using internal heavy analogs, taking advantage of the high mobility resolution (R = 150-250) prior to mass analysis. Five peptide biomarkers were separated, identified, and quantified using offline nanoESI-TIMS-CID-TOF MS; the results were in good agreement with measurements using a traditional LC-ESI-MS/MS proteomics workflow. The TIMS-TOF MS analysis permitted peptide biomarker detection based on accurate mobility, mass measurements, and high sequence coverage for concentrations in the 10-200 nM range, while simultaneously achieving discovery measurements of not initially targeted peptides as markers from the same proteins and, eventually, other proteins. [Figure not available: see fulltext.

TIM-1 glycoprotein binds the adhesion receptor P-selectin and mediates T cell trafficking during inflammation and autoimmunity

PubMed Central

Angiari, Stefano; Donnarumma, Tiziano; Rossi, Barbara; Dusi, Silvia; Pietronigro, Enrica; Zenaro, Elena; Della Bianca, Vittorina; Toffali, Lara; Piacentino, Gennj; Budui, Simona; Rennert, Paul; Xiao, Sheng; Laudanna, Carlo; Casasnovas, Jose M.; Kuchroo, Vijay K.; Constantin, Gabriela

2014-01-01

SUMMARY Selectins play a central role in leukocyte trafficking by mediating tethering and rolling on vascular surfaces. Here we have reported that T cell immunoglobulin and mucin domain 1 (TIM-1) is a P-selectin ligand. We have shown that human and murine TIM-1 binds to P-selectin, and that TIM-1 mediates tethering and rolling of T helper-1 (Th1) and Th17, but not Th2 and regulatory T cells on P-selectin. Th1 and Th17 cells lacking the TIM-1 mucin domain showed reduced rolling in thrombin-activated mesenteric venules and inflamed brain microcirculation. Inhibition of TIM-1 had no effect on naive T cell homing, but reduced T cell recruitment in a skin hypersensitivity model and blocked experimental autoimmune encephalomyelitis. Uniquely, the TIM-1 IgV domain was also required for P-selectin binding. Our data demonstrate that TIM-1 is a major P-selectin ligand with a specialized role in T cell trafficking during inflammatory responses and the induction of autoimmune disease. PMID:24703780

TIM Version 3.0 beta Technical Description and User Guide - Appendix A - User's Guidance for TIM v.3.0(beta)

EPA Pesticide Factsheets

Provides detailed guidance to the user on how to select input parameters for running the Terrestrial Investigation Model (TIM) and recommendations for default values that can be used when no chemical-specific or species-specific information are available.

Characterization of Human and Murine T-Cell Immunoglobulin Mucin Domain 4 (TIM-4) IgV Domain Residues Critical for Ebola Virus Entry.

PubMed

Rhein, Bethany A; Brouillette, Rachel B; Schaack, Grace A; Chiorini, John A; Maury, Wendy

2016-07-01

Phosphatidylserine (PtdSer) receptors that are responsible for the clearance of dying cells have recently been found to mediate enveloped virus entry. Ebola virus (EBOV), a member of the Filoviridae family of viruses, utilizes PtdSer receptors for entry into target cells. The PtdSer receptors human and murine T-cell immunoglobulin mucin (TIM) domain proteins TIM-1 and TIM-4 mediate filovirus entry by binding to PtdSer on the virion surface via a conserved PtdSer binding pocket within the amino-terminal IgV domain. While the residues within the TIM-1 IgV domain that are important for EBOV entry are characterized, the molecular details of virion-TIM-4 interactions have yet to be investigated. As sequences and structural alignments of the TIM proteins suggest distinct differences in the TIM-1 and TIM-4 IgV domain structures, we sought to characterize TIM-4 IgV domain residues required for EBOV entry. Using vesicular stomatitis virus pseudovirions bearing EBOV glycoprotein (EBOV GP/VSVΔG), we evaluated virus binding and entry into cells expressing TIM-4 molecules mutated within the IgV domain, allowing us to identify residues important for entry. Similar to TIM-1, residues in the PtdSer binding pocket of murine and human TIM-4 (mTIM-4 and hTIM-4) were found to be important for EBOV entry. However, additional TIM-4-specific residues were also found to impact EBOV entry, with a total of 8 mTIM-4 and 14 hTIM-4 IgV domain residues being critical for virion binding and internalization. Together, these findings provide a greater understanding of the interaction of TIM-4 with EBOV virions. With more than 28,000 cases and over 11,000 deaths during the largest and most recent Ebola virus (EBOV) outbreak, there has been increased emphasis on the development of therapeutics against filoviruses. Many therapies under investigation target EBOV cell entry. T-cell immunoglobulin mucin (TIM) domain proteins are cell surface factors important for the entry of many enveloped viruses

Characterization of Human and Murine T-Cell Immunoglobulin Mucin Domain 4 (TIM-4) IgV Domain Residues Critical for Ebola Virus Entry

PubMed Central

Rhein, Bethany A.; Brouillette, Rachel B.; Schaack, Grace A.; Chiorini, John A.

2016-01-01

ABSTRACT Phosphatidylserine (PtdSer) receptors that are responsible for the clearance of dying cells have recently been found to mediate enveloped virus entry. Ebola virus (EBOV), a member of the Filoviridae family of viruses, utilizes PtdSer receptors for entry into target cells. The PtdSer receptors human and murine T-cell immunoglobulin mucin (TIM) domain proteins TIM-1 and TIM-4 mediate filovirus entry by binding to PtdSer on the virion surface via a conserved PtdSer binding pocket within the amino-terminal IgV domain. While the residues within the TIM-1 IgV domain that are important for EBOV entry are characterized, the molecular details of virion–TIM-4 interactions have yet to be investigated. As sequences and structural alignments of the TIM proteins suggest distinct differences in the TIM-1 and TIM-4 IgV domain structures, we sought to characterize TIM-4 IgV domain residues required for EBOV entry. Using vesicular stomatitis virus pseudovirions bearing EBOV glycoprotein (EBOV GP/VSVΔG), we evaluated virus binding and entry into cells expressing TIM-4 molecules mutated within the IgV domain, allowing us to identify residues important for entry. Similar to TIM-1, residues in the PtdSer binding pocket of murine and human TIM-4 (mTIM-4 and hTIM-4) were found to be important for EBOV entry. However, additional TIM-4-specific residues were also found to impact EBOV entry, with a total of 8 mTIM-4 and 14 hTIM-4 IgV domain residues being critical for virion binding and internalization. Together, these findings provide a greater understanding of the interaction of TIM-4 with EBOV virions. IMPORTANCE With more than 28,000 cases and over 11,000 deaths during the largest and most recent Ebola virus (EBOV) outbreak, there has been increased emphasis on the development of therapeutics against filoviruses. Many therapies under investigation target EBOV cell entry. T-cell immunoglobulin mucin (TIM) domain proteins are cell surface factors important for the entry of many

Prospects for TIM3-Targeted Antitumor Immunotherapy.

PubMed

Ngiow, Shin Foong; Teng, Michele W L; Smyth, Mark J

2011-11-01

New insights into the control of T-cell activation and proliferation have led to the identification of checkpoint proteins that either up- or downmodulate T-cell reactivity. Monoclonal antibody immunotherapies that are reactive with cytotoxic T lymphocyte antigen 4 or programmed death receptor 1 have shown promising therapeutic outcomes in mice and humans with established cancer, highlighting the fact that cancer immunotherapy using T-cell checkpoint inhibitors is one of the most promising new therapeutic approaches. T-cell immunoglobulin and mucin domain 3 (TIM3) is one of many similar inhibitory molecules that are gaining attention as targets, but it remains relatively poorly studied in oncology. This review discusses our recent probing of the mechanism of action of anti-TIM3 antibody against established spontaneous and experimental tumors in mice, in the context of the exciting possibility of rationally combining agents that promote tumor-specific T-cell activation, proliferation, effector function, and survival. ©2011 AACR.

Tumor-infiltrating Tim-3+ T cells proliferate avidly except when PD-1 is co-expressed: Evidence for intracellular cross talk

PubMed Central

Li, Jing; Shayan, Gulidanna; Avery, Lyndsay; Jie, Hyun-Bae; Gildener-Leapman, Neil; Schmitt, Nicole; Lu, Bin Feng; Kane, Lawrence P.; Ferris, Robert L.

2016-01-01

ABSTRACT Programmed Death 1 (PD-1) and T cell Ig and mucin domain-3 protein (Tim-3) are immune checkpoint receptors highly expressed on tumor infiltrating T lymphocytes (TIL). PD-1 inhibits T cell activation and type-1 T cell responses, while Tim-3 is proposed to mark more extensively exhausted cells, although the mechanisms underlying Tim-3 function are not clear. Trials of anti-PD-1 therapy have identified a large subset of non-responder patients, likely due to expression of alternative checkpoint molecules like Tim-3. We investigated the phenotypic and functional characteristics of T cells with differential expression of PD-1 (high/low) and Tim-3 (positive/negative), using TIL directly isolated from head and neck squamous cell carcinomas (HNSCC). Unexpectedly, we found that expression of Tim-3 alone does not necessarily mark TIL as dysfunctional/exhausted. In Tim-3-TIL, PD-1 levels correlate with T cell dysfunction, with a PD-1low/intermed phenotype identifying recently activated and still functional cells, whereas PD-1hiTim-3− T cells are actually exhausted. Nonetheless, PD-1intermed cells are still potently suppressed by PD-L1. PD-1 expression was associated with reduced phosphorylation of ribosomal protein S6 (pS6), whereas Tim-3 expression was associated with increased pS6. Using a novel mouse model for inducible Tim-3 expression, we confirmed that expression of Tim-3 does not necessarily render T cells refractory to further activation. These results suggest the existence of PD-1 and Tim-3 crosstalk in regulating antitumor T cell responses, with important implications for anti-PD-1 immunotherapy. PMID:27853635

Active remodelling of the TIM23 complex during translocation of preproteins into mitochondria.

PubMed

Popov-Celeketić, Dusan; Mapa, Koyeli; Neupert, Walter; Mokranjac, Dejana

2008-05-21

The TIM23 (translocase of the mitochondrial inner membrane) complex mediates translocation of preproteins across and their insertion into the mitochondrial inner membrane. How the translocase mediates sorting of preproteins into the two different subcompartments is poorly understood. In particular, it is not clear whether association of two operationally defined parts of the translocase, the membrane-integrated part and the import motor, depends on the activity state of the translocase. We established conditions to in vivo trap the TIM23 complex in different translocation modes. Membrane-integrated part of the complex and import motor were always found in one complex irrespective of whether an arrested preprotein was present or not. Instead, we detected different conformations of the complex in response to the presence and, importantly, the type of preprotein being translocated. Two non-essential subunits of the complex, Tim21 and Pam17, modulate its activity in an antagonistic manner. Our data demonstrate that the TIM23 complex acts as a single structural and functional entity that is actively remodelled to sort preproteins into different mitochondrial subcompartments.

Active remodelling of the TIM23 complex during translocation of preproteins into mitochondria

PubMed Central

Popov-Čeleketić, Dus̆an; Mapa, Koyeli; Neupert, Walter; Mokranjac, Dejana

2008-01-01

The TIM23 (translocase of the mitochondrial inner membrane) complex mediates translocation of preproteins across and their insertion into the mitochondrial inner membrane. How the translocase mediates sorting of preproteins into the two different subcompartments is poorly understood. In particular, it is not clear whether association of two operationally defined parts of the translocase, the membrane-integrated part and the import motor, depends on the activity state of the translocase. We established conditions to in vivo trap the TIM23 complex in different translocation modes. Membrane-integrated part of the complex and import motor were always found in one complex irrespective of whether an arrested preprotein was present or not. Instead, we detected different conformations of the complex in response to the presence and, importantly, the type of preprotein being translocated. Two non-essential subunits of the complex, Tim21 and Pam17, modulate its activity in an antagonistic manner. Our data demonstrate that the TIM23 complex acts as a single structural and functional entity that is actively remodelled to sort preproteins into different mitochondrial subcompartments. PMID:18418384

Tim de Zeeuw to Become the Next Director General of ESO

NASA Astrophysics Data System (ADS)

2007-01-01

The ESO Council has just appointed Tim de Zeeuw, 50, as the next Director General of ESO, effective as of 1 September 2007, when the current Director General, Catherine Cesarsky will complete her mandate. ESO PR Photo 02/07 ESO PR Photo 03/07 Professor Tim de Zeeuw "ESO is Europe's flagship organisation for ground-based astronomy," said, Richard Wade, President of the ESO Council. "The ESO Council is very pleased that Professor de Zeeuw has accepted the task as its next Director General. He has played a key role over the last few years in developing a strategic vision for ESO, and I have every confidence that he will now lead the organisation in the realisation of that exciting vision." Tim de Zeeuw has an excellent record, both as a highly respected scientist and as a leader of an internationally recognised science institute in the Netherlands. He is Scientific Director of the Leiden Observatory, a research institute in the College of Mathematics and Natural Sciences of Leiden University. Tim de Zeeuw also has considerable experience as regards science policy issues. Catherine Cesarsky, ESO's current Director General commented: "Over the recent years, ESO has developed considerably with more activities and new member states, and with its ambitious project portfolio, ESO is clearly facing an exciting future. I shall be delighted to pass the baton to Tim de Zeeuw, who as a recent Council member is very familiar with our Organisation." "It is a great honour and an exciting challenge to lead this world-class organisation in the years to come in support of one of the most dynamic areas of science today," said de Zeeuw. "I look forward to overseeing the continued upgrading of the Very Large Telescope with the second-generation instrumentation and the completion of the ALMA project, and in particular to help developing the future European Extremely Large Telescope." Tim de Zeeuw's main research interests embrace the formation, structure and dynamics of galaxies

Tim-3 facilitates osteosarcoma proliferation and metastasis through the NF-κB pathway and epithelial-mesenchymal transition.

PubMed

Feng, Z M; Guo, S M

2016-09-02

The aim of this study was to investigate the expression of T-cell immunoglobulin mucin domain molecule-3 (Tim-3) in osteosarcoma tissues, and analyze its effect on cell proliferation and metastasis in an osteosarcoma cell line. Tim-3 mRNA and protein expression in osteosarcoma tissue was detected by reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. Additionally, the cell viability, apoptosis rate, and invasive ability of the osteosarcoma cell line MG-63 were tested using the methyl thiazolyl tetrazolium assay, Annexin V-propidium iodide flow cytometry, and a Transwell assay, respectively, following Tim-3 interference using small interfering RNA (siRNA). We also analyzed the expression of Snail, E-cadherin, vimentin, and nuclear factor (NF)-kB in the cells by western blot. We observed that Tim-3 mRNA and protein was significantly overexpressed in osteosarcoma tissues, compared to the adjacent normal tissue (P < 0.01). Moreover, MG-63 cells transfected with the Tim-3 siRNA presented lower cell viability, a greater number of apoptotic cells, and decreased invasive ability (P < 0.01), compared to control cells. Additionally, we observed a decrease in Snail and vimentin expression, an increase in the E-cadherin level, and an increase in NF-kB p65 phosphorylation (P < 0.01) in Tim-3 siRNA-transfected MG-63 cells. Based on these results, we concluded that Tim-3 is highly expressed in osteosarcoma tissue. Moreover, we speculated that interfering in Tim-3 expression could significantly suppress osteosarcoma cell (MG-63) proliferation and metastasis via the NF-kB/Snail signaling pathway and epithelial-mesenchymal transition.

Applications of TIMS data in agricultural areas and related atmospheric considerations

NASA Technical Reports Server (NTRS)

Pelletier, R. E.; Ochoa, M. C.

1986-01-01

While much of traditional remote sensing in agricultural research was limited to the visible and reflective infrared, advances in thermal infrared remote sensing technology are adding a dimension to digital image analysis of agricultural areas. The Thermal Infrared Multispectral Scanner (TIMS) an airborne sensor having six bands over the nominal 8.2 to 12.2 m range, offers the ability to calculate land surface emissivities unlike most previous singular broadband sensors. Preliminary findings on the utility of the TIMS for several agricultural applications and related atmospheric considerations are discussed.

Virion-associated phosphatidylethanolamine promotes TIM1-mediated infection by Ebola, dengue, and West Nile viruses.

PubMed

Richard, Audrey Stéphanie; Zhang, Adam; Park, Sun-Jin; Farzan, Michael; Zong, Min; Choe, Hyeryun

2015-11-24

Phosphatidylserine (PS) receptors contribute to two crucial biological processes: apoptotic clearance and entry of many enveloped viruses. In both cases, they recognize PS exposed on the plasma membrane. Here we demonstrate that phosphatidylethanolamine (PE) is also a ligand for PS receptors and that this phospholipid mediates phagocytosis and viral entry. We show that a subset of PS receptors, including T-cell immunoglobulin (Ig) mucin domain protein 1 (TIM1), efficiently bind PE. We further show that PE is present in the virions of flaviviruses and filoviruses, and that the PE-specific cyclic peptide lantibiotic agent Duramycin efficiently inhibits the entry of West Nile, dengue, and Ebola viruses. The inhibitory effect of Duramycin is specific: it inhibits TIM1-mediated, but not L-SIGN-mediated, virus infection, and it does so by blocking virus attachment to TIM1. We further demonstrate that PE is exposed on the surface of apoptotic cells, and promotes their phagocytic uptake by TIM1-expressing cells. Together, our data show that PE plays a key role in TIM1-mediated virus entry, suggest that disrupting PE association with PS receptors is a promising broad-spectrum antiviral strategy, and deepen our understanding of the process by which apoptotic cells are cleared.

T-bet-mediated Tim-3 expression dampens monocyte function during chronic hepatitis C virus infection.

PubMed

Yi, Wenjing; Zhang, Peixin; Liang, Yan; Zhou, Yun; Shen, Huanjun; Fan, Chao; Moorman, Jonathan P; Yao, Zhi Q; Jia, Zhansheng; Zhang, Ying

2017-03-01

Hepatitis C virus (HCV) induces a high rate of chronic infection via dysregulation of host immunity. We have previously shown that T-cell immunoglobulin and mucin domain protein-3 (Tim-3) is up-regulated on monocyte/macrophages (M/Mφ) during chronic HCV infection; little is known, however, about the transcription factor that controls its expression in these cells. In this study, we investigated the role of transcription factor, T-box expressed in T cells (T-bet), in Tim-3 expression in M/Mφ in the setting of HCV infection. We demonstrate that T-bet is constitutively expressed in resting CD14 + M/Mφ in the peripheral blood. M/Mφ from chronically HCV-infected individuals exhibit a significant increase in T-bet expression that positively correlates with an increased level of Tim-3 expression. Up-regulation of T-bet is also observed in CD14 + M/Mφ incubated with HCV + Huh7.5 cells, as well as in primary M/Mφ or monocytic THP-1 cells exposed to HCV core protein in vitro, which is reversible by blocking HCV core/gC1qR interactions. Moreover, the HCV core-induced up-regulation of T-bet and Tim-3 expression in M/Mφ can be abrogated by incubating the cells with SP600125 - an inhibitor for the c-Jun N-terminal kinase (JNK) signalling pathway. Importantly, silencing T-bet gene expression decreases Tim-3 expression and enhances interleukin-12 secretion as well as signal transducer and activator of transcription 1 phosphorylation. These data suggest that T-bet, induced by the HCV core/gC1qR interaction, enhances Tim-3 expression via the JNK pathway, leading to dampened M/Mφ function during HCV infection. These findings reveal a novel mechanism for Tim-3 regulation via T-bet during HCV infection, providing new targets to combat this global epidemic viral disease. © 2016 John Wiley & Sons Ltd.

Using the thermal infrared multispectral scanner (TIMS) to estimate surface thermal responses

NASA Technical Reports Server (NTRS)

Luvall, J. C.; Holbo, H. R.

1987-01-01

A series of measurements was conducted over the H.J. Andrews, Oregon, experimental coniferous forest, using airborne thermal infrared multispectral scanner (TIMS). Flight lines overlapped, with a 28-min time difference between flight lines. Concurrent radiosonde measurements of atmospheric profiles of air temperature and moisture were used for atmospheric radiance corrections of the TIMS data. Surface temperature differences over time between flight lines were used to develop thermal response numbers (TRNs) which characterized the thermal response (in KJ/sq m/C, where K is the measured incoming solar radiation) of the different surface types. The surface types included a mature forest (canopy dominated by dense crowns of Pseudosuga menziesii, with a secondary canopy of dense Tsuga heterophylla, and also a tall shrub layer of Acer circinatum) and a two-year-old clear-cut. The temperature distribution, within TIMS thermal images was found to reflect the surface type examined. The clear-cut surface had the lowest TRN, while mature Douglas fir the highest.

TIM1 (HAVCR1) Is Not Essential for Cellular Entry of Either Quasi-enveloped or Naked Hepatitis A Virions

PubMed Central

Das, Anshuman; Hirai-Yuki, Asuka; González-López, Olga; Rhein, Bethany; Moller-Tank, Sven; Brouillette, Rachel; Hensley, Lucinda; Misumi, Ichiro; Lovell, William; Cullen, John M.; Whitmire, Jason K.; Maury, Wendy

2017-01-01

ABSTRACT Receptor molecules play key roles in the cellular entry of picornaviruses, and TIM1 (HAVCR1) is widely accepted to be the receptor for hepatitis A virus (HAV), an unusual, hepatotropic human picornavirus. However, its identification as the hepatovirus receptor predated the discovery that hepatoviruses undergo nonlytic release from infected cells as membrane-cloaked, quasi-enveloped HAV (eHAV) virions that enter cells via a pathway distinct from naked, nonenveloped virions. We thus revisited the role of TIM1 in hepatovirus entry, examining both adherence and infection/replication in cells with clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-engineered TIM1 knockout. Cell culture-derived, gradient-purified eHAV bound Huh-7.5 human hepatoma cells less efficiently than naked HAV at 4°C, but eliminating TIM1 expression caused no difference in adherence of either form of HAV, nor any impact on infection and replication in these cells. In contrast, TIM1-deficient Vero cells showed a modest reduction in quasi-enveloped eHAV (but not naked HAV) attachment and replication. Thus, TIM1 facilitates quasi-enveloped eHAV entry in Vero cells, most likely by binding phosphatidylserine (PtdSer) residues on the eHAV membrane. Both Tim1−/− Ifnar1−/− and Tim4−/− Ifnar1−/− double-knockout mice were susceptible to infection upon intravenous challenge with infected liver homogenate, with fecal HAV shedding and serum alanine aminotransferase (ALT) elevations similar to those in Ifnar1−/− mice. However, intrahepatic HAV RNA and ALT elevations were modestly reduced in Tim1−/−Ifnar1−/− mice compared to Ifnar1−/− mice challenged with a lower titer of gradient-purified HAV or eHAV. We conclude that TIM1 is not an essential hepatovirus entry factor, although its PtdSer-binding activity may contribute to the spread of quasi-enveloped virus and liver injury in mice. PMID:28874468

Towards Discovery and Targeted Peptide Biomarker Detection Using nanoESI-TIMS-TOF MS

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

Garabedian, Alyssa; Benigni, Paolo; Ramirez, Cesar E.

Abstract. In the present work, the potential of trapped ion mobility spectrometry coupled to TOF mass spectrometry (TIMS-TOF MS) for discovery and targeted monitoring of peptide biomarkers from human-in-mouse xenograft tumor tissue was evaluated. In particular, a TIMS-MS workflow was developed for the detection and quantification of peptide biomarkers using internal heavy analogs, taking advantage of the high mobility resolution (R = 150–250) prior to mass analysis. Five peptide biomarkers were separated, identified, and quantified using offline nanoESI-TIMSCID- TOF MS; the results were in good agreement with measurements using a traditional LC-ESI-MS/MS proteomics workflow. The TIMS-TOF MS analysis permitted peptidemore » biomarker detection based on accurate mobility, mass measurements, and high sequence coverage for concentrations in the 10–200 nM range, while simultaneously achieving discovery measurements« less

Norfolk Schools Talked to Astronaut Tim Peake

ERIC Educational Resources Information Center

Grant, Stephanie

2016-01-01

Tim Peake's mission to the International Space Station captured the imagination of the UK and this article describes a live radio link with him, to help him to reach out to pupils across the country and inspire them in STEM subjects. It describes the project, from bidding for the opportunity to host it, to the planning and realisation of the…

Tim-3 and PD-1 regulate CD8+ T cell function to maintain early pregnancy in mice

PubMed Central

XU, Yuan-Yuan; WANG, Song-Cun; LIN, Yi-Kong; LI, Da-Jin; DU, Mei-Rong

2017-01-01

During pregnancy, CD8+ T cells are important regulators in the balance of fetal tolerance and antiviral immunity. T-cell immunoglobulin mucin-3 (Tim-3) and programmed cell death-1 (PD-1) are well-recognized negative co-stimulatory molecules involved in viral persistence and tumor metastasis. Here, we demonstrate that CD8+ T cells co-expressing Tim-3 and PD-1 were down-regulated in the deciduae of female mice in abortion-prone matings compared with normal pregnant mice. In addition to their reduced numbers, the Tim-3+PD-1+CD8+ T cells produced lower levels of the anti-inflammatory cytokines interleukin (IL)-4 and IL-10, as well as a higher level of the pro-inflammatory cytokine interferon (IFN)-γ, relative to those from normal pregnancy. Furthermore, normal pregnant CBA/J females challenged with Tim-3- and/or PD-1-blocking antibodies were more susceptible to fetal resorption. These findings indicate that Tim-3 and PD-1 pathways play critical roles in regulating CD8+ T cell function and maintaining normal pregnancy. PMID:28331165

Contrasting acute graft-versus-host disease effects of Tim-3/galectin-9 pathway blockade dependent upon the presence of donor regulatory T cells

PubMed Central

Veenstra, Rachelle G.; Taylor, Patricia A.; Zhou, Qing; Panoskaltsis-Mortari, Angela; Hirashima, Mitsuomi; Flynn, Ryan; Liu, Derek; Anderson, Ana C.; Strom, Terry B.; Kuchroo, Vijay K.

2012-01-01

T-cell immunoglobulin mucin-3 (Tim-3) is expressed on pathogenic T cells, and its ligand galectin-9 (gal-9) is up-regulated in inflamed tissues. When Tim-3+ T cells encounter high gal-9 levels, they are deleted. Tim-3 is up-regulated on activated T cells during GVHD. Inhibition of Tim-3/gal-9 binding by infusion of a Tim-3-Ig fusion protein or Tim-3−/− donor T cells increased T-cell proliferation and GVHD lethality. When the Tim-3/gal-9 pathway engagement was augmented using gal-9 transgenic recipients, GVHD lethality was slowed. Together, these data indicate a potential for modulating this pathway to reduce disease by increasing Tim-3 or gal-9 engagement. Paradoxically, when Tim-3/gal-9 was inhibited in the absence of donor T-regulatory cells (Tregs), GVHD was inhibited. GVHD reduction was associated with decreased colonic inflammatory cytokines as well as epithelial barrier destruction. CD25-depleted Tim-3−/− donor T cells underwent increased activation-induced cell death because of increased IFN-γ production. To our knowledge, these studies are the first to show that although the absence of Tim-3/gal-9 pathway interactions augments systemic GVHD, concurrent donor Treg depletion paradoxically and surprisingly inhibits GVHD. Thus, although donor Tregs typically inhibit GVHD, under some conditions, such Tregs actually may contribute to GVHD by reducing activation-induced T-cell death. PMID:22677125

GUM Analysis for TIMS Isotopic Ratios in BEP0 Graphite Qualification Samples, Round 2

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

Gerlach, David C.; Heasler, Patrick G.; Reid, Bruce D.

In May 2007, one set of three samples from NBL were addressed to Steve Petersen for TIMS analysis, and included BEP0 samples numbered 27008, 30986, and 50846. All cores were trimmed by tooling, and lightly cleaned by CO2 pellet blasting. Small discs were cut from the second set of samples for SIMS analysis, with the remainder of each used for TIMS preparation.

Co-expression of LAG3 and TIM3 identifies a potent Treg population that suppresses macrophage functions in colorectal cancer patients.

PubMed

Ma, Qiang; Liu, Junning; Wu, Guoliang; Teng, Mujian; Wang, Shaoxuan; Cui, Meng; Li, Yuantao

2018-06-15

Regulatory T (Treg) cells are critical suppressors of inflammation and are thought to exert mainly deleterious effects in cancers. In colorectal cancer (CRC), Foxp3 +  Treg accumulation in the tumor was associated with poor prognosis. Hence, we examined the circulating Treg cells in CRC patients. Compared to controls, CRC patients presented mild upregulations in CD4 + CD25 +/hi T cells and in the more canonical CD4 + CD25 +/hi Foxp3 + Treg cells in peripheral blood mononuclear cells. Both of these Treg populations could be roughly divided into LAG3 - TIM3 - and LAG3 + TIM3 + subsets. In CRC patients, the LAG3 + TIM3 + subset represented approximately half of CD4 + CD25 +/hi T cells and greater than 60% of CD4 + CD25 +/hi Foxp3 + Treg cells, which was significantly more frequent than in healthy controls. Compared to the LAG3 - TIM3 - CD4 + CD25 +/hi T cells, the LAG3 + TIM3 + CD4 + CD25 +/hi T cells presented considerably higher transforming growth factor (TGF)-β and slightly higher interleukin (IL)-10 secretion, together with higher CTLA-4 and Foxp3 expression levels. Notably, macrophages following incubation with LAG3 - TIM3 - CD4 + CD25 +/hi T cells and LAG3 + TIM3 + CD4 + CD25 +/hi T cells displayed different characteristics. Macrophages incubated with LAG3 + TIM3 + CD4 + CD25 +/hi T cells presented lower expression of MHC class II, CD80, CD86, and tumor necrosis factor alpha (TNFα) but higher expression of IL-10, than macrophages incubated with LAG3 - TIM3 - CD4 + CD25 +/hi T cells. Together, our investigations demonstrated that CRC patients presented an enrichment of circulating Treg cells, in which the LAG3 + TIM3 + subset exhibited more potent expression of inhibitory molecules, and furthermore, the LAG3 + TIM3 + Treg cells could suppress the proinflammatory activation of macrophages more potently than the LAG3 - TIM3 - Treg cells. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Interaction between Galectin-9/TIM-3 pathway and follicular helper CD4+ T cells contributes to viral persistence in chronic hepatitis C.

PubMed

Zhuo, Ya; Zhang, Yi-Fu; Wu, Hong-Jie; Qin, Lei; Wang, Yan-Ping; Liu, A-Min; Wang, Xin-Hong

2017-10-01

Both Galectin 9 (Gal-9)/T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) pathway and follicular helper CD4 + T (Tfh) cells play important roles in persistent hepatitis C virus (HCV) infection. Thus, we aimed to investigate the regulatory role of interaction between Gal-9/TIM-3 pathway and Tfh cells in chronic hepatitis C. A total of 44 chronic hepatitis C patients and 19 normal controls (NCs) were enrolled in this study. Purified CD4 + T cells were cultured by TIM-3 Fc protein, recombinant Gal-9, or IL-21 for 48h. TIM-3 expression, Tfh proportion, and IL-21 production was measured, respectively. The immunomodulatory role of Gal-9/TIM-3 and IL-21 was also investigated in HCV cell culture system in vitro. We found that the percentage corresponding to both TIM-3-positive and CXCR5 + ICOS + Tfh cells within CD4 + T cells, which correlated with HCV RNA replication, was significantly elevated in patients with chronic hepatitis C in comparison with those in NCs. Moreover, blockade of Gal-9/TIM-3 pathway by TIM-3 Fc protein increased Tfh cells proportion, IL-21 mRNA and protein expression within purified CD4 + T cells, while activation of Gal-9/TIM-3 signaling by Gal-9 stimulation decreased IL-21 production in both patients with chronic HCV infection and healthy individuals. Meanwhile, high concentrations (100 and 200ng/mL) of IL-21 stimulation also elevated TIM-3 expression on CD4 + T cells in chronic hepatitis C. Furthermore, TIM-3 blockage and IL-21 stimulation suppressed mRNA expressions of HCV-induced antiviral proteins (myxovirus resistance A and oligoadenylate synthetase) in Huh7.5 cells without affecting viral replication in HCV cell culture system. The interaction between Gal-9/TIM-3 pathway and Tfh cells contributed to viral persistent in chronic HCV infection, which might be pivotal for development of new therapeutic approaches for chronic hepatitis C. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Smart Mirrors for Photorefractive Control of Light with Tim Bunning, RX - Agile Filters Application

DTIC Science & Technology

2016-11-08

AFRL-AFOSR-UK-TR-2017-0008 Smart Mirrors for photorefractive control of light with Tim Bunning, RX-- Agile filters application Luciano De Sio...photorefractive control of light with Tim Bunning, RX-- Agile filters application 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER FA9550-14-1-0050 5c.  PROGRAM...photorefractive, switchable optical filters , liquide crystalline composite materials, Switchable reflective holographic gratings, polymer-dispersed liquid

Inverse European Latitudinal Cline at the timeless Locus of Drosophila melanogaster Reveals Selection on a Clock Gene: Population Genetics of ls-tim.

PubMed

Zonato, Valeria; Vanin, Stefano; Costa, Rodolfo; Tauber, Eran; Kyriacou, Charalambos P

2018-02-01

The spread of adaptive genetic variants in populations is a cornerstone of evolutionary theory but with relatively few biologically well-understood examples. Previous work on the ls-tim variant of timeless, which encodes the light-sensitive circadian regulator in Drosophila melanogaster, suggests that it may have originated in southeastern Italy. Flies characterized by the new allele show photoperiod-related phenotypes likely to be adaptive in seasonal environments. ls-tim may be spreading from its point of origin in Italy by directional selection, but there are alternative explanations for its observed clinal geographical distribution, including balancing selection and demography. From population analyses of ls-tim frequencies collected on the eastern side of the Iberian Peninsula, we show that ls-tim frequencies are inverted compared with those in Italy. This pattern is consistent with a scenario of directional selection rather than latitude-associated balancing selection. Neutrality tests further reveal the signature of directional selection at the ls-tim site, which is reduced a few kb pairs either side of ls-tim. A reanalysis of allele frequencies from a large number of microsatellite loci do not demonstrate any frequent ls-tim-like spatial patterns, so a general demographic effect or population expansion from southeastern Italy cannot readily explain current ls-tim frequencies. Finally, a revised estimate of the age of ls-tim allele using linkage disequilibrium and coalescent-based approaches reveals that it may be only 300 to 3000 years old, perhaps explaining why it has not yet gone to fixation. ls-tim thus provides a rare temporal snapshot of a new allele that has come under selection before it reaches equilibrium.

Blocking Tim-3 or/and PD-1 reverses dysfunction of tumor-infiltrating lymphocytes in HBV-related hepatocellular carcinoma.

PubMed

Liu, Furong; Zeng, Gucheng; Zhou, Shaotang; He, Xiaoshun; Sun, Nianfeng; Zhu, Xiaofeng; Hu, Anbin

2018-05-01

The immunosuppression of tumor-infiltrating lymphocytes (TILs) is associated with rapid progression of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). T cell Ig- and mucin-domain-containing molecule-3 (Tim-3) and programmed cell death 1 (PD-1) are important inhibitory molecules expressed on the surface of T cells, but their roles in the function of TILs in HBV-HCC are poorly understood. We aimed to study the roles of these two markers in HBV-HCC. Ninety patients with pathologically confirmed HBV-associated HCC were enrolled in our study. Blood samples, paired fresh tumor tissues and adjacent tissues were collected, and isolating peripheral blood mononuclear cells, TILs and adjacent-infiltrating lymphocytes were isolated from these samples. The patients were followed-up to allow survival analysis. Tim-3 or/and PD-1 was up-regulated expressed on CD4 + and CD8 + TILs in HBV-HCC patients and a higher proportion of TILs expressed PD-1 alone. Tim-3 + and PD-1 + TILs greatly decreased secretion of IFN-? and TNF-a. Expression of Tim-3 and PD-1 on TILs negatively correlated with disease-free survival of HCC patients. Direct blockade of Tim-3 and PD-1 in vitro significantly enhanced TILs proliferation and secretion of IFN-? and TNF-a. Expression of Tim-3 and/or PD-1 on TILs impairs their function and correlates negatively with disease-free survival in HBV-HCC. Direct blockade of Tim-3 and PD-1 restores anti-tumor effects of TILs, which suggests a potential target for novel immunotherapy in HBV-HCC. Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

27. YCC CREW THAT REBUILT PIMA POINT TRAILS. TIM BEALE, ...

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

27. YCC CREW THAT REBUILT PIMA POINT TRAILS. TIM BEALE, NPS TRAILS, FRONT ROW RIGHT; BERNIE PONYAH, NPS YCC SUPERVISOR, BACK ROW RIGHT. - West Rim Drive, Between Grand Canyon Village & Hermit Rest, Grand Canyon, Coconino County, AZ

Cis Association of Galectin-9 with Tim-3 Differentially Regulates IL-12/IL-23 Expressions in Monocytes via TLR Signaling

PubMed Central

Ma, Cheng J.; Li, Guang Y.; Cheng, Yong Q.; Wang, Jia M.; Ying, Ruo S.; Shi, Lei; Wu, Xiao Y.; Niki, Toshiro; Hirashima, Mitsumi; Li, Chuan F.; Moorman, Jonathan P.; Yao, Zhi Q.

2013-01-01

Human monocytes/macrophages (M/MФ) of the innate immunity sense and respond to microbial products via specific receptor coupling with stimulatory (such as TLR) and inhibitory (such as Tim-3) receptors. Current models imply that Tim-3 expression on M/MØ can deliver negative signaling to TLR-mediated IL-12 expression through trans association with its ligand Galectin-9 (Gal-9) presented by other cells. However, Gal-9 is also expressed within M/MØ, and the effect of intracellular Gal-9 on Tim-3 activities and inflammatory responses in the same M/MØ remains unknown. In this study, our data suggest that Tim-3 and IL-12/IL-23 gene transcriptions are regulated by enhanced or silenced Gal-9 expression within monocytes through synergizing with TLR signaling. Additionally, TLR activation facilitates Gal-9/Tim-3 cis association within the same M/MØ to differentially regulate IL-12/IL-23 expressions through STAT-3 phosphorylation. These results reveal a ligand (Gal-9) compartment-dependent regulatory effect on receptor (Tim-3) activities and inflammatory responses via TLR pathways—a novel mechanism underlying cellular responses to external or internal cues. PMID:23967307

Earth-Mars Telecommunications and Information Management System (TIMS): Antenna Visibility Determination, Network Simulation, and Management Models

NASA Technical Reports Server (NTRS)

Odubiyi, Jide; Kocur, David; Pino, Nino; Chu, Don

1996-01-01

This report presents the results of our research on Earth-Mars Telecommunications and Information Management System (TIMS) network modeling and unattended network operations. The primary focus of our research is to investigate the feasibility of the TIMS architecture, which links the Earth-based Mars Operations Control Center, Science Data Processing Facility, Mars Network Management Center, and the Deep Space Network of antennae to the relay satellites and other communication network elements based in the Mars region. The investigation was enhanced by developing Build 3 of the TIMS network modeling and simulation model. The results of several 'what-if' scenarios are reported along with reports on upgraded antenna visibility determination software and unattended network management prototype.

PD-1 and Tim-3 pathways are associated with regulatory CD8+ T-cell function in decidua and maintenance of normal pregnancy

PubMed Central

Wang, S-C; Li, Y-H; Piao, H-L; Hong, X-W; Zhang, D; Xu, Y-Y; Tao, Y; Wang, Y; Yuan, M-M; Li, D-J; Du, M-R

2015-01-01

CD8+ T cells are critical in the balance between fetal tolerance and antiviral immunity. T-cell immunoglobulin mucin-3 (Tim-3) and programmed cell death-1 (PD-1) are important negative immune regulatory molecules involved in viral persistence and tumor metastasis. Here, we demonstrate that Tim-3+PD-1+CD8+ T cells from decidua greatly outnumbered those from peripheral blood during human early pregnancy. Co-culture of trophoblasts with CD8+ T cells upregulated PD-1+ and/or Tim-3+ immune cells. Furthermore, the population of CD8+ T cells co-expressing PD-1 and Tim-3 was enriched within the intermediate memory subset in decidua. This population exhibited high proliferative activity and Th2-type cytokine producing capacity. Blockade of Tim-3 and PD-1 resulted in decreased in vitro proliferation and Th2-type cytokine production while increased trophoblast killing and IFN-γ producing capacities of CD8+ T cells. Pregnant CBA/J females challenged with Tim-3 and/or PD-1 blocking antibodies were more susceptible to fetal loss, which was associated with CD8+ T-cell dysfunction. Importantly, the number and function of Tim-3+PD-1+CD8+ T cells in decidua were significantly impaired in miscarriage. These findings underline the important roles of Tim-3 and PD-1 pathways in regulating decidual CD8+ T-cell function and maintaining normal pregnancy. PMID:25950468

Galectin-9 Signaling through TIM-3 Is Involved in Neutrophil-Mediated Gram-Negative Bacterial Killing: An Effect Abrogated within the Cystic Fibrosis Lung

PubMed Central

Vega-Carrascal, Isabel; Bergin, David A.; McElvaney, Oliver J.; McCarthy, Cormac; Banville, Nessa; Pohl, Kerstin; Hirashima, Mitsuomi; Kuchroo, Vijay K.; Reeves, Emer P.; McElvaney, Noel G.

2016-01-01

The T cell Ig and mucin domain–containing molecule (TIM) family of receptors have emerged as potential therapeutic targets to correct abnormal immune function in chronic inflammatory conditions. TIM-3 serves as a functional receptor in structural cells of the airways and via the ligand galectin-9 (Gal-9) can modulate the inflammatory response. The aim of this study was to investigate TIM-3 expression and function in neutrophils, focusing on its potential role in cystic fibrosis (CF) lung disease. Results revealed that TIM-3 mRNA and protein expression values of circulating neutrophils were equal between healthy controls (n = 20) and people with CF (n = 26). TIM-3 was detected on resting neutrophil membranes by FACS analysis, and expression levels significantly increased post IL-8 or TNF-α exposure (p < 0.05). Our data suggest a novel role for TIM-3/Gal-9 signaling involving modulation of cytosolic calcium levels. Via TIM-3 interaction, Gal-9 induced neutrophil degranulation and primed the cell for enhanced NADPH oxidase activity. Killing of Pseudomonas aeruginosa was significantly increased upon bacterial opsonization with Gal-9 (p < 0.05), an effect abrogated by blockade of TIM-3 receptors. This mechanism appeared to be Gram-negative bacteria specific and mediated via Gal-9/ LPS binding. Additionally, we have demonstrated that neutrophil TIM-3/Gal-9 signaling is perturbed in the CF airways due to proteolytic degradation of the receptor. In conclusion, results suggest a novel neutrophil defect potentially contributing to the defective bacterial clearance observed in the CF airways and suggest that manipulation of the TIM-3 signaling pathway may be of therapeutic value in CF, preferably in conjunction with antiprotease treatment. PMID:24477913

A polymorphism in TIM1 is associated with susceptibility to severe hepatitis A virus infection in humans

PubMed Central

Kim, Hye Young; Eyheramonho, María Belén; Pichavant, Muriel; Gonzalez Cambaceres, Carlos; Matangkasombut, Ponpan; Cervio, Guillermo; Kuperman, Silvina; Moreiro, Rita; Konduru, Krishnamurthy; Manangeeswaran, Mohanraj; Freeman, Gordon J.; Kaplan, Gerardo G.; DeKruyff, Rosemarie H.; Umetsu, Dale T.; Rosenzweig, Sergio D.

2011-01-01

During infection with the hepatitis A virus (HAV), most patients develop mild or asymptomatic disease. However, a small number of patients develop serious, life-threatening hepatitis. We investigated this variability in disease severity by examining 30 Argentinean patients with HAV-induced acute liver failure in a case-control, cross-sectional, observational study. We found that HAV-induced severe liver disease was associated with a 6-amino-acid insertion in TIM1/HAVCR1 (157insMTTTVP), the gene encoding the HAV receptor. This polymorphism was previously shown to be associated with protection against asthma and allergic diseases and with HIV progression. In binding assays, the TIM-1 protein containing the 157insMTTTVP insertion polymorphism bound HAV more efficiently. When expressed by human natural killer T (NKT) cells, this long form resulted in greater NKT cell cytolytic activity against HAV-infected liver cells, compared with the shorter TIM-1 protein without the polymorphism. To our knowledge, the 157insMTTTVP polymorphism in TIM1 is the first genetic susceptibility factor shown to predispose to HAV-induced acute liver failure. Furthermore, these results suggest that HAV infection has driven the natural selection of shorter forms of the TIM-1 protein, which binds HAV less efficiently, thereby protecting against severe HAV-induced disease, but which may predispose toward inflammation associated with asthma and allergy. PMID:21339644

Professor Tim de Zeeuw Takes Up Duty as New ESO Director General

NASA Astrophysics Data System (ADS)

2007-09-01

On 1 September, Tim de Zeeuw became the new ESO Director General, succeeding Catherine Cesarsky. In his first day in office, he kindly agreed to answer a few questions. ESO PR Photo 38/07 ESO PR Video 38/07 Watch the Video! How would you describe the current period for astronomy? Tim de Zeeuw: We are in an extremely exciting time for astronomy and I think this is understood worldwide and not just by astronomers. The technology is now available to look not only at the farthest objects in the Universe, where the light left a long time ago, allowing us to see how the Universe evolved and developed, but we can even detect signatures of planets around other stars, and that answers an age-old question which is a fundamental question in all of science, and really excites the general public. How do you see the role of ESO in this context? Tim de Zeeuw: ESO has a very important role in the context of European and worldwide astronomy because it is one of the leading organisations for ground-based astronomy. You may even say it is the pre-eminent organisation. Therefore, we have both an opportunity and a responsibility to lead the further developments in astronomy. Where do you see ESO developing in the coming years? Tim de Zeeuw: I see three main goals for ESO in the coming years. The first one is to get the best possible science out of the Very Large Telescope, the interferometer and the survey telescopes, all of them on Paranal. The second is to build ALMA, the new observatory at 5 000 metres in the high Andes. Together with our North American and East Asian partners, we need to deliver this on budget and on time, and prepare the European astronomers for leading the science. The third main goal is to design a world-leading Extremely Large Telescope (ELT), which may have a main mirror with a diameter larger than 40 metres and will enable wonderful science. And of course, we don't only want to design it, we also want to construct it. And what about La Silla? Tim de Zeeuw: La

Analysis of Eocene depositional environments - Preliminary TM and TIMS results, Wind River Basin, Wyoming

NASA Technical Reports Server (NTRS)

Stucky, Richard K.; Krishtalka, Leonard; Redline, Andrew D.; Lang, Harold R.

1987-01-01

Both Landsat TM and aircraft Thermal IR Multispectral Scanner (TIMS) data have been used to map the lithofacies of the Wind River Basin's Eocene physical and biological environments. Preliminary analyses of these data have furnished maps of a fault contact boundary and a complex network of fluvial ribbon channel sandstones. The synoptic view thereby emerging for Eocene fluvial facies clarifies the relationships of ribbon channel sandstones to fossil-bearing overbank/floodplain facies and certain peleosols. The utility of TM and TIMS data is thereby demonstrated.

A quantitative analysis of TIMS data obtained on the Learjet 23 at various altitudes

NASA Technical Reports Server (NTRS)

Jaggi, S.

1992-01-01

A series of Thermal Infrared Multispectral Scanner (TIMS) data acquisition flights were conducted on the NASA Learjet 23 at different altitudes over a test site. The objective was to monitor the performance of the TIMS (its estimation of the brightness temperatures of the ground scene) with increasing altitude. The results do not show any significant correlation between the brightness temperatures and the altitude. The analysis indicates that the estimation of the temperatures is a function of the accuracy of the atmospheric correction used for each altitude.

The Coordinated Actions of TIM-3 on Cancer and Myeloid Cells in the Regulation of Tumorigenicity and Clinical Prognosis in Clear Cell Renal Cell Carcinomas.

PubMed

Komohara, Yoshihiro; Morita, Tomoko; Annan, Dorcas A; Horlad, Hasita; Ohnishi, Koji; Yamada, Sohsuke; Nakayama, Toshiyuki; Kitada, Shohei; Suzu, Shinya; Kinoshita, Ichiro; Dosaka-Akita, Hirotoshi; Akashi, Koichi; Takeya, Motohiro; Jinushi, Masahisa

2015-09-01

Clear cell renal cell carcinoma (ccRCC) is one of most common cancers in urogenital organs. Although recent experimental and clinical studies have shown the immunogenic properties of ccRCC as illustrated by the clinical sensitivities to various immunotherapies, the detailed immunoregulatory machineries governing the tumorigenicity of human ccRCC remain largely obscure. In this study, we demonstrated the clinical significance and functional relevance of T-cell immunoglobulin and mucin domain-containing molecule-3 (TIM-3) expressed on tumor cells and myeloid cells in patients with ccRCC. TIM-3 expression was detected on cancer cells and CD204(+) tumor-associated macrophages (TAM), and higher expression level of TIM-3 was positively correlated with shorter progression-free survival (PFS) in patients with ccRCC. We found that TIM-3 expression was detected on a large number of tumors, and there was significant correlation between an increased number of TAMs and high expression level of TIM-3 in patients with ccRCC. Furthermore, TIM-3 rendered RCC cells with the ability to induce resistance to sunitinib and mTOR inhibitors, the standard regimen for patients with ccRCC, as well as stem cell activities. TIM-3 expression was induced on CD14(+) monocytes upon long-term stimulation with RCC cells, and TIM-3-expressing myeloid cells play a critical role in augmenting tumorigenic activities of TIM-3-negative RCC cells. More importantly, treatment with anti-TIM-3 mAb suppressed its tumorigenic effects in in vitro and in vivo settings. These findings indicate the coordinated action of TIM-3 in cancer cells and in myeloid cells regulates the tumorigenicity of human RCC. ©2015 American Association for Cancer Research.

For geological investigations with airborne thermal infrared multispectral images: Transfer of calibration from laboratory spectrometer to TIMS as alternative for removing atmospheric effects

NASA Technical Reports Server (NTRS)

Edgett, Kenneth S.; Anderson, Donald L.

1995-01-01

This paper describes an empirical method to correct TIMS (Thermal Infrared Multispectral Scanner) data for atmospheric effects by transferring calibration from a laboratory thermal emission spectrometer to the TIMS multispectral image. The method does so by comparing the laboratory spectra of samples gathered in the field with TIMS 6-point spectra for pixels at the location of field sampling sites. The transference of calibration also makes it possible to use spectra from the laboratory as endmembers in unmixing studies of TIMS data.

Tim-3 is differently expressed in genetically susceptible C57BL/6 and resistant BALB/c mice during oral infection with Toxoplasma gondii

PubMed Central

Berrocal Almanza, L. C.; Muñoz, M.; Kühl, A. A.; Kamradt, T.; Heimesaat, M. M.

2013-01-01

Tim-3 has opposing roles in innate and adaptive immunities. It not only dampens CD4+ and CD8+ T cells responses but also enhances the ability of macrophages to eliminate intracellular pathogens. After peroral infection with 100 cysts of Toxoplasma gondii genetically susceptible C57BL/6 mice develop an unchecked Th1 response associated with the development of small intestinal immunopathology. Here we report that upon infection with T. gondii, both susceptible C57BL/6 and resistant BALB/c mice exhibit increased frequencies of Tim-3+ cells in spleens and mesenteric lymph nodes. The number of Tim-3+ cells was significantly higher in C57BL/6 than in BALB/c mice. Tim-3 was expressed by macrophages, dendritic, natural killer, as well as CD4+ and CD8+ T cells. Highest frequencies of Tim-3+ cells were observed at the peak of Th1 responses (day 7 post infection) concurrent with the development of ileal immunopathology. Infected Tim-3-deficient BALB/c mice did not develop ileal immunopathology nor did their parasite loads differ from those in wildtype BALB/c mice. Thus, although Tim-3 is markedly upregulated upon infection and differentially regulated in susceptible and resistant mice upon infection with T. gondii, the absence of Tim-3 is not sufficient to overcome the genetic resistance of BALB/c mice to the development of Th1-driven small intestinal immunopathology. PMID:24265941

Tim-3 is differently expressed in genetically susceptible C57BL/6 and resistant BALB/c mice during oral infection with Toxoplasma gondii.

PubMed

Berrocal Almanza, L C; Muñoz, M; Kühl, A A; Kamradt, T; Heimesaat, M M; Liesenfeld, O

2013-09-01

Tim-3 has opposing roles in innate and adaptive immunities. It not only dampens CD4+ and CD8+ T cells responses but also enhances the ability of macrophages to eliminate intracellular pathogens. After peroral infection with 100 cysts of Toxoplasma gondii genetically susceptible C57BL/6 mice develop an unchecked Th1 response associated with the development of small intestinal immunopathology. Here we report that upon infection with T. gondii, both susceptible C57BL/6 and resistant BALB/c mice exhibit increased frequencies of Tim-3+ cells in spleens and mesenteric lymph nodes. The number of Tim-3+ cells was significantly higher in C57BL/6 than in BALB/c mice. Tim-3 was expressed by macrophages, dendritic, natural killer, as well as CD4+ and CD8+ T cells. Highest frequencies of Tim-3+ cells were observed at the peak of Th1 responses (day 7 post infection) concurrent with the development of ileal immunopathology. Infected Tim-3-deficient BALB/c mice did not develop ileal immunopathology nor did their parasite loads differ from those in wildtype BALB/c mice. Thus, although Tim-3 is markedly upregulated upon infection and differentially regulated in susceptible and resistant mice upon infection with T. gondii, the absence of Tim-3 is not sufficient to overcome the genetic resistance of BALB/c mice to the development of Th1-driven small intestinal immunopathology.

Progress integrating ID-TIMS U-Pb geochronology with accessory mineral geochemistry: towards better accuracy and higher precision time

NASA Astrophysics Data System (ADS)

Schoene, B.; Samperton, K. M.; Crowley, J. L.; Cottle, J. M.

2012-12-01

It is increasingly common that hand samples of plutonic and volcanic rocks contain zircon with dates that span between zero and >100 ka. This recognition comes from the increased application of U-series geochronology on young volcanic rocks and the increased precision to better than 0.1% on single zircons by the U-Pb ID-TIMS method. It has thus become more difficult to interpret such complicated datasets in terms of ashbed eruption or magma emplacement, which are critical constraints for geochronologic applications ranging from biotic evolution and the stratigraphic record to magmatic and metamorphic processes in orogenic belts. It is important, therefore, to develop methods that aid in interpreting which minerals, if any, date the targeted process. One promising tactic is to better integrate accessory mineral geochemistry with high-precision ID-TIMS U-Pb geochronology. These dual constraints can 1) identify cogenetic populations of minerals, and 2) record magmatic or metamorphic fluid evolution through time. Goal (1) has been widely sought with in situ geochronology and geochemical analysis but is limited by low-precision dates. Recent work has attempted to bridge this gap by retrieving the typically discarded elution from ion exchange chemistry that precedes ID-TIMS U-Pb geochronology and analyzing it by ICP-MS (U-Pb TIMS-TEA). The result integrates geochemistry and high-precision geochronology from the exact same volume of material. The limitation of this method is the relatively coarse spatial resolution compared to in situ techniques, and thus averages potentially complicated trace element profiles through single minerals or mineral fragments. In continued work, we test the effect of this on zircon by beginning with CL imaging to reveal internal zonation and growth histories. This is followed by in situ LA-ICPMS trace element transects of imaged grains to reveal internal geochemical zonation. The same grains are then removed from grain-mount, fragmented, and

Suppression of TIM-1 predicates clinical efficacy of sublingual immunotherapy for allergic rhinitis in children.

PubMed

Lin, Zhibin; Zhou, Lifeng; Luo, Xi; Xia, Wentong; Chen, Dehua; Xu, Rui; Wang, Jie; Luo, Renzhong; Xu, Geng; Li, Huabin

2013-08-01

To evaluate the clinical efficacy of sublingual immunotherapy (SLIT) with house-dust mite (HDM) extract and to examine the change of biomarkers (TIM-1, IL-5 and IL-10) after 6-month SLIT in children with allergic rhinitis (AR). One hundred and sixteen HDM-sensitized children with persistent AR were enrolled to assess the clinical efficacy of SLIT by determining the individual nasal symptom score (INSS) and total nasal symptom scores (TNSS) after 6-month SLIT. Moreover, the mRNA expression of TIM-1, IL-5 and IL-10 in peripheral blood mononuclear cells (PBMCs) was examined in 16 well-controlled and 12 uncontrolled AR patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR). After 6-month SLIT, both TNSS and INSS scores were significantly decreased compared with the baseline value (p < 0.01). The rates for well-controlled, partly controlled and uncontrolled children were 43.1%, 32.8% and 24.1%, respectively. Accordingly, the mRNA levels of TIM-1 and IL-5 decreased significantly and IL-10 mRNA level increased significantly compared with the baseline value in well-controlled children (p < 0.05). Our findings suggest SLIT with HDM extract is effective and safe for AR children and TIM-1 may be considered as an indicator for evaluating the clinical efficacy of SLIT. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

HTLV-1 Tax Specific CD8+ T Cells Express Low Levels of Tim-3 in HTLV-1 Infection: Implications for Progression to Neurological Complications

PubMed Central

Hasenkrug, Aaron M.; Jha, Aashish R.; Carvalho, Karina I.; Eccles-James, Ijeoma G.; Bruno, Fernanda R.; Vieira, Raphaella G. S.; York, Vanessa A.; Chew, Glen M.; Jones, R. Brad; Tanaka, Yuetsu; Neto, Walter K.; Sanabani, Sabri S.; Ostrowski, Mario A.; Segurado, Aluisio C.; Nixon, Douglas F.; Kallas, Esper G.

2011-01-01

The T cell immunoglobulin mucin 3 (Tim-3) receptor is highly expressed on HIV-1-specific T cells, rendering them partially “exhausted” and unable to contribute to the effective immune mediated control of viral replication. To elucidate novel mechanisms contributing to the HTLV-1 neurological complex and its classic neurological presentation called HAM/TSP (HTLV-1 associated myelopathy/tropical spastic paraparesis), we investigated the expression of the Tim-3 receptor on CD8+ T cells from a cohort of HTLV-1 seropositive asymptomatic and symptomatic patients. Patients diagnosed with HAM/TSP down-regulated Tim-3 expression on both CD8+ and CD4+ T cells compared to asymptomatic patients and HTLV-1 seronegative controls. HTLV-1 Tax-specific, HLA-A*02 restricted CD8+ T cells among HAM/TSP individuals expressed markedly lower levels of Tim-3. We observed Tax expressing cells in both Tim-3+ and Tim-3− fractions. Taken together, these data indicate that there is a systematic downregulation of Tim-3 levels on T cells in HTLV-1 infection, sustaining a profoundly highly active population of potentially pathogenic T cells that may allow for the development of HTLV-1 complications. PMID:21541358

Role of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells

PubMed Central

Sims, Brian; Farrow, Anitra L; Williams, Sparkle D; Bansal, Anju; Krendelchtchikov, Alexandre; Gu, Linlin; Matthews, Qiana L

2017-01-01

Exosomes, 30–200 nm nanostructures secreted from donor cells and internalized by recipient cells, can play an important role in the cellular entry of some viruses. These microvesicles are actively secreted into various body fluids, including blood, urine, saliva, cerebrospinal fluid, and breast milk. We successfully isolated exosomes from human breast milk and plasma. The size and concentration of purified exosomes were measured by nanoparticle tracking, while Western blotting confirmed the presence of the exosomal-associated proteins CD9 and CD63, clathrin, and T cell immunoglobulin and mucin proteins (TIMs). Through viral infection assays, we determined that HIV-1 utilizes an exosome-dependent mechanism for entry into human immune cells. The virus contains high amounts of phosphatidylserine (PtdSer) and may bind PtdSer receptors, such as TIMs. This mechanism is supported by our findings that exosomes from multiple sources increased HIV-1 entry into T cells and macrophages, and viral entry was potently blocked with anti-TIM-4 antibodies. PMID:28740388

Demonstration of Unmanned Aircraft Systems Use for Traffic Incident Management (UAS-TIM)

DOT National Transportation Integrated Search

2017-12-01

Previous investigations into technologies that can improve incident response, monitoring, and clearance resulted in the potential application of Unmanned Aerial System (UAS) for use in Traffic Incident Management (TIM). An initial investigation of UA...

Tim-4 inhibition of T-cell activation and T helper type 17 differentiation requires both the immunoglobulin V and mucin domains and occurs via the mitogen-activated protein kinase pathway

PubMed Central

Cao, Wei; Ryan, Michelle; Buckley, Deirdre; O'Connor, Rosemary; Clarkson, Michael R

2011-01-01

Emerging experimental data suggest an important role for the T-cell immunoglobulin mucin 1 (Tim-1):Tim-4 pathway in autoimmune and alloimmune responses in vivo. Using a Tim-4 ectodomain human IgG Fc fusion protein we studied the role of Tim-4 in T-cell activation, signalling and differentiation responses in vitro. We demonstrate that Tim-4Fc can inhibit naive and pre-activated T-cell activation, proliferation and cytokine secretion via a Tim-1-independent pathway. Tim-4 contains immunoglobulin variable (IgV) and mucin domains; to identify which domain accounts for the inhibitory effect novel Tim-4 fusion proteins containing either the IgV or mucin domain were generated. We demonstrate that both IgV and mucin domains are required for the inhibitory effects and that they are mediated at least in part by inhibition of extracellular signal-regulated kinase pathway activity. Given the emerging interest in the role of the Tim family in T helper type 17 (Th17) cells, which play an important role in autoimmune disease and transplantation tolerance, our data show that Tim-4Fc can prevent polarization of CD4+ T cells to the Th17 phenotype. Collectively, our results highlight an inhibitory role for Tim-4Fc in vitro, which we propose is mediated by a receptor other than Tim-1. In addition, this study provides new insights into the role of Tim-4Fc in regulating Th17 immune responses and may open a new avenue for autoimmune therapy. PMID:21463297

Wise Leadership for Student Success: An Interview with Tim White

ERIC Educational Resources Information Center

Kezar, Adrianna

2015-01-01

Adrianna Kezar recently sat down with Chancellor Tim White of the California State University system to discuss, among many other things, the newly released California State Graduation Initiative and what it will take to enact it. The key commitments of the initiative are: (1) hire more tenure-track faculty; (2) develop engaged advising; (3) solve…

When the CA-TIMS therapy fails: the over-enthusiastic, the mixed-up, and the stubborn zircon

NASA Astrophysics Data System (ADS)

Corfu, F.

2009-12-01

Mattinson’s CA-TIMS technique has proven to be highly successful in efficiently removing disturbed domains of zircon, thus enabling the determination of precise and accurate ages in a variety of geological situations. The method generally produces equal or better results than mechanical abrasion. There are, however, cases where CA-TIMS fails to achieve perfect concordance, and occasionally actually increases the degree of discordance. Such a behaviour (the over-reaction) is observed for example in U-rich (>1000 ppm) but texturally homogeneous zircon, a type quite common in highly differentiated portions of mafic intrusions, in granitic pegmatites, and in some metamorphic rocks. Because of their internal uniformity, such zircons do not exhibit large contrasts in crystallinity and solubility and after the baking stage of the CA-TIMS procedure they will either totally dissolve in the first HF attack, or produce discordant results. By contrast, mechanical abrasion of this type of zircon can isolate alteration-free zircon domains that yield concordant and reproducible data. This is due to the homogeneity of the crystals, the lack of zoning limiting contrasts in the degrees of metamictization and brittleness and preventing fracturing. The absence of fractures helps to confine alteration of zircon to the marginal domains, and these can be removed very efficiently by mechanical abrasion. This behaviour is exemplified by zircon populations from 252.0 Ma and 182.5 Ma mafic sills in Siberia and the Karoo basin. Another class of zircons that in general does not, or only partially comply with CA-TIMS includes populations from metamorphic and poly-orogenic rocks, typical of many Proterozoic orogens. The metamorphic reprocessing of zircon into low-U domains can freeze-in old Pb-loss patterns that cannot be undone by any technique. New metamorphic zircon growth can also create mixtures of different aged domains that cannot be resolved by CA-TIMS. In favourable circumstances

Insights into the fold organization of TIM barrel from interaction energy based structure networks.

PubMed

Vijayabaskar, M S; Vishveshwara, Saraswathi

2012-01-01

There are many well-known examples of proteins with low sequence similarity, adopting the same structural fold. This aspect of sequence-structure relationship has been extensively studied both experimentally and theoretically, however with limited success. Most of the studies consider remote homology or "sequence conservation" as the basis for their understanding. Recently "interaction energy" based network formalism (Protein Energy Networks (PENs)) was developed to understand the determinants of protein structures. In this paper we have used these PENs to investigate the common non-covalent interactions and their collective features which stabilize the TIM barrel fold. We have also developed a method of aligning PENs in order to understand the spatial conservation of interactions in the fold. We have identified key common interactions responsible for the conservation of the TIM fold, despite high sequence dissimilarity. For instance, the central beta barrel of the TIM fold is stabilized by long-range high energy electrostatic interactions and low-energy contiguous vdW interactions in certain families. The other interfaces like the helix-sheet or the helix-helix seem to be devoid of any high energy conserved interactions. Conserved interactions in the loop regions around the catalytic site of the TIM fold have also been identified, pointing out their significance in both structural and functional evolution. Based on these investigations, we have developed a novel network based phylogenetic analysis for remote homologues, which can perform better than sequence based phylogeny. Such an analysis is more meaningful from both structural and functional evolutionary perspective. We believe that the information obtained through the "interaction conservation" viewpoint and the subsequently developed method of structure network alignment, can shed new light in the fields of fold organization and de novo computational protein design.

Consumerism, Activism, Intrinsic Motivation, and Balance: An Interview with Tim Kasser

ERIC Educational Resources Information Center

Keeley, Jared

2010-01-01

A year after receiving his PhD in psychology from the University of Rochester, Tim Kasser accepted a position at Knox College, in Galesburg, Illinois, where he is currently professor of psychology. He regularly teaches psychology classes on personality, clinical and abnormal psychology, dreaming, and research methods, as well as an…

The use of TIMS for mapping different pahoehoe surfaces: Mauna Iki, Kilauea

NASA Technical Reports Server (NTRS)

Rowland, Scott K.

1992-01-01

S-type and p-type pahoehoe record different mechanisms and vigors of activity within an active flow field. There is some controversy about what these mechanisms are exactly, and this study was undertaken with the idea that an accurate map of the two surfaces within a pahoehoe flow field could be helpful in solving the problem. Thermal Infrared Multispectral Scanner (TIMS) allows discrimination between s-type and p-type pahoehoe, and this ability was used to map the two surface types on the Mauna Iki satellite shield (southwest rift zone, Kilauea Volcano). TIMS was previously used to discriminate a'a from pahoehoe as well as to determine relative age relationships of different flows. Although inter-flow variation was minor in the data published by these authors, a second goal presented is to understand such variations to better constrain intra-flow differences used for age dating.

Space Solar Power Exploratory Research and Technology (SERT) Technical Interchange Meeting 2 (SERT TIM 2)

NASA Technical Reports Server (NTRS)

Howell, Joe; Sanders, Clark W.

2000-01-01

The University of Alabama in Huntsville's (UAH) Propulsion Research Center hosted the Space Solar Power Exploratory Research & Technology (SERT) Technical Interchange Meeting TIM) 2 in Huntsville, Alabama December 7-10. 1999 with 126 people in attendance. The SERT program includes both competitively procured activities. which are being implemented through a portfolio of focused R&D investments--with the maximum leveraging of existing resources inside and outside NASA. and guided by these system studies. Axel Roth. Director of the Flight Projects Directorate NASA MSFC, welcomed the SERT TIM 2 participants and challenged them to develop the necessary technologies and demonstrations that will lead to Space Solar Power (SSP) International implementation. Joe Howell, NASA MSFC, reiterated the SERT TIM 2 objectives: 1) Refining and modeling systems approaches for the utilization of SSP concepts and technologies, ranging, from the near-term e.g. for space science, exploration and commercial space applications to the far-term (e. g. SSP for terrestrial markets), including systems concepts, technology, infrastructure (i.g., transportation), and economics. 2) Conducting technology research, development and demonstration activities to produce "proof- of-concept" validation of critical SSP elements for both the nearer and farther-term applications. 3) Initiating partnerships Nationality and Internationally that could be expanded, as appropriate, to pursue later SSP technology and applications (e.g., space science. colonization, etc.). Day one began with the NASA Centers presenting their SERT activities summary since SERT TIM 1 and wound up with a presentation by Masahiro Mori, NASDA titled "NASDA In-house Study for SSP". Demonstration for the Near-Term. Day two began with the SERT Systems Studies and Analysis reports resulting from NRA 8-23 followed by presentations of SERT Technology Demonstrations reports resulting from NRA 8-23. Day two closed with John Mankins presentation

Constructing a Writer's Voice: Ethos, Tim Cahill, and the Jonestown Massacre

ERIC Educational Resources Information Center

Miller, Rich

2007-01-01

For over twenty years, Tim Cahill's writing has appeared in popular publications such as "Outside" and "Rolling Stone," and in many academic contexts, ranging from remedial and freshman composition textbooks to the use of his novels and short story collections in a variety of upper division literary courses. Cahill, then, is a…

Adaptive NKG2C+CD57+ Natural Killer Cell and Tim-3 Expression During Viral Infections

PubMed Central

Kared, Hassen; Martelli, Serena; Tan, Shu Wen; Simoni, Yannick; Chong, Meng Li; Yap, Siew Hwei; Newell, Evan W.; Pender, Sylvia L. F.; Kamarulzaman, Adeeba; Rajasuriar, Reena; Larbi, Anis

2018-01-01

Repetitive stimulation by persistent pathogens such as human cytomegalovirus (HCMV) or human immunodeficiency virus (HIV) induces the differentiation of natural killer (NK) cells. This maturation pathway is characterized by the acquisition of phenotypic markers, CD2, CD57, and NKG2C, and effector functions—a process regulated by Tim-3 and orchestrated by a complex network of transcriptional factors, involving T-bet, Eomes, Zeb2, promyelocytic leukemia zinc finger protein, and Foxo3. Here, we show that persistent immune activation during chronic viral co-infections (HCMV, hepatitis C virus, and HIV) interferes with the functional phenotype of NK cells by modulating the Tim-3 pathway; a decrease in Tim-3 expression combined with the acquisition of inhibitory receptors skewed NK cells toward an exhausted and cytotoxic phenotype in an inflammatory environment during chronic HIV infection. A better understanding of the mechanisms underlying NK cell differentiation could aid the identification of new immunological targets for checkpoint blockade therapies in a manner that is relevant to chronic infection and cancer. PMID:29731749

GUM Analysis for TIMS and SIMS Isotopic Ratios in Graphite

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

Heasler, Patrick G.; Gerlach, David C.; Cliff, John B.

2007-04-01

This report describes GUM calculations for TIMS and SIMS isotopic ratio measurements of reactor graphite samples. These isotopic ratios are used to estimate reactor burn-up, and currently consist of various ratios of U, Pu, and Boron impurities in the graphite samples. The GUM calculation is a propagation of error methodology that assigns uncertainties (in the form of standard error and confidence bound) to the final estimates.

Techniques for noise removal and registration of TIMS data

USGS Publications Warehouse

Hummer-Miller, S.

1990-01-01

Extracting subtle differences from highly correlated thermal infrared aircraft data is possible with appropriate noise filters, constructed and applied in the spatial frequency domain. This paper discusses a heuristic approach to designing noise filters for removing high- and low-spatial frequency striping and banding. Techniques for registering thermal infrared aircraft data to a topographic base using Thematic Mapper data are presented. The noise removal and registration techniques are applied to TIMS thermal infrared aircraft data. -Author

Conjugated Bilirubin Upregulates TIM-3 Expression on CD4+CD25+ T Cells: Anti-Inflammatory Implications for Hepatitis A Virus Infection.

PubMed

Trujillo-Ochoa, Jorge L; Corral-Jara, Karla F; Charles-Niño, Claudia L; Panduro, Arturo; Fierro, Nora A

2018-04-01

Bilirubin (BR), a metabolite with increased concentrations in plasma during viral hepatitis, has been recognized as a potential immune-modulator. We recently reported that conjugated BR (CB) augments regulatory T cell (Treg) suppressor activity during acute hepatitis A virus (HAV) infection. However, the mechanisms related to the effects of CB on Treg function in the course of hepatotropic viral diseases have not been elucidated. T cell immunoglobulin domain and mucin domain 3 (TIM-3), via its interactions with galectin-9 (GAL-9), is a receptor associated with enhanced Treg function. Thus, TIM-3 expression may be related to the crosstalk between CB and Tregs during HAV infection. Herein, in vitro treatment with high concentrations of CB upregulated TIM-3 expression on Tregs from healthy donors. CB treatment in vitro did not induce de novo Treg generation, and in vitro stimulation with TGF-β, which shows increased secretion during HAV infection, resulted in a trend toward increased TIM-3 expression on Tregs and CD4 + T lymphocytes (TLs) from healthy donors. Interestingly, an upregulation of TIM-3 expression on CD4 + CD25 + T cells and an increase in the proportion of CD4 + TLs expressing GAL-9 were found in HAV-infected patients with abnormal CB values relative to healthy controls. In addition, a statistically significantly reduction in IL-17F production was observed after treatment of CD4 + TLs from healthy donors with high doses of CB in vitro. In summary, our results suggest that CB might regulate Treg activity via a TIM-3-mediated mechanism, ultimately leading to an anti-inflammatory hepatoprotective effect.

Discrimination of alkalinity in granitoid Rocks: A potential TIMS application

NASA Technical Reports Server (NTRS)

Ruff, Steven W.

1995-01-01

In mineral exploration, the ability to distinguish and map petrochemical variations of magmatic rocks can be a useful reconnaissance tool. Alkalinity is one such petrochemical parameter and is used in the characterization of granitoid rocks. In quartz normative plutonic rocks, alkalinity is related to the composition and abundance of feldspars. Together with quartz abundance, knowledge of feldspar modes allows the classification of these igneous rocks according to the Streckeisen diagram. Alternative classification schemes rely on whole rock geochemistry instead of mineral identifications. The relative ease of obtaining whole rock analyses means that geochemical classifications tend to be favored in exploration geology. But the technique of thermal infrared spectroscopy of rocks yields information on mineralogy and is one that can be applied remotely. The goal of the current work then is to establish whether data from TIMS can be used to distinguish the mineralogical variations that relate to alkalinity. An ideal opportunity to test this thesis arises from the work presented in a paper by Dewitt (1989). This paper contains the results of mapping and analysis of Proterozoic plutonic rocks in north-central Arizona. The map resulting from this work delineates plutons according to alkalinity in an effort to establish a trend or polarity in the regional magmatism. Also contained within this paper are brief descriptions of the mineralogy of half of the region's plutons. This combination of mineralogical and geochemical information was the rationale behind choosing this area as a site for TIMS over flights. A portion of the region centered on the northern Bradshaw Mountains was selected because it contains plutons of all three alkalinity classifications (alkali-calcic, calc-alkalic, and calic) present on DeWitt's map within a relatively small area. The site was flown in August of 1994 and the data received a few days before the writing of this manuscript. Most of this

Increased PD-1+ and TIM-3+ TILs during cetuximab therapy inversely correlates with response in head and neck cancer patients

PubMed Central

Jie, Hyun-Bae; Srivastava, Raghvendra M.; Argiris, Athanassios; Bauman, Julie E.; Kane, Lawrence P.; Ferris, Robert L.

2017-01-01

Despite emerging appreciation for the important role of immune checkpoint receptors in regulating the effector functions of T cells, it is unknown whether their expression is involved in determining the clinical outcome in response to cetuximab therapy. We examined the expression patterns of immune checkpoint receptors (including PD-1, CTLA-4, and TIM-3) and cytolytic molecules (including granzyme B and perforin) of CD8+ tumor-infiltrating lymphocytes (TILs) and compared them to those of peripheral blood T lymphocytes (PBLs) in patients with head and neck cancer (HNSCC) during cetuximab therapy. The frequency of PD-1 and TIM-3 expression was significantly increased in CD8+ TILs compared to CD8+ PBLs (P = 0.008 and P = 0.02, respectively). This increased CD8+ TIL population co-expressed granzyme B/perforin and PD-1/TIM-3, which suggests a regulatory role for these immune checkpoint receptors in cetuximab-promoting cytolytic activities of CD8+ TIL. Indeed, the increased frequency of PD-1+ and TIM-3+ CD8+ TILs was inversely correlated with clinical outcome of cetuximab therapy. These findings support the use of PD-1 and TIM-3 as biomarkers to reflect immune status of CD8+ T cells in the tumor microenvironment during cetuximab therapy. Blockade of these immune checkpoint receptors might enhance cetuximab-based cancer immunotherapy to reverse CD8+ TIL dysfunction, thus potentially improving clinical outcomes of HNSCC patients. PMID:28408386

Simulation modeling and preliminary analysis of TIMS data from the Carlin area and the northern Grapevine Mountains, Nevada

NASA Technical Reports Server (NTRS)

Watson, Ken; Hummer-Miller, Susanne; Kruse, Fred A.

1986-01-01

A theoretical radiance model was employed together with laboratory data on a suite of igneous rock to evaluate various algorithms for processing Thermal Infrared Multispectral Scanner (TIMS) data. Two aspects of the general problem were examined: extraction of emissivity information from the observed TIMS radiance data, and how to use emissivity data in a way that is geologically meaningful. The four algorithms were evaluated for appropriate band combinations of TIMS data acquired on both day and night overflights of the Tuscarora Mountains, including the Carlin gold deposit, in north-central Nevada. Analysis of a color composited PC decorrelated image (Bands 3, 4, 5--blue/green/red) of the Northern Grapevine Mountains, Nevada, area showed some useful correlation with the regional geology. The thermal infrared region provides fundamental spectral information that can be used to discriminate the major rock types occurring on the Earth's surface.

Enhanced upper genital tract pathologies by blocking Tim-3 and PD-L1 signaling pathways in mice intravaginally infected with Chlamydia muridarum.

PubMed

Peng, Bo; Lu, Chunxue; Tang, Lingli; Yeh, I-Tien; He, Zhimin; Wu, Yimou; Zhong, Guangming

2011-12-14

Although Tim-3 & PD-L1 signaling pathways play important roles in negatively regulating immune responses, their roles in chlamydial infection have not been evaluated. Neutralization antibodies targeting Tim-3 and PD-L1 were used to treat mice. Following an intravaginal infection with C. muridarum organisms, mice with or without the dual antibody treatment were compared for live chlamydial organism shedding from the lower genital tract and inflammatory pathology in the upper genital tract. Mice treated with anti-Tim-3 and anti-PD-L1 antibodies displayed a time course of live organism shedding similar to that of mice treated with equivalent amounts of isotype-matched IgG molecules. The combined antibody blocking failed to alter either the lower genital tract cytokine or systemic humoral and cellular adaptive responses to C. muridarum infection. However, the antibody blocking significantly enhanced C. muridarum-induced pathologies in the upper genital tract, including more significant hydrosalpinx and inflammatory infiltration in uterine horn and oviduct tissues. The Tim-3 and PD-L1-mediated signaling can significantly reduce pathologies in the upper genital tract without suppressing immunity against chlamydial infection, suggesting that Tim-3 and PD-L1-mediated negative regulation may be manipulated to attenuate tubal pathologies in women persistently infected with C. trachomatis organisms.

Tim-3 expression on PD-1+ HCV-specific human CTLs is associated with viral persistence, and its blockade restores hepatocyte-directed in vitro cytotoxicity

PubMed Central

McMahan, Rachel H.; Golden-Mason, Lucy; Nishimura, Michael I.; McMahon, Brian J.; Kemper, Michael; Allen, Todd M.; Gretch, David R.; Rosen, Hugo R.

2010-01-01

Having successfully developed mechanisms to evade immune clearance, hepatitis C virus (HCV) establishes persistent infection in approximately 75%–80% of patients. In these individuals, the function of HCV-specific CD8+ T cells is impaired by ligation of inhibitory receptors, the repertoire of which has expanded considerably in the past few years. We hypothesized that the coexpression of the negative regulatory receptors T cell immunoglobulin and mucin domain–containing molecule 3 (Tim-3) and programmed death 1 (PD-1) in HCV infection would identify patients at risk of developing viral persistence during and after acute HCV infection. The frequency of PD-1–Tim-3– HCV-specific CTLs greatly outnumbered PD-1+Tim-3+ CTLs in patients with acute resolving infection. Moreover, the population of PD-1+Tim-3+ T cells was enriched for within the central memory T cell subset and within the liver. Blockade of either PD-1 or Tim-3 enhanced in vitro proliferation of HCV-specific CTLs to a similar extent, whereas cytotoxicity against a hepatocyte cell line that expressed cognate HCV epitopes was increased exclusively by Tim-3 blockade. These results indicate that the coexpression of these inhibitory molecules tracks with defective T cell responses and that anatomical differences might account for lack of immune control of persistent pathogens, which suggests their manipulation may represent a rational target for novel immunotherapeutic approaches. PMID:21084749

Up-regulated expression of Tim-3/Gal-9 at maternal-fetal interface in pregnant woman with recurrent spontaneous abortion.

PubMed

Li, Jing; Li, Fan-fan; Zuo, Wei; Zhou, Yuan; Hao, Hai-yan; Dang, Jing; Jiang, Min; He, Meng-zhou; Deng, Dong-rui

2014-08-01

The relationship between T cell immunoglobulin domain and mucin domain protein 3 (Tim-3)/Galectin (Gal)-9 pathway and recurrent spontaneous abortion (RSA) was studied. Thirty-one pregnant women with RSA and 27 normal early gravidas were investigated to detect the levels of Tim-3 and Gal-9 in villi and deciduas by Western blotting. Meanwhile, the concentration of interleukin (IL)-4 and IL-12 in peripheral blood plasma was determined by ELISA in 25 healthy fertile non-pregnant controls, the normal early gravidas and pregnant women with RSA mentioned above, respectively. It was found that the relative expression levels of Tim-3 and Gal-9 in villi and deciduas were significantly increased in pregnant women with RSA as compared with those in the normal early gravidas. The concentration of IL-4 in peripheral blood plasma of pregnant women with RSA was lower than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05), but that of IL-2 in pregnant women with RSA was significantly higher than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05). It was suggested that the overexpression of Tim-3/Gal-9 pathway may be related to the pathogenesis of RSA.

Space Solar Power Technical Interchange Meeting 2: SSP TIM 2

NASA Technical Reports Server (NTRS)

Sanders, Jim; Hawk, Clark W.

1998-01-01

The 2nd Space Solar Power Technical Interchange Meeting (SSP TIM 2) was conducted September 21st through 24th with the first part consisting of a Plenary session. The summary results of this Plenary session are contained in part one of this report. The attendees were then organized into Working Breakout Sessions and Integrated Product Team (IPT) Sessions for the purpose of conducting in-depth discussions in specific topic areas and developing a consensus as to appropriate study plans and actions to be taken. The Second part covers the Plenary Summary Session, which contains the summary results of the Working Breakout Sessions and IPT Sessions. The appendix contains the list of attendees. The ob'jective was to provide an update for the study teams and develop plans for subsequent study activities. This SSP TIM 2 was initiated and the results reported electronically over the Internet. The International Space Station (ISS) could provide the following opportunities for conducting research and technology (R&T) which are applicable to SSP: (1) Automation and Robotics, (2) Advanced Power Generation, (3) Advanced Power Management & Distribution (PMAD), (4) Communications Systems and Networks, (5) Energy Storage, (6) In Space Propulsion (ISP), (7) Structural Dynamics and Control, and Assembly and (8) Wireless Power Transmission.

Reading and Understanding: Tim O'Brien and the Narrative of Failure

ERIC Educational Resources Information Center

Buchanan, Jeffrey

2008-01-01

Tim O'Brien's "The Things They Carried" is an example of what the author calls a narrative of failure. A narrative of failure is a term for a narrative that both fails in the enactment of its own telling and that takes failure or failing as one of its subjects. This paper discusses how, as a form for telling a teaching story, narratives…

Detection and mapping of volcanic rock assemblages and associated hydrothermal alteration with Thermal Infrared Multiband Scanner (TIMS) data Comstock Lode Mining District, Virginia City, Nevada

NASA Technical Reports Server (NTRS)

Taranik, James V.; Hutsinpiller, Amy; Borengasser, Marcus

1986-01-01

Thermal Infrared Multispectral Scanner (TIMS) data were acquired over the Virginia City area on September 12, 1984. The data were acquired at approximately 1130 hours local time (1723 IRIG). The TIMS data were analyzed using both photointerpretation and digital processing techniques. Karhuen-Loeve transformations were utilized to display variations in radiant spectral emittance. The TIMS image data were compared with color infrared metric camera photography, LANDSAT Thematic Mapper (TM) data, and key areas were photographed in the field.

Targeting Tim-1 to Circumvent Immune Tolerance in Prostate Cancer

DTIC Science & Technology

2012-09-01

findings that SIM2 is selectively expressed in PCa, that human HLA- A2.1–restricted SIM2 epitopes induce specific T cells in vivo, and that anti -SIM2...TAA, would include a vaccine in conjunction with biologic agents that are known to simultaneously augment antigen presentation by DCs and inhibit...such agents is the agonist antibody that targets TIM-1, a receptor expressed on lymphocytes and dendritic cells that enhances cytotoxic lymphocyte

User-friendly traffic incident management (TIM) program benefit-cost estimation tool, Version 1.2

DOT National Transportation Integrated Search

2016-01-01

Traffic incidents contribute significantly to the deterioration of the level of service of both freeways and arterials. Traffic Incident Management (TIM) programs have been introduced worldwide with the aim of mitigating the impact of traffic inciden...

Project TIMS (Teaching Integrated Math/Science)

NASA Technical Reports Server (NTRS)

Edwards, Leo, Jr.

1993-01-01

The goal of this project is to increase the scientific knowledge and appreciation bases and skills of pre-service and in-service middle school teachers, so as to impact positively on teaching, learning, and student retention. This report lists the objectives and summarizes the progress thus far. Included is the working draft of the TIMS (Teaching Integrated Math/Science) curriculum outline. Seven of the eight instructional subject-oriented modules are also included. The modules include informative materials and corresponding questions and educational activities in a textbook format. The subjects included here are the universe and stars; the sun and its place in the universe; our solar system; astronomical instruments and scientific measurements; the moon and eclipses; the earth's atmosphere: its nature and composition; and the earth: directions, time, and seasons. The module not included regards winds and circulation.

The auto-inhibitory state of Rho guanine nucleotide exchange factor ARHGEF5/TIM can be relieved by targeting its SH3 domain with rationally designed peptide aptamers.

PubMed

He, Ping; Tan, De-Li; Liu, Hong-Xiang; Lv, Feng-Lin; Wu, Wei

2015-04-01

The short isoform of Rho guanine nucleotide exchange factor ARHGEF5 is known as TIM, which plays diverse roles in, for example, tumorigenesis, neuronal development and Src-induced podosome formation through the activation of its substrates, the Rho family of GTPases. The activation is auto-inhibited by a putative helix N-terminal to the DH domain of TIM, which is stabilized by the intramolecular interaction of C-terminal SH3 domain with a poly-proline sequence between the putative helix and the DH domain. In this study, we systematically investigated the structural basis, energetic landscape and biological implication underlying TIM auto-inhibition by using atomistic molecular dynamics simulations and binding free energy analysis. The computational study revealed that the binding of SH3 domain to poly-proline sequence is the prerequisite for the stabilization of TIM auto-inhibition. Thus, it is suggested that targeting SH3 domain with competitors of the poly-proline sequence would be a promising strategy to relieve the auto-inhibitory state of TIM. In this consideration, we rationally designed a number of peptide aptamers for competitively inhibiting the SH3 domain based on modeled TIM structure and computationally generated data. Peptide binding test and guanine nucleotide exchange analysis solidified that these designed peptides can both bind to the SH3 domain potently and activate TIM-catalyzed RhoA exchange reaction effectively. Interestingly, a positive correlation between the peptide affinity and induced exchange activity was observed. In addition, separate mutation of three conserved residues Pro49, Pro52 and Lys54 - they are required for peptide recognition by SH3 domain -- in a designed peptide to Ala would completely abolish the capability of this peptide activating TIM. All these come together to suggest an intrinsic relationship between peptide binding to SH3 domain and the activation of TIM. Copyright © 2015 Elsevier B.V. and Société Française de

Investigation of T-cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) polymorphisms in essential thrombocythaemia (ET).

PubMed

Han, Fuyan; Wang, Guanghai; Li, Yuantang; Tian, Wenjun; Dong, Zhenfang; Cheng, Shiqing; Liu, Yiqing; Qu, Teng; Wang, Xiaoying; Wang, Yong; Zhang, Bingchang; Ju, Ying

2017-07-01

T-cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) is preferentially expressed on terminally differentiated Th1 cells and inhibits their IFN-γ production. It has been reported that chronic inflammation may be an important driving force for myeloproliferative neoplasms (MPNs). Therefore, we hypothesized that as an important inflammation regulator, TIM-3 may be involved in essential thrombocythaemia (ET). The goal of this study was to investigate whether the -1516G > T, -574G > T and +4259T > G single-nucleotide polymorphisms (SNPs) within the TIM-3 gene contribute to the genetic susceptibility of individuals to ET. Genotyping of the TIM-3 -1516G > T, -574G > T and + 4259T > G SNPs was performed in 175 patients with ET and in 151 controls via a polymerase chain reaction-restriction fragment length polymorphism assay. We also investigated the relationships between the genotypes of each SNP and the risk factors of ET such as routine blood indexes, age and JAK2 V617F mutation. The genotype and allele frequencies of the -1516G > T SNP (p = 0.016 and 0.019, respectively), the -574G > T SNP (p = 0.035 and 0.038, respectively) and the +4259T > G SNP (p = 0.036 and 0.038, respectively) of the ET patients and the controls were significantly different. A haplotype analysis found that the GGT and TGT haplotypes had significantly different distributions between ET and controls (p = 0.041 and 0.041, respectively). However, no significant differences were detected between the genotypes of all SNPs and routine blood indexes, age and JAK2V617F mutation. The -1516G > T, -574G > T and +4259T > G SNPs within TIM-3 gene might play an important role as a genetic risk factor in the pathogenesis of ET.

Tim-3-expressing macrophages are functionally suppressed and expanded in oral squamous cell carcinoma due to virus-induced Gal-9 expression.

PubMed

Dong, Jianfeng; Cheng, Lijun; Zhao, Minchao; Pan, Xiangfeng; Feng, Zhiqiang; Wang, Dawei

2017-05-01

Oropharyngeal head and neck squamous cell carcinoma is a common malignant tumor in the oral cavity. High-risk human papillomavirus 16 infection is a major cause of oropharyngeal head and neck squamous cell carcinoma development. Strong antitumor immune responses, especially CD8 + T cell responses, are thought to be essential to effective cancer treatment and are associated with better prognosis in oropharyngeal head and neck squamous cell carcinoma. In this study, we examined the role of the Tim-3/Gal-9 pathway in oropharyngeal head and neck squamous cell carcinoma patients. We found that Gal-9 expression by CD4 + T cells was increased in human papillomavirus-positive oropharyngeal head and neck squamous cell carcinoma patients, but not in human papillomavirus-negative oropharyngeal head and neck squamous cell carcinoma patients. Increased Gal-9 secretion by CD4 + T cells presented multiple immunosuppressive effects. Coculturing monocytes with high Gal-9-expressing CD4 + T cells resulted in the expansion of Tim-3 + monocytes, which suppressed interferon gamma production by activated CD8 + T cells. Subsequently, total monocytes incubated with exogenous Gal-9, or high Gal-9-expressing CD4 + T cells, suppressed the expression of interferon gamma by CD8 + T cells. Exogenous Gal-9 and high Gal-9-expressing CD4 + T cells also suppressed the secretion of both interleukin 10 and interleukin 12 by monocytes. These effects are Tim-3/Gal-9-dependent because blocking Tim-3 and/or Gal-9 could enhance the support of CD8 + T cell interferon gamma production and the interleukin 10 and interleukin 12 secretion by monocytes. Together, these data suggest that the high Tim-3 expression in monocytes could be utilized by tumor-promoting Gal-9 expression on CD4 + T cells. Immunotherapy in human papillomavirus-positive oropharyngeal head and neck squamous cell carcinoma patients therefore faces an additional challenge posed by Tim-3 and Gal-9 and likely requires the blockade of these

Structural analysis on mutation residues and interfacial water molecules for human TIM disease understanding

PubMed Central

2013-01-01

Background Human triosephosphate isomerase (HsTIM) deficiency is a genetic disease caused often by the pathogenic mutation E104D. This mutation, located at the side of an abnormally large cluster of water in the inter-subunit interface, reduces the thermostability of the enzyme. Why and how these water molecules are directly related to the excessive thermolability of the mutant have not been investigated in structural biology. Results This work compares the structure of the E104D mutant with its wild type counterparts. It is found that the water topology in the dimer interface of HsTIM is atypical, having a "wet-core-dry-rim" distribution with 16 water molecules tightly packed in a small deep region surrounded by 22 residues including GLU104. These water molecules are co-conserved with their surrounding residues in non-archaeal TIMs (dimers) but not conserved across archaeal TIMs (tetramers), indicating their importance in preserving the overall quaternary structure. As the structural permutation induced by the mutation is not significant, we hypothesize that the excessive thermolability of the E104D mutant is attributed to the easy propagation of atoms' flexibility from the surface into the core via the large cluster of water. It is indeed found that the B factor increment in the wet region is higher than other regions, and, more importantly, the B factor increment in the wet region is maintained in the deeply buried core. Molecular dynamics simulations revealed that for the mutant structure at normal temperature, a clear increase of the root-mean-square deviation is observed for the wet region contacting with the large cluster of interfacial water. Such increase is not observed for other interfacial regions or the whole protein. This clearly suggests that, in the E104D mutant, the large water cluster is responsible for the subunit interface flexibility and overall thermolability, and it ultimately leads to the deficiency of this enzyme. Conclusions Our study

High-precision isotopic characterization of USGS reference materials by TIMS and MC-ICP-MS

NASA Astrophysics Data System (ADS)

Weis, Dominique; Kieffer, Bruno; Maerschalk, Claude; Barling, Jane; de Jong, Jeroen; Williams, Gwen A.; Hanano, Diane; Pretorius, Wilma; Mattielli, Nadine; Scoates, James S.; Goolaerts, Arnaud; Friedman, Richard M.; Mahoney, J. Brian

2006-08-01

The Pacific Centre for Isotopic and Geochemical Research (PCIGR) at the University of British Columbia has undertaken a systematic analysis of the isotopic (Sr, Nd, and Pb) compositions and concentrations of a broad compositional range of U.S. Geological Survey (USGS) reference materials, including basalt (BCR-1, 2; BHVO-1, 2), andesite (AGV-1, 2), rhyolite (RGM-1, 2), syenite (STM-1, 2), granodiorite (GSP-2), and granite (G-2, 3). USGS rock reference materials are geochemically well characterized, but there is neither a systematic methodology nor a database for radiogenic isotopic compositions, even for the widely used BCR-1. This investigation represents the first comprehensive, systematic analysis of the isotopic composition and concentration of USGS reference materials and provides an important database for the isotopic community. In addition, the range of equipment at the PCIGR, including a Nu Instruments Plasma MC-ICP-MS, a Thermo Finnigan Triton TIMS, and a Thermo Finnigan Element2 HR-ICP-MS, permits an assessment and comparison of the precision and accuracy of isotopic analyses determined by both the TIMS and MC-ICP-MS methods (e.g., Nd isotopic compositions). For each of the reference materials, 5 to 10 complete replicate analyses provide coherent isotopic results, all with external precision below 30 ppm (2 SD) for Sr and Nd isotopic compositions (27 and 24 ppm for TIMS and MC-ICP-MS, respectively). Our results also show that the first- and second-generation USGS reference materials have homogeneous Sr and Nd isotopic compositions. Nd isotopic compositions by MC-ICP-MS and TIMS agree to within 15 ppm for all reference materials. Interlaboratory MC-ICP-MS comparisons show excellent agreement for Pb isotopic compositions; however, the reproducibility is not as good as for Sr and Nd. A careful, sequential leaching experiment of three first- and second-generation reference materials (BCR, BHVO, AGV) indicates that the heterogeneity in Pb isotopic compositions

Tim-3 is a Marker of Plasmacytoid Dendritic Cell Dysfunction during HIV Infection and Is Associated with the Recruitment of IRF7 and p85 into Lysosomes and with the Submembrane Displacement of TLR9.

PubMed

Schwartz, Jordan Ari; Clayton, Kiera L; Mujib, Shariq; Zhang, Hongliang; Rahman, A K M Nur-Ur; Liu, Jun; Yue, Feng Yun; Benko, Erika; Kovacs, Colin; Ostrowski, Mario A

2017-04-15

In chronic diseases, such as HIV infection, plasmacytoid dendritic cells (pDCs) are rendered dysfunctional, as measured by their decreased capacity to produce IFN-α. In this study, we identified elevated levels of T cell Ig and mucin-domain containing molecule-3 (Tim-3)-expressing pDCs in the blood of HIV-infected donors. The frequency of Tim-3-expressing pDCs correlated inversely with CD4 T cell counts and positively with HIV viral loads. A lower frequency of pDCs expressing Tim-3 produced IFN-α or TNF-α in response to the TLR7 agonists imiquimod and Sendai virus and to the TLR9 agonist CpG. Thus, Tim-3 may serve as a biomarker of pDC dysfunction in HIV infection. The source and function of Tim-3 was investigated on enriched pDC populations from donors not infected with HIV. Tim-3 induction was achieved in response to viral and artificial stimuli, as well as exogenous IFN-α, and was PI3K dependent. Potent pDC-activating stimuli, such as CpG, imiquimod, and Sendai virus, induced the most Tim-3 expression and subsequent dysfunction. Small interfering RNA knockdown of Tim-3 increased IFN-α secretion in response to activation. Intracellular Tim-3, as measured by confocal microscopy, was dispersed throughout the cytoplasm prior to activation. Postactivation, Tim-3 accumulated at the plasma membrane and associated with disrupted TLR9 at the submembrane. Tim-3-expressing pDCs had reduced IRF7 levels. Furthermore, intracellular Tim-3 colocalized with p85 and IRF7 within LAMP1 + lysosomes, suggestive of a role in degradation. We conclude that Tim-3 is a biomarker of dysfunctional pDCs and may negatively regulate IFN-α, possibly through interference with TLR signaling and recruitment of IRF7 and p85 into lysosomes, enhancing their degradation. Copyright © 2017 by The American Association of Immunologists, Inc.

A novel method for sampling the suspended sediment load in the tidal environment using bi-directional time-integrated mass-flux sediment (TIMS) samplers

NASA Astrophysics Data System (ADS)

Elliott, Emily A.; Monbureau, Elaine; Walters, Glenn W.; Elliott, Mark A.; McKee, Brent A.; Rodriguez, Antonio B.

2017-12-01

Identifying the source and abundance of sediment transported within tidal creeks is essential for studying the connectivity between coastal watersheds and estuaries. The fine-grained suspended sediment load (SSL) makes up a substantial portion of the total sediment load carried within an estuarine system and efficient sampling of the SSL is critical to our understanding of nutrient and contaminant transport, anthropogenic influence, and the effects of climate. Unfortunately, traditional methods of sampling the SSL, including instantaneous measurements and automatic samplers, can be labor intensive, expensive and often yield insufficient mass for comprehensive geochemical analysis. In estuaries this issue is even more pronounced due to bi-directional tidal flow. This study tests the efficacy of a time-integrated mass sediment sampler (TIMS) design, originally developed for uni-directional flow within the fluvial environment, modified in this work for implementation the tidal environment under bi-directional flow conditions. Our new TIMS design utilizes an 'L' shaped outflow tube to prevent backflow, and when deployed in mirrored pairs, each sampler collects sediment uniquely in one direction of tidal flow. Laboratory flume experiments using dye and particle image velocimetry (PIV) were used to characterize the flow within the sampler, specifically, to quantify the settling velocities and identify stagnation points. Further laboratory tests of sediment indicate that bidirectional TIMS capture up to 96% of incoming SSL across a range of flow velocities (0.3-0.6 m s-1). The modified TIMS design was tested in the field at two distinct sampling locations within the tidal zone. Single-time point suspended sediment samples were collected at high and low tide and compared to time-integrated suspended sediment samples collected by the bi-directional TIMS over the same four-day period. Particle-size composition from the bi-directional TIMS were representative of the array of

Integrated Modeling System for Analysis of Watershed Water Balance: A Case Study in the Tims Branch Watershed, South Carolina

NASA Astrophysics Data System (ADS)

Setegn, S. G.; Mahmoudi, M.; Lawrence, A.; Duque, N.

2015-12-01

The Applied Research Center at Florida International University (ARC-FIU) is supporting the soil and groundwater remediation efforts of the U.S. Department of Energy (DOE) Savannah River Site (SRS) by developing a surface water model to simulate the hydrology and the fate and transport of contaminants and sediment in the Tims Branch watershed. Hydrological models are useful tool in water and land resource development and decision-making for watershed management. Moreover, simulation of hydrological processes improves understanding of the environmental dynamics and helps to manage and protect water resources and the environment. MIKE SHE, an advanced integrated modeling system is used to simulate the hydrological processes of the Tim Branch watershed with the objective of developing an integrated modeling system to improve understanding of the physical, chemical and biological processes within the Tims Branch watershed. MIKE SHE simulates water flow in the entire land based phase of the hydrological cycle from rainfall to river flow, via various flow processes such as, overland flow, infiltration, evapotranspiration, and groundwater flow. In this study a MIKE SHE model is developed and applied to the Tim branch watershed to study the watershed response to storm events and understand the water balance of the watershed under different climatic and catchment characteristics. The preliminary result of the integrated model indicated that variation in the depth of overland flow highly depend on the amount and distribution of rainfall in the watershed. The ultimate goal of this project is to couple the MIKE SHE and MIKE 11 models to integrate the hydrological component in the land phase of hydrological cycle and stream flow process. The coupled MIKE SHE/MIKE 11 model will further be integrated with an Ecolab module to represent a range of water quality, contaminant transport, and ecological processes with respect to the stream, surface water and groundwater in the Tims

Correlation of fitness landscapes from three orthologous TIM barrels originates from sequence and structure constraints

PubMed Central

Chan, Yvonne H.; Venev, Sergey V.; Zeldovich, Konstantin B.; Matthews, C. Robert

2017-01-01

Sequence divergence of orthologous proteins enables adaptation to environmental stresses and promotes evolution of novel functions. Limits on evolution imposed by constraints on sequence and structure were explored using a model TIM barrel protein, indole-3-glycerol phosphate synthase (IGPS). Fitness effects of point mutations in three phylogenetically divergent IGPS proteins during adaptation to temperature stress were probed by auxotrophic complementation of yeast with prokaryotic, thermophilic IGPS. Analysis of beneficial mutations pointed to an unexpected, long-range allosteric pathway towards the active site of the protein. Significant correlations between the fitness landscapes of distant orthologues implicate both sequence and structure as primary forces in defining the TIM barrel fitness landscape and suggest that fitness landscapes can be translocated in sequence space. Exploration of fitness landscapes in the context of a protein fold provides a strategy for elucidating the sequence-structure-fitness relationships in other common motifs. PMID:28262665

Qualification of heavy water based irradiation device in the JSI TRIGA reactor for irradiations of FT-TIMS samples for nuclear safeguards

NASA Astrophysics Data System (ADS)

Radulović, Vladimir; Kolšek, Aljaž; Fauré, Anne-Laure; Pottin, Anne-Claire; Pointurier, Fabien; Snoj, Luka

2018-03-01

The Fission Track Thermal Ionization Mass Spectrometry (FT-TIMS) method is considered as the reference method for particle analysis in the field of nuclear Safeguards for measurements of isotopic compositions (fissile material enrichment levels) in micrometer-sized uranium particles collected in nuclear facilities. An integral phase in the method is the irradiation of samples in a very well thermalized neutron spectrum. A bilateral collaboration project was carried out between the Jožef Stefan Institute (JSI, Slovenia) and the Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA, France) to determine whether the JSI TRIGA reactor could be used for irradiations of samples for the FT-TIMS method. This paper describes Monte Carlo simulations, experimental activation measurements and test irradiations performed in the JSI TRIGA reactor, firstly to determine the feasibility, and secondly to design and qualify a purpose-built heavy water based irradiation device for FT-TIMS samples. The final device design has been shown experimentally to meet all the required performance specifications.

A monomeric TIM-barrel structure from Pyrococcus furiosus is optimized for extreme temperatures.

PubMed

Repo, Heidi; Oeemig, Jesper S; Djupsjöbacka, Janica; Iwaï, Hideo; Heikinheimo, Pirkko

2012-11-01

The structure of phosphoribosyl anthranilate isomerase (TrpF) from the hyperthermophilic archaeon Pyrococcus furiosus (PfTrpF) has been determined at 1.75 Å resolution. The PfTrpF structure has a monomeric TIM-barrel fold which differs from the dimeric structures of two other known thermophilic TrpF proteins. A comparison of the PfTrpF structure with the two known bacterial thermophilic TrpF structures and the structure of a related mesophilic protein from Escherichia coli (EcTrpF) is presented. The thermophilic TrpF structures contain a higher proportion of ion pairs and charged residues compared with the mesophilic EcTrpF. These residues contribute to the closure of the central barrel and the stabilization of the barrel and the surrounding α-helices. In the monomeric PfTrpF conserved structural water molecules are mostly absent; instead, the structural waters are replaced by direct side-chain-main-chain interactions. As a consequence of these combined mechanisms, the P. furiosus enzyme is a thermodynamically stable and entropically optimized monomeric TIM-barrel enzyme which defines a good framework for further protein engineering for industrial applications.

Enhanced ionization efficiency in TIMS analyses of plutonium and americium using porous ion emitters

DOE PAGES

Baruzzini, Matthew L.; Hall, Howard L.; Watrous, Matthew G.; ...

2016-12-05

Investigations of enhanced sample utilization in thermal ionization mass spectrometry (TIMS) using porous ion emitter (PIE) techniques for the analyses of trace quantities of americium and plutonium were performed. Repeat ionization efficiency (i.e., the ratio of ions detected to atoms loaded on the filament) measurements were conducted on sample sizes ranging from 10–100 pg for americium and 1–100 pg for plutonium using PIE and traditional (i.e., a single, zone-refined rhenium, flat filament ribbon with a carbon ionization enhancer) TIMS filament sources. When compared to traditional filaments, PIEs exhibited an average boost in ionization efficiency of ~550% for plutonium and ~1100%more » for americium. A maximum average efficiency of 1.09% was observed at a 1 pg plutonium sample loading using PIEs. Supplementary trials were conducted using newly developed platinum PIEs to analyze 10 pg mass loadings of plutonium. As a result, platinum PIEs exhibited an additional ~134% boost in ion yield over standard PIEs and ~736% over traditional filaments at the same sample loading level.« less

Approaches to vegetation mapping and ecophysiological hypothesis testing using combined information from TIMS, AVIRIS, and AIRSAR

NASA Technical Reports Server (NTRS)

Oren, R.; Vane, G.; Zimmermann, R.; Carrere, V.; Realmuto, V.; Zebker, Howard A.; Schoeneberger, P.; Schoeneberger, M.

1991-01-01

The Tropical Rainforest Ecology Experiment (TREE) had two primary objectives: (1) to design a method for mapping vegetation in tropical regions using remote sensing and determine whether the result improves on available vegetation maps; and (2) to test a specific hypothesis on plant/water relations. Both objectives were thought achievable with the combined information from the Thermal Infrared Multispectral Scanner (TIMS), Airborne Visible/Infrared Imaging Spectrometer (AVIRIS), and Airborne Synthetic Aperture Radar (AIRSAR). Implicitly, two additional objectives were: (1) to ascertain that the range within each variable potentially measurable with the three instruments is large enough in the site, relative to the sensitivity of the instruments, so that differences between ecological groups may be detectable; and (2) to determine the ability of the three systems to quantify different variables and sensitivities. We found that the ranges in values of foliar nitrogen concentration, water availability, stand structure and species composition, and plant/water relations were large, even within the upland broadleaf vegetation type. The range was larger when other vegetation types were considered. Unfortunately, cloud cover and navigation errors compromised the utility of the TIMS and AVIRIS data. Nevertheless, the AIRSAR data alone appear to have improved on the available vegetation map for the study area. An example from an area converted to a farm is given to demonstrate how the combined information from AIRSAR, TIMS, and AVIRIS can uniquely identify distinct classes of land use. The example alludes to the potential utility of the three instruments for identifying vegetation at an ecological scale finer than vegetation types.

The nucleotide exchange factor MGE exerts a key function in the ATP-dependent cycle of mt-Hsp70-Tim44 interaction driving mitochondrial protein import.

PubMed Central

Schneider, H C; Westermann, B; Neupert, W; Brunner, M

1996-01-01

Import of preproteins into the mitochondrial matrix is driven by the ATP-dependent interaction of mt-Hsp70 with the peripheral inner membrane import protein Tim44 and the preprotein in transit. We show that Mge1p, a co-chaperone of mt-Hsp70, plays a key role in the ATP-dependent import reaction cycle in yeast. Our data suggest a cycle in which the mt-Hsp70-Tim44 complex forms with ATP: Mge1p promotes assembly of the complex in the presence of ATP. Hydrolysis of ATP by mt-Hsp70 occurs in complex with Tim44. Mge1p is then required for the dissociation of the ADP form of mt-Hsp70 from Tim44 after release of inorganic phosphate but before release of ADP. ATP hydrolysis and complex dissociation are accompanied by tight binding of mt-Hsp70 to the preprotein in transit. Subsequently, the release of mt-Hsp70 from the polypeptide chain is triggered by Mge1p which promotes release of ADP from mt-Hsp70. Rebinding of ATP to mt-Hsp70 completes the reaction cycle. Images PMID:8918457

Isotope ratios of trace elements in samples from human nutrition studies determined by TIMS and ICP-MS: precision and accuracy compared.

PubMed

Turnlund, Judith R; Keyes, William R

2002-09-01

Stable isotopes are used with increasing frequency to trace the metabolic fate of minerals in human nutrition studies. The precision of the analytical methods used must be sufficient to permit reliable measurement of low enrichments and the accuracy should permit comparisons between studies. Two methods most frequently used today are thermal ionization mass spectrometry (TIMS) and inductively coupled plasma mass spectrometry (ICP-MS). This study was conducted to compare the two methods. Multiple natural samples of copper, zinc, molybdenum, and magnesium were analyzed by both methods to compare their internal and external precision. Samples with a range of isotopic enrichments that were collected from human studies or prepared from standards were analyzed to compare their accuracy. TIMS was more precise and accurate than ICP-MS. However, the cost, ease, and speed of analysis were better for ICP-MS. Therefore, for most purposes, ICP-MS is the method of choice, but when the highest degrees of precision and accuracy are required and when enrichments are very low, TIMS is the method of choice.

The Filmmaker as Humanist: An Interview with Tim Robbins on the Making of "Cradle Will Rock".

ERIC Educational Resources Information Center

Mason, Terrence C.

2000-01-01

Presents an interview with Tim Robbins that focuses on the making of the film "Cradle Will Rock." Robbins offers his perspectives on issues such as the power of art to convey important social messages and sources of violence in schools. Includes resources for teachers. (CMK)

easyDAS: Automatic creation of DAS servers

PubMed Central

2011-01-01

Background The Distributed Annotation System (DAS) has proven to be a successful way to publish and share biological data. Although there are more than 750 active registered servers from around 50 organizations, setting up a DAS server comprises a fair amount of work, making it difficult for many research groups to share their biological annotations. Given the clear advantage that the generalized sharing of relevant biological data is for the research community it would be desirable to facilitate the sharing process. Results Here we present easyDAS, a web-based system enabling anyone to publish biological annotations with just some clicks. The system, available at http://www.ebi.ac.uk/panda-srv/easydas is capable of reading different standard data file formats, process the data and create a new publicly available DAS source in a completely automated way. The created sources are hosted on the EBI systems and can take advantage of its high storage capacity and network connection, freeing the data provider from any network management work. easyDAS is an open source project under the GNU LGPL license. Conclusions easyDAS is an automated DAS source creation system which can help many researchers in sharing their biological data, potentially increasing the amount of relevant biological data available to the scientific community. PMID:21244646

Alternative Splice Variants in TIM Barrel Proteins from Human Genome Correlate with the Structural and Evolutionary Modularity of this Versatile Protein Fold

PubMed Central

Ochoa-Leyva, Adrián; Montero-Morán, Gabriela; Saab-Rincón, Gloria; Brieba, Luis G.; Soberón, Xavier

2013-01-01

After the surprisingly low number of genes identified in the human genome, alternative splicing emerged as a major mechanism to generate protein diversity in higher eukaryotes. However, it is still not known if its prevalence along the genome evolution has contributed to the overall functional protein diversity or if it simply reflects splicing noise. The (βα)8 barrel or TIM barrel is one of the most frequent, versatile, and ancient fold encountered among enzymes. Here, we analyze the structural modifications present in TIM barrel proteins from the human genome product of alternative splicing events. We found that 87% of all splicing events involved deletions; most of these events resulted in protein fragments that corresponded to the (βα)2, (βα)4, (βα)5, (βα)6, and (βα)7 subdomains of TIM barrels. Because approximately 7% of all the splicing events involved internal β-strand substitutions, we decided, based on the genomic data, to design β-strand and α-helix substitutions in a well-studied TIM barrel enzyme. The biochemical characterization of one of the chimeric variants suggests that some of the splice variants in the human genome with β-strand substitutions may be evolving novel functions via either the oligomeric state or substrate specificity. We provide results of how the splice variants represent subdomains that correlate with the independently folding and evolving structural units previously reported. This work is the first to observe a link between the structural features of the barrel and a recurrent genetic mechanism. Our results suggest that it is reasonable to expect that a sizeable fraction of splice variants found in the human genome represent structurally viable functional proteins. Our data provide additional support for the hypothesis of the origin of the TIM barrel fold through the assembly of smaller subdomains. We suggest a model of how nature explores new proteins through alternative splicing as a mechanism to diversify the

Simultaneous determination of the quantity and isotopic ratios of uranium in individual micro-particles by isotope dilution thermal ionization mass spectrometry (ID-TIMS).

PubMed

Park, Jong-Ho; Choi, Eun-Ju

2016-11-01

A method to determine the quantity and isotopic ratios of uranium in individual micro-particles simultaneously by isotope dilution thermal ionization mass spectrometry (ID-TIMS) has been developed. This method consists of sequential sample and spike loading, ID-TIMS for isotopic measurement, and application of a series of mathematical procedures to remove the contribution of uranium in the spike. The homogeneity of evaporation and ionization of uranium content was confirmed by the consistent ratio of n((233)U)/n((238)U) determined by TIMS measurements. Verification of the method was performed using U030 solution droplets and U030 particles. Good agreements of resulting uranium quantity, n((235)U)/n((238)U), and n((236)U)/n((238)U) with the estimated or certified values showed the validity of this newly developed method for particle analysis when simultaneous determination of the quantity and isotopic ratios of uranium is required. Copyright © 2016 Elsevier B.V. All rights reserved.

Quantitative estimation of granitoid composition from thermal infrared multispectral scanner (TIMS) data, Desolation Wilderness, northern Sierra Nevada, California

NASA Technical Reports Server (NTRS)

Sabine, Charles; Realmuto, Vincent J.; Taranik, James V.

1994-01-01

We have produced images that quantitatively depict modal and chemical parameters of granitoids using an image processing algorithm called MINMAP that fits Gaussian curves to normalized emittance spectra recovered from thermal infrared multispectral scanner (TIMS) radiance data. We applied the algorithm to TIMS data from the Desolation Wilderness, an extensively glaciated area near the northern end of the Sierra Nevada batholith that is underlain by Jurassic and Cretaceous plutons that range from diorite and anorthosite to leucogranite. The wavelength corresponding to the calculated emittance minimum lambda(sub min) varies linearly with quartz content, SiO2, and other modal and chemical parameters. Thematic maps of quartz and silica content derived from lambda(sub min) values distinguish bodies of diorite from surrounding granite, identify outcrops of anorthosite, and separate felsic, intermediate, and mafic rocks.

Acute myeloid leukemia stem cell markers in prognosis and targeted therapy: potential impact of BMI-1, TIM-3 and CLL-1.

PubMed

Darwish, Noureldien H E; Sudha, Thangirala; Godugu, Kavitha; Elbaz, Osama; Abdelghaffar, Hasan A; Hassan, Emad E A; Mousa, Shaker A

2016-09-06

Acute myeloid leukemia (AML) patients show high relapse rates and some develop conventional chemotherapy resistance. Leukemia Stem Cells (LSCs) are the main player for AML relapses and drug resistance. LSCs might rely on the B-cell-specific Moloney murine leukemia virus integration site-1 (BMI-1) in promoting cellular proliferation and survival. Growth of LSCs in microenvironments that are deprived of nutrients leads to up-regulation of the signaling pathways during the progression of the disease, which may illustrate the sensitivity of LSCs to inhibitors of those signaling pathways as compared to normal cells. We analyzed the expression of LSC markers (CD34, CLL-1, TIM-3 and BMI-1) using quantitative RT-PCR in bone marrow samples of 40 AML patients of different FAB types (M1, M2, M3, M4, M5, and M7). We also studied the expression of these markers in 2 AML cell lines (Kasumi-1 and KG-1a) using flow cytometry and quantitative RT-PCR. The overexpression of TIM-3, CLL-1, and BMI-1 was markedly correlated with poor prognosis in these patients. Our in vitro findings demonstrate that targeting BMI-1, which markedly increased in the leukemic cells, was associated with marked decrease in leukemic burden. This study also presents results for blocking LSCs' surface markers CD44, CLL-1, and TIM-3. These markers may play an important role in elimination of AML. Our study indicates a correlation between the expression of markers TIM-3, CLL-1, and especially of BMI-1 and the aggressiveness of AML and thus the potential impact of prognosis and therapies that target LSCs on improving the cure rates.

Development of a High Ionization Efficiency Molten Glass Ion Emitter for TIMS

NASA Astrophysics Data System (ADS)

Cheversia, M. B.; Farmer, G.; Koval, C.; David, D.

2006-12-01

Thermal ionization mass spectrometry (TIMS) remains the method of choice for many high precision isotope ratio determinations but is handicapped by the use of low efficiency ion emitters. For example, ionization efficiencies from molten glass emitters (Si-gel) used for such elements as Pb, Cr, Ru, and Ag are in the range of 0.05-2%, which limits the sample size and the precision to which isotope ratio determinations for these elements can be made. Our aim is to improve the ionization efficiency of the molten glass ion emitter using electrochemical methods. This work builds on recent observations indicating that many metals doped in borosilicate glasses (eg. Bi, Ag), are emitted from the liquid glass (in vacuo) primarily as the neutral metal atom. Our goal is to increase the proportion of singly charged metal atoms in metal-doped molten glasses via oxidation induced by electrochemical methods and to assess whether such in situ oxidation of metal atoms leads to an increase in emitted metal ions. Our experiments are performed in a vacuum chamber that mimics conditions in the sample chamber of the TIMS. A borosilicate glass sample is placed in a miniature ceramic crucible. The crucible contains working and reference Pt electrodes, and a Pt thermocouple. The entire apparatus is wrapped with a resistively heated Ta wire until temperatures in the glass reach approximately 1400°C, to ensure that the glass is molten. By this method, we have produced simple cyclic voltammograms that suggest that over a 100°C temperature range, the borosilicate glass undergoes a transition from resistive behavior as a solid, to a conductive electrolyte, as a molten liquid glass, as expected. The change is evident as an order of magnitude decrease in resistivity of the glass, as interpreted from the voltammograms. The voltammograms produced for the pure borosilicate glasses represent the baseline against which we will compare the electrochemical characteristics of Pb doped glasses. These

TIM Version 3.0 beta Technical Description and User Guide - Appendix B - Example input file for TIMv3.0

EPA Pesticide Factsheets

Terrestrial Investigation Model, TIM, has several appendices to its user guide. This is the appendix that includes an example input file in its preserved format. Both parameters and comments defining them are included.

Urban remote sensing applications: TIMS observations of the City of Scottsdale

NASA Technical Reports Server (NTRS)

Christensen, Philip R.; Melendrez, David E.; Anderson, Donald L.; Hamilton, Victoria E.; Wenrich, Melissa L.; Howard, Douglas

1995-01-01

A research program has been initiated between Arizona State University and the City of Scottsdale, Arizona to study the potential applications of TIMS (Thermal Infrared Multispectral Scanner) data for urban scene classification, desert environmental assessment, and change detection. This program is part of a long-term effort to integrate remote sensing observations into state and local planning activities to improve decision making and future planning. Specific test sites include a section of the downtown Scottsdale region that has been mapped in very high detail as part of a pilot program to develop an extensive GIS database. This area thus provides excellent time history of the evolution of the city infrastructure, such as the timing and composition of street repavement. A second area of study includes the McDowell intensive study by state and local agencies to assess potential sites for urban development as well as preservation. These activities are of particular relevance as the Phoenix metropolitan area undergoes major expansion into the surrounding desert areas. The objectives of this study in urban areas are aimed at determining potential applications of TIMS data for classifying and assessing land use and surface temperatures. Land use centers on surface impermeability studies for storm runoff assessment and pollution control. These studies focus on determining the areal abundance of urban vegetation and undeveloped soil. Highly experimental applications include assessment and monitoring of pavement condition. Temperature studies focus on determining swimming pool area and temperature for use in monitoring evaporating and urban water consumption. These activities are of particular relevance as the Phoenix metropolitan area undergoes major expansion into the surrounding desert area.

Creation of active TIM barrel enzymes through genetic fusion of half-barrel domain constructs derived from two distantly related glycosyl hydrolases.

PubMed

Sharma, Prerna; Kaila, Pallavi; Guptasarma, Purnananda

2016-12-01

Diverse unrelated enzymes that adopt the beta/alpha (or TIM) barrel topology display similar arrangements of beta/alpha units placed in a radial eight-fold symmetry around the barrel's axis. The TIM barrel was originally thought to be a single structural domain; however, it is now thought that TIM barrels arose from duplication and fusion of smaller half-barrels consisting of four beta/alpha units. We describe here the design, expression and purification, as well as characterization of folding, activity and stability, of chimeras of two TIM barrel glycosyl hydrolases, made by fusing different half-barrel domains derived from an endoglucanase from Clostridium cellulolyticum, CelCCA and a beta-glucosidase from Pyrococcus furiosus, CelB. We show that after refolding following purification from inclusion bodies, the two half-barrel fusion chimeras (CelCCACelB and CelBCelCCA) display catalytic activity although they assemble into large soluble oligomeric aggregated species containing chains of mixed beta and alpha structure. CelBCelCCA displays hyperthermophile-like structural stability as well as significant stability to chemical denaturation (C m of 2.6 m guanidinium hydrochloride), whereas CelCCACelB displays mesophile-like stability (T m of ~ 71 °C). The endoglucanase activities of both chimeras are an order of magnitude lower than those of CelB or CelCCA, whereas the beta-glucosidase activity of CelBCelCCA is about two orders of magnitude lower than that of CelB. The chimera CelCCACelB shows no beta-glucosidase activity. Our results demonstrate that half-barrel domains from unrelated sources can fold, assemble and function, with scope for improvement. Pyrococcus furiosus beta-glucosidase (CelB, EC: 3.2.1.21). Clostridium cellulolyticum endoglucanase A (CelCCA, EC: 3.2.1.4). © 2016 Federation of European Biochemical Societies.

TIM Version 3.0 beta Technical Description and User Guide - Appendix D - Avian Data to Support Generic and Custom Species

EPA Pesticide Factsheets

TIM Appendix D summarizes avian census studies from pesticide registrant submissions and literature. The purpose of this review is to identify avian species that are representative of those that commonly visit agricultural fields.

AVIRIS and TIMS data processing and distribution at the land processes distributed active archive center

NASA Technical Reports Server (NTRS)

Mah, G. R.; Myers, J.

1993-01-01

The U.S. Government has initiated the Global Change Research program, a systematic study of the Earth as a complete system. NASA's contribution of the Global Change Research Program is the Earth Observing System (EOS), a series of orbital sensor platforms and an associated data processing and distribution system. The EOS Data and Information System (EOSDIS) is the archiving, production, and distribution system for data collected by the EOS space segment and uses a multilayer architecture for processing, archiving, and distributing EOS data. The first layer consists of the spacecraft ground stations and processing facilities that receive the raw data from the orbiting platforms and then separate the data by individual sensors. The second layer consists of Distributed Active Archive Centers (DAAC) that process, distribute, and archive the sensor data. The third layer consists of a user science processing network. The EOSDIS is being developed in a phased implementation. The initial phase, Version 0, is a prototype of the operational system. Version 0 activities are based upon existing systems and are designed to provide an EOSDIS-like capability for information management and distribution. An important science support task is the creation of simulated data sets for EOS instruments from precursor aircraft or satellite data. The Land Processes DAAC, at the EROS Data Center (EDC), is responsible for archiving and processing EOS precursor data from airborne instruments such as the Thermal Infrared Multispectral Scanner (TIMS), the Thematic Mapper Simulator (TMS), and Airborne Visible and Infrared Imaging Spectrometer (AVIRIS). AVIRIS, TIMS, and TMS are flown by the NASA-Ames Research Center ARC) on an ER-2. The ER-2 flies at 65000 feet and can carry up to three sensors simultaneously. Most jointly collected data sets are somewhat boresighted and roughly registered. The instrument data are being used to construct data sets that simulate the spectral and spatial

Making Sense of Instruction on Fractions when a Student Lacks Necessary Fractional Schemes: The Case of Tim

ERIC Educational Resources Information Center

Olive, John; Vomvoridi, Eugenia

2006-01-01

This paper critically examines the discrepancies among the pre-requisite fractional concepts assumed by a curricular unit on operations with fractions, the teacher's assumptions about those concepts and a particular student's understanding of fractions. The paper focuses on the case of one student (Tim) in the teacher's 6th grade class who was…

IL-15 induces strong but short-lived tumor-infiltrating CD8 T cell responses through the regulation of Tim-3 in breast cancer.

PubMed

Heon, Elise K; Wulan, Hasi; Macdonald, Loch P; Malek, Adel O; Braunstein, Glenn H; Eaves, Connie G; Schattner, Mark D; Allen, Peter M; Alexander, Michael O; Hawkins, Cynthia A; McGovern, Dermot W; Freeman, Richard L; Amir, Eitan P; Huse, Jason D; Zaltzman, Jeffrey S; Kauff, Noah P; Meyers, Paul G; Gleason, Michelle H; Overholtzer, Michael G; Wiseman, Sam S; Streutker, Catherine D; Asa, Sylvia W; McAlindon, Timothy P; Newcomb, Polly O; Sorensen, Poul M; Press, Oliver A

2015-08-14

IL-15 has pivotal roles in the control of CD8(+) memory T cells and has been investigated as a therapeutic option in cancer therapy. Although IL-15 and IL-2 share many functions together, including the stimulation of CD8 T cell proliferation and IFN-γ production, the different in vivo roles of IL-15 and IL-2 have been increasingly recognized. Here, we explored the different effects of IL-15 and IL-2 on tumor-infiltrating (TI) T cells from resected breast tumors. We found that neither IL-2 nor IL-15 induced intratumoral CD8 T cell proliferation by itself, but after CD3/CD28-stimulation, IL-15 induced significantly higher proliferation than IL-2 during early time points, at day 2, day 3 and day 6. However, the IL-15-induced proliferation leveled off at day 9 and day 12, whereas IL-2 induced lower but progressive proliferation at each time point. Furthermore, IL-15 caused an early and robust increase of IFN-γ in the supernatant of TI cell cultures, which diminished at later time points, while the IL-2-induced IFN-γ production remained constant over time. In addition, the IL-15-costimulated CD8 T cells presented higher frequencies of apoptotic cells. The diminishing IL-15-induced response was possibly due to regulatory and/or exhaustion mechanisms. We did not observe increased IL-10 or PD-1 upregulation, but we have found an increase of Tim-3 upregulation on IL-15-, but not IL-2-stimulated cells. Blocking Tim-3 function using anti-Tim-3 antibodies resulted in increased IL-15-induced proliferation and IFN-γ production for a prolonged period of time, whereas adding Tim-3 ligand galectin 9 led to reduced proliferation and IFN-γ production. Our results suggest that IL-15 in combination of Tim-3 blocking antibodies could potentially act as an IL-2 alternative in tumor CD8 T cell expansion in vitro, a crucial step in adoptive T cell therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of a high fat meal matrix and protein complexation on the bioaccessibility of blueberry anthocyanins using the TNO gastrointestinal model (TIM-1)

PubMed Central

Ribnicky, David M.; Roopchand, Diana E.; Oren, Andrew; Grace, Mary; Poulev, Alexander; Lila, Mary Ann; Havenaar, Robert; Raskin, Ilya

2014-01-01

The TNO intestinal model (TIM-1) of the human upper gastrointestinal tract was used to compare intestinal absorption/bioaccessibility of blueberry anthocyanins under different digestive conditions. Blueberry polyphenol-rich extract was delivered to TIM-1 in the absence or presence of a high-fat meal. HPLC analysis of seventeen anthocyanins showed that delphinidin-3-glucoside, delphinidin-3-galactoside, delphinidin-3-arabinoside and petunidin-3-arabinoside were twice as bioaccessible in fed state, whilst delphinidin-3-(6″-acetoyl)-glucoside and malvidin-3-arabinoside were twice as bioaccessible under fasted conditions, suggesting lipid-rich matrices selectively effect anthocyanin bioaccessibility. TIM-1 was fed blueberry juice (BBJ) or blueberry polyphenol-enriched defatted soybean flour (BB-DSF) containing equivalent amounts of free or DSF-sorbed anthocyanins, respectively. Anthocyanin bioaccessibility from BB-DSF (36.0 ± 10.4) was numerically, but not significantly, greater than that from BBJ (26.3 ± 10.3). Ileal efflux samples collected after digestion of BB-DSF contained 2.8-fold more anthocyanins than same from BBJ, suggesting that protein-rich DSF protects anthocyanins during transit through upper digestive tract for subsequent colonic delivery/metabolism. PMID:24001852

Effects of a high fat meal matrix and protein complexation on the bioaccessibility of blueberry anthocyanins using the TNO gastrointestinal model (TIM-1).

PubMed

Ribnicky, David M; Roopchand, Diana E; Oren, Andrew; Grace, Mary; Poulev, Alexander; Lila, Mary Ann; Havenaar, Robert; Raskin, Ilya

2014-01-01

The TNO intestinal model (TIM-1) of the human upper gastrointestinal tract was used to compare intestinal absorption/bioaccessibility of blueberry anthocyanins under different digestive conditions. Blueberry polyphenol-rich extract was delivered to TIM-1 in the absence or presence of a high-fat meal. HPLC analysis of seventeen anthocyanins showed that delphinidin-3-glucoside, delphinidin-3-galactoside, delphinidin-3-arabinoside and petunidin-3-arabinoside were twice as bioaccessible in fed state, whilst delphinidin-3-(6″-acetoyl)-glucoside and malvidin-3-arabinoside were twice as bioaccessible under fasted conditions, suggesting lipid-rich matrices selectively effect anthocyanin bioaccessibility. TIM-1 was fed blueberry juice (BBJ) or blueberry polyphenol-enriched defatted soybean flour (BB-DSF) containing equivalent amounts of free or DSF-sorbed anthocyanins, respectively. Anthocyanin bioaccessibility from BB-DSF (36.0±10.4) was numerically, but not significantly, greater than that from BBJ (26.3±10.3). Ileal efflux samples collected after digestion of BB-DSF contained 2.8-fold more anthocyanins than same from BBJ, suggesting that protein-rich DSF protects anthocyanins during transit through upper digestive tract for subsequent colonic delivery/metabolism. Copyright © 2013 Elsevier Ltd. All rights reserved.

Astro Academy: Principia--Using Tracker to Analyse Experiments Undertaken by Tim Peake on the International Space Station

ERIC Educational Resources Information Center

Mobbs, Robin

2016-01-01

While on the International Space Station, Tim Peake undertook and recorded video files of experiments suitable for physics teaching coordinated by the National Space Academy. This article describes how the video of these experiments was prepared for use with tracking software. The tracking files of the videos are suitable for use by teachers or…

CB2 cannabinoid receptors modulate HIF-1α and TIM-3 expression in a hypoxia-ischemia mouse model.

PubMed

Kossatz, Elk; Maldonado, Rafael; Robledo, Patricia

2016-12-01

The role of CB2 cannabinoid receptors (CB 2 R) in global brain lesions induced by hypoxia-ischemia (HI) insult is still unresolved. The aim of this study was to evaluate the involvement of CB 2 R in the behavioural and biochemical underpinnings related to brain damage induced by HI in adult mice, and the mechanisms involved. CB 2 R knockout (KO) mice and wild-type littermates (WT) underwent permanent ligation of the left common carotid artery and hypoxia. Behavioural measurements in the rotarod, beam walking, object recognition, open field, and Irwin tests were carried out 24h, 72h and 7 days. In KO mice, more extensive brain injury was observed. Behavioural deficits in the Irwin test were observed in both genotypes; while WT mice showed progressive recovery by day 7, KO mice did not. Only KO mice showed alterations in motor learning, coordination and balance, and did not recover over time. A higher expression of microglia and astrocytes was observed in several brain areas of lesioned WT and KO mice. The possible alteration of the inflammatory-related factors HIF-1α and TIM-3 was evaluated in these animals. In both genotypes, HIF-1α and TIM-3 expression was observed in lesioned areas associated with activated microglia. However, the expression levels of these proteins were exacerbated in KO mice in several lesioned and non-lesioned brain structures. Our results indicate that CB 2 R may have a crucial neuroprotective role following HI insult through the modulation of the inflammatory-related HIF-1α/TIM-3 signalling pathway in microglia. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Application of Thermal Infrared Multiband Scanner (TIMS) data to mapping of Plutonic and stratified rock and assemblages in accreted terrains of the Northern Sierra, California

NASA Technical Reports Server (NTRS)

Taranik, James V.; Davis, David; Borengasser, Marcus

1986-01-01

The Thermal Infrared Multispectral Scanner (TIMS) data were acquired over the Donner Pass area in California on September 12, 1985. The higher peaks in the area approach 9,200 feet in elevation, while the canyon of the north fork of the American River is only 3000 feet in elevation. The vegetation is dominated by conifers, although manzanita and other shrubs are present in areas where soils have developed. The data contain noise patterns which cut across scan lines diagonally. The TIMS data were analyzed using both photointerpretative and digital processing techniques. Preliminary image interpretation and field analysis confirmed that TIMS image data displays the chert units and silicic volcanics as bright red. The imagery appears to display zoning in the batholithic and hypabyssal intrusive rocks, although this was not field checked at this time. Rocks which appear to be more dioritic in composition appear purple on the imagery, while rocks more granitic in composition appear shades of red and pink. Areas that have more than 40% vegetative cover appear green on the imagery.

Elevated frequencies of CD8 T cells expressing PD-1, CTLA-4 and Tim-3 within tumour from perineural squamous cell carcinoma patients.

PubMed

Linedale, Richard; Schmidt, Campbell; King, Brigid T; Ganko, Annabelle G; Simpson, Fiona; Panizza, Benedict J; Leggatt, Graham R

2017-01-01

Perineural spread of tumour cells along cranial nerves is a severe complication of primary cutaneous squamous cell carcinomas of the head and neck region. While surgical excision of the tumour is the treatment of choice, removal of all the tumour is often complicated by the neural location and recurrence is frequent. Non-invasive immune treatments such as checkpoint inhibitor blockade may be useful in this set of tumours although little is understood about the immune response to perineural spread of squamous cell carcinomas. Immunohistochemistry studies suggest that perineural tumour contains a lymphocyte infiltrate but it is difficult to quantitate the different proportions of immune cell subsets and expression of checkpoint molecules such as PD-1, Tim-3 and CTLA-4. Using flow cytometry of excised perineural tumour tissue, we show that a T cell infiltrate is prominent in addition to less frequent B cell, NK cell and NKT cell infiltrates. CD8 T cells are more frequent than other T cells in the tumour tissue. Amongst CD8 T cells, the frequency of Tim-3, CTLA-4 and PD-1 expressing cells was significantly greater in the tumour relative to the blood, a pattern that was repeated for Tim-3, CTLA-4 and PD-1 amongst non-CD8 T cells. Using immunohistochemistry, PD-1 and PD-L1-expression could be detected in close proximity amongst perineural tumour tissue. The data suggest that perineural SCC contains a mixture of immune cells with a predominant T cell infiltrate containing CD8 T cells. Elevated frequencies of tumour-associated Tim-3+, CTLA-4+ and PD-1+ CD8 T cells suggests that a subset of patients may benefit from local antibody blockade of these checkpoint inhibitors.

MyDas, an Extensible Java DAS Server

PubMed Central

Jimenez, Rafael C.; Quinn, Antony F.; Jenkinson, Andrew M.; Mulder, Nicola; Martin, Maria; Hunter, Sarah; Hermjakob, Henning

2012-01-01

A large number of diverse, complex, and distributed data resources are currently available in the Bioinformatics domain. The pace of discovery and the diversity of information means that centralised reference databases like UniProt and Ensembl cannot integrate all potentially relevant information sources. From a user perspective however, centralised access to all relevant information concerning a specific query is essential. The Distributed Annotation System (DAS) defines a communication protocol to exchange annotations on genomic and protein sequences; this standardisation enables clients to retrieve data from a myriad of sources, thus offering centralised access to end-users. We introduce MyDas, a web server that facilitates the publishing of biological annotations according to the DAS specification. It deals with the common functionality requirements of making data available, while also providing an extension mechanism in order to implement the specifics of data store interaction. MyDas allows the user to define where the required information is located along with its structure, and is then responsible for the communication protocol details. PMID:23028496

MyDas, an extensible Java DAS server.

PubMed

Salazar, Gustavo A; García, Leyla J; Jones, Philip; Jimenez, Rafael C; Quinn, Antony F; Jenkinson, Andrew M; Mulder, Nicola; Martin, Maria; Hunter, Sarah; Hermjakob, Henning

2012-01-01

A large number of diverse, complex, and distributed data resources are currently available in the Bioinformatics domain. The pace of discovery and the diversity of information means that centralised reference databases like UniProt and Ensembl cannot integrate all potentially relevant information sources. From a user perspective however, centralised access to all relevant information concerning a specific query is essential. The Distributed Annotation System (DAS) defines a communication protocol to exchange annotations on genomic and protein sequences; this standardisation enables clients to retrieve data from a myriad of sources, thus offering centralised access to end-users.We introduce MyDas, a web server that facilitates the publishing of biological annotations according to the DAS specification. It deals with the common functionality requirements of making data available, while also providing an extension mechanism in order to implement the specifics of data store interaction. MyDas allows the user to define where the required information is located along with its structure, and is then responsible for the communication protocol details.

Geochemistry, thermometry and isotope ratios on the same zircon crystals: the tandem use of quadrupole LA-ICPMS and CA-TIMS

NASA Astrophysics Data System (ADS)

Olin, P. H.; Schmitz, M. D.; Crowley, J. L.

2011-12-01

Current trends in igneous petrology include the extraction of diverse geochemical information from smaller sample targets by ever more efficient and cost effective means. Igneous zircons are repositories of several types of petrogenetic information, such as magmatic crystallization ages obtained using U-Pb geochronology, magmatic temperatures using Ti-in-zircon geothermometry, and magmatic differentiation and/or mixing trends using trace element contents. Here we demonstrate a tandem quadrupole LA-ICPMS and CA-TIMS approach on single zircon crystals and within domains in single crystals, which extracts all of these data from a single laser spot analysis and then guides the acquisition of CA-TIMS ages at precisions relevant to magmatic histories. We present data from zircon-bearing intrusive and extrusive rocks spanning the compositional spectrum, and highlight results from silicic volcanic rocks with different affinities. The utility of our approach is illustrated in zircons from the Temora diorite, a commonly used standard material which we analysed using 25-μm ablation spots placed on dozens of grains which had been previously annealed and chemically abraded prior to mounting in epoxy. Our LA-ICPMS results illustrate a 3- to 5-fold variation in trace element concentrations and trace element ratios over >150 degrees of cooling as estimated from Ti-in-zircon thermometry. Some geochemical parameters (e.g., Nb/Ta variations and Eu anomalies) are consistent with crystal fractionation during progressive crystallization, while others are bimodal (e.g., Hf and U contents), suggesting the mixing of crystal/magma batches prior to final solidification. LA-ICPMS U-Pb spot ages reproduce the accepted CA-TIMS age within 2% precision and accuracy, while our CA-TIMS results on the same grains constrain the development of the observed geochemical variability to within 100 ka. Other zircon standard materials to be presented include Plesovich syenite, FC1 gabbro, and R33 diorite

Coordinated Traffic Incident and Congestion Management (TIM-CM) : Mitigating Regional Impacts of Major Traffic Incidents in the Seattle I-5 Corridor

DOT National Transportation Integrated Search

2018-02-02

Within the Seattle metropolitan area, traffic incident management (TIM) operations provide a multi-jurisdictional and coordinated strategy to detect, respond to, and clear traffic incidents so that traffic flow can be restored quickly and safely. The...

Dr TIM: Ray-tracer TIM, with additional specialist scientific capabilities

NASA Astrophysics Data System (ADS)

Oxburgh, Stephen; Tyc, Tomáš; Courtial, Johannes

2014-03-01

We describe several extensions to TIM, a raytracing program for ray-optics research. These include relativistic raytracing; simulation of the external appearance of Eaton lenses, Luneburg lenses and generalised focusing gradient-index lens (GGRIN) lenses, which are types of perfect imaging devices; raytracing through interfaces between spaces with different optical metrics; and refraction with generalised confocal lenslet arrays, which are particularly versatile METATOYs. Catalogue identifier: AEKY_v2_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEKY_v2_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licencing provisions: GNU General Public License No. of lines in distributed program, including test data, etc.: 106905 No. of bytes in distributed program, including test data, etc.: 6327715 Distribution format: tar.gz Programming language: Java. Computer: Any computer capable of running the Java Virtual Machine (JVM) 1.6. Operating system: Any, developed under Mac OS X Version 10.6 and 10.8.3. RAM: Typically 130 MB (interactive version running under Mac OS X Version 10.8.3) Classification: 14, 18. Catalogue identifier of previous version: AEKY_v1_0 Journal reference of previous version: Comput. Phys. Comm. 183(2012)711 External routines: JAMA [1] (source code included) Does the new version supersede the previous version?: Yes Nature of problem: Visualisation of scenes that include scene objects that create wave-optically forbidden light-ray fields. Solution method: Ray tracing. Reasons for new version: Significant extension of the capabilities (see Summary of revisions), as demanded by our research. Summary of revisions: Added capabilities include the simulation of different types of camera moving at relativistic speeds relative to the scene; visualisation of the external appearance of generalised focusing gradient-index (GGRIN) lenses, including Maxwell fisheye, Eaton and Luneburg lenses; calculation of

High-Resolution Zircon U-Pb CA-TIMS Dating of the Carboniferous—Permian Successions, Paraná Basin, Brazil

NASA Astrophysics Data System (ADS)

Griffis, N. P.; Mundil, R.; Montanez, I. P.; Isbell, J.; Fedorchuk, N.; Lopes, R.; Vesely, F.; Iannuzzi, R.

2015-12-01

The late Paleozoic Ice Age (LPIA) is Earth's only record of a CO2-forced climatic transition from an icehouse to greenhouse state in a vegetated world. Despite a refined framework of Gondwanan ice distribution, questions remain about the timing, volume, and synchronicity of high-latitude continental ice and the subsequent deglaciation. These questions ultimately preclude our understanding of linkages between ice volume, sea level, and high- and low-latitude climate. Poor constraints on the timing and synchronicity of glacial and interglacial transitions reflect a lack of high-resolution radioisotopic dates from high-latitude, ice-proximal Carboniferous-Permian successions. The Rio Bonito Fm in Rio Grande do Sul State of southern Brazil hosts the oldest non-glaciogenic Carboniferous- Permian deposits of the Paraná Basin, thus recording the icehouse-to-greenhouse transition. Despite a widespread effort over the last two decades to constrain these deposits in time by means of U-Pb zircon geochronology, published data sets of the Candiota and Faxinal coals of the Rio Bonito Fm host discrepancies that may reflect post- eruptive open system behavior of zircon and analytical artifacts. These discrepancies have hindered the correlation of the Candiota and Faxinal sediments within the larger Gondwanan framework. Here we present the first U-Pb ages on closed system single zircons using CA-TIMS techniques on Permo-Carboniferous ash deposits of the Paraná Basin. Preliminary results indicate two major and distinct coal-forming periods that are separated by ca 10 Ma. Our results and conclusions are not in agreement with multi- crystal U-Pb TIMS and SIMS ages that suggest coeval deposition of the Candiota and Faxinal coals. CA-TIMS analyses applied to zircons from additional ash deposits are aimed at constructing a robust chronostratigraphic framework for the Carboniferous- Permian succession of the Paraná Basin, which will facilitate a better understanding of the timing and

A 6-amino acid insertion/deletion polymorphism in the mucin domain of TIM-1 confers protections against HIV-1 infection.

PubMed

Biasin, Mara; Sironi, Manuela; Saulle, Irma; Pontremoli, Chiara; Garziano, Micaela; Cagliani, Rachele; Trabattoni, Daria; Lo Caputo, Sergio; Vichi, Francesca; Mazzotta, Francesco; Forni, Diego; Riva, Stefania; Aguilar-Jimenez, Wbeimar; Cedeño, Samandhy; Sanchez, Jorge; Brander, Christian; Zapata, Wildeman; Rugeles, Maria Teresa; Clerici, Mario

2017-01-01

We investigated whether a 6-amino acid insertion/deletion polymorphism in the mucin domain of TIM-1 (T-cell immunoglobulin and mucin domain 1), modulates susceptibility to HIV-1 infection. The polymorphism was genotyped in three case/control cohorts of HIV-1 exposed seronegative individuals (HESN) and HIV-1 infected subjects from Italy, Peru, and Colombia; data from a Thai population were retrieved from the literature. Across all cohorts, homozygosity for the short TIM-1 allele was more common in HESNs than in HIV-1 infected subjects. A meta-analysis of the four association analyses yielded a p value of 0.005. In vitro infection assays of CD4+ T lymphocytes indicated that homozygosity for the short allele is associated with lower rate of HIV-1 replication. These results suggest that the deletion allele protects from HIV-1 infection with a recessive effect. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Summaries of the Third Annual JPL Airborne Geoscience Workshop. Volume 2: TIMS Workshop

NASA Technical Reports Server (NTRS)

Realmuto, Vincent J. (Editor)

1992-01-01

This publication contains the preliminary agenda and summaries for the Third Annual JPL Airborne Geoscience Workshop, held at the Jet Propulsion Laboratory, Pasadena, California, on 1-5 June 1992. This main workshop is divided into three smaller workshops as follows: (1) the Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) workshop, on June 1 and 2; the summaries for this workshop appear in Volume 1; (2) the Thermal Infrared Multispectral Scanner (TIMS) workshop, on June 3; the summaries for this workshop appear in Volume 2; and (3) the Airborne Synthetic Aperture Radar (AIRSAR) workshop, on June 4 and 5; the summaries for this workshop appear in Volume 3.

Isotope ratio measurements of pg-size plutonium samples using TIMS in combination with "multiple ion counting" and filament carburization

NASA Astrophysics Data System (ADS)

Jakopic, Rozle; Richter, Stephan; Kühn, Heinz; Benedik, Ljudmila; Pihlar, Boris; Aregbe, Yetunde

2009-01-01

A sample preparation procedure for isotopic measurements using thermal ionization mass spectrometry (TIMS) was developed which employs the technique of carburization of rhenium filaments. Carburized filaments were prepared in a special vacuum chamber in which the filaments were exposed to benzene vapour as a carbon supply and carburized electrothermally. To find the optimal conditions for the carburization and isotopic measurements using TIMS, the influence of various parameters such as benzene pressure, carburization current and the exposure time were tested. As a result, carburization of the filaments improved the overall efficiency by one order of magnitude. Additionally, a new "multi-dynamic" measurement technique was developed for Pu isotope ratio measurements using a "multiple ion counting" (MIC) system. This technique was combined with filament carburization and applied to the NBL-137 isotopic standard and samples of the NUSIMEP 5 inter-laboratory comparison campaign, which included certified plutonium materials at the ppt-level. The multi-dynamic measurement technique for plutonium, in combination with filament carburization, has been shown to significantly improve the precision and accuracy for isotopic analysis of environmental samples with low-levels of plutonium.

Summaries of the Fifth Annual JPL Airborne Earth Science Workshop. Volume 2: TIMS Workshop

NASA Technical Reports Server (NTRS)

Realmuto, Vincent J. (Editor)

1995-01-01

This publication is the second volume of the summaries for the Fifth Annual JPL Airborne Earth Science Workshop, held in Pasadena, California, on January 23-26, 1995. The main workshop is divided into three smaller workshops as follows: (1) The Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) workshop on January 23-24. The summaries for this workshop appear in Volume 1; (2) The Airborne Synthetic Aperture Radar (AIRSAR) workshop on January 25-26. The summaries for this workshop appear in volume 3; and (3) The Thermal Infrared Multispectral Scanner (TIMS) workshop on January 26. The summaries for this workshop appear in this volume.

Chemical Analysis of Water-accommodated Fractions of Crude Oil Spills Using TIMS-FT-ICR MS.

PubMed

Benigni, Paolo; Marin, Rebecca; Sandoval, Kathia; Gardinali, Piero; Fernandez-Lima, Francisco

2017-03-03

Multiple chemical processes control how crude oil is incorporated into seawater and also the chemical reactions that occur overtime. Studying this system requires the careful preparation of the sample in order to accurately replicate the natural formation of the water-accommodated fraction that occurs in nature. Low-energy water-accommodated fractions (LEWAF) are carefully prepared by mixing crude oil and water at a set ratio. Aspirator bottles are then irradiated, and at set time points, the water is sampled and extracted using standard techniques. A second challenge is the representative characterization of the sample, which must take into consideration the chemical changes that occur over time. A targeted analysis of the aromatic fraction of the LEWAF can be performed using an atmospheric-pressure laser ionization source coupled to a custom-built trapped ion mobility spectrometry-Fourier transform-ion cyclotron resonance mass spectrometer (TIMS-FT-ICR MS). The TIMS-FT-ICR MS analysis provides high-resolution ion mobility and ultrahigh-resolution MS analysis, which further allow the identification of isomeric components by their collision cross-sections (CCS) and chemical formula. Results show that as the oil-water mixture is exposed to light, there is significant photo-solubilization of the surface oil into the water. Over time, the chemical transformation of the solubilized molecules takes place, with a decrease in the number of identifications of nitrogen- and sulfur-bearing species in favor of those with a greater oxygen content than were typically observed in the base oil.

Comparison of Total Evaporation (TE) and Direct Total Evaporation (DTE) methods in TIMS by using NBL CRMs

NASA Astrophysics Data System (ADS)

Hasözbek, Altug; Mathew, Kattathu; Wegener, Michael

2013-04-01

The total evaporation (TE) is a well-established analytical method for safeguards measurement of uranium and plutonium isotope-amount ratios using the thermal ionization mass spectrometry (TIMS). High accuracy and precision isotopic measurements find many applications in nuclear safeguards, for e.g. assay measurements using isotope dilution mass spectrometry. To achieve high accuracy and precision in TIMS measurements, mass dependent fractionation effects are minimized by either the measurement technique or changes in the hardware components that are used to control sample heating and evaporation process. At NBL, direct total evaporation (DTE) method on the modified MAT261 instrument, uses the data system to read the ion signal intensity and its difference from a pre-determined target intensity, is used to control the incremental step at which the evaporation filament is heated. The feedback and control is achieved by proprietary hardware from SPECTROMAT that uses an analog regulator in the filament power supply with direct feedback of the detector intensity. Compared to traditional TE method on this instrument, DTE provides better precision (relative standard deviation, expressed as a percent) and accuracy (relative difference, expressed as a percent) of 0.05 to 0.08 % for low enriched and high enriched NBL uranium certified reference materials.

A field- and laboratory-based quantitative analysis of alluvium: Relating analytical results to TIMS data

NASA Technical Reports Server (NTRS)

Wenrich, Melissa L.; Hamilton, Victoria E.; Christensen, Philip R.

1995-01-01

Thermal Infrared Multispectral Scanner (TIMS) data were acquired over the McDowell Mountains northeast of Scottsdale, Arizona during August 1994. The raw data were processed to emphasize lithologic differences using a decorrelation stretch and assigning bands 5, 3, and 1 to red, green, and blue, respectively. Processed data of alluvium flanking the mountains exhibit moderate color variation. The objective of this study was to determine, using a quantitative approach, what environmental variable(s), in the absence of bedrock, is/are responsible for influencing the spectral properties of the desert alluvial surface.

Summaries of the 4th Annual JPL Airborne Geoscience Workshop. Volume 2: TIMS Workshop

NASA Technical Reports Server (NTRS)

Realmuto, Vincent J. (Editor)

1993-01-01

This is volume 2 of a three volume set of publications that contain the summaries for the Fourth Annual JPL Airborne Geoscience Workshop, held in Washington, D.C. on October 25-29, 1993. The main workshop is divided into three smaller workshops as follows: The Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) workshop, on October 25-26. The summaries for this workshop appear in Volume 1. The Thermal Infrared Multispectral Scanner (TIMS) workshop, on October 27. The summaries for this workshop appear in Volume 2. The Airborne Synthetic Aperture Radar (AIRSAR) workshop, on October 28-29. The summaries for this workshop appear in Volume 3.

Sensor 17 Thermal Isolation Mounting Structure (TIMS) Design Improvements

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

Enstrom, K.

2015-09-04

The SENSOR 17 thermographic camera weighs approximately 0.5lbs, has a fundamental mode of 167 Hz, and experiences 0.75W of heat leakage in through the TIMS. The configuration, shown in Figure 1, is comprised of four 300 Series SST washers paired in tandem with P.E.I (Ultem 100) washers. The SENSOR 17 sensor is mounted to a 300 series stainless plate with A-shaped arms. The Plate can be assumed to be at ambient temperatures (≈293K) and the I.R. Mount needs to be cooled to 45K. It is attached to the tip of a cryocooler by a ‘cold strap’ and is assumed tomore » be at the temperature of the cold-strap (≈45K). During flights SENSOR 17 experiences excitations at frequencies centered around 10-30Hz, 60Hz, and 120Hz from the aircraft flight environment. The temporal progression described below depicts the 1st Modal shape at the systems resonant frequency. This simulation indicates Modal articulation will cause a pitch rate of the camera with respect to the body axis of the airplane. This articulation shows up as flutter in the camera.« less

Behind their Cosmonaut Hotel crew quarters in Baikonur, Kazakhstan, Expedition 46-47 crewmember Tim Kopra of NASA (left), Yuri Malenchenko of the Russian Federal Space Agency (Roscosmos, center) and Tim Peake of the European Space Agency (right) pose for pictures Dec. 9 after a traditional tree-planting ceremony. The trio will launch Dec. 15 on their Soyuz TMA-19M spacecraft for a six-month mission on the International Space Station...NASA/Victor Zelentsov.

NASA Image and Video Library

2015-12-09

Behind their Cosmonaut Hotel crew quarters in Baikonur, Kazakhstan, Expedition 46-47 crewmember Tim Kopra of NASA (left), Yuri Malenchenko of the Russian Federal Space Agency (Roscosmos, center) and Tim Peake of the European Space Agency (right) pose for pictures Dec. 9 after a traditional tree-planting ceremony. The trio will launch Dec. 15 on their Soyuz TMA-19M spacecraft for a six-month mission on the International Space Station. NASA/Victor Zelentsov

Textural and U-Pb systematics (CA-TIMS) of stepwise leaching in zircon from granophyres in the Archean Stillwater Complex

NASA Astrophysics Data System (ADS)

Wall, C. J.; Scoates, J. S.; Friedman, R. M.; Meurer, W. P.

2011-12-01

The chemical abrasion-TIMS method or CA-TIMS uses a high-temperature annealing treatment to remove the effects of Pb-loss from radiation damaged parts of the zircon lattice and allows for highly precise and accurate U-Pb dating [1]. Zircon with high U-Th concentrations can be strongly metamict and it is not yet clear how effective the chemical abrasion treatment is when applied to these types of grains. In this study, we evaluate the link between the textural response and U-Pb systematics of zircon during chemical leaching for a granophyric rock from the Archean Stillwater Complex in Montana. The sample was selected based on the high abundance of zircon and the high degree of metamictization of the grains. Untreated and leached zircon grains were analyzed by scanning electron microscopy (SEM) and isotope dilution thermal ionization mass spectrometry (ID-TIMS). In thin section, zircon grains are euhedral in morphology and tend to be associated with amphibole-rich zones. Under the SEM, zircon grains typically have two distinct zones, a Ca-rich amorphous zone in the core and a more intact outer shell. Five acid-leaching steps were carried out on grains with each step increasing in temperature and acid strength until the zircon residue completely dissolved (starting at a 50% strength HF/HNO3 mixture at 100°C for 4 hours and finishing at full strength acid at 170°C for 4 hours). SEM imaging was conducted on grains after each step with a noticeable change in the morphology of the grains. As the leaching progressed, the acid leach created large pathways through the crystal lattice until only grain fragments remained, in some cases even boring large holes into the centre of the zircon grain. The acid preferentially dissolved the more soluble Ca-rich zones leaving behind fragile zircon "shells". U-Pb results of untreated grains are highly discordant (37-80%) and yield a chord with an upper intercept age of 1981 ± 140 Ma, whereas leached grains are slightly less

Comparison of preliminary results from Airborne Aster Simulator (AAS) with TIMS data

NASA Technical Reports Server (NTRS)

Kannari, Yoshiaki; Mills, Franklin; Watanabe, Hiroshi; Ezaka, Teruya; Narita, Tatsuhiko; Chang, Sheng-Huei

1992-01-01

The Japanese Advanced Spaceborne Thermal Emission and Reflection radiometer (ASTER), being developed for a NASA EOS-A satellite, will have 3 VNIR, 6 SWIR, and 5 TIR (8-12 micron) bands. An Airborne ASTER Simulator (AAS) was developed for Japan Resources Observation System Organization (JAROS) by the Geophysical Environmental Research Group (GER) Corp. to research surface temperature and emission features in the MWIR/TIR, to simulate ASTER's TIR bands, and to study further possibility of MWIR/TIR bands. ASTER Simulator has 1 VNIR, 3 MWIR (3-5 microns), and 20 (currently 24) TIR bands. Data was collected over 3 sites - Cuprite, Nevada; Long Valley/Mono Lake, California; and Death Valley, California - with simultaneous ground truth measurements. Preliminary data collected by AAS for Cuprite, Nevada is presented and AAS data is compared with Thermal Infrared Multispectral Scanner (TIMS) data.

Towards unsupervised polyaromatic hydrocarbons structural assignment from SA-TIMS-FTMS data.

PubMed

Benigni, Paolo; Marin, Rebecca; Fernandez-Lima, Francisco

2015-10-01

With the advent of high resolution ion mobility analyzers and their coupling to ultrahigh resolution mass spectrometers, there is a need to further develop a theoretical workflow capable of correlating experimental accurate mass and mobility measurements with tridimensional candidate structures. In the present work, a general workflow is described for unsupervised tridimensional structural assignment based on accurate mass measurements, mobility measurements, in silico 2D-3D structure generation, and theoretical mobility calculations. In particular, the potential of this workflow will be shown for the analysis of polyaromatic hydrocarbons from Coal Tar SRM 1597a using selected accumulation - trapped ion mobility spectrometry (SA-TIMS) coupled to Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS). The proposed workflow can be adapted to different IMS scenarios, can utilize different collisional cross-section calculators and has the potential to include MS n and IMS n measurements for faster and more accurate tridimensional structural assignment.

Second NASA Technical Interchange Meeting (TIM): Advanced Technology Lifecycle Analysis System (ATLAS) Technology Tool Box (TTB)

NASA Technical Reports Server (NTRS)

ONeil, D. A.; Mankins, J. C.; Christensen, C. B.; Gresham, E. C.

2005-01-01

The Advanced Technology Lifecycle Analysis System (ATLAS), a spreadsheet analysis tool suite, applies parametric equations for sizing and lifecycle cost estimation. Performance, operation, and programmatic data used by the equations come from a Technology Tool Box (TTB) database. In this second TTB Technical Interchange Meeting (TIM), technologists, system model developers, and architecture analysts discussed methods for modeling technology decisions in spreadsheet models, identified specific technology parameters, and defined detailed development requirements. This Conference Publication captures the consensus of the discussions and provides narrative explanations of the tool suite, the database, and applications of ATLAS within NASA s changing environment.

At the Cosmonaut Hotel crew quarters in Baikonur, Kazakhstan, Expedition 46-47 crewmember Tim Kopra of NASA took a turn on a tilt table to test his vestibular system Dec. 9 as part of his pre-launch training. Kopra, Tim Peake of the European Space Agency and Yuri Malenchenko of the Russian Federal Space Agency will launch Dec. 15 on their Soyuz TMA-19M spacecraft for a six-month mission on the International Space Station...NASA/Victor Zelentsov.

NASA Image and Video Library

2015-12-09

At the Cosmonaut Hotel crew quarters in Baikonur, Kazakhstan, Expedition 46-47 crewmember Tim Kopra of NASA took a turn on a tilt table to test his vestibular system Dec. 9 as part of his pre-launch training. Kopra, Tim Peake of the European Space Agency and Yuri Malenchenko of the Russian Federal Space Agency will launch Dec. 15 on their Soyuz TMA-19M spacecraft for a six-month mission on the International Space Station. NASA/Victor Zelentsov

Operations Manager Tim Miller checks out software for the Airborne Synthetic Aperature Radar (AIRSAR

NASA Technical Reports Server (NTRS)

1998-01-01

Tim Miller checks out software for the Airborne Synthetic Aperture Radar (AIRSAR). He was the AIRSAR operations manager for NASA's Jet Propulsion Laboratory. The AIRSAR produces imaging data for a range of studies conducted by the DC-8. NASA is using a DC-8 aircraft as a flying science laboratory. The platform aircraft, based at NASA's Dryden Flight Research Center, Edwards, Calif., collects data for many experiments in support of scientific projects serving the world scientific community. Included in this community are NASA, federal, state, academic and foreign investigators. Data gathered by the DC-8 at flight altitude and by remote sensing have been used for scientific studies in archeology, ecology, geography, hydrology, meteorology, oceanography, volcanology, atmospheric chemistry, soil science and biology.

Expression profiles and clinical value of plasma exosomal Tim-3 and Galectin-9 in non-small cell lung cancer.

PubMed

Gao, Jianwei; Qiu, Xiangyu; Li, Xinying; Fan, Hang; Zhang, Fang; Lv, Tangfeng; Song, Yong

2018-04-06

Exosomes are membrane-bound, virus-sized vesicles present in circulating blood. Tumor cells are avid producers of exosomes, which are thought to mimic molecular features of parent tumor cells. T-cell immunoglobulin- and mucin-domain-containing molecule 3 (Tim-3) is a the next-generation immune checkpoint that can be activated by its ligand Galectin-9 to negatively regulate the anti-tumor immune response. However, the characteristics of plasma exosomal Tim-3 and Galectin-9 (Exo-T/G) in cancer remained unknown. This study was conducted to investigate the expression patterns and clinical value of plasma exosomal total protein (Exo-pro) and Exo-T/G in non-small cell lung cancer (NSCLC). Plasma was collected from 103 NSCLC patients including 60 early stages and 43 advanced stages disease samples as well as 56 healthy subjects. Exosomes were isolated from plasma by commercial exosome precipitation solution and identified by western blotting of CD63 and transmission electron microscopy. Exo-pro concentration was measured by the BCA assay. Enzyme-linked immunosorbent assay was used to quantify Exo-T/G. Additionally, 34 NSCLC samples were applied to directly detect plasma TIM-3 (Plas-T) and Galectin-9 (Plas-G). Our results showed that Exo-pro, Exo-T, and Exo-G were significantly increased in NSCLC plasma compared to that in the healthy samples. High levels of Exo-T and Exo-G were all positively correlated with several malignant parameters, including larger tumor size, advanced stages, and more distant metastasis. High levels of Exo-pro and Exo-T were also correlated with more lymph node metastasis. Additionally, plasma from lung squamous cell carcinoma showed higher Exo-T and Exo-G compared with that from lung adenocarcinoma. ALK-positive patients showed to have decreased Exo-T and Exo-G levels. Pearson's correlation analysis revealed a significant correlation between Exo-pro and Exo-T/G, Exo-T and Exo-G, Exo-T and Plas-T, Exo-G and Plas-G, and Plas-T and Plas-G. Together

Thrombolytic-Related Asymptomatic Hemorrhagic Transformation Does Not Deteriorate Clinical Outcome: Data from TIMS in China.

PubMed

Jia, Weihua; Liao, Xiaoling; Pan, Yuesong; Wang, Yilong; Cui, Tao; Zhou, Lichun; Wang, Yongjun

2015-01-01

It has been unclear whether thrombolytic-related asymptomatic hemorrhagic transformation (AHT) affects the clinical outcome. To answer this question, we examined whether thrombolytic-related AHT affect short-term and long-term clinical outcome. All data were collected from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China) registry. The patients were diagnosed as having AHT group and non- hemorrhagic transformation (HT) group based on clinical and imaging data. The patients with symptomatic hemorrhagic transformation were excluded from this study. Thrombolytic-related AHT was defined according to European-Australasian Acute Stroke Study (ECASS) II criteria. 90-day functional outcome, 7-day National Institutes of Health Stroke Scale (NIHSS) score, 7-day and 90-day mortalities were compared between two groups. Logistic regression analysis was used to evaluate the effects of AHT on a short-term and long-term clinical outcome. 904 of all 1440 patients in TIMS-China registry were enrolled. 89 (9.6%) patients presented with AHT after thrombolysis within 24-36 h. These patients with AHT were more likely to be elder age, cardioembolic subtype, and to have higher National Institutes of Health Stroke Scale score before thrombolysis than patients without AHT. No significant difference was found on the odds of 7-day (95% CI:0.692 (0.218-2.195), (P = 0.532) or 90-day mortalities (95% CI:0.548 (0.237-1.268), P = 0.160) and modified Rankin Score(0-1) at 90-day (95% CI:0.798 (0.460-1.386), P = 0.423) or modified Rankin Score(0-2) at 90-day (95% CI:0.732 (0.429-1.253), P = 0.116) or modified Rankin Score(5-6) at 90-day (95% CI:0.375 (0.169-1.830), P = 0.116) between two groups. Thrombolytic-related AHT does not deteriorate short-term and long-term clinical outcome.

Mini-DIAL system measurements coupled with multivariate data analysis to identify TIC and TIM simulants: preliminary absorption database analysis.

NASA Astrophysics Data System (ADS)

Gaudio, P.; Malizia, A.; Gelfusa, M.; Martinelli, E.; Di Natale, C.; Poggi, L. A.; Bellecci, C.

2017-01-01

Nowadays Toxic Industrial Components (TICs) and Toxic Industrial Materials (TIMs) are one of the most dangerous and diffuse vehicle of contamination in urban and industrial areas. The academic world together with the industrial and military one are working on innovative solutions to monitor the diffusion in atmosphere of such pollutants. In this phase the most common commercial sensors are based on “point detection” technology but it is clear that such instruments cannot satisfy the needs of the smart cities. The new challenge is developing stand-off systems to continuously monitor the atmosphere. Quantum Electronics and Plasma Physics (QEP) research group has a long experience in laser system development and has built two demonstrators based on DIAL (Differential Absorption of Light) technology could be able to identify chemical agents in atmosphere. In this work the authors will present one of those DIAL system, the miniaturized one, together with the preliminary results of an experimental campaign conducted on TICs and TIMs simulants in cell with aim of use the absorption database for the further atmospheric an analysis using the same DIAL system. The experimental results are analysed with standard multivariate data analysis technique as Principal Component Analysis (PCA) to develop a classification model aimed at identifying organic chemical compound in atmosphere. The preliminary results of absorption coefficients of some chemical compound are shown together pre PCA analysis.

Role of the import motor in insertion of transmembrane segments by the mitochondrial TIM23 complex.

PubMed

Popov-Čeleketić, Dušan; Waegemann, Karin; Mapa, Koyeli; Neupert, Walter; Mokranjac, Dejana

2011-06-01

The TIM23 complex mediates translocation of proteins across, and their lateral insertion into, the mitochondrial inner membrane. Translocation of proteins requires both the membrane-embedded core of the complex and its ATP-dependent import motor. Insertion of some proteins, however, occurs in the absence of ATP, questioning the need for the import motor during lateral insertion. We show here that the import motor associates with laterally inserted proteins even when its ATPase activity is not required. Furthermore, our results suggest a role for the import motor in lateral insertion. Thus, the import motor is involved in ATP-dependent translocation and ATP-independent lateral insertion.

Role of the import motor in insertion of transmembrane segments by the mitochondrial TIM23 complex

PubMed Central

Popov-Čeleketić, Dušan; Waegemann, Karin; Mapa, Koyeli; Neupert, Walter; Mokranjac, Dejana

2011-01-01

The TIM23 complex mediates translocation of proteins across, and their lateral insertion into, the mitochondrial inner membrane. Translocation of proteins requires both the membrane-embedded core of the complex and its ATP-dependent import motor. Insertion of some proteins, however, occurs in the absence of ATP, questioning the need for the import motor during lateral insertion. We show here that the import motor associates with laterally inserted proteins even when its ATPase activity is not required. Furthermore, our results suggest a role for the import motor in lateral insertion. Thus, the import motor is involved in ATP-dependent translocation and ATP-independent lateral insertion. PMID:21546912

Crystal Structures of Two Bacterial 3-Hydroxy-3-methylglutaryl-CoA Lyases Suggest a Common Catalytic Mechanism among a Family of TIM Barrel Metalloenzymes Cleaving Carbon-Carbon Bonds

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

Forouhar,F.; Hussain, M.; Farid, R.

The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase catalyzes the terminal steps in ketone body generation and leucine degradation. Mutations in this enzyme cause a human autosomal recessive disorder called primary metabolic aciduria, which typically kills victims because of an inability to tolerate hypoglycemia. Here we present crystal structures of the HMG-CoA lyases from Bacillus subtilis and Brucella melitensis at 2.7 and 2.3 {angstrom} resolution, respectively. These enzymes share greater than 45% sequence identity with the human orthologue. Although the enzyme has the anticipated triose-phosphate isomerase (TIM) barrel fold, the catalytic center contains a divalent cation-binding site formed by a cluster ofmore » invariant residues that cap the core of the barrel, contrary to the predictions of homology models. Surprisingly, the residues forming this cation-binding site and most of their interaction partners are shared with three other TIM barrel enzymes that catalyze diverse carbon-carbon bond cleavage reactions believed to proceed through enolate intermediates (4-hydroxy-2-ketovalerate aldolase, 2-isopropylmalate synthase, and transcarboxylase 5S). We propose the name 'DRE-TIM metallolyases' for this newly identified enzyme family likely to employ a common catalytic reaction mechanism involving an invariant Asp-Arg-Glu (DRE) triplet. The Asp ligates the divalent cation, while the Arg probably stabilizes charge accumulation in the enolate intermediate, and the Glu maintains the precise structural alignment of the Asp and Arg. We propose a detailed model for the catalytic reaction mechanism of HMG-CoA lyase based on the examination of previously reported product complexes of other DRE-TIM metallolyases and induced fit substrate docking studies conducted using the crystal structure of human HMG-CoA lyase (reported in the accompanying paper by Fu, et al. (2006) J. Biol. Chem. 281, 7526-7532). Our model is consistent with extensive mutagenesis

JPL Researcher Tim Miller at the primary AirSAR station aboard NASA's DC-8 flying laboratory during the AirSAR 2004 campaign

NASA Image and Video Library

2004-03-03

JPL Researcher Tim Miller at the primary AirSAR station aboard NASA's DC-8 flying laboratory during the AirSAR 2004 campaign. AirSAR 2004 is a three-week expedition by an international team of scientists that will use an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR), in a mission ranging from the tropical rain forests of Central America to frigid Antarctica.

At the Cosmonaut Hotel crew quarters in Baikonur, Kazakhstan, Expedition 46-47 crewmember Tim Peake of the European Space Agency took a turn in a spinning chair to test his vestibular system Dec. 9 as part of his pre-launch training. Peake, Yuri Malenchenko of the Russian Federal Space Agency (Roscosmos) and Tim Kopra of NASA will launch Dec. 15 on their Soyuz TMA-19M spacecraft for a six-month mission on the International Space Station...NASA/Victor Zelentsov.

NASA Image and Video Library

2015-12-09

At the Cosmonaut Hotel crew quarters in Baikonur, Kazakhstan, Expedition 46-47 crewmember Tim Peake of the European Space Agency took a turn in a spinning chair to test his vestibular system Dec. 9 as part of his pre-launch training. Peake, Yuri Malenchenko of the Russian Federal Space Agency (Roscosmos) and Tim Kopra of NASA will launch Dec. 15 on their Soyuz TMA-19M spacecraft for a six-month mission on the International Space Station. NASA/Victor Zelentsov

Aerolian erosion, transport, and deposition of volcaniclastic sands among the shifting sand dunes, Christmas Lake Valley, Oregon: TIMS image analysis

NASA Technical Reports Server (NTRS)

Edgett, Kenneth S.; Ramsey, Michael S.; Christensen, Philip R.

1995-01-01

Remote sensing is a tool that, in the context of aeolian studies, offers a synoptic view of a dune field, sand sea, or entire desert region. Blount et al. (1990) presented one of the first studies demonstrating the power of multispectral images for interpreting the dynamic history of an aeolian sand sea. Blount's work on the Gran Desierto of Mexico used a Landsat TM scene and a linear spectral mixing model to show where different sand populations occur and along what paths these sands may have traveled before becoming incorporated into dunes. Interpretation of sand transport paths and sources in the Gran Desierto led to an improved understanding of the origin and Holocene history of the dunes. With the anticipated advent of the EOS-A platform and ASTER thermal infrared capability in 1998, it will become possible to look at continental sand seas and map sand transport paths using 8-12 mu m bands that are well-suited to tracking silicate sediments. A logical extension of Blount's work is to attempt a similar study using thermal infrared images. One such study has already begun by looking at feldspar, quartz, magnetite, and clay distributions in the Kelso Dunes of southern California. This paper describes the geology and application of TIMS image analysis of a less-well known Holocene dune field in south central Oregon using TIMS data obtained in 1991.

Thrombolytic-Related Asymptomatic Hemorrhagic Transformation Does Not Deteriorate Clinical Outcome: Data from TIMS in China

PubMed Central

Jia, Weihua; Liao, Xiaoling; Pan, Yuesong; Wang, Yilong; Cui, Tao; Zhou, Lichun; Wang, Yongjun

2015-01-01

Objective It has been unclear whether thrombolytic-related asymptomatic hemorrhagic transformation (AHT) affects the clinical outcome. To answer this question, we examined whether thrombolytic-related AHT affect short-term and long-term clinical outcome. Methods All data were collected from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China) registry. The patients were diagnosed as having AHT group and non- hemorrhagic transformation (HT) group based on clinical and imaging data. The patients with symptomatic hemorrhagic transformation were excluded from this study. Thrombolytic-related AHT was defined according to European-Australasian Acute Stroke Study (ECASS) II criteria. 90-day functional outcome, 7-day National Institutes of Health Stroke Scale (NIHSS) score, 7-day and 90-day mortalities were compared between two groups. Logistic regression analysis was used to evaluate the effects of AHT on a short-term and long-term clinical outcome. Results 904 of all 1440 patients in TIMS-China registry were enrolled. 89 (9.6%) patients presented with AHT after thrombolysis within 24-36h. These patients with AHT were more likely to be elder age, cardioembolic subtype, and to have higher National Institutes of Health Stroke Scale score before thrombolysis than patients without AHT. No significant difference was found on the odds of 7-day (95% CI:0.692 (0.218–2.195), (P = 0.532) or 90-day mortalities (95% CI:0.548 (0.237–1.268), P = 0.160) and modified Rankin Score(0–1) at 90-day (95% CI:0.798 (0.460–1.386), P = 0.423) or modified Rankin Score(0–2) at 90-day (95% CI:0.732 (0.429–1.253), P = 0.116) or modified Rankin Score(5–6) at 90-day (95% CI:0.375 (0.169–1.830), P = 0.116) between two groups. Conclusions Thrombolytic-related AHT does not deteriorate short-term and long-term clinical outcome. PMID:26619008

Behind the Cosmonaut Hotel crew quarters in Baikonur, Kazakhstan, Expedition 46-47 crewmember Tim Kopra of NASA (left) plants a tree at a site bearing his name Dec. 9 in a traditional pre-launch ceremony. Looking on are his crewmates, Tim Peake of the European Space Agency (center) and Yuri Malenchenko of the Russian Federal Space Agency (Roscosmos, right). The trio will launch Dec. 15 on their Soyuz TMA-19M spacecraft for a six-month mission on the International Space Station...NASA/Victor Zelentsov.

NASA Image and Video Library

2015-12-09

Behind the Cosmonaut Hotel crew quarters in Baikonur, Kazakhstan, Expedition 46-47 crewmember Tim Kopra of NASA (left) plants a tree at a site bearing his name Dec. 9 in a traditional pre-launch ceremony. Looking on are his crewmates, Tim Peake of the European Space Agency (center) and Yuri Malenchenko of the Russian Federal Space Agency (Roscosmos, right). The trio will launch Dec. 15 on their Soyuz TMA-19M spacecraft for a six-month mission on the International Space Station. NASA/Victor Zelentsov

Behind the Cosmonaut Hotel crew quarters in Baikonur, Kazakhstan, Expedition 46-47 crewmember Tim Peake of the European Space Agency (center) plants a tree at a site bearing his name Dec. 9 in a traditional pre-launch ceremony. Looking on are his crewmates, Yuri Malenchenko of the Russian Federal Space Agency (Roscosmos, left, and Tim Kopra of NASA (right). The trio will launch Dec. 15 on their Soyuz TMA-19M spacecraft for a six-month mission on the International Space Station...NASA/Victor Zelentsov.

NASA Image and Video Library

2015-12-09

Behind the Cosmonaut Hotel crew quarters in Baikonur, Kazakhstan, Expedition 46-47 crewmember Tim Peake of the European Space Agency (center) plants a tree at a site bearing his name Dec. 9 in a traditional pre-launch ceremony. Looking on are his crewmates, Yuri Malenchenko of the Russian Federal Space Agency (Roscosmos, left, and Tim Kopra of NASA (right). The trio will launch Dec. 15 on their Soyuz TMA-19M spacecraft for a six-month mission on the International Space Station. NASA/Victor Zelentsov

The Expedition 46-47 crewmembers arrive in Baikonur, Kazakhstan Nov. 30 for final pre-launch training following a flight from their training base at the Gagarin Cosmonaut Training Center in Star City, Russia and are greeted by school children. Tim Peake of the European Space Agency (left), Yuri Malenchenko of the Russian Federal Space Agency (Roscosmos, center) and Tim Kopra of NASA (right), will launch Dec. 15 on the Soyuz TMA-19M spacecraft for a six-month mission on the International Space Station...NASA / Victor Zelentsov .

NASA Image and Video Library

2015-11-30

The Expedition 46-47 crewmembers arrive in Baikonur, Kazakhstan Nov. 30 for final pre-launch training following a flight from their training base at the Gagarin Cosmonaut Training Center in Star City, Russia and are greeted by school children. Tim Peake of the European Space Agency (left), Yuri Malenchenko of the Russian Federal Space Agency (Roscosmos, center) and Tim Kopra of NASA (right), will launch Dec. 15 on the Soyuz TMA-19M spacecraft for a six-month mission on the International Space Station. NASA / Victor Zelentsov

Analysis of Mammalian Sphingolipids by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) and Tissue Imaging Mass Spectrometry (TIMS)

PubMed Central

Sullards, M. Cameron; Liu, Ying; Chen, Yanfeng; Merrill, Alfred H.

2011-01-01

Sphingolipids are a highly diverse category of molecules that serve not only as components of biological structures but also as regulators of numerous cell functions. Because so many of the structural features of sphingolipids give rise to their biological activity, there is a need for comprehensive or “sphingolipidomic” methods for identification and quantitation of as many individual subspecies as possible. This review defines sphingolipids as a class, briefly discusses classical methods for their analysis, and focuses primarily on liquid chromatography tandem mass spectrometry (LC-MS/MS) and tissue imaging mass spectrometry (TIMS). Recently, a set of evolving and expanding methods have been developed and rigorously validated for the extraction, identification, separation, and quantitation of sphingolipids by LC-MS/MS. Quantitation of these biomolecules is made possible via the use of an internal standard cocktail. The compounds that can be readily analyzed are free long-chain (sphingoid) bases, sphingoid base 1-phosphates, and more complex species such as ceramides, ceramide 1-phosphates, sphingomyelins, mono- and di-hexosylceramides sulfatides, and novel compounds such as the 1-deoxy- and 1-(deoxymethyl)-sphingoid bases and their N-acyl-derivatives. These methods can be altered slightly to separate and quantitate isomeric species such as glucosyl/galactosylceramide. Because these techniques require the extraction of sphingolipids from their native environment, any information regarding their localization in histological slices is lost. Therefore, this review also describes methods for TIMS. This technique has been shown to be a powerful tool to determine the localization of individual molecular species of sphingolipids directly from tissue slices. PMID:21749933

"Das Konkrete ist das Abstrakte, an das man sich schließlich gewöhnt hat." (Laurent Schwartz) Über den Ablauf des mathematischen Verstehens

NASA Astrophysics Data System (ADS)

Lowsky, Martin

Die im Titel genannte Aussage findet sich in den Lebenserinnerungen von Laurent Schwartz (1915-2002), einem der fruchtbarsten Mathematiker, Mitglied der Gruppe Bourbaki. Im Original lautet die Aussage: "un objet concret est un objet abstrait auquel on a fini par s'habituer." Schwartz erläutert sie am Beispiel des Integrals über {e^{-1/2{x^2}}} , das den Wert Wurzel aus 2π hat und in dem sich also die Zahlen e und π verknüpfen. Was Schwartz aber vor allem ausdrücken will, ist dies: Das mathematische Verständnisd geht langsam vor sich und es bedarf der Anstrengung. "Es ist eine Frage der Zeit und der Energie", sagt Schwartz, und gerade dies mache es so schwer, die höhere Mathematik unter das Volk zu bringen. Das Lernen und Lehren von Mathematik laufe eben mühevoll und langsam ab.

Integrating sequence and structural biology with DAS

PubMed Central

Prlić, Andreas; Down, Thomas A; Kulesha, Eugene; Finn, Robert D; Kähäri, Andreas; Hubbard, Tim JP

2007-01-01

Background The Distributed Annotation System (DAS) is a network protocol for exchanging biological data. It is frequently used to share annotations of genomes and protein sequence. Results Here we present several extensions to the current DAS 1.5 protocol. These provide new commands to share alignments, three dimensional molecular structure data, add the possibility for registration and discovery of DAS servers, and provide a convention how to provide different types of data plots. We present examples of web sites and applications that use the new extensions. We operate a public registry of DAS sources, which now includes entries for more than 250 distinct sources. Conclusion Our DAS extensions are essential for the management of the growing number of services and exchange of diverse biological data sets. In addition the extensions allow new types of applications to be developed and scientific questions to be addressed. The registry of DAS sources is available at PMID:17850653

Lag-3, Tim-3, and TIGIT co-inhibitory receptors with specialized functions in immune regulation

PubMed Central

Anderson, Ana C.; Joller, Nicole; Kuchroo, Vijay K.

2016-01-01

Summary Co-inhibitory receptors, such as CTLA-4 and PD-1, have an important role in regulating T cell responses and have proven to be effective targets in the setting of chronic diseases where constitutive co-inhibitory receptor expression on T cells dampens effector T cell responses. Unfortunately, many patients still fail to respond to therapies that target CTLA-4 and PD-1. The next wave of co-inhibitory receptor targets that are being explored in clinical trials include Lag-3, Tim-3, and TIGIT. These receptors while belonging to the same class of receptors as PD-1 and CTLA-4 exhibit unique functions especially at tissue sites where they regulate distinct aspects of immunity. Increased understanding of the specialized functions of these receptors will inform the rational application of therapies that target these receptors to the clinic. PMID:27192565

DASMiner: discovering and integrating data from DAS sources

PubMed Central

2009-01-01

Background DAS is a widely adopted protocol for providing syntactic interoperability among biological databases. The popularity of DAS is due to a simplified and elegant mechanism for data exchange that consists of sources exposing their RESTful interfaces for data access. As a growing number of DAS services are available for molecular biology resources, there is an incentive to explore this protocol in order to advance data discovery and integration among these resources. Results We developed DASMiner, a Matlab toolkit for querying DAS data sources that enables creation of integrated biological models using the information available in DAS-compliant repositories. DASMiner is composed by a browser application and an API that work together to facilitate gathering of data from different DAS sources, which can be used for creating enriched datasets from multiple sources. The browser is used to formulate queries and navigate data contained in DAS sources. Users can execute queries against these sources in an intuitive fashion, without the need of knowing the specific DAS syntax for the particular source. Using the source's metadata provided by the DAS Registry, the browser's layout adapts to expose only the set of commands and coordinate systems supported by the specific source. For this reason, the browser can interrogate any DAS source, independently of the type of data being served. The API component of DASMiner may be used for programmatic access of DAS sources by programs in Matlab. Once the desired data is found during navigation, the query is exported in the format of an API call to be used within any Matlab application. We illustrate the use of DASMiner by creating integrative models of histone modification maps and protein-protein interaction networks. These enriched datasets were built by retrieving and integrating distributed genomic and proteomic DAS sources using the API. Conclusion The support of the DAS protocol allows that hundreds of molecular biology

Atmospheric corrections for TIMS estimated emittance

NASA Technical Reports Server (NTRS)

Warner, T. A.; Levandowski, D. W.

1992-01-01

The estimated temperature of the average of 500 lines of Thermal Infrared Multispectral Scanner (TIMS) data of the Pacific Ocean, from flight line 94, collected on 30 Sep. 1988, at 1931 GMT is shown. With no atmospheric corrections, estimated temperature decreases away from nadir (the center of the scan line). A LOWTRAN modeled correction, using local radiosonde data and instrument scan angle information, results in reversed limb darkening effects for most bands, and does not adequately correct all bands to the same temperature. The atmosphere tends to re-radiate energy at the wavelengths at which it most absorbs, and thus the overall difference between corrected and uncorrected temperatures is approximately 40 C, despite the average LOWTRAN calculated transmittance of only 60 percent between 8.1 and 11.6 microns. An alternative approach to atmospheric correction is a black body normalization. This is done by calculating a normalization factor for each pixel position and wavelength, which when applied results in a single calculated temperature, as would be expected for a gray body with near uniform emittance. The black body adjustment is based on the atmospheric conditions over the sea. The ground elevation profile along the remaining 3520 scan lines (approximately 10 km) of flight line 94, up the slopes of Kilauea, determined from aircraft pressure and laser altimeter data is shown. This flight line includes a large amount of vegetation that is clearly discernible on the radiance image, being much cooler than the surrounding rocks. For each of the 3520 scan lines, pixels were classified as vegetation or 'other'. A moving average of 51 lines was applied to the composite vegetation emittance for each scan line, to reduce noise. Assuming vegetation to be like water, and to act as gray body with an emittance of 0.986 across the spectrum, it is shown that that the LOWTRAN induced artifacts are severe, and other than for the 0.9.9 micron channel, not significantly

Zim17/Tim15 links mitochondrial iron-sulfur cluster biosynthesis to nuclear genome stability.

PubMed

Díaz de la Loza, María Del Carmen; Gallardo, Mercedes; García-Rubio, María Luisa; Izquierdo, Alicia; Herrero, Enrique; Aguilera, Andrés; Wellinger, Ralf Erik

2011-08-01

Genomic instability is related to a wide-range of human diseases. Here, we show that mitochondrial iron-sulfur cluster biosynthesis is important for the maintenance of nuclear genome stability in Saccharomyces cerevisiae. Cells lacking the mitochondrial chaperone Zim17 (Tim15/Hep1), a component of the iron-sulfur biosynthesis machinery, have limited respiration activity, mimic the metabolic response to iron starvation and suffer a dramatic increase in nuclear genome recombination. Increased oxidative damage or deficient DNA repair do not account for the observed genomic hyperrecombination. Impaired cell-cycle progression and genetic interactions of ZIM17 with components of the RFC-like complex involved in mitotic checkpoints indicate that replicative stress causes hyperrecombination in zim17Δ mutants. Furthermore, nuclear accumulation of pre-ribosomal particles in zim17Δ mutants reinforces the importance of iron-sulfur clusters in normal ribosome biosynthesis. We propose that compromised ribosome biosynthesis and cell-cycle progression are interconnected, together contributing to replicative stress and nuclear genome instability in zim17Δ mutants.

Connecting the Dots in DAS

ERIC Educational Resources Information Center

Ford, Tracy

2012-01-01

Many institutions implement a distributed antenna system (DAS) as part of a holistic approach to providing better wireless coverage and capacity on campus. A DAS provides wireless service within a particular area or structure via a network of separate antenna nodes that are connected to a common source through fiber or coaxial cable. Because DAS…

Parent zonation in thermochronometers - resolving complexity revealed by ID-TIMS U-Pb dates and implications for the application of decay-based thermochronometers

NASA Astrophysics Data System (ADS)

Navin Paul, Andre; Spikings, Richard; Chew, David; Daly, J. Stephen; Ulyanov, Alexey

2017-04-01

High temperature (>350℃) U-Pb thermochronometers primarily use accessory minerals such as apatite, titanite and rutile, and assume that daughter isotopes are lost by thermally activated volume diffusion while the parent remains immobile. Studies exploiting such behaviour have been successfully used to reconstruct thermal histories spanning several hundred million years (e.g. Cochrane et al., 2014). However, outliers in date (ID-TIMS) vs diffusion length space are frequently observed, and grains are frequently found to be either too young or too old for expected thermal history solutions using the diffusion data of Cherniak et al. (2010). These deviations of single grain apatite U-Pb dates from expected behaviour could be caused by a combination of i) metamorphic (over-)growth, ii) fluid-aided Pb mobilisation during alteration/recrystallization, iii) parent isotope zonation, iv) metamictisation, and v) changes in diffusion length with time (e.g. fracturing). We present a large data set from the northern Andes of South America, where we compare apatite U-Pb ID-TIMS-(TEA) data with LA-ICP-MS element maps and in-situ apatite U-Pb LA-(MC)-ICP-MS dates. These are combined with U-Pb zircon and 40Ar/39Ar (muscovite) data to attempt to distinguish between thermally activated volume diffusion and secondary overgrowth/recrystallization. We demonstrate that in young (e.g. Phanerozoic) apatites that have not recrystallized or experienced metasomatic overgrowths, U-Pb dates are dominantly controlled by volume diffusion and intra-crystal uranium zonation. This implies that ID-TIMS analyses of apatites with zoned parent isotope distributions will not usually recover accurate thermal history solutions, and an in-situ dating method is required. Recovering the uranium distribution during in-situ analysis provides a means to account for parent zonation, substantially increasing the accuracy of the modelled t-T-paths. We present in-situ data from apatites where scatter in date v

Processing Approaches for DAS-Enabled Continuous Seismic Monitoring

NASA Astrophysics Data System (ADS)

Dou, S.; Wood, T.; Freifeld, B. M.; Robertson, M.; McDonald, S.; Pevzner, R.; Lindsey, N.; Gelvin, A.; Saari, S.; Morales, A.; Ekblaw, I.; Wagner, A. M.; Ulrich, C.; Daley, T. M.; Ajo Franklin, J. B.

2017-12-01

Distributed Acoustic Sensing (DAS) is creating a "field as laboratory" capability for seismic monitoring of subsurface changes. By providing unprecedented spatial and temporal sampling at a relatively low cost, DAS enables field-scale seismic monitoring to have durations and temporal resolutions that are comparable to those of laboratory experiments. Here we report on seismic processing approaches developed during data analyses of three case studies all using DAS-enabled seismic monitoring with applications ranging from shallow permafrost to deep reservoirs: (1) 10-hour downhole monitoring of cement curing at Otway, Australia; (2) 2-month surface monitoring of controlled permafrost thaw at Fairbanks, Alaska; (3) multi-month downhole and surface monitoring of carbon sequestration at Decatur, Illinois. We emphasize the data management and processing components relevant to DAS-based seismic monitoring, which include scalable approaches to data management, pre-processing, denoising, filtering, and wavefield decomposition. DAS has dramatically increased the data volume to the extent that terabyte-per-day data loads are now typical, straining conventional approaches to data storage and processing. To achieve more efficient use of disk space and network bandwidth, we explore improved file structures and data compression schemes. Because noise floor of DAS measurements is higher than that of conventional sensors, optimal processing workflow involving advanced denoising, deconvolution (of the source signatures), and stacking approaches are being established to maximize signal content of DAS data. The resulting workflow of data management and processing could accelerate the broader adaption of DAS for continuous monitoring of critical processes.

Application of U-Pb ID-TIMS dating to the end-Triassic global crisis: testing the limits on precision and accuracy in a multidisciplinary whodunnit (Invited)

NASA Astrophysics Data System (ADS)

Schoene, B.; Schaltegger, U.; Guex, J.; Bartolini, A.

2010-12-01

The ca. 201.4 Ma Triassic-Jurassic boundary is characterized by one of the most devastating mass-extinctions in Earth history, subsequent biologic radiation, rapid carbon cycle disturbances and enormous flood basalt volcanism (Central Atlantic Magmatic Province - CAMP). Considerable uncertainty remains regarding the temporal and causal relationship between these events though this link is important for understanding global environmental change under extreme stresses. We present ID-TIMS U-Pb zircon geochronology on volcanic ash beds from two marine sections that span the Triassic-Jurassic boundary and from the CAMP in North America. To compare the timing of the extinction with the onset of the CAMP, we assess the precision and accuracy of ID-TIMS U-Pb zircon geochronology by exploring random and systematic uncertainties, reproducibility, open-system behavior, and pre-eruptive crystallization of zircon. We find that U-Pb ID-TIMS dates on single zircons can be internally and externally reproducible at 0.05% of the age, consistent with recent experiments coordinated through the EARTHTIME network. Increased precision combined with methods alleviating Pb-loss in zircon reveals that these ash beds contain zircon that crystallized between 10^5 and 10^6 years prior to eruption. Mineral dates older than eruption ages are prone to affect all geochronologic methods and therefore new tools exploring this form of “geologic uncertainty” will lead to better time constraints for ash bed deposition. In an effort to understand zircon dates within the framework of a magmatic system, we analyzed zircon trace elements by solution ICPMS for the same volume of zircon dated by ID-TIMS. In one example we argue that zircon trace element patterns as a function of time result from a mix of xeno-, ante-, and autocrystic zircons in the ash bed, and approximate eruption age with the youngest zircon date. In a contrasting example from a suite of Cretaceous andesites, zircon trace elements

Data Acquisition System(DAS) Sustaining Engineering

NASA Technical Reports Server (NTRS)

1998-01-01

This paper presents general information describing the Data Acquisition System contract, a summary of objectives, tasks performed and completed. The hardware deliverables which are comprised of: 1) Two ground DAS units; 2) Two flight DAS units; 3) Logistic spares; and 4) Shipping containers are described. Also included are the data requirements and scope of the contract.

Comparative use of TIMS and SHRIMP for U Pb zircon dating of A-type granites and mafic tholeiitic layered complexes and dykes from the Corsican Batholith (France)

NASA Astrophysics Data System (ADS)

Cocherie, A.; Rossi, Ph.; Fanning, C. M.; Guerrot, C.

2005-05-01

The Corsica-Sardinia batholith in the southern realm of the Hercynian belt of Europe shows evidence for gravitational collapse of this part of the mountain belt, causing major felsic and mafic magmatism. The latest intrusions are composed of leucomonzogranite and late metaluminous and alkaline granite, associated with tholeiitic layered complexes and dykes. Three dating methods on zircon (Pb-evaporation, ID-TIMS and SHRIMP) were used to unravel the chronology of these felsic and mafic rocks. Dating of zircons by the conventional U-Pb method, using TIMS after zircon dissolution, achieved an analytical uncertainty of 1 Ma for favourable cases. The TIMS Pb-evaporation technique resulted in ages with an uncertainty range of 4 to 8 Ma. After 15 to 20 analyses with the SHRIMP method, a precision ranging from 2 to 5 Ma was obtained (all at 2 σ). The three methods applied to the same zircon population extracted from four A-type granites, show that the uncertainty ranges within 2-5 Ma according to the sample. This error seems to correspond to the real geochronological uncertainty that can be achieved. The results obtained show that all six tested alkaline granites were emplaced during a very short interval of about 3-5 Ma at about 288 Ma, almost contemporaneous with the leucomonzogranite emplacement (291-287 Ma) that ended the batholith formation. In addition, there is no significant gap with the age of emplacement of the mafic tholeiitic magmatism (around 286 Ma) crosscutting the "A-type" granites. The late alkaline granites definitely do not show up here as precursors of the Tethyan rifting that began at about 170 Ma, i.e. some 100 Ma after their emplacement. It is thus necessary to examine if alternative hypotheses to the anorogenic model of the A-type Younger Granite province better fit the new geochronological data. A model involving depleted continental-crust derived magma should be compatible with the timing and geodynamical constraints as far as isotopic data are

High precision calcium isotope analysis using 42Ca-48Ca double-spike TIMS technique

NASA Astrophysics Data System (ADS)

Feng, L.; Zhou, L.; Gao, S.; Tong, S. Y.; Zhou, M. L.

2014-12-01

Double spike techniques are widely used for determining calcium isotopic compositions of natural samples. The most important factor controlling precision of the double spike technique is the choice of appropriate spike isotope pair, the composition of double spikes and the ratio of spike to sample（CSp/CN）. We propose an optimal 42Ca-48Ca double spike protocol which yields the best internal precision for calcium isotopic composition determinations among all kinds of spike pairs and various spike compositions and ratios of spike to sample, as predicted by linear error propagation method. It is suggested to use spike composition of 42Ca/(42Ca+48Ca) = 0.44 mol/mol and CSp/(CN+ CSp)= 0.12mol/mol because it takes both advantages of the largest mass dispersion between 42Ca and 48Ca (14%) and lowest spike cost. Spiked samples were purified by pass through homemade micro-column filled with Ca special resin. K, Ti and other interference elements were completely separated, while 100% calcium was recovered with negligible blank. Data collection includes integration time, idle time, focus and peakcenter frequency, which were all carefully designed for the highest internal precision and lowest analysis time. All beams were automatically measured in a sequence by Triton TIMS so as to eliminate difference of analytical conditions between samples and standards, and also to increase the analytical throughputs. The typical internal precision of 100 duty cycles for one beam is 0.012‒0.015 ‰ (2δSEM), which agrees well with the predicted internal precision of 0.0124 ‰ (2δSEM). Our methods improve internal precisions by a factor of 2‒10 compared to previous methods of determination of calcium isotopic compositions by double spike TIMS. We analyzed NIST SRM 915a, NIST SRM 915b and Pacific Seawater as well as interspersed geological samples during two months. The obtained average δ44/40Ca (all relative to NIST SRM 915a) is 0.02 ± 0.02 ‰ (n=28), 0.72±0.04 ‰ (n=10) and 1

The TiM system: developing a novel telehealth service to improve access to specialist care in motor neurone disease using user-centered design.

PubMed

Hobson, Esther V; Baird, Wendy O; Partridge, Rebecca; Cooper, Cindy L; Mawson, Susan; Quinn, Ann; Shaw, Pamela J; Walsh, Theresa; Wolstenholme, Daniel; Mcdermott, Christopher J

2018-08-01

Attendance at a specialist multidisciplinary motor neurone disease (MND) clinic is associated with improved survival and may also improve quality of life and reduce hospital admissions. However, patients struggle to travel to clinic and may experience difficulties between clinic visits that may not be addressed in a timely manner. We wanted to explore how we could improve access to specialist MND care. We adopted an iterative, user-centered co-design approach, collaborating with those with experience of providing and receiving MND care including patients, carers, clinicians, and technology developers. We explored the unmet needs of those living with MND, how they might be met through service redesign and through the use of digital technologies. We developed a new digital solution and performed initial testing with potential users including clinicians, patients, and carers. We used these findings to develop a telehealth system (TiM) using an Android app into which patients and carers answer a series of questions about their condition on a weekly basis. The questions aim to capture all the physical, emotional, and social difficulties associated with MND. This information is immediately uploaded to the internet for review by the MND team. The data undergoes analysis in order to alert clinicians to any changes in a patient or carer's condition. We describe the benefits of developing a novel digitally enabled service underpinned by participatory design. Future trials must evaluate the feasibility and acceptability of the TiM system within a clinical environment.

With St. Basil���s Cathedral in Red Square in Moscow serving as a backdrop, Expedition 46-47 crewmembers Tim Kopra of NASA (left), Yuri Malenchenko of the Russian Federal Space Agency (Roscosmos, center) and Tim Peake of the European Space Agency (right) pose for pictures Nov. 23 after laying flowers at the Kremlin Wall where Russian space icons are interred. Peake, Malenchenko and Kopra will launch on Dec. 15 on the Soyuz TMA-19M spacecraft from the Baikonur Cosmodrome in Kazakhstan for a six-month mission on the International Space Station..NASA/Seth Marcantel

NASA Image and Video Library

2015-11-23

With St. Basil’s Cathedral in Red Square in Moscow serving as a backdrop, Expedition 46-47 crewmembers Tim Kopra of NASA (left), Yuri Malenchenko of the Russian Federal Space Agency (Roscosmos, center) and Tim Peake of the European Space Agency (right) pose for pictures Nov. 23 after laying flowers at the Kremlin Wall where Russian space icons are interred. Peake, Malenchenko and Kopra will launch on Dec. 15 on the Soyuz TMA-19M spacecraft from the Baikonur Cosmodrome in Kazakhstan for a six-month mission on the International Space Station. NASA/Seth Marcantel

Precise determination of δ88Sr in rocks, minerals, and waters by double-spike TIMS: A powerful tool in the study of chemical, geologic, hydrologic and biologic processes

USGS Publications Warehouse

Neymark, Leonid A.; Premo, Wayne R.; Mel'nikov, Nikolay N.; Emsbo, Poul

2014-01-01

We present strontium isotopic (88Sr/86Sr and 87Sr/86Sr) results obtained by 87Sr–84Sr double spike thermal ionization mass-spectrometry (DS-TIMS) for several standards as well as natural water samples and mineral samples of abiogenic and biogenic origin. The detailed data reduction algorithm and a user-friendly Sr-specific stand-alone computer program used for the spike calibration and the data reduction are also presented. Accuracy and precision of our δ88Sr measurements, calculated as permil (‰) deviations from the NIST SRM-987 standard, were evaluated by analyzing the NASS-6 seawater standard, which yielded δ88Sr = 0.378 ± 0.009‰. The first DS-TIMS data for the NIST SRM-607 potassium feldspar standard and for several US Geological Survey carbonate, phosphate, and silicate standards (EN-1, MAPS-4, MAPS-5, G-3, BCR-2, and BHVO-2) are also reported. Data obtained during this work for Sr-bearing solids and natural waters show a range of δ88Sr values of about 2.4‰, the widest observed so far in terrestrial materials. This range is easily resolvable analytically because the demonstrated external error (±SD, standard deviation) for measured δ88Sr values is typically ≤0.02‰. It is shown that the “true” 87Sr/86Sr value obtained by the DS-TIMS or any other external normalization method combines radiogenic and mass-dependent mass-fractionation effects, which cannot be separated. Therefore, the “true” 87Sr/86Sr and the δ87Sr parameter derived from it are not useful isotope tracers. Data presented in this paper for a wide range of naturally occurring sample types demonstrate the potential of the δ88Sr isotope tracer in combination with the traditional radiogenic 87Sr/86Sr tracer for studying a variety of biological, hydrological, and geological processes.

Mineralogic variability of the Kelso Dunes, Mojave Desert, California derived from Thermal Infrared Multispectral Scanner (TIMS) data

NASA Technical Reports Server (NTRS)

Ramsey, Michael S.; Howard, Douglas A.; Christensen, Philip R.; Lancaster, Nicholas

1993-01-01

Mineral identification and mapping of alluvial material using thermal infrared (TIR) remote sensing is extremely useful for tracking sediment transport, assessing the degree of weathering and locating sediment sources. As a result of the linear relation between a mineral's percentage in a given area (image pixel) and the depth of its diagnostic spectral features, TIR spectra can be deconvolved in order to ascertain mineralogic percentages. Typical complications such as vegetation, particle size and thermal shadowing are minimized upon examination of dunes. Actively saltating dunes contain little to no vegetation, are very well sorted and lack the thermal shadows that arise from rocky terrain. The primary focus of this work was to use the Kelso Dunes as a test location for an accuracy analysis of temperature/emissivity separation and linear unmixing algorithms. Accurate determination of ground temperature and component discrimination will become key products of future ASTER data. A decorrelation stretch of the TIMS image showed clear color variations within the active dunes. Samples collected from these color units were analyzed for mineralogy, grain size, and separated into endmembers. This analysis not only revealed that the dunes contained significant mineralogic variation, but were more immature (low quartz percentage) than previously reported. Unmixing of the TIMS data using the primary mineral endmembers produced unique variations within the dunes and may indicate near, rather than far, source locales for the dunes. The Kelso Dunes lie in the eastern Mojave Desert, California, approximately 95 km west of the Colorado River. The primary dune field is contained within a topographic basin bounded by the Providence, Granite Mountains, with the active region marked by three northeast trending linear ridges. Although active, the dunes appear to lie at an opposing regional wind boundary which produces little net movement of the crests. Previous studies have estimated

At the Kremlin Wall in Red Square in Moscow, Expedition 46-47 crewmember Tim Kopra of NASA lays flowers at the site where Russian space icons are interred in a ceremony Nov. 23. Looking on from left to right are backup crewmember Anatoly Ivanishin of the Russian Federal Space Agency (Roscosmos) and prime crewmembers Tim Peake of the European Space Agency and Yuri Malenchenko of Roscosmos. Peake, Malenchenko and Kopra will launch on Dec. 15 on the Soyuz TMA-19M spacecraft from the Baikonur Cosmodrome in Kazakhstan for a six-month mission on the International Space Station..NASA/Seth Marcantel

NASA Image and Video Library

2015-11-23

At the Kremlin Wall in Red Square in Moscow, Expedition 46-47 crewmember Tim Kopra of NASA lays flowers at the site where Russian space icons are interred in a ceremony Nov. 23. Looking on from left to right are backup crewmember Anatoly Ivanishin of the Russian Federal Space Agency (Roscosmos) and prime crewmembers Tim Peake of the European Space Agency and Yuri Malenchenko of Roscosmos. Peake, Malenchenko and Kopra will launch on Dec. 15 on the Soyuz TMA-19M spacecraft from the Baikonur Cosmodrome in Kazakhstan for a six-month mission on the International Space Station. NASA/Seth Marcantel

Bacillus coagulans GBI-30, 6086 increases plant protein digestion in a dynamic, computer-controlled in vitro model of the small intestine (TIM-1).

PubMed

Keller, D; Van Dinter, R; Cash, H; Farmer, S; Venema, K

2017-05-30

The aim of this study was to assess the potential of the probiotic Bacillus coagulans GBI-30, 6086 [GanedenBC 30 ] (BC30) to aid in protein digestion of alimentary plant proteins. To test this, three plant proteins, from pea, soy and rice, were digested in a validated in vitro model of the stomach and small intestine (TIM-1) in the absence and in the presence of BC30. Samples were taken from the TIM-1 fractions that mimic uptake of amino acids by the host and analysed for α-amino nitrogen (AAN) and total nitrogen (TN). Both were increased by BC30 for all three plant proteins sources. The ratio of TN/AAN indicated that for pea protein digestion was increased by BC30, but the degree of polymerisation of the liberated small peptides and free amino acids was not changed. For soy and rice, however, BC30 showed a 2-fold reduction in the TN/AAN ratio, indicating that the liberated digestion products formed during digestion in the presence of BC30 were shorter peptides and more free amino acids, than those liberated in the absence of BC30. As BC30 increased protein digestion and uptake in the upper gastrointestinal (GI) tract, it consequently also reduced the amount of protein that would be delivered to the colon, which could there be fermented into toxic metabolites by the gut microbiota. Thus, the enhanced protein digestion by BC30 showed a dual benefit: enhanced amino acid bioavailability from plant proteins in the upper GI tract, and a healthier environment in the colon.

The plutonic-volcanic connection in porphyry copper deposits: Evidence from zircon geochemistry and high-precision CA-ID-TIMS geochronology

NASA Astrophysics Data System (ADS)

Buret, Y.; Von Quadt, A.; Wotzlaw, J. F.; Heinrich, C. A.

2016-12-01

Porphyry Cu deposits represent the interface between plutonic and volcanic domains of upper crustal magmatic systems. These deposits are typically composed of multiple porphyritic intrusions which constrain the duration of ore formation to a maximum of several 104 years [1] and are commonly intruded into the base of volcanoes. The relationship between volcanic activity and porphyry stocks is often difficult to establish, as they are rarely exposed together unless later faulting and/or tilting occurred [2]. In order to investigate the relationships between extrusive magmatism and porphyry Cu formation we compare zircon petrochronology from late stage volcanic units with the nearby world class Bajo de la Alumbrera porphyry Cu deposit, from the Late Miocene Farallón Negro Volcanic Complex (FNVC) in Northwest Argentina. In this study we texturally characterise zircon crystals by CL-imaging prior to obtaining in-situ geochemical and geochronological information by LA-ICP-MS. Analysed zircon grains were then extracted and analysed by high precision CA-ID-TIMS. This approach has the two-fold benefit of screening for inherited cores, and obtaining texturally defined geochemical information, prior to dissolution of the zircon crystal for CA-ID-TIMS analysis. We use this information to establish temporal and geochemical links between studied volcanic and porphyry units in the FNVC. The results of this study suggest a close temporal and genetic link between the Bajo de la Alumbrera porphyry Cu deposit and the late stage volcanism at the FNVC. Voluminous explosive volcanism immediately following porphyry formation has important implications for the thermal and rheological state of the magma that is parental to the porphyries and fed the eruption. Further work investigating the geochemistry of other accessory and major minerals could shed further light on the evolution of the magmatic body prior to eruption/ emplacement. References: [1] Buret et al. (2016) EPSL 450:120-131; [2

Permian U-Pb (CA-TIMS) zircon ages from Australia and China: Constraining the time scale of environmental and biotic change

NASA Astrophysics Data System (ADS)

Denyszyn, S. W.; Mundil, R.; Metcalfe, I.; He, B.

2010-12-01

In eastern Australia, the interconnected Bowen and Sydney Basins are filled with terrestrial sediments of late Paleozoic to early Mesozoic age. These sedimentary units record significant evolutionary events of eastern Gondwana during the time interval between two major mass extinctions (end Middle Permian and Permian-Triassic), and also provide lithological evidence for the Carboniferous-Permian Late Paleozoic Ice Age of southern Pangea, considered to be divisible into up to seven discrete glaciation events in Australia [e.g., 1]. These glaciations are currently assigned ages that indicate that the last of the glaciations predate the end Middle Permian mass extinction at ca. 260 Ma. However, the estimates for the time and durations are largely based on biostratigraphy and lithostratigraphy that, in the absence of robust and precise radioisotopic ages, are unacceptably fragile for providing an accurate high-resolution framework. Interbedded with the sediments are numerous tuff layers that contain zircon, many of which are associated with extensive coal measures in the Sydney and Bowen Basins. Published SHRIMP U-Pb zircon ages [2, 3] have been shown to be less precise and inaccurate when compared to ages applying the CA-TIMS method to the same horizons. Also within the late Middle Permian, the eruption of the Emeishan flood basalts in SW China has been proposed to have caused the end Middle Permian mass extinction [e.g., 4], though a causal link between these events demands a rigorous test that can only be provided by high-resolution geochronology. We present new U-Pb (CA-TIMS) zircon ages on tuff layers from the Sydney and Bowen Basins, with the purpose of generating a timescale for the Upper Permian of Australia to allow correlation with different parts of the world. Initial results, with permil precision, date a tuff layer within the uppermost Bandanna Fm. to ca. 252 Ma, a tuff within the Moranbah Coal Measures to ca. 256 Ma, and a tuff within the Ingelara Fm. to

Uranium and Calcium Isotope Ratio Measurements using the Modified Total Evaporation Method in TIMS

NASA Astrophysics Data System (ADS)

Richter, S.; Kuehn, H.; Berglund, M.; Hennessy, C.

2010-12-01

A new version of the "modified total evaporation" (MTE) method for isotopic analysis by multi-collector thermal ionization mass spectrometry (TIMS), with high analytical performance and designed in a more user-friendly and routinely applicable way, is described in detail. It is mainly being used for nuclear safeguards measurements of U and Pu and nuclear metrology, but can readily be applied to other scientific tasks in geochemistry, e.g. for Sr, Nd and Ca, as well. The development of the MTE method was organized in collaboration of several "key nuclear mass spectrometry laboratories", namely the New Brunswick Laboratory (NBL), the Institute for Transuranium Elements (ITU), the Safeguards Analytical Laboratory (now Safeguards Analytical Services, SGAS) of the International Atomic Energy Agency (IAEA) and the Institute for Reference Materials and Measurements (IRMM), with IRMM taking the leading role. The manufacturer of the TRITON TIMS instrument, Thermo Fisher Scientific, integrated this method into the software of the instrument. The development has now reached its goal to become a user-friendly and routinely useable method for uranium isotope ratio measurements with high precision and accuracy. Due to the use of the “total evaporation” (TE) method the measurement of the "major" uranium isotope ratio 235U/238U is routinely being performed with a precision of 0.01% to 0.02%. The use of a (certified) reference material measured under comparable conditions is emphasized to achieve an accuracy at a level of 0.02% - depending on the stated uncertainty of the certified value of the reference material. In contrast to the total evaporation method (TE), in the MTE method the total evaporation sequence is interrupted on a regular basis to allow for correction for background from peak tailing, internal calibration of a secondary electron multiplier (SEM) detector versus the Faraday cups, and ion source re-focusing. Therefore, the most significant improvement using the

A simple model of circadian rhythms based on dimerization and proteolysis of PER and TIM

PubMed Central

Tyson, JJ; Hong, CI; Thron, CD; Novak, B

1999-01-01

Many organisms display rhythms of physiology and behavior that are entrained to the 24-h cycle of light and darkness prevailing on Earth. Under constant conditions of illumination and temperature, these internal biological rhythms persist with a period close to 1 day ("circadian"), but it is usually not exactly 24 h. Recent discoveries have uncovered stunning similarities among the molecular circuitries of circadian clocks in mice, fruit flies, and bread molds. A consensus picture is coming into focus around two proteins (called PER and TIM in fruit flies), which dimerize and then inhibit transcription of their own genes. Although this picture seems to confirm a venerable model of circadian rhythms based on time-delayed negative feedback, we suggest that just as crucial to the circadian oscillator is a positive feedback loop based on stabilization of PER upon dimerization. These ideas can be expressed in simple mathematical form (phase plane portraits), and the model accounts naturally for several hallmarks of circadian rhythms, including temperature compensation and the per(L) mutant phenotype. In addition, the model suggests how an endogenous circadian oscillator could have evolved from a more primitive, light-activated switch. PMID:20540926

The many Metaphysics within Physics. Essay review of 'The Metaphysics within Physics' by Tim Maudlin

NASA Astrophysics Data System (ADS)

Suárez, Mauricio

Tim Maudlin's new book The Metaphysics within Physics (Oxford University Press, 2007) collects six essays by one of the most thoughtful and original minds working in the philosophy of physics nowadays. Some had previously circulated informally for years. For example, Chapter 1 ('A Modest Proposal Concerning Laws, Counterfactuals and Explanations') is as old as my own philosophical career-I recall reading a draft in the early 1990s. The mere publication of such a long-awaited collection is therefore already good news. In addition, the degree of coherence and the lack of redundancy are greater than one would expect from a collection of disparate essays written at diverse times and with a range of different targets. The whole book can be understood coherently as an extended argument in favor of a particular 'physics-based' methodology for inquiry in metaphysics. This methodology recommends a detailed and thorough analysis of current physics as a benchmark for any thesis, dispute or argument in metaphysics. It follows that proper metaphysical inquiry must be suitably informed not just about the current state of play in analytical metaphysics but also about the current state of development of the relevant part of present day physics.

The Arctic Predictability and Prediction on Seasonal-to-Interannual TimEscales (APPOSITE) project: a summary

NASA Astrophysics Data System (ADS)

Hawkins, Ed; Day, Jonny; Tietsche, Steffen

2016-04-01

Recent years have seen significant developments in seasonal-to-interannual timescale climate prediction capabilities. However, until recently the potential of such systems to predict Arctic climate had not been assessed. We describe a multi-model predictability experiment which was run as part of the Arctic Predictability and Prediction On Seasonal to Inter-annual TimEscales (APPOSITE) project. The main goal of APPOSITE was to quantify the timescales on which Arctic climate is predictable. In order to achieve this, a coordinated set of idealised initial-value predictability experiments, with seven general circulation models, was conducted. This was the first model intercomparison project designed to quantify the predictability of Arctic climate on seasonal to inter-annual timescales. Here we provide a summary and update of the project's results which include: (1) quantifying the predictability of Arctic climate, especially sea ice; (2) the state-dependence of this predictability, finding that extreme years are potentially more predictable than neutral years; (3) analysing a spring 'predictability barrier' to skillful forecasts; (4) initial sea ice thickness information provides much of the skill for summer forecasts; (5) quantifying the sources of error growth and uncertainty in Arctic predictions. The dataset is now publicly available.

PD-1+Tim-3+ CD8+ T Lymphocytes Display Varied Degrees of Functional Exhaustion in Patients with Regionally Metastatic Differentiated Thyroid Cancer

PubMed Central

Severson, Jill J.; Serracino, Hilary S.; Mateescu, Valerica; Raeburn, Christopher D.; C.McIntyre, Robert; Sams, Sharon B.; Haugen, Bryan R.; French, Jena D.

2015-01-01

Regional metastatic differentiated thyroid cancer (mDTC) provides a unique model in which to study the tumor-immune interface. These lymph node (LN) metastases persist for years, generally without progression to distant metastases. While the immune system likely impedes disease progression, it is unsuccessful in eliminating disease. Our previous studies revealed that programmed death-1 (PD-1)+ T cells were enriched in tumor-involved lymph nodes (TILN). Tumor-associated leukocytes and tumor cells were collected from grossly involved LNs from 12 patients to further characterize the phenotype and functional potential of mDTC-associated PD-1+ T cells. PD-1+CD4+ and PD-1+CD8+ T cells were enriched in 8/12 TILN samples. PD-1+ T cells co-expressed Tim-3 and CD69 and failed to down-regulate CD27. CD8+ T cells, but not CD4+ T cells, from these samples were variably deficient in their ability to produce effector cytokines when compared to control TILNs that lacked resident PD-1+ T cells. PD-1+CD8+ T cells were capable of exocytosis but lacked intracellular perforin. Surprisingly, T-cell proliferative capacity was largely maintained in all samples. Thus, while PD-1 expression by mDTC-associated CD8+ T cells was associated with dysfunction, exhaustion was not complete. Notably, molecular markers of exhaustion did not translate to dysfunction in all samples or in CD4+ T cells. Regulatory T (Treg) cells, PD-L1, and galectin-9 were commonly found in mDTC and likely contributed to the initiation of T-cell exhaustion and disease progression. Therapies that release the effects of PD-1 and Tim-3 and reduce the suppressive effects of Tregs may encourage tumor elimination in patients with mDTC. PMID:25701326

Mexican Infrared-Optical New Technology Telescope: The TIM project

NASA Astrophysics Data System (ADS)

Salas, L.

1998-11-01

The scientific goals for TIM are an image quality of 0.25", consistent with the seeing at our site, optimization for the infrared as many scientific programs are going in that region of the spectrum, a M1 diameter in excess of 6.5 meters and a field of view limited to 10 arc minutes. Practical reasons, such as the limited funding available and the requirement of mexican financial agencies that the telescope should be built and installed in Mexico, lead us to decide for a segmented telescope, with a single secondary mirror, a single cassegrain focus and a light high stifness tubular structure. ALthough we are still working on the conceptual design of the telescope, there are some concepts that we are pursuing. The optical desing (M1+M2) is Ritchey-Cretien type with an hyperbolic primary 7.8 m od F/1.5 and a 0.9 m diameter f/15 secondary mirror. This will give a plate scale of 1.7 "/mm. This is 0.03 "/pix in direct mode, enough for AO goals. As for direct imaging, a factor of 5 reduction with 20 cm diam optical components would be able to produce 5' fields on a 2048, 20 microns type detector with 0.17"/pix. This implies that, with the use of auxiliary optics which is a common need for each particular instrument anyway, a wide variety of needs can be accomodated with a single secondary mirror. Choping for infrared observations would however introduce a additional cost in the secondary mirror. Alternatively the use of cold tertiary choping mirror is currently under study. The M1+M2 design currently aquires d80 of 0.17" in a 5' field without correction and 1" in a 10' field, that would require a field correcting lens. The M1 mirror will be segmented into 19 1.8 m diameter segments. There are 4 kinds of segments, the central, which we have kept to provide a reference for phasing, 6 more segments for the first ring and 12 in the outer ring, of two different kinds. The spacing between the segments is 5 mm, enough to reduce the inter-segment thermal background to half a

Pedagogical Basis of DAS Formalism in Engineering Education

ERIC Educational Resources Information Center

Hiltunen, J.; Heikkinen, E.-P.; Jaako, J.; Ahola, J.

2011-01-01

The paper presents a new approach for a bachelor-level curriculum structure in engineering. The approach is called DAS formalism according to its three phases: description, analysis and synthesis. Although developed specifically for process and environmental engineering, DAS formalism has a generic nature and it could also be used in other…

Comparing pre- and post-chemical abrasion ages for Miocene Peach Springs Tuff zircon from ID-TIMS and SIMS analyses

NASA Astrophysics Data System (ADS)

Lidzbarski, M. I.; Mundil, R.; Miller, J. S.; Vazquez, J. A.

2012-12-01

removes micro-inclusions that typically contain common Pb. Thermal annealing followed by CA techniques were used for ID-TIMS dating of a sub-set of zircon crystals previously analyzed by SIMS. Prior to TIMS analyses, zircon crystals were imaged by scanning electron microscopy (SEM) to evaluate the effects of CA on crystal domains sampled by SIMS. SEM images reveal that whole portions of crystals were removed by the CA technique, and a heterogeneous pattern of etching that was not confined to specific compositional zones visible in cathodoluminescence. Most of the SIMS sputter pits that yield spurious ages, are associated with etching and/or preferential annealing by the combined annealing and CA technique, suggesting that the young ages relative to the 40Ar/39Ar age may be due to Pb loss. ID-TIMS yields a coherent U-Pb age population of 18.8 Ma, with several older and younger crystals that might reflect xenocrysts, Pb-loss, and/or younger crystallization. In order to maintain spatial resolution and further evaluate the effects of Pb-loss in PST zircon, the annealing and CA-technique will be applied to zircon prior to SIMS dating. References: Reid and Coath, 2000, Geology 28: 443 Renne et al., 2010, GCA 78: 5349

Comparison of Different Ion Mobility Setups Using Poly (Ethylene Oxide) PEO Polymers: Drift Tube, TIMS, and T-Wave

NASA Astrophysics Data System (ADS)

Haler, Jean R. N.; Massonnet, Philippe; Chirot, Fabien; Kune, Christopher; Comby-Zerbino, Clothilde; Jordens, Jan; Honing, Maarten; Mengerink, Ynze; Far, Johann; Dugourd, Philippe; De Pauw, Edwin

2018-01-01

Over the years, polymer analyses using ion mobility-mass spectrometry (IM-MS) measurements have been performed on different ion mobility spectrometry (IMS) setups. In order to be able to compare literature data taken on different IM(-MS) instruments, ion heating and ion temperature evaluations have already been explored. Nevertheless, extrapolations to other analytes are difficult and thus straightforward same-sample instrument comparisons seem to be the only reliable way to make sure that the different IM(-MS) setups do not greatly change the gas-phase behavior. We used a large range of degrees of polymerization (DP) of poly(ethylene oxide) PEO homopolymers to measure IMS drift times on three different IM-MS setups: a homemade drift tube (DT), a trapped (TIMS), and a traveling wave (T-Wave) IMS setup. The drift time evolutions were followed for increasing polymer DPs (masses) and charge states, and they are found to be comparable and reproducible on the three instruments. [Figure not available: see fulltext.

M-DAS: System for multispectral data analysis. [in Saginaw Bay, Michigan

NASA Technical Reports Server (NTRS)

Johnson, R. H.

1975-01-01

M-DAS is a ground data processing system designed for analysis of multispectral data. M-DAS operates on multispectral data from LANDSAT, S-192, M2S and other sources in CCT form. Interactive training by operator-investigators using a variable cursor on a color display was used to derive optimum processing coefficients and data on cluster separability. An advanced multivariate normal-maximum likelihood processing algorithm was used to produce output in various formats: color-coded film images, geometrically corrected map overlays, moving displays of scene sections, coverage tabulations and categorized CCTs. The analysis procedure for M-DAS involves three phases: (1) screening and training, (2) analysis of training data to compute performance predictions and processing coefficients, and (3) processing of multichannel input data into categorized results. Typical M-DAS applications involve iteration between each of these phases. A series of photographs of the M-DAS display are used to illustrate M-DAS operation.

How to specify and measure sensitivity in Distributed Acoustic Sensing (DAS)?

NASA Astrophysics Data System (ADS)

Gabai, Haniel; Eyal, Avishay

2017-04-01

In Rayleigh-scattering-based Distributed Acoustic Sensing (DAS) an optical fiber is transformed into an array of thousands of 'virtual microphones'. This approach has gained tremendous popularity in recent years and is one of the most successful examples of a fiber-optic sensing method which made its way from the academia to the market. Despite the great amount of work done in this field, sensitivity, which is ones of the most critical parameters of any sensing technique, was rarely investigated in this context. In particular, little attention was given to its random characteristics. Without careful consideration of the random aspects of DAS, any attempt to specify its sensitivity or to compare between different DAS modalities is of limited value. Recently we introduced a new statistical parameter which defines DAS sensitivity and enables comparison between the performances of different DAS systems. In this paper we generalize the previous parameter and give a broader, simple and intuitive definition to DAS sensitivity. An important attribute of these parameters is that they can be easily extracted from the static backscatter profile of the sensing fiber. In the paper we derive the relation between DAS sensitivity and the static backscatter profile and present an experimental verification of this relation.

Using DAS for reflection seismology - lessons learned from three field studies

NASA Astrophysics Data System (ADS)

Freifeld, B. M.; Dou, S.; Ajo Franklin, J. B.; Robertson, M.; Wood, T.; Daley, T. M.; White, D. J.; Worth, K.; Pevzner, R.; Yavuz, S.; dos Santos Maia Correa, J.; McDonald, S.

2017-12-01

Distributed acoustic sensing (DAS) has rapidly gained recognition for its potential for seismic imaging. For surface reflection seismology, the wide spatial aperture afforded by DAS is a primary motivation for its application, however the lower SNR of DAS has proven to be a significant impediment to acquiring data that can replace conventional receiver arrays. A further limitation of DAS cables is that the strain-dependent response is insensitive to acoustic energy which arrives orthogonal to the cable axis, reducing its effectiveness at seeing energy reflected from the deep subsurface. To enhance the sensitivity of DAS cables for reflection seismology, we have trialed at three field sites DAS cables with helical construction in which there is a significant component of optical fiber that is coincident with arriving broadside energy. We have installed helically wound DAS cables at the PTRC Aquistore Project in Saskatchewan, Canada and the CO2CRC Otway Project in Nirranda South, Victoria, Australia in shallow trenches. For the ADM Intelligent Monitoring Systems Project in Decatur, Illinois, USA we used a horizontal directional drilling method to install DAS cables at a depth that is greater than can be achieved using trenched installation. At the Otway and ADM sites we operated surface orbital vibrators (SOVs) at fixed locations to enhance sensitivity by stacking large numbers of sweeps. We present survey results from the three sites. Analysis of both vibroseis survey and SOV results show that the helical cable design achieves its primary objective of improving sensitivity to reflected energy, with further gains needed to achieve the sensitivity of conventional geophones.

Study of morphometry to debit drainage basin (DAS) arau Padang city

NASA Astrophysics Data System (ADS)

Utama, Lusi; Amrizal, Berd, Isril; Zuherna

2017-11-01

High intensity rain that happened in Padang city cause the happening of floods at DAS Arau. Floods that happened in Padang besides caused high rain intensity, require to be by research about morphometry that is cause parameter the happening of floods. Morphometry drainage basin physical network (DAS) quantitatively related to DAS geomorphology that is related to form of DAS, river network, closeness of stream, ramp, usage of farm, high and gradient steepness of river. Form DAS will influence rain concentration to outlet. Make an index to closeness of stream depict closeness of river stream at one particular DAS. Speed of river stream influenced by storey, level steepness of river. Steepness storey, level is comparison of difference height of river downstream and upstream. Ever greater of steepness of river stream, excelsior speed of river stream that way on the contrary. High to lower speed of river stream influence occurrence of floods, more than anything else if when influenced by debit big. Usage of farm in glove its link to process of infiltration where if geology type which is impermeable, be difficult the happening of infiltration, this matter will enlarge value of run off. Research by descriptive qualitative that is about characteristic of DAS. Method the used is method survey with data collecting, in the form of rainfall data of year 2005 until year 2015 and Image of DEM IFSAR with resolution 5 meter, analyzed use Software ARGIS. Result of research got by DAS reside in at condition of floods gristle.

Ground Motion Analysis of Co-Located DAS and Seismometer Sensors

NASA Astrophysics Data System (ADS)

Wang, H. F.; Fratta, D.; Lord, N. E.; Lancelle, C.; Thurber, C. H.; Zeng, X.; Parker, L.; Chalari, A.; Miller, D.; Feigl, K. L.; Team, P.

2016-12-01

The PoroTomo research team deployed 8700-meters of Distributed Acoustic Sensing (DAS) cable in a shallow trench and 400-meters in a borehole at Brady Hot Springs, Nevada in March 2016 together with an array of 246, three-component geophones. The seismic sensors occupied a natural laboratory 1500 x 500 x 400 meters overlying the Brady geothermal field. The DAS cable was laid out in three parallel zig-zag lines with line segments approximately 100-meters in length and geophones were spaced at approximately 50-m intervals. In several line segments, geophones were co-located within one meter of the DAS cable. Both DAS and the conventional geophones recorded continuously over 15 days. A large Vibroseis truck (T-Rex) provided the seismic source at approximately 250 locations outside and within the array. The Vibroseis protocol called for excitation in one vertical and two orthogonal horizontal directions at each location. For each mode, three, 5-to-80-Hz upsweeps were made over 20 seconds. In addition, a moderate-sized earthquake with a local magnitude of 4.3 was recorded on March 21, 2016. Its epicenter was approximately 150-km away. Several DAS line segments with co-located geophone stations were used to test relationships between the strain rate recorded by DAS and ground velocity recorded by the geophones.

DAS: A Data Management System for Instrument Tests and Operations

NASA Astrophysics Data System (ADS)

Frailis, M.; Sartor, S.; Zacchei, A.; Lodi, M.; Cirami, R.; Pasian, F.; Trifoglio, M.; Bulgarelli, A.; Gianotti, F.; Franceschi, E.; Nicastro, L.; Conforti, V.; Zoli, A.; Smart, R.; Morbidelli, R.; Dadina, M.

2014-05-01

The Data Access System (DAS) is a and data management software system, providing a reusable solution for the storage of data acquired both from telescopes and auxiliary data sources during the instrument development phases and operations. It is part of the Customizable Instrument WorkStation system (CIWS-FW), a framework for the storage, processing and quick-look at the data acquired from scientific instruments. The DAS provides a data access layer mainly targeted to software applications: quick-look displays, pre-processing pipelines and scientific workflows. It is logically organized in three main components: an intuitive and compact Data Definition Language (DAS DDL) in XML format, aimed for user-defined data types; an Application Programming Interface (DAS API), automatically adding classes and methods supporting the DDL data types, and providing an object-oriented query language; a data management component, which maps the metadata of the DDL data types in a relational Data Base Management System (DBMS), and stores the data in a shared (network) file system. With the DAS DDL, developers define the data model for a particular project, specifying for each data type the metadata attributes, the data format and layout (if applicable), and named references to related or aggregated data types. Together with the DDL user-defined data types, the DAS API acts as the only interface to store, query and retrieve the metadata and data in the DAS system, providing both an abstract interface and a data model specific one in C, C++ and Python. The mapping of metadata in the back-end database is automatic and supports several relational DBMSs, including MySQL, Oracle and PostgreSQL.

Radiogenic Isotopes As Paleoceanographic Tracers in Deep-Sea Corals: Advances in TIMS Measurements of Pb Isotopes and Application to Southern Ocean Corals

NASA Astrophysics Data System (ADS)

Wilson, D. J.; van de Flierdt, T.; Bridgestock, L. J.; Paul, M.; Rehkamper, M.; Robinson, L. F.; Adkins, J. F.

2014-12-01

Deep-sea corals have emerged as a valuable archive of deep ocean paleoceanographic change, with uranium-series dating providing absolute ages and the potential for centennial resolution. In combination with measurements of radiocarbon, neodymium isotopes and clumped isotopes, this archive has recently been exploited to reconstruct changes in ventilation, water mass sourcing and temperature in relation to millennial climate change. Lead (Pb) isotopes in both corals and seawater have also been used to track anthropogenic inputs through space and time and to trace transport pathways within the oceans. Better understanding of the oceanic Pb cycle is emerging from the GEOTRACES programme. However, while Pb isotopes have been widely used in environmental studies, their full potential as a (pre-anthropogenic) paleoceanographic tracer remains to be exploited. In deep-sea corals, challenges exist from low Pb concentrations in aragonite in comparison to secondary coatings, the potential for contamination, and the efficient elemental separation required for measurement by thermal ionisation mass spectrometry (TIMS). Here we discuss progress in measuring Pb isotopes in coral aragonite using a 207Pb-204Pb double spike on a ThermoFinnigan Triton TIMS. For a 2 ng NIST-981 Pb standard, the long term reproducibility (using 1011 Ω resistors) is ~1000 ppm (2 s.d.) on 206Pb/204Pb, 207Pb/204Pb and 208Pb/204Pb ratios. We now show that using a new 1012 Ω resistor to measure the small 204Pb beam improves the internal precision on these ratios from ~500 ppm (2 s.e.) to ~250 ppm (2 s.e.) and we envisage a potential improvement in the long term reproducibility as a consequence. We further assess the internal precision and external reproducibility of our method using a BCR-2 rock standard and an in-house coral standard. Preliminary evidence on the application of this method to natural samples is derived from cleaning experiments and replication tests on deep-sea corals from the Southern

A preliminary psychometric evaluation of Music in Dementia Assessment Scales (MiDAS).

PubMed

McDermott, Orii; Orgeta, Vasiliki; Ridder, Hanne Mette; Orrell, Martin

2014-06-01

Music in Dementia Assessment Scales (MiDAS), an observational outcome measure for music therapy with people with moderate to severe dementia, was developed from qualitative data of focus groups and interviews. Expert and peer consultations were conducted at each stage of the scale development to maximize its content validity. This study aimed to evaluate the psychometric properties of MiDAS. Care home residents with dementia attended weekly group music therapy for up to ten sessions. Music therapists and care home staff were requested to complete weekly MiDAS ratings. The Quality of Life Scale (QoL-AD) was completed at three time-points. A total of 629 (staff = 306, therapist = 323) MiDAS forms were completed. The statistical analysis revealed that MiDAS has high therapist inter-rater reliability, low staff inter-rater reliability, adequate staff test-retest reliability, adequate concurrent validity, and good construct validity. High factor loadings between the five MiDAS Visual Analogue Scale (VAS) items, levels of Interest, Response, Initiation, Involvement, and Enjoyment, were found. This study indicates that MiDAS has good psychometric properties despite the small sample size. Future research with a larger sample size could provide a more in-depth psychometric evaluation, including further exploration of the underlying factors. MiDAS provides a measure of engagement with musical experience and offers insight into who is likely to benefit on other outcomes such as quality of life or reduction in psychiatric symptoms.

Crosslinking effect of dialdehyde starch (DAS) on decellularized porcine aortas for tissue engineering.

PubMed

Wang, Xu; Gu, Zhipeng; Qin, Huanhuan; Li, Li; Yang, Xu; Yu, Xixun

2015-08-01

Biological tissue-derived biomaterials must be chemically modified to avoid immediate degradation and immune response before being implanted in human body to replace malfunctioning organs. DAS with active aldehyde groups was employed to replace glutaraldehyde (GA), a most common synthetic crosslinking reagent in clinical practice, to fix bioprostheses for lower cytotoxicity. The aim of this research was to evaluate fixation effect of DAS. The tensile strength, crosslinking stability, cytotoxicity especially the anti-calcification capability of DAS-fixed tissues were investigated. The tensile strength and resistance to enzymatic degradation of samples were increased after DAS fixation, the values maintained stably in D-Hanks solution for several days. Meanwhile, ultrastructure of samples preserved well and the anti-calcification capability of samples were improved, the amount of positive staining points in the whole visual field of 15% DAS-fixed samples was only 0.576 times to GA-fixed ones. Moreover, both unreacted DAS and its hydrolytic products were nontoxic in cytotoxicity study. The results demonstrated DAS might be an effective crosslinking reagent to fix biological tissue-derived biomaterials in tissue engineering. Copyright © 2015 Elsevier B.V. All rights reserved.

A Safety Evaluation of DAS181, a Sialidase Fusion Protein, in Rodents

PubMed Central

Larson, Jeffrey L.; Kang, Seong-Kwi; Choi, Bo In; Hedlund, Maria; Aschenbrenner, Laura M.; Cecil, Beth; Machado, GloriaMay; Nieder, Matthew; Fang, Fang

2011-01-01

DAS181 is a novel inhaled drug candidate blocking influenza virus (IFV) and parainfluenza virus (PIV) infections through removal of sialic acid receptors from epithelial surface of the respiratory tract. To support clinical development, a 28-day Good Laboratory Practices inhalation toxicology study was conducted in Sprague-Dawley rats. In this study, achieved average daily doses based on exposure concentrations were 0.47, 0.90, 1.55, and 3.00 mg/kg/day of DAS181 in a dry powder formulation. DAS181 was well tolerated at all dose levels, and there were no significant toxicological findings. DAS181 administration did not affect animal body weight, food consumption, clinical signs, ophthalmology, respiratory parameters, or organ weight. Gross pathology evaluations were unremarkable. Histological examination of the lungs was devoid of pulmonary tissue damage, and findings were limited to mild and transient changes indicative of exposure and clearance of a foreign protein. DAS181 did not show any cytotoxic effects on human and animal primary cells, including hepatocytes, skeletal muscle cells, osteoblasts, or respiratory epithelial cells. DAS181 did not cause direct or indirect hemolysis. A laboratory abnormality observed in the 28-day toxicology study was mild and transient anemia in male rats at the 3.00 mg/kg dose, which is an expected outcome of enhanced clearance of desialylated red blood cells resulting from systemic exposure with DAS181. Another laboratory observation was a transient dose-dependent elevation in alkaline phosphatase (ALP), which can be attributed to reduced ALP clearance resulting from increased protein desialylation due to DAS181 systemic exposure. These laboratory parameters returned to normal at the end of the recovery period. PMID:21572096

Amerikas Einschätzung der deutschen Atomforschung: Das deutsche Uranprojekt

NASA Astrophysics Data System (ADS)

Walker, Mark

2002-07-01

Die amerikanischen Wissenschaftler und ihre emigrierten Kollegen, die am Bau der Atombombe beteiligt waren, verfügten über sehr widersprüchliche und großteils falsche Informationen über den Fortschritt des deutschen Uranprogramms. Noch nach Kriegsende lässt sich dies an Aussagen des Leiters der amerikanischen Alsos-Mission, Samuel Goudsmit, festmachen. Tatsächlich war das deutsche Programm hinsichtlich seiner wissenschaftlichen Grundlagen und des Managements nicht so unterlegen, wie vielfach behauptet wurde. Aber die deutschen Behörden waren nicht in der Lage, Geld und Ressourcen in gleichem Maße in das Uranprojekt zu investieren, wie etwa in das Peenemünder Raketenprojekt.

Magmatic Longevity Constrained by ID-TIMS U-Pb Dating of Zircon and Titanite

NASA Astrophysics Data System (ADS)

Szymanowski, D.; Wotzlaw, J. F.; Ellis, B. S.; Bachmann, O.; Von Quadt, A.

2016-12-01

Clues about the timescales and thermal conditions associated with the growth and evacuation of large silicic magma reservoirs are frequently drawn from radiometric dating, diffusion modelling, or thermomechanical modelling. A growing amount of petrological and geochronological evidence, supported by thermal modelling, suggests that many silicic magma reservoirs may exist for some 104-106 years in the form of high-crystallinity mushes at relatively low temperatures ( 700-750°C; [1-3]). Geochronological studies addressing this issue typically utilise the U-Pb system in zircon capable of recording extended periods of crystallisation, particularly in evolved calc-alkaline systems that spend most of their lifetime zircon-saturated. In this study, we integrate U-Pb dating of zircon and titanite to investigate the longevity of the magma reservoir that produced the Kneeling Nun Tuff, a 35 Ma, >900 km3 crystal-rich rhyolitic super-eruption from the Mogollon-Datil volcanic field in New Mexico (USA). High-precision ID-TIMS U-Pb dates of single crystals of both zircon and titanite independently record a continuous crystallisation history over >400,000 years. We combine the dating of both accessory phases with textural, major, trace element and isotopic studies of single crystals, placing tight constraints on the thermal conditions of magma accumulation and storage while recording differentiation and rejuvenation processes within the magma reservoir. The results suggest a protracted `cool' upper-crustal storage of magma prior to the Kneeling Nun Tuff eruption followed by a melting event which reduced the magma crystallinity and conditioned it for eruption. [1] Bachmann & Bergantz (2004), J. Petrol. 45, 1565-1582. [2] Gelman et al. (2013), Geology 41, 759-762. [3] Cooper & Kent (2014), Nature 506, 480-483.

DAS Microseismic and Strain Monitoring During Hydraulic Fracturing

NASA Astrophysics Data System (ADS)

Kahn, D.; Karrenbach, M. H.; Cole, S.; Boone, K.; Ridge, A.; Rich, J.; Langton, D.; Silver, K.

2017-12-01

Hydraulic fracturing operations in unconventional subsurface reservoirs are typically monitored using geophones located either at the surface or in adjacent wellbores. A novel approach to record hydraulic stimulations utilizes fiber-optic Distributed Acoustic Sensing (DAS). A fiber-optic cable was installed in a treatment well in a subsurface reservoir (Meramec formation). DAS data were recorded during fluid injection of same fibered well and also during injection into a nearby treatment well at a distance of 350m. For both scenarios the DAS sensing array consisted of approximately 1000 channels at a fine spatial and temporal sampling and with a large sensing aperture. Thus, the full strain wave field is measured along the borehole over its entire length. A variety of physical effects, such as temperature, low-frequency strain and microseismicity were measured and correlated with the treatment program during hydraulic fracturing of the wells. These physical effects occur at various frequency scales and produce complementary measurements. Microseismic events in the magnitude range of -0.5 and -2.0 at a maximum distance of 500m were observed and analyzed for recordings from the fiber-equipped treatment well and also neighboring treatment well. The analysis of this DAS data set demonstrates that current fiber-optic sensing technology can provide enough sensitivity to detect a significant number of microseismic events and that these events can be integrated with temperature and strain measurements for an improved subsurface reservoir description.

Distributed Acoustic Sensing (DAS) Data for Periodic Hydraulic Tests

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

Coleman, Thomas; Becker, Matthew

California State University Long Beach evaluated hydraulic connectivity among geothermal wells using Periodic Hydraulic Testing (PHT) and Distributed Acoustic Sensing (DAS). The principal was to create a pressure signal in one well and observe the responding pressure signals in one or more observation wells to assess the permeability and storage of the fracture network that connects the two wells. DAS measured strain at mHz frequency in monitoring wells in response to PHT.

Phenotypic and genotypic characterization of influenza virus mutants selected with the sialidase fusion protein DAS181

PubMed Central

Triana-Baltzer, Gallen B.; Sanders, Rebecca L.; Hedlund, Maria; Jensen, Kellie A.; Aschenbrenner, Laura M.; Larson, Jeffrey L.; Fang, Fang

2011-01-01

Background Influenza viruses (IFVs) frequently achieve resistance to antiviral drugs, necessitating the development of compounds with novel mechanisms of action. DAS181 (Fludase®), a sialidase fusion protein, may have a reduced potential for generating drug resistance due to its novel host-targeting mechanism of action. Methods IFV strains B/Maryland/1/59 and A/Victoria/3/75 (H3N2) were subjected to >30 passages under increasing selective pressure with DAS181. The DAS181-selected IFV isolates were characterized in vitro and in mice. Results Despite extensive passaging, DAS181-selected viruses exhibited a very low level of resistance to DAS181, which ranged between 3- and 18-fold increase in EC50. DAS181-selected viruses displayed an attenuated phenotype in vitro, as exhibited by slower growth, smaller plaque size and increased particle to pfu ratios relative to wild-type virus. Further, the DAS181 resistance phenotype was unstable and was substantially reversed over time upon DAS181 withdrawal. In mice, the DAS181-selected viruses exhibited no greater virulence than their wild-type counterparts. Genotypic and phenotypic analysis of DAS181-selected viruses revealed mutations in the haemagglutinin (HA) and neuraminidase (NA) molecules and also changes in HA and NA function. Conclusions Results indicate that resistance to DAS181 is minimal and unstable. The DAS181-selected IFV isolates exhibit reduced fitness in vitro, likely due to altered HA and NA functions. PMID:21097900

Evaluating the mush extraction + multiple magma batch model for the Lake City magmatic system (Colorado, USA) using zircon U/Pb TIMS-TEA

NASA Astrophysics Data System (ADS)

Pamukcu, A. S.; Schoene, B.; Deering, C. D.

2016-12-01

Volcanic eruptions that involve a wide range of magma types highlight questions on genetic and geometric relationships between magmas in the crust prior to eruption. The Lake City magmatic system (Colorado, USA) is one such example: exposed in the caldera are ignimbrites from the 23 Ma Sunshine Peak Tuff, which range in composition and crystallinity with time (crystal-poor rhyolite to crystal-rich trachyte), and resurgent intrusions of porphyritic syenite, monzonite, and dacite (Hon 1987). Field relations and bulk rock geochemistry suggest the Lake City magmatic system was complex, with magmas of these various types existing concurrently as multiple magma batches, though not necessarily always in contact (Kennedy et al. 2015). Geochemical modeling further suggests that the crystal-poor rhyolites were liquids extracted from a syenitic mush and that the crystal-rich trachytes are remobilized portions of this cumulate. To address the genetic and geometric links between these magmas in more detail, we utilize TIMS-TEA to assess U/Pb zircon geochronology and trace element geochemistry in concert. For each eruptive unit/magma type, zircons were roughly separated into size groupings (small, medium, large), imaged by cathodoluminescence (CL), and analyzed individually by CA-ID-TIMS. Preliminary results indicate that zircons crystallized over a period of 177±31 ky, which is within the range suggested by Ar/Ar geochronology (80-300 ky, Bove et al. 2001). Consistent with the current model for the Lake City system, zircons from the rhyolites and trachytes overlap in age, while those of the dacites are younger. There is no clear relationship between age and CL zoning pattern or crystal size (e.g., small crystals are not always the youngest). We can further address relationships between the rhyolite, trachyte, and syenite using TEA to assess trace elements of the dated zircons. Rhyolite-MELTS models suggest that zircons crystallized in a rhyolitic melt derived from the trachyte

User Manual for the AZ-101 Data Acquisition System (AS-101 DAS)

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

BRAYTON, D.D.

2000-02-17

User manual for the TK AZ-101 Waste Retrieval System Data Acquisition System. The purpose of this document is to describe use of the AZ-101 Data Acquisition System (AZ-101 DAS). The AZ-101 DAS is provided to fulfill the requirements for data collection and monitoring as defined in Letters of Instruction (LOI) from Numatec Hanford Corporation (NHC) to Fluor Federal Services (FFS). For a complete description of the system, including design, please refer to the AZ-101 DAS System Description document, RPP-5572.

U.S. Tsunami Information technology (TIM) Modernization: Performance Assessment of Tsunamigenic Earthquake Discrimination System

NASA Astrophysics Data System (ADS)

Hagerty, M. T.; Lomax, A.; Hellman, S. B.; Whitmore, P.; Weinstein, S.; Hirshorn, B. F.; Knight, W. R.

2015-12-01

Tsunami warning centers must rapidly decide whether an earthquake is likely to generate a destructive tsunami in order to issue a tsunami warning quickly after a large event. For very large events (Mw > 8 or so), magnitude and location alone are sufficient to warrant an alert. However, for events of smaller magnitude (e.g., Mw ~ 7.5), particularly for so-called "tsunami earthquakes", magnitude alone is insufficient to issue an alert and other measurements must be rapidly made and used to assess tsunamigenic potential. The Tsunami Information technology Modernization (TIM) is a National Oceanic and Atmospheric Administration (NOAA) project to update and standardize the earthquake and tsunami monitoring systems currently employed at the U.S. Tsunami Warning Centers in Ewa Beach, Hawaii (PTWC) and Palmer, Alaska (NTWC). We (ISTI) are responsible for implementing the seismic monitoring components in this new system, including real-time seismic data collection and seismic processing. The seismic data processor includes a variety of methods aimed at real-time discrimination of tsunamigenic events, including: Mwp, Me, slowness (Theta), W-phase, mantle magnitude (Mm), array processing and finite-fault inversion. In addition, it contains the ability to designate earthquake scenarios and play the resulting synthetic seismograms through the processing system. Thus, it is also a convenient tool that integrates research and monitoring and may be used to calibrate and tune the real-time monitoring system. Here we show results of the automated processing system for a large dataset of subduction zone earthquakes containing recent tsunami earthquakes and we examine the accuracy of the various discrimation methods and discuss issues related to their successful real-time application.

Structural analysis of kinetic folding intermediates for a TIM barrel protein, indole-3-glycerol phosphate synthase, by hydrogen exchange mass spectrometry and Gō-model simulation

PubMed Central

Gu, Zhenyu; Rao, Maithreyi K.; Forsyth, William R.

2009-01-01

The structures of partially-folded states appearing during the folding of a (βα)8 TIM barrel protein, the indole-3-glycerol phosphate synthase from S. solfataricus (sIGPS), was assessed by hydrogen exchange mass spectrometry (HX-MS) and Gō-model simulations. HX-MS analysis of the peptic peptides derived from the pulse-labeled product of the sub-millisecond folding reaction from the urea-denatured state revealed strong protection in the (βα)4 region, modest protection in the neighboring (βα)1–3 and (βα)5β6 segments and no significant protection in the remaining N- and C-terminal segments. These results demonstrate that this species is not a collapsed form of the unfolded state under native-favoring conditions nor is it the native state formed via fast-track folding. However, the striking contrast of these results with the strong protection observed in the (βα)2–5β6 region after 5 s of folding demonstrates that these species represent kinetically-distinct folding intermediates that are not identical as previously thought. A re-examination of the kinetic folding mechanism by chevron analysis of fluorescence data confirmed distinct roles for these two species: the burst-phase intermediate is predicted to be a misfolded, off-pathway intermediate while the subsequent 5 s intermediate corresponds to an on-pathway equilibrium intermediate. Comparison with the predictions using a Cα Gō-model simulation of the kinetic folding reaction for sIGPS shows good agreement with the core of structure offering protection against exchange in the on-pathway intermediate(s). Because the native-centric Gō-model simulations do not explicitly include sequence-specific information, the simulation results support the hypothesis that the topology of TIM barrel proteins is a primary determinant of the folding free energy surface for the productive folding reaction. The early misfolding reaction must involve aspects of non-native structure not detected by the G�

Chlorine Isotopes: As a Possible Tracer of Fluid/Bio-Activities on Mars and a Progress Report on Chlorine Isotope Analysis by TIMs

NASA Technical Reports Server (NTRS)

Nakamura, N.; Nyquist, L.E.; Reese, Y.; Shih, C-Y.; Numata, M.; Fujitani, T.; Okano, O.

2009-01-01

Significantly large mass fractionations between chlorine isotopes (Cl-35, Cl-37) have been reported for terrestrial materials including both geological samples and laboratory materials. Also, the chlorine isotopic composition can be used as a tracer for early solar system processes. Moreover, chlorine is ubiquitous on the Martian surface. Typical chlorine abundances in Gusev soils are approx.0.5 %. The global surface average chlorine abundance also is approx.0.5 %. Striking variations among outcrop rocks at Meridiani were reported with some chlorine abundances as high as approx.2%. Characterizing conditions under which chlorine isotopic fractionation may occur is clearly of interest to planetary science. Thus, we have initiated development of a chlorine isotopic analysis technique using TIMS at NASA-JSC. We present here a progress report on the current status of development at JSC and discuss the possible application of chlorine isotopic analysis to Martian meteorites in a search for fluid- and possibly biological activity on Mars.

Moisture Forecast Bias Correction in GEOS DAS

NASA Technical Reports Server (NTRS)

Dee, D.

1999-01-01

Data assimilation methods rely on numerous assumptions about the errors involved in measuring and forecasting atmospheric fields. One of the more disturbing of these is that short-term model forecasts are assumed to be unbiased. In case of atmospheric moisture, for example, observational evidence shows that the systematic component of errors in forecasts and analyses is often of the same order of magnitude as the random component. we have implemented a sequential algorithm for estimating forecast moisture bias from rawinsonde data in the Goddard Earth Observing System Data Assimilation System (GEOS DAS). The algorithm is designed to remove the systematic component of analysis errors and can be easily incorporated in an existing statistical data assimilation system. We will present results of initial experiments that show a significant reduction of bias in the GEOS DAS moisture analyses.

Comparison of TIMS and MC-ICP-MS Analyses of Pb Isotopic Compositions on Prehistoric Mauna Loa Basalts: Implications for Plume Source Components

NASA Astrophysics Data System (ADS)

De Jong, J.; Weis, D.; Maerschalk, C.; Rhodes, J. M.

2001-12-01

Recent isotopic studies on Hawaiian lavas have shown the necessity of constraining fractionation for Pb isotopes. This isotopic system presents systematic variations reflecting the presence of different plume components in the source of Hawaiian basalts. We have analyzed a series of 23 tholeiitic Mauna Loa basalts ranging in age from 36,780 to 140 y for their Pb isotopic compositions by TIMS (Micromass Sector 54) and MC-ICP-MS (Nu Plasma) to directly compare results from the same, carefully leached, samples. These analyses indicate an internal precision better than 120 ppm for the MC-ICP-MS Pb ratios, while for the TIMS ratios, it is in the per mil range. This results in a more coherent dataset for the MC-ICP-MS analyses, with the range of 207Pb/204Pb variations decreasing by a factor of 3 and of 208Pb/204Pb ratios by a factor of 1.5. The co-variations between the Pb isotopic data and other geochemical parameters for the Hawaiian lavas are now much stronger and better defined. There are clearly two groups amongst the prehistoric Mauna Loa basalts: one group with higher 87Sr/86Sr (>0.7038) and low 206Pb/204Pb (<18.15) that covers the entire range of Nb/Y (0.31 to 0.51) observed in this volcano, and the other group with low 87Sr/86Sr (<0.7038) and higher 206Pb/204Pb with Nb/Y<0.4. The second group is only present in basalts younger than 3,000 y or older than 24,000 y. The high 87Sr/86Sr group was not sampled in the HSDP I drill core, which covers an age range of 100,000 y. This either reflects a sampling bias, as the upper flow units (<10,000 y) were not sampled for geochemistry, or variations in magma supply. Altogether, Mauna Loa lava flows that are younger than 20,000 y show much more isotopic variation than older flows and there is a nearly continuous transition away from the Kilauea component. This may indicate that the transition between the Mauna Loa and Mauna Kea trends is not as sharp as previously documented. This study shows the importance of reducing the

Brady's Geothermal Field DAS Earthquake Data

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

Kurt Feigl

The submitted data correspond to the vibration caused by a 3.4 M earthquake and captured by the DAS horizontal and vertical arrays during the PoroTomo Experiment. Earthquake information : M 4.3 - 23km ESE of Hawthorne, Nevada Time: 2016-03-21 07:37:10 (UTC) Location: 38.479 N 118.366 W Depth: 9.9 km

Prevalence of mabDAS-1 positivity in biopsy specimens from the esophagogastric junction.

PubMed

Rogge-Wolf, Claudia; Seldenrijk, Cornelis A; Das, Kiron M; Timmer, Robin; Breumelhof, Ronald; Smout, André J P M; Amenta, Peter S; Griffel, Louis H

2002-12-01

Intestinal metaplasia (IM) is a precursor for malignancies at the esophagogastric junction. A monoclonal antibody, mAbDAS-1, can probably identify cellular characteristics of IM before the appearance of goblet cells. The aim of this study was to examine the prevalence of mAbDAS-1 positivity in biopsies from the squamocolumnar junction (SCJ) and to correlate this positivity with the presence of IM and clinical findings. In 559 patients, reflux symptoms were scored, and the presence of reflux esophagitis and hiatus hernia was evaluated during endoscopy. Two biopsy specimens were obtained from the SCJ. In a subset of patients (n = 99), biopsies from the endoscopically defined cardiac region (2 cm distal to proximal margin of gastric folds) were available. Biopsy specimens were stained with hematoxylin and eosin, Alcian Blue, modified Giemsa, and mAbDAS-1. mAbDAS-1 positivity was observed in the SCJ biopsies of 201 of 486 (41.4%) patients without IM and in 64 of 73 (87.7%) patients with IM. Patients without IM but with antibody positivity showed similar histological characteristics as patients with IM at the SCJ. Biopsies of 123 of 559 patients (22%) revealed a columnar-cuboidal epithelium, which was found to be mAbDAS-1 positive in 64.2% (77 of 123). Tissue specimens from the cardiac region without IM stained positive in 14.2% (13 of 91), 12 of those also stained at the SCJ. In patients without IM, a high prevalence of mAbDAS-1 positivity was observed. Biopsies of these patients showed similar histological characteristics as patients with IM. Although not all patients exhibiting this reactivity may develop IM, mAbDAS-1 reactivity may help in the understanding of the histogenesis of IM at the SCJ.

High-precision ID-TIMS zircon U-Pb geochronology using new 1013 Ohm resistors

NASA Astrophysics Data System (ADS)

Von Quadt, A.; Buret, Y.; Large, S.; Peytcheva, I.; Trinquier, A.; Wotzlaw, J. F.

2015-12-01

Faraday cups equipped with high gain amplifiers provide a means to measure small ion beams in static mode without the limited linear range of ion counting systems. We tested the application of newly available 1013 Ohm resistors to ID-TIMS zircon U-Pb geochronology using a range of natural and synthetic reference materials. The TritonPlus-RPQ at the Institute of Geochemistry and Petrology, ETH Zurich, is equipped with five new 1013 Ohm resistors and one MasCom secondary electron multiplier, allowing to measure the 202-204-205-206-207-208Pb masses in static mode. U is measured subsequently as U-oxide (265-267-270UO2) during a second step, also in static Faraday mode. The gain calibration of the 1013 Ohm resistors was performed using the procedure of Trinquier (2014), with 144Nd-146Nd being measured using 1011 Ohm resistor and 142-143-145-148-150Nd being measured using 1013 Ohm resitors (Trinquier, 2014; Koornneef et al., 2014). Standard deviations of the noise in all five new 1013 Ohm resistors are lower than 5.0 x 10-6 over a 6 month period, with no shift occurring over this time interval. This new detector set-up was tested by analyzing natural zircon standard materials and synthetic U/Pb solutions (www.earthime.org), ranging in age from ~2 Ma to ~600 Ma. All natural zircon standards were chemically abraded (Mattinson, 2005) and all samples were spiked with the ET2535 tracer solution. U-Pb dates obtained using the static measurement routine are compared to measurements employing dynamic peak jumping routines on the MasCom multiplier. This study illustrates the benefits and current limitations of using high gain amplifiers to measure small ion beams for zircon U-Pb geochronology compared to conventional dynamic ion counting techniques. Mattinson, J.M. (2005) Chemical Geology 220:47-66; Trinquier, A. (2014) Application Note 30281; Koornneef, J. et al (2014) Analytica Chimica Acta 819:49-55.

MiDAS: the field guide to the microbes of activated sludge.

PubMed

McIlroy, Simon Jon; Saunders, Aaron Marc; Albertsen, Mads; Nierychlo, Marta; McIlroy, Bianca; Hansen, Aviaja Anna; Karst, Søren Michael; Nielsen, Jeppe Lund; Nielsen, Per Halkjær

2015-01-01

The Microbial Database for Activated Sludge (MiDAS) field guide is a freely available online resource linking the identity of abundant and process critical microorganisms in activated sludge wastewater treatment systems to available data related to their functional importance. Phenotypic properties of some of these genera are described, but most are known only from sequence data. The MiDAS taxonomy is a manual curation of the SILVA taxonomy that proposes a name for all genus-level taxa observed to be abundant by large-scale 16 S rRNA gene amplicon sequencing of full-scale activated sludge communities. The taxonomy can be used to classify unknown sequences, and the online MiDAS field guide links the identity to the available information about their morphology, diversity, physiology and distribution. The use of a common taxonomy across the field will provide a solid foundation for the study of microbial ecology of the activated sludge process and related treatment processes. The online MiDAS field guide is a collaborative workspace intended to facilitate a better understanding of the ecology of activated sludge and related treatment processes--knowledge that will be an invaluable resource for the optimal design and operation of these systems. © The Author(s) 2015. Published by Oxford University Press.

MiDAS: the field guide to the microbes of activated sludge

PubMed Central

McIlroy, Simon Jon; Saunders, Aaron Marc; Albertsen, Mads; Nierychlo, Marta; McIlroy, Bianca; Hansen, Aviaja Anna; Karst, Søren Michael; Nielsen, Jeppe Lund; Nielsen, Per Halkjær

2015-01-01

The Microbial Database for Activated Sludge (MiDAS) field guide is a freely available online resource linking the identity of abundant and process critical microorganisms in activated sludge wastewater treatment systems to available data related to their functional importance. Phenotypic properties of some of these genera are described, but most are known only from sequence data. The MiDAS taxonomy is a manual curation of the SILVA taxonomy that proposes a name for all genus-level taxa observed to be abundant by large-scale 16 S rRNA gene amplicon sequencing of full-scale activated sludge communities. The taxonomy can be used to classify unknown sequences, and the online MiDAS field guide links the identity to the available information about their morphology, diversity, physiology and distribution. The use of a common taxonomy across the field will provide a solid foundation for the study of microbial ecology of the activated sludge process and related treatment processes. The online MiDAS field guide is a collaborative workspace intended to facilitate a better understanding of the ecology of activated sludge and related treatment processes—knowledge that will be an invaluable resource for the optimal design and operation of these systems. Database URL: http://www.midasfieldguide.org PMID:26120139

Determinants in the Ig Variable Domain of Human HAVCR1 (TIM-1) Are Required To Enhance Hepatitis C Virus Entry.

PubMed

Kachko, Alla; Costafreda, Maria Isabel; Zubkova, Iryna; Jacques, Jerome; Takeda, Kazuyo; Wells, Frances; Kaplan, Gerardo; Major, Marian E

2018-03-15

Hepatitis C virus (HCV) is the leading cause of chronic hepatitis in humans. Several host molecules participate in HCV cell entry, but this process remains unclear. The complete unraveling of the HCV entry process is important to further understand viral pathogenesis and develop therapeutics. Human hepatitis A virus (HAV) cellular receptor 1 (HAVCR1), CD365, also known as TIM-1, functions as a phospholipid receptor involved in cell entry of several enveloped viruses. Here, we studied the role of HAVCR1 in HCV infection. HAVCR1 antibody inhibited entry in a dose-dependent manner. HAVCR1 soluble constructs neutralized HCV, which did not require the HAVCR1 mucinlike region and was abrogated by a mutation of N to A at position 94 (N94A) in the Ig variable (IgV) domain phospholipid-binding pocket, indicating a direct interaction of the HAVCR1 IgV domain with HCV virions. However, knockout of HAVCR1 in Huh7 cells reduced but did not prevent HCV growth. Interestingly, the mouse HAVCR1 ortholog, also a phospholipid receptor, did not enhance infection and a soluble form failed to neutralize HCV, although replacement of the mouse IgV domain with the human HAVCR1 IgV domain restored the enhancement of HCV infection. Mutations in the cytoplasmic tail revealed that direct HAVCR1 signaling is not required to enhance HCV infection. Our data show that the phospholipid-binding function and other determinant(s) in the IgV domain of human HAVCR1 enhance HCV infection. Although the exact mechanism is not known, it is possible that HAVCR1 facilitates entry by stabilizing or enhancing attachment, leading to direct interactions with specific receptors, such as CD81. IMPORTANCE Hepatitis C virus (HCV) enters cells through a multifaceted process. We identified the human hepatitis A virus cellular receptor 1 (HAVCR1), CD365, also known as TIM-1, as a facilitator of HCV entry. Antibody blocking and silencing or knockout of HAVCR1 in hepatoma cells reduced HCV entry. Our findings that the

Dereplication, Aggregation and Scoring Tool (DAS Tool) v1.0

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

SIEBER, CHRISTIAN

Communities of uncultivated microbes are critical to ecosystem function and microorganism health, and a key objective of metagenomic studies is to analyze organism-specific metabolic pathways and reconstruct community interaction networks. This requires accurate assignment of genes to genomes, yet existing binning methods often fail to predict a reasonable number of genomes and report many bins of low quality and completeness. Furthermore, the performance of existing algorithms varies between samples and biotypes. Here, we present a dereplication, aggregation and scoring strategy, DAS Tool, that combines the strengths of a flexible set of established binning algorithms. DAS Tools applied to a constructedmore » community generated more accurate bins than any automated method. Further, when applied to samples of different complexity, including soil, natural oil seeps, and the human gut, DAS Tool recovered substantially more near-complete genomes than any single binning method alone. Included were three genomes from a novel lineage . The ability to reconstruct many near-complete genomes from metagenomics data will greatly advance genome-centric analyses of ecosystems.« less

GenExp: an interactive web-based genomic DAS client with client-side data rendering.

PubMed

Gel Moreno, Bernat; Messeguer Peypoch, Xavier

2011-01-01

The Distributed Annotation System (DAS) offers a standard protocol for sharing and integrating annotations on biological sequences. There are more than 1000 DAS sources available and the number is steadily increasing. Clients are an essential part of the DAS system and integrate data from several independent sources in order to create a useful representation to the user. While web-based DAS clients exist, most of them do not have direct interaction capabilities such as dragging and zooming with the mouse. Here we present GenExp, a web based and fully interactive visual DAS client. GenExp is a genome oriented DAS client capable of creating informative representations of genomic data zooming out from base level to complete chromosomes. It proposes a novel approach to genomic data rendering and uses the latest HTML5 web technologies to create the data representation inside the client browser. Thanks to client-side rendering most position changes do not need a network request to the server and so responses to zooming and panning are almost immediate. In GenExp it is possible to explore the genome intuitively moving it with the mouse just like geographical map applications. Additionally, in GenExp it is possible to have more than one data viewer at the same time and to save the current state of the application to revisit it later on. GenExp is a new interactive web-based client for DAS and addresses some of the short-comings of the existing clients. It uses client-side data rendering techniques resulting in easier genome browsing and exploration. GenExp is open source under the GPL license and it is freely available at http://gralggen.lsi.upc.edu/recerca/genexp.

GenExp: An Interactive Web-Based Genomic DAS Client with Client-Side Data Rendering

PubMed Central

Gel Moreno, Bernat; Messeguer Peypoch, Xavier

2011-01-01

Background The Distributed Annotation System (DAS) offers a standard protocol for sharing and integrating annotations on biological sequences. There are more than 1000 DAS sources available and the number is steadily increasing. Clients are an essential part of the DAS system and integrate data from several independent sources in order to create a useful representation to the user. While web-based DAS clients exist, most of them do not have direct interaction capabilities such as dragging and zooming with the mouse. Results Here we present GenExp, a web based and fully interactive visual DAS client. GenExp is a genome oriented DAS client capable of creating informative representations of genomic data zooming out from base level to complete chromosomes. It proposes a novel approach to genomic data rendering and uses the latest HTML5 web technologies to create the data representation inside the client browser. Thanks to client-side rendering most position changes do not need a network request to the server and so responses to zooming and panning are almost immediate. In GenExp it is possible to explore the genome intuitively moving it with the mouse just like geographical map applications. Additionally, in GenExp it is possible to have more than one data viewer at the same time and to save the current state of the application to revisit it later on. Conclusions GenExp is a new interactive web-based client for DAS and addresses some of the short-comings of the existing clients. It uses client-side data rendering techniques resulting in easier genome browsing and exploration. GenExp is open source under the GPL license and it is freely available at http://gralggen.lsi.upc.edu/recerca/genexp. PMID:21750706

Reisen im freien Fall - Teil 2: Das Zwillingsparadoxon aus dem Blickwinkel der ART

NASA Astrophysics Data System (ADS)

Sonne, Bernd; Weiß, Reinhard

2013-07-01

Nachdem wir uns mit den Prinzipien der ART und einigen Beispielen vertraut gemacht haben, kommen wir nun zur Berechnung des Zwillingsparadoxons aus Sicht des reisenden Zwillings. Dabei spielt das Äquivalenzprinzip eine große Rolle. Deshalb wird die Bewegungssituation noch einmal erläutert, diesmal aus Sicht von Katrin. Sie befindet sich in ihrem System S'in Ruhe. In ihrem System läuft die Zeit t'ab. Nach dem Start fühlt Katrin jedoch eine Kraft, die sie als Gravitationskraft interpretieren kann. Sie merkt es daran, dass sie in den Sitz gedrückt wird. Nach einiger Zeit werden die Triebwerke abgeschaltet, und das Raumschiff fliegt mit konstanter Geschwindigkeit weiter, Phase 2. Anschließend wird der Schub der Triebwerke solange umgekehrt, bis das Raumschiff irgendwo mit der Geschwindigkeit null am Umkehrpunkt U landet, Phase 3 (Abb. 15.1). Die Erde, auf der sich Michael befindet, bewegt sich mit x'(t') aus Sicht von Katrin im freien Fall von ihr weg, s. das Experiment mit dem steigenden Fahrstuhl in Abschn. 13.2.1.

Das Prinzip Bewegung - Herz und Gehirn als Metaphern des menschlichen Lebens

NASA Astrophysics Data System (ADS)

Otis, Laura

In diesem Jahr, in dem wir Charles Darwins gedenken, möchte ich etwas riskieren und eine Frage erörtern, die für die Literatur ebenso wie für die Biologie zentral ist: Was ist das Leben? Die Antwort auf diese Frage finden wir nicht in der Bibliothek und nicht im Labor, zumindest nicht an diesen erkenntnisproduzierenden Stellen allein. Als Literaturwissenschaftlerin und ehemalige Naturwissenschaftlerin glaube ich, dass wir das Leben nur verstehen werden, wenn wir seinen Wirkungen überall nachforschen, inklusive in der Literatur.

Improved 206Pb/238U microprobe geochronology by the monitoring of a trace-element-related matrix effect; SHRIMP, ID-TIMS, ELA-ICP-MS and oxygen isotope documentation for a series of zircon standards

USGS Publications Warehouse

Black, L.P.; Kamo, S.L.; Allen, C.M.; Davis, D.W.; Aleinikoff, J.N.; Valley, J.W.; Mundil, R.; Campbell, I.H.; Korsch, R.J.; Williams, I.S.; Foudoulis, C.

2004-01-01

Precise isotope dilution-thermal ionisation mass spectrometry (ID-TIMS) documentation is given for two new Palaeozoic zircon standards (TEMORA 2 and R33). These data, in combination with results for previously documented standards (AS3, SL13, QGNG and TEMORA 1), provide the basis for a detailed investigation of inconsistencies in 206Pb/238U ages measured by microprobe. Although these ages are normally consistent between any two standards, their relative age offsets are often different from those established by ID-TIMS. This is true for both sensitive high-resolution ion-microprobe (SHRIMP) and excimer laser ablation-inductively coupled plasma-mass spectrometry (ELA-ICP-MS) dating, although the age offsets are in the opposite sense for the two techniques. Various factors have been investigated for possible correlations with age bias, in an attempt to resolve why the accuracy of the method is worse than the indicated precision. Crystallographic orientation, position on the grain-mount and oxygen isotopic composition are unrelated to the bias. There are, however, striking correlations between the 206Pb/238U age offsets and P, Sm and, most particularly, Nd abundances in the zircons. Although these are not believed to be the primary cause of this apparent matrix effect, they indicate that ionisation of 206Pb/238U is influenced, at least in part, by a combination of trace elements. Nd is sufficiently representative of the controlling trace elements that it provides a quantitative means of correcting for the microprobe age bias. This approach has the potential to reduce age biases associated with different techniques, different instrumentation and different standards within and between laboratories. Crown Copyright ?? 2004 Published by Elsevier B.V. All rights reserved.

Establishment of feeder-free culture system for human induced pluripotent stem cell on DAS nanocrystalline graphene

NASA Astrophysics Data System (ADS)

Lee, Hyunah; Nam, Donggyu; Choi, Jae-Kyung; Araúzo-Bravo, Marcos J.; Kwon, Soon-Yong; Zaehres, Holm; Lee, Taehee; Park, Chan Young; Kang, Hyun-Wook; Schöler, Hans R.; Kim, Jeong Beom

2016-02-01

The maintenance of undifferentiated human pluripotent stem cells (hPSC) under xeno-free condition requires the use of human feeder cells or extracellular matrix (ECM) coating. However, human-derived sources may cause human pathogen contamination by viral or non-viral agents to the patients. Here we demonstrate feeder-free and xeno-free culture system for hPSC expansion using diffusion assisted synthesis-grown nanocrystalline graphene (DAS-NG), a synthetic non-biological nanomaterial which completely rule out the concern of human pathogen contamination. DAS-NG exhibited advanced biocompatibilities including surface nanoroughness, oxygen containing functional groups and hydrophilicity. hPSC cultured on DAS-NG could maintain pluripotency in vitro and in vivo, and especially cell adhesion-related gene expression profile was comparable to those of cultured on feeders, while hPSC cultured without DAS-NG differentiated spontaneously with high expression of somatic cell-enriched adhesion genes. This feeder-free and xeno-free culture method using DAS-NG will facilitate the generation of clinical-grade hPSC.

Detecting Changes Following the Provision of Assistive Devices: Utility of the WHO-DAS II

ERIC Educational Resources Information Center

Raggi, Alberto

2010-01-01

The World Health Organization Disability Assessment Schedule II (WHO-DAS II) is a non-disease-specific International Classification of Functioning, Disability, and Health-based disability assessment instrument developed to measure activity limitations and restrictions to participation. The aim of this pilot study is to evaluate WHO-DAS II…

Numerical study of anomalous dynamic scaling behaviour of (1+1)-dimensional Das Sarma-Tamborenea model

NASA Astrophysics Data System (ADS)

Xun, Zhi-Peng; Tang, Gang; Han, Kui; Hao, Da-Peng; Xia, Hui; Zhou, Wei; Yang, Xi-Quan; Wen, Rong-Ji; Chen, Yu-Ling

2010-07-01

In order to discuss the finite-size effect and the anomalous dynamic scaling behaviour of Das Sarma-Tamborenea growth model, the (1+1)-dimensional Das Sarma-Tamborenea model is simulated on a large length scale by using the kinetic Monte-Carlo method. In the simulation, noise reduction technique is used in order to eliminate the crossover effect. Our results show that due to the existence of the finite-size effect, the effective global roughness exponent of the (1+1)-dimensional Das Sarma-Tamborenea model systematically decreases with system size L increasing when L > 256. This finding proves the conjecture by Aarao Reis[Aarao Reis F D A 2004 Phys. Rev. E 70 031607]. In addition, our simulation results also show that the Das Sarma-Tamborenea model in 1+1 dimensions indeed exhibits intrinsic anomalous scaling behaviour.

Structure of L-Xylulose-5-Phosphate 3-Epimerase (UlaE) from the Anaerobic L-Ascorbate Utilization Pathway of Escherichia coli: Identification of a Novel Phosphate Binding Motif within a TIM Barrel Fold

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

Shi, Rong; Pineda, Marco; Ajamian, Eunice

2009-01-15

Three catabolic enzymes, UlaD, UlaE, and UlaF, are involved in a pathway leading to fermentation of L-ascorbate under anaerobic conditions. UlaD catalyzes a {beta}-keto acid decarboxylation reaction to produce L-xylulose-5-phosphate, which undergoes successive epimerization reactions with UlaE (L-xylulose-5-phosphate 3-epimerase) and UlaF (L-ribulose-5-phosphate 4-epimerase), yielding D-xylulose-5-phosphate, an intermediate in the pentose phosphate pathway. We describe here crystallographic studies of UlaE from Escherichia coli O157:H7 that complete the structural characterization of this pathway. UlaE has a triosephosphate isomerase (TIM) barrel fold and forms dimers. The active site is located at the C-terminal ends of the parallel {beta}-strands. The enzyme binds Zn{sup 2+},more » which is coordinated by Glu155, Asp185, His211, and Glu251. We identified a phosphate-binding site formed by residues from the {beta}1/{alpha}1 loop and {alpha}3' helix in the N-terminal region. This site differs from the well-characterized phosphate-binding motif found in several TIM barrel superfamilies that is located at strands {beta}7 and {beta}8. The intrinsic flexibility of the active site region is reflected by two different conformations of loops forming part of the substrate-binding site. Based on computational docking of the L-xylulose 5-phosphate substrate to UlaE and structural similarities of the active site of this enzyme to the active sites of other epimerases, a metal-dependent epimerization mechanism for UlaE is proposed, and Glu155 and Glu251 are implicated as catalytic residues. Mutation and activity measurements for structurally equivalent residues in related epimerases supported this mechanistic proposal.« less

Earthquake recording at the Stanford DAS Array with fibers in existing telecomm conduits

NASA Astrophysics Data System (ADS)

Biondi, B. C.; Martin, E. R.; Yuan, S.; Cole, S.; Karrenbach, M. H.

2017-12-01

The Stanford Distributed Acoustic Sensing Array (SDASA-1) has been continuously recording seismic data since September 2016 on 2.5 km of single mode fiber optics in existing telecommunications conduits under Stanford's campus. The array is figure-eight shaped and roughly 600 m along its widest side with a channel spacing of roughly 8 m. This array is easy to maintain and is nonintrusive, making it well suited to urban environments, but it sacrifices some cable-to-ground coupling compared to more traditional seismometers. We have been testing its utility for earthquake recording, active seismic, and ambient noise interferometry. This talk will focus on earthquake observations. We will show comparisons between the strain rates measured throughout the DAS array and the particle velocities measured at the nearby Jasper Ridge Seismic Station (JRSC). In some of these events, we will point out directionality features specific to DAS that can require slight modifications in data processing. We also compare repeatability of DAS and JRSC recordings of blasts from a nearby quarry. Using existing earthquake databases, we have created a small catalog of DAS earthquake observations by pulling records of over 700 Northern California events spanning Sep. 2016 to Jul. 2017 from both the DAS data and JRSC. On these events we have tested common array methods for earthquake detection and location including beamforming and STA/LTA analysis in time and frequency. We have analyzed these events to approximate thresholds on what distances and magnitudes are clearly detectible by the DAS array. Further analysis should be done on detectability with methods tailored to small events (for example, template matching). In creating this catalog, we have developed open source software available for free download that can manage large sets of continuous seismic data files (both existing files, and files as they stream in). This software can both interface with existing earthquake networks, and

Psychometric Properties of the Disability Assessment Schedule (DAS) for Behavior Problems: An Independent Investigation

ERIC Educational Resources Information Center

Tsakanikos, Elias; Underwood, Lisa; Sturmey, Peter; Bouras, Nick; McCarthy, Jane

2011-01-01

The present study employed the Disability Assessment Schedule (DAS) to assess problem behaviors in a large sample of adults with ID (N = 568) and evaluate the psychometric properties of this instrument. Although the DAS problem behaviors were found to be internally consistent (Cronbach's [alpha] = 0.87), item analysis revealed one weak item…

Anbindung des SISIS-SunRise-Bibliothekssystems an das zentrale Identitätsmanagement

NASA Astrophysics Data System (ADS)

Ebner, Ralf; Pretz, Edwin

Wir berichten über Konzepte und Implementierungen zur Datenprovisionierung aus den Personenverwaltungssystemen der Technischen Universität München (TUM) über das zentrale Metadirectory am Leibniz-Rechenzentrum (LRZ) in das SISIS-SunRise-Bibliothekssystem der Universitätsbibliothek der TUM (TUB). Es werden drei Implementierungsvarianten diskutiert, angefangen von der Generierung und Übertragung einfacher CSV-Dateien über ein OpenLDAP-basiertes Konzept als Backend für die SISIS-Datenbank bis zur endgültigen Implementierung mit dem OCLC IDM Connector.

Annotation and visualization of endogenous retroviral sequences using the Distributed Annotation System (DAS) and eBioX

PubMed Central

Martínez Barrio, Álvaro; Lagercrantz, Erik; Sperber, Göran O; Blomberg, Jonas; Bongcam-Rudloff, Erik

2009-01-01

Background The Distributed Annotation System (DAS) is a widely used network protocol for sharing biological information. The distributed aspects of the protocol enable the use of various reference and annotation servers for connecting biological sequence data to pertinent annotations in order to depict an integrated view of the data for the final user. Results An annotation server has been devised to provide information about the endogenous retroviruses detected and annotated by a specialized in silico tool called RetroTector. We describe the procedure to implement the DAS 1.5 protocol commands necessary for constructing the DAS annotation server. We use our server to exemplify those steps. Data distribution is kept separated from visualization which is carried out by eBioX, an easy to use open source program incorporating multiple bioinformatics utilities. Some well characterized endogenous retroviruses are shown in two different DAS clients. A rapid analysis of areas free from retroviral insertions could be facilitated by our annotations. Conclusion The DAS protocol has shown to be advantageous in the distribution of endogenous retrovirus data. The distributed nature of the protocol is also found to aid in combining annotation and visualization along a genome in order to enhance the understanding of ERV contribution to its evolution. Reference and annotation servers are conjointly used by eBioX to provide visualization of ERV annotations as well as other data sources. Our DAS data source can be found in the central public DAS service repository, , or at . PMID:19534743

New Ca-Tims and La-Icp Analyses of GJ-1, Plesovice, and FC1 Reference Materials

NASA Astrophysics Data System (ADS)

Feldman, J. D.; Möller, A.; Walker, J. D.

2014-12-01

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) U-Pb zircon geochronology relies on external reference standards to monitor and correct for different mass fractionation effects and instrument drift. Common zircon reference materials used within the community, including the KU Isotope Geochemistry Laboratory, are GJ-1 (207Pb/206Pb age: 608.53 +/- 0.37Ma; Jackson et al., 2004), Plesovice (337.13 +/- 0.37 Ma; Slama et al., 2008), and FC-1 (1099.0 +/-0.6 Ma; Paces and Miller, 1993). The age distribution of zircon reference material varies slightly from sample fraction to sample fraction, and the published results for GJ-1 are slightly discordant. As a result, using the published data for the distributed standard splits can lead to small systematic variations when comparing datasets from different labs, and more high precision data are needed to evaluate potential inhomogeneity of sample splits used in different laboratories. Here we characterize these reference materials with cathodoluminescence, LA-ICP-MS traverses across grains, and high precision CA-TIMS to better constrain the ages and assess zoning of these standards, and present the data for comparison with other laboratories. Reducing systematic error by dating our own reference material lends confidence to our analyses and allows for inter-laboratory age reproducibility of unknowns. Additionally, the reduction in propagated uncertainties (especially in GJ-1, for which both the red and yellow variety will be analyzed) will be used to improve long-term reproducibility, comparisons between samples of similar age, detrital populations and composite pluton zircons. Jackson, S.E., et al., 2004, Chemical Geology, v. 211, p. 47-69. Paces, J.B. & Miller, J.D., 1993, Journal of Geophysical Research, v. 80, p. 13997-14013. Slama, J., et al., 2008, Chemical Geology, v. 249. p. 1-35.

Molecular identification, immunolocalization, and characterization of Clonorchis sinensis triosephosphate isomerase.

PubMed

Zhou, Juanjuan; Liao, Hua; Li, Shan; Zhou, Chenhui; Huang, Yan; Li, Xuerong; Liang, Chi; Yu, Xinbing

2015-08-01

Clonorchis sinensis triosephosphate isomerase (CsTIM) is a key regulatory enzyme of glycolysis and gluconeogenesis, which catalyzes the interconversion of glyceraldehyde 3-phosphate to dihydroxyacetone phosphate. In this study, the biochemical characterizations of CsTIM have been examined. A full-length complementary DNA (cDNA; Cs105350) sequence encoding CsTIM was obtained from our C. sinensis cDNA library. The open reading frame of CsTIM contains 759 bp which encodes 252 amino acids. The amino acid sequence of CsTIM shares 60-65% identity with other species. Western blot analysis displayed that recombinant CsTIM (rCsTIM) can be probed by anti-rCsTIM rat serum and anti-C. sinensis excretory/secretory products (anti-CsESPs) rat serum. Quantitative reverse transcription (RT)-PCR and western blotting analysis revealed that CsTIM messenger RNA (mRNA) and protein were differentially expressed in development cycle stages of the parasite, including adult worm, metacercaria, excysted metacercaria, and egg. In addition, immunolocalization assay showed that CsTIM was located in the seminal vesicle, eggs, and testicle. Moreover, rCsTIM exhibited active enzyme activity in catalytic reactions. The Michaelis constant (K m) of rCsTIM was 0.33 mM, when using glyceraldehyde 3-phosphate as the substrate. The optimal temperature and pH of CsTIM were 37 °C and 7.5-9.5, respectively. Collectively, these results suggest that CsTIM is an important protein involved in glycometabolism, and CsTIM possibly take part in many biological functions in the growth and development of C. sinensis.

Multicenter, Randomized, Controlled Study Comparing Tafluprost/Timolol Fixed Combination with Latanoprost/Timolol Fixed Combination in Primary Open-Angle Glaucoma and Ocular Hypertension.

PubMed

Suzuki, Katsuyoshi; Otsuka, Naomi; Hizaki, Hiroko; Hashimoto, Masayo; Kuwayama, Yasuaki

2018-06-05

This was the first exploratory randomized controlled study to compare the efficacy and safety of a preserved tafluprost/timolol fixed combination (TAF/TIM) with a preserved latanoprost/timolol fixed combination (LAT/TIM). This prospective, randomized, open-label study was conducted in Japanese patients with primary open-angle glaucoma, including normal-tension glaucoma or ocular hypertension. Following a 4-week LAT/TIM run-in period, eligible patients entered a 12-week treatment period, during which they received either LAT/TIM or TAF/TIM. The efficacy endpoint was the change in intraocular pressure (IOP) from baseline to week 12 and the safety endpoints included the changes from baseline to week 12 in superficial punctate keratopathy (SPK) score, tear breakup time (TBUT), and hyperemia score, as well as adverse events (AEs). At week 6, ocular symptoms were evaluated using a questionnaire. In total, 131 patients provided informed consent. Of these, 115 completed the run-in period and were assigned to receive TAF/TIM (n = 60) or LAT/TIM (n = 55). At week 12, there were no significant differences between the TAF/TIM and LAT/TIM groups in the change from baseline in trough IOP and IOP at 4-6 h after instillation. There were no significant differences between the two groups in the change from baseline to week 12 in SPK score, TBUT, and hyperemia score. However, only in the TAF/TIM group, the total SPK score and the inferior cornea SPK score were significantly lower at week 12 compared with baseline. Eye irritation and eye pain were significantly decreased in the TAF/TIM group compared with the LAT/TIM group. Two treatment-related AEs were reported in the TAF/TIM group (3.3%) and none in the LAT/TIM group, while no serious AEs were reported in either group. TAF/TIM is as effective as LAT/TIM in terms of IOP-reducing effect, with fewer ocular symptoms. TAF/TIM was associated with a significant improvement in SPK scores. UMIN Clinical Trials Registry Identifier

A 90 day chronic toxicity study of Nigerian herbal preparation DAS-77 in rats

PubMed Central

2012-01-01

Background The herbal preparation DAS-77, used for the treatment of various ailments in Nigeria, contains the milled bark of Mangifera indica L. and root of Carica papaya L. Toxicological assessment of the preparation was carried out in this study. Methods In the acute toxicity study, DAS-77 was administered to mice p.o. up to 20 g/kg in divided doses and i.p. at 250–3000 mg/kg. Mortality within 24 h was recorded. In the chronic toxicity study, rats were treated p.o. for 90 days at doses of 80, 400 (therapeutic dose, TD) and 2000 mg/kg. By 90 days, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination, antioxidants and histopathological assessments. Results DAS-77 did not produce any lethality administered p.o. up to 20 g/kg in divided doses but the i.p. LD50 was 1122.0 mg/kg. At TD, DAS-77 produced significant (p < 0.05) reductions in body weight, food intake and K+, and increases in ovary weight, neutrophils and HDL, which were reversible. Histopathological presentations were generally normal. Effects at the other doses were comparable to those at TD except for reversible increases in antioxidants in the liver, kidney and testes, and sperm abnormality, and reductions in liver enzymes, sperm motility and count. Conclusions Findings in this study revealed that DAS-77 is relatively safe with the potential for enhancing in vivo antioxidant activity. However, possibly reversible side-effects include electrolyte imbalance and sterility in males. PMID:22892317

A 90 day chronic toxicity study of Nigerian herbal preparation DAS-77 in rats.

PubMed

Afolabi, Saheed O; Akindele, Abidemi J; Awodele, Olufunsho; Anunobi, Chidozie C; Adeyemi, Olufunmilayo O

2012-06-28

The herbal preparation DAS-77, used for the treatment of various ailments in Nigeria, contains the milled bark of Mangifera indica L. and root of Carica papaya L. Toxicological assessment of the preparation was carried out in this study. In the acute toxicity study, DAS-77 was administered to mice p.o. up to 20 g/kg in divided doses and i.p. at 250-3000 mg/kg. Mortality within 24 h was recorded. In the chronic toxicity study, rats were treated p.o. for 90 days at doses of 80, 400 (therapeutic dose, TD) and 2000 mg/kg. By 90 days, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination, antioxidants and histopathological assessments. DAS-77 did not produce any lethality administered p.o. up to 20 g/kg in divided doses but the i.p. LD50 was 1122.0 mg/kg. At TD, DAS-77 produced significant (p < 0.05) reductions in body weight, food intake and K+, and increases in ovary weight, neutrophils and HDL, which were reversible. Histopathological presentations were generally normal. Effects at the other doses were comparable to those at TD except for reversible increases in antioxidants in the liver, kidney and testes, and sperm abnormality, and reductions in liver enzymes, sperm motility and count. Findings in this study revealed that DAS-77 is relatively safe with the potential for enhancing in vivo antioxidant activity. However, possibly reversible side-effects include electrolyte imbalance and sterility in males.

Efficacy and tolerability of fixed-combination bimatoprost/timolol versus fixed-combination dorzolamide/brimonidine/timolol in patients with primary open-angle glaucoma or ocular hypertension: a multicenter, prospective, crossover study.

PubMed

García-López, Alfonso; Paczka, José A; Jiménez-Román, Jesús; Hartleben, Curt

2014-12-19

Fixed-combination ocular hypotensives have multiple advantages, but triple-therapy dorzolamide/brimonidine/timolol (dorz/brim/tim) is only available in Latin and South America, and information on its relative efficacy is limited. This study compares the efficacy and tolerability of fixed-combination bimatoprost/timolol (bim/tim) and dorz/brim/tim in Mexican patients with primary open-angle glaucoma or ocular hypertension. In this investigator-masked, crossover study, patients with unmet target intraocular pressure (IOP) on once-daily bim/tim or twice-daily dorz/brim/tim received the opposite medication for 3 months before returning to their pre-baseline medication for 3 months. IOP was evaluated before and after morning instillation at months 2, 3, 5 and 6. Primary endpoints were mean IOP change and Ocular Surface Disease Index© (OSDI) score at each visit. The intent-to-treat population was the a priori analysis population, but due to the number of discontinuations, the per-protocol and intent-to-treat populations were used for the primary efficacy and sensitivity analyses, respectively. Seventy-eight and 56 patients were included in the intent-to-treat and per-protocol populations, respectively. At month 3, statistically significant IOP reductions from baseline were observed in the bim/tim (P < 0.01) and dorz/brim/tim (P < 0.0001) groups, regardless of assessment time. At month 6, patients returned to bim/tim exhibited no significant IOP increase (regardless of assessment time), but patients returned to dorz/brim/tim exhibited a statistically significant IOP increase (P < 0.001) when assessed before instillation of study treatment. Results were similar in both intent-to-treat and per-protocol analysis populations. In the per-protocol analysis, 70% of patients on bim/tim at month 3 had an IOP <14 mm Hg, which declined to 58% (P = 0.0061) at month 6 (ie, after 3 months of dorz/brim/tim treatment). In patients receiving dorz/brim/tim at month 3

Das CARNOTsche Paradigma und seine erkenntnistheoretischen Implikationen

NASA Astrophysics Data System (ADS)

Schöpf, Hans-Georg

Der vorliegende historisch-kritische Essay führt die Eigentümlichkeiten der klassischen phänomenologischen Thermodynamik auf das von CARNOT geschaffene Paradigma zurück und greift einige damit zusammenhängende Fragen auf.Translated AbstractCARNOT's Paradigm and its Epistemological ImplicationsThe present historic-critical essay traces the pecularities of classical phenomenological thermodynamics back to the paradigm, created by CARNOT, and takes up some questions to which this paradigm gives rise.

The SeaDAS Processing and Analysis System: SeaWiFS, MODIS, and Beyond

NASA Astrophysics Data System (ADS)

MacDonald, M. D.; Ruebens, M.; Wang, L.; Franz, B. A.

2005-12-01

The SeaWiFS Data Analysis System (SeaDAS) is a comprehensive software package for the processing, display, and analysis of ocean data from a variety of satellite sensors. Continuous development and user support by programmers and scientists for more than a decade has helped to make SeaDAS the most widely used software package in the world for ocean color applications, with a growing base of users from the land and sea surface temperature community. Full processing support for past (CZCS, OCTS, MOS) and present (SeaWiFS, MODIS) sensors, and anticipated support for future missions such as NPP/VIIRS, enables end users to reproduce the standard ocean archive product suite distributed by NASA's Ocean Biology Processing Group (OBPG), as well as a variety of evaluation and intermediate ocean, land, and atmospheric products. Availability of the processing algorithm source codes and a software build environment also provide users with the tools to implement custom algorithms. Recent SeaDAS enhancements include synchronization of MODIS processing with the latest code and calibration updates from the MODIS Calibration Support Team (MCST), support for all levels of MODIS processing including Direct Broadcast, a port to the Macintosh OS X operating system, release of the display/analysis-only SeaDAS-Lite, and an extremely active web-based user support forum.

Brady's Geothermal Field - Map of DAS, Nodal, Vibroseis and Reftek Station Deployment

DOE Data Explorer

Kurt Feigl

2016-10-15

Map of DAS, nodal, vibroseis and Reftek stations during March 2016 deployment. The plot on the left has nodal stations labeled; the plot on the right has vibroseis observations labeled. Stations are shown in map-view using Brady's rotated X-Y coordinates with side plots denoting elevation with respect to the WGS84 ellipsoid. Blue circles denote vibroseis data, x symbols denote DAS (cyan for horizontal and magenta for vertical), black asterisks denote Reftek data, and red plus signs denote nodal data. This map can be found on UW-Madison's askja server at /PoroTomo/DATA/MAPS/Deployment_Stations.pdf

Global Gridded Data from the Goddard Earth Observing System Data Assimilation System (GEOS-DAS)

NASA Technical Reports Server (NTRS)

2001-01-01

The Goddard Earth Observing System Data Assimilation System (GEOS-DAS) timeseries is a globally gridded atmospheric data set for use in climate research. This near real-time data set is produced by the Data Assimilation Office (DAO) at the NASA Goddard Space Flight Center in direct support of the operational EOS instrument product generation from the Terra (12/1999 launch), Aqua (05/2002 launch) and Aura (01/2004 launch) spacecrafts. The data is archived in the EOS Core System (ECS) at the Goddard Earth Sciences Data and Information Services Center/Distributed Active Archive Center (GES DISC DAAC). The data is only a selection of the products available from the GEOS-DAS. The data is organized chronologically in timeseries format to facilitate the computation of statistics. GEOS-DAS data will be available for the time period January 1, 2000, through present.

Measuring Primary Teachers' Attitudes Toward Teaching Science: Development of the Dimensions of Attitude Toward Science (DAS) Instrument

NASA Astrophysics Data System (ADS)

van Aalderen-Smeets, Sandra; Walma van der Molen, Juliette

2013-03-01

In this article, we present a valid and reliable instrument which measures the attitude of in-service and pre-service primary teachers toward teaching science, called the Dimensions of Attitude Toward Science (DAS) Instrument. Attention to the attitudes of primary teachers toward teaching science is of fundamental importance to the professionalization of these teachers in the field of primary science education. With the development of this instrument, we sought to fulfill the need for a statistically and theoretically valid and reliable instrument to measure pre-service and in-service teachers' attitudes. The DAS Instrument is based on a comprehensive theoretical framework for attitude toward (teaching) science. After pilot testing, the DAS was revised and subsequently validated using a large group of respondents (pre-service and in-service primary teachers) (N = 556). The theoretical underpinning of the DAS combined with the statistical data indicate that the DAS possesses good construct validity and that it proves to be a promising instrument that can be utilized for research purposes, and also as a teacher training and coaching tool. This instrument can therefore make a valuable contribution to progress within the field of science education.

Brady's Geothermal Field DAS Vibroseis Data

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

Kurt Feigl

2016-03-25

The submitted data correspond to the monitored vibrations caused by a vibroseis seismically exciting the ground in the vertical direction and captured by the DAS horizontal and vertical arrays during the PoroTomo Experiment. The data also include a file with the acceleration record at the Vibroseis. Vibroseis Sweep Details: Sweep on location T84 Stage 4 (Mode P 60 s long record ) Time: 2016-03-25 14:01:15 (UTC) Location: 39.80476089N, -119.0027625W Elevation: 1272.0M (on ground surface at the site) Sweep length: 20 seconds Frequencies: 5 Hz to 20 Hz

Efficient Delivery and Visualization of Long Time-Series Datasets Using Das2 Tools

NASA Astrophysics Data System (ADS)

Piker, C.; Granroth, L.; Faden, J.; Kurth, W. S.

2017-12-01

For over 14 years the University of Iowa Radio and Plasma Wave Group has utilized a network transparent data streaming and visualization system for most daily data review and collaboration activities. This system, called Das2, was originally designed in support of the Cassini Radio and Plasma Wave Science (RPWS) investigation, but is now relied on for daily review and analysis of Voyager, Polar, Cluster, Mars Express, Juno and other mission results. In light of current efforts to promote automatic data distribution in space physics it seems prudent to provide an overview of our open source Das2 programs and interface definitions to the wider community and to recount lessons learned. This submission will provide an overview of interfaces that define the system, describe the relationship between the Das2 effort and Autoplot and will examine handling Cassini RPWS Wideband waveforms and dynamic spectra as examples of dealing with long time-series data sets. In addition, the advantages and limitations of the current Das2 tool set will be discussed, as well as lessons learned that are applicable to other data sharing initiatives. Finally, plans for future developments including improved catalogs to support 'no-software' data sources and redundant multi-server fail over, as well as new adapters for CSV (Comma Separated Values) and JSON (Javascript Object Notation) output to support Cassini closeout and the HAPI (Heliophysics Application Programming Interface) initiative are outlined.

A causa das estações do ano: modelos mentais

NASA Astrophysics Data System (ADS)

de Campos, J. A. S.; de Araujo, J. F. S.

2003-08-01

A década de 70 do século passado foi marcada pelo estudo das concepções alternativas que os alunos trazem para a sala de aula. A identificação destas concepções foi o ponto de partida para promover a mudança conceitual, onde as pré-concepções seriam trocadas pelas concepções científicas. Na década seguinte, surgiram muitas propostas de estratégias educacionais para facilitar esta troca, na sua maioria baseadas na idéia do conflito cognitivo, proposta por Piaget. Entretanto, os resultados pouco animadores conduziram à percepção de que a mudança conceitual é um processo mais complexo. Pelas idéias da Ciência Cognitiva, a mudança conceitual é uma mudança progressiva dos modelos mentais que o aluno tem sobre o mundo físico, através de enriquecimento e revisão. A causa das Estações do Ano é um tópico sobre o qual a maioria dos estudantes apresenta concepções alternativas. Os autores fizeram um levantamento sobre as pré-concepções encontradas em trabalhos sobre o tema (16 referências), procurando encontrar elementos comuns que indicassem a presença de modelos mentais específicos. As pré-concepções encontradas na literatura foram obtidas usando-se diversas metodologias (desde entrevistas clínicas até questionários de múltipla escolha) e envolvendo alunos e professores de diferentes regiões geográficas. A partir de uma análise aprofundada de cada trabalho, e utilizando-se a técnica das Redes Sistêmicas, chegou-se a conclusão que as diversas pré-concepções identificadas (em torno de 50), poderiam ser representadas por 6 modelos mentais, onde a explicação da causa das estações do ano tem um mecanismo causal responsável. Os mecanismos causais identificados foram: a dependência da distância, a dependência da orientação, a dependência conjunta da distância e orientação, a dependência da obstrução, a dependência da velocidade e a dependência da inclinação dos raios solares. Foram ainda identificadas

Safety evaluation of genetically modified DAS-40278-9 maize in a subchronic rodent feeding study.

PubMed

Zou, Shiying; Lang, Tianqi; Liu, Xu; Huang, Kunlun; He, Xiaoyun

2018-07-01

Genetically modified (GM) maize, DAS-40278-9, expresses the aryloxyalkanoate dioxygenase-1 (AAD-1) protein, which confers tolerance to 2,4-dichlorophenoxyacetic acid (2,4-D) and aryloxyphenoxypropionate (AOPP) herbicides. The aad-1 gene, which expresses the AAD-1 protein, was derived from Gram-negative soil bacterium, Sphingobium herbicidovorans. A 90-day sub-chronic toxicity study was conducted on rats as a component of the safety evaluation of DAS-40278-9 maize. Rats were given formulated diets containing maize grain from DAS-40278-9 or a non-GM near isogenic control comparator at an incorporation rate of 12.5%, 25%, or 50% (w/w), respectively for 90 days. In addition, another group of rats was fed a basic rodent diet. Animals were evaluated by cage-side and hand-held detailed clinical observations, ophthalmic examinations, body weights/body weight gains, feed consumption, hematology, serum chemistry, selected organ weights, and gross and histopathological examinations. Under the condition of this study, DAS-40278-9 maize did not cause any treatment-related effects in rats compared with rats fed diets containing non-GM maize. Copyright © 2018 Elsevier Inc. All rights reserved.

Revision of an automated microseismic location algorithm for DAS - 3C geophone hybrid array

NASA Astrophysics Data System (ADS)

Mizuno, T.; LeCalvez, J.; Raymer, D.

2017-12-01

Application of distributed acoustic sensing (DAS) has been studied in several areas in seismology. One of the areas is microseismic reservoir monitoring (e.g., Molteni et al., 2017, First Break). Considering the present limitations of DAS, which include relatively low signal-to-noise ratio (SNR) and no 3C polarization measurements, a DAS - 3C geophone hybrid array is a practical option when using a single monitoring well. Considering the large volume of data from distributed sensing, microseismic event detection and location using a source scanning type algorithm is a reasonable choice, especially for real-time monitoring. The algorithm must handle both strain rate along the borehole axis for DAS and particle velocity for 3C geophones. Only a small quantity of large SNR events will be detected throughout a large aperture encompassing the hybrid array; therefore, the aperture is to be optimized dynamically to eliminate noisy channels for a majority of events. For such hybrid array, coalescence microseismic mapping (CMM) (Drew et al., 2005, SPE) was revised. CMM forms a likelihood function of location of event and its origin time. At each receiver, a time function of event arrival likelihood is inferred using an SNR function, and it is migrated to time and space to determine hypocenter and origin time likelihood. This algorithm was revised to dynamically optimize such a hybrid array by identifying receivers where a microseismic signal is possibly detected and using only those receivers to compute the likelihood function. Currently, peak SNR is used to select receivers. To prevent false results due to small aperture, a minimum aperture threshold is employed. The algorithm refines location likelihood using 3C geophone polarization. We tested this algorithm using a ray-based synthetic dataset. Leaney (2014, PhD thesis, UBC) is used to compute particle velocity at receivers. Strain rate along the borehole axis is computed from particle velocity as DAS microseismic

Assimilation of SBUV Version 8 Radiances into the GEOS Ozone DAS

NASA Technical Reports Server (NTRS)

Mueller, Martin D.; Stajner, Ivanka; Bhartia, Pawan K.

2004-01-01

In operational weather forecasting, the assimilation of brightness temperatures from satellite sounders, instead of assimilation of 1D-retrievals has become increasingly common practice over the last two decades. Compared to these systems, assimilation of trace gases is still at a relatively early stage of development, and efforts to directly assimilate radiances instead of retrieved products have just begun a few years ago, partially because it requires much more computation power due to the employment of a radiative transport forward model (FM). This paper will focus on a method to assimilate SBUV/2 radiances (albedos) into the Global Earth Observation System Ozone Data Assimilation Scheme (GEOS-03DAS). While SBUV-type instruments cannot compete with newer sensors in terms of spectral and horizontal resolution, they feature a continuous data record back to 1978, which makes them very valuable for trend studies. Assimilation can help spreading their ground coverage over the whole globe, as has been previously demonstrated with the GEOS-03DAS using SBUV Version 6 ozone profiles. Now, the DAS has been updated to use the newly released SBUV Version 8 data. We will compare pre]lmlnarv results of SBUV radiance assimilation with the assimilation of retrieved ozone profiles, discuss methods to deal with the increased computational load, and try to assess the error characteristics and future potential of the new approach.

Einfluss des Internets auf das Informations-, Einkaufs- und Verkehrsverhalten

NASA Astrophysics Data System (ADS)

Nerlich, Mark R.; Schiffner, Felix; Vogt, Walter

Mit Daten aus eigenen Erhebungen können das einkaufsbezogene Informations- und Einkaufsverhalten im Zusammenhang mit den verkehrlichen Aspekten (Distanzen, Verkehrsmittel, Wegekopplungen) dargestellt werden. Die Differenzierung in die drei Produktkategorien des täglichen, mittelfristigen und des langfristigen Bedarfs berücksichtigt in erster Linie die Wertigkeit eines Gutes, die seine Erwerbshäufigkeit unmittelbar bestimmt. Der Einsatz moderner IKT wie das Internet eröffnet dem Endverbraucher neue Möglichkeiten bei Information und Einkauf. Die verkehrliche Relevanz von Online-Shopping wird deutlich, wenn man berücksichtigt, dass im Mittel rund 17% aller Online-Einkäufe, die die Probanden durchgeführt haben, Einkäufe in Ladengeschäften ersetzen. Dies gilt in verstärktem Maße für Online-Informationen: etwa die Hälfte hätte alternativ im stationären Einzelhandel stattgefunden. Da der Erwerb von Gütern des täglichen Bedarfs häufig nahräumlich und in relevantem Anteil nicht-motorisiert erfolgen kann, sind in diesem Segment - im Gegensatz zum mittel- und langfristigen Bedarf - nur geringe Substitutionseffekte zu beobachten.

CULLIN-3 Controls TIMELESS Oscillations in the Drosophila Circadian Clock

PubMed Central

Lamouroux, Annie; Chélot, Elisabeth; Rouyer, François

2012-01-01

Eukaryotic circadian clocks rely on transcriptional feedback loops. In Drosophila, the PERIOD (PER) and TIMELESS (TIM) proteins accumulate during the night, inhibit the activity of the CLOCK (CLK)/CYCLE (CYC) transcriptional complex, and are degraded in the early morning. The control of PER and TIM oscillations largely depends on post-translational mechanisms. They involve both light-dependent and light-independent pathways that rely on the phosphorylation, ubiquitination, and proteasomal degradation of the clock proteins. SLMB, which is part of a CULLIN-1-based E3 ubiquitin ligase complex, is required for the circadian degradation of phosphorylated PER. We show here that CULLIN-3 (CUL-3) is required for the circadian control of PER and TIM oscillations. Expression of either Cul-3 RNAi or dominant negative forms of CUL-3 in the clock neurons alters locomotor behavior and dampens PER and TIM oscillations in light-dark cycles. In constant conditions, CUL-3 deregulation induces behavioral arrhythmicity and rapidly abolishes TIM cycling, with slower effects on PER. CUL-3 affects TIM accumulation more strongly in the absence of PER and forms protein complexes with hypo-phosphorylated TIM. In contrast, SLMB affects TIM more strongly in the presence of PER and preferentially associates with phosphorylated TIM. CUL-3 and SLMB show additive effects on TIM and PER, suggesting different roles for the two ubiquitination complexes on PER and TIM cycling. This work thus shows that CUL-3 is a new component of the Drosophila clock, which plays an important role in the control of TIM oscillations. PMID:22879814

Distributed Acoustic Sensing (DAS) for Periodic Hydraulic Tests: Laboratory Data

DOE Data Explorer

Coleman, Thomas

2015-02-27

These data were collected in the laboratory located at California State University Long Beach. They consist of DAS data collected from a fiber optic cable placed in a tank of water, subjected to oscillating head. These tests are described in the article linked below.

A trypanosomal orthologue of an intermembrane space chaperone has a non-canonical function in biogenesis of the single mitochondrial inner membrane protein translocase.

PubMed

Wenger, Christoph; Oeljeklaus, Silke; Warscheid, Bettina; Schneider, André; Harsman, Anke

2017-08-01

Mitochondrial protein import is essential for Trypanosoma brucei across its life cycle and mediated by membrane-embedded heterooligomeric protein complexes, which mainly consist of trypanosomatid-specific subunits. However, trypanosomes contain orthologues of small Tim chaperones that escort hydrophobic proteins across the intermembrane space. Here we have experimentally analyzed three novel trypanosomal small Tim proteins, one of which contains only an incomplete Cx3C motif. RNAi-mediated ablation of TbERV1 shows that their import, as in other organisms, depends on the MIA pathway. Submitochondrial fractionation combined with immunoprecipitation and BN-PAGE reveals two pools of small Tim proteins: a soluble fraction forming 70 kDa complexes, consistent with hexamers and a second fraction that is tightly associated with the single trypanosomal TIM complex. RNAi-mediated ablation of the three proteins leads to a growth arrest and inhibits the formation of the TIM complex. In line with these findings, the changes in the mitochondrial proteome induced by ablation of one small Tim phenocopy the effects observed after ablation of TbTim17. Thus, the trypanosomal small Tims play an unexpected and essential role in the biogenesis of the single TIM complex, which for one of them is not linked to import of TbTim17.

Structural and biochemical characterization of a recombinant triosephosphate isomerase from Rhipicephalus (Boophilus) microplus

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

Moraes, Jorge; Arreola, Rodrigo; Cabrera, Nallely

2012-02-06

Triosephosphate isomerase (TIM) is an enzyme with a role in glycolysis and gluconeogenesis by catalyzing the interconversion between glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. This enzyme has been used as a target in endoparasite drug development. In this work we cloned, expressed, purified and studied kinetic and structural characteristics of TIM from tick embryos, Rhipicephalus (Boophilus) microplus (BmTIM). The Km and Vmax of the recombinant BmTIM with glyceraldehyde 3-phosphate as substrate, were 0.47 mM and 6031 {micro}mol min{sup -1} mg protein{sup -1}, respectively. The resolution of the diffracted crystal was estimated to be 2.4 {angstrom} and the overall data showed thatmore » BmTIM is similar to other reported dimeric TIMs. However, we found that, in comparison to other TIMs, BmTIM has the highest content of cysteine residues (nine cysteine residues per monomer). Only two cysteines could make disulfide bonds in monomers of BmTIM. Furthermore, BmTIM was highly sensitive to the action of the thiol reagents dithionitrobenzoic acid and methyl methane thiosulfonate, suggesting that there are five cysteines exposed in each dimer and that these residues could be employed in the development of species-specific inhibitors.« less

Increased expression of T cell immunoglobulin and mucin domain 3 aggravates brain inflammation via regulation of the function of microglia/macrophages after intracerebral hemorrhage in mice.

PubMed

Xu, ChangJun; Wang, Tao; Cheng, Si; Liu, YuGuang

2013-12-01

Microglia/macrophages are known to play important roles in initiating brain inflammation after spontaneous intracerebral hemorrhage (ICH). T cell immunoglobulin and mucin domain-3 (Tim-3) have been proven to play a critical part in several inflammatory diseases through regulation of both adaptive and innate immune responses. Tim-3 can be expressed by microglia/macrophages and regulates their function in the innate immune response. However, the effect of Tim-3 on inflammatory responses following ICH is unclear. In this study, we investigated Tim-3 expression, the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and brain water content in peri-hematomal brain tissue at 12 hours and at 1, 3, 5, and 7 days post-ICH in wild type (WT) ICH and Tim-3-/- ICH mice. The numbers of Tim-3 positive cells,astrocytes, neutrophils and microglia/macrophages were detected using immunofluorescence staining. Cytokines were measured by ELISA. Double immunofluorescence labeling was performed to identify the cellular source of Tim-3 expression. Mouse neurological deficit scores were assessed through animal behavior. Expression of Tim-3 increased early in mouse peri-hematomal brain tissue after autologous blood injection, peaked at day 1, and was positively correlated with the concentrations of TNF-α, IL-1β, and brain water content. Tim-3 was predominantly expressed in microglia/macrophages. Compared with WT mice, Tim-3-/- mice had reduced ICH-induced brain inflammation with decreased TNF-α and IL-1β, cerebral edema and neurological deficit scores. Moreover, Tim-/- inhibited activation of microglia/macrophages. The number of activated microglia/macrophages in Tim-3-/- ICH mice was much lower than that in WT ICH mice. Our findings demonstrate that Tim-3 plays an important role in brain inflammation after ICH, and may be a potential treatment target.

50 CFR 648.53 - Acceptable biological catch (ABC), annual catch limits (ACL), annual catch targets (ACT), DAS...

Code of Federal Regulations, 2013 CFR

2013-10-01

... catch limits (ACL), annual catch targets (ACT), DAS allocations, and individual fishing quotas (IFQ... limits (ACL), annual catch targets (ACT), DAS allocations, and individual fishing quotas (IFQ). (a... process specified in § 648.55 and is equal to the overall scallop fishery ACL. The ABC/ACL shall be...

50 CFR 648.53 - Acceptable biological catch (ABC), annual catch limits (ACL), annual catch targets (ACT), DAS...

Code of Federal Regulations, 2014 CFR

2014-10-01

... catch limits (ACL), annual catch targets (ACT), DAS allocations, and individual fishing quotas (IFQ... limits (ACL), annual catch targets (ACT), DAS allocations, and individual fishing quotas (IFQ). (a... process specified in § 648.55 and is equal to the overall scallop fishery ACL. The ABC/ACL shall be...

Teaching Foreign Cultural Literacy with Margarethe von Trotta's "Das Versprechen"

ERIC Educational Resources Information Center

Kuttenberg, Eva

2003-01-01

This article describes model units for an in-depth cultural analysis of "Das Versprechen" in undergraduate college courses including intermediate German, German culture and civilization, advanced conversation and composition, and film. Practical suggestions for pre-viewing, viewing, and post-viewing activities as well as assessment in…

[Pleural mesothelioma in a school teacher: asbestos exposure due to DAS paste].

PubMed

Barbieri, Pietro Gino; Somigliana, Anna; Girelli, Roberto; Lombardi, Sandra; Sarnico, Michela; Silvestri, Stefano

2016-03-24

Malignant mesothelioma cases among primary school teachers are usually linked with asbestos exposure due to the mineral contained in the building structure. Among the approximately 12,000 cases of mesothelioma described in the fourth report of the National Mesothelioma Register, 11 cases of primary school teachers are reported, in spite of the fact that the "catalogue of asbestos use" does not describe circumstances of asbestos exposure other than or different to that due to asbestos contained in the buildings. Four cases in the Brescia Provincial Mesothelioma Register are identified as teachers, without this circumstance of exposure. To characterize the asbestos concentration and fibre type retained in the lungs of a teacher reported as a new mesothelioma case and preliminarily classified as of unknown asbestos exposure. The mesothelioma case presented here was diagnosed at age 78 and malignant mesothelioma was confirmed at autopsy; the patient was interviewed directly for occupational history. Samples of lung parenchyma from necropsies were collected, stored and analyzed by scanning electron microscope (SEM) and samples of DAS paste were analyzed by SEM to detect asbestos fibre content. It was possible to confirm past exposure to DAS paste in forming and finishing dry items and toys during school recreational activity almost every day from the mid-60s to about the mid-70s. Subsequent SEM analysis showed: i) chrysotile fibres were found in an old and unused pack of DAS paste; ii) a lung burden of 1,400 asbestos bodies, 310.000 total asbestos fibres (33% chrysotile, 67% amphibole) and 210.000 talc fibre per gr/dry lung tissue was detected from necropsies performed on the subject. These results seem to be in agreement with an occupational exposure to asbestos due to past use of DAS paste. After the investigation, this case was reclassified from "unknowun" to " sure" occupational asbestos exposure. The occupational origin of the tumour was recognized by the Italian

Surveillance of traffic incident management-related occupational fatalities in Kentucky, 2005-2016.

PubMed

Bunn, T L; Slavova, S; Chandler, M; Hanner, N; Singleton, M

2018-05-19

Traffic incidents occurring on roadways require the coordinated effort of multiple responder and recovery entities, including communications, law enforcement, fire and rescue, emergency medical services, hazardous materials, transportation agencies, and towing and recovery. The objectives of this study were to (1) identify and characterize transportation incident management (TIM)-related occupational fatalities; (2) assess concordance of surveillance data sources in identifying TIM occupations, driver vs. pedestrian status, and occupational fatality incident location; and (3) determine and compare U.S. occupational fatality rates for TIM industries. The Kentucky Fatality Assessment and Control Evaluation (FACE) program analyzed 2005-2016 TIM occupational fatality data using multiple data sources: death certificate data, Collision Report Analysis for Safer Highways (CRASH) data, and media reports, among others. Literal text analysis was performed on FACE data, and a multiple linear regression model and SAS proc sgpanel were used to estimate and visualize the U.S. TIM occupational mortality trend lines and confidence bounds. There were 29 TIM fatalities from 2005 to 2015 in Kentucky; 41% of decedents were in the police protection occupation, and 21% each were in the fire protection and motor vehicle towing industries. Over one half of the TIM decedents were performing work activities as pedestrians when they died. Media reports identified the majority of the occupational fatalities as TIM related (28 of 29 TIM-related deaths); the use of death certificates as the sole surveillance data source only identified 17 of the 29 deaths as TIM related, and the use of CRASH data only identified 4 of the 29 deaths as TIM related. Injury scenario text analysis showed that law enforcement vehicle pursuit, towing and recovery vehicle loading, and disabled vehicle response were particular high-risk activities that led to TIM deaths. Using U.S. data, the motor vehicle towing

Incorporating Parallel Computing into the Goddard Earth Observing System Data Assimilation System (GEOS DAS)

NASA Technical Reports Server (NTRS)

Larson, Jay W.

1998-01-01

Atmospheric data assimilation is a method of combining actual observations with model forecasts to produce a more accurate description of the earth system than the observations or forecast alone can provide. The output of data assimilation, sometimes called the analysis, are regular, gridded datasets of observed and unobserved variables. Analysis plays a key role in numerical weather prediction and is becoming increasingly important for climate research. These applications, and the need for timely validation of scientific enhancements to the data assimilation system pose computational demands that are best met by distributed parallel software. The mission of the NASA Data Assimilation Office (DAO) is to provide datasets for climate research and to support NASA satellite and aircraft missions. The system used to create these datasets is the Goddard Earth Observing System Data Assimilation System (GEOS DAS). The core components of the the GEOS DAS are: the GEOS General Circulation Model (GCM), the Physical-space Statistical Analysis System (PSAS), the Observer, the on-line Quality Control (QC) system, the Coupler (which feeds analysis increments back to the GCM), and an I/O package for processing the large amounts of data the system produces (which will be described in another presentation in this session). The discussion will center on the following issues: the computational complexity for the whole GEOS DAS, assessment of the performance of the individual elements of GEOS DAS, and parallelization strategy for some of the components of the system.

I/O Parallelization for the Goddard Earth Observing System Data Assimilation System (GEOS DAS)

NASA Technical Reports Server (NTRS)

Lucchesi, Rob; Sawyer, W.; Takacs, L. L.; Lyster, P.; Zero, J.

1998-01-01

The National Aeronautics and Space Administration (NASA) Data Assimilation Office (DAO) at the Goddard Space Flight Center (GSFC) has developed the GEOS DAS, a data assimilation system that provides production support for NASA missions and will support NASA's Earth Observing System (EOS) in the coming years. The GEOS DAS will be used to provide background fields of meteorological quantities to EOS satellite instrument teams for use in their data algorithms as well as providing assimilated data sets for climate studies on decadal time scales. The DAO has been involved in prototyping parallel implementations of the GEOS DAS for a number of years and is now embarking on an effort to convert the production version from shared-memory parallelism to distributed-memory parallelism using the portable Message-Passing Interface (MPI). The GEOS DAS consists of two main components, an atmospheric General Circulation Model (GCM) and a Physical-space Statistical Analysis System (PSAS). The GCM operates on data that are stored on a regular grid while PSAS works with observational data that are scattered irregularly throughout the atmosphere. As a result, the two components have different data decompositions. The GCM is decomposed horizontally as a checkerboard with all vertical levels of each box existing on the same processing element(PE). The dynamical core of the GCM can also operate on a rotated grid, which requires communication-intensive grid transformations during GCM integration. PSAS groups observations on PEs in a more irregular and dynamic fashion.

Detection and Mapping of the September 2017 Mexico Earthquakes Using DAS Fiber-Optic Infrastructure Arrays

NASA Astrophysics Data System (ADS)

Karrenbach, M. H.; Cole, S.; Williams, J. J.; Biondi, B. C.; McMurtry, T.; Martin, E. R.; Yuan, S.

2017-12-01

Fiber-optic distributed acoustic sensing (DAS) uses conventional telecom fibers for a wide variety of monitoring purposes. Fiber-optic arrays can be located along pipelines for leak detection; along borders and perimeters to detect and locate intruders, or along railways and roadways to monitor traffic and identify and manage incidents. DAS can also be used to monitor oil and gas reservoirs and to detect earthquakes. Because thousands of such arrays are deployed worldwide and acquiring data continuously, they can be a valuable source of data for earthquake detection and location, and could potentially provide important information to earthquake early-warning systems. In this presentation, we show that DAS arrays in Mexico and the United States detected the M8.1 and M7.2 Mexico earthquakes in September 2017. At Stanford University, we have deployed a 2.4 km fiber-optic DAS array in a figure-eight pattern, with 600 channels spaced 4 meters apart. Data have been recorded continuously since September 2016. Over 800 earthquakes from across California have been detected and catalogued. Distant teleseismic events have also been recorded, including the two Mexican earthquakes. In Mexico, fiber-optic arrays attached to pipelines also detected these two events. Because of the length of these arrays and their proximity to the event locations, we can not only detect the earthquakes but also make location estimates, potentially in near real time. In this presentation, we review the data recorded for these two events recorded at Stanford and in Mexico. We compare the waveforms recorded by the DAS arrays to those recorded by traditional earthquake sensor networks. Using the wide coverage provided by the pipeline arrays, we estimate the event locations. Such fiber-optic DAS networks can potentially play a role in earthquake early-warning systems, allowing actions to be taken to minimize the impact of an earthquake on critical infrastructure components. While many such fiber

Timing of metamorphism and exhumation in the Nordøyane ultra-high-pressure domain, Western Gneiss Region, Norway: New constraints from complementary CA-ID-TIMS and LA-MC-ICP-MS geochronology

NASA Astrophysics Data System (ADS)

Butler, J. P.; Jamieson, R. A.; Dunning, G. R.; Pecha, M. E.; Robinson, P.; Steenkamp, H. M.

2018-06-01

We present the results of a combined CA-ID-TIMS and LA-MC-ICP-MS U-Pb geochronology study of zircon and associated rutile and titanite from the Nordøyane ultra-high-pressure (UHP) domain in the Western Gneiss Region (WGR) of Norway. The dated samples include 4 eclogite bodies, 2 host-rock migmatites, and 2 cross-cutting pegmatites and leucosomes, all from the island of Harøya. Zircon from a coesite eclogite yielded an age of ca. 413 Ma, interpreted as the time of UHP metamorphism in this sample. Zircon data from the other eclogite bodies yielded metamorphic ages of ca. 413 Ma, 407 Ma, and 406 Ma; zircon trace-element data associated with 413 Ma and 407 Ma ages are consistent with eclogite-facies crystallization. In all of the eclogites, U-Pb dates from zircon cores, interpreted as the times of protolith crystallization, range from ca. 1680-1586 Ma, consistent with Gothian ages from orthogneisses in Nordøyane and elsewhere in the WGR. A zircon core age of ca. 943 Ma from one sample agrees with Sveconorwegian ages of felsic gneisses and pegmatites in the western part of the area. Migmatites hosting the eclogite bodies yielded zircon core ages of ca. 1657-1591 Ma and rim ages of ca. 395-392 Ma, interpreted as the times of Gothian protolith formation and Scandian partial melt crystallization, respectively. Pegmatite in an eclogite boudin neck yielded a crystallization age of ca. 388 Ma, interpreted as the time of melt crystallization. Rutile and titanite from 3 samples (an eclogite and two migmatites) yielded concordant ID-TIMS ages of 378-376 Ma. The results are similar to existing U-Pb data from other Nordøyane eclogites (415-405 Ma). In combination with previous pressure-temperature data from the coesite eclogite, these ages indicate that peak metamorphic conditions of 3 GPa/760 °C were reached ca. 413 Ma, followed by decompression to 1 GPa/810 °C by ca. 397 Ma and cooling below ca. 600 °C by ca. 375 Ma. The results are compatible with protracted UHP

Development of a Stable Cell Line, Overexpressing Human T-cell Immunoglobulin Mucin 1

PubMed Central

Ebrahimi, Mina; Kazemi, Tohid; Ganjalikhani-hakemi, Mazdak; Majidi, Jafar; khanahmad, Hossein; Rahimmanesh, Ilnaz; Homayouni, Vida; Kohpayeh, Shirin

2015-01-01

Background Recent researches have demonstrated that human T-cell immunoglobulin mucin 1 (TIM-1) glycoprotein plays important roles in regulation of autoimmune and allergic diseases, as well as in tumor immunity and response to viral infections. Therefore, targeting TIM-1 could be a potential therapeutic approach against such diseases. Objectives In this study, we aimed to express TIM-1 protein on Human Embryonic kidney (HEK) 293T cell line in order to have an available source of the TIM-1 antigen. Materials and Methods The cDNA was synthesized after RNA extraction from peripheral blood mononuclear cells (PBMC) and TIM-1 cDNA was amplified by PCR with specific primers. The PCR product was cloned in pcDNA™3.1/Hygro (+) and transformed in Escherichia coli TOP 10 F’. After cloning, authenticity of DNA sequence was checked and expressed in HEK 293T cells. Finally, expression of TIM-1 was analyzed by flow cytometry and real-time PCR. Results The result of DNA sequencing demonstrated correctness of TIM-1 DNA sequence. The flow cytometry results indicated that TIM-1 was expressed in about 90% of transfected HEK 293T cells. The real-time PCR analysis showed TIM-1 mRNA expression increased 195-fold in transfected cells compared with un-transfected cells. Conclusions Findings of present study demonstrated the successful cloning and expression of TIM-1 on HEK 293T cells. These cells could be used as an immunogenic source for production of specific monoclonal antibodies, nanobodies and aptamers against human TIM-1. PMID:28959306

Garlic extract diallyl sulfide (DAS) activates nuclear receptor CAR to induce the Sult1e1 gene in mouse liver.

PubMed

Sueyoshi, Tatsuya; Green, William D; Vinal, Kellie; Woodrum, Tyler S; Moore, Rick; Negishi, Masahiko

2011-01-01

Constituent chemicals in garlic extract are known to induce phase I and phase II enzymes in rodent livers. Here we have utilized Car(+/+) and Car(-/-) mice to demonstrate that the nuclear xenobiotic receptor CAR regulated the induction of the estrogen sulfotransferase Sult1e1 gene by diallyl sulfide (DAS) treatment in mouse liver. DAS treatment caused CAR accumulation in the nucleus, resulting in a remarkable increase of SULT1E1 mRNA (3,200 fold) and protein in the livers of Car(+/+) females but not of Car(-/-) female mice. DAS also induced other CAR-regulated genes such as Cyp2b10, Cyp3a11 and Gadd45β. Compared with the rapid increase of these mRNA levels, which began as early as 6 hours after DAS treatment, the levels of SULT1E1 mRNA began increasing after 24 hours. This slow response to DAS suggested that CAR required an additional factor to activate the Sult1e1 gene or that this activation was indirect. Despite the remarkable induction of SULT1E1, there was no decrease in the serum levels of endogenous E2 or increase of estrone sulfate while the clearance of exogenously administrated E2 was accelerated in DAS treated mice.

(Re)locating (I)dentity With(in) Politicized (Re)presentation of Fe/Male Body in Kamala Das' Poetry

ERIC Educational Resources Information Center

Sultana, Sharmin; Sarwar, Nadia

2016-01-01

This paper is going to argue that the selected poems of renowned Indian poet Kamala Das are inclined to relocate both feminine and masculine identity through the politicized representation of body. Kamala Das' representation of body in her poems has always been viewed as a medium of re-historicizing the pain, sufferings, and psychological trauma…

The Deaf Acculturation Scale (DAS): Development and Validation of a 58-Item Measure

PubMed Central

Maxwell-McCaw, Deborah; Zea, Maria Cecilia

2011-01-01

This study involved the development and validation of the Deaf Acculturation Scale (DAS), a new measure of cultural identity for Deaf and hard-of-hearing (hh) populations. Data for this study were collected online and involved a nation-wide sample of 3,070 deaf/hh individuals. Results indicated strong internal reliabilities for all the subscales, and construct validity was established by demonstrating that the DAS could discriminate groups based on parental hearing status, school background, and use of self-labels. Construct validity was further demonstrated through factorial analyses, and findings resulted in a final 58-item measure. Directions for future research are discussed. PMID:21263041

Statistical Quality Control of Moisture Data in GEOS DAS

NASA Technical Reports Server (NTRS)

Dee, D. P.; Rukhovets, L.; Todling, R.

1999-01-01

A new statistical quality control algorithm was recently implemented in the Goddard Earth Observing System Data Assimilation System (GEOS DAS). The final step in the algorithm consists of an adaptive buddy check that either accepts or rejects outlier observations based on a local statistical analysis of nearby data. A basic assumption in any such test is that the observed field is spatially coherent, in the sense that nearby data can be expected to confirm each other. However, the buddy check resulted in excessive rejection of moisture data, especially during the Northern Hemisphere summer. The analysis moisture variable in GEOS DAS is water vapor mixing ratio. Observational evidence shows that the distribution of mixing ratio errors is far from normal. Furthermore, spatial correlations among mixing ratio errors are highly anisotropic and difficult to identify. Both factors contribute to the poor performance of the statistical quality control algorithm. To alleviate the problem, we applied the buddy check to relative humidity data instead. This variable explicitly depends on temperature and therefore exhibits a much greater spatial coherence. As a result, reject rates of moisture data are much more reasonable and homogeneous in time and space.

U-Pb geochronology of zircon and polygenetic titanite from the Glastonbury Complex, Connecticut, USA: An integrated SEM, EMPA, TIMS, and SHRIMP study

USGS Publications Warehouse

Aleinikoff, J.N.; Wintsch, R.P.; Fanning, C.M.; Dorais, M.J.

2002-01-01

U-Pb ages for zircon and titanite from a granodioritic gneiss in the Glastonbury Complex, Connecticut, have been determined using both isotope dilution thermal ionization mass spectrometry (TIMS) and the sensitive high resolution ion microprobe (SHRIMP). Zircons occur in three morphologic populations: (1) equant to stubby, multifaceted, colorless, (2) prismatic, dark brown, with numerous cracks, and (3) elongate, prismatic, light tan to colorless. Cathodoluminescence (CL) imaging of the three populations shows simple concentric oscillatory zoning. The zircon TIMS age [weighted average of 207Pb/206Pb ages from Group 3 grains-450.5 ?? 1.6 Ma (MSWD=1.11)] and SHRIMP age [composite of 206Pb/238 U age data from all three groups-448.2 ?? 2.7 Ma (MSWD = 1.3)], are interpreted to suggest a relatively simple crystallization history. Titanite from the granodioritic gneiss occurs as both brown and colorless varieties. Scanning electron microscope backscatter (BSE) images of brown grains show multiple cross-cutting oscillatory zones of variable brightness and dark overgrowths. Colorless grains are unzoned or contain subtle wispy or very faint oscillatory zoning. Electron microprobe analysis (EMPA) clearly distinguishes the two populations. Brown grains contain relatively high concentrations of Fe2O3, Ce2O3 (up to ~ 1.5 wt.%), Nb2O5, and Zr. Cerium concentration is positively correlated with total REE + Y concentration, which together can exceed 3.5 wt.%. Oscillatory zoning in brown titanite is correlated with variations in REE concentrations. In contrast, colorless titanite (both as discrete grains and overgrowths on brown titanite) contains lower concentrations of Y, REE, Fe2O3, and Zr, but somewhat higher Al2O3 and Nb2O5. Uranium concentrations and Th/U discriminate between brown grains (typically 200-400 ppm U; all analyses but one have Th/U between about 0.8 and 2) and colorless grains (10-60 ppm U; Th/U of 0-0.17). In contrast to the zircon U-Pb age results, SHRIMP U

Measurement of Sulfur Isotopic Composition (δ34S) by Multiple-Collector Thermal Ionization Mass Spectrometry (MC-TIMS) Using a 33S/36S Double Spike

NASA Astrophysics Data System (ADS)

Mann, J. L.; Kelly, W. R.

2006-05-01

A new analytical technique for the determination of δ34S will be described. The technique is based on the production of singularly charged arsenic sulfide molecular ions (AsS+) by thermal ionization using silica gel as an emitter and combines multiple-collector thermal ionization mass spectrometry (MC-TIMS) with a 33S/36S double spike to correct instrumental fractionation. Because the double spike is added to the sample before chemical processing, both the isotopic composition and sulfur concentration are measured simultaneously. The accuracy and precision of the double spike technique is comparable to or better than modern gas source mass spectrometry, but requires about a factor of 10 less sample. Δ33S effects can be determined directly in an unspiked sample without any assumptions about the value of k (mass dependent fractionation factor) which is currently required by gas source mass spectrometry. Three international sulfur standards (IAEA-S-1, IAEA-S-2, and IAEA-S-3) were measured to evaluate the precision and accuracy of the new technique and to evaluate the consensus values for these standards. Two different double spike preparations were used. The δ34S values (reported relative to Vienna Canyon Diablo Troilite (VCDT), (δ34S (‰) = 34S/32S)sample/(34S/32S)VCDT - 1) x 1000]), 34S/32SVCDT = 0.0441626) determined were -0.32‰ ± 0.04‰ (1σ, n=4) and -0.31‰ ± 0.13‰ (1σ, n=8) for IAEA-S-1, 22.65‰ ± 0.04‰ (1σ, n=7) and 22.60‰ ± 0.06‰ (1σ, n=5) for IAEA- S-2, and -32.47‰ ± 0.07‰ (1σ, n=8) for IAEA-S-3. The amount of natural sample used for these analyses ranged from 0.40 μmoles to 2.35 μmoles. Each standard showed less than 0.5‰ variability (IAEA-S-1 < 0.4‰, IAEA-S-2 < 0.2‰, and IAEA-S-3 < 0.2‰). Our values for S-1 and S-2 are in excellent agreement with the consensus values and the values reported by other laboratories using both SF6 and SO2. Our value for S-3 differs statistically from the Institute for Reference

Tim Watkins

EPA Pesticide Factsheets

Tim’s expertise and interests lie in the area of air pollution exposure assessment, including ambient air monitoring, personal monitoring, source apportionment, and air quality and exposure modeling.

Novas determinações dos parâmetros atmosféricos das estrelas anãs brancas DA

NASA Astrophysics Data System (ADS)

Giovannini, O.; Costa, A. F. M.; Kepler, S. O.

2003-08-01

Nós temos selecionado uma amostra de estrelas anãs brancas DA (atmosfera de hidrogênio) a partir dos índices de Strömgren cujos valores estão próximos a região de instabilidade das estrelas anãs brancas DA variáveis, as chamadas estrelas DAV ou ZZ Ceti. O objetivo é determinar os parâmetros fundamentais (temperatura efetiva, Teff, aceleração da gravidade, log g, e massa) destas estrelas para verificar quais os parâmetros estelares estão envolvidos com o mecanismo de pulsação das estrelas DAV. Nós obtemos, até agora, mais de 120 espectros óticos de estrelas DA. Entre as estrelas selecionadas há 20 estrelas variáveis (DAV). Assim, podemos verificar se existem ou não estrelas não variáveis dentro da faixa de instabilidade das estrelas ZZ Ceti. Neste trabalho nós apresentamos a determinação dos parâmetros atmosféricos (temperatura efetiva, Teff, e aceleração da gravidade, log g) das estrelas anãs brancas DA usando os novos modelos de atmosfera ML2/a = 0.6. Estes modelos têm sido utilizados recentemente por fornecerem uma excelente consistência interna na determinação das temperaturas nas regiões do ultra-violeta e ótico. Os parâmetros atmosféricos são determinados espectroscopicamente através da comparação do fluxo de energia das linhas de Balmer (Hb à H9) entre os espectros observados e sintéticos (gerados pelos modelos de atmosfera). As temperaturas obtidas com os novos modelos são, em geral, menores (~ 1000 K menos) que as temperaturas determinadas anteriormente, com modelos ML1. Os valores de log g não mudaram significativamente (menos de 10%). A faixa de instabilidade das DAVs está entre 11000 e 13000 K, consistente com dados de outros autores.

A fluorescence assay for peptide translocation into mitochondria.

PubMed

Martinez-Caballero, Sonia; Peixoto, Pablo M V; Kinnally, Kathleen W; Campo, María Luisa

2007-03-01

Translocation of the presequence is an early event in import of preproteins across the mitochondrial inner membrane by the TIM23 complex. Import of signal peptides, whose sequences mimic mitochondrial import presequences, was measured using a novel, qualitative, fluorescence assay in about 1h. This peptide assay was used in conjunction with classical protein import analyses and electrophysiological approaches to examine the mechanisms underlying the functional effects of depleting two TIM23 complex components. Tim23p forms, at least in part, the pore of this complex while Tim44p forms part of the translocation motor. Depletion of Tim23p eliminates TIM23 channel activity, which interferes with both peptide and preprotein translocation. In contrast, depletion of Tim44p disrupts preprotein but not peptide translocation, which has no effect on TIM23 channel activity. Two conclusions were made. First, this fluorescence peptide assay was validated as two different mutants were accurately identified. Hence, this assay could provide a rapid means of screening mutants to identify those that fail an initial step in import, i.e., translocation of the presequence. Second, translocation of signal peptides required normal channel activity and disruption of the presequence translocase-associated motor complex did not modify TIM23 channel activity nor prevent presequence translocation.

Temperature-dependent resetting of the molecular circadian oscillator in Drosophila

PubMed Central

Goda, Tadahiro; Sharp, Brandi; Wijnen, Herman

2014-01-01

Circadian clocks responsible for daily time keeping in a wide range of organisms synchronize to daily temperature cycles via pathways that remain poorly understood. To address this problem from the perspective of the molecular oscillator, we monitored temperature-dependent resetting of four of its core components in the fruitfly Drosophila melanogaster: the transcripts and proteins for the clock genes period (per) and timeless (tim). The molecular circadian cycle in adult heads exhibited parallel responses to temperature-mediated resetting at the levels of per transcript, tim transcript and TIM protein. Early phase adjustment specific to per transcript rhythms was explained by clock-independent temperature-driven transcription of per. The cold-induced expression of Drosophila per contrasts with the previously reported heat-induced regulation of mammalian Period 2. An altered and more readily re-entrainable temperature-synchronized circadian oscillator that featured temperature-driven per transcript rhythms and phase-shifted TIM and PER protein rhythms was found for flies of the ‘Tim 4’ genotype, which lacked daily tim transcript oscillations but maintained post-transcriptional temperature entrainment of tim expression. The accelerated molecular and behavioural temperature entrainment observed for Tim 4 flies indicates that clock-controlled tim expression constrains the rate of temperature cycle-mediated circadian resetting. PMID:25165772

CEACAM1 regulates TIM–3–mediated tolerance and exhaustion

PubMed Central

Huang, Yu-Hwa; Zhu, Chen; Kondo, Yasuyuki; Anderson, Ana C.; Gandhi, Amit; Russell, Andrew; Dougan, Stephanie K.; Petersen, Britt-Sabina; Melum, Espen; Pertel, Thomas; Clayton, Kiera L.; Raab, Monika; Chen, Qiang; Beauchemin, Nicole; Yazaki, Paul J.; Pyzik, Michal; Ostrowski, Mario A.; Glickman, Jonathan N.; Rudd, Christopher E.; Ploegh, Hidde L.; Franke, Andre; Petsko, Gregory A.; Kuchroo, Vijay K.; Blumberg, Richard S.

2014-01-01

T-cell immunoglobulin domain and mucin domain-3 (TIM-3, also known as HAVCR2) is an activation-induced inhibitory molecule involved in tolerance and shown to induce T-cell exhaustion in chronic viral infection and cancers1–5. Under some conditions, TIM-3 expression has also been shown to be stimulatory. Considering that TIM-3, like cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death 1 (PD-1), is being targeted for cancer immunotherapy, it is important to identify the circumstances under which TIM-3 can inhibit and activate T-cell responses. Here we show that TIM-3 is co-expressed and forms a heterodimer with carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), another well-known molecule expressed on activated T cells and involved in T-cell inhibition6–10. Biochemical, biophysical and X-ray crystallography studies show that the membrane-distal immunoglobulin-variable (IgV)-like amino-terminal domain of each is crucial to these interactions. The presence of CEACAM1 endows TIM-3 with inhibitory function. CEACAM1 facilitates the maturation and cell surface expression of TIM-3 by forming a heterodimeric interaction in cis through the highly related membrane-distal N-terminal domains of each molecule. CEACAM1 and TIM-3 also bind in trans through their N-terminal domains. Both cis and trans interactions between CEACAM1 and TIM-3 determine the tolerance-inducing function of TIM-3. In a mouse adoptive transfer colitis model, CEACAM1-deficient T cells are hyper-inflammatory with reduced cell surface expression of TIM-3 and regulatory cytokines, and this is restored by T-cell-specific CEACAM1 expression. During chronic viral infection and in a tumour environment, CEACAM1 and TIM-3 mark exhausted T cells. Co-blockade of CEACAM1 and TIM-3 leads to enhancement of anti-tumour immune responses with improved elimination of tumours in mouse colorectal cancer models. Thus, CEACAM1 serves as a heterophilic ligand for TIM-3 that is required for its ability to

Distributed Acoustic Sensing (DAS) Array near a Highway for Traffic Monitoring and Near-Surface Shear-Wave Velocity Profiles

NASA Astrophysics Data System (ADS)

Wang, H. F.; Fratta, D.; Lancelle, C.; Ak, E. Ms; Lord, N. E.

2017-12-01

Monitoring traffic is important for many technical reasons. It allows for better design of future roads and assessment of the state of current roads. The number, size, weight, and speed of vehicles control deterioration rate. Also, real-time information supplies data to intelligent information systems to help control traffic. Recently there have been studies looking at monitoring traffic seismically as vibrations from traffic are not sensitive to weather and poor visibility. Furthermore, traffic noise can be used to image S-wave velocity distribution in the near surface by capturing and interpreting Rayleigh and Love waves (Nakata, 2016; Zeng et al. 2016). The capability of DAS for high spatial sampling (1 m), temporal sampling (up to 10 kHz), and distributed nature (tens of kilometers) allows for a closer look at the traffic as it passes and how the speed of the vehicle may change over the length of the array. The potential and difficulties of using DAS for these objectives were studied using two DAS arrays. One at Garner Valley in Southern California (a 700-meter array adjacent to CA Highway 74) and another in Brady Hot Springs, Nevada (an 8700-meter array adjacent to Interstate 80). These studies experimentally evaluated the use of DAS data for monitoring traffic and assessing the use of traffic vibration as non-localized sources for seismic imaging. DAS arrays should also be resilient to issues with lighting conditions that are problematic for video monitoring and it may be sensitive to the weight of a vehicle. This study along a major interstate provides a basis for examining DAS' potential and limitations as a key component of intelligent highway systems.

A review and empirical study of the composite scales of the Das-Naglieri cognitive assessment system.

PubMed

McCrea, Simon M

2009-01-01

Alexander Luria's model of the working brain consisting of three functional units was formulated through the examination of hundreds of focal brain-injury patients. Several psychometric instruments based on Luria's syndrome analysis and accompanying qualitative tasks have been developed since the 1970s. In the mid-1970s, JP Das and colleagues defined a specific cognitive processes model based directly on Luria's two coding units termed simultaneous and successive by studying diverse cross-cultural, ability, and socioeconomic strata. The cognitive assessment system is based on the PASS model of cognitive processes and consists of four composite scales of Planning-Attention-Simultaneous-Successive (PASS) devised by Naglieri and Das in 1997. Das and colleagues developed the two new scales of planning and attention to more closely model Luria's theory of higher cortical functions. In this paper a theoretical review of Luria's theory, Das and colleagues elaboration of Luria's model, and the neural correlates of PASS composite scales based on extant studies is summarized. A brief empirical study of the neuropsychological specificity of the PASS composite scales in a sample of 33 focal cortical stroke patients using cluster analysis is then discussed. Planning and simultaneous were sensitive to right hemisphere lesions. These findings were integrated with recent functional neuroimaging studies of PASS scales. In sum it was found that simultaneous is strongly dependent on dual bilateral occipitoparietal interhemispheric coordination whereas successive demonstrated left frontotemporal specificity with some evidence of interhemispheric coordination across the prefrontal cortex. Hence, support for the validity of the PASS composite scales was found as well as for the axiom of the independence of code content from code type originally specified in 1994 by Das, Naglieri, and Kirby.

Garlic Extract Diallyl Sulfide (DAS) Activates Nuclear Receptor CAR to Induce the Sult1e1 Gene in Mouse Liver

PubMed Central

Sueyoshi, Tatsuya; Green, William D.; Vinal, Kellie; Woodrum, Tyler S.; Moore, Rick; Negishi, Masahiko

2011-01-01

Constituent chemicals in garlic extract are known to induce phase I and phase II enzymes in rodent livers. Here we have utilized Car +/+ and Car −/− mice to demonstrate that the nuclear xenobiotic receptor CAR regulated the induction of the estrogen sulfotransferase Sult1e1 gene by diallyl sulfide (DAS) treatment in mouse liver. DAS treatment caused CAR accumulation in the nucleus, resulting in a remarkable increase of SULT1E1 mRNA (3,200 fold) and protein in the livers of Car +/+ females but not of Car −/− female mice. DAS also induced other CAR-regulated genes such as Cyp2b10, Cyp3a11 and Gadd45β. Compared with the rapid increase of these mRNA levels, which began as early as 6 hourrs after DAS treatment, the levels of SULT1E1 mRNA began increasing after 24 hours. This slow response to DAS suggested that CAR required an additional factor to activate the Sult1e1 gene or that this activation was indirect. Despite the remarkable induction of SULT1E1, there was no decrease in the serum levels of endogenous E2 or increase of estrone sulfate while the clearance of exogenously administrated E2 was accelerated in DAS treated mice. PMID:21698271

Brady's Geothermal Field DAS and DTS Surface and Borehole Array Metadata

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

Dante Fratta

This metadata submission includes the coordinates of the DAS and DTS surface and borehole arrays, the list of file names, and the list of recorded files during testing at the PoroTomo Natural Laboratory at Brady Hot Spring in Nevada. Testing was completed during March 2016.

Architecture and ssDNA interaction of the Timeless-Tipin-RPA complex

PubMed Central

Witosch, Justine; Wolf, Eva; Mizuno, Naoko

2014-01-01

The Timeless-Tipin (Tim-Tipin) complex, also referred to as the fork protection complex, is involved in coordination of DNA replication. Tim-Tipin is suggested to be recruited to replication forks via Replication Protein A (RPA) but details of the interaction are unknown. Here, using cryo-EM and biochemical methods, we characterized complex formation of Tim-Tipin, RPA and single-stranded DNA (ssDNA). Tim-Tipin and RPA form a 258 kDa complex with a 1:1:1 stoichiometry. The cryo-EM 3D reconstruction revealed a globular architecture of the Tim-Tipin-RPA complex with a ring-like and a U-shaped domain covered by a RPA lid. Interestingly, RPA in the complex adopts a horse shoe-like shape resembling its conformation in the presence of long ssDNA (>30 nucleotides). Furthermore, the recruitment of the Tim-Tipin-RPA complex to ssDNA is modulated by the RPA conformation and requires RPA to be in the more compact 30 nt ssDNA binding mode. The dynamic formation and disruption of the Tim-Tipin-RPA-ssDNA complex implicates the RPA-based recruitment of Tim-Tipin to the replication fork. PMID:25348395

U.S. Tsunami Information technology (TIM) Modernization:Developing a Maintainable and Extensible Open Source Earthquake and Tsunami Warning System

NASA Astrophysics Data System (ADS)

Hellman, S. B.; Lisowski, S.; Baker, B.; Hagerty, M.; Lomax, A.; Leifer, J. M.; Thies, D. A.; Schnackenberg, A.; Barrows, J.

2015-12-01

Tsunami Information technology Modernization (TIM) is a National Oceanic and Atmospheric Administration (NOAA) project to update and standardize the earthquake and tsunami monitoring systems currently employed at the U.S. Tsunami Warning Centers in Ewa Beach, Hawaii (PTWC) and Palmer, Alaska (NTWC). While this project was funded by NOAA to solve a specific problem, the requirements that the delivered system be both open source and easily maintainable have resulted in the creation of a variety of open source (OS) software packages. The open source software is now complete and this is a presentation of the OS Software that has been funded by NOAA for benefit of the entire seismic community. The design architecture comprises three distinct components: (1) The user interface, (2) The real-time data acquisition and processing system and (3) The scientific algorithm library. The system follows a modular design with loose coupling between components. We now identify the major project constituents. The user interface, CAVE, is written in Java and is compatible with the existing National Weather Service (NWS) open source graphical system AWIPS. The selected real-time seismic acquisition and processing system is open source SeisComp3 (sc3). The seismic library (libseismic) contains numerous custom written and wrapped open source seismic algorithms (e.g., ML/mb/Ms/Mwp, mantle magnitude (Mm), w-phase moment tensor, bodywave moment tensor, finite-fault inversion, array processing). The seismic library is organized in a way (function naming and usage) that will be familiar to users of Matlab. The seismic library extends sc3 so that it can be called by the real-time system, but it can also be driven and tested outside of sc3, for example, by ObsPy or Earthworm. To unify the three principal components we have developed a flexible and lightweight communication layer called SeismoEdex.

Integriertes Informationsmanagement an der Westfälischen Wilhelms-Universität Münster - Das Projekt MIRO

NASA Astrophysics Data System (ADS)

Vogl, Raimund; Gildhorn, Antje; Labitzke, Jörg; Wibberg, Michael

An der Westfälischen Wilhelms-Universität Münster (WWU) wurde bereits 1996 ein tragfähiges, kooperativ ausgerichtetes System der IT-Governance im Zusammenspiel zentraler und dezentraler IT-Leistungserbringer etabliert. Um den Anforderungen an ein integriertes Informationsmanagement im Überlappungsfeld von Information, Kommunikation und Medien (IKM) durch das Zusammenspiel der zentralen Einrichtungen Universitätsverwaltung (UniV), Universitäts- und Landesbibliothek (ULB) und Zentrum für Informationsverarbeitung (ZIV) gerecht zu werden, wurde 2003 der IKM-Service institutionalisiert. In diesem Rahmen wurde das Projekt Münster Information System for Research and Organization (MIRO) entwickelt, das als Leistungszentrum für Forschungsinformation von der DFG gefördert wird. Die bisherigen Projekterfahrungen, erreichten Ziele und verbleibenden Aufgaben werden dargestellt. Im Projektverlauf haben sich insbesondere die etablierten IT-Governance und Versorgungs-Strukturen sowie die Unterstützung der Hochschulleitung als essentielle Erfolgskriterien erwiesen.

Cyclic lipopeptide signature as fingerprinting for the screening of halotolerant Bacillus strains towards microbial enhanced oil recovery.

PubMed

Farias, Bárbara C S; Hissa, Denise C; do Nascimento, Camila T M; Oliveira, Samuel A; Zampieri, Davila; Eberlin, Marcos N; Migueleti, Deivid L S; Martins, Luiz F; Sousa, Maíra P; Moyses, Danuza N; Melo, Vânia M M

2018-02-01

Cyclic lipopeptides (CLPs) are non-ribosomal biosurfactants produced by Bacillus species that exhibit outstanding interfacial activity. The synthesis of CLPs is under genetic and environmental influence, and representatives from different families are generally co-produced, generating isoforms that differ in chemical structure and biological activities. This study to evaluate the effect of low and high NaCl concentrations on the composition and surface activity of CLPs produced by Bacillus strains TIM27, TIM49, TIM68, and ICA13 towards microbial enhanced oil recovery (MEOR). The strains were evaluated in mineral medium containing NaCl 2.7, 66, or 100 g L -1 and growth, surface tension and emulsification activity were monitored. Based on the analysis of 16S rDNA, gyrB and rpoB sequences TIM27 and TIM49 were assigned to Bacillus subtilis, TIM68 to Bacillus vallismortis, and ICA13 to Bacillus amyloliquefaciens. All strains tolerated up to 100-g L -1 NaCl, but only TIM49 and TIM68 were able to reduce surface tension at this concentration. TIM49 also showed emulsification activity at concentrations up to 66-g L -1 NaCl. ESI-MS analysis showed that the strains produced a mixture of CLPs, which presented distinct CLP profiles at low and high NaCl concentrations. High NaCl concentration favored the synthesis of surfactins and/or fengycins that correlated with the surface activities of TIM49 and TIM68, whereas low concentration favored the synthesis of iturins. Taken together, these findings suggest that the determination of CLP signatures under the expected condition of oil reservoirs can be useful in the guidance for choosing well-suited strains to MEOR.

The effect of specific proline residues on the kinetic stability of the triosephosphate isomerases of two trypanosomes.

PubMed

Guzmán-Luna, Valeria; Quezada, Andrea G; Díaz-Salazar, A Jessica; Cabrera, Nallely; Pérez-Montfort, Ruy; Costas, Miguel

2017-04-01

The effect of specific residues on the kinetic stability of two closely related triosephosphate isomerases (from Trypanosoma cruzi, TcTIM and Trypanosoma brucei, TbTIM) has been studied. Based on a comparison of their β-turn occurrence, we engineered two chimerical enzymes where their super secondary β-loop-α motifs 2 ((βα) 2 ) were swapped. Differential scanning calorimetry (DSC) experiments showed that the (βα) 2 motif of TcTIM inserted into TbTIM (2Tc) increases the kinetic stability. On the other hand, the presence of the (βα) 2 motif of TbTIM inserted into TcTIM (2Tb) gave a chimerical protein difficult to purify in soluble form and with a significantly reduced kinetic stability. The comparison of the contact maps of the (βα) 2 of TbTIM and TcTIM showed differences in the contact pattern of residues 43 and 49. In TcTIM these residues are prolines, located at the N-terminal of loop-2 and the C-terminal of α-helix-2. Twelve mutants were engineered involving residues 43 and 49 to study the effect over the unfolding activation energy barrier (E A ). A systematic analysis of DSC data showed a large decrease on the E A of TcTIM (ΔE A ranging from 468 to 678 kJ/mol) when the single and double proline mutations are present. The relevance of Pro43 to the kinetic stability is also revealed by mutation S43P, which increased the free energy of the transition state of TbTIM by 17.7 kJ/mol. Overall, the results indicate that protein kinetic stability can be severely affected by punctual mutations, disturbing the complex network of interactions that, in concerted action, determine protein stability. Proteins 2017; 85:571-579. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

L to R; Walter Klein (in tan flight suit), Tim Miller, and David Bushman briefing press in Santiago, Chile, for NASA's AirSAR 2004 mission

NASA Image and Video Library

2004-03-10

L to R; NASA Dryden Mission Manager Walter Klein (in tan flight suit), JPL AirSAR Scientist Tim Miller, and Mission Manager David Bushman briefing press in Santiago, Chile, for NASA's AirSAR 2004 mission. AirSAR 2004 is a three-week expedition by an international team of scientists that uses an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR) which is located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world including NASA's Jet Propulsion Laboratory are combining ground research done in several areas in Central and South America with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. In South America and Antarctica, AirSAR collected imagery and data to help determine the contribution of Southern Hemisphere glaciers to sea level rise due to climate change. In Patagonia, researchers found this contribution had more than doubled from 1995 to 2000, compared to the previous 25 years. AirSAR data will make it possible to determine whether that trend is continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

Comparison of Distributed Acoustic Sensing (DAS) from Fiber-Optic Cable to Three Component Geophones in an Underground Mine

NASA Astrophysics Data System (ADS)

Speece, M. A.; Nesladek, N. J.; Kammerer, C.; Maclaughlin, M.; Wang, H. F.; Lord, N. E.

2017-12-01

We conducted experiments in the Underground Education Mining Center on the Montana Tech campus, Butte, Montana, to make a direct comparison between Digital Acoustic Sensing (DAS) and three-component geophones in a mining setting. The sources used for this project where a vertical sledgehammer, oriented shear sledgehammer, and blasting caps set off in both unstemmed and stemmed drillholes. Three-component Geospace 20DM geophones were compared with three different types of fiber-optic cable: (1) Brugg strain, (2) Brugg temperature, and (3) Optical Cable Corporation strain. We attached geophones to the underground mine walls and on the ground surface above the mine. We attached fiber-optic cables to the mine walls and placed fiber-optic cable in boreholes drilled through an underground pillar. In addition, we placed fiber-optic cables in a shallow trench at the surface of the mine. We converted the DAS recordings from strain rate to strain prior to comparison with the geophone data. The setup of the DAS system for this project led to a previously unknown triggering problem that compromised the early samples of the DAS traces often including the first-break times on the DAS records. Geophones clearly recorded the explosives; however, the large amount of energy and its close distance from the fiber-optic cables seemed to compromise the entire fiber loop. The underground hammer sources produced a rough match between the DAS records and the geophone records. However, the sources on the surface of the mine, specifically the sources oriented inline with the fiber-optic cables, produced a close match between the fiber-optic traces and the geophone traces. All three types of fiber-optic cable that were in the mine produced similar results, and one type did not clearly outperform the others. Instead, the coupling of the cable to rock appears to be the most important factor determining DAS data quality. Moreover, we observed the importance of coupling in the boreholes, where

The DAS28-ESR cutoff value necessary to achieve remission under the new Boolean-based remission criteria in patients receiving tocilizumab.

PubMed

Hirabayashi, Yasuhiko; Ishii, Tomonori

2013-01-01

To seek the cutoff value of the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) that is necessary to achieve remission under the new Boolean-based criteria, we analyzed the data for 285 patients with rheumatoid arthritis registered between May 2008 and November 2009 by the Michinoku Tocilizumab Study Group and observed for 1 year after receiving tocilizumab (TCZ) in real clinical practice. Remission rates under the DAS28-ESR criteria and the Boolean criteria were assessed every 6 months after the first TCZ dose. The DAS28-ESR cutoff value necessary to achieve remission under the new criteria was analyzed by receiver operating characteristic (ROC) analysis. Data were analyzed using last observation carried forward. After 12 months of TCZ use, remission was achieved in 164 patients (57.5 %) by DAS28-ESR and 71 patients (24.9 %) under the new criteria for clinical trials. CRP levels scarcely affected remission rates, and the difference between remission rates defined by DAS28-ESR and by the new criteria was mainly due to patient global assessment (PGA). Improvement of PGA was inversely related to disease duration. ROC analysis revealed that the DAS28-ESR cutoff value necessary to predict remission under the new criteria for clinical trials was 1.54, with a sensitivity of 88.7 %, specificity of 85.5 %, positive predictive value of 67.0 %, and negative predictive value of 95.8 %. A DAS28-ESR cutoff value of 1.54 may be reasonable to predict achievement of remission under the new Boolean-based criteria for clinical trials in patients receiving TCZ.

Ocean Color Measurements from Landsat-8 OLI using SeaDAS

NASA Technical Reports Server (NTRS)

Franz, Bryan Alden; Bailey, Sean W.; Kuring, Norman; Werdell, P. Jeremy

2014-01-01

The Operational Land Imager (OLI) is a multi-spectral radiometer hosted on the recently launched Landsat-8 satellite. OLI includes a suite of relatively narrow spectral bands at 30-meter spatial resolution in the visible to shortwave infrared that make it a potential tool for ocean color radiometry: measurement of the reflected spectral radiance upwelling from beneath the ocean surface that carries information on the biogeochemical constituents of the upper ocean euphotic zone. To evaluate the potential of OLI to measure ocean color, processing support was implemented in SeaDAS, which is an open-source software package distributed by NASA for processing, analysis, and display of ocean remote sensing measurements from a variety of satellite-based multi-spectral radiometers. Here we describe the implementation of OLI processing capabilities within SeaDAS, including support for various methods of atmospheric correction to remove the effects of atmospheric scattering and absorption and retrieve the spectral remote-sensing reflectance (Rrs; sr exp 1). The quality of the retrieved Rrs imagery will be assessed, as will the derived water column constituents such as the concentration of the phytoplankton pigment chlorophyll a.

Identification of triosephosphate isomerase as a novel allergen in Octopus fangsiao.

PubMed

Yang, Yang; Chen, Zhong-Wei; Hurlburt, Barry K; Li, Gui-Ling; Zhang, Yong-Xia; Fei, Dan-Xia; Shen, Hai-Wang; Cao, Min-Jie; Liu, Guang-Ming

2017-05-01

Octopus is an important mollusk in human dietary for its nutritional value, however it also causes allergic reactions in humans. Major allergens from octopus have been identified, while the knowledge of novel allergens remains poor. In the present study, a novel allergen with molecular weight of 28kDa protein was purified from octopus (Octopus fangsiao) and identified as triosephosphate isomerase (TIM) by mass spectrometry. TIM aggregated beyond 45°C, and its IgE-binding activity was affected under extreme pH conditions due to the altered secondary structure. In simulated gastric fluid digestion, TIM can be degraded into small fragments, while retaining over 80% of the IgE-binding activity. The full-length cDNA of O. fangsiao TIM (1140bp) was cloned, which encodes 247 amino acid residues, and the entire recombinant TIM was successfully expressed in Escherichia coli BL21, which showed similar immunoreactivity to the native TIM. Different intensity of cross-reactivity among TIM from related species revealed the complexity of its epitopes. Eight linear epitopes of TIM were predicted following bioinformatic analysis. Furthermore, a conformational epitope (A 71 G 74 S 69 D 75 T 73 F 72 V 67 ) was confirmed by the phage display technology. The results revealed the physicochemical and immunological characteristics of TIM, which is significant in the development of hyposensitivity food and allergy diagnosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Architecture and ssDNA interaction of the Timeless-Tipin-RPA complex.

PubMed

Witosch, Justine; Wolf, Eva; Mizuno, Naoko

2014-11-10

The Timeless-Tipin (Tim-Tipin) complex, also referred to as the fork protection complex, is involved in coordination of DNA replication. Tim-Tipin is suggested to be recruited to replication forks via Replication Protein A (RPA) but details of the interaction are unknown. Here, using cryo-EM and biochemical methods, we characterized complex formation of Tim-Tipin, RPA and single-stranded DNA (ssDNA). Tim-Tipin and RPA form a 258 kDa complex with a 1:1:1 stoichiometry. The cryo-EM 3D reconstruction revealed a globular architecture of the Tim-Tipin-RPA complex with a ring-like and a U-shaped domain covered by a RPA lid. Interestingly, RPA in the complex adopts a horse shoe-like shape resembling its conformation in the presence of long ssDNA (>30 nucleotides). Furthermore, the recruitment of the Tim-Tipin-RPA complex to ssDNA is modulated by the RPA conformation and requires RPA to be in the more compact 30 nt ssDNA binding mode. The dynamic formation and disruption of the Tim-Tipin-RPA-ssDNA complex implicates the RPA-based recruitment of Tim-Tipin to the replication fork. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Identification of a Degradation Signal Sequence within Substrates of the Mitochondrial i-AAA Protease.

PubMed

Rampello, Anthony J; Glynn, Steven E

2017-03-24

The i-AAA protease is a component of the mitochondrial quality control machinery that regulates respiration, mitochondrial dynamics, and protein import. The protease is required to select specific substrates for degradation from among the diverse complement of proteins present in mitochondria, yet the rules that govern this selection are unclear. Here, we reconstruct the yeast i-AAA protease, Yme1p, to examine the in vitro degradation of two intermembrane space chaperone subunits, Tim9 and Tim10. Yme1p degrades Tim10 more rapidly than Tim9 despite high sequence and structural similarity, and loss of Tim10 is accelerated by the disruption of conserved disulfide bonds within the substrate. An unstructured N-terminal region of Tim10 is necessary and sufficient to target the substrate to the protease through recognition of a short phenylalanine-rich motif, and the presence of similar motifs in other small Tim proteins predicts robust degradation by the protease. Together, these results identify the first specific degron sequence within a native i-AAA protease substrate. Copyright © 2017 Elsevier Ltd. All rights reserved.

The plant i-AAA protease controls the turnover of an essential mitochondrial protein import component.

PubMed

Opalińska, Magdalena; Parys, Katarzyna; Murcha, Monika W; Jańska, Hanna

2018-01-29

Mitochondria are multifunctional organelles that play a central role in energy metabolism. Owing to the life-essential functions of these organelles, mitochondrial content, quality and dynamics are tightly controlled. Across the species, highly conserved ATP-dependent proteases prevent malfunction of mitochondria through versatile activities. This study focuses on a molecular function of the plant mitochondrial inner membrane-embedded AAA protease (denoted i -AAA) FTSH4, providing its first bona fide substrate. Here, we report that the abundance of the Tim17-2 protein, an essential component of the TIM17:23 translocase (Tim17-2 together with Tim50 and Tim23), is directly controlled by the proteolytic activity of FTSH4. Plants that are lacking functional FTSH4 protease are characterized by significantly enhanced capacity of preprotein import through the TIM17:23-dependent pathway. Taken together, with the observation that FTSH4 prevents accumulation of Tim17-2, our data point towards the role of this i -AAA protease in the regulation of mitochondrial biogenesis in plants. © 2018. Published by The Company of Biologists Ltd.

On the Law of Inertia. Translation of: Ueber das Beharrungsgesetz

NASA Astrophysics Data System (ADS)

Lange, Ludwig

2014-04-01

This article is a translation of Ludwig Lange: "Ueber das Beharrungsgesetz" in: Berichte ueber Verhandlungen der Koenigl. Saechsischen Gesellschaft der Wissenschaften, math.-physik. Klasse (Leipzig, 1885), SS. 333-351. Translated by Herbert Pfister, Institut für Theoretische Physik, Universität Tübingen, Auf der Morgenstelle 14, 72076 Tübingen, Germany; herbert.pfister@uni-tuebingen.de. Kind assistance by Julian Barbour is acknowledged.

Validation of Land-Surface Mosaic Heterogeneity in the GEOS DAS

NASA Technical Reports Server (NTRS)

Bosilovich, Michael G.; Molod, Andrea; Houser, Paul R.; Schubert, Siegfried

1999-01-01

The Mosaic Land-surface Model (LSM) has been included into the current GEOS Data Assimilation System (DAS). The LSM uses a more advanced representation of physical processes than previous versions of the GEOS DAS, including the representation of sub-grid heterogeneity of the land-surface through the Mosaic approach. As a first approximation, Mosaic assumes that all similar surface types within a grid-cell can be lumped together as a single'tile'. Within one GCM grid-cell, there might be 1 - 5 different tiles or surface types. All tiles are subjected to the grid-scale forcing (radiation, air temperature and specific humidity, and precipitation), and the sub-grid variability is a function of the tile characteristics. In this paper, we validate the LSM sub-grid scale variability (tiles) using a variety of surface observing stations from the Southern Great Plains (SGP) site of the Atmospheric Radiation Measurement (ARM) Program. One of the primary goals of SGP ARM is to study the variability of atmospheric radiation within a G,CM grid-cell. Enough surface data has been collected by ARM to extend this goal to sub-grid variability of the land-surface energy and water budgets. The time period of this study is the Summer of 1998 (June I - September 1). The ARM site data consists of surface meteorology, energy flux (eddy correlation and bowen ratio), soil water observations spread over an area similar to the size of a G-CM grid-cell. Various ARM stations are described as wheat and alfalfa crops, pasture and range land. The LSM tiles considered at the grid-space (2 x 2.5) nearest the ARM site include, grassland, deciduous forests, bare soil and dwarf trees. Surface energy and water balances for each tile type are compared with observations. Furthermore, we will discuss the land-surface sub-grid variability of both the ARM observations and the DAS.

50 CFR 648.10 - VMS and DAS requirements for vessel owners/operators.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false VMS and DAS requirements for vessel owners/operators. 648.10 Section 648.10 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE FISHERIES OF THE NORTHEASTERN...

Phase Velocity and Full-Waveform Analysis of Co-located Distributed Acoustic Sensing (DAS) Channels and Geophone Sensor

NASA Astrophysics Data System (ADS)

Parker, L.; Mellors, R. J.; Thurber, C. H.; Wang, H. F.; Zeng, X.

2015-12-01

A 762-meter Distributed Acoustic Sensing (DAS) array with a channel spacing of one meter was deployed at the Garner Valley Downhole Array in Southern California. The array was approximately rectangular with dimensions of 180 meters by 80 meters. The array also included two subdiagonals within the rectangle along which three-component geophones were co-located. Several active sources were deployed, including a 45-kN, swept-frequency, shear-mass shaker, which produced strong Rayleigh waves across the array. Both DAS and geophone traces were filtered in 2-Hz steps between 4 and 20 Hz to obtain phase velocities as a function of frequency from fitting the moveout of travel times over distances of 35 meters or longer. As an alternative to this traditional means of finding phase velocity, it is theoretically possible to find the Rayleigh-wave phase velocity at each point of co-location as the ratio of DAS and geophone responses, because DAS is sensitive to ground strain and geophones are sensitive to ground velocity, after suitable corrections for instrument response (Mikumo & Aki, 1964). The concept was tested in WPP, a seismic wave propagation program, by first validating and then using a 3D synthetic, full-waveform seismic model to simulate the effect of increased levels of noise and uncertainty as data go from ideal to more realistic. The results obtained from this study provide a better understanding of the DAS response and its potential for being combined with traditional seismometers for obtaining phase velocity at a single location. This analysis is part of the PoroTomo project (Poroelastic Tomography by Adjoint Inverse Modeling of Data from Seismology, Geodesy, and Hydrology, http://geoscience.wisc.edu/feigl/porotomo).

Microbial Metabolism Shifts Towards an Adverse Profile with Supplementary Iron in the TIM-2 In vitro Model of the Human Colon

DOE PAGES

Kortman, Guus A. M.; Dutilh, Bas E.; Maathuis, Annet J. H.; ...

2016-01-06

Oral iron administration in African children can increase the risk for infections. However, it remains unclear to what extent supplementary iron affects the intestinal microbiome. We here explored the impact of iron preparations on microbial growth and metabolism in the well-controlled TNO's in vitro model of the large intestine (TIM-2). The model was inoculated with a human microbiota, without supplementary iron, or with 50 or 250 μmol/L ferrous sulfate, 50 or 250 μmol/L ferric citrate, or 50 μmol/L hemin. High resolution responses of the microbiota were examined by 16S rDNA pyrosequencing, microarray analysis, and metagenomic sequencing. The metabolome was assessedmore » by fatty acid quantification, gas chromatography-mass spectrometry (GC-MS), and 1H-NMR spectroscopy. Cultured intestinal epithelial Caco-2 cells were used to assess fecal water toxicity. Microbiome analysis showed, among others, that supplementary iron induced decreased levels of Bifidobacteriaceae and Lactobacillaceae, while it caused higher levels of Roseburia and Prevotella. Metagenomic analyses showed an enrichment of microbial motility-chemotaxis systems, while the metabolome markedly changed from a saccharolytic to a proteolytic profile in response to iron. Branched chain fatty acids and ammonia levels increased significantly, in particular with ferrous sulfate. Importantly, the metabolite-containing effluent from iron-rich conditions showed increased cytotoxicity to Caco-2 cells. In conclusion, our explorations indicate that in the absence of host influences, iron induces a more hostile environment characterized by a reduction of microbes that are generally beneficial, and increased levels of bacterial metabolites that can impair the barrier function of a cultured intestinal epithelial monolayer.« less

Microbial Metabolism Shifts Towards an Adverse Profile with Supplementary Iron in the TIM-2 In vitro Model of the Human Colon

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

Kortman, Guus A. M.; Dutilh, Bas E.; Maathuis, Annet J. H.

Oral iron administration in African children can increase the risk for infections. However, it remains unclear to what extent supplementary iron affects the intestinal microbiome. We here explored the impact of iron preparations on microbial growth and metabolism in the well-controlled TNO's in vitro model of the large intestine (TIM-2). The model was inoculated with a human microbiota, without supplementary iron, or with 50 or 250 μmol/L ferrous sulfate, 50 or 250 μmol/L ferric citrate, or 50 μmol/L hemin. High resolution responses of the microbiota were examined by 16S rDNA pyrosequencing, microarray analysis, and metagenomic sequencing. The metabolome was assessedmore » by fatty acid quantification, gas chromatography-mass spectrometry (GC-MS), and 1H-NMR spectroscopy. Cultured intestinal epithelial Caco-2 cells were used to assess fecal water toxicity. Microbiome analysis showed, among others, that supplementary iron induced decreased levels of Bifidobacteriaceae and Lactobacillaceae, while it caused higher levels of Roseburia and Prevotella. Metagenomic analyses showed an enrichment of microbial motility-chemotaxis systems, while the metabolome markedly changed from a saccharolytic to a proteolytic profile in response to iron. Branched chain fatty acids and ammonia levels increased significantly, in particular with ferrous sulfate. Importantly, the metabolite-containing effluent from iron-rich conditions showed increased cytotoxicity to Caco-2 cells. In conclusion, our explorations indicate that in the absence of host influences, iron induces a more hostile environment characterized by a reduction of microbes that are generally beneficial, and increased levels of bacterial metabolites that can impair the barrier function of a cultured intestinal epithelial monolayer.« less

Quantitative parameters of complexes of tris(1-alkylindol-3-yl)methylium salts with serum albumin: Relevance for the design of drug candidates.

PubMed

Durandin, Nikita A; Tsvetkov, Vladimir B; Bykov, Evgeny E; Kaluzhny, Dmitry N; Lavrenov, Sergey N; Tevyashova, Anna N; Preobrazhenskaya, Maria N

2016-09-01

Triarylmethane derivatives are extensively investigated as antitumor and antibacterial drug candidates alone and as photoactivatable compounds. In the series of tris(1-alkylindol-3-yl)methylium salts (TIMs) these two activities differed depending on the length of N-alkyl chain, with C4-5 derivatives being the most potent compared to the shorter or longer chain analogs and to the natural compound turbomycin A (no N-substituent). Given that the human serum albumin (HSA) is a major transporter protein with which TIMs can form stable complexes, and that the formation of these complexes might be advantageous for phototoxicity of TIMs we determined the quantitative parameters of TIMs-HSA binding using spectroscopic methods and molecular docking. TIMs bound to HSA (1:1 stoichiometry) altered the protein's secondary structure by changing the α-helix/β-turn ratio. The IIa subdomain (Sudlow site I) is the preferred TIM binding site in HSA as determined in competition experiments with reference drugs ibuprofen and warfarin. The values of binding constants increased with the number of CH2 groups from 0 to 6 and then dropped down for C10 compound, a dependence similar to the one observed for cytocidal potency of TIMs. We tend to attribute this non-linear dependence to an interplay between hydrophobicity and steric hindrance, the two key characteristics of TIMs-HSA complexes calculated in the molecular docking procedure. These structure-activity relationships provide evidence for rational design of TIMs-based antitumor and antimicrobial drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

Event DAS-444Ø6-6 soybean grown in Brazil is compositionally equivalent to non-transgenic soybean.

PubMed

Fast, Brandon J; Galan, Maria P; Schafer, Ariane C

2016-04-02

Soybean event DAS-444Ø6-6 is tolerant to the herbicides 2,4-D, glyphosate, and glufosinate. An investigation of potential unintended adverse compositional changes in a genetically modified crop is required to meet government regulatory requirements in various geographies. A study to meet these requirements in Brazil was completed demonstrating compositional equivalency between DAS-444Ø6-6 and non-transgenic soybean. This study supplements the extensive literature supporting transgenesis as less disruptive of crop composition compared with traditional breeding methods.

Kinetics and intrapulmonary disposition of tilmicosin after single and repeated oral bolus administrations to rabbits.

PubMed

Gallina, G; Lucatello, L; Drigo, I; Cocchi, M; Scandurra, S; Agnoletti, F; Montesissa, C

2010-06-01

Tilmicosin (TIM, Pulmotil) was administered to eight rabbits by oral gavage at a dose of 12.5 mg/kg body weight for 2, 5, and 7 days, and its plasma kinetics and intrapulmonary disposition were investigated. TIM concentrations in plasma samples collected after days 1 and 6 of treatment were measured by high-performance liquid chromatography with ultraviolet detection. The pharmacokinetic parameters, obtained by non-compartmental analysis of TIM plasma concentrations, did not show any significant variations between days 1 and 6. From the second day of treatment, TIM concentrations attained in lung tissue and pulmonary alveolar macrophages (PAM) exceeded those in plasma by 7- and 400-fold, respectively, and high levels were maintained in lung tissues during the entire treatment duration. After the first day of withdrawal, a fast decline in TIM levels in both plasma and lung tissue was observed, but in PAM, much higher concentrations were maintained after 3 days of TIM withdrawal.

A Brief History of the J.P. Das Developmental Disabilities Centre

ERIC Educational Resources Information Center

Sobsey, Dick

2008-01-01

The J.P. Das Developmental Disabilities Centre celebrated its 40th anniversary on September 1, 2007, followed by The University of Alberta's 100th anniversary in 2008. The year 2008 also brought the appointment of a new Director for the Centre. As the immediate past Director of the Centre, the author recounts some of the history of the J.P. Das…

Identification of triosephosphate isomerase as a novel allergen in octopus fangsiao

USDA-ARS?s Scientific Manuscript database

A 28 kDa-protein was purified from octopus (Octopus fangsiao) and identified to be triosephosphate isomerase (TIM). The purified TIM is a glycoprotein with 1.7% carbohydrates and the isoelectric point is 7.6. TIM aggregated after heating above 45 °C, and the secondary structure was altered in extre...

Efficacy and tolerability of fixed-combination brinzolamide/timolol in Latin American patients with open-angle glaucoma or ocular hypertension previously on brimonidine/timolol fixed combination.

PubMed

Alezzandrini, Arturo; Hubatsch, Douglas; Alfaro, Rene

2014-09-01

Fixed-combination glaucoma medications are commonly used to achieve target intraocular pressure (IOP) reduction in patients uncontrolled with monotherapy; however, ocular discomfort associated with eye drops can decrease adherence. This study assessed the efficacy and tolerability of twice-daily fixed-combination brinzolamide 1%/timolol 0.5% (BRINZ/TIM-FC) in Latin American patients transitioned from fixed-combination brimonidine 0.2%/timolol 0.5% (BRIM/TIM-FC) because of insufficient IOP control or treatment intolerance. This 8-week, open-label, prospective study was conducted at six sites in Argentina, Chile, and Mexico. Enrolled patients were aged ≥18 years with open-angle glaucoma (including primary, exfoliative, or pigment-dispersion glaucoma) or ocular hypertension with IOP of 19-35 mmHg in ≥1 eye at baseline (on BRIM/TIM-FC). Patients self-administered BRINZ/TIM-FC to both eyes at 8 a.m. and 8 p.m. daily for 8 weeks. The primary and secondary efficacy endpoints were mean IOP change from baseline at week 8 and percentage of patients achieving target IOP (≤18 mmHg) at week 8, respectively. Exploratory endpoints included patient and investigator preference for treatment at week 8. Adverse events (AEs) were assessed as the safety endpoint. Fifty patients (mean ± SD age, 66.7 ± 11.5 years) received BRINZ/TIM-FC, and 49 were included in the intent-to-treat population. Mean ± SD IOP was significantly reduced from baseline after 8 weeks of treatment with BRINZ/TIM-FC (-3.6 ± 3.0 mmHg; P < 0.0001, Wilcoxon signed-rank test; 17.1% reduction). Overall, 55.3% of patients achieved IOP ≤18 mmHg at week 8. Significantly more patients (89.4%) and investigators (95.7%) preferred BRINZ/TIM-FC to BRIM/TIM-FC (both P < 0.0001, exact binomial test). Of the 13 AEs observed, 8 were related to BRINZ/TIM-FC; the most common treatment-related AEs were eye irritation (n = 4) and abnormal sensation in the eye (n = 2). BRINZ/TIM-FC provides an

Brief note on Ashtekar-Magnon-Das conserved quantities in quadratic curvature theories

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

Pang Yi

2011-04-15

In this note, we correct a mistake in the mass formula in [N. Okuyama and J. i. Koga, Phys. Rev. D 71, 084009 (2005).] which generalizes the Ashtekar-Magnon-Das method to incorporate extended gravities with quadratic curvature terms. The corrected mass formula confirms that the black hole masses for recently discovered critical gravities vanish.

Effects of vocal training in a musicophile with congenital amusia.

PubMed

Wilbiks, Jonathan M P; Vuvan, Dominique T; Girard, Pier-Yves; Peretz, Isabelle; Russo, Frank A

2016-12-01

Congenital amusia is a condition in which an individual suffers from a deficit of musical pitch perception and production. Individuals suffering from congenital amusia generally tend to abstain from musical activities. Here, we present the unique case of Tim Falconer, a self-described musicophile who also suffers from congenital amusia. We describe and assess Tim's attempts to train himself out of amusia through a self-imposed 18-month program of formal vocal training and practice. We tested Tim with respect to music perception and vocal production across seven sessions including pre- and post-training assessments. We also obtained diffusion-weighted images of his brain to assess connectivity between auditory and motor planning areas via the arcuate fasciculus (AF). Tim's behavioral and brain data were compared to that of normal and amusic controls. While Tim showed temporary gains in his singing ability, he did not reach normal levels, and these gains faded when he was not engaged in regular lessons and practice. Tim did show some sustained gains with respect to the perception of musical rhythm and meter. We propose that Tim's lack of improvement in pitch perception and production tasks is due to long-standing and likely irreversible reduction in connectivity along the AF fiber tract.

50 CFR 648.10 - VMS and DAS requirements for vessel owners/operators.

Code of Federal Regulations, 2010 CFR

2010-10-01

... notification. The owner of a vessel issued a limited access monkfish or red crab permit who is participating in... confirmation numbers for the current and immediately prior NE multispecies, monkfish, or red crab fishing trip... specified in § 648.94(c); and any vessel issued a limited access red crab permit subject to the red crab DAS...

The Glycolytic Enzyme Triosephosphate Isomerase of Trichomonas vaginalis Is a Surface-Associated Protein Induced by Glucose That Functions as a Laminin- and Fibronectin-Binding Protein

PubMed Central

Miranda-Ozuna, Jesús F. T.; Hernández-García, Mar S.; Brieba, Luis G.; Benítez-Cardoza, Claudia G.; Ortega-López, Jaime; González-Robles, Arturo

2016-01-01

Triosephosphate isomerase of Trichomonas vaginalis (TvTIM) is a 27-kDa cytoplasmic protein encoded by two genes, tvtim1 and tvtim2, that participates in glucose metabolism. TvTIM is also localized to the parasite surface. Thus, the goal of this study was to identify the novel functions of the surface-associated TvTIM in T. vaginalis and to assess the effect of glucose as an environmental factor that regulates its expression and localization. Reverse transcription-PCR (RT-PCR) showed that the tvtim genes were differentially expressed in response to glucose concentration. tvtim1 was overexpressed under glucose-restricted (GR) conditions, whereas tvtim2 was overexpressed under glucose-rich, or high-glucose (HG), conditions. Western blot and indirect immunofluorescence assays also showed that glucose positively affected the amount and surface localization of TvTIM in T. vaginalis. Affinity ligand assays demonstrated that the recombinant TvTIM1 and TvTIM2 proteins bound to laminin (Lm) and fibronectin (Fn) but not to plasminogen. Moreover, higher levels of adherence to Lm and Fn were detected in parasites grown under HG conditions than in those grown under GR conditions. Furthermore, pretreatment of trichomonads with an anti-TvTIMr polyclonal antibody or pretreatment of Lm- or Fn-coated wells with both recombinant proteins (TvTIM1r and TvTIM2r) specifically reduced the binding of live parasites to Lm and Fn in a concentration-dependent manner. Moreover, T. vaginalis was exposed to different glucose concentrations during vaginal infection of women with trichomoniasis. Our data indicate that TvTIM is a surface-associated protein under HG conditions that mediates specific binding to Lm and Fn as a novel virulence factor of T. vaginalis. PMID:27481251

The Glycolytic Enzyme Triosephosphate Isomerase of Trichomonas vaginalis Is a Surface-Associated Protein Induced by Glucose That Functions as a Laminin- and Fibronectin-Binding Protein.

PubMed

Miranda-Ozuna, Jesús F T; Hernández-García, Mar S; Brieba, Luis G; Benítez-Cardoza, Claudia G; Ortega-López, Jaime; González-Robles, Arturo; Arroyo, Rossana

2016-10-01

Triosephosphate isomerase of Trichomonas vaginalis (TvTIM) is a 27-kDa cytoplasmic protein encoded by two genes, tvtim1 and tvtim2, that participates in glucose metabolism. TvTIM is also localized to the parasite surface. Thus, the goal of this study was to identify the novel functions of the surface-associated TvTIM in T. vaginalis and to assess the effect of glucose as an environmental factor that regulates its expression and localization. Reverse transcription-PCR (RT-PCR) showed that the tvtim genes were differentially expressed in response to glucose concentration. tvtim1 was overexpressed under glucose-restricted (GR) conditions, whereas tvtim2 was overexpressed under glucose-rich, or high-glucose (HG), conditions. Western blot and indirect immunofluorescence assays also showed that glucose positively affected the amount and surface localization of TvTIM in T. vaginalis Affinity ligand assays demonstrated that the recombinant TvTIM1 and TvTIM2 proteins bound to laminin (Lm) and fibronectin (Fn) but not to plasminogen. Moreover, higher levels of adherence to Lm and Fn were detected in parasites grown under HG conditions than in those grown under GR conditions. Furthermore, pretreatment of trichomonads with an anti-TvTIMr polyclonal antibody or pretreatment of Lm- or Fn-coated wells with both recombinant proteins (TvTIM1r and TvTIM2r) specifically reduced the binding of live parasites to Lm and Fn in a concentration-dependent manner. Moreover, T. vaginalis was exposed to different glucose concentrations during vaginal infection of women with trichomoniasis. Our data indicate that TvTIM is a surface-associated protein under HG conditions that mediates specific binding to Lm and Fn as a novel virulence factor of T. vaginalis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Vertically Aligned and Interconnected Boron Nitride Nanosheets for Advanced Flexible Nanocomposite Thermal Interface Materials.

PubMed

Chen, Jin; Huang, Xingyi; Sun, Bin; Wang, Yuxin; Zhu, Yingke; Jiang, Pingkai

2017-09-13

The continuous evolution toward semiconductor technology in the "more-than-Moore" era and rapidly increasing power density of modern electronic devices call for advanced thermal interface materials (TIMs). Here, we report a novel strategy to construct flexible polymer nanocomposite TIMs for advanced thermal management applications. First, aligned polyvinyl alcohol (PVA) supported and interconnected 2D boron nitride nanosheets (BNNSs) composite fiber membranes were fabricated by electrospinning. Then, the nanocomposite TIMs were constructed by rolling the PVA/BNNS composite fiber membranes to form cylinders and subsequently vacuum-assisted impregnation of polydimethylsiloxane (PDMS) into the porous cylinders. The nanocomposite TIMs not only exhibit a superhigh through-plane thermal conductivity enhancement of about 10 times at a low BNNS loading of 15.6 vol % in comparison with the pristine PDMS but also show excellent electrical insulating property (i.e., high volume electrical resistivity). The outstanding thermal management capability of the nanocomposite TIMs was practically confirmed by capturing the surface temperature variations of a working LED chip integrated with the nanocomposite TIMs.

Integration of DAS (distributed acoustic sensing) vertical seismic profile and geostatistically modeled lithology data to characterize an enhanced geothermal system.

NASA Astrophysics Data System (ADS)

Cronin, S. P.; Trainor Guitton, W.; Team, P.; Pare, A.; Jreij, S.; Powers, H.

2017-12-01

In March 2016, a 4-week field data acquisition took place at Brady's Natural Lab (BNL), an enhanced geothermal system (EGS) in Fallan, NV. During these 4 weeks, a vibe truck executed 6,633 sweeps, recorded by nodal seismometers, horizontal distributed acoustic sensing (DAS) cable, and 400 meters of vertical DAS cable. DAS provides lower signal to noise ratio than traditional geophones but better spatial resolution. The analysis of DAS VSP included Fourier transform, and filtering to remove all up-going energy. Thus, allowing for accurate first arrival picking. We present an example of the Gradual Deformation Method (GDM) using DAS VSP and lithological data to produce a distribution of valid velocity models of BNL. GDM generates continuous perturbations of prior model realizations seeking the best match to the data (i.e. minimize the misfit). Prior model realizations honoring the lithological data were created using sequential Gaussian simulation, a commonly used noniterative geostatistical method. Unlike least-squares-based methods of inversion, GDM readily incorporates a priori information, such as a variogram calculated from well-based lithology information. Additionally, by producing a distribution of models, as opposed to one optimal model, GDM allows for uncertainty quantification. This project aims at assessing the integrated technologies ability to monitor changes in the water table (possibly to one meter resolution) by exploiting the dependence of seismic wave velocities on water saturation of the subsurface. This project, which was funded in part by the National Science Foundation, is a part of the PoroTomo project, funded by a grant from the U.S. Department of Energy.

Learning to Grow

ERIC Educational Resources Information Center

Rodia, Becky

2004-01-01

What does the National Football League have in common with a small K-6 school in Iowa City, Iowa? Two things: one is San Diego Chargers wide receiver Tim Dwight, who grew up in Iowa City, where he attended Mark Twain Elementary; the other is Twain third grade teacher Julie Busch, Tim's former teacher and--thanks to Tim's thoughtful…

Uncle Tim's Dilemma

ERIC Educational Resources Information Center

DiBiase, Warren

2009-01-01

In this investigation, students make predictions and observations of a counterintuitive phenomenon. Given the scenario of a boat filled with a set of large rocks placed in a swimming pool, the students investigate what happens to both the water level in the pool and the level at which the boat floats when the rocks are taken out of the boat and…

Acoustic Measurement and Model Predictions for the Aural Nondetectability of Two Night-Vision Goggles

DTIC Science & Technology

2013-11-01

Acoustic Measurement and Model Predictions for the Aural Nondetectability of Two Night-Vision Goggles by Jeremy Gaston, Tim Mermagen, and...Goggles Jeremy Gaston, Tim Mermagen, and Kelly Dickerson Human Research and Engineering Directorate, ARL...5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Jeremy Gaston, Tim Mermagen, and Kelly Dickerson 5d. PROJECT NUMBER 74A 5e. TASK NUMBER 5f. WORK

The development of Music in Dementia Assessment Scales (MiDAS).

PubMed

McDermott, Orii; Orrell, Martin; Ridder, Hanne Mette

2015-07-03

There is a need to develop an outcome measure specific to music therapy in dementia that reflects a holistic picture of the therapy process and outcome. This study aimed to develop a clinically relevant and scientifically robust music therapy outcome measure incorporating the values and views of people with dementia. Focus groups and interviews were conducted to obtain qualitative data on what music meant to people with dementia and the observed effects of music. Expert and peer consultations were conducted at each stage of the measure development to maximise its content validity. The new measure was field-tested by clinicians in a care home. Feedback from the clinicians and music therapy experts were incorporated during the review and refinement process of the measure. A review of the existing literature, the experiential results and the consensus process enabled the development of the new outcome measure "Music in Dementia Assessment Scales (MiDAS)". Analysis of the qualitative data identified five key areas of the impact of music on people with dementia and they were transformed as the five Visual Analogue Scale (VAS) items: levels of Interest, Response, Initiation, Involvement and Enjoyment. MiDAS comprises the five VAS items and a supplementary checklist of notable positive and negative reactions from the individual. This study demonstrates that it is possible to design and develop an easy to apply and rigorous quantitative outcome measure which has a high level of clinical relevance for people with dementia, care home staff and music therapists.

Former President George H.W. Bush paid a visit to NASA's Johnson Space Center to speak with Expedition 46 Commander Scott Kelly and Flight Engineer Tim Kopra and take a tour of the Space Vehicle Mockup Facility. Kelly���s twin brother, Mark Kelly and his wife, former Congresswoman Gabrielle Giffords were also present. Photo Date: February 5, 2016. Location: Building 30 - ISS Flight Control Room. Photographer: Robert Markowitz

NASA Image and Video Library

2016-02-05

Former President George H.W. Bush paid a visit to NASA's Johnson Space Center to speak with Expedition 46 Commander Scott Kelly and Flight Engineer Tim Kopra and take a tour of the Space Vehicle Mockup Facility. Kelly’s twin brother, Mark Kelly and his wife, former Congresswoman Gabrielle Giffords were also present. Photo Date: February 5, 2016. Location: Building 30 - ISS Flight Control Room. Photographer: Robert Markowitz

Impact of the introduction of mandatory generic substitution in South Africa: private sector sales of generic and originator medicines for chronic diseases.

PubMed

Gray, Andrew Lofts; Santa-Ana-Tellez, Yared; J Wirtz, Veronika

2016-12-01

To assess the impact of mandatory offer of generic substitution, introduced in South Africa in May 2003, on private sector sales of generic and originator medicines for chronic diseases. Private sector sales data (June 2001 to May 2005) were obtained from IMS Health for proton pump inhibitors (PPIs; ATC code A02BC), HMG-CoA reductase inhibitors (statins; C10AA), dihydropyridine calcium antagonists (C08CA), angiotensin-converting enzyme inhibitors (ACE-I; C09AA) and selective serotonin reuptake inhibitors (SSRIs; N06AB). Monthly sales were expressed as defined daily doses per 1000 insured population per month (DDD/TIM). Interrupted time-series models were used to estimate the changes in slope and level of medicines use after the policy change. ARIMA models were used to correct for autocorrelation and stationarity. Only the SSRIs saw a significant rise in level of generic utilisation (0.2 DDD/TIM; P < 0.001) and a fall in originator usage (-0.1 DDD/TIM; P < 0.001) after the policy change. Utilisation of generic PPIs fell (level 0.06 DDD/TIM, P = 0.048; slope 0.01 DDD/TIM, P = 0.043), but utilisation of originator products also grew (level 0.05 DDD/TIM, P < 0.001; slope 0.003, P = 0.001). Generic calcium antagonists and ACE-I showed an increase in slope (0.01 DDD/TIM, P = 0.016; 0.02 DDD/TIM, P < 0.001), while the originators showed a decrease in slope (-0.003 DDD/TIM, P = 0.046; -0.01 DDD/TIM, P < 0.001). There were insufficient data on generic statin use before the policy change to allow for analysis. The mandatory offer of generic substitution appeared to have had a quantifiable effect on utilisation patterns in the 2 years after May 2003. Managed care interventions that were already in place before the intervention may have blunted the extent of the changes seen in this period. Generic policies are an important enabling provision for cost-containment efforts. However, decisions taken outside of official policy may anticipate or differ from that policy, with

DAS photonics developments for analogue and digital photonic links for intra-satellite communications

NASA Astrophysics Data System (ADS)

Blasco, Julián.; Rico, Eloy; Genovard, Pablo; Sáez, Cristina; Navasquillo, Olga; Martí, Javier

2017-11-01

During past years, special efforts have been invested to develop optical links, both digital and analogue, for space applications, such as reference signal distribution or digital communication cables. The aim of this paper is to present the current DAS developments for these applications as well as future work to increase TRL levels and flight opportunities.

Protein translocation channel of mitochondrial inner membrane and matrix-exposed import motor communicate via two-domain coupling protein.

PubMed

Banerjee, Rupa; Gladkova, Christina; Mapa, Koyeli; Witte, Gregor; Mokranjac, Dejana

2015-12-29

The majority of mitochondrial proteins are targeted to mitochondria by N-terminal presequences and use the TIM23 complex for their translocation across the mitochondrial inner membrane. During import, translocation through the channel in the inner membrane is coupled to the ATP-dependent action of an Hsp70-based import motor at the matrix face. How these two processes are coordinated remained unclear. We show here that the two domain structure of Tim44 plays a central role in this process. The N-terminal domain of Tim44 interacts with the components of the import motor, whereas its C-terminal domain interacts with the translocation channel and is in contact with translocating proteins. Our data suggest that the translocation channel and the import motor of the TIM23 complex communicate through rearrangements of the two domains of Tim44 that are stimulated by translocating proteins.

Hermann Cohen's Das Princip der Infinitesimal-Methode: The history of an unsuccessful book.

PubMed

Giovanelli, Marco

2016-08-01

This paper offers an introduction to Hermann Cohen's Das Princip der Infinitesimal-Methode (1883), and recounts the history of its controversial reception by Cohen's early sympathizers, who would become the so-called 'Marburg school' of Neo-Kantianism, as well as the reactions it provoked outside this group. By dissecting the ambiguous attitudes of the best-known representatives of the school (Paul Natorp and Ernst Cassirer), as well as those of several minor figures (August Stadler, Kurd Lasswitz, Dimitry Gawronsky, etc.), this paper shows that Das Princip der Infinitesimal-Methode is a unicum in the history of philosophy: it represents a strange case of an unsuccessful book's enduring influence. The "puzzle of Cohen's Infinitesimalmethode," as we will call it, can be solved by looking beyond the scholarly results of the book, and instead focusing on the style of philosophy it exemplified. Moreover, the paper shows that Cohen never supported, but instead explicitly opposed, the doctrine of the centrality of the 'concept of function', with which Marburg Neo-Kantianism is usually associated. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tower Illuminance Model

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

Ho, Clifford K.; Sims, Cianan

TIM is a real-time interactive concentrating solar field simulation. TIM models a concentrating tower (receiver), heliostat field, and potential reflected glare based on user-specified parameters such as field capacity, tower height and location. TIM provides a navigable 3D interface, allowing the user to “fly” around the field to determine the potential glare hazard from off-target heliostats. Various heliostat aiming strategies are available for specifying how heliostats behave when in standby mode. Strategies include annulus, point-per-group, up-aiming and single-point-focus. Additionally, TIM includes an avian path feature for approximating the irradiance and feather temperature of a bird flying through the field airspace.

The Deaf Acculturation Scale (DAS): Development and Validation of a 58-Item Measure

ERIC Educational Resources Information Center

Maxwell-McCaw, Deborah; Zea, Maria Cecilia

2011-01-01

This study involved the development and validation of the Deaf Acculturation Scale (DAS), a new measure of cultural identity for Deaf and hard-of-hearing (hh) populations. Data for this study were collected online and involved a nation-wide sample of 3,070 deaf/hh individuals. Results indicated strong internal reliabilities for all the subscales,…

Structural insights from a novel invertebrate triosephosphate isomerase from Litopenaeus vannamei

PubMed Central

Lopez-Zavala, Alonso A.; Carrasco-Miranda, Jesus S.; Ramirez-Aguirre, Claudia D.; López-Hidalgo, Marisol; Benitez-Cardoza, Claudia G.; Ochoa-Leyva, Adrian; Cardona-Felix, Cesar S.; Diaz-Quezada, Corina; Rudiño-Piñera, Enrique; Sotelo-Mundo, Rogerio R.; Brieba, Luis G.

2016-01-01

Triosephosphate isomerase (TIM; EC 5.3.1.1) is a key enzyme involved in glycolysis and gluconeogenesis. Glycolysis is one of the most regulated metabolic pathways, however little is known about the structural mechanisms for its regulation in non-model organisms, like crustaceans. To understand the structure and function of this enzyme in invertebrates, we obtained the crystal structure of triosephosphate isomerase from the marine Pacific whiteleg shrimp (Litopenaeus vannamei, LvTIM) in complex with its inhibitor 2-phosphogyceric acid (2-PG) at 1.7 Å resolution. LvTIM assembles as a homodimer with residues 166-176 covering the active site and residue Glu166 interacting with the inhibitor. We found that LvTIM is the least stable TIM characterized to date, with the lowest range of melting temperatures, and with the lowest activation enthalpy associated with the thermal unfolding process reported. In TIMs dimer stabilization is maintained by an interaction of loop 3 by a set of hydrophobic contacts between subunits. Within these contacts, the side chain of a hydrophobic residue of one subunit fits into a cavity created by a set of hydrophobic residues in the neighboring subunit, via a "ball and socket" interaction. LvTIM presents a Cys47 at the "ball" inter-subunit contact indicating that the character of this residue is responsible for the decrease in dimer stability. Mutational studies show that this residue plays a role in dimer stability but is not a solely determinant for dimer formation. PMID:27614148

Reactivation of triosephosphate isomerase from three trypanosomatids and human: effect of suramin.

PubMed Central

Gao, X G; Garza-Ramos, G; Saavedra-Lira, E; Cabrera, N; De Gómez-Puyou, M T; Perez-Montfort, R; Gómez-Puyou, A

1998-01-01

The reactivation of the homodimeric triosephosphate isomerases (TIMs) from Trypanosoma brucei, T. cruzi, Leishmania mexicana and humans was determined after their denaturation with guanidine hydrochloride. In the range of 2-32 microg of T. brucei TIM per ml and 0.2-5 microg of the other enzymes per ml, the rate and extent of TIM reactivation depended on protein concentration, indicating that at these protein concentrations, the rate-limiting step of reactivation is monomer association and not monomer folding. The rate of monomer association was more than one order of magnitude lower in the T. brucei enzyme than in the other three enzymes. Suramin is a drug of choice in the treatment of sleeping sickness, but its mechanism of action is not known. At micromolar concentrations, Suramin inhibited the reactivation of the four enzymes, but the extent of inhibition by Suramin decreased with increasing protein concentration as consequence of a diminution of the life time of the folded monomer. Since the life time of the monomer of T. brucei TIM is longer than that of the other enzymes, Suramin is a more effective inhibitor of the reactivation of TIM from T. brucei, particularly at monomer concentrations above 1 microg of protein per ml (monomer concentration approx. 37 nM). Compounds that are structurally related to Suramin also inhibit TIM reactivation; their effect was about five times more pronounced in the enzyme from T. brucei than in human TIM. PMID:9576855

The Great War and Remembrance in Jose Leon Machado's "Memoria das Estrelas sem Brilho"

ERIC Educational Resources Information Center

Azevedo, Milton M.

2011-01-01

This article analyzes Jose Leon Machado's novel, "Memoria das Estrelas sem Brilho," as a multilayered historical novel in which a war story provides a background for comments on aspects of early twentieth-century Portuguese society, such as male bonding, religion, sexual mores, and social stratification. (Contains 11 notes.)

CLAES Product Improvement by Use of the GSFC Data Assimilation System (DAS)

NASA Technical Reports Server (NTRS)

Kumer, J. B.; Douglass, Anne (Technical Monitor)

2000-01-01

This report presents the Cryogenic Limb Array Etalon Spectrometer (CLAES) product improvement by use of the GSFC Data Assimilation System (DAS). The first task is to plug line of sight gradients derived from the CTM for 2/20/92 into the forward model of our retrieval software (RSW) in order to assess the impact on the retrieved quantities. The reporting period covers 12 May 2000 - 21 December 2000.

Protein translocation channel of mitochondrial inner membrane and matrix-exposed import motor communicate via two-domain coupling protein

PubMed Central

Banerjee, Rupa; Gladkova, Christina; Mapa, Koyeli; Witte, Gregor; Mokranjac, Dejana

2015-01-01

The majority of mitochondrial proteins are targeted to mitochondria by N-terminal presequences and use the TIM23 complex for their translocation across the mitochondrial inner membrane. During import, translocation through the channel in the inner membrane is coupled to the ATP-dependent action of an Hsp70-based import motor at the matrix face. How these two processes are coordinated remained unclear. We show here that the two domain structure of Tim44 plays a central role in this process. The N-terminal domain of Tim44 interacts with the components of the import motor, whereas its C-terminal domain interacts with the translocation channel and is in contact with translocating proteins. Our data suggest that the translocation channel and the import motor of the TIM23 complex communicate through rearrangements of the two domains of Tim44 that are stimulated by translocating proteins. DOI: http://dx.doi.org/10.7554/eLife.11897.001 PMID:26714107

Differential effects on enzyme stability and kinetic parameters of mutants related to human triosephosphate isomerase deficiency.

PubMed

Cabrera, Nallely; Torres-Larios, Alfredo; García-Torres, Itzhel; Enríquez-Flores, Sergio; Perez-Montfort, Ruy

2018-06-01

Human triosephosphate isomerase (TIM) deficiency is a very rare disease, but there are several mutations reported to be causing the illness. In this work, we produced nine recombinant human triosephosphate isomerases which have the mutations reported to produce TIM deficiency. These enzymes were characterized biophysically and biochemically to determine their kinetic and stability parameters, and also to substitute TIM activity in supporting the growth of an Escherichia coli strain lacking the tim gene. Our results allowed us to rate the deleteriousness of the human TIM mutants based on the type and severity of the alterations observed, to classify four "unknown severity mutants" with altered residues in positions 62, 72, 122 and 154 and to explain in structural terms the mutation V231M, the most affected mutant from the kinetic point of view and the only homozygous mutation reported besides E104D. Copyright © 2018 Elsevier B.V. All rights reserved.

Dense Vertically Aligned Copper Nanowire Composites as High Performance Thermal Interface Materials.

PubMed

Barako, Michael T; Isaacson, Scott G; Lian, Feifei; Pop, Eric; Dauskardt, Reinhold H; Goodson, Kenneth E; Tice, Jesse

2017-12-06

Thermal interface materials (TIMs) are essential for managing heat in modern electronics, and nanocomposite TIMs can offer critical improvements. Here, we demonstrate thermally conductive, mechanically compliant TIMs based on dense, vertically aligned copper nanowires (CuNWs) embedded into polymer matrices. We evaluate the thermal and mechanical characteristics of 20-25% dense CuNW arrays with and without polydimethylsiloxane infiltration. The thermal resistance achieved is below 5 mm 2 K W -1 , over an order of magnitude lower than commercial heat sink compounds. Nanoindentation reveals that the nonlinear deformation mechanics of this TIM are influenced by both the CuNW morphology and the polymer matrix. We also implement a flip-chip bonding protocol to directly attach CuNW composites to copper surfaces, as required in many thermal architectures. Thus, we demonstrate a rational design strategy for nanocomposite TIMs that simultaneously retain the high thermal conductivity of aligned CuNWs and the mechanical compliance of a polymer.

The development of Music in Dementia Assessment Scales (MiDAS)

PubMed Central

McDermott, Orii; Orrell, Martin; Ridder, Hanne Mette

2015-01-01

There is a need to develop an outcome measure specific to music therapy in dementia that reflects a holistic picture of the therapy process and outcome. This study aimed to develop a clinically relevant and scientifically robust music therapy outcome measure incorporating the values and views of people with dementia. Focus groups and interviews were conducted to obtain qualitative data on what music meant to people with dementia and the observed effects of music. Expert and peer consultations were conducted at each stage of the measure development to maximise its content validity. The new measure was field-tested by clinicians in a care home. Feedback from the clinicians and music therapy experts were incorporated during the review and refinement process of the measure. A review of the existing literature, the experiential results and the consensus process enabled the development of the new outcome measure “Music in Dementia Assessment Scales (MiDAS)”. Analysis of the qualitative data identified five key areas of the impact of music on people with dementia and they were transformed as the five Visual Analogue Scale (VAS) items: levels of Interest, Response, Initiation, Involvement and Enjoyment. MiDAS comprises the five VAS items and a supplementary checklist of notable positive and negative reactions from the individual. This study demonstrates that it is possible to design and develop an easy to apply and rigorous quantitative outcome measure which has a high level of clinical relevance for people with dementia, care home staff and music therapists. PMID:26246670

Exploring Trends in Metal-Metal Bonding, Spectroscopic Properties, and Conformational Flexibility in a Series of Heterobimetallic Ti/M and V/M Complexes (M = Fe, Co, Ni, and Cu).

PubMed

Wu, Bing; Wilding, Matthew J T; Kuppuswamy, Subramaniam; Bezpalko, Mark W; Foxman, Bruce M; Thomas, Christine M

2016-12-05

To understand the metal-metal bonding and conformational flexibility of first-row transition metal heterobimetallic complexes, a series of heterobimetallic Ti/M and V/M complexes (M = Fe, Co, Ni, and Cu) have been investigated. The titanium tris(phosphinoamide) precursors ClTi(XylNP i Pr 2 ) 3 (1) and Ti(XylNP i Pr 2 ) 3 (2) have been used to synthesize Ti/Fe (3), Ti/Ni (4, 4 THF ), and Ti/Cu (5) heterobimetallic complexes. A series of V/M (M = Fe (7), Co (8), Ni (9), and Cu (10)) complexes have been generated starting from the vanadium tris(phosphinoamide) precursor V(XylNP i Pr 2 ) 3 (6). The new heterobimetallic complexes were characterized and studied by NMR spectroscopy, X-ray crystallography, electron paramagnetic resonance, and Mössbauer spectroscopy, where applicable, and computational methods (DFT). Compounds 3, 4 THF , 7, and 8 are C 3 -symmetric with three bridging phosphinoamide ligands, while compounds 9 and 10 adopt an asymmetric geometry with two bridging phosphinoamides and one phosphinoamide ligand bound η 2 to vanadium. Compounds 4 and 5, on the other hand, are asymmetric in the solid state but show evidence for fluxional behavior in solution. A correlation is established between conformational flexibility and metal-metal bond order, which has important implications for the future reactivity of these and other heterobimetallic molecules.

Efficacy of Soybean’s Event DAS-81419-2 Expressing Cry1F and Cry1Ac to Manage Key Tropical Lepidopteran Pests Under Field Conditions in Brazil

PubMed Central

Marques, L H; Castro, B A; Rossetto, J; Silva, O A B N; Moscardini, V F; Zobiole, L H S; Santos, A C; Valverde-Garcia, P; Babcock, J M; Rule, D M; Fernandes, O A

2016-01-01

Abstract Bacillus thuringiensis (Bt) event DAS-81419-2 (Conkesta technology) in soybean, Glycine max (L.) Merrill, expresses Cry1F and Cry1Ac proteins to provide protection from feeding by several lepidopteran pests. A total of 27 field experiments across nine locations were conducted from 2011 to 2015 in southern and central Brazil to characterize the efficacy of DAS-81419-2 soybean infested with Anticarsia gemmatalis Hübner (Lepidoptera: Erebidae), Chrysodeixis includens (Walker) (Lepidoptera: Noctuidae), Heliothis virescens (F.) (Lepidoptera: Noctuidae), and Spodoptera cosmioides (Walker) (Lepidoptera: Noctuidae) during vegetative (V4) and reproductive (R2 and R4) crop developmental stages. The efficacy of DAS-81419-2 was compared to that of a non-Bt isogenic variety managed with or without applications of commercial foliar insecticides for lepidopteran control. DAS-81419-2 soybean consistently experienced defoliation levels of 0.5% or less (compared with 20.05–56.74% in the non-Bt, nonsprayed treatment) and larval survival of < 0.1% in all four species across the vegetative and reproductive plant stages evaluated. The efficacy of DAS-81419-2 was significantly higher than commercial foliar insecticides applied to the non-Bt variety. DAS-81419-2 soybeans containing two highly effective Bt proteins are expected to be a more robust IRM tool compared to single-trait Bt technologies. The consistent efficacy of DAS-81419-2 soybeans across years, locations, and crop stages suggests that it will be a valuable product for management of hard-to-control key lepidopteran pests in South American soybean production. PMID:27401112

MiDas: Automatic Extraction of a Common Domain of Discourse in Sleep Medicine for Multi-center Data Integration

PubMed Central

Sahoo, Satya S.; Ogbuji, Chimezie; Luo, Lingyun; Dong, Xiao; Cui, Licong; Redline, Susan S.; Zhang, Guo-Qiang

2011-01-01

Clinical studies often use data dictionaries with controlled sets of terms to facilitate data collection, limited interoperability and sharing at a local site. Multi-center retrospective clinical studies require that these data dictionaries, originating from individual participating centers, be harmonized in preparation for the integration of the corresponding clinical research data. Domain ontologies are often used to facilitate multi-center data integration by modeling terms from data dictionaries in a logic-based language, but interoperability among domain ontologies (using automated techniques) is an unresolved issue. Although many upper-level reference ontologies have been proposed to address this challenge, our experience in integrating multi-center sleep medicine data highlights the need for an upper level ontology that models a common set of terms at multiple-levels of abstraction, which is not covered by the existing upper-level ontologies. We introduce a methodology underpinned by a Minimal Domain of Discourse (MiDas) algorithm to automatically extract a minimal common domain of discourse (upper-domain ontology) from an existing domain ontology. Using the Multi-Modality, Multi-Resource Environment for Physiological and Clinical Research (Physio-MIMI) multi-center project in sleep medicine as a use case, we demonstrate the use of MiDas in extracting a minimal domain of discourse for sleep medicine, from Physio-MIMI’s Sleep Domain Ontology (SDO). We then extend the resulting domain of discourse with terms from the data dictionary of the Sleep Heart and Health Study (SHHS) to validate MiDas. To illustrate the wider applicability of MiDas, we automatically extract the respective domains of discourse from 6 sample domain ontologies from the National Center for Biomedical Ontologies (NCBO) and the OBO Foundry. PMID:22195180

MiDas: automatic extraction of a common domain of discourse in sleep medicine for multi-center data integration.

PubMed

Sahoo, Satya S; Ogbuji, Chimezie; Luo, Lingyun; Dong, Xiao; Cui, Licong; Redline, Susan S; Zhang, Guo-Qiang

2011-01-01

Clinical studies often use data dictionaries with controlled sets of terms to facilitate data collection, limited interoperability and sharing at a local site. Multi-center retrospective clinical studies require that these data dictionaries, originating from individual participating centers, be harmonized in preparation for the integration of the corresponding clinical research data. Domain ontologies are often used to facilitate multi-center data integration by modeling terms from data dictionaries in a logic-based language, but interoperability among domain ontologies (using automated techniques) is an unresolved issue. Although many upper-level reference ontologies have been proposed to address this challenge, our experience in integrating multi-center sleep medicine data highlights the need for an upper level ontology that models a common set of terms at multiple-levels of abstraction, which is not covered by the existing upper-level ontologies. We introduce a methodology underpinned by a Minimal Domain of Discourse (MiDas) algorithm to automatically extract a minimal common domain of discourse (upper-domain ontology) from an existing domain ontology. Using the Multi-Modality, Multi-Resource Environment for Physiological and Clinical Research (Physio-MIMI) multi-center project in sleep medicine as a use case, we demonstrate the use of MiDas in extracting a minimal domain of discourse for sleep medicine, from Physio-MIMI's Sleep Domain Ontology (SDO). We then extend the resulting domain of discourse with terms from the data dictionary of the Sleep Heart and Health Study (SHHS) to validate MiDas. To illustrate the wider applicability of MiDas, we automatically extract the respective domains of discourse from 6 sample domain ontologies from the National Center for Biomedical Ontologies (NCBO) and the OBO Foundry.

Determination of the turbulence integral model parameters for a case of a coolant angular flow in regular rod-bundle

NASA Astrophysics Data System (ADS)

Bayaskhalanov, M. V.; Vlasov, M. N.; Korsun, A. S.; Merinov, I. G.; Philippov, M. Ph

2017-11-01

Research results of “k-ε” turbulence integral model (TIM) parameters dependence on the angle of a coolant flow in regular smooth cylindrical rod-bundle are presented. TIM is intended for the definition of efficient impulse and heat transport coefficients in the averaged equations of a heat and mass transfer in the regular rod structures in an anisotropic porous media approximation. The TIM equations are received by volume-averaging of the “k-ε” turbulence model equations on periodic cell of rod-bundle. The water flow across rod-bundle under angles from 15 to 75 degrees was simulated by means of an ANSYS CFX code. Dependence of the TIM parameters on flow angle was as a result received.

Antimicrobial capacity of the freshwater planarians against S. aureus is under the control of Timeless.

PubMed

Tsoumtsa, Landry Laure; Torre, Cedric; Trouplin, Virginie; Coiffard, Benjamin; Gimenez, Gregory; Mege, Jean-Louis; Ghigo, Eric

2017-10-03

Planarians, which are non-parasitic flatworms, are highly resistant to bacterial infections. To better understand the mechanisms underlying this resistance, we investigated the role of the circadian machinery in the anti-bacterial response of the freshwater planarian Schmidtea mediterranea. We identified Smed-Tim from S. mediterranea as a homolog of the mammalian clock gene Tim. We showed via RNA interference that Smed-Tim is required for the anti-microbial activities of Schmidtea mediterranea against Staphylococcus aureus infection during the light/dark cycle. Indeed, S. aureus infection leads to the expression of Smed-Tim, which in turn promotes Smed-Traf6 and Smed-morn2, but not Smed-p38 MAPK expression, 2 master regulators of planarian anti-microbial responses.

Smart Home, Smart Grid, Smart Meter - digitale Konzepte und das Recht an Daten

NASA Astrophysics Data System (ADS)

Spiecker genannt Döhmann, Indra

Modernes Energiemanagement setzt auf ein intelligent gesteuertes Energieinformationsnetz, das Smart Grid. In diesem ist der Smart Meter, die intelligente Messstelle beim Nutzer, ein zentrales Instrument für den wechselseitigen Austausch von Informationen. Allerdings werfen die über diverse Gesetze forcierten Informationsströme erhebliche datenschutzrechtliche Fragen auf. Der Beitrag stellt zentrale datenschutzrechtliche Leitlinien und Probleme vor und behandelt auch offene Fragestellungen.

Timing of K-alkaline magmatism in the Balkan segment of southeast European Variscan edifice: ID-TIMS and LA-ICP-MS study

NASA Astrophysics Data System (ADS)

Dyulgerov, Momchil; Ovtcharova-Schaltegger, Maria; Ulianov, Alexey; Schaltegger, Urs

2018-06-01

The Variscan orogen in southeast Europe is exposed in isolated remnants, affected by a subsequent Alpine tectono-magmatic overprint. Unlike the central European Variscides, in SE Europe the juxtaposition and correlation of the events and products are impeded by the scarcity of Variscan domains with preserved magmatic, metamorphic, sedimentological and structural characteristics. To reveal the particular evolution of the Variscan orogen in Balkan Mts, we present the results of ID-TIMS and LA-ICP-MS dating of three potassic-alkaline intrusions: Svidnya, Buhovo-Seslavtsi and Shipka. The age determinations from the plutons do not permit to establish their unequivocal ages, but they bracket the time interval of emplacements. Based on geochronological, tectonic and stratigraphic evidence the emplacement interval for plutons could be: 317-310 Ma for Svidnya, 330-310 Ma for Buhovo-Seslavtsi and 320-303 Ma for Shipka. These results show that the generation of potassic-alkaline magmas was post-Visean and is contemporaneous with the adjacent numerous calc-alkaline granitoid plutons. Thus, the Variscan orogen in the Balkan Mts is not characterized by a time-dependent geochemical evolution of magma generation. Hence, the observed differences in the rocks' compositions can be interpreted solely by distinction between the magma sources. The available data for both potassic-alkaline and calc-alkaline rocks indicate that the major episodes of crustal stacking and shearing in the Balkan part of the Variscan edifice are pre-Visean ( 330 Ma). The present study reveals that the potassic-alkaline rocks from the Balkan Mts are younger than the central European potassic granitoids (durbachites). It suggests that melting of enriched mantle source took place at different times throughout the Variscan orogen. In spite of the alkaline character of the magmas, the studied zircons show a complex nature, with inherited cores and magmatic overgrowths. The observed heterogeneities in the zircons

Scientific Evaluation of Edible Fruits and Spices Used for the Treatment of Peptic Ulcer in Traditional Iranian Medicine

PubMed Central

Farzaei, Mohammad Hosein; Shams-Ardekani, Mohammad Reza; Abbasabadi, Zahra; Rahimi, Roja

2013-01-01

In traditional Iranian medicine (TIM), several edible fruits and spices are thought to have protective and healing effects on peptic ulcer (PU). The present study was conducted to verify anti-PU activity of these remedies. For this purpose, edible fruits and spices proposed for the management of PU in TIM were collected from TIM sources, and they were searched in modern medical databases to find studies that confirmed their efficacy. Findings from modern investigations support the claims of TIM about the efficacy of many fruits and spices in PU. The fruit of Phyllanthus emblica as a beneficial remedy for PU in TIM has been demonstrated to have antioxidant, wound healing, angiogenic, anti-H. pylori, cytoprotective, antisecretory, and anti-inflammatory properties. The fruit of Vitis vinifera has been found to be anti-H. pylori, anti-inflammatory, wound healing, angiogenic, cytoprotective, and antioxidant. The fruit and aril of seed from Myristica fragrans exert their beneficial effects in PU by increasing prostaglandin, modulation of nitric oxide and inflammatory mediators, wound healing, antisecretory, antacid, antioxidant, and anti-H. pylori activities, and improving angiogenesis. Pharmacological and clinical studies for evaluation of efficacy of all TIM fruits and spices in PU and their possible mechanisms of action are recommended. PMID:24066235

The Oligomeric Nature of Triosephosphate Isomerase. Studies of Monomerization

NASA Astrophysics Data System (ADS)

Zárate-Pérez, Francisco; Vázquez-Contreras, Edgar

2008-02-01

In this work, we report the implications of the monomerization of triosephosphate isomerase (TIM) from T. cruzi (TcTIM). A monomeric mutant (monoTcTIM) of this species was constructed by genetic engineering, shortening the main loop of interdigitation, which is fundamental for its dimerization. The properties of monoTcTIM were compared with those of the other TIM monomeric versions: genetically engineered mutants, or equilibrium intermediates obtained by chemical denaturation. The stability for almost all the monomeric variants so far reported appears in the same range, and also presents similar structural characteristics. Regarding the catalytic activity of monomeric mutants, when it is present is in several orders of magnitude lower than those observed in their respective wild-type enzyme. The change in the hydrophobic surface of TcTIM after and before monomerization was also studied and corresponds to an extensive area of the interface region, which becomes exposed when monomers are dissociated. This fact could be related with conformational changes in the local environment of the catalytic amino acids responsible for the isomerization of the substrate and consequently the inactivation of its catalytic properties. Comparison of the structural, folding and unfolding properties, as well as stability studies could give answers on why this enzyme is an obligate oligomer.

Species-Specific Inactivation of Triosephosphate Isomerase from Trypanosoma brucei: Kinetic and Molecular Dynamics Studies.

PubMed

Vázquez-Raygoza, Alejandra; Cano-González, Lucia; Velázquez-Martínez, Israel; Trejo-Soto, Pedro Josué; Castillo, Rafael; Hernández-Campos, Alicia; Hernández-Luis, Francisco; Oria-Hernández, Jesús; Castillo-Villanueva, Adriana; Avitia-Domínguez, Claudia; Sierra-Campos, Erick; Valdez-Solana, Mónica; Téllez-Valencia, Alfredo

2017-11-24

Human African Trypanosomiasis (HAT), a disease that provokes 2184 new cases a year in Sub-Saharan Africa, is caused by Trypanosoma brucei . Current treatments are limited, highly toxic, and parasite strains resistant to them are emerging. Therefore, there is an urgency to find new drugs against HAT. In this context, T. brucei depends on glycolysis as the unique source for ATP supply; therefore, the enzyme triosephosphate isomerase (TIM) is an attractive target for drug design. In the present work, three new benzimidazole derivatives were found as TbTIM inactivators (compounds 1 , 2 and 3 ) with an I 50 value of 84, 82 and 73 µM, respectively. Kinetic analyses indicated that the three molecules were selective when tested against human TIM (HsTIM) activity. Additionally, to study their binding mode in TbTIM, we performed a 100 ns molecular dynamics simulation of TbTIM-inactivator complexes. Simulations showed that the binding of compounds disturbs the structure of the protein, affecting the conformations of important domains such as loop 6 and loop 8. In addition, the physicochemical and drug-like parameters showed by the three compounds suggest a good oral absorption. In conclusion, these molecules will serve as a guide to design more potent inactivators that could be used to obtain new drugs against HAT.

The Relationship Between Function and Disease Activity as Measured by the HAQ and DAS28 Varies Over Time and by Rheumatoid Factor Status in Early Inflammatory Arthritis (EIA). Results from the CATCH Cohort.

PubMed

Boyd, Tristan A; Bonner, A; Thorne, C; Boire, G; Hitchon, C; Haraoui, B P; Keystone, E C; Bykerk, V P; Pope, J E

2013-01-01

To investigate the relationship between function and disease activity in early inflammatory arthritis (EIA). Canadian Early Arthritis Cohort (CATCH) (n=1143) is a multi-site EIA cohort. Correlations between the Health Assessment Questionnaire Disability Index (HAQ) and DAS28 were done at every 3 months for the first year and then at 18 and 24 months. We also investigated the relationship between HAQ and DAS28 by age (<65 versus ≥65) and RF (positive vs negative). Mean HAQ and DAS28 scores were highest at the initial visit with HAQ decreasing over 24 months from a baseline of 0.94 to 0.40 and DAS28 scores decreasing from 4.54 to 2.29. All correlations between HAQ and DAS28 were significant at all time points (p<0.01). The correlations between HAQ and DAS28 were variable over time. The strongest correlation between HAQ and DAS28 occurred at initial visit (most DMARD naive) (n=1,143) and 18 months (r=0.57, n=321) and 24 months (r=0.59, n=214). The baseline correlation between HAQ and DAS28 was significantly different than correlations obtained at 3, 6, and 12 months (p=0.02, 0.01, and 0.01, respectively). Age did not change the association between HAQ and DAS28 {<65 years old (r=0.50, n=868) versus ≥65 (r=0.48, n=254), p=0.49}. The correlation between HAQ and DAS28 was stronger with RF+ patients (r=0.63, n=636) vs RF negative (r=0.47, n=477), p=0.0043. Over 2 years in EIA, HAQ and DAS both improved; correlations at time points were different over 2 years and RF status affected the correlations.

Uranium(iii) complexes supported by hydrobis(mercaptoimidazolyl)borates: synthesis and oxidation chemistry.

PubMed

Maria, Leonor; Santos, Isabel C; Santos, Isabel

2018-05-23

The reaction of [UI3(thf)4] with the sodium or lithium salts of hydrobis(2-mercapto-1-methylimidazolyl)borate ligands ([H(R)B(timMe)2]-) in a 1 : 2 ratio, in tetrahydrofuran, gave the U(iii) complexes [UI{κ3-H,S,S'-H(R)B(timMe)2}2(thf)2] (R = H (1), Ph (2)) in good yields. Crystals of [UI{κ3-H,S,S'-H(Ph)B(timMe)2}2(thf)2] (2) were obtained by recrystallization from a tetrahydrofuran/acetonitrile solution, and the ion-separated uranium complex [U{κ3-H,S,S'-H(Ph)B(timMe)2}2(CH3CN)3][I] (3-I) was obtained by dissolution of 2 in acetonitrile followed by recrystallization. One-electron oxidation of 2 with AgBPh4 or I2 resulted in the formation of the cationic U(iv) complexes [U{κ3-H,S,S'-H(Ph)B(timMe)2}3][X] (X = BPh4 (6-BPh4), I (6-I)), due to a ligand redistribution process. These complexes are the first examples of homoleptic poly(azolyl)borate U(iv) complexes. Treatment of complex 2 with azobenzene led to the isolation of crystals of the U(iv) compound [UI{κ3-H(Ph)B(timMe)2}2(κ2-timMe)] (7). Treatment of 2 with pyridine-N oxide (pyNO) led to the formation of the uranyl complex [UO2{κ2-S,S'-H(Ph)B(timMe)2}2] (8) and of complex 6-I, while from the reaction of [U{κ3-H(Ph)B(timMe)2}2(thf)3][BPh4] (5) with pyNO, the oxo-bridged U(iv) complex [{U{κ3-H(Ph)B(timMe)2}2(pyNO)}2(μ-O)][BPh4]2 (9) was also obtained. In the U(iii) and U(iv) complexes, the bis(azolyl)borate ligands bind to the uranium center in a κ3-H,S,S' coordination mode, while in the U(vi) complex the ligands bind to the metal in a κ2-S,S' mode. The presence of UH-B interactions in the solid-state, for the nine-coordinate complexes 1, 2, 3, 6 and 7 and for the eight-coordinate complex 9, was supported by IR spectroscopy and/or X-ray diffraction analysis.

The Long-Term U.S. Strategic Implications of Huawei’s Penetration in Latin America

DTIC Science & Technology

2013-03-01

TIM Brasil Picks NSN, Ericsson and Huawei to Deliver LTE 2012, para. 1). This shows a commitment to a long-term relationship between Huawei and...statement of Eliot L. Engel, congressional representative from New York). 1-37. "TIM Brasil Picks NSN, Ericsson and Huawei to Deliver LTE...34 TeleGeography. October 31, 2012. Accessed January 21, 2013. http://www.telegeography.com/products/commsupdate/arti cles/2012/10/31/tim- brasil -picks-nsn

Link Correlated Military Data for Better Decision Support

DTIC Science & Technology

2011-06-01

automatically translated into URI based links, thus can greatly reduce man power cost on software development. 3 Linked Data Technique Tim Berners - Lee ...Linked Data - while Linked Data is usually considered as part of Semantic Web, or “the Semantic Web done right” as described by Tim himself - has been...Required data of automatic link construction mechanism on more kinds of correlations. References [1] B. L. Tim , “The next Web of open, linked data

Preparation of bone-implants by coating hydroxyapatite nanoparticles on self-formed titanium dioxide thin-layers on titanium metal surfaces.

PubMed

Wijesinghe, W P S L; Mantilaka, M M M G P G; Chathuranga Senarathna, K G; Herath, H M T U; Premachandra, T N; Ranasinghe, C S K; Rajapakse, R P V J; Rajapakse, R M G; Edirisinghe, Mohan; Mahalingam, S; Bandara, I M C C D; Singh, Sanjleena

2016-06-01

Preparation of hydroxyapatite coated custom-made metallic bone-implants is very important for the replacement of injured bones of the body. Furthermore, these bone-implants are more stable under the corrosive environment of the body and biocompatible than bone-implants made up of pure metals and metal alloys. Herein, we describe a novel, simple and low-cost technique to prepare biocompatible hydroxyapatite coated titanium metal (TiM) implants through growth of self-formed TiO2 thin-layer (SFTL) on TiM via a heat treatment process. SFTL acts as a surface binder of HA nanoparticles in order to produce HA coated implants. Colloidal HA nanorods prepared by a novel surfactant-assisted synthesis method, have been coated on SFTL via atomized spray pyrolysis (ASP) technique. The corrosion behavior of the bare and surface-modified TiM (SMTiM) in a simulated body fluid (SBF) medium is also studied. The highest corrosion rate is found to be for the bare TiM plate, but the corrosion rate has been reduced with the heat-treatment of TiM due to the formation of SFTL. The lowest corrosion rate is recorded for the implant prepared by heat treatment of TiM at 700 °C. The HA-coating further assists in the passivation of the TiM in the SBF medium. Both SMTiM and HA coated SMTiM are noncytotoxic against osteoblast-like (HOS) cells and are in high-bioactivity. The overall production process of bone-implant described in this paper is in high economic value. Copyright © 2016 Elsevier B.V. All rights reserved.

A novel abundant family of retroposed elements (DAS-SINEs) in the nine-banded armadillo (Dasypus novemcinctus).

PubMed

Churakov, Gennady; Smit, Arian F A; Brosius, Jürgen; Schmitz, Jürgen

2005-04-01

About half of the mammalian genome is composed of retroposons. Long interspersed elements (LINEs) and short interspersed elements (SINEs) are the most abundant repetitive elements and account for about 21% and 13% of the human genome, respectively. SINEs have been detected in all major mammalian lineages, except for the South American order Xenarthra, also termed Edentata (armadillos, anteaters, and sloths). Investigating this order, we discovered a novel high-copy-number family of tRNA derived SINEs in the nine-banded armadillo Dasypus novemcinctus, a species that successfully crossed the Central American land bridge to North America in the Pliocene. A specific computer algorithm was developed, and we detected and extracted 687 specific SINEs from databases. Termed DAS-SINEs, we further divided them into six distinct subfamilies. We extracted tRNA(Ala)-derived monomers, two types of dimers, and three subfamilies of chimeric fusion products of a tRNA(Ala) domain and an approximately 180-nt sequence of thus far unidentified origin. Comparisons of secondary structures of the DAS-SINEs' tRNA domains suggest selective pressure to maintain a tRNA-like D-arm structure in the respective founder RNAs, as shown by compensatory mutations. By analysis of subfamily-specific genetic variability, comparison of the proportion of direct repeats, and analysis of self-integrations as well as key events of dimerization and deletions or insertions, we were able to delineate the evolutionary history of the DAS-SINE subfamilies.

Antimicrobial capacity of the freshwater planarians against S. aureus is under the control of Timeless

PubMed Central

Tsoumtsa, Landry Laure; Torre, Cedric; Trouplin, Virginie; Coiffard, Benjamin; Gimenez, Gregory; Mege, Jean-Louis; Ghigo, Eric

2017-01-01

ABSTRACT Planarians, which are non-parasitic flatworms, are highly resistant to bacterial infections. To better understand the mechanisms underlying this resistance, we investigated the role of the circadian machinery in the anti-bacterial response of the freshwater planarian Schmidtea mediterranea. We identified Smed-Tim from S. mediterranea as a homolog of the mammalian clock gene Tim. We showed via RNA interference that Smed-Tim is required for the anti-microbial activities of Schmidtea mediterranea against Staphylococcus aureus infection during the light/dark cycle. Indeed, S. aureus infection leads to the expression of Smed-Tim, which in turn promotes Smed-Traf6 and Smed-morn2, but not Smed-p38 MAPK expression, 2 master regulators of planarian anti-microbial responses. PMID:28051908

SU-F-BRE-03: Consideration of a Track-Interaction Model for Radiochromic Film Response

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

Rosen, B; DeWerd, L

2014-06-15

Purpose: Conventional methods for characterizing the energy response of radiochromic film (RCF) typically involve assessing changes in response when exposed to various beam qualities and use Monte Carlo to determine absorbed dose. These methods represent RCF as a dose integrator of a homogeneous energy deposition volume. Apparent film saturation, nonlinearity, and intrinsic energy dependence are unpredicted with conventional methods. Recent work has shown significant RCF intrinsic energy dependence, which limits its use in absolute dosimetry. This work introduces a track-interaction model (TIM) for RCF and assesses its ability to predict total energy response. Methods: A TIM based on Katz single-hitmore » theory was developed to accumulate energy flux along particle tracks within active crystals, represented as (1×1×20)um{sup 3} prisms about the Gafchromic™ EBT3 active volume using MCNP5 and Matlab. Energy flux contributed to film response only if near the threshold energy for polymerization in polydiacetylenes (2.5eV/monomer). Energy deposition in excess of maximum efficiency represented crystal saturation and did not contribute to film response. The TIM was applied to RCF exposed in air to various monoenergetic photon beams and Co-60. Geometric distribution of energy flux was found for each beam quality in a (1×1)mm{sup 2} RCF area. RCF response relative to Co-60 absorbed dose-to-water (S-TIM) was determined and compared to published values (S-PUB). Results: TIM successfully predicted that lower energy radiation is less effective at inducing polymerization, though the magnitude of the phenomenon was overpredicted. S-TIM was −29% and +20% for 20 and 40 keV, respectively. This agreed qualitatively with S-PUB of −27% and +16%. TIM-generated sensitometric curves contained the non-linearity and saturation apparent in RCF. Conclusion: This work indicates the possibility for TIMs to predict changes in RCF response to various energies. Future work will refine

50 CFR 648.53 - Target total allowable catch, DAS allocations, and individual fishing quotas.

Code of Federal Regulations, 2010 CFR

2010-10-01

... specified in paragraph (h)(1) of this section. Two percent of total available DAS will be set aside to pay... observers. The obligation to carry and pay for an observer shall not be waived due to the absence of set... pay the fee to NMFS by January 1 of each year. Cost recovery payments shall be made electronically via...

Ejecta patterns of Meteor Crater, Arizona derived from the linear un-mixing of TIMS data and laboratory thermal emission spectra

NASA Technical Reports Server (NTRS)

Ramsey, Michael S.; Christensen, Philip R.

1992-01-01

Accurate interpretation of thermal infrared data depends upon the understanding and removal of complicating effects. These effects may include physical mixing of various mineralogies and particle sizes, atmospheric absorption and emission, surficial coatings, geometry effects, and differential surface temperatures. The focus is the examination of the linear spectral mixing of individual mineral or endmember spectra. Linear addition of spectra, for particles larger than the wavelength, allows for a straight-forward method of deconvolving the observed spectra, predicting a volume percent of each endmember. The 'forward analysis' of linear mixing (comparing the spectra of physical mixtures to numerical mixtures) has received much attention. The reverse approach of un-mixing thermal emission spectra was examined with remotely sensed data, but no laboratory verification exists. Understanding of the effects of spectral mixing on high resolution laboratory spectra allows for the extrapolation to lower resolution, and often more complicated, remotely gathered data. Thermal Infrared Multispectral Scanner (TIMS) data for Meteor Crater, Arizona were acquired in Sep. 1987. The spectral un-mixing of these data gives a unique test of the laboratory results. Meteor Crater (1.2 km in diameter and 180 m deep) is located in north-central Arizona, west of Canyon Diablo. The arid environment, paucity of vegetation, and low relief make the region ideal for remote data acquisition. Within the horizontal sedimentary sequence that forms the upper Colorado Plateau, the oldest unit sampled by the impact crater was the Permian Coconino Sandstone. A thin bed of the Toroweap Formation, also of Permian age, conformably overlays the Coconino. Above the Toroweap lies the Permian Kiabab Limestone which, in turn, is covered by a thin veneer of the Moenkopi Formation. The Moenkopi is Triassic in age and has two distinct sub-units in the vicinity of the crater. The lower Wupatki member is a fine

AhR activation increases IL-2 production by alloreactive CD4+ T cells initiating the differentiation of mucosal-homing Tim3+ Lag3+ Tr1 cells.

PubMed

Ehrlich, Allison K; Pennington, Jamie M; Tilton, Susan; Wang, Xisheng; Marshall, Nikki B; Rohlman, Diana; Funatake, Castle; Punj, Sumit; O'Donnell, Edmond; Yu, Zhen; Kolluri, Siva K; Kerkvliet, Nancy I

2017-11-01

Activation of the aryl hydrocarbon receptor (AhR) by immunosuppressive ligands promotes the development of regulatory T (Treg) cells. Although AhR-induced Foxp3 + Treg cells have been well studied, much less is known about the development and fate of AhR-induced Type 1 Treg (AhR-Tr1) cells. In the current study, we identified the unique transcriptional and functional changes in murine CD4 + T cells that accompany the differentiation of AhR-Tr1 cells during the CD4 + T-cell-dependent phase of an allospecific cytotoxic T lymphocyte (allo-CTL) response. AhR activation increased the expression of genes involved in T-cell activation, immune regulation and chemotaxis, as well as a global downregulation of genes involved in cell cycling.  Increased IL-2 production was responsible for the early AhR-Tr1 activation phenotype previously characterized as CD25 + CTLA4 + GITR + on day 2. The AhR-Tr1 phenotype was further defined by the coexpression of the immunoregulatory receptors Lag3 and Tim3 and non-overlapping expression of CCR4 and CCR9. Consistent with the increased expression of CCR9, real-time imaging showed enhanced migration of AhR-Tr1 cells to the lamina propria of the small intestine and colon. The discovery of mucosal imprinting of AhR-Tr1 cells provides an additional mechanism by which therapeutic AhR ligands can control immunopathology. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Novel polymer composite having diamond particles and boron nitride platelets for thermal management of electric vehicle motors

NASA Astrophysics Data System (ADS)

Nakajima, Anri; Shoji, Atsushi; Yonemori, Kei; Seo, Nobuhide

2016-02-01

Thermal conductivities of silicone matrix polymers including fillers of diamond particles and/or hexagonal boron nitride (h-BN) platelets were systematically investigated in an attempt to find a thermal interface material (TIM) having high isotropic thermal conductivity and high electrical insulating ability to enable efficient heat dissipation from the motor coil ends of electric vehicles. The TIM with mixed fillers of diamond particles and h-BN platelets had a maximum thermal conductivity of 6.1 W m-1 K-1 that was almost isotropic. This is the highest value among the thermal conductivities of TIMs with silicone matrix polymer reported to date. The mechanism behind the thermal conductivity of the TIMs was also examined from the viewpoint of the change in the number of thermally conductive networks and/or a decrease in the thermal resistivity of junctions of neighboring diamond particles through the incorporation of h-BN platelets. The TIMs developed in this study will make it possible to manage the heat of electric motors and will help to popularize electric vehicles.

77 FR 27817 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Approving a Proposed Rule Change To List...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-11

... its parent company or its affiliates. See id. \\9\\ See email from Tim Malinowski, Senior Director, NYSE... IIV is no longer calculated or available as required. \\17\\ See email from Tim Malinowski, Senior...

Medicinal properties of Peganum harmala L. in traditional Iranian medicine and modern phytotherapy: a review.

PubMed

Mina, Cheraghi Niroumand; Farzaei, Mohammad Hosein; Gholamreza, Amin

2015-02-01

To review the pharmacological activities of Peganum harmala L. (P. harmala, Nitrariaceae) in traditional Iranian medicine (TIM) and modern phytotherapy. Opinions of TIM and modern phytotherapy about safety and acceptable dosage of this plant are discussed. Various medical properties of P. harmala were collected from important TIM references and added to scientific reports derived from modern medical databases like PubMed, Scirus, ScienceDirect and Scopus. The main medicinal part of the plant is the seed. In TIM resources, this plant possesses various Pharmacological activities such as carminative, galactagogue, diuretic, emmenagogue, antithrombotic and analgesic. In modern phytotherapy, P. harmala demonstrated numerous medicinal effects including cardiovascular, neurologic, antimicrobial, insecticidal, antineoplasmic, antiproliferative, gastrointestinal and antidiabetic effects. Adverse events such as neuro-sensorial symptoms, visual hallucination, bradycardia, hypotension, agitation, tremors, ataxia, abortion and vomiting cause people to use this plant cautiously. P. harmala is contraindicated during pregnancy, due to its abortive and mutagenic activities. Because of increasing the expression of CYP1A2, 2C19, and 3A4 and inhibition of monoamine oxidase, the pharmacokinetic parameters of drugs which are mainly metabolized by these enzymes may be affected by P. harmala. The medicinal properties declared for this plant in TIM are compared with those showed in modern phytotherapy. Some of the TIM properties were confirmed in modern phytotherapy like emetic and analgesic activities and some have not been evaluated in modern phytotherapy such as its therapeutic effects on paralysis, epilepsy and numbness. Finally, the current review provides the evidence for other researchers to use TIM properties of P. harmala as an efficacious natural drug. Further preclinical and clinical studies for adequate evaluating safety and therapeutic efficacy are recommended.

Achieving DoD’s Net Centric Vision of Information Sharing While Overcoming Cultural Biases to Control Information

DTIC Science & Technology

2008-05-09

using better technology as a means might be an effective strategy to achieve desired effects and to reduce risk. Tim Berners - Lee , founder of the World...of information disclosure persecution. Tim Berners - Lee advises, “human communication scales up only if we can be tolerant of the differences while we...the government to define intended use Figure 1: Slide by Tim Berners - Lee at http://www.w3.org/2000/Talks/1206-xml2k- tbl.27 The Author added the

Increased Expression of T Cell Immunoglobulin and Mucin Domain 3 on CD14+ Monocytes Is Associated with Systemic Inflammatory Reaction and Brain Injury in Patients with Spontaneous Intracerebral Hemorrhage.

PubMed

Xu, ChangJun; Ge, HaiTao; Wang, Tao; Qin, JianBing; Liu, De; Liu, YuGuang

2018-05-01

To study the expression of T cell immunoglobulin and mucin domain 3 (Tim-3) on peripheral blood immunocytes, and the relationship between Tim-3 and the systemic inflammatory response or brain injury in patients with intracerebral hemorrhage (ICH). According to the volume of hematoma at 12 hours after onset of ICH, 60 newly diagnosed patients with ICH were divided into the small (volume of hematoma <30 mL, 30 cases) and large (volume of hematoma ≥30 mL, 30 cases) ICH groups. The expression of Tim-3 on peripheral blood immunocytes was analyzed by flow cytometry. Real-time reverse transcriptase polymerase chain reaction was used to detect Tim-3 mRNA on peripheral blood mononuclear cells (PBMCs). Meanwhile, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and S-100B protein were measured by enzyme-linked immunosorbent assay. Glasgow outcome scale (GOS) score at Day 30 was used to estimate prognosis of patients. The leukocyte count, neutrophil count, monocyte count, TNF-α, IL-1β, and S-100B protein increased remarkably after ICH. However, all of them in the large ICH group increased more obviously, and there were significant differences when compared with those in the small ICH group (P < .01). The expression of Tim-3 mRNA on PBMCs in the large ICH group increased remarkably, peaked at Day 3, and was positively associated with the concentrations of TNF-α, IL-1β, and S-100B protein (P < .01). Tim-3 was predominantly expressed itself on CD14 + monocytes. There was a negative correlation between GOS score and Tim-3 mRNA, TNF-α, IL-1β, or S-100B protein. The expression of Tim-3 on CD14 + monocytes involves in systemic inflammatory reaction after ICH and may be a novel treatment target. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Travoprost 0.004%/timolol 0.5%-fixed combination with and without benzalkonium chloride: a prospective, randomized, doubled-masked comparison of safety and efficacy

PubMed Central

Kitazawa, Y; Smith, P; Sasaki, N; Kotake, S; Bae, K; Iwamoto, Y

2011-01-01

Purpose The purpose of this study is to compare the safety and intraocular pressure (IOP)-lowering efficacy of travoprost/timolol in a benzalkonium chloride (BAK)-free fixed combination preserved with polyquaternium-1 (TRA/TIM BAK-free), with travoprost/timolol-fixed combination preserved with BAK (TRA/TIM), in patients with open-angle glaucoma or ocular hypertension. Methods In this prospective randomized controlled trial, subjects with IOP of at least 22 mm Hg in one or both eyes at 0900 h, and IOP of at least 21 mm Hg in one or both eyes at 1100 h and 1600 h at two eligibility visits were randomly assigned to receive either TRA/TIM BAK-free (n=195) or TRA/TIM (n=193), dosed once daily in the morning (0900 h) for 6 weeks. IOP was assessed at 0900 h, 1100 h, and 1600 h at each scheduled visit (baseline, 2 and 6 weeks after randomization). Results Mean IOP reduction across all visits and time points was 8.0 mm Hg in the TRA/TIM BAK-free group and 8.4 mm Hg in the TRA/TIM group (P=0.0943). The difference in mean IOP between groups ranged from 0.2 to 0.7 mm Hg across visits and time points, with a mean pooled difference of 0.4 mm Hg (95% CI: −0.1 to 0.8), demonstrating equivalence of the two formulations. The most common drug-related adverse event was hyperemia of the eye (ocular hyperemia and conjunctival hyperemia combined), occurring in 11.8% of the TRA/TIM BAK-free group and 13.0% of the TRA/TIM group. Conclusion Travoprost/timolol BAK-free demonstrated equivalence to travoprost/timolol preserved with BAK in efficacy. No clinically relevant differences in the safety profiles of travoprost/timolol BAK-free and travoprost/timolol preserved with BAK were identified. PMID:21701528

Travoprost 0.004%/timolol 0.5%-fixed combination with and without benzalkonium chloride: a prospective, randomized, doubled-masked comparison of safety and efficacy.

PubMed

Kitazawa, Y; Smith, P; Sasaki, N; Kotake, S; Bae, K; Iwamoto, Y

2011-09-01

The purpose of this study is to compare the safety and intraocular pressure (IOP)-lowering efficacy of travoprost/timolol in a benzalkonium chloride (BAK)-free fixed combination preserved with polyquaternium-1 (TRA/TIM BAK-free), with travoprost/timolol-fixed combination preserved with BAK (TRA/TIM), in patients with open-angle glaucoma or ocular hypertension. In this prospective randomized controlled trial, subjects with IOP of at least 22  mm Hg in one or both eyes at 0900  h, and IOP of at least 21  mm Hg in one or both eyes at 1100  h and 1600  h at two eligibility visits were randomly assigned to receive either TRA/TIM BAK-free (n=195) or TRA/TIM (n=193), dosed once daily in the morning (0900  h) for 6 weeks. IOP was assessed at 0900  h, 1100  h, and 1600  h at each scheduled visit (baseline, 2 and 6 weeks after randomization). Mean IOP reduction across all visits and time points was 8.0  mm Hg in the TRA/TIM BAK-free group and 8.4  mm Hg in the TRA/TIM group (P=0.0943). The difference in mean IOP between groups ranged from 0.2 to 0.7  mm Hg across visits and time points, with a mean pooled difference of 0.4  mm Hg (95% CI: -0.1 to 0.8), demonstrating equivalence of the two formulations. The most common drug-related adverse event was hyperemia of the eye (ocular hyperemia and conjunctival hyperemia combined), occurring in 11.8% of the TRA/TIM BAK-free group and 13.0% of the TRA/TIM group. Travoprost/timolol BAK-free demonstrated equivalence to travoprost/timolol preserved with BAK in efficacy. No clinically relevant differences in the safety profiles of travoprost/timolol BAK-free and travoprost/timolol preserved with BAK were identified.

Making the connection: advancing traffic incident management in transportation planning : a primer.

DOT National Transportation Integrated Search

2013-07-01

"The intent of this primer is to inform and guide traffic incident management (TIM) professionals and transportation planners to initiate and develop collaborative relationships and advance TIM programs through the metropolitan planning process. The ...

Concurrent Validity of the WISC-IV and DAS-II in Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Kuriakose, Sarah

2014-01-01

Cognitive assessments are used for a variety of research and clinical purposes in children with autism spectrum disorder (ASD). This study establishes concurrent validity of the Wechsler Intelligence Scales for Children-fourth edition (WISC-IV) and Differential Ability Scales-second edition (DAS-II) in a sample of children with ASD with a broad…

Can baseline ultrasound results help to predict failure to achieve DAS28 remission after 1 year of tight control treatment in early RA patients?

PubMed

Ten Cate, D F; Jacobs, J W G; Swen, W A A; Hazes, J M W; de Jager, M H; Basoski, N M; Haagsma, C J; Luime, J J; Gerards, A H

2018-01-30

At present, there are no prognostic parameters unequivocally predicting treatment failure in early rheumatoid arthritis (RA) patients. We investigated whether baseline ultrasonography (US) findings of joints, when added to baseline clinical, laboratory, and radiographical data, could improve prediction of failure to achieve Disease Activity Score assessing 28 joints (DAS28) remission (<2.6) at 1 year in newly diagnosed RA patients. A multicentre cohort of newly diagnosed RA patients was followed prospectively for 1 year. US of the hands, wrists, and feet was performed at baseline. Clinical, laboratory, and radiographical parameters were recorded. Primary analysis was the prediction by logistic regression of the absence of DAS28 remission 12 months after diagnosis and start of therapy. Of 194 patients included, 174 were used for the analysis, with complete data available for 159. In a multivariate model with baseline DAS28 (odds ratio (OR) 1.6, 95% confidence interval (CI) 1.2-2.2), the presence of rheumatoid factor (OR 2.3, 95% CI 1.1-5.1), and type of monitoring strategy (OR 0.2, 95% CI 0.05-0.85), the addition of baseline US results for joints (OR 0.96, 95% CI 0.89-1.04) did not significantly improve the prediction of failure to achieve DAS28 remission (likelihood ratio test, 1.04; p = 0.31). In an early RA population, adding baseline ultrasonography of the hands, wrists, and feet to commonly available baseline characteristics did not improve prediction of failure to achieve DAS28 remission at 12 months. Clinicaltrials.gov, NCT01752309 . Registered on 19 December 2012.

Agronomic performance of insect-protected and herbicide-tolerant MON 89034 × TC1507 × NK603 × DAS-40278-9 corn is equivalent to that of conventional corn.

PubMed

de Cerqueira, Denise T Rezende; Schafer, Ariane C; Fast, Brandon J; Herman, Rod A

2017-07-03

Agronomic characteristics of genetically modified (GM) MON 89034 × TC1507 × NK603 × DAS-40278-9 (PowerCore™ Enlist™), MON 89034 × TC1507 × NK603 (PowerCore™), and DAS-40278-9 (Enlist™) corn, a non-GM near-isogenic hybrid, and 2 commercial non-GM hybrids were assessed in a field study to determine if the agronomic performance of the GM corn hybrids is equivalent to that of non-transgenic hybrid corn. The MON 89034 × TC1507 × NK603 × DAS-40278-9 hybrid corn was developed through stacking of 4 individual transgenic events, MON 89034, TC1507, NK603, and DAS-40278-9 by traditional breeding and contains the cry1A.105 and cry2Ab2 (MON 89034), cry1F and pat (TC1507), cp4 epsps (NK603) and aad-1 (DAS-40278-9) transgenes. These transgenes encode the proteins Cry1A.105, Cry2Ab2, and Cry1F, which confer insect resistance, PAT, CP4 EPSPS, and AAD-1, which confer herbicide tolerance. The following agronomic characteristics were assessed in the study: initial and final stand count, seedling vigor, time to silk, time to pollen shed, pollen viability, plant height, ear height, stalk lodging, root lodging, days to maturity, stay green, disease incidence, insect damage, herbicide injury, and yield. The agronomic assessment was conducted in 2 regions of Brazil (Indianopolis-MG; Cravinhos-SP). The agronomic attributes for all GM entries were statistically indistinguishable from the non-GM near-isogenic hybrid. In addition, most of the agronomic assessments fell within the range of the commercial varieties included in the study. Taken together, MON 89034 × TC1507 × NK603 × DAS-40278, MON 89034 × TC1507 × NK603, and DAS-40278-9 were found to be agronomically equivalent to non-GM corn.

OCT-based in vivo tissue injury mapping

NASA Astrophysics Data System (ADS)

Baran, Utku; Li, Yuandong; Wang, Ruikang K.

2016-03-01

Tissue injury mapping (TIM) is developed by using a non-invasive in vivo optical coherence tomography to generate optical attenuation coefficient and microvascular map of the injured tissue. Using TIM, the infarct region development in mouse cerebral cortex during stroke is visualized. Moreover, we demonstrate the in vivo human facial skin structure and microvasculature during an acne lesion development. The results indicate that TIM may help in the study and the treatment of various diseases by providing high resolution images of tissue structural and microvascular changes.

76 FR 64382 - Agency Information Collection Activities: Proposed Collection; Comments Requested

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-18

... Collection Under Review: Office for Victims of Crime Trafficking Information Management System (TIMS). The... following information collection request to the Office of Management and Budget (OMB) for review and... Trafficking Information Management System (TIMS) Online. [[Page 64383

System integration case study : FAST-TRAC : preliminary IV deliverable : #2-systems integration case study

DOT National Transportation Integrated Search

1999-02-12

This report focuses on the system integration aspect of the Transportation Information Management System (TIMS), a component of the FAST-TRAC project. The TIMS functions as the center of a communications network which integrates advanced traffic cont...

DasPy – Open Source Multivariate Land Data Assimilation Framework with High Performance Computing

NASA Astrophysics Data System (ADS)

Han, Xujun; Li, Xin; Montzka, Carsten; Kollet, Stefan; Vereecken, Harry; Hendricks Franssen, Harrie-Jan

2015-04-01

Data assimilation has become a popular method to integrate observations from multiple sources with land surface models to improve predictions of the water and energy cycles of the soil-vegetation-atmosphere continuum. In recent years, several land data assimilation systems have been developed in different research agencies. Because of the software availability or adaptability, these systems are not easy to apply for the purpose of multivariate land data assimilation research. Multivariate data assimilation refers to the simultaneous assimilation of observation data for multiple model state variables into a simulation model. Our main motivation was to develop an open source multivariate land data assimilation framework (DasPy) which is implemented using the Python script language mixed with C++ and Fortran language. This system has been evaluated in several soil moisture, L-band brightness temperature and land surface temperature assimilation studies. The implementation allows also parameter estimation (soil properties and/or leaf area index) on the basis of the joint state and parameter estimation approach. LETKF (Local Ensemble Transform Kalman Filter) is implemented as the main data assimilation algorithm, and uncertainties in the data assimilation can be represented by perturbed atmospheric forcings, perturbed soil and vegetation properties and model initial conditions. The CLM4.5 (Community Land Model) was integrated as the model operator. The CMEM (Community Microwave Emission Modelling Platform), COSMIC (COsmic-ray Soil Moisture Interaction Code) and the two source formulation were integrated as observation operators for assimilation of L-band passive microwave, cosmic-ray soil moisture probe and land surface temperature measurements, respectively. DasPy is parallelized using the hybrid MPI (Message Passing Interface) and OpenMP (Open Multi-Processing) techniques. All the input and output data flow is organized efficiently using the commonly used NetCDF file

[Trachoma epidemiological school survey in the city of Embu das Artes--SP].

PubMed

Caninéo, Paulo Antonio; Nishimura, Shizuko; Medina, Norma Helen; Koizumi, Inês Kazue; Cardoso, Maria Regina Alves

2012-01-01

To estimate the trachoma prevalence in school children in Embu das Artes - SP, aiming the implementation of the disease epidemiological surveillance. The city of Embu das Artes - SP, is 25 km far from the capital of the State. In the years of 2003-2004, a trachoma survey was conducted in a cluster sample of school children with the same methodology of the national trachoma student's survey of the Ministry of Health. Previously to the trachoma active search, activities of health education were performed in all schools. External ocular examinations were done in all students to detect trachoma according to the WHO criteria. All cases of trachoma were notified and their families were submitted to an external ocular examination. The cases were treated with 1% tetracycline ointment or systemic azithromycin. 2,374 students from nine sampled selected public schools were examined. The prevalence of follicular inflammatory trachoma (TF) was 3.1% (IC 95%: 2.4-3.9), varying from 0.5% to 4.2% in the examined schools. The prevalence for males was 3.2% and for females was 3.0%. The greater prevalence (8.6%) was found in 6 year-old children. The disease showed a mild behavior in this city, because no cases of intense inflammatory trachoma or cicatricial trachoma were detected. However, the prevalence was greater than the one found in the city of São Paulo. Epidemiological surveillance activities of trachoma must be continuous, mainly in places where the greater prevalence had been found.

Autologous Stem Cell Transplantation in Patients With Multiple Myeloma: An Activity-based Costing Analysis, Comparing a Total Inpatient Model Versus an Early Discharge Model.

PubMed

Martino, Massimo; Console, Giuseppe; Russo, Letteria; Meliado', Antonella; Meliambro, Nicola; Moscato, Tiziana; Irrera, Giuseppe; Messina, Giuseppe; Pontari, Antonella; Morabito, Fortunato

2017-08-01

Activity-based costing (ABC) was developed and advocated as a means of overcoming the systematic distortions of traditional cost accounting. We calculated the cost of high-dose chemotherapy and autologous stem cell transplantation (ASCT) in patients with multiple myeloma using the ABC method, through 2 different care models: the total inpatient model (TIM) and the early-discharge outpatient model (EDOM) and compared this with the approved diagnosis related-groups (DRG) Italian tariffs. The TIM and EDOM models involved a total cost of €28,615.15 and €16,499.43, respectively. In the TIM model, the phase with the greatest economic impact was the posttransplant (recovery and hematologic engraftment) with 36.4% of the total cost, whereas in the EDOM model, the phase with the greatest economic impact was the pretransplant (chemo-mobilization, apheresis procedure, cryopreservation, and storage) phase, with 60.4% of total expenses. In an analysis of each episode, the TIM model comprised a higher absorption than the EDOM. In particular, the posttransplant represented 36.4% of the total costs in the TIM and 17.7% in EDOM model, respectively. The estimated reduction in cost per patient using an EDOM model was over €12,115.72. The repayment of the DRG in Calabrian Region for the ASCT procedure is €59,806. Given the real cost of the transplant, the estimated cost saving per patient is €31,190.85 in the TIM model and €43,306.57 in the EDOM model. In conclusion, the actual repayment of the DRG does not correspond to the real cost of the ASCT procedure in Italy. Moreover, using the EDOM, the cost of ASCT is approximately the half of the TIM model. Copyright © 2017 Elsevier Inc. All rights reserved.

Previsional space during direct laryngoscopy

PubMed Central

Park, Seongjoo; Han, Ji-Won; Cha, Sukwon; Han, Sung-Hee; Kim, Jin-Hee

2017-01-01

Abstract The laryngoscope should displace oral soft tissues forward out of the operator's vision. Therefore, the space in front of the view may be critical for determining the laryngoscopic view. The aim was to investigate the difference in the previsional space during difficult versus easy laryngoscopy (EL). Under general anesthesia, digital photographs of the lateral view of the head and neck were taken in the horizontal sniffing position, after head extension, and during laryngoscopy with a defined force (50 N). Three points (thyroid notch (T), maxillary incisor (I), and mandibular mentum (M)) were marked on the photograph. The previsional space was defined as the TIM triangle. We compared these areas and other variables of the TIM triangle between male patients with difficult laryngoscopy (DL: Cormack–Lehane III–IV, n = 12) versus those of age- and body mass index-matched male patients with EL (Cormack–Lehane I–II, n = 12). When the head was extended, the areas TIM triangle in DL were significantly smaller than in EL. During laryngoscopy, all values of the TIM triangle in DL, including the TIM area (16.4 ± 3.7 vs 22.6 ± 2.8 cm2, P < .01), were significantly smaller than the values in EL. The previsional space was smaller in patients with DL than in those with EL. The TIM triangle could suggest new way to explain the mechanism underlying DL. PMID:28682897

Interspecific studies of circadian genes period and timeless in Drosophila.

PubMed

Noreen, Shumaila; Pegoraro, Mirko; Nouroz, Faisal; Tauber, Eran; Kyriacou, Charalambos P

2018-03-30

The level of rescue of clock function in genetically arrhythmic Drosophila melanogaster hosts using interspecific clock gene transformation was used to study the putative intermolecular coevolution between interacting clock proteins. Among them PER and TIM are the two important negative regulators of the circadian clock feedback loop. We transformed either the D. pseudoobscura per or tim transgenes into the corresponding arrhythmic D. melanogaster mutant (per01 or tim01) and observed >50% rhythmicity but the period of activity rhythm was either longer (D. pseudoobscura-per) or shorter than 24 h (D. pseudoobscura-tim) compared to controls. By introducing both transgenes simultaneously into double mutants, we observed that the period of the activity rhythm was rescued by the pair of hemizygous transgenes (~24 h). These flies also showed a more optimal level of temperature compensation for the period. Under LD 12:12 these flies have a D. pseudoobscura like activity profile with the absence of morning anticipation as well as a very prominent earlier evening peak of activity rhythm. These observation are consistent with the view that TIM and PER form a heterospecific coevolved module at least for the circadian period of activity rhythms. However the strength of rhythmicity was reduced by having both transgenes present, so while evidence for a coevolution between PER and TIM is observed for some characters it is not for others. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Previsional space during direct laryngoscopy: Implication in the difficult laryngoscopy.

PubMed

Park, Seongjoo; Han, Ji-Won; Cha, Sukwon; Han, Sung-Hee; Kim, Jin-Hee

2017-07-01

The laryngoscope should displace oral soft tissues forward out of the operator's vision. Therefore, the space in front of the view may be critical for determining the laryngoscopic view. The aim was to investigate the difference in the previsional space during difficult versus easy laryngoscopy (EL).Under general anesthesia, digital photographs of the lateral view of the head and neck were taken in the horizontal sniffing position, after head extension, and during laryngoscopy with a defined force (50 N). Three points (thyroid notch (T), maxillary incisor (I), and mandibular mentum (M)) were marked on the photograph. The previsional space was defined as the TIM triangle. We compared these areas and other variables of the TIM triangle between male patients with difficult laryngoscopy (DL: Cormack-Lehane III-IV, n = 12) versus those of age- and body mass index-matched male patients with EL (Cormack-Lehane I-II, n = 12).When the head was extended, the areas TIM triangle in DL were significantly smaller than in EL. During laryngoscopy, all values of the TIM triangle in DL, including the TIM area (16.4 ± 3.7 vs 22.6 ± 2.8 cm, P < .01), were significantly smaller than the values in EL.The previsional space was smaller in patients with DL than in those with EL. The TIM triangle could suggest new way to explain the mechanism underlying DL.

The Mitochondrial Protein Import Component, TRANSLOCASE OF THE INNER MEMBRANE17-1, Plays a Role in Defining the Timing of Germination in Arabidopsis1[W][OPEN

PubMed Central

Wang, Yan; Law, Simon R.; Ivanova, Aneta; van Aken, Olivier; Kubiszewski-Jakubiak, Szymon; Uggalla, Vindya; van der Merwe, Margaretha; Duncan, Owen; Narsai, Reena; Whelan, James; Murcha, Monika W.

2014-01-01

In Arabidopsis (Arabidopsis thaliana), small gene families encode multiple isoforms for many of the components of the mitochondrial protein import apparatus. There are three isoforms of the TRANSLOCASE OF THE INNER MEMBRANE17 (Tim17). Transcriptome analysis indicates that AtTim17-1 is only detectable in dry seed. In this study, two independent transfer DNA insertional mutant lines of tim17-1 exhibited a germination-specific phenotype, showing a significant increase in the rate of germination. Microarray analyses revealed that Attim17-1 displayed alterations in the temporal sequence of transcriptomic events during germination, peaking earlier compared with the wild type. Promoter analysis of AtTim17-1 further identified an abscisic acid (ABA)-responsive element, which binds ABA-responsive transcription factors, acting to repress the expression of AtTim17-1. Attim17-1 dry seeds contained significantly increased levels of ABA and gibberellin, 2- and 5-fold, respectively. These results support the model that mitochondrial biogenesis is regulated in a tight temporal sequence of events during germination and that altering mitochondrial biogenesis feeds back to alter the germination rate, as evidenced by the altered levels of the master regulatory hormones that define germination. PMID:25253887

Thermally Conductive-Silicone Composites with Thermally Reversible Cross-links.

PubMed

Wertz, J T; Kuczynski, J P; Boday, D J

2016-06-08

Thermally conductive-silicone composites that contain thermally reversible cross-links were prepared by blending diene- and dienophile-functionalized polydimethylsiloxane (PDMS) with an aluminum oxide conductive filler. This class of thermally conductive-silicones are useful as thermal interface materials (TIMs) within Information Technology (IT) hardware applications to allow rework of valuable components. The composites were rendered reworkable via retro Diels-Alder cross-links when temperatures were elevated above 130 °C and required little mechanical force to remove, making them advantageous over other TIM materials. Results show high thermal conductivity (0.4 W/m·K) at low filler loadings (45 wt %) compared to other TIM solutions (>45 wt %). Additionally, the adhesion of the material was found to be ∼7 times greater at lower temperatures (25 °C) and ∼2 times greater at higher temperatures (120 °C) than commercially available TIMs.

Sensitivity of polar ozone recovery predictions of the GMI 3D CTM to GCM and DAS dynamics

NASA Astrophysics Data System (ADS)

Considine, D.; Connell, P.; Strahan, S.; Douglass, A.; Rotman, D.

2003-04-01

The Global Modeling Initiative (GMI) 3-D chemistry and transport model has been used to generate 2 simulations of the 1995-2030 time period. The 36-year simulations both used the source gas and aerosol boundary conditions of the 2002 World Meteorological Organization assessment exercise MA2. The first simulation was based on a single year of meteorological data (winds, temperatures) generated by the new Goddard Space Flight Center "Finite Volume" General Circulation Model (FVGCM), repeated for each year of the simulation. The second simulation used a year of meteorological data generated by a new data assimilation system based on the FVGCM (FVDAS), using observations for July 1, 1999 - June 30, 2000. All other aspects of the two simulations were identical. The increase in vortex-averaged south polar springtime ozone concentrations in the lower stratosphere over the course of the simulations is more robust in the simulation driven by the GCM meteorological data than in the simulation driven by DAS winds. At the same time, the decrease in estimated chemical springtime ozone loss is similar. We thus attribute the differences between the two simulations to differences in the representations of polar dynamics which reduce the sensitivity of the simulation driven by DAS winds to changes in vortex chemistry. We also evaluate the representations in the two simulations of trace constituent distributions in the current polar lower stratosphere using various observations. In these comparisons the GCM-based simulation often is in better agreement with the observations than the DAS-based simulation.

Division of Forestry Directory

Science.gov Websites

Regional Regional Forester Tim Dabney tim.dabney@alaska.gov (907) 761-6238 Fairbanks/Delta Area Fairbanks Sanford, Fire Management Officer (907) 451-2634 edward.sanford@alaska.gov Delta Office P.O. Box 1149 Delta

Binding thermodynamics of phosphorylated inhibitors to triosephosphate isomerase and the contribution of electrostatic interactions.

PubMed

Serratos, Iris N; Pérez-Hernández, Gerardo; Garza-Ramos, Georgina; Hernández-Arana, Andrés; González-Mondragón, Edith; Zubillaga, Rafael A

2011-01-07

Electrostatic interactions have a central role in some biological processes, such as recognition of charged ligands by proteins. We characterized the binding energetics of yeast triosephosphate isomerase (TIM) with phosphorylated inhibitors 2-phosphoglycollate (2PG) and phosphoglycolohydroxamate (PGH). We determined the thermodynamic parameters of the binding process (K(b), ΔG(b), ΔH(b), ΔS(b) and ΔC(p)) with different concentrations of NaCl, using fluorimetric and calorimetric titrations in the conventional mode of ITC and a novel method, multithermal titration calorimetry (MTC), which enabled us to measure ΔC(p) in a single experiment. We ruled out specific interactions of Na(+) and Cl(-) with the native enzyme and did not detect significant linked protonation effects upon the binding of inhibitors. Increasing ionic strength (I) caused K(b), ΔG(b) and ΔH(b) to become less favorable, while ΔS(b) became less unfavorable. From the variation of K(b) with I, we determined the electrostatic contribution of TIM-2PG and TIM-PGH to ΔG(b) at I=0.06 M and 25 °C to be 36% and 26%, respectively. The greater affinity of PGH for TIM is due to a more favorable ΔH(b) compared to 2PG (by 19-24 kJ mol(-1) at 25 °C). This difference is compatible with PGH establishing up to five more hydrogen bonds with TIM. Both binding ΔC(p)s were negative, and less negative with increasing ionic strength. ΔC(p)s at I=0.06 M were much more negative than predicted by surface area models. Water molecules trapped in the interface when ligands bind to protein could explain the highly negative ΔCps. Thermodynamic binding functions for TIM-2PG changed more with ionic strength than those for TIM-PGH. This greater dependence is consistent with linked, but compensated, protonation equilibriums yielding the dianionic species of 2PG that binds to TIM, process that is not required for PGH. Copyright © 2010 Elsevier Ltd. All rights reserved.

Identification of the critical residues responsible for differential reactivation of the triosephosphate isomerases of two trypanosomes

PubMed Central

Rodríguez-Bolaños, Monica; Cabrera, Nallely

2016-01-01

The reactivation of triosephosphate isomerase (TIM) from unfolded monomers induced by guanidine hydrochloride involves different amino acids of its sequence in different stages of protein refolding. We describe a systematic mutagenesis method to find critical residues for certain physico-chemical properties of a protein. The two similar TIMs of Trypanosoma brucei and Trypanosoma cruzi have different reactivation velocities and efficiencies. We used a small number of chimeric enzymes, additive mutants and planned site-directed mutants to produce an enzyme from T. brucei with 13 mutations in its sequence, which reactivates fast and efficiently like wild-type (WT) TIM from T. cruzi, and another enzyme from T. cruzi, with 13 slightly altered mutations, which reactivated slowly and inefficiently like the WT TIM of T. brucei. Our method is a shorter alternative to random mutagenesis, saturation mutagenesis or directed evolution to find multiple amino acids critical for certain properties of proteins. PMID:27733588

INTERIM RESULTS FROM A STUDY OF THE IMPACTS OF TIN(II) BASED MERCURY TREATMENT IN A SMALL STREAM ECOSYSTEM: TIMS BRANCH, SAVANNAH RIVER SITE

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

Looney, B.; Bryan, L.; Mathews, T.

2012-03-30

source control measures have resulted in rapid responses in lake or reservoir fisheries (Joslin 1994, Turner and Southworth 1999; Orihel et al., 2007), but examples of similar responses in Hg-contaminated stream ecosystems are less common. Recent work suggests that stream systems may actually be more susceptible to mercury bioaccumulation than lakes, highlighting the need to better understand the ecological drivers of mercury bioaccumulation in stream-dwelling fish (Chasar et al. 2009, Ward et al. 2010). In the present study we examine the response of fish to remedial actions in Tims Branch, a point-source contaminated stream on the Department of Energy's (DOE) Savannah River Site in Aiken, South Carolina. This second order stream received inorganic mercury inputs at its headwaters from the 1950s-2000s which contaminated the water, sediments, and biota downstream. In 2007, an innovative mercury removal system using tin (II) chloride (stannous chloride, SnCl{sub 2}) was implemented at a pre-existing air stripper. Tin(II) reduces dissolved Hg (II) to Hg (0), which is removed by the air stripper. During this process, tin(II) is oxidized to tin (IV) which is expected to precipitate as colloidal tin(IV) oxides and hydroxides, particulate materials with relatively low toxicity (Hallas and Cooney, 1981, EPA 2002, ATSDR, 2005). The objectives of the present research are to provide an initial assessment of the net impacts of the tin(II) based mercury treatment on key biota and to document the distribution and fate of inorganic tin in this small stream ecosystem after the first several years of operating a full scale system. To support these objectives, we collected fish, sediment, water, invertebrates, and biofilm samples from Tims Branch to quantify the general behavior and accumulation patterns for mercury and tin in the ecosystem and to determine if the treatment process has resulted in: (1) a measurable beneficial impact on (i.e., decrease of) mercury concentration in upper

An RNAi Screen To Identify Protein Phosphatases That Function Within the Drosophila Circadian Clock.

PubMed

Agrawal, Parul; Hardin, Paul E

2016-12-07

Circadian clocks in eukaryotes keep time via cell-autonomous transcriptional feedback loops. A well-characterized example of such a transcriptional feedback loop is in Drosophila, where CLOCK-CYCLE (CLK-CYC) complexes activate transcription of period (per) and timeless (tim) genes, rising levels of PER-TIM complexes feed-back to repress CLK-CYC activity, and degradation of PER and TIM permits the next cycle of CLK-CYC transcription. The timing of CLK-CYC activation and PER-TIM repression is regulated posttranslationally, in part through rhythmic phosphorylation of CLK, PER, and TIM. Previous behavioral screens identified several kinases that control CLK, PER, and TIM levels, subcellular localization, and/or activity, but two phosphatases that function within the clock were identified through the analysis of candidate genes from other pathways or model systems. To identify phosphatases that play a role in the clock, we screened clock cell-specific RNA interference (RNAi) knockdowns of all annotated protein phosphatases and protein phosphatase regulators in Drosophila for altered activity rhythms. This screen identified 19 protein phosphatases that lengthened or shortened the circadian period by ≥1 hr (p ≤ 0.05 compared to controls) or were arrhythmic. Additional RNAi lines, transposon inserts, overexpression, and loss-of-function mutants were tested to independently confirm these RNAi phenotypes. Based on genetic validation and molecular analysis, 15 viable protein phosphatases remain for future studies. These candidates are expected to reveal novel features of the circadian timekeeping mechanism in Drosophila that are likely to be conserved in all animals including humans. Copyright © 2016 Agrawal and Hardin.

Efficacy and Safety of Switching Prostaglandin Analog Monotherapy to Tafluprost/Timolol Fixed-Combination Therapy

PubMed Central

Kitamura, Kazuyoshi; Chiba, Tatsuya; Mabuchi, Fumihiko; Ishijima, Kiyotaka; Omoto, Shu; Kashiwagi, Fumiko; Godo, Takashi; Kogure, Satoshi; Goto, Teruhiko; Shibuya, Takashi; Tanabe, Jhoji; Tsukahara, Shigeo; Tsuchiya, Tadaharu; Tokunaga, Takaharu; Hosaka, Osamu; Saito, Tetsunori

2018-01-01

Purpose To assess the efficacy and safety of switching from prostaglandin analog (PGA) monotherapy to tafluprost/timolol fixed-combination (Taf/Tim) therapy. Subjects and Methods Patients with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension who had received PGA monotherapy for at least 3 months were enrolled. Patients were examined at 1, 2, and 3 months after changing therapies. Subsequently, the patients were returned to PGA monotherapy. The examined parameters included intraocular pressure (IOP) and adverse events. A questionnaire survey was conducted after the switch to Taf/Tim therapy. Results Forty patients with a mean age of 66.5 ± 10.3 years were enrolled; 39 of these patients completed the study protocol. Switching to Taf/Tim significantly reduced the IOP from 18.2 ± 2.6 mmHg at baseline to 14.8 ± 2.5 mmHg at 1 month, 15.2 ± 2.8 mmHg at 2 months, and 14.9 ± 2.5 mmHg at 3 months (P < 0.001). Switching back to the original PGA monotherapy returned the IOP values to baseline levels. Taf/Tim reduced the pulse rate insignificantly. No significant differences were observed in blood pressure, conjunctival hyperemia, or corneal adverse events. A questionnaire showed that the introduction of Taf/Tim did not significantly influence symptoms. Conclusions Compared with PGA monotherapy, Taf/Tim fixed-combination therapy significantly reduced IOP without severe adverse events. PMID:29675274

Timolol LA: a double-masked, active-controlled, randomized, crossover, comfort, ocular safety, and systemic bioavailability study in healthy volunteers.

PubMed

Mundorf, Thomas K; Ogawa, Takahiro; Inui, Noritsugu; Naka, Hiroaki; Novack, Gary D; Crockett, R Stephens

2005-03-01

A new formulation of timolol with sorbic acid, timolol-LA (TLA) (Istaloldagger), has been developed which increases its ocular bioavailability. In the present study, we desired to evaluate the ocular comfort and systemic bioavailability of TLA in healthy volunteers in comparison to standard timolol maleate ophthalmic solution (TIM). This study was a randomized, double-masked, active-controlled, crossover evaluation of 0.5% TLA and 0.5% TIM, bid, in 12 normal healthy volunteers. Visits were at Days 0, 1, 2, 4 and 8 in each period, and there was a minimum 7 day interperiod washout. At all three post-dosing evaluation times (Day 1: Peak, Day 8: Trough, and Day 8: Peak), the 95% confidence interval for the difference between TLA and TIM was not more than 0.37 ng/mL. After administration of TLA, there was a greater incidence of burning/stinging and tearing, but not foreign body sensation, relative to TIM. In general, most symptoms were mild in intensity, and no subject discontinued treatment due to ocular discomfort. Both treatments decreased IOP to a similar level. TLA was relatively comfortable, with a safety profile consistent with further clinical development, and, with bid dosing (exaggerated [2X] that anticipated for clinical use), had a systemic bioavailability similar to that of TIM 0.5%, bid. The incidence of burning and stinging was higher with TLA than with TIM, although reports were mild in severity and did not result in any patient discontin uations. Although the results are of interest, further evaluation in a larger trial may be warranted.

76 FR 50499 - Agency Information Collection Activities: Proposed Collection; Comments Requested; Office for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-15

... Information Management System (TIMS) ACTION: 60-Day Notice of Information Collection Under Review. The... information collection request to the Office of Management and Budget (OMB) for review and approval in...: Trafficking Information Management System (TIMS) Online. (3) The Agency form number, if any, and the...

Carbon nanotube thermal interfaces and related applications

NASA Astrophysics Data System (ADS)

Hodson, Stephen L.

The development of thermal interface materials (TIMs) is necessitated by the temperature drop across interfacing materials arising from macro and microscopic irregularities of their surfaces that constricts heat through small contact regions as well as mismatches in their thermal properties. Similar to other types of TIMs, CNT TIMs alleviate the thermal resistance across the interface by thermally bridging two materials together with cylindrical, high-aspect ratio, and nominally vertical conducting elements. Within the community of TIM engineers, the vision driving the development of CNT TIMs was born from measurements that revealed impressively high thermal conductivities of individual CNTs. This vision was then projected to efforts focused on packing many individual CNTs on a single substrate that efficiently conduct heat in parallel and ultimately through many contact regions at CNT-to-substrate contacts. This thesis encompasses a comprehensive investigation of the viability of carbon nanotube based thermal interface materials (CNT TIMs) to efficiently conduct heat across two contacting materials. The efforts in this work were initially devoted to engaging CNT TIMs with an opposing substrate using two bonding techniques. Using palladium hexadecanethiolate, Pd(SC16H35)2 the CNT ends were bonded to an opposing substrate (one-sided interface) or opposing CNT array (two-sided interface) to enhance contact conductance while maintaining a compliant joint. The palladium weld is particularly attractive for its mechanical stability at high temperatures. The engagement of CNT TIMs with an opposing substrate was also achieved by inserting a solder foil between the CNT TIM and opposing substrate and subsequently raising the temperature of the interface above the eutectic point of the solder foil. This bonding technique creates a strong weld that not only reduces the thermal resistance significantly but also minimizes the change in thermal resistance with an applied

Reconstitution of the protein insertion machinery of the mitochondrial inner membrane.

PubMed Central

Haucke, V; Schatz, G

1997-01-01

We have reconstituted the protein insertion machinery of the yeast mitochondrial inner membrane into proteoliposomes. The reconstituted proteoliposomes have a distinct morphology and protein composition and correctly insert the ADP/ATP carrier (AAC) and Tim23p, two multi-spanning integral proteins of the mitochondrial inner membrane. The reconstituted system requires a membrane potential, but not Tim44p or mhsp70, both of which are required for the ATP-driven translocation of proteins into the matrix. The protein insertion machinery can thus operate independently of the energy-transducing Tim44p-mhsp70 complex. PMID:9303300

Virtual Airspace Modeling and Simulation (VAMS) Project First Technical Interchange Meeting

NASA Technical Reports Server (NTRS)

Beard, Robert; Kille, Robert; Kirsten, Richard; Rigterink, Paul; Sielski, Henry; Gratteau, Melinda F. (Editor)

2002-01-01

A three-day NASA Virtual Airspace and Modeling Project (VAMS) Technical Interchange Meeting (TIM) was held at the NASA Ames Research Center in Mountain View, CA. on May 21 through May 23,2002. The purpose of this meeting was to share initial concept information sponsored by the VAMS Project. An overall goal of the VAMS Project is to develop validated, blended, robust and transition-able air transportation system concepts over the next five years that will achieve NASA's long-term Enterprise Aviation Capacity goals. This document describes the presentations at the TIM, their related questions and answers, and presents the TIM recommendations.

Measuring Primary Teachers' Attitudes toward Teaching Science: Development of the Dimensions of Attitude toward Science (DAS) Instrument

ERIC Educational Resources Information Center

van Aalderen-Smeets, Sandra; Walma van der Molen, Juliette

2013-01-01

In this article, we present a valid and reliable instrument which measures the attitude of in-service and pre-service primary teachers toward teaching science, called the Dimensions of Attitude Toward Science (DAS) Instrument. Attention to the attitudes of primary teachers toward teaching science is of fundamental importance to the…

CK1/Doubletime activity delays transcription activation in the circadian clock

PubMed Central

O'Neil, Jenna L; Merz, Gregory E; Dusad, Kritika; Crane, Brian R; Young, Michael W

2018-01-01

In the Drosophila circadian clock, Period (PER) and Timeless (TIM) proteins inhibit Clock-mediated transcription of per and tim genes until PER is degraded by Doubletime/CK1 (DBT)-mediated phosphorylation, establishing a negative feedback loop. Multiple regulatory delays within this feedback loop ensure ~24 hr periodicity. Of these delays, the mechanisms that regulate delayed PER degradation (and Clock reactivation) remain unclear. Here we show that phosphorylation of certain DBT target sites within a central region of PER affect PER inhibition of Clock and the stability of the PER/TIM complex. Our results indicate that phosphorylation of PER residue S589 stabilizes and activates PER inhibitory function in the presence of TIM, but promotes PER degradation in its absence. The role of DBT in regulating PER activity, stabilization and degradation ensures that these events are chronologically and biochemically linked, and contributes to the timing of an essential delay that influences the period of the circadian clock. PMID:29611807

Expression of immune checkpoints in T cells of esophageal cancer patients.

PubMed

Xie, Jinhua; Wang, Ji; Cheng, Shouliang; Zheng, Liangfeng; Ji, Feiyue; Yang, Lin; Zhang, Yan; Ji, Haoming

2016-09-27

Inhibition of immune checkpoint proteins (checkpoints) has become a promising anti-esophageal cancer strategy. We here tested expressions of immune checkpoints in human esophageal cancers. Our results showed the expressions of many immune checkpoints, including CD28, CD27, CD137L, programmed death 1 (PD-1), T cell immunoglobulin mucin-3 (TIM-3), T cell Ig and ITIM domain (TIGIT), CD160, cytotoxic T lymphocyte antigen 4 (CTLA-4), CD200, CD137 and CD158, were dysregulated in peripheral T cells of esophageal cancer patients. Further, the expressions of PD-1, TIM-3 and TIGIT were upregulated in tumor infiltrating lymphocytes (TILs), which might be associated with TILs exhaustion. Meanwhile, the expressions of PD-1 and TIM-3 on CD4+ T cells were closely associated with clinic pathological features of esophageal cancer patients. These results indicate that co-inhibitory receptors PD-1, TIM-3 and TIGIT may be potential therapeutic oncotargets for esophageal cancer.

Código para imageamento indireto de estrelas em sistemas binarios: simulação de variações elipsoidais e do perfil das linhas

NASA Astrophysics Data System (ADS)

Souza, T. R.; Baptista, R.

2003-08-01

As estrelas secundárias em variáveis cataclí smicas (VCs) e binárias-x de baixa massa (BXBMs) são cruciais para o entendimento da origem, evolução e comportamento destas binárias interagentes. Elas são estrelas magneticamente ativas submetidas a condições ambientais extremas [e.g., estão muito próximas de uma fonte quente e irradiante; têm rotação extremamente rápida e forma distorcida; estão perdendo massa a taxas de 10-8-10-10 M¤/ano] que contribuem para que suas propriedades sejam distintas das de estrelas de mesma massa na seqüência principal. Por outro lado, o padrão de irradiação na face da secundária fornece informação sobre a geometria das estruturas de acréscimo em torno da estrela primária. Assim, a obtenção de imagens da superfície destas estrelas é de grande interesse astrofísico. A Tomografia Roche usa as variações no perfil das linhas de emissão/absorção da estrela secundária em função da fase orbital para mapear a distribuição de brilho em sua superfície. Neste trabalho apresentamos os resultados iniciais do desenvolvimento de um programa para o mapeamento da distribuição de brilho na superfí cie das estrelas secundárias em VCs e BXBMs com técnicas de astro-tomografia. Presentemente temos em operação um código que simula as variações no perfil das linhas em conseqüência de efeito Doppler resultante da combinação de rotação e translação de uma estrela em forma de lobo de Roche em torno do centro de massa da binária, em função da distribuição de brilho na superfície desta estrela. O código igualmente produz a curva de luz resultante das variações de aspecto da estrela em função da fase orbital (variações elipsoidais).

Sobre o uso das séries de Puiseux em mecanica celeste

NASA Astrophysics Data System (ADS)

Miloni, O. I.

2003-08-01

Neste trabalho é apresentada uma demonstração do uso dos diferentes desenvolvimentos em séries para as equações de perturbação em Mecânica Celeste no marco Hamiltoniano. Em trabalhos clássicos como os de Poincaré (Poincaré, 1893) por exemplo, já esta planteado o uso de potências não inteiras no pequeno parâmetro, o que evidencia a não analiticidade das funções quando uma ressonância ocorre. Nestes trabalhos os desenvolvimentos são na raíz quadrada da massa de Júpiter (o pequeno parâmetro). Mais recentemente (Ferraz-Mello, 1985) outros tipos de desenvolvimentos foram aplicados modificando substancialmente as ordens de grandeza e a velocidade de convergência das séries. Com esta abordagem, os desenvolvimentos foram expressados em termos da raíz cúbica do pequeno parâmetro. Neste trabalho apresentamos um enfoque geral, onde os diferentes tipos de desenvolvimentos em séries de Puiseux (Valiron, 1950) são obtidos a partir da aplicação de Teorema de Preparação de Weierstrass (Goursat, 1916) considerando a equação de Hamilton-Jacobi como uma equação algébrica. Os resultados são aplicados ao problema restrito dos três corpos em ressonância de primeira ordem e, dependendo da grandeza da excentricidade do asteróide em relação à de Júpiter, obtemos os diferentes desenvolvimentos, em raíz quadrada ou raíz cúbica da massa de Júpiter.

Shaping the Air Force Operational Environment in Cyberspace

DTIC Science & Technology

2009-02-12

the Internet. The World Wide Web was created in 1989 by English scientist Tim Berners - Lee , working at the European Organization for Nuclear Research...www.af.mil/news/story.asp?id=123013440 Goldsmith, Jack L. and Wu, Tim . Who Controls the Internet?: Illusions of a Borderless World. New York

Structure–Function Studies of Hydrophobic Residues That Clamp a Basic Glutamate Side Chain during Catalysis by Triosephosphate Isomerase

PubMed Central

2016-01-01

Kinetic parameters are reported for the reactions of whole substrates (kcat/Km, M–1 s–1) (R)-glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP) and for the substrate pieces [(kcat/Km)E·HPi/Kd, M–2 s–1] glycolaldehyde (GA) and phosphite dianion (HPi) catalyzed by the I172A/L232A mutant of triosephosphate isomerase from Trypanosoma brucei brucei (TbbTIM). A comparison with the corresponding parameters for wild-type, I172A, and L232A TbbTIM-catalyzed reactions shows that the effect of I172A and L232A mutations on ΔG⧧ for the wild-type TbbTIM-catalyzed reactions of the substrate pieces is nearly the same as the effect of the same mutations on TbbTIM previously mutated at the second side chain. This provides strong evidence that mutation of the first hydrophobic side chain does not affect the functioning of the second side chain in catalysis of the reactions of the substrate pieces. By contrast, the effects of I172A and L232A mutations on ΔG⧧ for wild-type TbbTIM-catalyzed reactions of the whole substrate are different from the effect of the same mutations on TbbTIM previously mutated at the second side chain. This is due to the change in the rate-determining step that determines the barrier to the isomerization reaction. X-ray crystal structures are reported for I172A, L232A, and I172A/L232A TIMs and for the complexes of these mutants to the intermediate analogue phosphoglycolate (PGA). The structures of the PGA complexes with wild-type and mutant enzymes are nearly superimposable, except that the space opened by replacement of the hydrophobic side chain is occupied by a water molecule that lies ∼3.5 Å from the basic side chain of Glu167. The new water at I172A mutant TbbTIM provides a simple rationalization for the increase in the activation barrier ΔG⧧ observed for mutant enzyme-catalyzed reactions of the whole substrate and substrate pieces. By contrast, the new water at the L232A mutant does not predict the decrease in �

Conjugated Bilirubin Differentially Regulates CD4+ T Effector Cells and T Regulatory Cell Function through Outside-In and Inside-Out Mechanisms: The Effects of HAV Cell Surface Receptor and Intracellular Signaling

PubMed Central

Corral-Jara, Karla F.; Gómez-Leyva, Juan F.; Rosenstein, Yvonne; Jose-Abrego, Alexis; Roman, Sonia

2016-01-01

We recently reported an immune-modulatory role of conjugated bilirubin (CB) in hepatitis A virus (HAV) infection. During this infection the immune response relies on CD4+ T lymphocytes (TLs) and it may be affected by the interaction of HAV with its cellular receptor (HAVCR1/TIM-1) on T cell surface. How CB might affect T cell function during HAV infection remains to be elucidated. Herein, in vitro stimulation of CD4+ TLs from healthy donors with CB resulted in a decrease in the degree of intracellular tyrosine phosphorylation and an increase in the activity of T regulatory cells (Tregs) expressing HAVCR1/TIM-1. A comparison between CD4+ TLs from healthy donors and HAV-infected patients revealed changes in the TCR signaling pathway relative to changes in CB levels. The proportion of CD4+CD25+ TLs increased in patients with low CB serum levels and an increase in the percentage of Tregs expressing HAVCR1/TIM-1 was found in HAV-infected patients relative to controls. A low frequency of 157insMTTTVP insertion in the viral receptor gene HAVCR1/TIM-1 was found in patients and controls. Our data revealed that, during HAV infection, CB differentially regulates CD4+ TLs and Tregs functions by modulating intracellular pathways and by inducing changes in the proportion of Tregs expressing HAVCR1/TIM-1. PMID:27578921

CD163(+) M2-type tumor-associated macrophage support the suppression of tumor-infiltrating T cells in osteosarcoma.

PubMed

Han, Qinglin; Shi, Hongguang; Liu, Fan

2016-05-01

Osteosarcoma is one of the most common childhood cancers with high numbers of cancer-related deaths. Progress in conventional therapies is showing limited improvement. An adaptive T cell-based immunotherapy represents a promising new therapeutic option, but to improve its efficacy, regulatory mechanisms in osteosarcoma need further elucidation. Here, to evaluate the regulatory effect of tumor microenvironment of T cells in osteosarcoma, we examined the peripheral blood (PB) and tumor infiltrating (TI) T cells, and their correlations with PB and tumor immune characteristics. We found that TI T cells contained significantly higher levels of TIM-3(+)PD-1(-) and TIM-3(+)PD-1(+) cells than their PB counterparts. Similar to that in chronic HIV and HCV infections, these TIM-3(+)PD-1(-) and TIM-3(+)PD-1(+) T cells presented reduced proliferation and proinflammatory cytokine secretion in response to stimulation. Presence of M2-type (CD163(+)) macrophages exacerbated T cell immunosuppression, since frequencies of CD163(+) tumor-associated macrophages were directly correlated with the frequencies of suppressed TIM-3(+)PD-1(+) T cells. Moreover, depletion of CD163(+) macrophages significantly improved T cell proliferation and proinflammatory cytokine production. Overall, our data presented an intratumoral T cell-specific immunosuppression that was amplified by M2-type tumor-associated macrophages. Copyright © 2016. Published by Elsevier B.V.

Triosephosphate isomerase and filamin C share common epitopes as novel allergens of Procambarus clarkii

USDA-ARS?s Scientific Manuscript database

Triosephosphate isomerase (TIM) is a key enzyme in glycolysis and has been identified as an allergen in saltwater products. In this study, TIM with a molecular mass of 28 kDa was purified from the freshwater crayfish (Procambarus clarkii) muscle. A 90-kDa protein that showed IgG/IgE cross-reactivity...

Cross-Domain Information Exchange Framework (CIEF): Road Map to Web 2.0

DTIC Science & Technology

2007-06-22

open to debate, and some technology experts, notably Tim Berners - Lee , have questioned whether the term has meaning. developerWorks Interviews So the...better the more people use them." Tim O’Reilly (2006-12-10). Web 2.0 Compact Definition: Trying Again Problem: Its (Web 2.0) exact meaning remains

Effects of different sweet preloads on incretin hormone secretion, gastric emptying, and postprandial glycemia in healthy humans.

PubMed

Wu, Tongzhi; Zhao, Beiyi R; Bound, Michelle J; Checklin, Helen L; Bellon, Max; Little, Tanya J; Young, Richard L; Jones, Karen L; Horowitz, Michael; Rayner, Christopher K

2012-01-01

Macronutrient "preloads" can stimulate glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), slow gastric emptying, and reduce postprandial glycemic excursions. After sweet preloads, these effects may be signaled by sodium-glucose cotransporter-1 (SGLT1), sweet taste receptors, or both. We determined the effects of 4 sweet preloads on GIP and GLP-1 release, gastric emptying, and postprandial glycemia. Ten healthy subjects were studied on 4 separate occasions each. A preload drink containing 40 g glucose, 40 g tagatose/isomalt mixture (TIM), 40 g 3-O-methylglucose (3OMG; a nonmetabolized substrate of SGLT1), or 60 mg sucralose was consumed 15 min before a (13)C-octanoic acid-labeled mashed potato meal. Blood glucose, plasma total GLP-1 and GIP, serum insulin, and gastric emptying were determined. Both glucose and 3OMG stimulated GLP-1 and GIP release in advance of the meal (each P < 0.05), whereas TIM and sucralose did not. The overall postprandial GLP-1 response was greater after glucose, 3OMG, and TIM than after sucralose (P < 0.05), albeit later after TIM than the other preloads. The blood glucose and insulin responses in the first 30 min after the meal were greatest after glucose (each P < 0.05). Gastric emptying was slower after both 3OMG and TIM than after sucralose (each P < 0.05). In healthy humans, SGLT1 substrates stimulate GLP-1 and GIP and slow gastric emptying, regardless of whether they are metabolized, whereas the artificial sweetener sucralose does not. Poorly absorbed sweet tastants (TIM), which probably expose a greater length of gut to nutrients, result in delayed GLP-1 secretion but not in delayed GIP release. These observations have the potential to optimize the use of preloads for glycemic control. This trial was registered at www.actr.org.au as ACTRN12611000775910.

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

Realmuto, V.J.; Abrams, M.J.; Buongiorno, M.F.

The authors have found that image data acquired with NASA's airborne Thermal Infrared Multispectral Scanner (TIMS) can be used to make estimates of the SO[sub 2] content of volcanic plumes. TIMS image data are most applicable to the study of partially transparent SO[sub 2] plumes, such as those released during quiescent periods or nonexplosive eruptions. The estimation procedure is based on the LOWTRAN 7 radiative transfer code, which the authors use to model the radiance perceived by TIMS as it views the ground through an SO[sub 2] plume. The input to the procedure includes the altitudes of the aircraft andmore » ground, the altitude and thickness of the SO[sub 2] plume, the emissivity of the ground, and altitude profiles of the atmospheric pressure, temperature, and relative humidity. They use the TIMS data to estimate both ground temperatures beneath a plume and SO[sub 2] concentrations within a plume. Applying this procedure to TIMS data acquired over Mount Etna, Sicily, on July 29, 1986, the authors estimate that the SO[sub 2] flux from the volcano was approximately 6700 t d[sup [minus]1]. The use of TIMS to study SO[sub 2] plumes represents a bridge between highly localized methods, such as correlation spectroscopy or direct sampling, and small-scale mapping techniques involving satellite instruments such as the Total Ozone Mapping Spectrometer or Microwave Limb Sounder. The authors require further airborne experiments to refine their estimation procedure. This refinement is a necessary preparation for the scheduled 1998 launch of the Advanced Spaceborne Thermal Emission and Reflectance Radiometer, which will allow large-scale multispectral thermal infrared image data to be collected over virtually any volcano on Earth at least once every 16 days.« less

DasPy 1.0 - the Open Source Multivariate Land Data Assimilation Framework in combination with the Community Land Model 4.5

NASA Astrophysics Data System (ADS)

Han, X.; Li, X.; He, G.; Kumbhar, P.; Montzka, C.; Kollet, S.; Miyoshi, T.; Rosolem, R.; Zhang, Y.; Vereecken, H.; Franssen, H.-J. H.

2015-08-01

Data assimilation has become a popular method to integrate observations from multiple sources with land surface models to improve predictions of the water and energy cycles of the soil-vegetation-atmosphere continuum. Multivariate data assimilation refers to the simultaneous assimilation of observation data from multiple model state variables into a simulation model. In recent years, several land data assimilation systems have been developed in different research agencies. Because of the software availability or adaptability, these systems are not easy to apply for the purpose of multivariate land data assimilation research. We developed an open source multivariate land data assimilation framework (DasPy) which is implemented using the Python script language mixed with the C++ and Fortran programming languages. LETKF (Local Ensemble Transform Kalman Filter) is implemented as the main data assimilation algorithm, and uncertainties in the data assimilation can be introduced by perturbed atmospheric forcing data, and represented by perturbed soil and vegetation parameters and model initial conditions. The Community Land Model (CLM) was integrated as the model operator. The implementation allows also parameter estimation (soil properties and/or leaf area index) on the basis of the joint state and parameter estimation approach. The Community Microwave Emission Modelling platform (CMEM), COsmic-ray Soil Moisture Interaction Code (COSMIC) and the Two-Source Formulation (TSF) were integrated as observation operators for the assimilation of L-band passive microwave, cosmic-ray soil moisture probe and land surface temperature measurements, respectively. DasPy has been evaluated in several assimilation studies of neutron count intensity (soil moisture), L-band brightness temperature and land surface temperature. DasPy is parallelized using the hybrid Message Passing Interface and Open Multi-Processing techniques. All the input and output data flows are organized efficiently

16TH Annual Review of Progress in Applied Computational Electromagnetics of the Naval Postgraduate School, Monterey, CA. Volume I

DTIC Science & Technology

2000-03-24

Element Method for Designing Plasma Reactors" Leo Kempel, Paul Rummel, Tim Grotjohn and John Amrhein ............................................ 28...34Finite Element Method for Designing Plasma Reactors" Leo Kempel, Paul Rummel, Tim Grotjohn and John Amrhein...548 "lime-Domain Simulation of Electromagnetic Wave Propagation in a Magnetized Plasma" J. Paul , C. Christopoulos, and

UPA Fill Drain Valve Modification kit installation

NASA Image and Video Library

2016-01-25

ISS046e023885 (01/25/2016) --- NASA astronaut Tim Kopra performs regular maintenance on the Urine Processing Assembly (UPA) aboard the International Space Station. The UPA is used by the crew to recycle water for use on the station. The image shows Tim replacing the brine filter from the UPA Fill Drain Valve enclosure.

Connecting Active-Site Loop Conformations and Catalysis in Triosephosphate Isomerase: Insights from a Rare Variation at Residue 96 in the Plasmodial Enzyme.

PubMed

Pareek, Vidhi; Samanta, Moumita; Joshi, Niranjan V; Balaram, Hemalatha; Murthy, Mathur R N; Balaram, Padmanabhan

2016-04-01

Despite extensive research into triosephosphate isomerases (TIMs), there exists a gap in understanding of the remarkable conjunction between catalytic loop-6 (residues 166-176) movement and the conformational flip of Glu165 (catalytic base) upon substrate binding that primes the active site for efficient catalysis. The overwhelming occurrence of serine at position 96 (98% of the 6277 unique TIM sequences), spatially proximal to E165 and the loop-6 residues, raises questions about its role in catalysis. Notably, Plasmodium falciparum TIM has an extremely rare residue--phenylalanine--at this position whereas, curiously, the mutant F96S was catalytically defective. We have obtained insights into the influence of residue 96 on the loop-6 conformational flip and E165 positioning by combining kinetic and structural studies on the PfTIM F96 mutants F96Y, F96A, F96S/S73A, and F96S/L167V with sequence conservation analysis and comparative analysis of the available apo and holo structures of the enzyme from diverse organisms. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Laser-Induced Ionization Efficiency Enhancement On A Filament For Thermal Ionization Mass Spectrometry

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

Siegfried, M.

2015-10-14

The evaluation of trace Uranium and Plutonium isotope ratios for nanogram to femtogram material quantities is a vital tool for nuclear counter-proliferation and safeguard activities. Thermal Ionization Mass Spectrometry (TIMS) is generally accepted as the state of the art technology for highly accurate and ultra-trace measurements of these actinide ratios. However, the very low TIMS ionization yield (typically less than 1%) leaves much room for improvement. Enhanced ionization of Nd and Sm from a TIMS filament was demonstrated using wavelength resonance with a nanosecond (pulse width) laser operating at 10 Hz when light was directed toward the filament.1 For thismore » study, femtosecond and picosecond laser capabilities were to be employed to study the dissociation and ionization mechanisms of actinides/lanthanides and measure the enhanced ionization of the metal of interest. Since the underlying chemistry of the actinide/lanthanide carbides produced and dissociated on a TIMS filament is not well understood, the experimental parameters affecting the photodissociation and photoionization with one and two laser beams were to be investigated.« less

System Study: Technology Assessment and Prioritizing

NASA Technical Reports Server (NTRS)

2005-01-01

The objective of this NASA funded project is to assess and prioritize advanced technologies required to achieve the goals for an "Intelligent Propulsion System" through collaboration among GEAE, NASA, and Georgia Tech. Key GEAE deliverables are parametric response surface equations (RSE's) relating technology features to system benefits (sfc, weight, fuel burn, design range, acoustics, emission, etc...) and listings of Technology Impact Matrix (TIM) with benefits, debits, and approximate readiness status. TIM has been completed for GEAE and NASA proposed technologies. The combined GEAE and NASA TIM input requirement is shown in Table.1. In the course of building the RSE's and TIM, significant parametric technology modeling and RSE accuracy improvements were accomplished. GEAE has also done preliminary ranking of the technologies using Georgia Tech/GEAE USA developed technology evaluation tools. System level impact was performed by combining beneficial technologies with minimum conflict among various system figures of merits to assess their overall benefits to the system. The shortfalls and issues with modeling the proposed technologies are identified, and recommendations for future work are also proposed.

A comparison of lead-isotope measurements on exploration-type samples using inductively coupled plasma and thermal ionization mass spectrometry

USGS Publications Warehouse

Gulson, B.L.; Meier, A.L.; Church, S.E.; Mizon, K.J.

1989-01-01

Thermal ionization mass spectrometry (TI-MS) has long been the method of choice for Pb-isotope determinations. More recently, however, inductively coupled plasma mass spectrometry (ICP-MS) has been used to determine Pb-isotope ratios for mineral exploration. The ICP-MS technique, although not as precise as TI-MS, may promote a wider application of Ph-isotope ratio methods because it allows individual isotopes to be determined more rapidly, generally without need for chemical separation (e.g., Smith et al., 1984; Hinners et al., 1987). To demonstrate the utility of the ICP-MS method, we have conducted a series of Pb-isotope measurements on several suites of samples using both TI-MS and ICP-MS. ?? 1989.

Doing Literary Criticism: Helping Students Engage with Challenging Texts

ERIC Educational Resources Information Center

Gillespie, Tim

2010-01-01

One of the greatest challenges for English language arts teachers today is the call to engage students in more complex texts. Tim Gillespie, who has taught in public schools for almost four decades, has found the lenses of literary criticism a powerful tool for helping students tackle challenging literary texts. Tim breaks down the dense language…

Characterization of the heat transfer properties of thermal interface materials

NASA Astrophysics Data System (ADS)

Fullem, Travis Z.

Physicists have studied the thermal conductivity of solids for decades. As a result of these efforts, thermal conduction in crystalline solids is well understood; there are detailed theories describing thermal conduction due to electrons and phonons. Phonon scattering and transmission at solid/solid interfaces, particularly above cryogenic temperatures, is not well understood and more work is needed in this area. The desire to solve engineering problems which require good thermal contact between mating surfaces has provided enhanced motivation for furthering the state of the art on this topic. Effective thermal management is an important design consideration in microelectronic systems. A common technique for removing excess heat from an electronic device is to attach a heatsink to the device; it is desirable to minimize the thermal resistance between the device and the heatsink. This can be accomplished by placing a thermal interface material (TIM) between the two surfaces. Due to the ever-increasing power densities found in electronic components, there is a desire to design better TIMs, which necessitates the ability to characterize TIM bondlines and to better understand the physics of heat conduction through TIM bondlines. A micro Fourier apparatus which employs Pt thin film thermometers of our design has been built and is capable of precisely quantifying the thermal resistance of thermal interface materials. In the present work several types of commercially available TIMs have been studied using this apparatus, including: greases, filled epoxies, and thermally conductive pads. In the case of filled epoxies, bondlines of various thicknesses, ranging from thirty microns to several hundred microns, have been measured. The microstructure of these bondlines has been investigated using optical microscopy and acoustic microscopy. Measured values of thermal conductivity are considered in terms of microstructural features such as percolation networks and filler particle

Processing data for a spatial watershed model to evaluate hydrological responses of the Ribeirão das Posses, Brazil

USDA-ARS?s Scientific Manuscript database

Southeastern Brazil has experienced drought conditions that have impacted the conservation of watersheds and the management of water quality and quantity for agricultural and urban demands. The Ribeirão das Posses watershed is being monitored as a headwater of the Jaguarí River, which is one of the ...

Latent Factor Structure of the Das-Naglieri Cognitive Assessment System: A Confirmatory Factor Analysis in a Chinese Setting

ERIC Educational Resources Information Center

Deng, Ci-ping; Liu, Ming; Wei, Wei; Chan, Raymond C. K.; Das, J. P.

2011-01-01

This study aims to measure the psychometric properties of the Das-Naglieri Cognitive Assessment System (D-N CAS) and to determine its clinical utility in a Chinese context. Confirmatory factor analysis (CFA) was conducted to examine the construct validity of the Chinese version of the D-N CAS among a group of 567, normally developed children.…

Learning to Teach--Tim's Story

ERIC Educational Resources Information Center

Rowland, Tim

2006-01-01

This article is both a sequel and a companion to the account by Gill Hatch, published in "MT196," of her experience in her first teaching post--as a College of Education Assistant Lecturer. A chance remark by Gill in 2001 made the author aware that their careers as mathematics teachers had begun in similar environments. They set about compiling a…

Verknüpfung von DQ-Indikatoren mit KPIs und Auswirkungen auf das Return on Investment

NASA Astrophysics Data System (ADS)

Block, Frank

Häufig ist nicht klar, welche Beziehungen zwischen Datenqualitätsindikatoren (DQI, Definition folgt weiter unten) und Key Performance Indicators (KPI, s. Abschnitt 1.3 für weitere Details) eines Unternehmens oder einer Organisation bestehen. Dies ist insbesondere deshalb von Bedeutung, da die Kenntnis dieser Beziehungen maßgeblich die Ausprägung eines Datenqualitätsprojekts beeinflusst. Sie ist als Entscheidungsgrundlage unabdingbar und gibt Antworten auf folgende Fragen: Was kostet unserem Unternehmen/unserer Organisation1 schlechte Datenqualität? Können wir uns das leisten?

An Ontological Approach to Developing Information Operations Applications for Use on the Semantic Web

DTIC Science & Technology

2008-09-01

IWPC 21 Berners - Lee , Tim . (1999). Weaving the Web. New York: HarperCollins Publishers, Inc. 22... Berners - Lee , Tim . (1999). Weaving the Web. New York: HarperCollins Publishers, Inc. Berners - Lee , T., Hendler, J., & Lassila, O. (2001). The Semantic...environment where software agents roaming from page to page can readily carry out sophisticated tasks for users. T. Berners - Lee , J. Hendler, and O

3D shear wave velocity structure revealed with ambient noise tomography on a DAS array

NASA Astrophysics Data System (ADS)

Zeng, X.; Thurber, C. H.; Wang, H. F.; Fratta, D.

2017-12-01

An 8700-m Distributed Acoustic Sensing (DAS) cable was deployed at Brady's Hot Springs, Nevada in March 2016 in a 1.5 by 0.5 km study area. The layout of the DAS array was designed with a zig-zag geometry to obtain relatively uniform areal and varied angular coverage, providing very dense coverage with a one-meter channel spacing. This array continuously recorded signals of a vibroseis truck, earthquakes, and traffic noise during the 15-day deployment. As shown in a previous study (Zeng et al., 2017), ambient noise tomography can be applied to DAS continuous records to image shear wave velocity structure in the near surface. To avoid effects of the vibroseis truck operation, only continuous data recorded during the nighttime was used to compute noise cross-correlation functions for channel pairs within a given linear segment. The frequency band of whitening was set at 5 to 15 Hz and the length of the cross-correlation time window was set to 60 second. The phase velocities were determined using the multichannel analysis of surface waves (MASW) methodology. The phase velocity dispersion curve was then used to invert for shear wave velocity profiles. A preliminarily velocity model at Brady's Hot Springs (Lawrence Livermore National Laboratory, 2015) was used as the starting model and the sensitivity kernels of Rayleigh wave group and phase velocities were computed with this model. As the sensitivity kernel shows, shear wave velocity in the top 200 m can be constrained with Rayleigh wave group and phase velocities in our frequency band. With the picked phase velocity data, the shear wave velocity structure can be obtained via Occam's inversion (Constable et al., 1987; Lai 1998). Shear wave velocity gradually increases with depth and it is generally faster than the Lawrence Livermore National Laboratory (2015) model. Furthermore, that model has limiting constraints at shallow depth. The strong spatial variation is interpreted to reflect the different sediments and

Multispectral thermal infrared mapping of sulfur dioxide plumes: A case study from the East Rift Zone of Kilauea Volcano, Hawaii

NASA Astrophysics Data System (ADS)

Realmuto, V. J.; Sutton, A. J.; Elias, T.

1997-07-01

The synoptic perspective and rapid mode of data acquisition provided by remote sensing are well suited for the study of volcanic SO2 plumes. In this paper we describe a plume-mapping procedure that is based on image data acquired with NASA's airborne thermal infrared multispectral scanner (TIMS) and apply the procedure to TIMS data collected over the East Rift Zone of Kilauea Volcano, Hawaii, on September 30, 1988. These image data covered the Pu`u `O `o and Kupaianaha vents and a skylight in the lava tube that was draining the Kupaianaha lava pond. Our estimate of the SO2 emission rate from Pu`u `O `o (17-20 kg s-1) is roughly twice the average of estimates derived from correlation spectrometer (COSPEC) measurements collected 10 days prior to the TIMS overflight (10 kg s-1). The agreement between the TIMS and COSPEC results improves when we compare SO2 burden estimates, which are relatively independent of wind speed. We demonstrate the feasibility of mapping Pu`u `O `o - scale SO2 plumes from space in anticipation of the 1998 launch of the advanced spaceborne thermal emission and reflectance radiometer (ASTER).

Calculation of day and night emittance values

NASA Technical Reports Server (NTRS)

Kahle, Anne B.

1986-01-01

In July 1983, the Thermal Infrared Multispectral Scanner (TIMS) was flown over Death Valley, California on both a midday and predawn flight within a two-day period. The availability of calibrated digital data permitted the calculation of day and night surface temperature and surface spectral emittance. Image processing of the data included panorama correction and calibration to radiance using the on-board black bodies and the measured spectral response of each channel. Scene-dependent isolated-point noise due to bit drops, was located by its relatively discontinuous values and replaced by the average of the surrounding data values. A method was developed in order to separate the spectral and temperature information contained in the TIMS data. Night and day data sets were processed. The TIMS is unique in allowing collection of both spectral emittance and thermal information in digital format with the same airborne scanner. For the first time it was possible to produce day and night emittance images of the same area, coregistered. These data add to an understanding of the physical basis for the discrimination of difference in surface materials afforded by TIMS.

Is the catalytic activity of triosephosphate isomerase fully optimized? An investigation based on maximization of entropy production.

PubMed

Bonačić Lošić, Željana; Donđivić, Tomislav; Juretić, Davor

2017-03-01

Triosephosphate isomerase (TIM) is often described as a fully evolved housekeeping enzyme with near-maximal possible reaction rate. The assumption that an enzyme is perfectly evolved has not been easy to confirm or refute. In this paper, we use maximization of entropy production within known constraints to examine this assumption by calculating steady-state cyclic flux, corresponding entropy production, and catalytic activity in a reversible four-state scheme of TIM functional states. The maximal entropy production (MaxEP) requirement for any of the first three transitions between TIM functional states leads to decreased total entropy production. Only the MaxEP requirement for the product (R-glyceraldehyde-3-phosphate) release step led to a 30% increase in enzyme activity, specificity constant k cat /K M , and overall entropy production. The product release step, due to the TIM molecular machine working in the physiological direction of glycolysis, has not been identified before as the rate-limiting step by using irreversible thermodynamics. Together with structural studies, our results open the possibility for finding amino acid substitutions leading to an increased frequency of loop six opening and product release.

Graphene-enhanced thermal interface materials for heat removal from photovoltaic solar cells

NASA Astrophysics Data System (ADS)

Saadah, M.; Gamalath, D.; Hernandez, E.; Balandin, A. A.

2016-09-01

The increase in the temperature of photovoltaic (PV) solar cells affects negatively their power conversion efficiency and decreases their lifetime. The negative effects are particularly pronounced in concentrator solar cells. Therefore, it is crucial to limit the PV cell temperature by effectively removing the excess heat. Conventional thermal phase change materials (PCMs) and thermal interface materials (TIMs) do not possess the thermal conductivity values sufficient for thermal management of the next generation of PV cells. In this paper, we report the results of investigation of the increased efficiency of PV cells with the use of graphene-enhanced TIMs. Graphene reveals the highest values of the intrinsic thermal conductivity. It was also shown that the thermal conductivity of composites can be increased via utilization of graphene fillers. We prepared TIMs with up to 6% of graphene designed specifically for PV cell application. The solar cells were tested using the solar simulation module. It was found that the drop in the output voltage of the solar panel under two-sun concentrated illumination can be reduced from 19% to 6% when grapheneenhanced TIMs are used. The proposed method can recover up to 75% of the power loss in solar cells.

Estimating Thruster Impulses From IMU and Doppler Data

NASA Technical Reports Server (NTRS)

Lisano, Michael E.; Kruizinga, Gerhard L.

2009-01-01

A computer program implements a thrust impulse measurement (TIM) filter, which processes data on changes in velocity and attitude of a spacecraft to estimate the small impulsive forces and torques exerted by the thrusters of the spacecraft reaction control system (RCS). The velocity-change data are obtained from line-of-sight-velocity data from Doppler measurements made from the Earth. The attitude-change data are the telemetered from an inertial measurement unit (IMU) aboard the spacecraft. The TIM filter estimates the threeaxis thrust vector for each RCS thruster, thereby enabling reduction of cumulative navigation error attributable to inaccurate prediction of thrust vectors. The filter has been augmented with a simple mathematical model to compensate for large temperature fluctuations in the spacecraft thruster catalyst bed in order to estimate thrust more accurately at deadbanding cold-firing levels. Also, rigorous consider-covariance estimation is applied in the TIM to account for the expected uncertainty in the moment of inertia and the location of the center of gravity of the spacecraft. The TIM filter was built with, and depends upon, a sigma-point consider-filter algorithm implemented in a Python-language computer program.

In vitro digestion of short-dough biscuits enriched in proteins and/or fibres, using a multi-compartmental and dynamic system (1): viscosity measurement and prediction.

PubMed

Villemejane, C; Wahl, R; Aymard, P; Denis, S; Michon, C

2015-09-01

The effects of biscuit composition on the viscosity generated during digestion were investigated. A control biscuit, one with proteins, one with fibres, and one with both proteins and fibres were digested under the same conditions, using the TNO intestinal model (TIM-1). The TIM-1 is a multi-compartmental and dynamic in vitro system, simulating digestion in the upper tract (stomach and small intestine) of healthy adult humans. Digesta were collected at different times, in the different compartments of the TIM-1 (stomach, duodenum, jejunum and ileum) and viscosity was measured with a dynamic rheometer. Results showed a marked effect of biscuit composition on chyme viscosity. Highest viscosity was obtained with biscuits containing viscous soluble fibres, followed by those enriched in both proteins and fibres, then by protein-enriched and control biscuits. The viscosity was maintained throughout the gut up to the ileal compartment. A prediction of the evolution of the chyme viscosity in each compartment of the TIM-1 was built, based on model curves describing the evolution of the viscosity as a function of biscuit concentration, and on dilution factors measured by spectrophotometry on a blank digestion. Copyright © 2015 Elsevier Ltd. All rights reserved.

Validation of the World Health Organization Disability Assessment Schedule (WHO-DAS II) in Greek and its added value to the Short Form 36 (SF-36) in a sample of people with or without disabilities.

PubMed

Xenouli, Georgia; Xenoulis, Kostis; Sarafis, Pavlos; Niakas, Dimitris; Alexopoulos, Evangelos C

2016-07-01

There is controversy and ongoing interest on the measurement of functionality in the personal and social level. (1) to validate the Greek version of the World Health Organization Disability Assessment Schedule (WHO DAS II) and (2) to determine its added value to the physical and psychological health subscales of the Short Form 36 (SF-36). In a cross-sectional design, data were collected between December 2014 and March 2015 by using three questionnaires (WHO DAS II, SF-36, PSS-14) in a sample of people with disabilities (n = 101) and without disabilities (n = 109) in Athens, Greece. WHO DAS II internal consistency, construct and criterion-related validity were assessed by Cronbach alpha, exploratory factor analysis and correlations; its added value by multivariable linear regression. Cronbach Alpha's were satisfactory for the WHO DAS II, PSS-14 and SF-36 (0.85, 0.88 and 0.96 respectively). Exploratory factor analysis confirmed the existence of one or two factors in people with or without disabilities, respectively. WHO DAS II score showed significant negative correlation with the physical and mental health scale of SF-36 score, especially strong for physical health while was positively related to PSS-14 score. In multivariate analysis mental health appraisal was related to perceived stress in both groups. This study support the validity of the Greek version of WHO DAS II and warranted its use in assessment and follow up of people with disabilities, contributing to the development of suitable policies to cover their needs and providing comparable data with other surveys using the same instrument. Copyright © 2016 Elsevier Inc. All rights reserved.

Multispectral Analysis of Surface Wave (MASW) Analysis of Near-Surface Structure at Brady Hot Springs from Active Source and Ambient Noise Using a 8700-meter Distributed Acoustic Sensing (DAS) Array

NASA Astrophysics Data System (ADS)

Wang, H. F.; Lord, N. E.; Zeng, X.; Fratta, D.; Feigl, K. L.; Team, P.

2016-12-01

The Porotomo research team deployed 8700-meters of Distributed Acoustic Sensing (DAS) cable in a shallow trench on the surface and 400 meters down a borehole at Brady Hot Springs, Nevada in March 2016. The goal of the experiment was to detect changes in geophysical properties associated with hydrologic changes. The DAS cable occupied a natural laboratory of 1500-by-500-by-400-meters overlying a commercial, geothermal field operated by Ormat Technologies. The DAS cable was laid out in three parallel zig-zag lines with line segments approximately 120-meters in length. A large Vibroseis truck (T-Rex) provided the seismic source with a sweep frequency between 5 and 80 Hz over 20 seconds. Over the 15 days of the experiment, the Vibroseis truck re-occupied approximately 250 locations outside and within the array days while changes were made in water reinjection from the power plant into wells in the field. At each source location, one vertical and two orthogonal horizontal modes were excited. Dispersion curves were constructed using MASW and a Vibroseis source location approximately in line with each DAS cable segment or from ambient noise correlation functions. Representative fence diagrams of S-wave profiles were constructed by inverting the dispersion curves obtained for several different line segments.

Test Review: Naglieri, J. A., Das, J. P., & Goldstein, S. (2014). Cognitive Assessment System-Second Edition (2nd Ed.)

ERIC Educational Resources Information Center

McGill, Ryan J.

2015-01-01

The Cognitive Assessment System-Second Edition (CAS2) is an individually administered measure of cognitive ability designed for children and adolescents ages 5 through 18 years. The measure, authored by Jack A. Naglieri, J. P. Das, and Sam Goldstein, was published by Pro-Ed in 2014 and is the first revision of the Cognitive Assessment System (CAS;…

A competent catalytic active site is necessary for substrate induced dimer assembly in triosephosphate isomerase.

PubMed

Jimenez-Sandoval, Pedro; Vique-Sanchez, Jose Luis; Hidalgo, Marisol López; Velazquez-Juarez, Gilberto; Diaz-Quezada, Corina; Arroyo-Navarro, Luis Fernando; Moran, Gabriela Montero; Fattori, Juliana; Jessica Diaz-Salazar, A; Rudiño-Pinera, Enrique; Sotelo-Mundo, Rogerio; Figueira, Ana Carolina Migliorini; Lara-Gonzalez, Samuel; Benítez-Cardoza, Claudia G; Brieba, Luis G

2017-11-01

The protozoan parasite Trichomonas vaginalis contains two nearly identical triosephosphate isomerases (TvTIMs) that dissociate into stable monomers and dimerize upon substrate binding. Herein, we compare the role of the "ball and socket" and loop 3 interactions in substrate assisted dimer assembly in both TvTIMs. We found that point mutants at the "ball" are only 39 and 29-fold less catalytically active than their corresponding wild-type counterparts, whereas Δloop 3 deletions are 1502 and 9400-fold less active. Point and deletion mutants dissociate into stable monomers. However, point mutants assemble as catalytic competent dimers upon binding of the transition state substrate analog PGH, whereas loop 3 deletions remain monomeric. A comparison between crystal structures of point and loop 3 deletion monomeric mutants illustrates that the catalytic residues in point mutants and wild-type TvTIMs are maintained in the same orientation, whereas the catalytic residues in deletion mutants show an increase in thermal mobility and present structural disorder that may hamper their catalytic role. The high enzymatic activity present in monomeric point mutants correlates with the formation of dimeric TvTIMs upon substrate binding. In contrast, the low activity and lack of dimer assembly in deletion mutants suggests a role of loop 3 in promoting the formation of the active site as well as dimer assembly. Our results suggest that in TvTIMs the active site is assembled during dimerization and that the integrity of loop 3 and ball and socket residues is crucial to stabilize the dimer. Copyright © 2017 Elsevier B.V. All rights reserved.

Equilibrium and kinetic folding of rabbit muscle triosephosphate isomerase by hydrogen exchange mass spectrometry.

PubMed

Pan, Hai; Raza, Ashraf S; Smith, David L

2004-03-05

Unfolding and refolding of rabbit muscle triosephosphate isomerase (TIM), a model for (betaalpha)8-barrel proteins, has been studied by amide hydrogen exchange/mass spectrometry. Unfolding was studied by destabilizing the protein in guanidine hydrochloride (GdHCl) or urea, pulse-labeling with 2H2O and analyzing the intact protein by HPLC electrospray ionization mass spectrometry. Bimodal isotope patterns were found in the mass spectra of the labeled protein, indicating two-state unfolding behavior. Refolding experiments were performed by diluting solutions of TIM unfolded in GdHCl or urea and pulse-labeling with 2H2O at different times. Mass spectra of the intact protein labeled after one to two minutes had three envelopes of isotope peaks, indicating population of an intermediate. Kinetic modeling indicates that the stability of the folding intermediate in water is only 1.5 kcal/mol. Failure to detect the intermediate in the unfolding experiments was attributed to its low stability and the high concentrations of denaturant required for unfolding experiments. The folding status of each segment of the polypeptide backbone was determined from the deuterium levels found in peptic fragments of the labeled protein. Analysis of these spectra showed that the C-terminal half folds to form the intermediate, which then forms native TIM with folding of the N-terminal half. These results show that TIM folding fits the (4+4) model for folding of (betaalpha)8-barrel proteins. Results of a double-jump experiment indicate that proline isomerization does not contribute to the rate-limiting step in the folding of TIM.

Vertically aligned carbon nanotube arrays as thermal interface material for vibrational structure of piezoelectric transformer

NASA Astrophysics Data System (ADS)

Chen, Lie; Ju, Bin; Feng, Zhihua; Zhao, Yang

2018-07-01

The application and characterization of thermal interface material (TIM) for vibrational structures is investigated in this paper. The vibrating feature during the operation requires unique solution for its thermal management, since the connection between the device and heat dissipater should be able to conduct heat efficiently and impose minimum constraint onto the vibration simultaneously. As a typical vibrational device, piezoelectric transformers (PTs) are discussed in this paper. The PTs have urgent demands for thermal dissipation since their power conversion efficiency decrease rapidly with the rising temperature. A novel method by applying vertically aligned carbon nanotube (VACNT) arrays to the interface between PT and heat dissipater is presented to enhance the performance of piezoelectric transformers. VACNT arrays are one of the excellent TIMs. It can directly establish thermal contact between two surfaces by van der Waals’ forces. In addition, the unique anisotropic character of CNT arrays provides enough flexibility to accommodate the vibration during the operation. Different configurations of TIMs are compared with each other in this work, including CNT arrays, tape of polypropylene (PP) membrane and without heat transfer structure (HTS). The results indicate that the temperature rise is lowest and the efficiency is highest at the same power density while CNT arrays served as the TIM. Almost no significant fretting and wearing damage occurred on PT electrode surface with CNT arrays TIM even after working continuously for 120 days. Meanwhile, the thermo-physical properties of CNT arrays at contact interface are measured by optical transient thermo-reflectance technique.

Antimicrobial activity of plants used as medicinals on an indigenous reserve in Rio das Cobras, Paraná, Brazil.

PubMed

Moura-Costa, Gislaine F; Nocchi, Samara R; Ceole, Ligia F; de Mello, João Carlos P; Nakamura, Celso Vataru; Dias Filho, Benedito Prado; Temponi, Livia G; Ueda-Nakamura, Tania

2012-09-28

A considerable percentage of global biodiversity is located in Brazil, a country that also has rich cultural and ethnic diversity. In the community of Rio das Cobras, Paraná, plants are still widely used in the health care not only by indigenous people but also by the non-indigenous population that inhabits the region. The investigation of the efficacy and safety of these plants in the treatment of infectious diseases provides insights for future studies of these species allowing the appropriated use by the indigenous people, since few or none study has been conducted so far. Evaluate the antimicrobial activity and cytotoxicity of some plants used as medicinal on an indigenous reserve in Rio das Cobras, Paraná, Brazil. The aqueous extracts were obtained by decoction and the 50% and 70% hydroalcoholic extracts by turbo extraction. The extracts were tested against strains of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Candida albicans, Candida parapsilosis, Candida tropicalis, Leishmania amazonensis, Poliovirus and HSV-1. Cytotoxicity assay using VERO cells were also performed. None of the extracts had a selectivity index (SI)>1 for any of the tested bacteria. Only Campomanesia eugenioides and Schinus terebinthifolius had an SI>1.0 for all of the tested Candida species. The best anti-Leishmania activity was obtained with Zanthoxylum rhoifolium and Schinus terebinthifolius. Extracts of Cordia americana were the most effective against herpes simplex virus type 1. Zanthoxylum rhoifolium was the most effective against Poliovirus, and Ocimum gratissimum was effective against both Poliovirus and Herpes Simplex virus. Among the plants investigated in the present study, Zanthoxylum rhoifolium had the fewest cytotoxic effect. The plants investigated in the present study exhibited potential for future pharmacological uses, but additional studies, especially with regard to in vivo toxicity, must be conducted. The results of this

Effect of preservative removal from fixed-combination bimatoprost/timolol on intraocular pressure lowering: a potential timolol dose–response phenomenon

PubMed Central

Shen, Jie; Bejanian, Marina

2016-01-01

Purpose Many patients with glaucoma require combination therapies to achieve target intraocular pressure (IOP) and preserve visual function. Ocular hypotensives often contain a preservative (eg, benzalkonium chloride [BAK]), but preservative-free (PF) formulations have been developed for patients with sensitivity. A Phase III study found the efficacy of bimatoprost 0.03%/timolol 0.5% (bim/tim, Ganfort®) PF to be equivalent to that of preserved bim/tim, although a trend favoring bim/tim PF was observed. As BAK is a corneal penetration enhancer, this literature review aims to explain these findings by exploring the relationship between timolol concentration and its IOP-lowering effect. Methods Systematic searches were performed in Scopus and PubMed for clinical trials published in English between 1960 and July 2014 using the keywords “timolol”, “intraocular pressure”, and the concentrations “1%, 0.5%, OR 0.25%”. Articles that directly compared IOP-lowering effects of ≥2 concentrations of timolol were identified by manual screening, and cross-checked for duplication. Results Seventeen studies that included 10–371 patients were evaluated; the majority were randomized (16/17), double-masked (14/17), and enrolled patients with open-angle glaucoma or ocular hypertension (12/17). All studies investigated timolol in preserved formulations. Timolol concentrations tested ranged from 0.008% to 1.5%. Of 13 studies comparing timolol 0.25% versus 0.5%, two found the 0.25% dose to have greater IOP-lowering effects, and three reported the opposite; eight reported similar IOP lowering. Results also indicate that timolol 0.5% may be more effective than higher concentrations. Conclusion The evidence suggests that timolol may have an inverted U-shaped dose–response curve, and that its optimal IOP-lowering concentration is between 0.25% and 0.5%. Compared with bim/tim, removal of the permeability enhancer BAK in bim/tim PF could have resulted in a lower timolol